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...

BEHAVIOR OF PERSISTENT BIOACCUMULATIVE TOXICANTS IN FISH EARLY LIFE STAGES

EPA Science Inventory

Whether through environmental criteria or site-specific risk assessments, many EPA programs rely on linking environmental exposures to levels of adverse effect (or no effect) in fish and wildlife. While empirical relationships of exposure to effect can be used for such assessmen...

Ceftaroline as Salvage Monotherapy for Persistent MRSA Bacteremia.

PubMed

Burnett, Yvonne J; Echevarria, Kelly; Traugott, Kristi A

2016-12-01

To summarize published data regarding the use of ceftaroline as salvage monotherapy for persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. PubMed (January 1980-June 2016) was searched using combinations of the search terms methicillin-resistant Staphylococcus aureus, MRSA, bacteremia, ceftaroline, refractory, and persistent Supplemental references were generated through review of identified literature citations. Available English-language, full-text articles pertaining to the use of ceftaroline for persistent MRSA bacteremia (MRSAB) were included. The PubMed search yielded 23 articles for evaluation. There are no randomized controlled trials to date-only case series and reports. Four retrospective case series detailing the use of ceftaroline as monotherapy for persistent MRSAB were included. Most patients received at least 4 days of an appropriate anti-MRSA antimicrobial prior to ceftaroline and were able to clear bacteremia within 3 days. The most common rationales for ceftaroline use were progression of disease or nonresponse to current therapy. Higher off-label dosing of ceftaroline is often utilized to achieve optimal pharmacokinetic/pharmacodynamic parameters. Adverse events are not well described due to lack of follow-up; however, neutropenia has been associated with prolonged use. Treatment options for persistent MRSAB remain few and far between. Ceftaroline is an effective agent for the salvage treatment of MRSAB. Off-label doses up to 600 mg every 8 hours are often used to achieve optimal pharmacokinetic/pharmacodynamic parameters. Because of lack of follow-up in these reports, the incidence of adverse effects of prolonged use of ceftaroline is not well defined. © The Author(s) 2016.

Prospective Observational Post-Marketing Study of Tafluprost for Glaucoma and Ocular Hypertension: Effectiveness and Treatment Persistence.

PubMed

Kuwayama, Yasuaki; Hashimoto, Masako; Kakegawa, Reiko; Nomura, Akio; Shimada, Fumiki

2017-06-01

The aim of this study was to investigate the long-term intraocular pressure (IOP)-lowering effect and safety of tafluprost, a prostaglandin analogue, in actual clinical practice and to determine persistency of tafluprost as an indicator of its benefit-risk balance. This was a large-scale, post-marketing, multicenter, non-interventional, open-label, long-term study. Patients with glaucoma or ocular hypertension who initiated tafluprost treatment were registered and prospectively observed over a 2-year period in the real-world setting in Japan. Long-term IOP and safety data were collected. Of the 4502 patients registered from 553 medical institutions, 4265 patients were analyzed. The majority of patients had normal-tension glaucoma (44.4%) and primary open-angle glaucoma (37.8%), and patients with ocular hypertension constituted 7.0%. Treatment patterns with tafluprost during the study period were as follows: naïve monotherapy (48.1%), switching monotherapy (18.4%), and concomitant therapy (33.5%). In all patients analyzed, mean IOP was significantly reduced from 18.6 ± 5.9 mmHg (month 0) to 15 mmHg or below throughout the 2-year observation period after initiation of tafluprost. Significant IOP-lowering effects were shown in various treatment patterns and disease types. Adverse reactions were observed in 795 patients (18.64%). Major adverse reactions included eyelid pigmentation, ocular hyperemia, eyelash changes, eyelid hypertrichosis, and iris hyperpigmentation. Kaplan-Meier curves showed that 84.6% and 76.1% of patients were persistent on tafluprost for 1 and 2 years, respectively, when discontinuation due to insufficient efficacy or adverse events was defined as a treatment failure event. Furthermore, among treatment-naïve patients (n = 2304), the persistency rates on tafluprost monotherapy were 77.0% for 1 year and 67.0% for 2 years. Tafluprost showed significant long-term IOP-lowering effects regardless of treatment patterns or diagnosis, with minimum safety concerns in the actual clinical practice. The observed treatment persistence suggests that tafluprost can be used long term owing to its benefit-risk profile. Santen Pharmaceutical Co., Ltd., Osaka, Japan.

Brominated Flame Retardants.

EPA Science Inventory

BFRs belong to a growing group of organohalogen chemicals. They can be highly persistent, bioaccumulative and cause adverse effects in humans and wildlife. Although some BFRs are banned or voluntarily withdrawn from usage by the manufacturer, emerging and existing BFRs continue t...

IS THERE A VIABILITY-VULNERABILITY TRADEOFF? SEX DIFFERENCES IN FETAL PROGRAMMING

PubMed Central

SANDMAN, CURT A; GLYNN, LAURA M; DAVIS, ELYSIA POGGI

2013-01-01

OBJECTIVE In this paper we evaluate the evidence for sex differences in fetal programming within the context of the proposed viability-vulnerability tradeoff. METHODS We briefly review the literature on the factors contributing to primary and secondary sex ratios. Sex differences in fetal programming are assessed by summarizing previously published sex difference findings from our group (6 studies) and also new analyses of previously published findings in which sex differences were not reported (6 studies). RESULTS The review and reanalysis of studies from our group are consistent with the overwhelming evidence of increasing risk for viability among males exposed to environmental adversity early in life. New evidence reported here support the argument that females, despite their adaptive agility, also are influenced by exposure to early adversity. Two primary conclusions are (i) female fetal exposure to psychobiological stress selectively influences fear/anxiety, and (ii) the effects of female fetal exposure to stress persist into preadolescence. These persisting effects are reflected in increased levels of anxiety, impaired executive function and neurological markers associated with these behaviors. CONCLUSIONS A tacit assumption is that females, with their adaptive flexibility early in gestation, escape the consequences of early life exposure to adversity. We argue that the consequences of male exposure to early adversity threatens their viability, effectively culling the weak and the frail and creating a surviving cohort of the fittest. Females adjust to early adversity with a variety of strategies, but their escape from the risk of early mortality and morbidity has a price of increased vulnerability expressed later in development. PMID:24119938

Somatic complications of epilepsy surgery over 25 years at a single center.

PubMed

Gooneratne, Inuka K; Mannan, Shahidul; de Tisi, Jane; Gonzalez, Juan C; McEvoy, Andrew W; Miserocchi, Anna; Diehl, Beate; Wehner, Tim; Bell, Gail S; Sander, Josemir W; Duncan, John S

2017-05-01

Epilepsy surgery is an effective treatment for refractory focal epilepsy. Risks of surgery need to be considered when advising individuals of treatment options. We describe the frequency and nature of physical adverse events associated with epilepsy surgery in a single center. We reviewed the prospectively maintained records of adults who underwent epilepsy surgery at our center between 1990 and 2014 to identify peri/postsurgical adverse events. These were categorized into neurological deficits and those related to surgery (e.g. wound infections). Neurological deficits were categorized as expected or unexpected and into transient (≤3 months) or persistent (>3 months), RESULTS: There were 911 procedures with no peri-operative deaths. Persistent neurological adverse events were seen following 157 (17.2%) procedures. The most common persistent expected complication was quadrantanopia after temporal lobe resections (72/764, 9.4%). Unexpected persistent neurological complications occurred in 20 procedures (2.2%) and included: quadrantanopia (6, 0.7%); hemianopia (2, 0.2%); hemi/mono-paresis/sensory loss (9, 1%); dysphasia (10, 1%); frontalis muscle weakness (2, 0.2%); and oculomotor weakness (1, 0.1%). 106 surgery related adverse events occurred in 83 procedures, with severe infections requiring bone-flap removal in 24 (2.6%) procedures and intracranial infections in 8 (0.9%). The risk of post-resective severe infection increased by 4 fold (OR 4.32, 95% CI 2.1-8.9, p<0.001) with use of subdural EEG monitoring prior to resection. In consequence, in August 2011 we introduced antibiotic coverage in all individuals undergoing intracranial monitoring. Also, after August 2011 there was greater use of Stereo-EEG (SEEG) than subdural (OR 9.0 CI 0.36-224.2, p=0.18ns). One complicated by severe infection. Other surgical complications included haematoma (0.3%), hydrocephalus (0.3%) and CSF leak (1.2%). None had permanent complications. Adverse event rates are similar to other series. Epilepsy surgery carries well defined surgical and neurological risks. The risks of somatic adverse events, in addition to neuropsychiatric and neuropsychological complications need to be made clear to individuals considering this treatment option. Copyright © 2017 Elsevier B.V. All rights reserved.

Adherence, persistence, and medication discontinuation in patients with attention-deficit/hyperactivity disorder – a systematic literature review

PubMed Central

Gajria, Kavita; Lu, Mei; Sikirica, Vanja; Greven, Peter; Zhong, Yichen; Qin, Paige; Xie, Jipan

2014-01-01

Untreated attention-deficit/hyperactivity disorder (ADHD) can lead to substantial adverse social, economic, and emotional outcomes for patients. The effectiveness of current pharmacologic treatments is often reduced, due to low treatment adherence and medication discontinuation. This current systematic literature review analyzes the current state of knowledge surrounding ADHD medication discontinuation, focusing on: 1) the extent of patient persistence; 2) adherence; and 3) the underlying reasons for patients’ treatment discontinuation and how discontinuation rates and reasons vary across patient subgroups. We selected 91 original studies (67 with persistence/discontinuation results, 26 with adherence results, and 41 with reasons for discontinuation, switching, or nonadherence) and 36 expert opinion reviews on ADHD medication discontinuation, published from 1990 to 2013. Treatment persistence on stimulants, measured by treatment duration during the 12-month follow-up periods, averaged 136 days for children and adolescents and 230 days for adults. Owing to substantial study heterogeneity, comparisons across age or medication type subgroups were generally inconclusive; however, long-acting formulations and amphetamines were associated with longer treatment duration than short-acting formulations and methylphenidates. The medication possession ratio, used to measure adherence, was <0.7 for all age groups and medication classes during a 12-month period. Adverse effects were the most commonly cited reason for discontinuation in all studies. Original research studies reported the lack of symptom control as a common discontinuation reason, followed by dosing inconvenience, social stigma associated with ADHD medication, and the patient’s attitude. In summary, although there was a lack of consistency in the measurement of adherence and persistence, these findings indicate that drug adherence and persistence are generally poor among patients with ADHD. Clinicians may be able to help improve adherence and persistence to ADHD treatment by educating caregivers and patients on treatment goals, administering long-acting medications, and following-up with patients to verify if medication is still effective and well-tolerated. PMID:25187718

The risk for persistent adult alcohol and nicotine dependence: the role of childhood maltreatment.

PubMed

Elliott, Jennifer C; Stohl, Malka; Wall, Melanie M; Keyes, Katherine M; Goodwin, Renee D; Skodol, Andrew E; Krueger, Robert F; Grant, Bridget F; Hasin, Deborah S

2014-05-01

Alcohol and nicotine dependence are associated with considerable morbidity and mortality, especially when cases are persistent. The risk for alcohol and nicotine dependence is increased by childhood maltreatment. However, the influence of childhood maltreatment on dependence course is unknown, and is evaluated in the current study. Physical, sexual and emotional abuse, and physical and emotional neglect, were evaluated as predictors of persistent alcohol and nicotine dependence over 3 years of follow-up, with and without control for other childhood adversities. National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). NESARC participants completing baseline and follow-up who met criteria at baseline for past-year alcohol dependence (n = 1172) and nicotine dependence (n = 4017). Alcohol Use Disorder and Associated Disabilities Interview Schedule (AUDADIS) measures of alcohol/nicotine dependence, childhood maltreatment and other adverse childhood experiences (e.g. parental divorce). Controlling for demographics only, physical, sexual and emotional abuse and physical neglect predicted 3-year persistence of alcohol dependence [adjusted odds ratio (AOR) = 1.50-2.99; 95% CI = 1.04-4.68] and nicotine dependence (AOR = 1.37-1.74; 95% CI = 1.13-2.11). With other childhood adversities also controlled, maltreatment types remained predictive for alcohol persistence (AOR = 1.53-3.02; 95% CI = 1.07-4.71) and nicotine persistence (AOR = 1.35-1.72; 95% CI = 1.11-2.09). Further, a greater number of maltreatment types incrementally influenced persistence risk (AOR = 1.19-1.36; 95% CI = 1.11-1.56). A history of childhood maltreatment predicts persistent adult alcohol and nicotine dependence. This association, robust to control for other childhood adversities, suggests that maltreatment (rather than a generally difficult childhood) affects the course of dependence. © 2014 Society for the Study of Addiction.

Adverse Outcome Pathways and Ecological Risk Assessment: Bridging to Population Level Effects: Report of Pellston Workgroup 3

EPA Science Inventory

The continuing persistence and genetic diversity of populations is a key concern for environmental regulations. Population-level responses integrate the cumulative effects of chemical stressors on individuals as those individuals interact with and are affected by their con-speci...

Prenatal zinc supplementation of zinc-adequate rats adversely affects immunity in offspring

USDA-ARS?s Scientific Manuscript database

We previously showed that zinc (Zn) supplementation of Zn-adequate dams induced immunosuppressive effects that persist in the offspring after weaning. We investigated whether the immunosuppressive effects were due to in utero exposure and/or mediated via milk using a cross-fostering design. Pregnant...

From the Cradle to the Grave: The Effect of Adverse Caregiving Environments on Attachment and Relationships Throughout the Lifespan

PubMed Central

Doyle, Colleen; Cicchetti, Dante

2017-01-01

This paper reviews research examining the effects of adverse early caregiving on relationships throughout the lifespan. Central attachment constructs are summarized and integrated into a review of research on the long-term effects of institutional rearing and child maltreatment. Findings are interpreted within the organizational perspective on development, which conceptualizes attachment as a stage-salient task of infancy that influences the reorganization of adaptive/maladaptive functioning around subsequent stage-salient tasks. Children who experience adverse early caregiving are more likely to exhibit aberrant attachment behaviors, deficits in social-emotional competencies, and persisting difficulties in social functioning and relationship outcomes. Disorganized attachment behavior stemming from adverse early caregiving has been a major focus of this work. Intervention efforts that target mental representations related to attachment relationships can facilitate improved social functioning. Clinical implications of this work are discussed. PMID:28924334

Neuroendocrine Actions of Organohalogens: Thyroid Hormones, Arginine Vasopressin, and Neuroplasticity

EPA Science Inventory

Organohalogen compounds are global environmental pollutants. They are highly persistent, bioaccumulative, and cause adverse effects in humans and wildlife. Because of the widespread use of these organohalogens in household items and consumer products, indoor contamination may be ...

Neurotoxic, inflammatory, and mucosecretory responses in the nasal airways of mice repeatedly exposed to the macrocyclic trichothecene mycotoxin roridin A: dose-response and persistence of injury.

PubMed

Corps, Kara N; Islam, Zahidul; Pestka, James J; Harkema, Jack R

2010-04-01

Macrocyclic trichothecene mycotoxins encountered in water-damaged buildings have been suggested to contribute to illnesses of the upper respiratory tract. Here, the authors characterized the adverse effects of repeated exposures to roridin A (RA), a representative macrocyclic trichothecene, on the nasal airways of mice and assessed the persistence of these effects. Young, adult, female C57BL/6 mice were exposed to single daily, intranasal, instillations of RA (0.4, 2, 10, or 50 microg/kg body weight [bw]) in saline (50 microl) or saline alone (controls) over 3 weeks or 250 microg/kg RA over 2 weeks. Histopathologic, immunohistochemical, and morphometric analyses of nasal airways conducted 24 hr after the last instillation revealed that the lowest-effect level was 10 microg/kg bw. RA exposure induced a dose-dependent, neutrophilic rhinitis with mucus hypersecretion, atrophy and exfoliation of nasal transitional and respiratory epithelium, olfactory epithelial atrophy and loss of olfactory sensory neurons (OSNs). In a second study, the persistence of lesions in mice instilled with 250 microg/kg bw RA was assessed. Nasal inflammation and excess luminal mucus were resolved after 3 weeks, but OSN loss was still evident in olfactory epithelium (OE). These results suggest that nasal inflammation, mucus hypersecretion, and olfactory neurotoxicity could be important adverse health effects associated with short-term, repeated, airborne exposures to macrocyclic trichothecenes.

Iatrogenic hypervitaminosis D as an unusual cause of persistent vomiting: a case report.

PubMed

Bansal, Rinkesh Kumar; Tyagi, Pankaj; Sharma, Praveen; Singla, Vikas; Arora, Veronica; Bansal, Naresh; Kumar, Ashish; Arora, Anil

2014-02-26

Vitamin D is increasingly recognized to have several beneficial effects. Vitamin D deficiency is widely prevalent. Physicians often treat patients with high doses of vitamin D for various ailments without any monitoring for adverse effects and the prescribed doses often far exceed requirements resulting in toxicity. We present here a classic case of iatrogenic hypervitaminosis D, which presented with persistent vomiting and acute renal failure. Here we present a case of a 45-year-old Asian Indian woman who presented to us with persistent vomiting the cause of which was iatrogenic hypervitaminosis D. She was treated with intravenous fluid, diuretics and calcitonin and had clinical improvement. We suggest that in any patient presenting with persistent vomiting and hypercalcemia, particularly in the presence of normal parathyroid hormone, a diagnosis of overdose of vitamin D should be suspected. Its treatment not only alleviates symptoms but also prevents ongoing acute kidney injury.

Delayed adverse effects of neonatal exposure to diethylstilbestrol and their dose dependency in female rats.

PubMed

Yoshida, Midori; Takahashi, Miwa; Inoue, Kaoru; Hayashi, Seigo; Maekawa, Akihiko; Nishikawa, Akiyoshi

2011-08-01

Neonatal exposure to estrogenic chemicals causes irreversible complex damage to the hypothalamus-pituitary-gonadal axis and reproductive system in females. Some lesions are noted after maturation as delayed adverse effects. We investigated the characteristics and dose dependence of delayed effects using female rats neonatally exposed to diethylstilbestrol (DES). Female Donryu rats were subcutaneously injected with a single dose of DES of 0 (control), 0.15, 1.5, 15, 150, or 1,500 µg/kg bw after birth. All except the lowest dose had estrogenic activity in a uterotrophic assay. All rats at 1500 µg/kg and some at 150 µg/kg showed abnormal morphologies in the genital tract, indicating they were androgenized before maturation. Although no morphological abnormalities were noted at 15 µg/kg or lower, onset of persistent estrus was significantly accelerated in the 1.5, 15, and 150 µg/kg groups with dose dependency, and the latest onset was from seventeen to twenty-one weeks of age at 1.5 µg/kg. The neonatal exposure to DES increased uterine adenocarcinoma development only at 150 µg/kg, although uterine anomalies were detected at 1,500 µg/kg. These results indicate that neonatal exposure to DES, which exerts estrogenic activity in vivo, induces delayed adverse effects in female rats in a dose-dependent manner. Early onset of persistent estrus appears to be the most sensitive parameter.

The impact of childhood adversity on the persistence of psychotic symptoms: a systematic review and meta-analysis.

PubMed

Trotta, A; Murray, R M; Fisher, H L

2015-01-01

Evidence suggests that childhood adversity is associated with the development of psychotic experiences (PE), psychotic symptoms and disorders. However, less is known regarding the impact of early adversity on the persistence of PE and clinically relevant psychosis. Thus we conducted a systematic review of the association between childhood adversity and the course of PE and symptoms over time. A systematic search of Medline, EMBASE and PsychINFO databases was undertaken to identify articles published between January 1956 and November 2014. We included studies conducted on general population samples, individuals at ultra-high risk (UHR) of psychosis, and patients with full-blown psychotic disorders. A meta-analysis was performed on a subgroup. A total of 20 studies were included. Of these, 17 reported positive associations between exposure to overall or specific subtypes of childhood adversity and persistence of PE or clinically relevant psychotic symptoms. A meta-analysis of nine studies yielded a weighted odds ratio of 1.76 [95% confidence interval (CI) 1.19-2.32, p < 0.001] for general population studies and 1.55 (95% CI 0.32-2.77, p = 0.007) for studies conducted using clinical populations. The available evidence is limited but tentatively suggests that reported exposure to adverse events in childhood is associated with persistence of PE and clinically relevant psychotic symptoms. This partially strengthens the case for addressing the consequences of early adversity in individuals presenting with psychotic phenomena to improve long-term outcomes. However, the heterogeneity of studies was high which urges caution in interpreting the results and highlights the need for more methodologically robust studies.

Adverse Effects of Electroconvulsive Therapy.

PubMed

Andrade, Chittaranjan; Arumugham, Shyam Sundar; Thirthalli, Jagadisha

2016-09-01

Electroconvulsive therapy (ECT) is an effective treatment commonly used for depression and other major psychiatric disorders. We discuss potential adverse effects (AEs) associated with ECT and strategies for their prevention and management. Common acute AEs include headache, nausea, myalgia, and confusion; these are self-limiting and are managed symptomatically. Serious but uncommon AEs include cardiovascular, pulmonary, and cerebrovascular events; these may be minimized with screening for risk factors and by physiologic monitoring. Although most cognitive AEs of ECT are short-lasting, troublesome retrograde amnesia may rarely persist. Modifications of and improvements in treatment techniques minimize cognitive and other AEs. Copyright © 2016 Elsevier Inc. All rights reserved.

POSSIBLE EFFECTS OF CHRONIC EXPOSURE TO ENVIRONMENTAL AIRBORNE MANGANESE ON NEUROLOGICAL FUNCTION IN CHILDREN.

EPA Science Inventory

Evidence suggests that the estuarine dinoflagellate, Pfiesteria piscicida, and/or morphologically related organisms (Pf-MRO) may release a toxin(s) which kills fish and adversely affects human health. The North Carolina study investigated the potential for persistent health effec...

Evaluating Chemical Persistence in a Multimedia Environment: ACART Analysis

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

Bennett, D.H.; McKone, T.E.; Kastenberg, W.E.

1999-02-01

For the thousands of chemicals continuously released into the environment, it is desirable to make prospective assessments of those likely to be persistent. Persistent chemicals are difficult to remove if adverse health or ecological effects are later discovered. A tiered approach using a classification scheme and a multimedia model for determining persistence is presented. Using specific criteria for persistence, a classification tree is developed to classify a chemical as ''persistent'' or ''non-persistent'' based on the chemical properties. In this approach, the classification is derived from the results of a standardized unit world multimedia model. Thus, the classifications are more robustmore » for multimedia pollutants than classifications using a single medium half-life. The method can be readily implemented and provides insight without requiring extensive and often unavailable data. This method can be used to classify chemicals when only a few properties are known and be used to direct further data collection. Case studies are presented to demonstrate the advantages of the approach.« less

Efficacy and safety of oxymetazoline cream 1.0% for treatment of persistent facial erythema associated with rosacea: Findings from the 52-week open label REVEAL trial.

PubMed

Draelos, Zoe Diana; Gold, Michael H; Weiss, Robert A; Baumann, Leslie; Grekin, Steven K; Robinson, Deanne Mraz; Kempers, Steven E; Alvandi, Nancy; Weng, Emily; Berk, David R; Ahluwalia, Gurpreet

2018-06-01

Limited treatments are available for persistent erythema of rosacea. To examine the long-term safety and efficacy of oxymetazoline cream 1.0% in patients with rosacea with moderate-to-severe persistent erythema. Patients applied oxymetazoline once daily for 52 weeks. Safety assessments included treatment-emergent adverse events (TEAEs), skin blanching, inflammatory lesion counts, telangiectasia, disease severity, and rebound effect. Efficacy was assessed by the Clinician Erythema Assessment and Subject Self-Assessment composite score at 3 and 6 hours after the dose on day 1 and at weeks 4, 26, and 52. Among 440 patients, 8.2% reported treatment-related TEAEs; the most common were application-site dermatitis, paresthesia, pain, and pruritus. The rate of discontinuation due to adverse events (mostly application-site TEAEs) was 3.2%. No clinically meaningful changes were observed in skin blanching, inflammatory lesions, or telangiectasia. At week 52, 36.7%, and 43.4% of patients achieved a 2-grade or greater composite improvement from baseline in both Clinician Erythema Assessment and Subject Self-Assessment 3 and 6 hours after a dose, respectively. Less than 1% of patients experienced a rebound effect following treatment cessation. A vehicle-control group was not included. This long-term study demonstrated sustained safety, tolerability, and efficacy of oxymetazoline for moderate-to-severe persistent erythema of rosacea. Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Long term effects of early adversity on cognitive function.

PubMed

Richards, M; Wadsworth, M E J

2004-10-01

To investigate long term effects of early adverse circumstances on cognitive function. Associations between early material home circumstances, parental divorce, maternal management and understanding, and cognitive function in childhood, adolescence, and adulthood were analysed using multiple linear regression, controlling for sex, parental SES, and birth order in 1339 males and females from the MRC National Survey of Health and Development. Early adverse circumstances were strongly associated with lower cognitive ability in childhood and adolescence, and were detectable on measures of verbal ability, memory, and speed and concentration in midlife. However, these long term effects were mostly explained by the effects of adversity on childhood or adolescent cognitive ability or by differences in educational attainment and adult social class. An exception was the effect of poor material home conditions on visual search speed at 53 years, which was maintained after controlling for adolescent ability, as well as further control for educational attainment, adult social class, physical growth, cigarette smoking, and affective state. There was no evidence of more rapid decline in memory and psychomotor function across middle age in those exposed to early adversity. The effect of early adversity on cognitive function tracks across the life course at least as far as middle age, although there was little evidence from this study of effect amplification over this interval. Nevertheless, in view of the persistence of child poverty in the industrialised world, these findings give cause for concern.

Gene expression profiles in the cerebellum and hippocampus following exposure to a neurotoxicant, Aroclor 1254: Developmental effects.

EPA Science Inventory

The developmental consequences of exposure to the polychlorinated biphenyls (PCBs) have been widely studied, making PCBs a unique model to understand issues related to environmental mixture of persistent chemicals. PCB exposure in humans adversely affects neurocognitive developm...

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...

Mindfulness and zest for life buffer the negative effects of experimentally-induced perceived burdensomeness and thwarted belongingness: Implications for theories of suicide.

PubMed

Collins, Khan R L; Best, Ida; Stritzke, Werner G K; Page, Andrew C

2016-07-01

Suicide research can be enhanced by an ability to safely manipulate putative causal variables. The present studies developed an experimental task to modify risk factors identified by the interpersonal theory of suicide (perceived burdensomeness and thwarted belongingness) and examine their hypothesized suppressive effect on persistence in adversity in undergraduate university students. Variables that may moderate the impact of these risk factors on persistence (zest for life and mindful awareness) were incorporated as potential resilience factors. Study 1 (N = 92) found elevated burdensomeness and diminished belongingness significantly impaired persistence. Additionally, these predicted effects were moderated by individual differences in zest for life. In Study 2 (N = 52), individuals trained in mindfulness prior to the experimental task displayed greater persistence relative to controls. Findings provide experimental support for the role of perceived burdensomeness and thwarted belongingness in the manner predicted by the interpersonal theory, and demonstrate a way to experimentally test the effects of resilience factors that reduce the impact of these interpersonal factors. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Industrial wind turbines and adverse health effects.

PubMed

Jeffery, Roy D; Krogh, Carmen M E; Horner, Brett

2014-01-01

Some people living in the environs of industrial wind turbines (IWTs) report experiencing adverse health and socioeconomic effects. This review considers the hypothesis that annoyance from audible IWTs is the cause of these adverse health effects. We searched PubMed and Google Scholar for articles published since 2000 that included the terms "wind turbine health," "wind turbine infrasound," "wind turbine annoyance," "noise annoyance" or "low frequency noise" in the title or abstract. Industrial wind turbines produce sound that is perceived to be more annoying than other sources of sound. Reported effects from exposure to IWTs are consistent with well-known stress effects from persistent unwanted sound. If placed too close to residents, IWTs can negatively affect the physical, mental and social well-being of people. There is sufficient evidence to support the conclusion that noise from audible IWTs is a potential cause of health effects. Inaudible low-frequency noise and infrasound from IWTs cannot be ruled out as plausible causes of health effects.

Cumulative trauma, adversity and grief symptoms associated with fronto-temporal regions in life-course persistent delinquent boys.

PubMed

Lansing, Amy E; Virk, Agam; Notestine, Randy; Plante, Wendy Y; Fennema-Notestine, Christine

2016-08-30

Delinquent youth have substantial trauma exposure, with life-course persistent delinquents [LCPD] demonstrating notably elevated cross-diagnostic psychopathology and cognitive deficits. Because adolescents remain in the midst of brain and neurocognitive development, tailored interventions are key to improving functional outcomes. This structural magnetic resonance imaging study compared neuroanatomical profiles of 23 LCPD and 20 matched control adolescent boys. LCPD youth had smaller overall gray matter, and left hippocampal, volumes alongside less cortical surface area and folding within the left pars opercularis and supramarginal cortex. LCPD youth had more adversity-related exposures, and their higher Cumulative Trauma, Adversity and Grief [C-TAG] symptoms were associated with less surface area and folding in the pars opercularis and lingual gyrus. Neuroanatomical differences between LCPD and control youth overlap with data from both maltreatment and antisocial literatures. The affected left frontal regions also share connections to language- and executive-related functions, aligning well with LCPD youths' cognitive and behavioral difficulties. These data also dovetail with research suggesting the possibility of neurodevelopmental delays or disruptions related to cumulative adversity burden. Thus, concurrent treatment of LCPD youths' C-TAG symptoms and, cognitive deficits with overlapping neuroanatomical bases, may be most effective in improving outcomes and optimizing neurodevelopmental trajectories. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Immediate effects of lumacaftor/ivacaftor administration on lung function in patients with severe cystic fibrosis lung disease.

PubMed

Popowicz, Natalia; Wood, Jamie; Tai, Anna; Morey, Sue; Mulrennan, Siobhain

2017-05-01

Safety-data for lumacaftor/ivacaftor (LUM/IVA) combination therapy in patients with severe lung disease (percent predicted forced expiratory volume in 1s [ppFEV 1 ] <40) remain limited. We report immediate post-dose respiratory-related adverse events in 12 patients with severe cystic fibrosis (CF) lung disease (median [IQR] ppFEV 1 : 34 [31-36]) prescribed LUM/IVA. All patients experienced a decline in ppFEV 1 from baseline at 2-hours (median [IQR] relative change: -19 [-21 to -11]%, p<0.001) that persisted at 24-hours but recovered in most patients at 1-month. No pre- and post-differences in bronchodilator response were observed. Ten (83.3%) patients reported non-severe respiratory-related adverse events within 24-hours of LUM/IVA initiation. At 1-month, eight (67%) patients had persistent symptoms and six (50%) were treated for a pulmonary exacerbation. Our results highlight that LUM/IVA respiratory-related adverse events are common in patients with a ppFEV 1 <40. We recommend close assessment of adverse events. Further studies are required to evaluate the efficacy of LUM/IVA in patients with severe lung disease. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Phentolamine mesylate to reverse oral soft-tissue local anesthesia: A systematic review and meta-analysis.

PubMed

Prados-Frutos, Juan Carlos; Rojo, Rosa; González-Serrano, José; González-Serrano, Carlos; Sammartino, Gilberto; Martínez-González, José María; Sánchez-Monescillo, Andrés

2015-10-01

Knowing that patients desire reduced duration of local anesthesia, the authors performed a meta-analysis to evaluate the efficacy of phentolamine mesylate (PM) in reducing anesthesia duration and the occurrence of adverse effects. The authors searched studies in 4 electronic databases up to December 18, 2014. For each study, the methodological quality was assessed according to the Cochrane Collaboration's tool for assessing risk of bias. Randomized controlled trials (RCTs) that used PM met the inclusion criteria. Six RCTs met the inclusion criteria and were used to carry out a meta-analysis of the effectiveness of PM and a qualitative analysis of its adverse effects. The use of PM was more effective in reversing the anesthetic effect on the lower lip and tongue than was applying a placebo. Adverse effects reported in the studies were not statistically significant, the most frequent being headache, pain during injection, and postprocedure pain. Based on limited evidence, PM is effective in reducing the persistence of anesthesia duration on the lower lip and tongue, with infrequent adverse effects of little clinical significance. Copyright © 2015 American Dental Association. Published by Elsevier Inc. All rights reserved.

The wage effects of obesity: a longitudinal study.

PubMed

Baum, Charles L; Ford, William F

2004-09-01

We use National Longitudinal Survey of Youth (NLSY) data to examine the effects of obesity on wages by gender. Sample means indicate that both men and women experience a persistent obesity wage penalty over the first two decades of their careers. We then control for a standard set of socioeconomic and familial variables but find that standard covariates do not explain why obese workers experience persistent wage penalties. This suggests that other variables -- including job discrimination, health-related factors and/or obese workers' behavior patterns -- may be the channels through which obesity adversely affects wages. The study closes with a discussion of the public policy implications suggested by these findings.

EXPOSURE TO AREA-LEVEL PRETERM BIRTH DISPARITY AND EFFECTS ON BIRTH OUTCOMES

EPA Science Inventory

Black–white disparity in preterm birth (PTB) is persistent and not explained by individual factors. Given that exposure to inequality is associated with increased risk of adverse health, we examined PTB risk (birth <37 weeks gestational age) explained by living in U.S. census tra...

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

PubMed Central

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

2017-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2017-01-01

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

Iatrogenic hypervitaminosis D as an unusual cause of persistent vomiting: a case report

PubMed Central

2014-01-01

Introduction Vitamin D is increasingly recognized to have several beneficial effects. Vitamin D deficiency is widely prevalent. Physicians often treat patients with high doses of vitamin D for various ailments without any monitoring for adverse effects and the prescribed doses often far exceed requirements resulting in toxicity. We present here a classic case of iatrogenic hypervitaminosis D, which presented with persistent vomiting and acute renal failure. Case presentation Here we present a case of a 45-year-old Asian Indian woman who presented to us with persistent vomiting the cause of which was iatrogenic hypervitaminosis D. She was treated with intravenous fluid, diuretics and calcitonin and had clinical improvement. Conclusions We suggest that in any patient presenting with persistent vomiting and hypercalcemia, particularly in the presence of normal parathyroid hormone, a diagnosis of overdose of vitamin D should be suspected. Its treatment not only alleviates symptoms but also prevents ongoing acute kidney injury. PMID:24571630

Occupational exposure associated with reproductive dysfunction.

PubMed

Kumar, Sunil

2004-01-01

Evidence suggestive of harmful effects of occupational exposure on the reproductive system and related outcomes has gradually accumulated in recent decades, and is further compounded by persistent environmental endocrine disruptive chemicals. These chemicals have been found to interfere with the function of the endocrine system, which is responsible for growth, sexual development and many other essential physiological functions. A number of occupations are being reported to be associated with reproductive dysfunction in males as well as in females. Generally, occupations involving the manufacture/or application of some of the persistent chemicals that are not easily degradable as well as bio-accumulative chemicals, occupations involving intensive exposure to heat and radiation, occupations involving the use of toxic solvents as well as toxic fumes are reported to be associated with reproductive dysfunction. Occupational exposure of males to various persistent chemicals have been reported to have male mediated adverse reproductive outcomes in the form of abortion, reduction in fertility etc. with inconclusive or limited evidence. Nevertheless, there is a need for more well designed studies in order to implicate any individual chemical having such effects as in most occupations workers are exposed to raw, intermediate and finished products and there are also several confounding factors associated with lifestyles responsible for reproductive dysfunction. There is an urgent need to look at indiscriminate use of persistent chemicals especially pesticides and persistent organic pollutants (POP's) as these chemicals enter the food chain also and could be potential for exposure during the critical period of development. It is also necessary to impart information, and to educate about the safe use of these chemicals, as a very sensitive reproduction issue is involved with exposure to these chemicals. Occupational exposures often are higher than environmental exposures, so that epidemiological studies should be conducted on these chemicals, on a priority basis, which are reported to have adverse effects on reproduction in the experimental system.

Systematic review of adverse outcomes of external cephalic version and persisting breech presentation at term.

PubMed

Nassar, Natasha; Roberts, Christine L; Barratt, Alexandra; Bell, Jane C; Olive, Emily C; Peat, Brian

2006-03-01

The aim of this study was to determine the frequency of adverse maternal and fetal outcomes of both external cephalic version (ECV) and persisting breech presentation at term. We conducted a systematic review of the literature using Medline, Embase and All Evidence Based Medicine (EBM) Reviews databases. Data were extracted from studies that compared women who had an ECV from 36 weeks' gestation with a similar control group of women enrolled at the same gestational age, eligible for, but who did not have an ECV. Eleven studies with a total of 2503 women were included. Adverse outcomes related to ECV were rarely reported and in most studies there was no evidence that relevant outcomes were ascertained among similar women who did not have an ECV. There was no increased risk of antepartum fetal death associated with ECV, but numbers were small. There were no reported cases of uterine rupture, placental abruption, prelabour rupture of membranes or cord prolapse, but these outcomes were not examined among controls. Onset of labour within 24 h and nuchal cord was non-significantly higher among women who had an ECV compared with those with a persisting breech. Despite limited reporting and small numbers, the results of our review suggest that adverse maternal and fetal outcomes of both ECV and persisting breech presentation are rare. Only with improved reporting and collection of safety data on ECV and persisting breech presentation can we provide high-quality information to assist informed decision making by pregnant women with a breech presentation at term.

Persistent effects of chlorine inhalation on respiratory health

PubMed Central

Hoyle, Gary W.; Svendsen, Erik R.

2016-01-01

Chlorine gas is a toxic respiratory irritant that is considered a chemical threat agent because of the potential for release in industrial accidents or terrorist attacks. Chlorine inhalation damages the respiratory tract, including the airways and distal lung, and can result in acute lung injury. Some individuals exposed to chlorine experience a full recovery from acute injury, whereas others develop persistent adverse effects, such as respiratory symptoms, inflammation, and lung-function decrements. In animal models, chlorine can produce persistent inflammation, remodeling, and obstruction in large or small airways, depending on species. Airways with pseudostratified epithelium are repaired efficiently, with surviving basal epithelial cells serving as progenitor cells that repopulate the complement of differentiated cell types. Distal airways lacking basal cells are repaired less efficiently, leading to chronic inflammation and fibrosis at these sites. Persistent chlorine-induced airway disease in humans is treated with asthma medication to relieve symptoms. However, such treatment does not ameliorate the underlying disease pathogenesis, so treatments that are more effective at preventing initial development of airway disease after irritant gas exposure and at reversing established disease are needed. PMID:27385061

Intermittent blood pressure control: potential consequences for outcome.

PubMed

Leenen, F H

1999-05-01

Although both blood pressure (BP) and left ventricular (LV) mass at initial evaluation predict future cardiovascular risk, the actual BP and LV mass achieved over years of treatment more clearly relate to cardiovascular event rates. Intermittent compliance or noncompliance is the major reason for uncontrolled hypertension and presumably persistent LV hypertrophy. In general, drugs with rapid onset and short duration of action are not desirable because this profile may lead to large variations in BP lowering effect during actual drug intake and rapid disappearance of the antihypertensive effect with missed doses. In addition, intermittent compliance per se introduces the potential for adverse events. For drugs requiring several dose-titrations (e.g., alpha1-blockers), restarting at full doses may lead to excessive drug action and symptomatic hypotension. For other drugs (e.g., short acting beta-blockers or clonidine-like drugs), sudden discontinuation with intermittent compliance may lead to rebound-enhanced sympathetic responsiveness after one to two days, resulting not only in side effects, but also in adverse events, particularly in patients with (silent) coronary artery disease. The rapid onset, short acting dihydropyridines cause intermittent BP control at each dosing, particularly at higher doses. This intermittent control of BP is even more apparent at dosing intervals that are long relative to the duration of action. Thus, sympathetic activation and potential for adverse events can be anticipated at each dosing unless these drugs are being taken frequently at relatively low doses. For diuretics, angiotensin-converting enzyme inhibitors and angiotensin I receptor blockers, no adverse effects have been identified with intermittent compliance. Intermittent BP control is, in general, not an appropriate approach to the management of hypertension and introduces additional risks depending on the type of antihypertensive drug. In contrast, drugs with slow onset and long duration of action provide a more consistent effect during actual drug intake and a more persistent effect during short periods of noncompliance.

Developmental Programming: Priming Disease Susceptibility for Subsequent Generations.

PubMed

Messer, L C; Boone-Heinonen, J; Mponwane, L; Wallack, L; Thornburg, K L

2015-03-01

Racial and/or ethnic minorities carry the highest burden of many adverse health outcomes intergenerationally We propose a paradigm in which developmental programming exacerbates the effects of racial patterning of adverse environmental conditions, thereby contributing to health disparity persistence. Evidence that developmental programming induces a heightened response to adverse exposures ("second hits") encountered later in life is considered. We evaluated the evidence for the second hit phenomenon reported in animal and human studies from three domains (air, stress, nutrition). Original research including a gestational exposure and a childhood or adulthood second hit exposure was reviewed. Evidence from animal studies suggest that prenatal exposure to air pollutants is associated with an exaggerated reaction to postnatal air pollution exposure, which results in worse health outcomes. It also indicates offspring exposed to prenatal maternal stress produce an exaggerated response to subsequent stressors, including anxiety and hyper-responsiveness of the hypothalamic-pituitary-adrenal axis. Similarly, prenatal and postnatal Western-style diets induce synergistic effects on weight gain, metabolic dysfunction, and atherosclerotic risk. Cross-domain second hits (e.g., gestational air pollution followed by childhood stressor) were also considered. Suboptimal gestational environments induce exaggerated offspring responses to subsequent environmental and social exposures. These developmental programming effects may result in enhanced sensitivity of ongoing, racially patterned, adverse exposures in race/ethnic minorities, thereby exacerbating health disparities from one generation to the next. Empirical assessment of the hypothesized role of priming processes in the propagation of health disparities is needed. Future social epidemiology research must explicitly consider synergistic relationships among social environmental conditions to which gestating females are exposed and offspring exposures when assessing causes for persistent health disparities.

Developmental Programming: Priming Disease Susceptibility for Subsequent Generations

PubMed Central

Boone-Heinonen, J.; Mponwane, L.; Wallack, L.; Thornburg, K. L.

2015-01-01

Racial and/or ethnic minorities carry the highest burden of many adverse health outcomes intergenerationally We propose a paradigm in which developmental programming exacerbates the effects of racial patterning of adverse environmental conditions, thereby contributing to health disparity persistence. Evidence that developmental programming induces a heightened response to adverse exposures (“second hits”) encountered later in life is considered. We evaluated the evidence for the second hit phenomenon reported in animal and human studies from three domains (air, stress, nutrition). Original research including a gestational exposure and a childhood or adulthood second hit exposure was reviewed. Evidence from animal studies suggest that prenatal exposure to air pollutants is associated with an exaggerated reaction to postnatal air pollution exposure, which results in worse health outcomes. It also indicates offspring exposed to prenatal maternal stress produce an exaggerated response to subsequent stressors, including anxiety and hyper-responsiveness of the hypothalamic–pituitary–adrenal axis. Similarly, prenatal and postnatal Western-style diets induce synergistic effects on weight gain, metabolic dysfunction, and atherosclerotic risk. Cross-domain second hits (e.g., gestational air pollution followed by childhood stressor) were also considered. Suboptimal gestational environments induce exaggerated offspring responses to subsequent environmental and social exposures. These developmental programming effects may result in enhanced sensitivity of ongoing, racially patterned, adverse exposures in race/ethnic minorities, thereby exacerbating health disparities from one generation to the next. Empirical assessment of the hypothesized role of priming processes in the propagation of health disparities is needed. Future social epidemiology research must explicitly consider synergistic relationships among social environmental conditions to which gestating females are exposed and offspring exposures when assessing causes for persistent health disparities. PMID:26366336

Understanding patient compliance and persistence with osteoporosis therapy.

PubMed

Gold, Deborah T

2011-04-01

Chronic non-terminal diseases, including postmenopausal osteoporosis, are associated with poor treatment compliance and persistence. The longer a patient with osteoporosis complies and persists with treatment, the lower the risk of fracture. Retrospective studies with emphasis on real-world data have led to a greater understanding of the factors affecting medication compliance and persistence, and their association with improved treatment outcomes. However, these data do not contain information about patient choices of medication or patient commitment to particular medication regimens. Patient preferences can affect compliance and persistence behaviours. While recent evidence questions the importance of dosing regimen in patient preferences, other recent data show that medication efficacy and safety remain the most important determinants of patient preference. Informed patient decision making about treatment options, adverse effects and outcomes can have a beneficial impact on medication-taking behaviour. Healthcare professionals play a crucial role in the management of factors associated with poor compliance and persistence with osteoporosis therapies. Education about disease consequences and differences among treatment options, as well as treatment monitoring and positive reinforcement, are crucial to improving medication compliance and persistence in osteoporotic patients.

Chronic exposure to adverse psychosocial work factors and high psychological distress among white-collar workers: A 5-year prospective study.

PubMed

Ndjaboue, Ruth; Brisson, Chantal; Talbot, Denis; Vézina, Michel

2017-03-01

Prospective studies which evaluated whether the effects of chronic exposure to psychosocial work factors on mental health persisted over time are scarce. For the first time, this study evaluated: 1) the effect of chronic exposure to effort-reward imbalance over 5years on the prevalence of high psychological distress among men and women, and 2) the persistence of this effect over time. Overall, 1747 white-collar workers from three public organizations participated in a prospective study. Psychological distress and effort-reward imbalance were measured using validated questionnaires at baseline, and at 3- and 5-year follow-ups. Prevalence ratios (PRs) of high psychological distress were estimated using log-binomial regression according to baseline and repeated exposure. Compared to unexposed workers, those with repeated exposure to effort-reward imbalance had a higher prevalence of high psychological distress. Workers exposed only at some time-points also had a higher prevalence. The deleterious effect of repeated exposure observed at the 3-year follow-up persisted at the 5-year follow-up among women (PR=2.48 95% confidence interval (CI) 1.97-3.11) and men (PR=1.91 95% CI 1.20-3.04). These effects were greater than those found using a single baseline measurement. The current study supported a deleterious effect of repeated exposure to effort-reward imbalance on psychological distress, and a lack of adaptation to these effects over time among men and women. Since psychological distress may later lead to severe mental problems, current results highlight the need to consider exposure to these adverse work factors in primary and secondary preventions aimed at reducing mental health problems at work. Copyright © 2017 Elsevier Inc. All rights reserved.

Discrepancies in the evaluation of the safety of the human papillomavirus vaccine.

PubMed

Cervantes, Jorge L; Doan, Amy Hoanganh

2018-01-01

Despite being more than ten years since its introduction, global acceptance to the human papillomavirus (HPV) vaccine is still low. The immunogenetic background of the host, and HPV antigen recognition, are important in natural HPV infection, and should be taken into account in the understanding of adverse autoimmune reactions by the HPV vaccine in certain groups. There is no doubt of the benefit of vaccines in the reduction of the incidence of infectious diseases, and in the case of HPV, the prevention of persistent infection that would lead to cervical cancer. Side-effects, however, should be closely monitored and reported without any bias, to ensure that the benefits of vaccines outweigh the risks of adverse reactions. In this article we bring the attention on certain adverse effects of the vaccine against HPV that have not been well studied as they are not well defined. We also compare the different approaches on HPV vaccine policies regarding its adverse reactions in countries like Japan and Colombia, vs. the recommendations issued by the WHO.

A Discordant Monozygotic Twin Design Shows Blunted Cortisol Reactivity among Bullied Children

ERIC Educational Resources Information Center

Ouellet-Morin, Isabelle; Danese, Andrea; Bowes, Lucy; Shakoor, Sania; Ambler, Antony; Pariante, Carmine M.; Papadopoulos, Andrew S.; Caspi, Avshalom; Moffitt, Terrie E.; Arseneault, Louise

2011-01-01

Objective: Childhood adverse experiences are known to engender persistent changes in stress-related systems and brain structures involved in mood, cognition, and behavior in animal models. Uncertainty remains about the causal effect of early stressful experiences on physiological response to stress in human beings, as the impact of these…

40 CFR 158.34 - Flagging of studies for potential adverse effects.

Code of Federal Regulations, 2013 CFR

2013-07-01

... in malformations, pre- or post-natal deaths, or persistent functional or behavioral changes on a... statistically significant (pairwise p≤0.05) increase of any type of neoplasm in any test group, males or females... type of uncommon or rare neoplasms in any test group, males or females animals at any dose level...

40 CFR 158.34 - Flagging of studies for potential adverse effects.

Code of Federal Regulations, 2010 CFR

2010-07-01

... in malformations, pre- or post-natal deaths, or persistent functional or behavioral changes on a... statistically significant (pairwise p≤ 0.05) increase of any type of neoplasm in any test group, males or... type of uncommon or rare neoplasms in any test group, males or females animals at any dose level...

40 CFR 158.34 - Flagging of studies for potential adverse effects.

Code of Federal Regulations, 2011 CFR

2011-07-01

... in malformations, pre- or post-natal deaths, or persistent functional or behavioral changes on a... statistically significant (pairwise p≤ 0.05) increase of any type of neoplasm in any test group, males or... type of uncommon or rare neoplasms in any test group, males or females animals at any dose level...

40 CFR 158.34 - Flagging of studies for potential adverse effects.

Code of Federal Regulations, 2014 CFR

2014-07-01

... in malformations, pre- or post-natal deaths, or persistent functional or behavioral changes on a... statistically significant (pairwise p≤0.05) increase of any type of neoplasm in any test group, males or females... type of uncommon or rare neoplasms in any test group, males or females animals at any dose level...

40 CFR 158.34 - Flagging of studies for potential adverse effects.

Code of Federal Regulations, 2012 CFR

2012-07-01

... in malformations, pre- or post-natal deaths, or persistent functional or behavioral changes on a... statistically significant (pairwise p≤0.05) increase of any type of neoplasm in any test group, males or females... type of uncommon or rare neoplasms in any test group, males or females animals at any dose level...

Persistent Oxytetracycline Exposure Induces an Inflammatory Process That Improves Regenerative Capacity in Zebrafish Larvae

PubMed Central

Barros-Becker, Francisco; Romero, Jaime; Pulgar, Alvaro; Feijóo, Carmen G.

2012-01-01

Background The excessive use of antibiotics in aquaculture can adversely affect not only the environment, but also fish themselves. In this regard, there is evidence that some antibiotics can activate the immune system and reduce their effectiveness. None of those studies consider in detail the adverse inflammatory effect that the antibiotic remaining in the water may cause to the fish. In this work, we use the zebrafish to analyze quantitatively the effects of persistent exposure to oxytetracycline, the most common antibiotic used in fish farming. Methodology We developed a quantitative assay in which we exposed zebrafish larvae to oxytetracycline for a period of 24 to 96 hrs. In order to determinate if the exposure causes any inflammation reaction, we evaluated neutrophils infiltration and quantified their total number analyzing the Tg(mpx:GFP)i114 transgenic line by fluorescence stereoscope, microscope and flow cytometry respectively. On the other hand, we characterized the process at a molecular level by analyzing several immune markers (il-1β, il-10, lysC, mpx, cyp1a) at different time points by qPCR. Finally, we evaluated the influence of the inflammation triggered by oxytetracycline on the regeneration capacity in the lateral line. Conclusions Our results suggest that after 48 hours of exposure, the oxytetracycline triggered a widespread inflammation process that persisted until 96 hours of exposure. Interestingly, larvae that developed an inflammation process showed an improved regeneration capacity in the mechanosensory system lateral line. PMID:22590621

TOOL FOR MONITORING HYDROPHILIC CONTAMINANTS ...

EPA Pesticide Factsheets

Global emissions of persistent bioconcentratable organic chemicals have resulted in a wide range of adverse ecological effects. Consequently, industry was led to develop less persistent, more water soluble, polar or hydrophilic organic compounds (HpOCs), which generally have low bioconcentration factors. However, evidence is growing that the large fluxes of these seemingly more environmentally friendly compounds (e.g., pesticides, prescription and non-prescription drugs, personal care and common consumer products, industrial and domestic-use chemicals and their degradation products) into aquatic systems on a world-wide basis may be responsible for incidents of acute toxicity and sub-lethal chronic abnormalities. These adverse effects include altered behavior, neurotoxicity, and severely impaired reproduction. Furthermore, the presence of these HpOCs likely plays a major role in the endocrine disrupting effects of complex mixtures of chemicals present in aquatic environments. In regard to physiological effects, pharmaceuticals are of particular concern because they are designed to elicit diverse pharmacological responses at very low doses. Unfortunately, the effects of this class of HpOCs on non-target, aquatic organisms are largely unknown. The research focused on in the subtasks is the development and application of state-of the-art technologies to meet the needs of the public, Office of Water, and ORD in the area of Water Quality. Located In the subtasks are

Chloramphenicol Toxicity Revisited: A 12-Year-Old Patient With a Brain Abscess

PubMed Central

Wiest, Donald B.; Cochran, Joel B.; Tecklenburg, Fred W.

2012-01-01

Chloramphenicol, a broad-spectrum antibiotic, is rarely used in the United States due to its well-described adverse effects. Because of its limited use, many clinicians are unfamiliar with its indications, spectrum of activity, and potential adverse drug effects. We describe a 12-year-old patient who presented after two craniotomies for a persistent brain abscess complicated by long-term chloramphenicol administration. Findings for this patient were consistent with many of the adverse drug effects associated with chloramphenicol, including elevated chloramphenicol serum concentrations, anemia, thrombocytopenia, reticulocytopenia, and severe metabolic acidosis. Rare manifestations of chloramphenicol toxicity that developed in this patient included neutropenia, visual field changes, and peripheral neuropathy. Chloramphenicol administration was discontinued, and hemodialysis was initiated for severe metabolic acidosis. The patient recovered with severe visual field deficits. Although chloramphenicol is rarely indicated, it remains an effective antibiotic. Healthcare providers should become familiar with the pharmacology, toxicology, and monitoring parameters for appropriate use of this antibiotic. PMID:23118672

Childhood personality as a harbinger of competence and resilience in adulthood.

PubMed

Shiner, Rebecca L; Masten, Ann S

2012-05-01

This study examined the significance of childhood Big Five personality traits for competence and resilience in early adulthood. Resilience was defined in terms of adaptive success in age-salient developmental tasks despite significant adversity throughout childhood/adolescence. The Project Competence Longitudinal Study tracked 205 young people from childhood (around age 10) to emerging adulthood (EA, age 20) and young adulthood (YA, age 30; 90% retention). Multimethod composites were created for personality traits, adversity exposure, and adult outcomes of academic achievement, work, rule-abiding conduct, friendship, and romantic relationships. Regressions showed significant main effects of childhood personality predicting adult outcomes, controlling for adversity, with few interaction effects. In person-focused analyses, the resilient group in EA and YA (high competence, high adversity) showed higher childhood conscientiousness, agreeableness, and openness and lower neuroticism than the maladaptive group (low competence, high adversity). The competent (high competence, low adversity) and resilient groups showed similar childhood traits. Turnaround cases, who changed from the maladaptive group in EA to the resilient group in YA, exhibited higher childhood conscientiousness than persistently maladaptive peers. Findings suggest that children on pathways to success in adulthood, whether facing low or high adversity, have capacities for emotion regulation, empathy and connection, dedication to schoolwork, and mastery and exploration.

Consequences of the Allee effect and intraspecific competition on population persistence under adverse environmental conditions.

PubMed

Petrovskii, Sergei; Blackshaw, Rod; Li, Bai-Lian

2008-02-01

The impact of intraspecific interactions on ecological stability and population persistence in terms of steady state(s) existence is considered theoretically based on a general competition model. We compare persistence of a structured population consisting of a few interacting (competitive) subpopulations, or groups, to persistence of the corresponding unstructured population. For a general case, we show that if the intra-group competition is stronger than the inter-group competition, then the structured population is less prone to extinction, i.e. it can persist in a parameter range where the unstructured population goes extinct. For a more specific case of a population with hierarchical competition, we show that relative viability of structured and unstructured populations depend on the type of density dependence in the population growth. Namely, while in the case of logistic growth, structured and unstructured populations exhibit equivalent persistence; in the case of Allee dynamics, the persistence of a hierarchically structured population is shown to be higher. We then apply these results to the case of behaviourally structured populations and demonstrate that an extreme form of individual aggression can be beneficial at the population level and enhance population persistence.

Evaluating multimedia chemical persistence: Classification and regression tree analysis

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

Bennett, D.H.; McKone, T.E.; Kastenberg, W.E.

2000-04-01

For the thousands of chemicals continuously released into the environment, it is desirable to make prospective assessments of those likely to be persistent. Widely distributed persistent chemicals are impossible to remove from the environment and remediation by natural processes may take decades, which is problematic if adverse health or ecological effects are discovered after prolonged release into the environment. A tiered approach using a classification scheme and a multimedia model for determining persistence is presented. Using specific criteria for persistence, a classification tree is developed to classify a chemical as persistent or nonpersistent based on the chemical properties. In thismore » approach, the classification is derived from the results of a standardized unit world multimedia model. Thus, the classifications are more robust for multimedia pollutants than classifications using a single medium half-life. The method can be readily implemented and provides insight without requiring extensive and often unavailable data. This method can be used to classify chemicals when only a few properties are known and can be used to direct further data collection. Case studies are presented to demonstrate the advantages of the approach.« less

A correlation-based flux partitioning method and its application to a vineyard in California’s central valley: a case Study

USDA-ARS?s Scientific Manuscript database

The persistent and ongoing California drought has not only tasked already-limited water resources, it has also hampered crop production and damaged the state’s economy. In order to minimize the adverse effects of drought and ensure the sustainability of California agriculture, policymakers, resource...

Interactive effects of deficit irrigation, elevated temperature, and elevated [CO2] on peanut growth in low irrigation production settings

USDA-ARS?s Scientific Manuscript database

Improving crop water use (both agronomic and biological) is critical to most cropping areas around the world. The persistance of adverse climate conditions and predicted decreased availability of fresh water for crop production are the largest challenges to agriculture in the coming decades. Our pri...

Implementation of Antibullying Legislation in Iowa Schools: A Qualitative Examination of School Administrators' Perceived Barriers and Facilitators

ERIC Educational Resources Information Center

Bruening, Rebecca A.; Orengo-Aguayo, Rosaura E.; Onwuachi-Willig, Angela; Ramirez, Marizen

2018-01-01

Adolescent bullying is linked to numerous adverse psychosocial effects that can persist into adulthood. In response to this problem, in 2007 Iowa adopted an antibullying statute requiring all school districts to adopt an antibullying policy. From 2013-2014, 47 semistructured interviews were conducted with school and district administrators in…

Applications of ion chromatography to study pollution effects on forest trees

Treesearch

Walter C. Shortle; Rakesh Minocha

1990-01-01

Air pollution and acidic deposition can influence forest tree growth and survival by causing ionic imbalances in the rooting zone. Altered nutrient status suppresses tree growth and weakens its immune system. Internal infections spread more quickly in response to weakened tree defenses. As adverse conditions persist, many trees die and the survivors are less healthy....

RACIAL RESIDENTIAL SEGREGATION AND ADVERSE BIRTH OUTCOMES

EPA Science Inventory

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

Bradycardia and Hypothermia Complicating Azithromycin Treatment.

PubMed

Benn, Kerri; Salman, Sam; Page-Sharp, Madhu; Davis, Timothy M E; Buttery, Jim P

2017-08-11

BACKGROUND Azithromycin is a macrolide antibiotic widely used to treat respiratory, urogenital, and other infections. Gastrointestinal upset, headache, and dizziness are common adverse effects, and prolongation of the rate-corrected electrocardiographic QT interval and malignant arrhythmias have been reported. There are rare reports of bradycardia and hypothermia but not in the same patient. CASE REPORT A 4-year-old boy given intravenous azithromycin as part of treatment for febrile neutropenia complicating leukemia chemotherapy developed hypothermia (rectal temperature 35.2°C) and bradycardia (65 beats/minute) after the second dose, which resolved over several days post-treatment, consistent with persistence of high tissue azithromycin concentrations relative to those in plasma. A sigmoid Emax pharmacokinetic/pharmacodynamic model suggested a maximal azithromycin-associated reduction in heart rate of 23 beats/minute. Monitoring for these potential adverse effects should facilitate appropriate supportive care in similar cases. CONCLUSIONS Recommended azithromycin doses can cause at least moderate bradycardia and hypothermia in vulnerable pediatric patients, adverse effects that should prompt appropriate monitoring and which may take many days to resolve.

Immunohistochemical Evaluation of Androgen Receptor and Nerve Structure Density in Human Prepuce from Patients with Persistent Sexual Side Effects after Finasteride Use for Androgenetic Alopecia

PubMed Central

Di Loreto, Carla; La Marra, Francesco; Mazzon, Giorgio; Belgrano, Emanuele; Trombetta, Carlo; Cauci, Sabina

2014-01-01

Finasteride is an inhibitor of 5-α-reductase used against male androgenetic alopecia (AGA). Reported side effects of finasteride comprise sexual dysfunction including erectile dysfunction, male infertility, and loss of libido. Recently these effects were described as persistent in some subjects. Molecular events inducing persistent adverse sexual symptoms are unexplored. This study was designed as a retrospective case-control study to assess if androgen receptor (AR) and nerve density in foreskin prepuce specimens were associated with persistent sexual side effects including loss of sensitivity in the genital area due to former finasteride use against AGA. Cases were 8 males (aged 29–43 years) reporting sexual side effects including loss of penis sensitivity over 6 months after discontinuation of finasteride who were interviewed and clinically visited. After informed consent they were invited to undergo a small excision of skin from prepuce. Controls were 11 otherwise healthy matched men (aged 23–49 years) who undergone circumcision for phimosis, and who never took finasteride or analogues. Differences in AR expression and nerve density in different portions of dermal prepuce were evaluated in the 2 groups. Density of nuclear AR in stromal and epithelial cells was higher in cases (mean 40.0%, and 80.6% of positive cells, respectively) than controls (mean 23.4%, and 65.0% of positive cells, respectively), P = 0.023 and P = 0.043, respectively. Conversely, percentage of vessel smooth muscle cells positive for AR and density of nerves were similar in the 2 groups. The ratio of AR positive stromal cells % to serum testosterone concentrations was 2-fold higher in cases than in controls (P = 0.001). Our findings revealed that modulation of local AR levels might be implicated in long-term side effects of finasteride use. This provides the first evidence of a molecular objective difference between patients with long-term adverse sexual effects after finasteride use versus drug untreated healthy controls in certain tissues. PMID:24959691

RISK CHARACTERIZATION OF PERSISTENT NEUROTOXIC CONTAMINANTS

EPA Science Inventory

Neurotoxicity is an adverse change in structure or function of the central and/or peripheral nervous system following exposure to a chemical, physical, or biological agent. Thousands of chemicals have been estimated to have neurotoxic potential. Many persistent and bioaccumulat...

Placebo and nocebo reactions in randomized trials of pharmacological treatments for persistent depressive disorder. A meta-regression analysis.

PubMed

Meister, Ramona; Jansen, Alessa; Härter, Martin; Nestoriuc, Yvonne; Kriston, Levente

2017-06-01

We aimed to investigate placebo and nocebo reactions in randomized controlled trials (RCT) of pharmacological treatments for persistent depressive disorder (PDD). We conducted a systematic electronic search and included RCTs investigating antidepressants for the treatment of PDD. Outcomes were the number of patients experiencing response and remission in placebo arms (=placebo reaction). Additional outcomes were the incidence of patients experiencing adverse events and related discontinuations in placebo arms (=nocebo reaction). A priori defined effect modifiers were analyzed using a series of meta-regression analyses. Twenty-three trials were included in the analyses. We found a pooled placebo response rate of 31% and a placebo remission rate of 22%. The pooled adverse event rate and related discontinuations were 57% and 4%, respectively. All placebo arm outcomes were positively associated with the corresponding medication arm outcomes. Placebo response rate was associated with a greater proportion of patients with early onset depression, a smaller chance to receive placebo and a larger sample size. The adverse event rate in placebo arms was associated with a greater proportion of patients with early onset depression, a smaller proportion of females and a more recent publication. Pooled placebo and nocebo reaction rates in PDD were comparable to those in episodic depression. The identified effect modifiers should be considered to assess unbiased effects in RCTs, to influence placebo and nocebo reactions in practice. Limitations result from the methodology applied, the fact that we conducted only univariate analyses, and the number and quality of included trials. Copyright © 2017 Elsevier B.V. All rights reserved.

Association of PCBs and allergies in children.

PubMed

Tsuji, Mayumi; Kawamoto, Toshihiro; Koriyama, Chihaya; Yamamoto, Megumi; Tsuchiya, Takuto; Matsumura, Fumio

2015-05-01

Recently, the incidence rates of childhood allergies have been rising around the world. The presence of persistent chemical pollutants in the environment and exposure to air pollutants are often cited as potential causes of childhood allergies. Accordingly, epidemiological studies of the associations between exposure to low levels of pollutants and adverse health effects are essential. However, at present no useful biomarkers for evaluating such associations have been developed. Thus, using a molecular epidemiological approach we planned to identify candidate biomarkers of pollutant-induced adverse health effects that can be used in children. In asthmatic children, we found that the serum levels of several polychlorinated biphenyl (PCB) congener sub-types were significantly positively correlated with interleukin (IL)-8 mRNA expression, whereas in a sub-group of children who displayed positive immunoglobulin E (IgE) responses to milk or egg proteins IL-22 mRNA expression was demonstrated to be useful for detecting the adverse health effects of environmental pollutants, particularly PCB congeners. In conclusion, the mRNA expression levels of IL-8 and IL-22 can be used to detect children who are at particular risk of adverse health events caused by environmental pollutants, especially PCBs. Copyright © 2014 Elsevier Inc. All rights reserved.

A Preliminary Account of the Effect of Otitis Media on 15-Month- Olds' Categorization and Some Implications for Early Language Learning.

ERIC Educational Resources Information Center

Roberts, Kenneth

1997-01-01

Infants (N=24) with history of otitis media and tube placement were tested for categorical responding within a visual familiarization-discrimination model. Findings suggest that even mild hearing loss may adversely affect categorical responding under specific input conditions, which may persist after normal hearing is restored, possibly because…

Antibiotics for the common cold and acute purulent rhinitis.

PubMed

Kenealy, Tim; Arroll, Bruce

2013-06-04

It has long been believed that antibiotics have no role in the treatment of common colds yet they are often prescribed in the belief that they may prevent secondary bacterial infections. To determine the efficacy of antibiotics compared with placebo for reducing general and specific nasopharyngeal symptoms of acute upper respiratory tract infections (URTIs) (common colds).To determine if antibiotics have any influence on the outcomes for acute purulent rhinitis and acute clear rhinitis lasting less than 10 days before the intervention.To determine whether there are significant adverse outcomes associated with antibiotic therapy for participants with a clinical diagnosis of acute URTI or acute purulent rhinitis. For this 2013 update we searched CENTRAL 2013, Issue 1, MEDLINE (March 2005 to February week 2, 2013), EMBASE (January 2010 to February 2013), CINAHL (2005 to February 2013), LILACS (2005 to February 2013) and Biosis Previews (2005 to February 2013). Randomised controlled trials (RCTs) comparing any antibiotic therapy against placebo in people with symptoms of acute upper respiratory tract infection for less than seven days, or acute purulent rhinitis less than 10 days in duration. Both review authors independently assessed trial quality and extracted data. This updated review included 11 studies. Six studies contributed to one or more analyses related to the common cold, with up to 1047 participants. Five studies contributed to one or more analyses relating to purulent rhinitis, with up to 791 participants. One study contributed only to data on adverse events and one met the inclusion criteria but reported only summary statistics without providing any numerical data that could be included in the meta-analyses. Interpretation of the combined data is limited because some studies included only children, or only adults, or only males; a wide range of antibiotics were used and outcomes were measured in different ways. There was a moderate risk of bias because of unreported methods details or because an unknown number of participants were likely to have chest or sinus infections.Participants receiving antibiotics for the common cold did no better in terms of lack of cure or persistence of symptoms than those on placebo (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.59 to 1.51, (random-effects)), based on a pooled analysis of six trials with a total of 1047 participants. The RR of adverse effects in the antibiotic group was 1.8, 95% CI 1.01 to 3.21, (random-effects). Adult participants had a significantly greater risk of adverse effects with antibiotics than with placebo (RR 2.62, 95% CI 1.32 to 5.18) (random-effects) while there was no greater risk in children (RR 0.91, 95% CI 0.51 to 1.63).The pooled RR for persisting acute purulent rhinitis with antibiotics compared to placebo was 0.73 (95% CI 0.47 to 1.13) (random-effects), based on four studies with 723 participants. There was an increase in adverse effects in the studies of antibiotics for acute purulent rhinitis (RR 1.46, 95% CI 1.10 to 1.94). There is no evidence of benefit from antibiotics for the common cold or for persisting acute purulent rhinitis in children or adults. There is evidence that antibiotics cause significant adverse effects in adults when given for the common cold and in all ages when given for acute purulent rhinitis. Routine use of antibiotics for these conditions is not recommended.

Radioactive Iodine Administration Is Associated with Persistent Related Symptoms in Patients with Differentiated Thyroid Cancer

PubMed Central

Droppelmann, Nicolás

2016-01-01

Context. Radioiodine (RAI) administration has adverse effects in patients treated for thyroid cancer (DTC), but there is scarce information regarding their intensity and duration. Objective. To evaluate frequency and intensity of early and late RAI-related symptoms in patients with DTC. Design. Observational prospective study. Patients. DTC patients who underwent thyroidectomy, with or without RAI. Measurements. Patients answered 2 surveys: (1) from 0 to 6 months and (2) between 6 and 18 months after initial treatment. Results. 110 patients answered the first survey and 61 both. Nearly 80 percent received RAI. Among early symptoms, periorbital edema, excessive tearing, salivary gland disturbances, dry mouth, taste disorders, and nausea were more frequent and intense among RAI patients. Regarding late symptoms, periorbital edema, salivary gland pain and swelling, and dry mouth were more frequent and intense in RAI patients. Frequency and intensity of adverse effects were not different between low and high RAI doses (50 versus ≥100 mCi). Conclusion. RAI-related symptoms are frequent and usually persist after 6 months of administration, even when low doses are given. This finding must be considered when deciding RAI administration, especially in low risk patients, among whom RAI benefit is controversial. PMID:27867395

Radioactive Iodine Administration Is Associated with Persistent Related Symptoms in Patients with Differentiated Thyroid Cancer.

PubMed

Florenzano, Pablo; Guarda, Francisco J; Jaimovich, Rodrigo; Droppelmann, Nicolás; González, Hernán; Domínguez, José M

2016-01-01

Context . Radioiodine (RAI) administration has adverse effects in patients treated for thyroid cancer (DTC), but there is scarce information regarding their intensity and duration. Objective . To evaluate frequency and intensity of early and late RAI-related symptoms in patients with DTC. Design . Observational prospective study. Patients . DTC patients who underwent thyroidectomy, with or without RAI. Measurements . Patients answered 2 surveys: (1) from 0 to 6 months and (2) between 6 and 18 months after initial treatment. Results . 110 patients answered the first survey and 61 both. Nearly 80 percent received RAI. Among early symptoms, periorbital edema, excessive tearing, salivary gland disturbances, dry mouth, taste disorders, and nausea were more frequent and intense among RAI patients. Regarding late symptoms, periorbital edema, salivary gland pain and swelling, and dry mouth were more frequent and intense in RAI patients. Frequency and intensity of adverse effects were not different between low and high RAI doses (50 versus ≥100 mCi). Conclusion . RAI-related symptoms are frequent and usually persist after 6 months of administration, even when low doses are given. This finding must be considered when deciding RAI administration, especially in low risk patients, among whom RAI benefit is controversial.

Collaborative Care for Perinatal Depression Among Socioeconomically Disadvantaged Women: Adverse Neonatal Birth Events and Treatment Response.

PubMed

Bhat, Amritha; Grote, Nancy K; Russo, Joan; Lohr, Mary Jane; Jung, Hyunzee; Rouse, Caroline E; Howell, Elaine C; Melville, Jennifer L; Carson, Kathy; Katon, Wayne

2017-01-01

The study examined the effectiveness of a perinatal collaborative care intervention in moderating the effects of adverse neonatal birth events on risks of postpartum depressive symptoms and impaired functioning among women of lower socioeconomic status with antenatal depression. A randomized controlled trial with blinded outcome assessments was conducted in ten public health centers, comparing MOMCare (choice of brief interpersonal psychotherapy, pharmacotherapy, or both) with intensive maternity support services (MSS-Plus). Participants had probable diagnoses of major depressive disorder or dysthymia during pregnancy. Generalized estimating equations estimated differences in depression and functioning measures between groups with and without adverse birth events within the treatment arms. A total of 160 women, 43% of whom experienced at least one adverse birth event, were included in the analyses. For women who received MOMCare, postpartum depression scores (measured with the Symptom Checklist-20) did not differ by whether or not they experienced an adverse birth event (mean±SD scores of .86±.51 for mothers with an adverse birth event and .83±.56 for mothers with no event; p=.78). For women who received MSS-Plus, having an adverse birth event was associated with persisting depression in the postpartum period (mean scores of 1.20±.0.61 for mothers with an adverse birth event and .93±.52 for mothers without adverse birth event; p=.04). Similar results were seen for depression response rates and functioning. MOMCare mitigated the risk of postpartum depressive symptoms and impaired functioning among women of low socioeconomic status who had antenatal depression and who experienced adverse birth events.

Immediate balloon deflation for prevention of persistent phrenic nerve palsy during pulmonary vein isolation by balloon cryoablation.

PubMed

Ghosh, Justin; Sepahpour, Ali; Chan, Kim H; Singarayar, Suresh; McGuire, Mark A

2013-05-01

Persistent phrenic nerve palsy is the most frequent complication of cryoballoon ablation for atrial fibrillation and can be disabling. To describe a technique-immediate balloon deflation (IBD)-for the prevention of persistent phrenic nerve palsy, provide data for its use, and describe in vitro simulations performed to investigate the effect of IBD on the atrium and pulmonary vein. Cryoballoon procedures for atrial fibrillation were analyzed retrospectively (n = 130). IBD was performed in patients developing phrenic nerve dysfunction (n = 22). In vitro simulations were performed by using phantoms. No adverse events occurred, and all patients recovered normal phrenic nerve function before leaving the procedure room. No patient developed persistent phrenic nerve palsy. The mean cryoablation time to onset of phrenic nerve dysfunction was 144 ± 64 seconds. Transient phrenic nerve dysfunction was seen more frequently with the 23-mm balloon than with the 28-mm balloon (11 of 39 cases vs 11 of 81 cases; P = .036). Balloon rewarming was faster following IBD. The time to return to 0 and 20° C was shorter in the IBD group (6.7 vs 8.9 seconds; P = .007 and 16.7 vs 37.6 seconds; P<.0001). In vitro simulations confirmed that IBD caused more rapid tissue warming (time to 0°C, 14.0 ± 3.4 seconds vs 46.0 ± 8.1; P = .0001) and is unlikely to damage the atrium or pulmonary vein. IBD results in more rapid tissue rewarming, causes no adverse events, and appears to prevent persistent phrenic nerve palsy. Simulations suggest that IBD is unlikely to damage the atrium or pulmonary vein. Copyright © 2013 Heart Rhythm Society. All rights reserved.

Influence of side-effects on early therapy persistence with letrozole in post-menopausal patients with early breast cancer: Results of the prospective EvAluate-TM study.

PubMed

Nabieva, N; Fehm, T; Häberle, L; de Waal, J; Rezai, M; Baier, B; Baake, G; Kolberg, H-C; Guggenberger, M; Warm, M; Harbeck, N; Wuerstlein, R; Deuker, J-U; Dall, P; Richter, B; Wachsmann, G; Brucker, C; Siebers, J W; Popovic, M; Kuhn, T; Wolf, C; Vollert, H-W; Breitbach, G-P; Janni, W; Landthaler, R; Kohls, A; Rezek, D; Noesselt, T; Fischer, G; Henschen, S; Praetz, T; Heyl, V; Kühn, T; Krauss, T; Thomssen, C; Hohn, A; Tesch, H; Mundhenke, C; Hein, A; Hack, C C; Schmidt, K; Belleville, E; Brucker, S Y; Kümmel, S; Beckmann, M W; Wallwiener, D; Hadji, P; Fasching, P A

2018-06-01

Endocrine treatment (ET) with an aromatase inhibitor (AI) is the treatment of choice in post-menopausal patients with hormone receptor-positive early breast cancer (EBC). However, adverse events (AEs) often lead to treatment discontinuation. This analysis aimed to identify side-effects that lead to patients failing to persist with letrozole treatment. Post-menopausal hormone receptor-positive EBC patients starting ET with letrozole were enroled in EvAluate-TM, a non-interventional study. Information regarding treatment compliance and persistence was gathered in months 6 and 12. Persistence was defined as the time from 30 d after the start to the end of treatment. The influence on persistence of musculoskeletal syndrome, menopausal disorder, sleep disorder and other AEs within the first 30 d was analysed using Cox regression analyses. Among 3887 patients analysed, the persistence rate after 12 months was >85%. In all, 568 patients (14.6%) discontinued the treatment, 358 of whom (63.0%) did so only because of side-effects. The main AEs influencing persistence were musculoskeletal symptoms (hazard ratio [HR] 2.55; 95% confidence interval [CI], 1.90-3.42), sleep disorders (HR 1.95; 95% CI, 1.41-2.70) and other AEs (HR 2.03; 95% CI, 1.51-2.73). Menopausal disorder was not associated with non-persistence (HR 1.17; 95% CI, 0.74-1.84). These results suggest that side-effects of AIs such as musculoskeletal syndrome and sleep disorder lead to ET discontinuation within the first treatment year in significant numbers of EBC patients. Compliance programmes adapted for subgroups that are at risk for early non-persistence might help to ensure the recommended therapy duration. CFEM345DDE19. Copyright © 2018 Elsevier Ltd. All rights reserved.

Controlled clinical trial of zolpidem for the treatment of insomnia associated with attention-deficit/ hyperactivity disorder in children 6 to 17 years of age.

PubMed

Blumer, Jeffrey L; Findling, Robert L; Shih, Weichung Joe; Soubrane, Christina; Reed, Michael D

2009-05-01

The goal was to evaluate the hypnotic efficacy of zolpidem at 0.25 mg/kg per day (maximum of 10 mg/day), compared with placebo, in children 6 through 17 years of age who were experiencing insomnia associated with attention-deficit/hyperactivity disorder. An 8-week, North American, multicenter, double-blind, placebo-controlled, parallel-group study was conducted. Patients underwent stratification according to age (6-11 years [N = 111] or 12-17 years [N = 90]) and were assigned randomly to receive treatment with the study drug or placebo (in a 2:1 ratio). The primary efficacy variable was latency to persistent sleep between weeks 3 and 6. Secondary efficacy variables also were assessed, and behavioral and cognitive components of attention-deficit/hyperactivity disorder were monitored. Safety was assessed on the basis of reports of adverse events, abnormal laboratory data, vital signs, and physical examination findings. The potential for next-day residual effects also was assessed. The baseline-adjusted mean change in latency to persistent sleep at week 4 did not differ significantly between the zolpidem and placebo groups (-20.28 vs -21.27 minutes). However, differences favoring zolpidem were observed for the older age group in Clinical Global Impression scores at weeks 4 and 8. No next-day residual effects of treatment were associated with zolpidem, and no rebound phenomena occurred after treatment discontinuation. Central nervous system and psychiatric disorders were the most-frequent treatment-emergent adverse events (>5%) that were observed more frequently with zolpidem than with placebo; these included dizziness, headache, and hallucinations. Ten (7.4%) patients discontinued zolpidem treatment because of adverse events. Zolpidem at a dose of 0.25 mg/kg per day to a maximum of 10 mg failed to reduce the latency to persistent sleep on polysomnographic recordings after 4 weeks of treatment in children and adolescents 6 through 17 years of age who had attention-deficit/hyperactivity disorder-associated insomnia.

Large-particle calcium hydroxylapatite injection for correction of facial wrinkles and depressions.

PubMed

Alam, Murad; Havey, Jillian; Pace, Natalie; Pongprutthipan, Marisa; Yoo, Simon

2011-07-01

Small-particle calcium hydroxylapatite (Radiesse, Merz, Frankfurt, Germany) is safe and effective for facial wrinkle reduction, and has medium-term persistence for this indication. There is patient demand for similar fillers that may be longer lasting. We sought to assess the safety and persistence of effect in vivo associated with use of large-particle calcium hydroxylapatite (Coaptite, Merz) for facial augmentation and wrinkle reduction. This was a case series of 3 patients injected with large-particle calcium hydroxylapatite. Large-particle calcium hydroxylapatite appears to be effective and well tolerated for correction of facial depressions, including upper mid-cheek atrophy, nasolabial creases, and HIV-associated lipoatrophy. Adverse events included erythema and edema, and transient visibility of the injection sites. Treated patients, all of whom had received small-particle calcium hydroxylapatite correction before, noted improved persistence at 6 and 15 months with the large-particle injections as compared with prior small-particle injections. This is a small case series, and there was no direct control to compare the persistence of small-particle versus large-particle correction. For facial wrinkle correction, large-particle calcium hydroxylapatite has a safety profile comparable with that of small-particle calcium hydroxylapatite. The large-particle variant may have longer persistence that may be useful in selected clinical circumstances. Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Persistent Microvascular Obstruction After Myocardial Infarction Culminates in the Confluence of Ferric Iron Oxide Crystals, Proinflammatory Burden, and Adverse RemodelingCLINICAL PERSPECTIVE

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

Kali, Avinash; Cokic, Ivan; Tang, Richard

Emerging evidence now supports the notion that persistent microvascular obstruction (PMO) may be more predictive of major adverse cardiovascular events than MI size itself. But, how PMO, a phenomenon limited to the acute/sub-acute period of MI, imparts adverse remodeling throughout the post MI period, particularly after its resolution, is incompletely understood. We hypothesized that PMOs resolve into chronic iron crystals within MI territories and actively impart a proinflammatory burden and adverse remodeling of infarction and LV in the chronic phase of MI. Canine models reperfused (n=20) and non-reperfused (n=20) with and without PMO were studied with serial cardiac MRI tomore » characterize the spatiotemporal relationships between PMO, iron deposition, and infarct and LV remodeling indices between acute (day 7, post MI) and chronic (week 8, post MI). Histopathology and immunohistochemistry were used to validate the iron deposition, microscopically map and quantify the relationship between iron-rich chronic MI regions against pro-inflammatory macrophages, proinflammatory cytokines and matrix metalloproteinase. Atomic resolution transmission electron microscopy (TEM) was used to determine the crystallinity of iron and assess the physical effects of iron on lysosomes within macrophages, and energy-dispersive X-ray spectroscopy (EDS) to identify the chemical composition of the iron composite. Results showed that PMOs lead to iron deposition within chronic MI and that the extent of chronic iron deposition is strongly related to PMO Volume (r>0.6, p<0.001). TEM and EDS analysis showed that iron within chronic MI is found within macrophages as aggregates of nanocrystals of ~2.5 nm diameter in ferric state. Correlative histological studies showed that iron content, proinflammatory burden and collagen degrading enzyme were highly correlated (r >0.7, p<0.001). Iron within chronic MI was significantly associated with infarct resorption (r>0.5, p<0.001) and adverse structural (r>0.5, p<0.001) remodeling. Territories of PMO in the acute phase of MI resolve into iron oxide nanocrystals in ferric state in the chronic phase of MI. The amount of iron deposition is determined by the extent of persistent microvascular obstruction and is directly related to the extent of pro-inflammatory burden, infarct thinning and adverse LV remodeling. Resolution of PMO into iron deposition could be a potential contributing source to the adverse remodeling of the heart in the chronic phase of MI.« less

Current status of persistent organic pesticides residues in air, water, and soil, and their possible effect on neighboring countries: a comprehensive review of India.

PubMed

Yadav, Ishwar Chandra; Devi, Ningombam Linthoingambi; Syed, Jabir Hussain; Cheng, Zhineng; Li, Jun; Zhang, Gan; Jones, Kevin C

2015-04-01

Though the use of pesticides has offered significant economic benefits by enhancing the production and yield of food and fibers and the prevention of vector-borne diseases, evidence suggests that their use has adversely affected the health of human populations and the environment. Pesticides have been widely distributed and their traces can be detected in all areas of the environment (air, water and soil). Despite the ban of DDT and HCH in India, they are still in use, both in domestic and agricultural settings. In this comprehensive review, we discuss the production and consumption of persistent organic pesticides, their maximum residual limit (MRL) and the presence of persistent organic pesticides in multicomponent environmental samples (air, water and soil) from India. In order to highlight the global distribution of persistent organic pesticides and their impact on neighboring countries and regions, the role of persistent organic pesticides in Indian region is reviewed. Based on a review of research papers and modeling simulations, it can be concluded that India is one of the major contributors of global persistent organic pesticide distribution. This review also considers the health impacts of persistent organic pesticides, the regulatory measures for persistent organic pesticides, and the status of India's commitment towards the elimination of persistent organic pesticides. Copyright © 2014 Elsevier B.V. All rights reserved.

The combination of fluticasone furoate and vilanterol trifenatate in the management of asthma: clinical trial evidence and experience

PubMed Central

Albertson, Timothy E.; Richards, John R.; Zeki, Amir A.

2015-01-01

The treatment of persistent asthma has been aided by the recent approval of new medications. The combined inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) powder inhaler fluticasone furoate (FF)/vilanterol trifenatate (VI) is one of these new agents, which was recently approved as a maintenance therapy for persistent asthma. This once-daily ICS/LABA inhaler has previously been approved and used in chronic obstructive pulmonary disease as a maintenance therapy. Both FF and VI individually have been shown to have efficacy in the treatment of persistent asthma; the combination of FF/VI at the dose of 100/25 μg daily improves trough peak expiratory flows and forced expiratory volume in 1 s. It also reduces the frequency of asthma exacerbations in patients with persistent asthma. The once-daily dosing is well tolerated, with limited clinically significant adverse events; the once-daily inhaled dosing regimen should also improve medication adherence. The data supporting the use of the FF/VI inhaler in persistent asthma are reviewed. The dry powder inhaler of FF/VI (100/25 μg) is an effective and well tolerated once-daily maintenance treatment for patients with persistent asthma. PMID:26668137

Repeated weekly exposure to MDMA, methamphetamine or their combination: long-term behavioural and neurochemical effects in rats.

PubMed

Clemens, Kelly J; Cornish, Jennifer L; Hunt, Glenn E; McGregor, Iain S

2007-01-12

In recent work we have documented lasting adverse neurochemical and behavioural effects in rats given short-term 'binge' dosing with methylenedioxymethamphetamine (MDMA, Ecstasy), methamphetamine (METH) or their combination. Here we investigated whether similar effects persist in rats given 16 weekly injections followed by a 10 week period of abstinence. Female rats received MDMA (8 mg/kg, i.p.), METH (8 mg/kg), or a MDMA/METH combination (4 mg/kg MDMA + 4 mg/kg METH), once a week for 16 weeks, with locomotor activity and body temperature measured on weeks 1, 8 and 16. The MDMA and MDMA/METH groups showed acute drug-induced hyperthermia on week 1 only. MDMA-treated rats demonstrated an acute hyperactivity while METH and MDMA/METH treated rats showed pronounced stereotypy. Seven weeks after drug-treatment concluded, a decrease in social interaction was observed in all chronically drug-treated rats. No group differences were evident on the emergence, object recognition or forced swim tests. Neurochemical analysis revealed modest noradrenaline and serotonin depletion in chronically treated rats that was not evident following a single equivalent administration. These results indicate that although chronic, intermittent exposure to MDMA, METH or their combination, may not lead to significant long-term monoamine depletion, lasting adverse behavioural effects may persist, especially those related to social behaviour.

The Diverse Forms of Lactose Intolerance and the Putative Linkage to Several Cancers

PubMed Central

Amiri, Mahdi; Diekmann, Lena; von Köckritz-Blickwede, Maren; Naim, Hassan Y.

2015-01-01

Lactase-phlorizin hydrolase (LPH) is a membrane glycoprotein and the only β-galactosidase of the brush border membrane of the intestinal epithelium. Besides active transcription, expression of the active LPH requires different maturation steps of the polypeptide through the secretory pathway, including N- and O-glycosylation, dimerization and proteolytic cleavage steps. The inability to digest lactose due to insufficient lactase activity results in gastrointestinal symptoms known as lactose intolerance. In this review, we will concentrate on the structural and functional features of LPH protein and summarize the cellular and molecular mechanism required for its maturation and trafficking. Then, different types of lactose intolerance are discussed, and the molecular aspects of lactase persistence/non-persistence phenotypes are investigated. Finally, we will review the literature focusing on the lactase persistence/non-persistence populations as a comparative model in order to determine the protective or adverse effects of milk and dairy foods on the incidence of colorectal, ovarian and prostate cancers. PMID:26343715

The Diverse Forms of Lactose Intolerance and the Putative Linkage to Several Cancers.

PubMed

Amiri, Mahdi; Diekmann, Lena; von Köckritz-Blickwede, Maren; Naim, Hassan Y

2015-08-28

Lactase-phlorizin hydrolase (LPH) is a membrane glycoprotein and the only β-galactosidase of the brush border membrane of the intestinal epithelium. Besides active transcription, expression of the active LPH requires different maturation steps of the polypeptide through the secretory pathway, including N- and O-glycosylation, dimerization and proteolytic cleavage steps. The inability to digest lactose due to insufficient lactase activity results in gastrointestinal symptoms known as lactose intolerance. In this review, we will concentrate on the structural and functional features of LPH protein and summarize the cellular and molecular mechanism required for its maturation and trafficking. Then, different types of lactose intolerance are discussed, and the molecular aspects of lactase persistence/non-persistence phenotypes are investigated. Finally, we will review the literature focusing on the lactase persistence/non-persistence populations as a comparative model in order to determine the protective or adverse effects of milk and dairy foods on the incidence of colorectal, ovarian and prostate cancers.

Changes in behavior as side effects in methylphenidate treatment: review of the literature.

PubMed

Konrad-Bindl, Doris Susanne; Gresser, Ursula; Richartz, Barbara Maria

2016-01-01

Our review of the scientific literature focused on an analysis of studies describing instances of methylphenidate treatment leading (or not) to behavioral changes in the pediatric, adolescent, and adult populations. We conducted a literature search in PubMed, Medline, and Google using the keywords "methylphenidate", "behavioral changes", "adverse effects", and "side effects". A total of 44 studies were identified as reporting on the effects and adverse effects of methylphenidate administration, and were included in the analysis. Five studies specifically set out to study, record, and discuss changes in behavior. Eight studies did not set out to study behavioral effects, but record and discuss them. A total of 28 studies recorded behavioral effects, but failed to discuss these further. Three studies did not include behavioral effects. This review records what data have been published in respect of changes in behavior in association with the use of methylphenidate. While there is some evidence to suggest that methylphenidate causes changes in behavior, the majority of the studies reviewed paid little or no attention to this issue. Based on the available data, it is impossible to determine the point at which such behavioral effects occur. The frequency of occurrence of behavioral effects is also impossible to determine with certainty. Based on the available data, it is not possible to rule out whether behavioral effects may persist or not persist once treatment is discontinued. In conclusion, despite countless publications and extensive administration, especially to children, we have insufficient data to judge the long-term effects and risks of methylphenidate taking.

Neurotoxicity of Legacy and Emerging Persistent Organic Chemicals: A Proteomic Approach to Understand Adverse Outcome Pathways

EPA Science Inventory

During the past century, a vast number of persistent organic chemicals (POCs) have been manufactured and used in industrial, agricultural, public health, consumer products and other applications. Widespread use of legacy POCs, including chlorinated, brominated and fluorinated com...

Using torsional forces to explain the gradient temperature Raman spectra of endosulfan isomers and its irreversible isomerization

USDA-ARS?s Scientific Manuscript database

Since the 1950's, the broad-spectrum, organochlorine insecticide endosulfan (6,7,8, 9,10,10-hexachloro-1,5,5a,6,9,9a-hexahydro-6,9-methano-2,4,3-benzodioxathiepine-3-oxide) has been used on numerous crops. Due to its persistence, bioaccumulation, long-range transport, and adverse effects to human he...

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

The influence of stress responses on surgical performance and outcomes: Literature review and the development of the surgical stress effects (SSE) framework.

PubMed

Chrouser, Kristin L; Xu, Jie; Hallbeck, Susan; Weinger, Matthew B; Partin, Melissa R

2018-02-22

Surgical adverse events persist despite several decades of system-based quality improvement efforts, suggesting the need for alternative strategies. Qualitative studies suggest stress-induced negative intraoperative interpersonal dynamics might contribute to performance errors and undesirable patient outcomes. Understanding the impact of intraoperative stressors may be critical to reducing adverse events and improving outcomes. We searched MEDLINE, psycINFO, EMBASE, Business Source Premier, and CINAHL databases (1996-2016) to assess the relationship between negative (emotional and behavioral) responses to acute intraoperative stressors and provider performance or patient surgical outcomes. Drawing on theory and evidence from reviewed studies, we present the Surgical Stress Effects (SSE) framework. This illustrates how emotional and behavioral responses to stressors can influence individual surgical provider (e.g. surgeon, nurse) performance, team performance, and patient outcomes. It also demonstrates how uncompensated intraoperative threats and errors can lead to adverse events, highlighting evidence gaps for future research efforts. Published by Elsevier Inc.

The fate of pharmaceuticals and personal care products (PPCPs), endocrine disrupting contaminants (EDCs), metabolites and illicit drugs in a WWTW and environmental waters.

PubMed

Archer, Edward; Petrie, Bruce; Kasprzyk-Hordern, Barbara; Wolfaardt, Gideon M

2017-05-01

A large number of emerging contaminants (ECs) are known to persist in surface waters, and create pressure on wastewater treatment works (WWTW) for their effective removal. Although a large database for the levels of these pollutants in water systems exist globally, there is still a lack in the correlation of the levels of these pollutants with possible long-term adverse health effects in wildlife and humans, such as endocrine disruption. The current study detected a total of 55 ECs in WWTW influent surface water, 41 ECs in effluent, and 40 ECs in environmental waters located upstream and downstream of the plant. A list of ECs persisted through the WWTW process, with 28% of all detected ECs removed by less than 50%, and 18% of all ECs were removed by less than 25%. Negative mass balances of some pharmaceuticals and metabolites were observed within the WWTW, suggesting possible back-transformation of ECs during wastewater treatment. Three parental illicit drug compounds were detected within the influent of the WWTW, with concentrations ranging between 27.6 and 147.0 ng L -1 for cocaine, 35.6-120.6 ng L -1 for mephedrone, and 270.9-450.2 ng L -1 for methamphetamine. The related environmental risks are also discussed for some ECs, with particular reference to their ability to disrupt endocrine systems. The current study propose the potential of the pharmaceuticals carbamazepine, naproxen, diclofenac and ibuprofen to be regarded as priority ECs for environmental monitoring due to their regular detection and persistence in environmental waters and their possible contribution towards adverse health effects in humans and wildlife. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Persistent organic pesticide residues in sediments of Vasai Creek near Mumbai: Assessment of sources and potential ecological risk.

PubMed

Singare, Pravin U

2015-11-15

Thirteen persistent organic pesticides were investigated in the sediments of Vasai Creek near Mumbai to evaluate their pollution levels and potential risks. It was observed that ΣOCPs level was in the range of 597-1538ng/g dw, with an average value of 1115.25ng/g dw. The level of ΣOPPs was in the range of 492-1034ng/g dw, with an average value of 798.15ng/g dw. The values o,p'-DDT/p,p'-DDT ratio gives an indication of use of technical DDT as the prime source of DDT, while the α/γ-BHC ratio indicate that BHCs in study area might have been received from fresh lindane. The results of an ecological risk assessment showed that sediment bound organic pesticides are of more ecotoxicological concern as they might create adverse ecological risk to the marine breeding habitats. These pesticides residues may get remobilize and released to overlying waters creating adverse effects on terrestrial and aquatic organisms. Copyright © 2015 Elsevier Ltd. All rights reserved.

Preventing the development of chronic pain after orthopaedic surgery with preventive multimodal analgesic techniques.

PubMed

Reuben, Scott S; Buvanendran, Asokumar

2007-06-01

The prevalences of complex regional pain syndrome, phantom limb pain, chronic donor-site pain, and persistent pain following total joint arthroplasty are alarmingly high. Central nervous system plasticity that occurs in response to tissue injury may contribute to the development of persistent postoperative pain. Many researchers have focused on methods to prevent central neuroplastic changes from occurring through the utilization of preemptive or preventive multimodal analgesic techniques. Multimodal analgesia allows a reduction in the doses of individual drugs for postoperative pain and thus a lower prevalence of opioid-related adverse events. The rationale for this strategy is the achievement of sufficient analgesia due to the additive effects of, or the synergistic effects between, different analgesics. Effective multimodal analgesic techniques include the use of nonsteroidal anti-inflammatory drugs, local anesthetics, alpha-2 agonists, ketamine, alpha(2)-delta ligands, and opioids.

Persistent tachycardia in clozapine treated patients: A 24-hour ambulatory electrocardiogram study.

PubMed

Nilsson, Björn M; Lindström, Leif; Mohsen, Issam; Holmlöv, Karolina; Bodén, Robert

2018-03-27

Tachycardia is associated with cardiovascular mortality. Tachycardia is also a known clozapine adverse effect. However, whether clozapine-associated tachycardia is persistent is not known. Thirty clozapine-treated patients with clinical tachycardia were investigated with 24-hour ambulatory electrocardiography (ECG). Baseline peripheral heart rate (HR) was 106.7±7.8. The ambulatory ECG 24-hour-HR was 98.7±9.7. Baseline HR and 24-hour-HR correlated strongly (r=0.74, p=0.000003). Daytime HR was 106.4±9.9 and nighttime HR 89.2±12.0. Low dose bisoprolol reduced HR significantly. The high 24-hour-HR indicates a persistent tachycardia. Tachycardia should not discourage from clozapine use but the findings indicate a need of guidelines for detection and treatment of clozapine-associated tachycardia. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Nebivolol Induced Hyperkalemia: Case Report

PubMed

Altabas, Karmela; Altabas, Velimir; Gulin, Tonko

2016-12-01

In this article, we document a conclusive case of nebivolol-induced hyperkalemia for the first time in the known medical literature. Hyperkalemia is associated with serious conditions such as cardiac arrhythmias and sudden cardiac death. Nebivolol was not known to cause hyperkalemia, and this event is not listed in its summary of product characteristics (SmPC). For older beta blockers, hyperkalemia is recognized as a rare adverse event linked to cytochrome P450 2D6 (CYP2D6) polymorphism and poor drug degradation. Our patient, a 47-year-old woman taking nebivolol for hypertension developed persistent hyperkalemia, with serum potassium levels up to 6.4 mmol/L. After extensive diagnostic evaluation and exclusion of other known conditions leading to hyperkalemia, its cause remained occult. Since hyperkalemia coincided with increased doses of nebivolol, dose reduction and discontinuation were attempted, resulting in normalized serum potassium. Poor drug metabolism could not explain this adverse effect, since pharmacogenetic testing showed no relevant aberrations. In conclusion, hyperkalemia is a harmful adverse event with possible lethal outcome, and it may be caused by nebivolol. Therefore, medical professionals have to be aware of this side effect and hyperkalemia should be listed as an adverse event in nebivolol SmPC.

Dichloroacetate treatment for mitochondrial cytopathy: long-term effects in MELAS.

PubMed

Mori, Masato; Yamagata, Takanori; Goto, Tamako; Saito, Shigeko; Momoi, Mariko Y

2004-10-01

The long-term effects of the sodium salt of dichloroacetic acid (DCA) were evaluated in four patients with mitochondrial encephalomyelopathy with lactic acidosis and stroke-like episodes (MELAS) carrying A3243G mutation. Oral administration of DCA in MELAS patients was followed for an average of 5 years 4 months. Serum levels of lactate and pyruvate were maintained at around 10 and 0.6 mg/dl, respectively. Serum levels of DCA were 40-136 microg/ml. Symptoms responding to treatment included persistent headache, abdominal pain, muscle weakness, and stroke-like episodes. In contrast, no improvements in mental status, deafness, short stature, or neuroelectrophysiological findings were observed. Adverse effects included mild liver dysfunction in all patients, hypocalcemia in three and peripheral neuropathy in one. None of these adverse events was severe enough to require discontinuation of treatment. To determine suitable indications for DCA therapy, analysis of many more patients who have undergone DCA administration is required.

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

ERIC Educational Resources Information Center

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

2007-01-01

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

Pranlukast: a review of its use in the management of asthma.

PubMed

Keam, Susan J; Lyseng-Williamson, Katherine A; Goa, Karen L

2003-01-01

Pranlukast (Onon, Azlaire), is an orally administered, selective, competitive antagonist of the cysteinyl leukotrienes (LT) C(4), LTD(4) and LTE(4). It is indicated for the prophylactic treatment of chronic bronchial asthma in paediatric and adult patients. The efficacy of pranlukast 225mg twice daily in adults with mild to moderate asthma was demonstrated in double-blind, placebo- or azelastine-controlled studies of 4 or 8 weeks' duration. The drug at this dosage was superior to both comparators in improving mean attack scores and morning and/or evening peak expiratory flow rates, and decreasing the use of rescue bronchodilators (p < 0.05). In limited clinical studies, pranlukast 225mg twice daily appeared to be as effective as montelukast 10mg once daily and zafirlukast 40mg twice daily in adults with mild to moderate asthma. Tachyphylaxis was absent when the drug was administered for up to 4 years. In patients requiring high-dose inhaled corticosteroid therapy, pranlukast 225 mg twice daily plus a halved dosage of inhaled corticosteroid was as effective as the original dosage of inhaled corticosteroid. Pranlukast was also effective in patients with mild to severe asthma in a clinical practice setting. In a double-blind trial, greater improvements in most outcome measures were observed with pranlukast than with oxatomide in children and adolescents with asthma. In clinical trials, pranlukast was well tolerated in adult and paediatric patients with asthma, with an adverse event profile similar to that of placebo. Gastrointestinal events and hepatic function abnormalities were the most commonly reported adverse events. No clinically significant differences in adverse event profiles between pranlukast, zafirlukast or montelukast were shown in limited comparisons. Although Churg-Strauss syndrome has been noted in pranlukast recipients, a direct causal relationship is unlikely. Pranlukast is a well tolerated and effective preventative treatment in adult and paediatric patients with persistent asthma of all severities. In some patients, pranlukast may be beneficial when added to low-dose inhaled corticosteroids; it may also be a viable alternative to increasing inhaled corticosteroid dosages. The efficacy of pranlukast relative to placebo has been confirmed; its efficacy relative to other therapy awaits further investigation. Nonetheless, pranlukast is a useful therapeutic option (with as-required short-acting beta(2)-agonists), either as preventative monotherapy for the treatment of mild persistent asthma or in conjunction with inhaled corticosteroids in the management of moderate or severe persistent asthma.

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.

Aircraft Trajectory Optimization and Contrails Avoidance in the Presence of Winds

NASA Technical Reports Server (NTRS)

Ng, Hok K.; Chen, Neil Y.

2010-01-01

There are indications that persistent contrails can lead to adverse climate change, although the complete effect on climate forcing is still uncertain. A flight trajectory optimization algorithm with fuel and contrails models, which develops alternative flight paths, provides policy makers the necessary data to make tradeoffs between persistent contrails mitigation and aircraft fuel consumption. This study develops an algorithm that calculates wind-optimal trajectories for cruising aircraft while avoiding the regions of airspace prone to persistent contrails formation. The optimal trajectories are developed by solving a non-linear optimal control problem with path constraints. The regions of airspace favorable to persistent contrails formation are modeled as penalty areas that aircraft should avoid and are adjustable. The tradeoff between persistent contrails formation and additional fuel consumption is investigated, with and without altitude optimization, for 12 city-pairs in the continental United States. Without altitude optimization, the reduction in contrail travel times is gradual with increase in total fuel consumption. When altitude is optimized, a two percent increase in total fuel consumption can reduce the total travel times through contrail regions by more than six times. Allowing further increase in fuel consumption does not seem to result in proportionate decrease in contrail travel times.

Persistence with anti-tumour necrosis factor therapies in patients with psoriatic arthritis: observational study from the British Society of Rheumatology Biologics Register.

PubMed

Saad, Amr A; Ashcroft, Darren M; Watson, Kath D; Hyrich, Kimme L; Noyce, Peter R; Symmons, Deborah P M

2009-01-01

Anti-TNF therapies represent a breakthrough in the treatment of severe psoriatic arthritis. However, little is known about long-term drug persistence with these treatments in patients with psoriatic arthritis in routine clinical practice. The aim of this study was to assess persistence with first-course and second-course treatment with anti-TNF agents in a prospective cohort of psoriatic arthritis patients and to identify factors associated with and reasons for drug discontinuation. A total of 566 patients with psoriatic arthritis were registered with the British Society for Rheumatology Biologics Register (first anti-TNF agent: etanercept, n = 316; infliximab, n = 162; and adalimumab, n = 88). Treating physicians completed 6-monthly follow-up questionnaires detailing changes to anti-TNF therapies. Persistence with treatment was examined using Kaplan-Meier survival analysis. Reasons for withdrawal were classified as due to inefficacy, adverse events or other reasons. Univariate and multivariate Cox proportional hazard models were developed to examine potential predictors of withdrawals due to inefficacy or adverse events, using a range of demographic, baseline disease-specific and therapeutic variables. At baseline, the mean (standard deviation) age of patients was 45.7 (11.1) years, 53% were female and the mean disease duration was 12.4 (8.7) years. Persistence data were available for a mean (standard deviation) follow-up of 2.3 (0.9) person-years. In total, 422 patients had completed at least 12 months of follow-up, 75.5% of whom remained on their first anti-TNF drug while 9.5% discontinued due to inefficacy, 10.0% due to adverse events and 5.0% due to other reasons. During the period of follow-up, 178 patients received a second anti-TNF therapy. The survivor function on second anti-TNF for switchers was 74% at 12 months. Psoriatic arthritis patients show high persistence rates with both initial and second anti-TNF therapies.

Prenatal Family Adversity and Maternal Mental Health and Vulnerability to Peer Victimisation at School

ERIC Educational Resources Information Center

Lereya, Suzet Tanya; Wolke, Dieter

2013-01-01

Background: Prenatal stress has been shown to predict persistent behavioural abnormalities in offspring. Unknown is whether prenatal stress makes children more vulnerable to peer victimisation. Methods: The current study is based on the Avon Longitudinal Study of Parents and Children, a prospective community-based study. Family adversity, maternal…

Glycopyrrolate-induced craniofacial compensatory hyperhidrosis successfully treated with oxybutynin: report of a novel adverse effect and subsequent successful treatment.

PubMed

Prouty, Megan E; Fischer, Ryan; Liu, Deede

2016-10-15

Hyperhidrosis, or abnormally increased sweating, is a condition that may have a primary or secondary cause. Usually medication- induced secondary hyperhidrosis manifests with generalized, rather than focal sweating. We report a 32-year-old woman with a history of palmoplantar hyperhidrosis for 15 years who presented for treatment and was prescribed oral glycopyrrolate. One month later, the palmoplantar hyperhidrosis had resolved, but she developed new persistent craniofacial sweating. After an unsuccessful trial of clonidine, oxybutynin resolved the craniofacial hyperhidrosis. To our knowledge, this is the first case of compensatory hyperhidrosis secondary to glycopyrrolate reported in the literature. The case highlights the importance of reviewing medication changes that correlate with new onset or changing hyperhidrosis. It also demonstrates a rare drug adverse effect with successful treatment.

Repeated Δ9-Tetrahydrocannabinol Exposure in Adolescent Monkeys: Persistent Effects Selective for Spatial Working Memory

PubMed Central

Verrico, Christopher D.; Gu, Hong; Peterson, Melanie L.; Sampson, Allan R.; Lewis, David A.

2014-01-01

Objective Epidemiological findings suggest that, relative to adults, adolescents are more vulnerable to the adverse persistent effects of cannabis on working memory. However, the potential confounds inherent in human studies preclude direct determination of a cause-and-effect relationship between adolescent cannabis use and heightened susceptibility to persistent working memory impairments. Consequently, the authors examined the effects of repeated exposure to Δ9-tetrahydrocannabinol (THC) on performance of spatial and object working memory tasks in adolescent monkeys. Method Seven pairs of male adolescent rhesus monkeys, matched for baseline cognitive performance, received vehicle or THC intravenously 5 days/week for 6 months. Performance on spatial and object memory tasks was assessed 23 or 71 hours after drug administration throughout the study. In addition, acute effects on working memory were also assessed at the beginning and end of the 6-month period. Results Relative to the vehicle-exposed control animals, those with repeated THC exposure had a blunted trajectory of accuracy improvements on the spatial working memory task in a delay-dependent manner. Accuracy improvements on the object working memory task did not differ between groups. Relative to the acute effects of THC on working memory at the beginning of the study, neither sensitivity nor tolerance was evident after 6 months of THC exposure. Conclusions Because maturation of performance is later for spatial than for object working memory, these findings suggest that persistent effects of THC on cognitive abilities are more evident when exposure coincides with the developmental stage during which the underlying neural circuits are actively maturing. PMID:24577206

Repeated Δ9-tetrahydrocannabinol exposure in adolescent monkeys: persistent effects selective for spatial working memory.

PubMed

Verrico, Christopher D; Gu, Hong; Peterson, Melanie L; Sampson, Allan R; Lewis, David A

2014-04-01

Epidemiological findings suggest that, relative to adults, adolescents are more vulnerable to the adverse persistent effects of cannabis on working memory. However, the potential confounds inherent in human studies preclude direct determination of a cause-and-effect relationship between adolescent cannabis use and heightened susceptibility to persistent working memory impairments. Consequently, the authors examined the effects of repeated exposure to Δ9-tetrahydrocannabinol (THC) on performance of spatial and object working memory tasks in adolescent monkeys. Seven pairs of male adolescent rhesus monkeys, matched for baseline cognitive performance, received vehicle or THC intravenously 5 days/week for 6 months. Performance on spatial and object memory tasks was assessed 23 or 71 hours after drug administration throughout the study. In addition, acute effects on working memory were also assessed at the beginning and end of the 6-month period. Relative to the vehicle-exposed control animals, those with repeated THC exposure had a blunted trajectory of accuracy improvements on the spatial working memory task in a delay-dependent manner. Accuracy improvements on the object working memory task did not differ between groups. Relative to the acute effects of THC on working memory at the beginning of the study, neither sensitivity nor tolerance was evident after 6 months of THC exposure. Because maturation of performance is later for spatial than for object working memory, these findings suggest that persistent effects of THC on cognitive abilities are more evident when exposure coincides with the developmental stage during which the underlying neural circuits are actively maturing.

Changes in behavior as side effects in methylphenidate treatment: review of the literature

PubMed Central

Konrad-Bindl, Doris Susanne; Gresser, Ursula; Richartz, Barbara Maria

2016-01-01

Background Our review of the scientific literature focused on an analysis of studies describing instances of methylphenidate treatment leading (or not) to behavioral changes in the pediatric, adolescent, and adult populations. Materials and methods We conducted a literature search in PubMed, Medline, and Google using the keywords “methylphenidate”, “behavioral changes”, “adverse effects”, and “side effects”. A total of 44 studies were identified as reporting on the effects and adverse effects of methylphenidate administration, and were included in the analysis. Results Five studies specifically set out to study, record, and discuss changes in behavior. Eight studies did not set out to study behavioral effects, but record and discuss them. A total of 28 studies recorded behavioral effects, but failed to discuss these further. Three studies did not include behavioral effects. Conclusion This review records what data have been published in respect of changes in behavior in association with the use of methylphenidate. While there is some evidence to suggest that methylphenidate causes changes in behavior, the majority of the studies reviewed paid little or no attention to this issue. Based on the available data, it is impossible to determine the point at which such behavioral effects occur. The frequency of occurrence of behavioral effects is also impossible to determine with certainty. Based on the available data, it is not possible to rule out whether behavioral effects may persist or not persist once treatment is discontinued. In conclusion, despite countless publications and extensive administration, especially to children, we have insufficient data to judge the long-term effects and risks of methylphenidate taking. PMID:27789952

Persistent ovarian masses and pregnancy outcomes.

PubMed

Goh, William A; Rincon, Monica; Bohrer, Justin; Tolosa, Jorge E; Sohaey, Roya; Riaño, Rene; Davis, James; Zalud, Ivica

2013-07-01

To determine if persistent ovarian masses in pregnancy are associated with increased adverse outcomes. This is a retrospective cohort of 126 pregnant women with a persistent ovarian mass measuring 5 cm or greater who delivered at two university hospitals between 2001 and 2009. Maternal outcomes included gestational age (GA) at diagnosis, delivery and surgery as well as miscarriage, preterm birth (PTB), ovarian torsion and hospital admission for pain. Neonatal outcomes included birth weight, respiratory distress syndrome (RDS), intra-ventricular hemorrhage (IVH), death and sepsis. A total of 1225 ovarian masses were identified (4.9%) in 24,868 patients. A persistent ovarian mass was found in 0.7%. Average GA at diagnosis was 17.8 weeks. Miscarriage rate was 3.3%. Average GA at delivery was 37.9 weeks. Of the patients, 8.5% had ovarian torsion, 10.3% had admission for pain and 9.3% had PTBs. The mean cesarean delivery rate was 46.3%. The average neonatal weight was 3273 g. There was one neonatal death in this cohort. The rate of RDS was 2.8%, IVH 0.9% and neonatal sepsis 1.9%. The most common surgical pathologic diagnosis was dermoids (37.6%). No overt malignancies were seen. A persistent ovarian mass in pregnancy does not confer an increased risk of adverse pregnancy outcomes.

Role Models and the Psychological Characteristics That Buffer Low-Socioeconomic-Status Youth from Cardiovascular Risk

ERIC Educational Resources Information Center

Chen, Edith; Lee, William K.; Cavey, Lisa; Ho, Amanda

2013-01-01

Little is understood about why some youth from low-socioeconomic-status (SES) environments exhibit good health despite adversity. This study tested whether role models and "shift-and-persist" approaches (reframing stressors more benignly while persisting with future optimism) protect low-SES youth from cardiovascular risk. A total of 163…

Pesticide Exposure, Safety Issues, and Risk Assessment Indicators

PubMed Central

Damalas, Christos A.; Eleftherohorinos, Ilias G.

2011-01-01

Pesticides are widely used in agricultural production to prevent or control pests, diseases, weeds, and other plant pathogens in an effort to reduce or eliminate yield losses and maintain high product quality. Although pesticides are developed through very strict regulation processes to function with reasonable certainty and minimal impact on human health and the environment, serious concerns have been raised about health risks resulting from occupational exposure and from residues in food and drinking water. Occupational exposure to pesticides often occurs in the case of agricultural workers in open fields and greenhouses, workers in the pesticide industry, and exterminators of house pests. Exposure of the general population to pesticides occurs primarily through eating food and drinking water contaminated with pesticide residues, whereas substantial exposure can also occur in or around the home. Regarding the adverse effects on the environment (water, soil and air contamination from leaching, runoff, and spray drift, as well as the detrimental effects on wildlife, fish, plants, and other non-target organisms), many of these effects depend on the toxicity of the pesticide, the measures taken during its application, the dosage applied, the adsorption on soil colloids, the weather conditions prevailing after application, and how long the pesticide persists in the environment. Therefore, the risk assessment of the impact of pesticides either on human health or on the environment is not an easy and particularly accurate process because of differences in the periods and levels of exposure, the types of pesticides used (regarding toxicity and persistence), and the environmental characteristics of the areas where pesticides are usually applied. Also, the number of the criteria used and the method of their implementation to assess the adverse effects of pesticides on human health could affect risk assessment and would possibly affect the characterization of the already approved pesticides and the approval of the new compounds in the near future. Thus, new tools or techniques with greater reliability than those already existing are needed to predict the potential hazards of pesticides and thus contribute to reduction of the adverse effects on human health and the environment. On the other hand, the implementation of alternative cropping systems that are less dependent on pesticides, the development of new pesticides with novel modes of action and improved safety profiles, and the improvement of the already used pesticide formulations towards safer formulations (e.g., microcapsule suspensions) could reduce the adverse effects of farming and particularly the toxic effects of pesticides. In addition, the use of appropriate and well-maintained spraying equipment along with taking all precautions that are required in all stages of pesticide handling could minimize human exposure to pesticides and their potential adverse effects on the environment. PMID:21655127

Persistence of Infarct Zone T2 Hyperintensity at 6 Months After Acute ST-Segment–Elevation Myocardial Infarction

PubMed Central

Carberry, Jaclyn; Carrick, David; Haig, Caroline; Ahmed, Nadeem; Mordi, Ify; McEntegart, Margaret; Petrie, Mark C.; Eteiba, Hany; Hood, Stuart; Watkins, Stuart; Lindsay, Mitchell; Davie, Andrew; Mahrous, Ahmed; Ford, Ian; Sattar, Naveed; Welsh, Paul; Radjenovic, Aleksandra; Oldroyd, Keith G.

2017-01-01

Background— The incidence and clinical significance of persistent T2 hyperintensity after acute ST-segment–elevation myocardial infarction (STEMI) is uncertain. Methods and Results— Patients who sustained an acute STEMI were enrolled in a cohort study (BHF MR-MI: NCT02072850). Two hundred eighty-three STEMI patients (mean age, 59±12 years; 75% male) had cardiac magnetic resonance with T2 mapping performed at 2 days and 6 months post-STEMI. Persisting T2 hyperintensity was defined as infarct T2 >2 SDs from remote T2 at 6 months. Infarct zone T2 was higher than remote zone T2 at 2 days (66.3±6.1 versus 49.7±2.1 ms; P<0.001) and 6 months (56.8±4.5 versus 49.7±2.3 ms; P<0.001). Remote zone T2 did not change over time (mean change, 0.0±2.7 ms; P=0.837), whereas infarct zone T2 decreased (−9.5±6.4 ms; P<0.001). At 6 months, T2 hyperintensity persisted in 189 (67%) patients, who were more likely to have Thrombus in Myocardial Infarction flow 0 or 1 in the culprit artery (P=0.020), incomplete ST-segment resolution (P=0.037), and higher troponin (P=0.024). Persistent T2 hyperintensity was associated with NT-proBNP (N-terminal pro-B-type natriuretic peptide) concentration (0.57 on a log scale [0.42–0.72]; P=0.004) and the likelihood of adverse left ventricular remodeling (>20% change in left ventricular end-diastolic volume; 21.91 [2.75–174.29]; P=0.004). Persistent T2 hyperintensity was associated with all-cause death and heart failure, but the result was not significant (P=0.051). ΔT2 was associated with all-cause death and heart failure (P=0.004) and major adverse cardiac events (P=0.013). Conclusions— Persistent T2 hyperintensity occurs in two thirds of STEMI patients. Persistent T2 hyperintensity was associated with the initial STEMI severity, adverse remodeling, and long-term health outcome. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT02072850. PMID:29242240

Long Term Consequences: Effects on Normal Development Profile after Concussion

PubMed Central

Daneshvar, Daniel H.; Riley, David O.; Nowinski, Christopher J.; McKee, Ann C.; Stern, Robert A.; Cantu, Robert C.

2011-01-01

Each year in the United States, approximately 1.7 million people are diagnosed with a traumatic brain injury (TBI); an estimated 75% of these injuries are classified as mild TBIs (mTBI) or concussions. The symptoms of such injuries include a variety of somatic, cognitive, and behavioral deficits. While these symptoms typically resolve in a matter of weeks, both children and adults may suffer from Post-Concussion Syndrome (PCS) for months or longer. Suffering from PCS-related symptoms for an extended time may delay an individual’s return to work, adversely affect one’s quality of life, and result in additional social and economic costs. Though a consensus has not been reached on the cause of long-term PCS, it is likely that biological, physiological, psychological, and social elements all play a role in symptom persistence. Additionally, persistent PCS may adversely affect one’s developmental trajectory. The enduring effects of head trauma are not limited to PCS-related effects, however. A progressive tauopathy, chronic traumatic encephalopathy (CTE) is believed to stem from repeated brain trauma. While CTE was originally associated with boxing, it has recently been found in other cases of repetitive head injury including former football and hockey players, and professional wrestlers. In addition to this observed pathology, repetitive brain trauma is also associated with Alzheimer’s-like dementia, Parkinsonism, and motor neuron disease including Amyotrophic Lateral Sclerosis (ALS). With these significant long-term effects of head injuries, there is a clear need to develop effective diagnoses, treatments, and education plans to reduce future burden and incidence. PMID:22050943

In the Shadow of Coal: How Large-Scale Industries Contributed to Present-Day Regional Differences in Personality and Well-Being.

PubMed

Obschonka, Martin; Stuetzer, Michael; Rentfrow, Peter J; Shaw-Taylor, Leigh; Satchell, Max; Silbereisen, Rainer K; Potter, Jeff; Gosling, Samuel D

2017-11-20

Recent research has identified regional variation of personality traits within countries but we know little about the underlying drivers of this variation. We propose that the Industrial Revolution, as a key era in the history of industrialized nations, has led to a persistent clustering of well-being outcomes and personality traits associated with psychological adversity via processes of selective migration and socialization. Analyzing data from England and Wales, we examine relationships between the historical employment share in large-scale coal-based industries (coal mining and steam-powered manufacturing industries that used this coal as fuel for their steam engines) and today's regional variation in personality and well-being. Even after controlling for possible historical confounds (historical energy supply, education, wealth, geology, climate, population density), we find that the historical local dominance of large-scale coal-based industries predicts today's markers of psychological adversity (lower Conscientiousness [and order facet scores], higher Neuroticism [and anxiety and depression facet scores], lower activity [an Extraversion facet], and lower life satisfaction and life expectancy). An instrumental variable analysis, using the historical location of coalfields, supports the causal assumption behind these effects (with the exception of life satisfaction). Further analyses focusing on mechanisms hint at the roles of selective migration and persisting economic hardship. Finally, a robustness check in the U.S. replicates the effect of the historical concentration of large-scale industries on today's levels of psychological adversity. Taken together, the results show how today's regional patterns of personality and well-being (which shape the future trajectories of these regions) may have their roots in major societal changes underway decades or centuries earlier. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Electrophysiologic profile and results of invasive risk stratification in asymptomatic children and adolescents with the Wolff-Parkinson-White electrocardiographic pattern.

PubMed

Kubuš, Peter; Vít, Pavel; Gebauer, Roman A; Materna, Ondřej; Janoušek, Jan

2014-04-01

Data on the results and clinical effect of an invasive risk stratification strategy in asymptomatic young patients with the Wolff-Parkinson-White electrocardiographic pattern are scarce. Eighty-five consecutive patients aged<18 years with a Wolff-Parkinson-White pattern and persistent preexcitation at maximum exercise undergoing invasive risk stratification were retrospectively studied. Adverse accessory pathway (AP) properties were defined according to currently consented criteria as any of the following: shortest preexcited RR interval during atrial fibrillation/rapid atrial pacing≤250 ms (or antegrade effective refractory period≤250 ms if shortest preexcited RR interval was not available) or inducible atrioventricular re-entrant tachycardia. Age at evaluation was median 14.9 years. Eighty-two patients had a structurally normal heart and 3 had hypertrophic cardiomyopathy. A single manifest AP was present in 80, 1 manifest and 1 concealed AP in 4, and 2 manifest APs in 1 patient. Adverse AP properties were present in 32 of 85 patients (37.6%) at baseline and in additional 16 of 44 (36.4%) after isoproterenol. Ablation was performed in 41 of these 48 patients. Ablation was deferred in the remaining 7 for pathway proximity to the atrioventricular node. In addition, 18 of the low-risk patients were ablated based on patient/parental decision. Adverse AP properties at baseline were exhibited by 37.6% of the evaluated patients with an asymptomatic Wolff-Parkinson-White preexcitation persisting at peak exercise. Isoproterenol challenge yielded additional 36.4% of those tested at higher risk. Ablation was performed in a total of 69.4% of patients subjected to invasive risk stratification.

In elective arch surgery with circulatory arrest, does the arterial cannulation site really matter? A propensity score analysis of right axillary and innominate artery cannulation.

PubMed

Preventza, Ourania; Price, Matt D; Spiliotopoulos, Konstantinos; Amarasekara, Hiruni S; Cornwell, Lorraine D; Omer, Shuab; de la Cruz, Kim I; Zhang, Qianzi; Green, Susan Y; LeMaire, Scott A; Rosengart, Todd K; Coselli, Joseph S

2018-05-01

The preferred arterial cannulation site for elective proximal aortic procedures requiring circulatory arrest varies, and different sites have been tried. We evaluated the relationships between arterial cannulation site and adverse outcomes, including stroke, in patients undergoing elective aortic arch surgery. We reviewed the records of 938 patients who underwent elective hemiarch or total arch surgery with circulatory arrest between 2006 and 2016. Five cannulation sites were used: the right axillary (n = 515; 54.9%), innominate (n = 376; 40.1%), and right common carotid arteries (n = 15; 1.6%), each with a side graft; the ascending aorta (n = 19; 2.0%); and the femoral artery (n = 13; 1.4%). Multivariable logistic regression analysis was used to model the effects of cannulation site on adverse outcomes for the entire cohort and for a subcohort of 891 patients who underwent innominate or axillary artery cannulation. Propensity-matching yielded 564 patients (282 pairs) from the right axillary and innominate artery groups. For the entire cohort, mortality, stroke, and composite adverse outcome (operative death or persistent stroke or renal failure at hospital discharge) rates were 7.0%, 4.1%, and 9.8%. In the multivariable analysis of the axillary/innominate subcohort, cannulation site did not independently predict operative mortality, persistent stroke, or composite adverse event. These results were confirmed with the propensity-matched analysis, where both axillary and innominate artery cannulation provided equivalent composite adverse event rates, operative death rates, and overall stroke rates. During elective arch surgery, right axillary artery cannulation and innominate artery cannulation (both via a side graft) produce excellent results and can be used interchangeably. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

PubMed Central

2000-01-01

• A cream containing 0.05% tretinoin (Retinova® is approved for treatment of sun-induced skin damage (“photoaging”). • Three trials comparing tretinoin with the excipient show that the effects of tretinoin cream are at best limited and slow to occur. Furthermore, they disappear on treatment cessation, necessitating long-term use. • The 0.05% tretinoin cream has poor local tolerability: most subjects develop irritation and fragile skin and require longer intervals between each application. Systemic adverse effects occur in some circumstances. • There are persistent doubts about whether it is safe to use tretinoin during pregnancy. PMID:10790815

Early-Life Effects on Adult Physical Activity: Concepts, Relevance, and Experimental Approaches.

PubMed

Garland, Theodore; Cadney, Marcell D; Waterland, Robert A

Locomotion is a defining characteristic of animal life and plays a crucial role in most behaviors. Locomotion involves physical activity, which can have far-reaching effects on physiology and neurobiology, both acutely and chronically. In human populations and in laboratory rodents, higher levels of physical activity are generally associated with positive health outcomes, although excessive exercise can have adverse consequences. Whether and how such relationships occur in wild animals is unknown. Behavioral variation among individuals arises from genetic and environmental factors and their interactions as well as from developmental programming (persistent effects of early-life environment). Although tremendous progress has been made in identifying genetic and environmental influences on individual differences in behavior, early-life effects are not well understood. Early-life effects can in some cases persist across multiple generations following a single exposure and, in principle, may constrain or facilitate the rate of evolution at multiple levels of biological organization. Understanding the mechanisms of such transgenerational effects (e.g., exposure to stress hormones in utero, inherited epigenetic alterations) may prove crucial to explaining unexpected and/or sex-specific responses to selection as well as limits to adaptation. One area receiving increased attention is early-life effects on adult physical activity. Correlational data from epidemiological studies suggest that early-life nutritional stress can (adversely) affect adult human activity levels and associated physiological traits (e.g., body composition, metabolic health). The few existing studies of laboratory rodents demonstrate that both maternal and early-life exercise can affect adult levels of physical activity and related phenotypes. Going forward, rodents offer many opportunities for experimental studies of (multigenerational) early-life effects, including studies that use maternal exposures and cross-fostering designs.

Probable topiramate-induced diarrhea in a 2-month-old breast-fed child - A case report.

PubMed

Westergren, Tone; Hjelmeland, Knut; Kristoffersen, Bjørg; Johannessen, Svein Ivar; Kalikstad, Betty

2014-01-01

An infant developed a severe condition of recurrent and persistent watery diarrhea at 40 days of age. The child had been partially breast-fed, and the mother used topiramate for epilepsy. Hospital examination excluded a viral or bacterial infection and failed to identify any other potential cause. After two weeks, topiramate exposure was suspected to be the cause, and breast-feeding was suspended. The diarrhea ceased within 2 days. Analysis of the breast milk showed a topiramate concentration of 15.7 μmol/L (5.3 μg/mL). There is little information on the use of topiramate in breast-feeding women. The potential effects on the children are not known. Topiramate passes into breast milk, and the concentration may equal the therapeutic plasma concentration. In this case, the infant may have ingested up to 40% of the mother's weight-adjusted dose. Diarrhea is a well-known adverse reaction to topiramate and has the potential to cause serious electrolyte disturbances in neonates and infants. The condition improved rapidly after suspension of breast-feeding. Topiramate in breast milk may reach levels that cause adverse effects in infants. Based on the adverse reaction profile of topiramate and the milk concentration, the diarrhea was assessed as a probable adverse drug reaction in the infant.

Chromium-induced kidney disease.

PubMed

Wedeen, R P; Qian, L F

1991-05-01

Kidney disease is often cited as one of the adverse effects of chromium, yet chronic renal disease due to occupational or environmental exposure to chromium has not yet been reported. Occasional cases of acute tubular necrosis (ATN) following massive absorption of chromate have been described. Chromate-induced ATN has been extensively studied in experimental animals following parenteral administration of large doses of potassium chromate (hexavalent) (15 mg/kg body weight). The chromate is selectively accumulated in the convoluted proximal tubule where necrosis occurs. An adverse long-term effect of low-dose chromium exposure on the kidneys is suggested by reports of low molecular weight (LMW) proteinuria in chromium workers. Excessive urinary excretion of beta 2-microglobulin, a specific proximal tubule brush border protein, and retinol-binding protein has been reported among chrome platers and welders. However, LMW proteinuria occurs after a variety of physiologic stresses, is usually reversible, and cannot by itself be considered evidence of chronic renal disease. Chromate-induced ATN and LMW proteinuria in chromium workers, nevertheless, raise the possibility that low-level, long-term exposure may produce persistent renal injury. The absence of evidence of chromate-induced exposure may produce persistent renal injury. The absence of evidence of chromate-induced chronic renal disease cannot be interpreted as evidence of the absence of such injury. Rather, it must be recognized that no prospective cohort or case-control study of the delayed renal effects of low-level, long-term exposure to chromium has been published.

The novel sodium channel modulator GS-458967 (GS967) is an effective treatment in a mouse model of SCN8A encephalopathy.

PubMed

Baker, Erin M; Thompson, Christopher H; Hawkins, Nicole A; Wagnon, Jacy L; Wengert, Eric R; Patel, Manoj K; George, Alfred L; Meisler, Miriam H; Kearney, Jennifer A

2018-06-01

De novo mutations of SCN8A, encoding the voltage-gated sodium channel Na V 1.6, have been associated with a severe infant onset epileptic encephalopathy. Individuals with SCN8A encephalopathy have a mean age of seizure onset of 4-5 months, with multiple seizure types that are often refractory to treatment with available drugs. Anecdotal reports suggest that high-dose phenytoin is effective for some patients, but there are associated adverse effects and potential for toxicity. Functional characterization of several SCN8A encephalopathy variants has shown that elevated persistent sodium current is one of several common biophysical defects. Therefore, specifically targeting elevated persistent current may be a useful therapeutic strategy in some cases. The novel sodium channel modulator GS967 has greater preference for persistent as opposed to peak current and nearly 10-fold greater potency than phenytoin. We evaluated the therapeutic effect of GS967 in the Scn8a N1768D/+ mouse model carrying an SCN8A patient mutation that results in elevated persistent sodium current. We also performed patch clamp recordings to assess the effect of GS967 on peak and persistent sodium current and excitability in hippocampal neurons from Scn8a N1768D/+ mice. GS967 potently blocked persistent sodium current without affecting peak current, normalized action potential morphology, and attenuated excitability in neurons from heterozygous Scn8a N1768D/+ mice. Acute treatment with GS967 provided dose-dependent protection against maximal electroshock-induced seizures in Scn8a N1768D/+ and wild-type mice. Chronic treatment of Scn8a N1768D/+ mice with GS967 resulted in lower seizure burden and complete protection from seizure-associated lethality observed in untreated Scn8a N1768D/+ mice. Protection was achieved at a chronic dose that did not cause overt behavioral toxicity or sedation. Persistent sodium current modulators like GS967 may be an effective precision targeting strategy for SCN8A encephalopathy and other functionally similar channelopathies when elevated persistent sodium current is the primary dysfunction. Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.

The origin and evolution of assessment criteria for persistent, bioaccumulative and toxic (PBT) chemicals and persistent organic pollutants (POPs).

PubMed

Matthies, Michael; Solomon, Keith; Vighi, Marco; Gilman, Andy; Tarazona, Jose V

2016-09-14

General public concern over the effects of persistent chemicals began in the early 1960s. Since then, significant scientific advances have increased our understanding of persistent, bioaccumulative, and toxic (PBT) chemicals and the properties and processes that influence their fates in, and adverse effects on, human health and the environment. In addition to the scientific advances, a number of legislations and agreements for national, international, and global identification and control of PBT chemicals have been adopted. However, some of the rationales and thoughts that were relied upon when the first criteria were developed to identify and categorize PBT chemicals and then POPs (persistent organic pollutants) have not been carried forward. Criteria have been based upon available data of neutral hydrophobic substances as reference chemicals, derived under laboratory conditions. They evolved over the last decades due to the diversification of the protection aims under various national regulatory frameworks and international agreements, advances in methods for estimation of physical/chemical properties, and the identification of chemicals which are non-traditional POPs. Criteria are not defined purely by science; they also are subject to the aims of policy. This paper offers a historical perspective on the development of criteria for PBT chemicals and POPs. It also offers suggestions for rationalization of protection goals, describes some emerging procedures for identification of compounds of concern, and proposes information that needs to be considered when applying criteria to screening and/or evaluation of new chemicals.

Predicting regime shifts in flow of the Colorado River

USGS Publications Warehouse

Gangopadhyay, Subhrendu; McCabe, Gregory J.

2010-01-01

The effects of continued global warming on water resources are a concern for water managers and stake holders. In the western United States, where the combined climatic demand and consumptive use of water is equal to or greater than the natural supply of water for some locations, there is growing concern regarding the sustainability of future water supplies. In addition to the adverse effects of warming on water supply, another issue for water managers is accounting for, and managing, the effects of natural climatic variability, particularly persistently dry and wet periods. Analyses of paleo-reconstructions of Upper Colorado River basin (UCRB) flow demonstrate that severe sustained droughts, and persistent pluvial periods, are a recurring characteristic of hydroclimate in the Colorado River basin. Shifts between persistently dry and wet regimes (e.g., decadal to multi-decadal variability (D2M)) have important implications for water supply and water management. In this study paleo-reconstructions of UCRB flow are used to compute the risks of shifts between persistently wet and dry regimes given the length of time in a specific regime. Results indicate that low frequency variability of hydro-climatic conditions and the statistics that describe this low frequency variability can be useful to water managers by providing information about the risk of shifting from one hydrologic regime to another. To manage water resources in the future water managers will have to understand the joint hydrologic effects of natural climate variability and global warming. These joint effects may produce future hydrologic conditions that are unprecedented in both the instrumental and paleoclimatic records.

Current Status and Regulatory Aspects of Pesticides Considered to be Persistent Organic Pollutants (POPs) in Taiwan

PubMed Central

Tsai, Wen-Tien

2010-01-01

Organochlorine pesticides (OCPs) are capable of persisting in the environment, transporting between phase media and accumulating to high levels, implying that they could pose a risk of causing adverse effects to human health and the environment. Consequently, most OCPs are designated as persistent organic pollutants (POPs) and even as endocrine disrupting chemicals (EDCs). The objective of this paper was to review the current status of pesticide POPs in Taiwan, including aldrin, chlordane, chlordecone, DDT, dieldrin, endrin, heptachlor, hexachlorobenzene, α/β-hexachlorocyclohexanes, lindane, mirex, pentachloro-benzene, and toxaphene. The information about their environmental properties, banned use, carcinogenic toxicity and environmental levels, can be connected with the regulatory infrastructure, which has been established by the joint-venture of the central competent authorities (i.e., Environmental Protection Administration, Department of Health, Council of Agriculture, and Council of Labor Affairs). The significant progress to be reported is that the residual levels of these pesticide-POPs, ranging from trace amounts to a few ppb, have declined notably in recent years. PMID:21139852

Current status and regulatory aspects of pesticides considered to be persistent organic pollutants (POPs) in Taiwan.

PubMed

Tsai, Wen-Tien

2010-10-01

Organochlorine pesticides (OCPs) are capable of persisting in the environment, transporting between phase media and accumulating to high levels, implying that they could pose a risk of causing adverse effects to human health and the environment. Consequently, most OCPs are designated as persistent organic pollutants (POPs) and even as endocrine disrupting chemicals (EDCs). The objective of this paper was to review the current status of pesticide POPs in Taiwan, including aldrin, chlordane, chlordecone, DDT, dieldrin, endrin, heptachlor, hexachlorobenzene, α/β-hexachlorocyclohexanes, lindane, mirex, pentachloro-benzene, and toxaphene. The information about their environmental properties, banned use, carcinogenic toxicity and environmental levels, can be connected with the regulatory infrastructure, which has been established by the joint-venture of the central competent authorities (i.e., Environmental Protection Administration, Department of Health, Council of Agriculture, and Council of Labor Affairs). The significant progress to be reported is that the residual levels of these pesticide-POPs, ranging from trace amounts to a few ppb, have declined notably in recent years.

Effects of age, sex and reproductive status on persistent organic pollutant concentrations in "Southern Resident" killer whales.

PubMed

Krahn, Margaret M; Hanson, M Bradley; Schorr, Gregory S; Emmons, Candice K; Burrows, Douglas G; Bolton, Jennie L; Baird, Robin W; Ylitalo, Gina M

2009-10-01

"Southern Resident" killer whales (Orcinus orca) that comprise three fish-eating "pods" (J, K and L) were listed as "endangered" in the US and Canada following a 20% population decline between 1996 and 2001. Blubber biopsy samples from Southern Resident juveniles had statistically higher concentrations of certain persistent organic pollutants than were found for adults. Most Southern Resident killer whales, including the four juveniles, exceeded the health-effects threshold for total PCBs in marine mammal blubber. Maternal transfer of contaminants to the juveniles during rapid development of their biological systems may put these young whales at greater risk than adults for adverse health effects (e.g., immune and endocrine system dysfunction). Pollutant ratios and field observations established that two of the pods (K- and L-pod) travel to California to forage. Nitrogen stable isotope values, supported by field observations, indicated possible changes in the diet of L-pod over the last decade.

Measuring Stress in Young Children Using Hair Cortisol: The State of the Science.

PubMed

Bates, Randi; Salsberry, Pamela; Ford, Jodi

2017-10-01

Extensive literature suggests that adverse experiences in early childhood may deleteriously impact later health. These effects are thought to be related to the impact of persistent or chronic stress on various biological processes, mediated by dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, and ultimately irregularities in cortisol levels. Ameliorating persistent stress in young children requires accurately measuring the chronicity of physiologic stress, which is difficult in young children because of unreliable self-report and the burden and inaccuracy associated with using invasive acute-stress biomeasures. A better way to approximate persistent stress in young children is measuring hair cortisol concentration (HCC), as it only requires one noninvasive collection to measure months of HPA-axis activity or experienced stress. However, few studies measure HCC in young children despite wide use in adult stress research. This article reviews and synthesizes research that uses HCC to approximate persistent stress in healthy children, 12-60 months of age. Reviewed studies indicate that HCC is elevated in young children who are experiencing forms of persistent stress such as low socioeconomic status and maternal distress. Hair cortisol is thus a promising measure of early childhood persistent stress, but due to the limited use of HCC in this population, much research is still needed. Specifically, nurse researchers may need to measure several factors associated with early childhood persistent stress and HCC to identify which children are at risk for stress-related disease.

Comprehensive Analysis of Drought Persistence, Hazard, and Recovery across the CONUS

NASA Astrophysics Data System (ADS)

Zarekarizi, M.; Ahmadi, B.; Moradkhani, H.

2017-12-01

Drought is a creeping intertwined natural hazard affecting society more than any other natural disaster and causing enormous damages on economy and ecosystems. Better understanding of potential drought hazard can help water managers and stakeholders devising mitigation plans to minimize the adverse effects of droughts. In this study, soil moisture, simulated by the Variable Infiltration Capacity (VIC) land surface model, is used to analyze the probability of agricultural drought with different severities across the CONUS. Due to the persistence of soil moisture, a drought episode at a particular time is affected by its earlier status; therefore, this study has utilized a Copula function to model the selected hydrologic variable over the time. The probability of drought intensity for each unit is presented spatially. If the unit remains in the drought condition at the same or lower intensity, drought persists and if it improves above a pre-defined threshold, the unit recovers. Results show that the west of US is more vulnerable to drought persistence in summer and spring while the Midwest and Northeast of US are experiencing drought persistence in fall and winter. In addition, the analysis reveals that as the intensity of drought in a given season decreases the following season has higher chance of recovery.

Bronchial Thermoplasty – Long Term Safety and Effectiveness in Severe Persistent Asthma

PubMed Central

Wechsler, Michael E.; Laviolette, Michel; Rubin, Adalberto S.; Fiterman, Jussara; Lapa e Silva, Jose R.; Shah, Pallav L.; Fiss, Elie; Olivenstein, Ronald; Thomson, Neil C.; Niven, Robert M.; Pavord, Ian D.; Simoff, Michael; Hales, Jeff B.; McEvoy, Charlene; Slebos, Dirk-Jan; Holmes, Mark; Phillips, Martin J.; Erzurum, Serpil C.; Hanania, Nicola A.; Sumino, Kaharu; Kraft, Monica; Cox, Gerard; Sterman, Daniel H.; Hogarth, Kyle; Kline, Joel N.; Mansur, Adel H.; Louie, Brian E.; Leeds, William M.; Barbers, Richard G.; Austin, John H.M.; Shargill, Narinder S.; Quiring, John; Armstrong, Brian; Castro, Mario

2014-01-01

Background Bronchial thermoplasty (BT) has previously been shown to improve asthma control out to 2 years in patients with severe persistent asthma. Objective To assess effectiveness and safety of BT in asthma patients 5 years post therapy. Methods BT-treated subjects from the Asthma Intervention Research 2 (AIR2) Trial (ClinicalTrials.gov NCT01350414) were evaluated annually for 5 years to assess long-term safety of BT and durability of treatment effect. Outcomes assessed post-BT included severe exacerbations, adverse events, healthcare utilization, spirometry data, and high resolution computed tomography (HRCT) scans. Results 162/190 BT-treated subjects (85.3%) from the AIR2 Trial completed 5 years of follow-up. The proportion of subjects experiencing severe exacerbations and Emergency Room visits, and the rates of events in each of years 1 to 5 remained low and were less than those observed in the 12 months prior to BT treatment (average 5 year reduction in proportions: 44% for exacerbations and 78% for ER visits). Respiratory adverse events and respiratory-related hospitalizations remained unchanged in Years 2 through 5 as compared to the first year after BT. Pre-BD FEV1 values remained stable between years 1 and 5 after BT, despite a 17% reduction in average daily inhaled corticosteroid dose. HRCT scans from baseline to 5 years after BT showed no structural abnormalities that could be attributed to BT. Conclusions These data demonstrate the 5-year durability of the benefits of BT with regard to both asthma control (based on maintained reduction in severe exacerbations and ER visits for respiratory symptoms) and safety. BT has become an important addition to our treatment armamentarium and should be considered for patients with severe persistent asthma who remain symptomatic despite taking ICS (inhaled corticosteroids) and LABA (long-acting-β2-agonists). PMID:23998657

Effectiveness of betahistine (48 mg/day) in patients with vestibular vertigo during routine practice: The VIRTUOSO study.

PubMed

Parfenov, Vladimir A; Golyk, Volodymyr A; Matsnev, Eduard I; Morozova, Svetlana V; Melnikov, Oleg A; Antonenko, Ludmila M; Sigaleva, Elena E; Situkho, Maksym I; Asaulenko, Olena I; Popovych, Vasyl I; Zamergrad, Maxim V

2017-01-01

Vestibular vertigo is associated with substantially reduced quality of life. Betahistine is effective in improving vertigo-associated symptoms, with longer treatment periods leading to greater improvements; however, it is not known whether these effects persist after treatment cessation. VIRTUOSO was a prospective, multinational, non-comparative, post-marketing observational programme investigating the effectiveness of betahistine (48 mg/day) and the course of vertigo after the discontinuation of treatment. Patients with vestibular vertigo who were prescribed 48 mg/day betahistine were enrolled in Russia and Ukraine. Treatment duration was up to 2 months, and patients were followed up for 2 months after discontinuation of betahistine. Efficacy endpoints included clinical response (assessed by change in vertigo severity), monthly attack frequency, and physician and patient grading of overall clinical response and improvement of vertigo-associated symptoms. Overall, 309 patients were enrolled and 305 completed the study. Clinical response was rated as good, very good or excellent in 74.1% of patients at end of treatment, with vertigo severity significantly decreased from baseline (p < 0.001). Monthly vertigo attack frequency decreased significantly during the 2 months of treatment (p < 0.001 from baseline) and further decreased during the 2-month follow-up (p < 0.001 from end of treatment). Overall, clinical response was graded as good or excellent by 94.4% of physicians and 95.4% of patients. Clinical improvement was considered either good or excellent by 82.6-90.5% of physicians and patients for nausea, vomiting and faintness. Only one adverse event was reported, with no serious adverse events. Our findings suggest that betahistine (48 mg/day) therapy is effective in treating vertigo in routine clinical settings. The observed effects persisted for 2 months after treatment cessation, suggesting that betahistine may facilitate lasting vestibular compensation.

Children's Executive Function in a CPS-Involved Sample: Effects of Cumulative Adversity and Specific Types of Adversity.

PubMed

Roos, Leslie E; Kim, Hyoun K; Schnabler, Simone; Fisher, Philip A

2016-12-01

Prior research has identified the presence of executive function (EF) deficits in child protective service (CPS) involved (versus non-involved) children but minimal work has examined predictors that might explain individual differences within these CPS-involved children. Here, we sought to characterize EF in a large sample (N=694) of CPS-involved children and examine how specific adversities (physical abuse, neglect, caregiver domestic violence, and caregiver substance dependence) and cumulative adversity (at ages 0-3 and 3-6 years) predict EF (at approximately 5-6 years). It was expected that the sample would exhibit low EF overall based on previous research in maltreated children. Specific adversity and cumulative adversity analyses were largely exploratory given the limited previous work in this area. Results indicated poor EF overall, with 43.5% of children performing worse than chance. Amongst children who performed greater than chance, higher cumulative adversity, physical abuse, and caregiver substance use (at ages 3-6 years) predicted better EF. These findings join literature documenting that, within CPS-involved children, the presence of certain adversities predicts variable cognitive function. Findings highlight the potential relevance of evolutionary psychology to understanding how alterations in behavior linked to harsh and unpredictable early environments may cue accelerated brain development underlying relative cognitive advantages, within at-risk, low performing samples. Longitudinal studies are critical to determine if the relative EF advantages linked to higher adversity persist over time or result in lower EF later on, reflecting a more rapid, but overall limited, trajectory of cognitive development.

Factors associated with high 24-month persistence with denosumab: results of a real-world, non-interventional study of women with postmenopausal osteoporosis in Germany, Austria, Greece, and Belgium.

PubMed

Fahrleitner-Pammer, A; Papaioannou, N; Gielen, E; Feudjo Tepie, M; Toffis, C; Frieling, I; Geusens, P; Makras, P; Boschitsch, E; Callens, J; Anastasilakis, A D; Niedhart, C; Resch, H; Kalouche-Khalil, L; Hadji, P

2017-12-01

Persistence with osteoporosis therapy is vital for fracture prevention. This non-interventional study of postmenopausal women receiving denosumab in Germany, Austria, Greece, and Belgium found that persistence with denosumab remains consistently high after 24 months in patients at high risk of fracture. Continued persistence with osteoporosis therapy is vital for fracture prevention. This non-interventional study of clinical practice evaluated medication-taking behavior of postmenopausal women receiving denosumab in Germany, Austria, Greece, and Belgium and factors influencing persistence. Subcutaneous denosumab (60 mg every 6 months) was assigned according to prescribing information and local guidelines before and independently of enrollment; outcomes were recorded during routine practice for up to 24 months. Persistence was defined as receiving the subsequent injection within 6 months + 8 weeks of the previous injection and adherence as administration of subsequent injections within 6 months ± 4 weeks of the previous injection. Medication coverage ratio (MCR) was calculated as the proportion of time a patient was covered by denosumab. Associations between pre-specified baseline covariates and 24-month persistence were assessed using multivariable logistic regression. The 24-month analyses included 1479 women (mean age 66.3-72.5 years) from 140 sites; persistence with denosumab was 75.1-86.0%, adherence 62.9-70.1%, and mean MCR 87.4-92.4%. No covariate had a significant effect on persistence across all four countries. For three countries, a recent fall decreased persistence; patients were generally older with chronic medical conditions. In some countries, other covariates (e.g., older age, comorbidity, immobility, and prescribing reasons) decreased persistence. Adverse drug reactions were reported in 2.3-6.9% patients. Twenty-four-month persistence with denosumab is consistently high among postmenopausal women in Europe and may be influenced by patient characteristics. Further studies are needed to identify determinants of low persistence.

Low-level laser/light therapy for androgenetic alopecia.

PubMed

Gupta, Aditya K; Lyons, Danika C A; Abramovits, William

2014-01-01

Androgenetic alopecia (AGA) is a persistent and pervasive condition that affects men worldwide. Some common treatment options for AGA include hair prosthetics, oral and topical medications, and surgical hair restoration (SHR). Pharmaceutical and SHR treatments are associated with limitations including adverse side effects and significant financial burden. Low-level laser or light (LLL) devices offer alternative treatment options that are not typically associated with adverse side effects or significant costs. There are clinic- and home-based LLL devices. One home-based laser comb device has set a standard for others; however, this device requires time devoted to carefully moving the comb through the hair to allow laser penetration to the scalp. A novel helmet-like LLL device for hair growth has proven effective in preliminary trials and allows for hands-free use. Regardless, there are few clinical trials that have been conducted regarding LLL devices for AGA and results are mixed. Further research is required to establish the true efficacy of these devices for hair growth in comparison to existing alternative therapies.

The influence of endocrine disruptors on growth and development of children.

PubMed

DiVall, Sara A

2013-02-01

This review describes the most recent data about the effects of endocrine disrupting compounds (EDCs) on infant and early childhood growth and reproductive tract development as well as controversies in the field. EDCs are present in pregnant women, young children and adolescents. Whether the level of exposure contributes to disease is an ongoing debate. Epidemiological studies suggest associations between prenatal EDC exposure and disease outcome, but animal studies using controlled EDC exposure have varying results with underlying mechanisms largely unknown. Human exposure to EDCs is widespread; bisphenol A, phthalates and persistent organic pollutants are detectable in all age groups and geographical locations in the USA. Epidemiological and animal studies suggest that phthalates and bisphenol A have adverse effects on birth weight, promote development of childhood obesity and adversely affect male reproductive tract development. Differences in the interpretation of available studies underlie the disparate conclusions of scientific and regulatory body's panels on potential toxicological effects of EDCs at current levels of human exposure.

Fixed and Growth Mindset in Education and How Grit Helps Students Persist in the Face of Adversity

ERIC Educational Resources Information Center

Hochanadel, Aaron; Finamore, Dora

2015-01-01

Students face a wealth of challenges in college for example a lack of support, sometimes making it difficult to persevere. However, in an academic environment that teaches grit and fosters growth, students can learn to persist. Those who believe intelligence is fixed and cannot be changed exert less effort to succeed. Students who persevere when…

Relapse outcomes, safety, and treatment patterns in patients diagnosed with relapsing-remitting multiple sclerosis and initiated on subcutaneous interferon β-1a or dimethyl fumarate: a real-world study.

PubMed

Ernst, Frank R; Barr, Peri; Elmor, Riad; Wong, Schiffon L

2017-12-01

To estimate real-world treatment patterns, safety, and relapse outcomes of subcutaneous (sc) interferon (IFN) β-1a (Rebif) vs dimethyl fumarate (DMF; Tecfidera), to treat relapsing-remitting multiple sclerosis (RRMS). A US retrospective chart review of 450 randomly selected adults newly diagnosed with RRMS who received sc IFN β-1a (n = 143) or DMF (n = 307) was conducted. Patients were either (a) treatment-naïve, initiating first-line treatment with sc IFN β-1a or DMF, or (b) previously treated, switching to sc IFN β-1a or DMF. Two years' follow-up data were captured. Patient characteristics, persistence, and adverse events between treatment groups were compared using t-tests or Chi-square tests. Kaplan-Meier curves with log-rank tests and Cox proportional hazards models were used to compare time to, and risk of non-persistence. Annualized Relapse Rates (ARR) were calculated using a robust variance Poisson model adjusting for covariates. Propensity scores were used to address possible selection bias. One hundred and twelve patients became non-persistent, most commonly due to an adverse event (n = 37). No difference was observed in time to overall non-persistence between sc IFN β-1a and DMF patients. Among treatment-naïve patients, those receiving DMF had 2.4-times the risk (HR = 2.439, 95% CI = 1.007-5.917, p = .0483) of experiencing a discontinuation than patients receiving sc IFN β-1a. Non-persistent patients receiving DMF had 2.3-times the risk (HR = 2.311, 95% CI = 1.350-3.958, p = .0023) of experiencing an adverse event at a given time point than patients prescribed sc IFN β-1a. No differences in relapse risk or ARR between sc IFN β-1a- and DMF-treated patients were observed. sc IFN β-1a-treated patients had comparable persistence and relapse outcomes, and better safety outcomes vs DMF-treated patients across 2 years.

Effects of vaginal lactobacilli in Chlamydia trachomatis infection.

PubMed

Mastromarino, Paola; Di Pietro, Marisa; Schiavoni, Giovanna; Nardis, Chiara; Gentile, Massimo; Sessa, Rosa

2014-07-01

Increasing evidence indicates that abnormal vaginal flora lacking lactobacilli facilitates the acquisition of several sexually transmitted diseases including Chlamydia trachomatis. C. trachomatis, the most common bacterial agent of genital infections worldwide, can progress from the lower to upper reproductive tract and induce severe sequelae. The ability of C. trachomatis to develop into a persistent form has been suggested as key pathogenetic mechanism underlying chronic infections and sequelae. The aim of our study was to investigate the C. trachomatis interaction with vaginal microbiota analyzing the effects of Lactobacillus strains (L. brevis and L. salivarius) on the different phases of C. trachomatis developmental cycle. In addition, the effect of lactobacilli on persistent chlamydial forms induced by HSV-2 coinfection has also been evaluated. Our results demonstrated significant inhibition of C. trachomatis multiplication by vaginal lactobacilli. L. brevis was significantly more effective than L. salivarius (p<0.05) on all the steps of chlamydial infection cycle suggesting that the ability of lactobacilli to protect from infection is strain-dependent. Lactobacilli had an adverse effect on elementary chlamydial bodies (p<0.05), on chlamydial adsorption to epithelial cells (p<0.001) and on intracellular phases of chlamydial replication (p<0.0001). Our study also demonstrated a protective effect of lactobacilli toward persistent C. trachomatis forms induced by HSV-2 coinfection. A significant increase in the production of C. trachomatis infectious progeny was observed in C. trachomatis/HSV-2 coinfection in the presence of L. brevis (p=0.01) despite a significant inhibition of C. trachomatis multiplication (p=0.028). Our data suggest that a healthy vaginal microbiota can reduce the risk of acquiring C. trachomatis infection and counteract the development of persistent chlamydial forms. Copyright © 2014 Elsevier GmbH. All rights reserved.

Double probing of human spermatozoa for persistent histones, surplus cytoplasm, apoptosis and DNA fragmentation.

PubMed

Sati, Leyla; Ovari, Laszlo; Bennett, David; Simon, Stephen D; Demir, Ramazan; Huszar, Gabor

2008-04-01

Individual spermatozoa were assessed with pairs of probes for persistent histones and cytoplasmic retention, persistent histones and DNA fragmentation, and persistent histones and apoptotic markers. The individual spermatozoa were treated sequentially with combinations of probes for these cytoplasmic and nuclear biochemical markers. Sperm fields were recorded with computer-assisted imaging, and staining patterns with the two probes in the same spermatozoa were examined and scored as light, intermediate or dark (mature to arrested-maturity spermatozoa). The effects of arrested sperm maturation were similar with respect to the cytoplasmic and nuclear characteristics of spermatozoa in 84% of cells, indicating that cytoplasmic and nuclear attributes of arrested sperm maturation are related. However, there were moderate (intermediate-dark or intermediate-light patterns, 14.5% of cells) or major (light-dark patterns, 1.6% of cells) discrepancies in the intensity of the double staining patterns. Thus, testing with single maturity markers may not be fully reliable. These findings are important with respect to: (i) arrested sperm maturation; (ii) potential efficacy of antioxidant and similar therapeutic strategies in subfertile men, as spermatozoa with infrastructure defects due to mismaturation or maturation arrest are unlikely to respond to interventions; and (iii) detection of adverse male environmental exposures.

Economic Adversity Transitions From Childhood to Older Adulthood Are Differentially Associated With Later-Life Physical Performance Measures in Men and Women in Middle and High-Income Sites.

PubMed

Hwang, Phoebe W; Dos Santos Gomes, Cristiano; Auais, Mohammad; Braun, Kathryn L; Guralnik, Jack M; Pirkle, Catherine M

2017-10-01

This study examines the relationship between economic adversity transitions from childhood to older adulthood and older adulthood physical performance among 1,998 community-dwelling older adults from five demographically diverse sites from middle and high-income countries. The principal exposure variable was economic adversity transition. No adversity encompassed not experiencing poverty in both childhood and older adulthood, improved described having only experienced poverty in childhood, worsened captured having experienced poverty in older adulthood, and severe is having experienced poverty in both childhood and older adulthood. The short physical performance battery (SPPB) was used for outcome measures. Analyses of the continuous SPPB score used linear regression, while analysis of a binary outcome (SPPB < 8 vs. ≥8) used Poisson regression models with robust error variance, both adjusting for sex, education, and site location. In sex-stratified models, the SPPB < 8 prevalence rate ratio (PRR) was higher for the severe (PRR: 2.80, 95% confidence interval [CI] = [1.70, 4.61]), worsened (PRR: 2.40, 95% CI = [1.41, 4.09]), and improved (PRR: 1.82, 95% CI = [1.11, 3.01]) groups, compared with those with no adversity in childhood or as adults, but only for females. Findings from this study indicate that persistent economic adversity has a negative effect on older adult physical performance, especially among women.

Childhood adversity profiles and adult psychopathology in a representative Northern Ireland study.

PubMed

McLafferty, Margaret; Armour, Cherie; McKenna, Aine; O'Neill, Siobhan; Murphy, Sam; Bunting, Brendan

2015-10-01

Childhood adversities are key aetiological factors in the onset and persistence of psychopathology. The aims of this study were to identify childhood adversity profiles, and investigate the relationship between the adversity classes and psychopathology in Northern Ireland. The study utilized data from the Northern Ireland Study of Health and Stress, an epidemiological survey (N=1986), which used the CIDI to examine mental health disorders and associated risk factors. Latent Class Analysis revealed 3 distinct typologies; a low risk class (n=1709; 86%), a poly-adversity class (n=122; 6.1%), and an economic adversity class (n=155; 7.8%). Logistic Regression models revealed that individuals in the economic adversity class had a heightened risk of anxiety and substance disorders, with individuals in the poly-adversity class more likely to have a range of mental health problems and suicidality. The findings indicate the importance of considering the impact of co-occurring childhood adversities when planning treatment, prevention, and intervention programmes. Copyright © 2015 Elsevier Ltd. All rights reserved.

Preliminary data on Pemphigus vulgaris treatment by a proteomics-defined peptide: a case report

PubMed Central

Angelini, Giovanni; Bonamonte, Domenico; Lucchese, Alberta; Favia, Gianfranco; Serpico, Rosario; Mittelman, Abraham; Simone, Simone; Sinha, Animesh A; Kanduc, Darja

2006-01-01

Background Although described by Hippocrates in 400 B.C., pemphigus disease still needs a safe therapeutical approach, given that the currently used therapies (i.e. corticosteroids and immunosuppressive drugs) often provoke collateral effects. Here we present preliminary data on the possible use of a proteomics derived desmoglein peptide which appears promising in halting disease progression without adverse effects. Methods The low-similarity Dsg349–60REWVKFAKPCRE peptide was topically applied for 1 wk onto a lesion in a patient with a late-stage Pemphigus vulgaris (PV) complicated by diabetes and cataract disease. The peptide was applied as an adjuvant in combination with the standard corticosteroid-based immunosuppressive treatment. Results After 1 wk, the treated PV eroded lesion appeared dimensionally reduced and with an increased rate of re-epithelization when compared to adjacent non-treated lesions. Short-term benefits were: decrease of anti-Dsg antibody titer and reduction of the corticosteroid dosage. Long-term benefits: after two years following the unique 1-wk topical treatment, the decrease of anti-Dsg antibody titer persists. The patient is still at the low cortisone dosage. Adverse effects: no adverse effect could be monitored. Conclusion With the limits inherent to any preliminary study, this case report indicates that topical treatment with Dsg349–60REWVKFAKPCRE peptide may represent a feasible first step in the search for a simple, effective and safe treatment of PV. PMID:17062151

Pulmonary atelectasis: a pathogenic perioperative entity.

PubMed

Duggan, Michelle; Kavanagh, Brian P

2005-04-01

Atelectasis occurs in the dependent parts of the lungs of most patients who are anesthetized. Development of atelectasis is associated with decreased lung compliance, impairment of oxygenation, increased pulmonary vascular resistance, and development of lung injury. The adverse effects of atelectasis persist into the postoperative period and can impact patient recovery. This review article focuses on the causes, nature, and diagnosis of atelectasis. The authors discuss the effects and implications of atelectasis in the perioperative period and illustrate how preventive measures may impact outcome. In addition, they examine the impact of atelectasis and its prevention in acute lung injury.

Outcomes of Pituitary Radiation for Cushing's Disease.

PubMed

Ironside, Natasha; Chen, Ching-Jen; Lee, Cheng-Chia; Trifiletti, Daniel M; Vance, Mary Lee; Sheehan, Jason P

2018-06-01

Achievement of biochemical remission with preservation of normal pituitary function is the goal of treatment for Cushing's disease. For patients with persistent or recurrent Cushing's disease after transsphenoidal resection, radiation therapy may be a safe and effective treatment. Stereotactic radiosurgery is favored over conventional fractionated external beam radiation. Hormonal recurrence rates range from 0% to 36% at 8 years after treatment. Tumor control rates are high. New pituitary hormone deficiency is the most common adverse effect after stereotactic radiosurgery and external beam radiation. The effects of radiation planning optimization and use of adjuvant medication on endocrine remission rates warrant investigation. Copyright © 2018 Elsevier Inc. All rights reserved.

Long-term hepatic outcomes in survivors of stage 4S and 4 neuroblastoma in infancy.

PubMed

French, Amy E; Irwin, Meredith S; Navarro, Oscar M; Greenberg, Mark; Nathan, Paul C

2012-02-01

Infants with stage 4 and 4S neuroblastoma (NB) have a superior prognosis to older children. However, they often require intensive therapy including abdominal radiation. We aimed to investigate the long-term hepatic outcomes in infants with stage 4S and 4 NB. We reviewed the charts of 38 infants diagnosed with stage 4S and 4 NB between 1984 and 2002. We included only those with available follow-up 5 years following diagnosis. We assessed hepatic imaging and function (transaminases, bilirubin, alkaline phosphatase) at all available time points from diagnosis. Abnormalities present at more than 5 years from diagnosis were considered persistent late changes. We identified 15 stage 4S and 12 stage 4 patients. Twelve of 15 stage 4S patients had hepatic involvement at diagnosis, 8 of whom required abdominal radiation. Five of eight demonstrated late imaging changes. Two of four with hepatic metastases but no radiation demonstrated late imaging changes. The late imaging changes resolved over time and without intervention in 3/7 survivors. The persistent lesions included liver fibrosis (1) and focal nodular hyperplasia (FNH) (3). Five of 12 stage 4 NB patients had hepatic involvement at diagnosis; none required radiation or had late hepatic imaging changes. In stage 4S NB, adverse hepatic effects are infrequent, may resolve over time, and occur with or without radiation. FNH should be considered in those with persistent late imaging changes. Adverse hepatic outcomes after liver involvement or radiation in infants with stage 4 NB rarely occur. Copyright © 2011 Wiley Periodicals, Inc.

Study and treatment of post Lyme disease (STOP-LD): a randomized double masked clinical trial.

PubMed

Krupp, L B; Hyman, L G; Grimson, R; Coyle, P K; Melville, P; Ahnn, S; Dattwyler, R; Chandler, B

2003-06-24

To determine whether post Lyme syndrome (PLS) is antibiotic responsive. The authors conducted a single-center randomized double-masked placebo-controlled trial on 55 patients with Lyme disease with persistent severe fatigue at least 6 or more months after antibiotic therapy. Patients were randomly assigned to receive 28 days of IV ceftriaxone or placebo. The primary clinical outcomes were improvement in fatigue, defined by a change of 0.7 points or more on an 11-item fatigue questionnaire, and improvement in cognitive function (mental speed), defined by a change of 25% or more on a test of reaction time. The primary laboratory outcome was an experimental measure of CSF infection, outer surface protein A (OspA). Outcome data were collected at the 6-month visit. Patients assigned to ceftriaxone showed improvement in disabling fatigue compared to the placebo group (rate ratio, 3.5; 95% CI, 1.50 to 8.03; p = 0.001). No beneficial treatment effect was observed for cognitive function or the laboratory measure of persistent infection. Four patients, three of whom were on placebo, had adverse events associated with treatment, which required hospitalization. Ceftriaxone therapy in patients with PLS with severe fatigue was associated with an improvement in fatigue but not with cognitive function or an experimental laboratory measure of infection in this study. Because fatigue (a nonspecific symptom) was the only outcome that improved and because treatment was associated with adverse events, this study does not support the use of additional antibiotic therapy with parenteral ceftriaxone in post-treatment, persistently fatigued patients with PLS.

A review of the pathophysiology, etiology, and treatment of attention-deficit hyperactivity disorder (ADHD).

PubMed

Sharma, Alok; Couture, Justin

2014-02-01

To review the pathophysiology, etiology, and treatment of attention-deficit hyperactivity disorder (ADHD). A literature search was conducted in PubMed and EMBASE using the terms attention deficit hyperactive disorder, ADHD, pathophysiology, etiology, and neurobiology. Limits applied were the following: published in the past 10 years (January 2003 to August 2013), humans, review, meta-analysis, and English language. These yielded 63 articles in PubMed and 74 in EMBASE. After removing duplicate/irrelevant articles, 86 articles and their relevant reference citations were reviewed. ADHD is a neurological disorder that affects children, but symptoms may persist into adulthood. Individuals suffering from this disorder exhibit hyperactivity, inattention, impulsivity, and problems in social interaction and academic performance. Medications used to treat ADHD such as methylphenidate, amphetamine, and atomoxetine indicate a dopamine/norepinephrine deficit as the neurochemical basis of ADHD, but the etiology is more complex. Moreover, these agents have poor adverse effect profiles and a multitude of drug interactions. Because these drugs are also dispensed to adults who may have concomitant conditions or medications, a pharmacist needs to be aware of these adverse events and drug interactions. This review, therefore, focuses on the pathophysiology, etiology, and treatment of ADHD and details the adverse effects and drug interaction profiles of the drugs used to treat it. Published research shows the benefit of drug therapy for ADHD in children, but given the poor adverse effect and drug interaction profiles, these must be dispensed with caution.

Association of Long-term Proton Pump Inhibitor Therapy with Bone Fractures and effects on Absorption of Calcium, Vitamin B12, Iron, and Magnesium

PubMed Central

Ito, Tetsuhide; Jensen, Robert T.

2010-01-01

Proton pump inhibitors (PPI) are now one of the most widely used classes of drugs. PPIs have proven to have a very favorable safety profile and it is unusual for a patient to stop these drugs because of side effects. However, increasing numbers of patients are chronically taking PPIs for gastroesophageal reflux disease and a number of other common persistent conditions, therefore the long-term potential adverse effects are receiving increasing attention. One area that is receiving much attention and generally has been poorly studied, is the long-term effects of chronic acid suppression on the absorption of vitamins and nutrients. This area has received increased attention because of the reported potential adverse effect of chronic PPI treatment leading to an increased occurrence of bone fractures. This has led to an increased examination of the effects of PPIs on calcium absorption/metabolism as well as numerous cohort, case control and prospective studies of their ability to affect bone density and cause bone fractures. In this article these studies are systematically examined, as well as the studies of the effects of chronic PPI usage on VB12, iron and magnesium absorption. In general the studies in each of thee areas have led to differing conclusions, but when examined systematically, a number of the studies are showing consistent results that support the conclusion that long-term adverse effects on these processes can have important clinical implications. PMID:20882439

Sucroferric oxyhydroxide decreases serum phosphorus level and fibroblast growth factor 23 and improves renal anemia in hemodialysis patients.

PubMed

Shima, Hisato; Miya, Keiko; Okada, Kazuyoshi; Minakuchi, Jun; Kawashima, Shu

2018-06-08

Sucroferric oxyhydroxide, a novel iron-based phosphate-binder, has been shown to have beneficial effects in lowering serum phosphorus levels and improving renal anemia in clinical studies. Although an effect of this agent on fibroblast growth factor 23 (FGF23) has been reported in an animal study, there is little clinical data supporting this finding. This study aimed to evaluate the effect on chronic kidney disease-mineral and bone disorder, FGF23, renal anemia, iron-related parameters, adverse events of sucroferric oxyhydroxide in hemodialysis patients. Hemodialysis patients, receiving existing hyperphosphatemia drugs with insufficient benefit, were administered sucroferric oxyhydroxide with/without calcium carbonate for 16 weeks. Serum phosphorus level declined rapidly in Week 8 (p < 0.0001) and this decrease persisted until Week 16 (p < 0.0001). FGF23 decreased (p = 0.0412, Week 16), and hemoglobin increased (p < 0.0001, Week 16). Cumulative dose of erythropoiesis-stimulating agents (p = 0.0122, Week 16), and intravenous iron (p = 0.0233, Week 12) decreased. All adverse reactions were mild, and diarrhea was the most frequently observed adverse reaction (16.7%). Therefore, hyperphosphatemia treatment with sucroferric oxyhydroxide may safely improve serum phosphorus level, renal anemia, FGF23, and other factors that affect the prognosis of hemodialysis patients.

Effects of caffeine, sleep loss, and stress on cognitive performance and mood during U.S. Navy SEAL training. Sea-Air-Land.

PubMed

Lieberman, Harris R; Tharion, William J; Shukitt-Hale, Barbara; Speckman, Karen L; Tulley, Richard

2002-11-01

When humans are acutely exposed to multiple stressors, cognitive performance is substantially degraded. Few practical strategies are available to sustain performance under such conditions. This study examined whether moderate doses of caffeine would reduce adverse effects of sleep deprivation and exposure to severe environmental and operational stress on cognitive performance. Volunteers were 68 U.S. Navy Sea-Air-Land (SEAL) trainees, randomly assigned to receive either 100, 200, or 300 mg caffeine or placebo in capsule form after 72 h of sleep deprivation and continuous exposure to other stressors. Cognitive tests administered included scanning visual vigilance, four-choice visual reaction time, a matching-to-sample working memory task and a repeated acquisition test of motor learning and memory. Mood state, marksmanship, and saliva caffeine were also assessed. Testing was conducted 1 and 8 h after treatment. Sleep deprivation and environmental stress adversely affected performance and mood. Caffeine, in a dose-dependent manner, mitigated many adverse effects of exposure to multiple stressors. Caffeine (200 and 300 mg) significantly improved visual vigilance, choice reaction time, repeated acquisition, self-reported fatigue and sleepiness with the greatest effects on tests of vigilance, reaction time, and alertness. Marksmanship, a task that requires fine motor coordination and steadiness, was not affected by caffeine. The greatest effects of caffeine were present 1 h post-administration, but significant effects persisted for 8 h. Even in the most adverse circumstances, moderate doses of caffeine can improve cognitive function, including vigilance, learning, memory, and mood state. When cognitive performance is critical and must be maintained during exposure to severe stress, administration of caffeine may provide a significant advantage. A dose of 200 mg appears to be optimal under such conditions.

Efficacy and persistence of low-dose mirabegron (25 mg) in patients with overactive bladder: analysis in a real-world urological practice.

PubMed

Shen, Yuan Chi; Wang, Hung Jen; Chuang, Yao Chi

2018-06-07

Mirabegron is a relatively new drug to treat overactive bladder (OAB). The therapeutic doses are between 25 and 100 mg in clinical trials. We aimed to evaluate the efficacy and persistence of low-dose mirabegron (25 mg) in patients with OAB in daily urological practice. The study was a retrospective consecutive cohort of 177 OAB patients (101 male and 76 female) treated with 25 mg of mirabegron mg since January 2016 to November 2016. The therapeutic outcomes were assessed at baseline, 4, 12, and 24 weeks. Mirabegron usage was associated with a statistically significant decrease in Overactive Bladder Symptom Score, Urgency Severity Score, urge urinary incontinence, International Prostate Symptom Score (both storage and voiding symptom) at 4-week follow-up, and the therapeutic effects were further improved at 12- and 24-week follow-up. Among them, 118 patients (66.7%) and 84 patients (47.5%) were maintained on mirabegron therapy for more than 3 and 6 months, respectively. However, 29 patients (16%) had poor response with drug discontinuation within 3 months and 8 patients (4.5%) stopped medication due to adverse effects. The overall side effect was 10.2%, and the most common side effect was elevated blood pressure (2.8%) and increased post-void residual (2.8%). Between male and female patients, there was no statistical difference of symptom improvement and drug persistence rate. Low-dose mirabegron (25 mg) improves clinical outcomes in two-thirds of OAB patients with good safety profile and high persistence in daily urological practice. The therapeutic effect is similar between the genders.

Immunogenicity, safety and antibody persistence of a purified vero cell cultured rabies vaccine (Speeda) administered by the Zagreb regimen or Essen regimen in post-exposure subjects.

PubMed

Shi, Nianmin; Zhang, Yibin; Zheng, Huizhen; Zhu, Zhenggang; Wang, Dingming; Li, Sihai; Li, Yuhua; Yang, Liqing; Zhang, Junnan; Bai, Yunhua; Lu, Qiang; Zhang, Zheng; Luo, Fengji; Yu, Chun; Li, Li

2017-06-03

To compare the safety, immunogenicity and long-term effect of a purified vero cell cultured rabies vaccine in post-exposure subjects following 2 intramuscular regimens, Zagreb or Essen regimen. Serum samples were collected before vaccination and on days 7, 14, 42, 180 and 365 post vaccination. Solicited adverse events were recorded for 7 d following each vaccine dose, and unsolicited adverse events throughout the entire study period. This study was registered with ClinicalTrials.gov (NCT01821911 and NCT01827917). No serious adverse events were reported. Although Zagreb regimen had a higher incidence of adverse reactions than Essen regimen at the first and second injection, the incidence was similar at the third and fourth injection between these 2 groups as well. At day 42, 100% subjects developed adequate rabies virus neutralizing antibody concentrations (≥ 0.5IU/ml) for both regimens. At days 180 and 365, the antibody level decreased dramatically, however, the percentage of subjects with adequate antibody concentrations still remained high (above 75% and 50% respectively). None of confirmed rabies virus exposured subjects had rabies one year later, and percentage of subjects with adequate antibody concentrations reached 100% at days 14 and 42. Rabies post-exposure prophylaxis vaccination with PVRV following a Zagreb regimen had a similar safety, immunogenicity and long-term effect to the Essen regimen in China.

Cost implications of reduced work hours and workloads for resident physicians.

PubMed

Nuckols, Teryl K; Bhattacharya, Jay; Wolman, Dianne Miller; Ulmer, Cheryl; Escarce, José J

2009-05-21

Although the Accreditation Council for Graduate Medical Education (ACGME) limits the work hours of residents, concerns about fatigue persist. A new Institute of Medicine (IOM) report recommends, among other changes, improved adherence to the 2003 ACGME limits, naps during extended shifts, a 16-hour limit for shifts without naps, and reduced workloads. We used published data to estimate labor costs associated with transferring excess work from residents to substitute providers, and we examined the effects of our assumptions in sensitivity analyses. Next, using a probability model to represent labor costs as well as mortality and costs associated with preventable adverse events, we determined the net costs to major teaching hospitals and cost-effectiveness across a range of hypothetical changes in the rate of preventable adverse events. Annual labor costs from implementing the IOM recommendations were estimated to be $1.6 billion (in 2006 U.S. dollars) across all ACGME-accredited programs ($1.1 billion to $2.5 billion in sensitivity analyses). From a 10% decrease to a 10% increase in preventable adverse events, net costs per admission ranged from $99 to $183 for major teaching hospitals and from $17 to $266 for society. With 2.5% to 11.3% decreases in preventable adverse events, costs to society per averted death ranged from $3.4 million to $0. Implementing the four IOM recommendations would be costly, and their effectiveness is unknown. If highly effective, they could prevent patient harm at reduced or no cost from the societal perspective. However, net costs to teaching hospitals would remain high. 2009 Massachusetts Medical Society

[Mental health of children, adolescents and young adults--part 2: burden of illness, deficits of the German health care system and efficacy and effectiveness of early intervention services].

PubMed

Karow, A; Bock, T; Naber, D; Löwe, B; Schulte-Markwort, M; Schäfer, I; Gumz, A; Degkwitz, P; Schulte, B; König, H H; Konnopka, A; Bauer, M; Bechdolf, A; Correll, C; Juckel, G; Klosterkötter, J; Leopold, K; Pfennig, A; Lambert, M

2013-11-01

Numerous birth-control studies, epidemiological studies, and observational studies investigated mental health and health care in childhood, adolescence and early adulthood, including prevalence, age at onset, adversities, illness persistence, service use, treatment delay and course of illness. Moreover, the impact of the burden of illness, of deficits of present health care systems, and the efficacy and effectiveness of early intervention services on mental health were evaluated. According to these data, most mental disorders start during childhood, adolescence and early adulthood. Many children, adolescents and young adults are exposed to single or multiple adversities, which increase the risk for (early) manifestations of mental diseases as well as for their chronicity. Early-onset mental disorders often persist into adulthood. Service use of children, adolescents and young adults is low, even lower than in adult patients. Moreover, there is often a long delay between onset of illness and first adequate treatment with a variety of linked consequences for poorer psychosocial prognosis. This leads to a large burden of illness with respect to disability and costs. As a consequence several countries have implemented so-called "early intervention services" at the border of child and adolescent and adult psychiatry. Emerging studies show that these health care structures are effective and efficient. Part 2 of the present review focuses on illness burden including disability and costs, deficits of the present health care system in Germany, and efficacy and efficiency of early intervention services. © Georg Thieme Verlag KG Stuttgart · New York.

Parsing apart the persisters: Etiological mechanisms and criminal offense patterns of moderate- and high-level persistent offenders.

PubMed

Amemiya, Jamie; Vanderhei, Susan; Monahan, Kathryn C

2017-08-01

Longitudinal investigations that have applied Moffitt's dual taxonomic framework to criminal offending have provided support for the existence of adolescent-limited and life-course persistent antisocial individuals, but have also identified additional trajectories. For instance, rather than a single persistent trajectory, studies have found both high-level and moderate-level persistent offenders. To inform theory and progress our understanding of chronic antisocial behavior, the present study used a sample of serious adolescent offenders (N =1,088) followed from middle adolescence to early adulthood (14-25 years), and examined how moderate-level persistent offenders differed from low-rate, desisting, and high-level persistent offenders. Results indicated that moderate-level persisters' etiology and criminal offense patterns were most similar to high-level persisters, but there were notable differences. Specifically, increasing levels of contextual adversity characterized both moderate-level and high-level persisting trajectories, but moderate-level persisters reported consistently lower levels of environmental risk. While both high- and moderate-level persisters committed more drug-related offenses in early adulthood compared to adolescence, moderate-level persisters engaged in lower levels of antisocial behavior across all types of criminal offenses. Taken cumulatively, the findings of this study suggest that sociocontextual interventions may be powerful in reducing both moderate- and high-level persistence in crime.

Efficacy and Safety of Transdermal Buprenorphine versus Oral Tramadol/Acetaminophen in Patients with Persistent Postoperative Pain after Spinal Surgery.

PubMed

Lee, Jae Hyup; Kim, Jin-Hyok; Kim, Jin-Hwan; Kim, Hak-Sun; Min, Woo-Kie; Park, Ye-Soo; Lee, Kyu-Yeol; Lee, Jung-Hee

2017-01-01

Control of persistent pain following spinal surgery is an unmet clinical need. This study compared the efficacy and safety of buprenorphine transdermal system (BTDS) to oral tramadol/acetaminophen (TA) in Korean patients with persistent, moderate pain following spinal surgery. Open-label, interventional, randomized multicenter study. Adults with persistent postoperative pain (Numeric Rating Scale [NRS] ≥ 4 at 14-90 days postsurgery) were enrolled. Patients received once-weekly BTDS ( n = 47; 5  μ g/h titrated to 20  μ g/h) or twice-daily TA ( n = 40; tramadol 37.5 mg/acetaminophen 325 mg, one tablet titrated to 4 tablets) for 6 weeks. The study compared pain reduction with BTDS versus TA at week 6. Quality of life (QoL), treatment satisfaction, medication compliance, and adverse events (AEs) were assessed. At week 6, both groups reported significant pain reduction (mean NRS change: BTDS -2.02; TA -2.76, both P < 0.0001) and improved QoL (mean EQ-5D index change: BTDS 0.10; TA 0.19, both P < 0.05). The BTDS group achieved better medication compliance (97.8% versus 91.0%). Incidence of AEs (26.1% versus 20.0%) and adverse drug reactions (20.3% versus 16.9%) were comparable between groups. For patients with persistent pain following spinal surgery, BTDS is an alternative to TA for reducing pain and supports medication compliance. This trial is registered with Clinicaltrials.gov: NCT01983111.

Repeated combined endovascular therapy with milrinone and nimodipine for the treatment of severe vasospasm: preliminary results.

PubMed

Sherif, Camillo; Wambacher, Bernhard; Loyoddin, Michel; Karaic, Radenko; Krafft, Peter; Valentin, Andreas; Tscholakoff, Dimiter; Kleinpeter, Guenther

2015-01-01

Delayed vasospasm (VSP) following aneurysmal subarachnoid hemorrhage (aSAH) remains a major source of morbidity. Milrinone was recently suggested as an invasive VSP treatment option. It is a phosphodiesterase III inhibitor with vasodilating and additional positive inotrope and anti-inflammatory effects. In this preliminary series, we included patients with severe VSP and unsuccessful maximum conservative therapy. Inclusion criteria were (1) transcranial Doppler (TCD) mean >180 cm/s; (2) increase of >50 % of TCD mean values within 6 h to values >150 cm/s; and/or (3) neurological deterioration (after exclusion of hemorrhage, hydrocephalus, and other systemic reasons). Patients received endovascular therapy with nimodipine 2 mg followed by milrinone 4-8 mg. Reinterventions were indicated aggressively in cases of persistent neurological deficits or persistent high mean TCD >180 cm/s. Of 121 consecutive aSAH patients, 16 (13.2 %) received endovascular VSP therapy. Of these, 11 patients (68.5 %) received ≥ 3 interventions (median 4; maximum 9); 14 (87.5 %) showed postinterventional angiographic improvement of vessel diameters; and 11 (68.5 %) showed improvement of their neurological deficits after a mean follow-up time of 4.5 months. No cardiovascular adverse events attributed to milrinone were observed. Milrinone may be a useful supplementary substance for endovascular VSP therapy. Aggressive reintervention indications did not cause additional adverse events.

Adverse Childhood Experiences and Arrest Patterns in a Sample of Sexual Offenders.

PubMed

Levenson, Jill S; Socia, Kelly M

2016-06-01

Developmental psychopathology theories suggest that childhood adversity can contribute to antisocial conduct and delinquent activities. The purpose of this study was to explore the influence of adverse childhood experiences (ACE) on arrest patterns in a sample of sexual offenders (N = 740). Higher ACE scores were associated with a variety of arrest outcomes, indicating that the accumulation of early trauma increased the likelihood of versatility and persistence of criminal behavior. Rapists of adults had higher ACE scores, lower levels of specialization, and higher levels of persistence than sex offenders with minor victims only. Child sexual abuse, emotional neglect, and domestic violence in the childhood home were significant predictors of a higher number of sex crime arrests. For measures of nonsexual arrests and criminal versatility, it was the household dysfunction factors-substance abuse, unmarried parents, and incarceration of a family member-that were predictive, suggesting that family dysfunction and a chaotic home environment contributed significantly to increased risk of general criminal behavior. Sex offenders inspire little sympathy in our society but may be among those most in need of trauma-informed models of treatment that recognize the influence of early adversity on maladaptive schema and self-regulation deficits related to criminal behavior. © The Author(s) 2015.

Differential exposure and differential vulnerability as counteracting forces linking the psychosocial work environment to socioeconomic health differences.

PubMed

Vanroelen, C; Levecque, K; Louckx, F

2010-10-01

In this article, the link between (1) psychosocial working conditions (job demands, job autonomy, task variation, social support), (2) self-reported health (persistent fatigue, musculoskeletal complaints, emotional well-being) and (3) socioeconomic position (skill levels, occupational status) is explored. The two theoretical pathways linking the psychosocial work environment to socioeconomic differences in health are explored: differential exposure and differential vulnerability. Previously, the focus has often been on social inequalities in exposure to the stressors. The pathway of differential vulnerability in different socioeconomic positions is often neglected. In a representative cross-sectional sample of 11,099 Flemish (Belgian) wage earners, 16-65 years of age (47.5% women), logit modelling is applied. Higher exposure to psychosocial occupational stressors is associated with a higher prevalence of adverse health outcomes. Lower skill levels and subordinate occupational positions show a higher prevalence of musculoskeletal complaints, but not of persistent fatigue or emotional well-being. High demands, job strain and iso-strain are more common in higher-skilled, supervisory and managerial positions, but have the strongest health-damaging effects in lower socioeconomic positions. Low control is more prevalent in lower-skilled and subordinate positions, while having stronger adverse health effects in higher socioeconomic positions-the same holds for social support, although it has no clear socioeconomic distribution. Differential exposure and differential vulnerability constitute two counteracting forces in constituting the association between the psychosocial work environment and socioeconomic differences in self-reported health complaints among wage earners.

Effects of pesticides on Canada Geese

USGS Publications Warehouse

Blus, L.J.; Rusch, Donald H.; Samuel, Michael D.; Humburg, Dale D.; Sullivan, Brian D.

1998-01-01

This paper summarizes published and unpublished sources relating to exposure of Canada geese (Branta canadensis) to pesticides, emphasizing documented episodes of poisoning by organochlorine (OC), organophosphorus (OP), and carbamate compounds. Canada geese accumulate the lipid-soluble OC compounds, although they have a lower potential for biomagnification of these pesticides than animals at higher trophic levels in food webs. Low residues of p,p'-DDT and its metabolite p,p'-DDE were frequently found in tissues and eggs of Canada geese, but they had no apparent adverse effects on reproductive success or eggshell thickness. Likewise, in an orchard system in central Washington state, the OC rodenticide endrin accumulated in tissues and eggs of Canada geese without apparent adverse effect. In contrast, ingestion of seeds treated with the OC heptachlor caused mortality, lowered reproductive success, and caused a local population decline of geese in Oregon and Washington. In recent years, the most persistent OC's have been banned by law and replaced with less persistent carbamate and OP compounds that do not readily accumulate in animal tissues. However, many of these compounds are acutely toxic and have caused numerous die-offs of Canada geese. Among OP compounds, diazinon was responsible for most reported die-offs (41 incidents involving >535 geese), whereas parathion applied alone or jointly with methyl parathion accounted for most reported mortalities (8 incidents involving >3,000 geese). Three other OP's, a carbamate (carbofuran), zinc phosphide, and strychnine also caused goose die-offs. Mortality from anticholinesterase (antiChE) compounds occurs relatively soon after exposure and death can usually be diagnosed by evaluation of brain cholinesterase (thE) activity. Because geese are primarily grazers, the main route of exposure to antiChE's is apparently ingestion of contaminated grasses and forbs; dermal absorption and inhalation are other routes. Despite the widespread die-offs of Canada geese from antiChE insecticides, there is no evidence of adverse effects on population levels. It is not known how sublethal antiChE exposure relates to long-term survival and reproductive success of birds.

First report on the diagnosis and treatment of encephalic and urinary paracoccidioidomycosis in a cat.

PubMed

Gonzalez, Juan F; Montiel, Nestor A; Maass, Rodrigo L

2010-08-01

A male Persian cat was presented with persistent fever, anorexia, weakness, hypopyon, nystagmus, and intention tremors. The hemogram showed severe neutropenia and laboratory analysis on cerebrospinal fluid (CSF) smears revealed abundant yeast cells compatible with Paracoccidioides brasiliensis. Urinalysis demonstrated persistent funguria and an increased urine protein-to-creatinine ratio (UPC) in addition to mild azotemia. Long-term therapy with oral fluconazole was effective in controlling the nervous system signs. Funguria was resolved with subcutaneous administration of diluted amphotericin B in a large volume of saline solution for a period of 12 weeks during the second year after initial diagnosis. Throughout 5 years of treatment, no adverse effects were observed and tolerance to the drugs was normal. Due to development of progressive uremic syndrome the animal was euthanased. To the best of our knowledge, this report is the first clinical case described of a nervous and urinary system infection caused by the P brasiliensis in a cat. Copyright 2010 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.

Adverse childhood experiences and risk of paternity in teen pregnancy.

PubMed

Anda, Robert F; Chapman, Daniel P; Felitti, Vincent J; Edwards, Valerie; Williamson, David F; Croft, Janet B; Giles, Wayne H

2002-07-01

Few studies have investigated risk factors that predispose males to be involved in teen pregnancies. To provide new information on such factors, we examined the relationships of eight common adverse childhood experiences to a male's risk of impregnating a teenager. We conducted a retrospective cohort study using questionnaire responses from 7399 men who visited a primary care clinic of a large health maintenance organization in California. Data included age of the youngest female ever impregnated; the man's own age at the time; his history of childhood emotional, physical, or sexual abuse; having a battered mother; parental separation or divorce; and having household members who were substance abusers, mentally ill, or criminals. Odds ratios (ORs) for the risk of involvement in a teen pregnancy were adjusted for age, race, and education. At least one adverse childhood experience was reported by 63% of participants, and 34% had at least two adverse childhood experiences; 19% of men had been involved in a teen pregnancy. Each adverse childhood experience was positively associated with impregnating a teenager, with ORs ranging from 1.2 (sexual abuse) to 1.8 (criminal in home). We found strong graded relationships (P <.001) between the number of adverse childhood experiences and the risk of involvement in a teen pregnancy for each of four birth cohorts during the last century. Compared with males with no adverse childhood experiences, a male with at least five adverse childhood experiences had an OR of 2.6 (95% confidence interval [CI] 2.0, 3.4) for impregnating a teenager. The magnitude of the ORs for the adverse childhood experiences was reduced 64-100% by adjustment for potential intermediate variables (age at first intercourse, number of sexual partners, having a sexually transmitted disease, and alcohol or drug abuse) that also exhibited a strong graded relationship to adverse childhood experiences. Adverse childhood experiences have an important relationship to male involvement in teen pregnancy. This relationship has persisted throughout four successive birth cohorts dating back to 1900-1929, suggesting that the effects of adverse childhood experiences transcend changing sexual mores and contraceptive methods. Efforts to prevent teen pregnancy will likely benefit from preventing adverse childhood experiences and their associated effects on male behaviors that might mediate the increased risk of teen pregnancy.

Adverse life events as risk factors for behavioural and emotional problems in a 7-year follow-up of a population-based child cohort.

PubMed

Rasmussen, Cathrine Skovmand; Nielsen, Louise Gramstrup; Petersen, Dorthe Janne; Christiansen, Erik; Bilenberg, Niels

2014-04-01

The aim of the study was to identify risk factors for significant changes in emotional and behavioural problem load in a community-based cohort of Danish children aged 9-16 years, the risk factors being seven parental and two child-related adverse life events. Data on emotional and behavioural problems was obtained from parents filling in the Child Behavior Checklist (CBCL) when the child was 8-9 and again when 15 years old. Data on risk factors was drawn from Danish registers. Analysis used was logistic regression for crude and adjusted change. Parental divorce significantly raised the odds ratio of an increase in emotional and behavioural problems; furthermore, the risk of deterioration in problem behaviour rose significantly with increasing number of adverse life events. By dividing the children into four groups based on the pathway in problem load (increasers, decreasers, high persisters and low persisters), we found that children with a consistently high level of behavioural problems also had the highest number of adverse life events compared with any other group. Family break-up was found to be a significant risk factor. This supports findings in previous studies. The fact that no other risk factor proved to be of significance might be due to lack of power in the study. Children experiencing high levels of adverse life events are at high risk of chronic problem behaviour. Thus these risk factors should be assessed in daily clinical practice.

Early postnatal exposure to ultrafine particulate matter air pollution: persistent ventriculomegaly, neurochemical disruption, and glial activation preferentially in male mice.

PubMed

Allen, Joshua L; Liu, Xiufang; Pelkowski, Sean; Palmer, Brian; Conrad, Katherine; Oberdörster, Günter; Weston, Douglas; Mayer-Pröschel, Margot; Cory-Slechta, Deborah A

2014-09-01

Air pollution has been associated with adverse neurological and behavioral health effects in children and adults. Recent studies link air pollutant exposure to adverse neurodevelopmental outcomes, including increased risk for autism, cognitive decline, ischemic stroke, schizophrenia, and depression. We sought to investigate the mechanism(s) by which exposure to ultrafine concentrated ambient particles (CAPs) adversely influences central nervous system (CNS) development. We exposed C57BL6/J mice to ultrafine (< 100 nm) CAPs using the Harvard University Concentrated Ambient Particle System or to filtered air on postnatal days (PNDs) 4-7 and 10-13, and the animals were euthanized either 24 hr or 40 days after cessation of exposure. Another group of males was exposed at PND270, and lateral ventricle area, glial activation, CNS cytokines, and monoamine and amino acid neurotransmitters were quantified. We observed ventriculomegaly (i.e., lateral ventricle dilation) preferentially in male mice exposed to CAPs, and it persisted through young adulthood. In addition, CAPs-exposed males generally showed decreases in developmentally important CNS cytokines, whereas in CAPs-exposed females, we observed a neuroinflammatory response as indicated by increases in CNS cytokines. We also saw changes in CNS neurotransmitters and glial activation across multiple brain regions in a sex-dependent manner and increased hippocampal glutamate in CAPs-exposed males. We observed brain region- and sex-dependent alterations in cytokines and neurotransmitters in both male and female CAPs-exposed mice. Lateral ventricle dilation (i.e., ventriculomegaly) was observed only in CAPs-exposed male mice. Ventriculomegaly is a neuropathology that has been associated with poor neurodevelopmental outcome, autism, and schizophrenia. Our findings suggest alteration of developmentally important neurochemicals and lateral ventricle dilation may be mechanistically related to observations linking ambient air pollutant exposure and adverse neurological/neurodevelopmental outcomes in humans.

12 CFR 715.12 - Statutory audit remedies for Federal credit unions.

Code of Federal Regulations, 2010 CFR

2010-01-01

..., a qualified opinion on the credit union's financial statements. An adverse opinion or disclaimer of opinion should be the exception rather than the norm. (c) “Serious and persistent recordkeeping...

Physical and chemical control of released microorganisms at field sites

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

Donegan, K.; Seidler, R.; Matyac, C.

1991-01-01

An important consideration in the environmental release of a genetically engineered microorganism (GEM) is the capability for reduction or elimination of GEM populations once their function is completed or if adverse environmental effects are observed. The decontamination treatments of burning and biocide application, alone and in combination with tilling, were evaluated for their ability to reduce populations of bacteria released on the phylloplane. Field plots of bush beans sprayed with the bacterium Erwinia herbicola, received the following treatments: (1) control, (2) control + till, (3) burn, (4) burn + till, (5) Kocide (cupric hydroxide), (6) Kocide + till, (7) Agri-strepmore » (streptomycin sulfate), and (8) Agri-strept + till. Leaves and soil from the plots were sampled -1, 1, 5, 8, 12, 15, 19, and 27 days after application of the decontamination treatments. Burning produced a significant and persistent reduction in the number of bacteria whereas tilling, alone or in combination with the biocide treatments, stimulated a significant and persistent reduction in the number of bacteria, whereas tilling, alone or in combination with the biocide treatments, stimulated a significant increase in bacterial populations that persisted for several weeks.« less

[Exposure to persistent and non-persistent pesticides in a non-occupationally exposed population in Tenerife Island (Spain)].

PubMed

Burillo-Putze, Guillermo; Luzardo, Octavio P; García, Carlos Pérez; Zumbado, Manuel; Yanes, Carmen; Trujillo-Martín, María del Mar; Boada Fernández del Campo, Carlos; Boada, Luis D

2014-01-01

Chronic exposure to non-persistent pesticides (NPPs) is of concern because these substances have been associated with chronic diseases. However, few studies have addressed chronic exposure to NPPs in Spanish populations. We determined the presence of 24 pesticide residues by gas chromatography/mass spectrometry in 363 serum samples obtained from non-occupationally exposed adults from Tenerife island in 2007. Most of the samples (99.45%) showed detectable residues (6 ± 2 pesticides per sample). The most frequently detected pesticides were pyrethrins (96.1%), organophosphates (93.9%) and organochlorines (92.3%). The neurotoxicants bifenthrin and malathion were detected in 81% of the samples and hexachlorobenzene DDT and buprofezin in more than 50%. Malation, an "environmental obesogen", was detected in 82%, and "endocrine disrupter" pesticides were present in 97.2% of the samples. Because there is clear, continuous and inadvertent exposure to NPPs that may be inducing adverse effects on human health, NPPs should be included in biomonitoring studies. Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.

Nanoparticulate carbon black in cigarette smoke induces DNA cleavage and Th17-mediated emphysema.

PubMed

You, Ran; Lu, Wen; Shan, Ming; Berlin, Jacob M; Samuel, Errol Lg; Marcano, Daniela C; Sun, Zhengzong; Sikkema, William Ka; Yuan, Xiaoyi; Song, Lizhen; Hendrix, Amanda Y; Tour, James M; Corry, David B; Kheradmand, Farrah

2015-10-05

Chronic inhalation of cigarette smoke is the major cause of sterile inflammation and pulmonary emphysema. The effect of carbon black (CB), a universal constituent of smoke derived from the incomplete combustion of organic material, in smokers and non-smokers is less known. In this study, we show that insoluble nanoparticulate carbon black (nCB) accumulates in human myeloid dendritic cells (mDCs) from emphysematous lung and in CD11c(+) lung antigen presenting cells (APC) of mice exposed to smoke. Likewise, nCB intranasal administration induced emphysema in mouse lungs. Delivered by smoking or intranasally, nCB persisted indefinitely in mouse lung, activated lung APCs, and promoted T helper 17 cell differentiation through double-stranded DNA break (DSB) and ASC-mediated inflammasome assembly in phagocytes. Increasing the polarity or size of CB mitigated many adverse effects. Thus, nCB causes sterile inflammation, DSB, and emphysema and explains adverse health outcomes seen in smokers while implicating the dangers of nCB exposure in non-smokers.

Short-term effects of different genetically modified maize varieties on arthropod food web properties: an experimental field assessment.

PubMed

Szénási, Ágnes; Pálinkás, Zoltán; Zalai, Mihály; Schmitz, Oswald J; Balog, Adalbert

2014-06-17

There is concern that genetically modified (GM) plants may have adverse affects on the arthropod biodiversity comprising agricultural landscapes. The present study report on a two year field experimental test of whether four different genotypic lines, some are novel with no previous field tests, of GM maize hybrids alter the structure of arthropod food webs that they harbour, relative to non-GM maize (control) that is widely used in agriculture. The different GM genotypes produced either Bt toxins, conferred glyphosate tolerance or a combination of the two traits. Quantitative food web analysis, based on short-term assessment assigning a total of 243,896 arthropod individuals collected from the treatments to their positions in food webs, revealed that complex and stable food webs persisted in each maize treatment. Moreover, food web structure remained relatively unchanged by the GM-genotype. The results suggest that at least in short-term period these particular GM maize genotypes will not have adverse effects on arthropod biota of agricultural landscapes.

Drug packaging in 2013: small changes would reap big benefits.

PubMed

2014-05-01

Drug packaging is important both in protecting and informing patients. Some improvements were made in 2013, but many of the products examined by Prescrire still had poor-quality or even dangerous packaging. Problem packaging is a major concern for patients who are more vulnerable to adverse effects, particularly children and pregnant women. Several problems were noted with products intended for self-medication (umbrella brands), oral solutions sold with dosing devices, and injectable drugs. Looking back at 20 years of Red Cards that Prescrire has issued to products with dangerous packaging reveals several improvements, but too many dangers persist. Urgent action needs to be taken by regulatory agencies and drug companies: patient leaflets must be more explicit with regard to adverse effects, especially those of nonsteroidal anti-inflammatory drugs during pregnancy; accidental ingestion by children must be prevented; and companies must design safer dosing devices. Healthcare professionals and patients must remain vigilant and report all packaging issues to the relevant authorities.

Factors Associated With the Onset and Persistence of Post–Lumbar Puncture Headache

PubMed Central

Monserrate, Andrés E.; Ryman, Davis C.; Ma, Shengmei; Xiong, Chengjie; Noble, James M.; Ringman, John M.; Morris, John C.; Danek, Adrian; Müller-Sarnowski, Felix; Clifford, David B.; McDade, Eric M.; Brooks, William S.; Darby, David G.; Masters, Colin L.; Weston, Philip S. J.; Farlow, Martin R.; Graff-Radford, Neill R.; Salloway, Stephen P.; Fagan, Anne M.; Oliver, Angela; Bateman, Randall J.

2015-01-01

IMPORTANCE This study assesses factors associated with the most common adverse event following lumbar puncture. OBJECTIVE To identify factors associated with the risk, onset, and persistence of post–dural puncture headache (PDPH). DESIGN, SETTING, AND PARTICIPANTS We performed univariate and multivariable analyses of 338 lumbar punctures in the Dominantly Inherited Alzheimer Network observational study using linear mixed models, adjusting for participant-level and family-level random effects. MAIN OUTCOMES AND MEASURES We directly evaluated associations of 3 post–lumbar puncture outcomes (immediate postprocedural headache, PDPH at 24-hour follow-up, and PDPH receiving a therapeutic blood patch) with participant age and sex, positioning, collection method, needle size, needle insertion site, and cerebrospinal fluid (CSF) volume collected. RESULTS The incidence of adverse events included 73 immediate postprocedural headaches (21.6%), 59 PDPHs at 24-hour follow-up (17.5%), and 15 PDPHs receiving a therapeutic blood patch (4.4%). Greater volume of CSF collected was associated with increased risk of immediate postprocedural headache, largely owing to a nonlinear increase in risk on collection of volumes above 30 mL (odds ratio, 3.73 for >30 mL and 0.98 for <17 mL). In contrast, collection of higher volumes showed a protective effect in decreasing rates of PDPH at 24-hour follow-up and rates of PDPH receiving a therapeutic blood patch (odds ratio, 0.35 per 10 mL). Although differences in needle size did not reach statistical significance, no participant in the 24G needle group received a therapeutic blood patch compared to 8 of 253 for the larger 22G needles. CONCLUSIONS AND RELEVANCE Factors that acutely lower CSF pressure (eg, seated positioning or extracting very high volumes of CSF) may be associated with transient post-lumbar puncture headache, without increasing rates of persistent PDPH or therapeutic blood patch. Collection of up to 30 mL of CSF appears to be well tolerated and safe. PMID:25622095

Effects of plants genetically modified for insect resistance on nontarget organisms.

PubMed

O'Callaghan, Maureen; Glare, Travis R; Burgess, Elisabeth P J; Malone, Louise A

2005-01-01

Insect resistance, based on Bacillus thuringiensis (Bt) endotoxins, is the second most widely used trait (after herbicide resistance) in commercial genetically modified (GM) crops. Other modifications for insect resistance, such as proteinase inhibitors and lectins, are also being used in many experimental crops. The extensive testing on nontarget plant-feeding insects and beneficial species that has accompanied the long-term and wide-scale use of Bt plants has not detected significant adverse effects. GM plants expressing other insect-resistant proteins that have a broader spectrum of activity have been tested on only a limited number of nontarget species. Little is known about the persistence of transgene-derived proteins in soil, with the exception of Bt endotoxins, which can persist in soil for several months. Bt plants appear to have little impact on soil biota such as earthworms, collembolans, and general soil microflora. Further research is required on the effects of GM plants on soil processes such as decomposition. Assessment of nontarget impacts is an essential part of the risk assessment process for insect-resistant GM plants.

Adverse events and treatment interruption in tuberculosis patients with and without HIV co‐infection

PubMed Central

Breen, R A M; Miller, R F; Gorsuch, T; Smith, C J; Schwenk, A; Holmes, W; Ballinger, J; Swaden, L; Johnson, M A; Cropley, I; Lipman, M C I

2006-01-01

Background Serious treatment associated adverse events are thought to occur more frequently in individuals with tuberculosis (TB) who are co‐infected with HIV. A study was undertaken to assess the frequency of serious (grade III/IV) adverse events and interruption of anti‐TB treatment in the era of effective antiretroviral therapy. Methods The incidence of serious adverse events was retrospectively compared in 312 individuals treated for TB, 156 of whom were co‐infected with HIV. Results 111 HIV infected individuals (71%) received highly active antiretroviral therapy at the same time as anti‐TB treatment. Serious adverse events were recorded in 40% HIV infected and 26% HIV uninfected individuals (p = 0.008). Peripheral neuropathy and persistent vomiting were more common in co‐infected patients (p<0.001; p = 0.006), although all cause interruption of anti‐TB treatment occurred with similar frequency in the two groups (13% in HIV infected patients and 15% in HIV uninfected patients; p = 0.74). In 85% of HIV infected patients and 87% of HIV uninfected individuals this was due to hepatotoxicity, which typically presented within 2 months of starting treatment. The median delay in restarting treatment was 4 weeks, so most individuals required full TB re‐treatment. Conclusion Despite a greater rate of serious (grade III/IV) adverse events among HIV infected individuals, discontinuation of anti‐TB treatment occurred with a similar frequency in HIV infected and HIV uninfected individuals. PMID:16844730

Social relationships and longitudinal changes in body mass index and waist circumference: the coronary artery risk development in young adults study.

PubMed

Kershaw, Kiarri N; Hankinson, Arlene L; Liu, Kiang; Reis, Jared P; Lewis, Cora E; Loria, Catherine M; Carnethon, Mercedes R

2014-03-01

Few studies have examined longitudinal associations between close social relationships and weight change. Using data from 3,074 participants in the Coronary Artery Risk Development in Young Adults Study who were examined in 2000, 2005, and 2010 (at ages 33-45 years in 2000), we estimated separate logistic regression random-effects models to assess whether patterns of exposure to supportive and negative relationships were associated with 10% or greater increases in body mass index (BMI) (weight (kg)/height (m)(2)) and waist circumference. Linear regression random-effects modeling was used to examine associations of social relationships with mean changes in BMI and waist circumference. Participants with persistently high supportive relationships were significantly less likely to increase their BMI values and waist circumference by 10% or greater compared with those with persistently low supportive relationships after adjustment for sociodemographic characteristics, baseline BMI/waist circumference, depressive symptoms, and health behaviors. Persistently high negative relationships were associated with higher likelihood of 10% or greater increases in waist circumference (odds ratio = 1.62, 95% confidence interval: 1.15, 2.29) and marginally higher BMI increases (odds ratio = 1.50, 95% confidence interval: 1.00, 2.24) compared with participants with persistently low negative relationships. Increasingly negative relationships were associated with increases in waist circumference only. These findings suggest that supportive relationships may minimize weight gain, and that adverse relationships may contribute to weight gain, particularly via central fat accumulation.

Social Relationships and Longitudinal Changes in Body Mass Index and Waist Circumference: The Coronary Artery Risk Development in Young Adults Study

PubMed Central

Kershaw, Kiarri N.; Hankinson, Arlene L.; Liu, Kiang; Reis, Jared P.; Lewis, Cora E.; Loria, Catherine M.; Carnethon, Mercedes R.

2014-01-01

Few studies have examined longitudinal associations between close social relationships and weight change. Using data from 3,074 participants in the Coronary Artery Risk Development in Young Adults Study who were examined in 2000, 2005, and 2010 (at ages 33–45 years in 2000), we estimated separate logistic regression random-effects models to assess whether patterns of exposure to supportive and negative relationships were associated with 10% or greater increases in body mass index (BMI) (weight (kg)/height (m)2) and waist circumference. Linear regression random-effects modeling was used to examine associations of social relationships with mean changes in BMI and waist circumference. Participants with persistently high supportive relationships were significantly less likely to increase their BMI values and waist circumference by 10% or greater compared with those with persistently low supportive relationships after adjustment for sociodemographic characteristics, baseline BMI/waist circumference, depressive symptoms, and health behaviors. Persistently high negative relationships were associated with higher likelihood of 10% or greater increases in waist circumference (odds ratio = 1.62, 95% confidence interval: 1.15, 2.29) and marginally higher BMI increases (odds ratio = 1.50, 95% confidence interval: 1.00, 2.24) compared with participants with persistently low negative relationships. Increasingly negative relationships were associated with increases in waist circumference only. These findings suggest that supportive relationships may minimize weight gain, and that adverse relationships may contribute to weight gain, particularly via central fat accumulation. PMID:24389018

Effect of a herbal compound for treatment of sarcoptic mange infestations on dogs.

PubMed

Das, S S

1996-06-01

Charmil gel, a herbal product was tried against Sarcoptes scabei var canis on dogs and its efficacy was compared with that of amitraz. Mite scrapings examined at scheduled intervals after the topical application of Charmil gel caused complete recovery after 14 days in severe infestation and 7 to 10 days in mild to moderate infestations with regrowth of hair on Day 28 post-treatment. No adverse reactions were observed except mild irritation and restlessness, which persisted for a few hours soon after application.

Enalapril and diltiazem co-administration and respiratory side effects of enalapril.

PubMed

Franová, S; Nosál'ová, G; Antosová, M; Nosál', S

2005-01-01

A persistent, chronic dry cough is the most common adverse effect of angiotensin converting enzyme (ACE) inhibitors therapy. The mechanism of this respiratory adverse effect is related to the inhibition of ACE and the accumulation of bradykinin, substance P, prostanoids and other inflammatory neuropeptides in the airways. The aim of this study was to follow the relationship between 15-day administration of enalapril and the defense reflexes (cough and bronchoconstriction) of the airways in experimental animals, as well as the possibility of their pharmacological restriction with simultaneous diltiazem administration. Cough reflex was investigated by the method of mechanical irritation of laryngopharyngeal and tracheobronchial area in non-anesthetized cats. The reactivity of tracheal smooth muscles of the airways to bronchoconstrictor mediators (histamine 10 nM - 1 mM, acetylcholine 10 nM - 1 mM and KCl 1 mM - 100 mM) was evaluated by an in vitro method in guinea pigs. Enalapril 5 mg/kg/day and diltiazem 30 mg/kg/day were administered perorally for 15 days. The results showed that long-lasting administration of enalapril resulted in a significant increase of measured cough parameters and increased reactivity of tracheal smooth muscle to histamine and KCl. Simultaneous administration of enalapril together with diltiazem significantly decreased the enalapril induced cough, and decreased enalapril induced hyperreactivity of tracheal smooth muscles to KCl. The results showed a partially protective effect of diltiazem and enalapril co-administration on the respiratory adverse effects induced by enalapril therapy.

The Role of Opioid Analgesics in Geriatric Pain Management.

PubMed

Naples, Jennifer Greene; Gellad, Walid F; Hanlon, Joseph T

2016-11-01

When possible, chronic noncancer pain (CNCP) in older adults should be managed by nonpharmacologic modalities in conjunction with nonopioid analgesics. If moderate-to-severe pain persists despite these approaches, however, nonparenteral opioids may be considered as adjunctive therapy. This article reviews the epidemiology of opioid use and their effectiveness for CNCP in older adults and summarizes important age-related changes in opioid pharmacokinetics and pharmacodynamics that increase the risks of adverse effects in the elderly. Finally, to assist clinicians with selecting appropriate therapy, the article concludes with an evidence-based approach to optimize opioid prescribing in older adults with CNCP. Copyright © 2016 Elsevier Inc. All rights reserved.

POSSIBLE MOLECULAR TARGETS OF HALOGENATED ARMOATIC HYDROCARBONS IN NEURONAL CELLS.

EPA Science Inventory

Halogenated aromatic hydrocarbons including polychlorinated biphenyls (PCBs) are persistent bioaccumulative toxicants. Due to these characteristics, there is considerable regulatory concern over the potential adverse health affects, especially to children, associated with exposur...

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.

β-Arrestins: Regulatory Role and Therapeutic Potential in Opioid and Cannabinoid Receptor-Mediated Analgesia

PubMed Central

Bohn, Laura M.

2016-01-01

Pain is a complex disorder with neurochemical and psychological components contributing to the severity, the persistence, and the difficulty in adequately treating the condition. Opioid and cannabinoids are two classes of analgesics that have been used to treat pain for centuries and are arguably the oldest of “pharmacological” interventions used by man. Unfortunately, they also produce several adverse side effects that can complicate pain management. Opioids and cannabinoids act at G protein-coupled receptors (GPCRs), and much of their effects are mediated by the mu-opioid receptor (MOR) and cannabinoid CB1 receptor (CB1R), respectively. These receptors couple to intracellular second messengers and regulatory proteins to impart their biological effects. In this chapter, we review the role of the intracellular regulatory proteins, β-arrestins, in modulating MOR and CB1R and how they influence the analgesic and side-effect profiles of opioid and cannabinoid drugs in vivo. This review of the literature suggests that the development of opioid and cannabinoid agonists that bias MOR and CB1R toward G protein signaling cascades and away from β-arrestin interactions may provide a novel mechanism by which to produce analgesia with less severe adverse effects. PMID:24292843

Use patterns and self-reported effects of Salvia divinorum: an internet-based survey.

PubMed

Baggott, Matthew J; Erowid, Earth; Erowid, Fire; Galloway, Gantt P; Mendelson, John

2010-10-01

There is growing use of Salvia divinorum (SD), a psychoactive plant that produces hallucinogen-like effects through a kappa opioid receptor (KOR) mechanism. Little is known about KOR agonist effects in humans and about users of SD. To characterize the reasons, methods, and reported consequences of SD use. Individuals reading SD-related pages of a drug-information website were invited to anonymously complete an online questionnaire if they had used SD. Participants (N=500) were 92.6% male and 23.4 ± 8.7 (mean ± s.d.) years old. They had used a median of six times (range 1-250). 80.6% probably or definitely would use SD again. Most participants (92.6%) typically smoked or vaporized SD product. When smoked, the drug's main effects were estimated to last 14.1 ± 12.8 (range 0.5-120) minutes. When asked to compare SD effects to other methods of altering consciousness, the most common answer was that SD was unique (38.4%). 25.8% reported persisting (≥ 24 h) positive effects (often described as increased sense of well-being) on at least one occasion. 4.4% reported persisting negative effects (most often anxiety). SD is typically smoked, acute effects are brief, and persistent adverse effects are uncommon. In addition to acute hallucinogenic effects, SD may produce subacute increases in subjective well-being. Such a subacute effect would be unusual for a drug that is used non-medically, as withdrawal from other drugs typically either does not affect mood or causes dysphoria. Findings from this convenience sample should be confirmed and extended using surveys of random samples and controlled clinical studies. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Efficacy and Safety of Transdermal Buprenorphine versus Oral Tramadol/Acetaminophen in Patients with Persistent Postoperative Pain after Spinal Surgery

PubMed Central

Kim, Jin-Hwan; Kim, Hak-Sun; Min, Woo-Kie; Park, Ye-Soo; Lee, Kyu-Yeol; Lee, Jung-Hee

2017-01-01

Purpose Control of persistent pain following spinal surgery is an unmet clinical need. This study compared the efficacy and safety of buprenorphine transdermal system (BTDS) to oral tramadol/acetaminophen (TA) in Korean patients with persistent, moderate pain following spinal surgery. Methods Open-label, interventional, randomized multicenter study. Adults with persistent postoperative pain (Numeric Rating Scale [NRS] ≥ 4 at 14–90 days postsurgery) were enrolled. Patients received once-weekly BTDS (n = 47; 5 μg/h titrated to 20 μg/h) or twice-daily TA (n = 40; tramadol 37.5 mg/acetaminophen 325 mg, one tablet titrated to 4 tablets) for 6 weeks. The study compared pain reduction with BTDS versus TA at week 6. Quality of life (QoL), treatment satisfaction, medication compliance, and adverse events (AEs) were assessed. Findings At week 6, both groups reported significant pain reduction (mean NRS change: BTDS −2.02; TA −2.76, both P < 0.0001) and improved QoL (mean EQ-5D index change: BTDS 0.10; TA 0.19, both P < 0.05). The BTDS group achieved better medication compliance (97.8% versus 91.0%). Incidence of AEs (26.1% versus 20.0%) and adverse drug reactions (20.3% versus 16.9%) were comparable between groups. Implications For patients with persistent pain following spinal surgery, BTDS is an alternative to TA for reducing pain and supports medication compliance. This trial is registered with Clinicaltrials.gov: NCT01983111. PMID:29056859

Does progestin-only contraceptive use after pregnancy affect recovery from pelvic girdle pain? A prospective population study

PubMed Central

Owe, Katrine Mari; Nordeng, Hedvig Marie Egeland; Engdahl, Bo Lars; Kristiansson, Per; Vangen, Siri; Eberhard-Gran, Malin

2017-01-01

Objective To estimate associations of progestin-only contraceptives with persistent pelvic girdle pain 18 months after delivery. Methods Prospective population based cohort study during the years 2003–2011. We included 20,493 women enrolled in the Norwegian Mother and Child Cohort Study who reported pelvic girdle pain in pregnancy week 30. Data were obtained by 3 self-administered questionnaires and the exposure was obtained by linkage to the Prescription Database of Norway. The outcome was pelvic girdle pain 18 months after delivery. Results Pelvic girdle pain 18 months after delivery was reported by 9.7% (957/9830) of women with dispense of a progestin-only contraceptive and by 10.5% (1114/10,663) of women without dispense (adjusted odds ratio 0.93; 95% CI 0.84–1.02). In sub-analyses, long duration of exposure to a progestin intrauterine device or progestin-only oral contraceptives was associated with reduced odds of persistent pelvic girdle pain (Ptrend = 0.021 and Ptrend = 0.005). Conversely, long duration of exposure to progestin injections and/or a progestin implant was associated with modest increased odds of persistent pelvic girdle pain (Ptrend = 0.046). Early timing of progestin-only contraceptive dispense following delivery (≤3 months) was not significantly associated with persistent pelvic girdle pain. Conclusions Our findings suggest a small beneficial effect of progestin intrauterine devices and progestin-only oral contraceptives on recovery from pelvic girdle pain. We cannot completely rule out an opposing adverse effect of exposure to progestin injections and/or progestin implants. However, the modest increased odds of persistent pelvic girdle pain among these users could be a result of unmeasured confounding. PMID:28892506

Does progestin-only contraceptive use after pregnancy affect recovery from pelvic girdle pain? A prospective population study.

PubMed

Bjelland, Elisabeth Krefting; Owe, Katrine Mari; Nordeng, Hedvig Marie Egeland; Engdahl, Bo Lars; Kristiansson, Per; Vangen, Siri; Eberhard-Gran, Malin

2017-01-01

To estimate associations of progestin-only contraceptives with persistent pelvic girdle pain 18 months after delivery. Prospective population based cohort study during the years 2003-2011. We included 20,493 women enrolled in the Norwegian Mother and Child Cohort Study who reported pelvic girdle pain in pregnancy week 30. Data were obtained by 3 self-administered questionnaires and the exposure was obtained by linkage to the Prescription Database of Norway. The outcome was pelvic girdle pain 18 months after delivery. Pelvic girdle pain 18 months after delivery was reported by 9.7% (957/9830) of women with dispense of a progestin-only contraceptive and by 10.5% (1114/10,663) of women without dispense (adjusted odds ratio 0.93; 95% CI 0.84-1.02). In sub-analyses, long duration of exposure to a progestin intrauterine device or progestin-only oral contraceptives was associated with reduced odds of persistent pelvic girdle pain (Ptrend = 0.021 and Ptrend = 0.005). Conversely, long duration of exposure to progestin injections and/or a progestin implant was associated with modest increased odds of persistent pelvic girdle pain (Ptrend = 0.046). Early timing of progestin-only contraceptive dispense following delivery (≤3 months) was not significantly associated with persistent pelvic girdle pain. Our findings suggest a small beneficial effect of progestin intrauterine devices and progestin-only oral contraceptives on recovery from pelvic girdle pain. We cannot completely rule out an opposing adverse effect of exposure to progestin injections and/or progestin implants. However, the modest increased odds of persistent pelvic girdle pain among these users could be a result of unmeasured confounding.

Persistent pain in the older adult: what should we do now in light of the 2009 American geriatrics society clinical practice guideline?

PubMed

Katz, James D; Shah, Tina

2009-12-01

The recent publication of revised guidelines for the management of persistent pain in the older adult (American Geriatric Society, 2009) has posed a dilemma for clinicians. In essence, these revised guidelines now downplay the use of nonsteroidal anti-inflammatory drugs (NSAIDs) relative to prior year's recommendations. The strong recommendation for caution when employing NSAIDs is because of the numerous, well-documented, potential adverse effects including renal failure, stroke, hypertension, heart failure exacerbations, and gastrointestinal complications. Nevertheless, physicians still have a substantial arsenal for combating chronic pain due to such conditions as degenerative arthritis and back problems. Options for intervention include physical therapy, topical nonsteroidals, capsaicin, topical lidocaine, intra-articular therapies, and judicious use of narcotics. In the future, cyclooxygenase-inhibiting nitric oxide-donating drugs may represent a technical improvement in the toxicity profile of traditional NSAIDs.

Race, socioeconomic status, and health. The added effects of racism and discrimination.

PubMed

Williams, D R

1999-01-01

Higher disease rates for blacks (or African Americans) compared to whites are pervasive and persistent over time, with the racial gap in mortality widening in recent years for multiple causes of death. Other racial/ethnic minority populations also have elevated disease risk for some health conditions. This paper considers the complex ways in which race and socioeconomic status (SES) combine to affect health. SES accounts for much of the observed racial disparities in health. Nonetheless, racial differences often persist even at "equivalent" levels of SES. Racism is an added burden for nondominant populations. Individual and institutional discrimination, along with the stigma of inferiority, can adversely affect health by restricting socioeconomic opportunities and mobility. Racism can also directly affect health in multiple ways. Residence in poor neighborhoods, racial bias in medical care, the stress of experiences of discrimination and the acceptance of the societal stigma of inferiority can have deleterious consequences for health.

Attention problems and academic achievement: Do persistent and earlier-emerging problems have more adverse long-term effects?

PubMed Central

Rabiner, David L.; Carrig, Madeline; Dodge, Kenenth A.

2013-01-01

This study examined whether the negative association between children’s attention difficulties and their academic functioning is largely confined to children whose attention problems persist across early grades and whether it depends on when attention problems emerge in children’s schooling. Children from the normative sample of the Fast Track study were classified into four attention problem groups based on the presence vs. absence of attention problems in first and second grade. Those with attention problems in both grades showed a decline in reading and math achievement during the K-5 interval relative to children with attention problems in first grade only. Both groups of inattentive first graders also performed worse than comparison children. In contrast, children whose attention problems emerged in second grade did not differ from comparison children on any achievement outcome performed significantly better than inattentive first graders. The implications of these findings are discussed. PMID:24141101

The tuberculosis vaccine H4:IC31 is safe and induces a persistent polyfunctional CD4 T cell response in South African adults: A randomized controlled trial.

PubMed

Geldenhuys, Hennie; Mearns, Helen; Miles, David J C; Tameris, Michele; Hokey, David; Shi, Zhongkai; Bennett, Sean; Andersen, Peter; Kromann, Ingrid; Hoff, Søren T; Hanekom, Willem A; Mahomed, Hassan; Hatherill, Mark; Scriba, Thomas J; van Rooyen, Michele; Bruce McClain, J; Ryall, Robert; de Bruyn, Guy

2015-07-09

New, more effective vaccines to prevent tuberculosis (TB) disease are needed urgently. H4:IC31 is an investigational vaccine that contains a fusion protein of the immunodominant antigens TB10.4 and Ag85B, formulated in IC31 adjuvant. We assessed the safety and immunogenicity of H4:IC31 in South African adults from a TB endemic setting. In this double blind, placebo controlled, phase I trial, Mycobacterium tuberculosis-uninfected, HIV-uninfected, healthy adults with a history of childhood BCG vaccination were randomly allocated to two intramuscular vaccinations with 5, 15, 50 or 150 μg H4 formulated in 500nmol IC31, two months apart. Vaccinees were followed for six months to assess safety; immunogenicity was measured by ELISpot and intracellular cytokine staining assays. Thirty-two participants received H4:IC31 and 8 received placebo. Injection site adverse events were common but mild; mild fatigue was the most common systemic adverse event. Frequencies of adverse events did not differ between dosage groups. Detectable antigen-specific CD4 T cell responses were induced by all doses of H4:IC31, but doses below 50 μg induced the highest frequencies of CD4 T cells, comprised predominantly of IFN-γ(+)TNF-α(+)IL-2(+) or TNF-α(+)IL-2(+) cells. These memory responses persisted up to the end of follow up, on study day 182. H4:IC31 demonstrated an acceptable safety profile and was immunogenic in South African adults. In this trial, the 15 μg dose appeared to induce the most optimal immune response. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Practical guideline for the management of adverse events associated with BCG installations].

PubMed

Rodríguez, Fernando; Palou, Juan; Martínez, R; Rodríguez, O; Rosales, A; Huguet, Jorge; Villavicencio, Humberto

2008-06-01

Morbidity secondary to intravesical Bacillus Calmette-Guèrin (BCG) may present both locally and systemically. Most patients suffer a self-limited irritative voiding syndrome. Often, there are not unified criteria for the management of BCG side effects. After treating more than 500 patients with BCG we developed a practical guideline for the management of its morbidity. We present clearly and schematically the practice guideline we follow in our Center when the patient presents symptoms and morbidity secondary to BCG intravesical installations. We analyze and describe, following the literature and our own experience, the management of adverse events experienced by patients treated with intravesical BCG, since the initial implementation of the protocol for its indication in patients with high risk non-muscle invasive bladder tumors and/or CIS. Irritative voiding symptoms are among the most frequent symptoms, generally self-limited; but if they persist (> 48 hours) will have the urologist treat them depending on intensity and duration. Macroscopic hematuria is not unfrequent and diminishes with an expectant approach and water intake. But, it may also be a urinary tract infection or residual tumor. A febrile syndrome, if present, is usually self-limited to the first 24-48 hours and below 38.5 degrees C without general status affectation. In cases of persistence and/or sepsis, tuberculostatic treatment and/or corticoids should be started. Other clinical pictures may appear, such as orchyoepididymitis, arthritis, etc. Proper diagnosis and treatment of adverse events after BCG therapy are basic to allow intravesical immunotherapy be properly prescribed and managed by urologists, enabling a proper treatment of patients and avoiding the possibility of more severe complications.

Augmentative Biocontrol in Natural Marine Habitats: Persistence, Spread and Non-Target Effects of the Sea Urchin Evechinus chloroticus

PubMed Central

Atalah, Javier; Hopkins, Grant A.; Forrest, Barrie M.

2013-01-01

Augmentative biocontrol aims to control established pest populations through enhancement of their indigenous enemies. To our knowledge, this approach has not been applied at an operational scale in natural marine habitats, in part because of the perceived risk of adverse non-target effects on native ecosystems. In this paper, we focus on the persistence, spread and non-target effects of the sea urchin Evechinus chloroticus when used as biocontrol agent to eradicate an invasive kelp from Fiordland, New Zealand. Rocky reef macrobenthic assemblages were monitored over 17 months in areas where the indigenous algal canopy was either removed or left intact prior to the translocation of a large number of urchins (>50 ind.·m−2). Urchin densities in treated areas significantly declined ∼9 months after transplant, and began spreading to adjacent sites. At the end of the 17-month study, densities had declined to ∼5 ind.·m−2. Compared to controls, treatment sites showed persistent shifts from kelp forest to urchin barrens, which were accompanied by significant reductions in taxa richness. Although these non-target effects were pronounced, they were considered to be localised and reversible, and arguably outweigh the irreversible and more profound ecological impacts associated with the establishment of an invasive species in a region of high conservation value. Augmentative biocontrol, used in conjunction with traditional control methods, represents a promising tool for the integrated management of marine pests. PMID:24260376

Experimental study on the evolution of Peregrine breather with uniform-depth adverse currents

NASA Astrophysics Data System (ADS)

Liao, B.; Ma, Y.; Ma, X.; Dong, G.

2018-05-01

A series of laboratory experiments were performed to study the evolution of Peregrine breather (PB) in a wave flume in finite depth, and wave trains were initially generated in a region of quiescent water and then propagated into an adverse current region for which the current velocity strength gradually increased from zero to an approximately stable value. The PB is often considered as a prototype of oceanic freak waves that can focus wave energy into a single wave packet. In the experiment, the cases were selected with the relative water depths k0h (k0 is the wave number in quiescent water and h is the water depth) varying from 3.11 through 8.17, and the initial wave steepness k0a0 (a0 is the background wave amplitude) ranges between 0.065 and 0.120. The experimental results show the persistence of the breather evolution dynamics even in the presence of strong opposing currents. We have shown that the characteristic spectrum of the PB persists even on strong currents, thus making it a viable characteristic for prediction of freak waves. It was also found that the adverse currents tend to shift the focusing point upstream compared to the cases without currents. Furthermore, it was found that uniform-depth adverse currents can reduce the breather extension in time domain.

The impact of childhood adversity on suicidality and clinical course in treatment-resistant depression.

PubMed

Tunnard, Catherine; Rane, Lena J; Wooderson, Sarah C; Markopoulou, Kalypso; Poon, Lucia; Fekadu, Abebaw; Juruena, Mario; Cleare, Anthony J

2014-01-01

Childhood adversity is a risk factor for the development of depression and can also affect clinical course. We investigated this specifically in treatment-resistant depression (TRD). One hundred and thirty-seven patients with TRD previously admitted to an inpatient affective disorders unit were included. Clinical, demographic and childhood adversity (physical, sexual, emotional abuse; bullying victimization, traumatic events) data were obtained during admission. Associations between childhood adversity, depressive symptoms and clinical course were investigated. Most patients had experienced childhood adversity (62%), with traumatic events (35%) and bullying victimization (29%) most commonly reported. Childhood adversity was associated with poorer clinical course, including earlier age of onset, episode persistence and recurrence. Logistic regression analyses revealed childhood adversity predicted lifetime suicide attempts (OR 2.79; 95% CI 1.14, 6.84) and childhood physical abuse predicted lifetime psychosis (OR 3.42; 95% CI 1.00, 11.70). The cross-sectional design and retrospective measurement of childhood adversity are limitations of the study. Childhood adversity was common amongst these TRD patients and was associated with poor clinical course, psychosis and suicide attempts. Routine assessment of early adversity may help identify at risk individuals and inform clinical intervention. Copyright © 2013 Elsevier B.V. All rights reserved.

Immunogenicity, safety and antibody persistence of a purified vero cell cultured rabies vaccine (Speeda) administered by the Zagreb regimen or Essen regimen in post-exposure subjects

PubMed Central

Shi, Nianmin; Zhang, Yibin; Zheng, Huizhen; Zhu, Zhenggang; Wang, Dingming; Li, Sihai; Li, Yuhua; Yang, Liqing; Zhang, Junnan; Bai, Yunhua; Lu, Qiang; Zhang, Zheng; Luo, Fengji; Yu, Chun; Li, Li

2017-01-01

ABSTRACT Aim: To compare the safety, immunogenicity and long-term effect of a purified vero cell cultured rabies vaccine in post-exposure subjects following 2 intramuscular regimens, Zagreb or Essen regimen. Methods: Serum samples were collected before vaccination and on days 7, 14, 42, 180 and 365 post vaccination. Solicited adverse events were recorded for 7 d following each vaccine dose, and unsolicited adverse events throughout the entire study period. This study was registered with ClinicalTrials.gov (NCT01821911 and NCT01827917). Results: No serious adverse events were reported. Although Zagreb regimen had a higher incidence of adverse reactions than Essen regimen at the first and second injection, the incidence was similar at the third and fourth injection between these 2 groups as well. At day 42, 100% subjects developed adequate rabies virus neutralizing antibody concentrations (≥ 0.5IU/ml) for both regimens. At days 180 and 365, the antibody level decreased dramatically, however, the percentage of subjects with adequate antibody concentrations still remained high (above 75% and 50% respectively). None of confirmed rabies virus exposured subjects had rabies one year later, and percentage of subjects with adequate antibody concentrations reached 100% at days 14 and 42. Conclusions: Rabies post-exposure prophylaxis vaccination with PVRV following a Zagreb regimen had a similar safety, immunogenicity and long-term effect to the Essen regimen in China. PMID:28121231

Transcriptome Analysis of Bombyx mori Larval Midgut during Persistent and Pathogenic Cytoplasmic Polyhedrosis Virus Infection

PubMed Central

Kolliopoulou, Anna; Van Nieuwerburgh, Filip; Stravopodis, Dimitrios J.; Deforce, Dieter; Swevers, Luc; Smagghe, Guy

2015-01-01

Many insects can be persistently infected with viruses but do not show any obvious adverse effects with respect to physiology, development or reproduction. Here, Bombyx mori strain Daizo, persistently infected with cytoplasmic polyhedrosis virus (BmCPV), was used to study the host’s transcriptional response after pathogenic infection with the same virus in midgut tissue of larvae persistently and pathogenically infected as 2nd and 4th instars. Next generation sequencing revealed that from 13,769 expressed genes, 167 were upregulated and 141 downregulated in both larval instars following pathogenic infection. Several genes that could possibly be involved in B. mori immune response against BmCPV or that may be induced by the virus in order to increase infectivity were identified, whereas classification of differentially expressed transcripts (confirmed by qRT-PCR) resulted in gene categories related to physical barriers, immune responses, proteolytic / metabolic enzymes, heat-shock proteins, hormonal signaling and uncharacterized proteins. Comparison of our data with the available literature (pathogenic infection of persistently vs. non-persistently infected larvae) unveiled various similarities of response in both cases, which suggests that pre-existing persistent infection does not affect in a major way the transcriptome response against pathogenic infection. To investigate the possible host’s RNAi response against BmCPV challenge, the differential expression of RNAi-related genes and the accumulation of viral small RNAs (vsRNAs) were studied. During pathogenic infection, siRNA-like traces like the 2-fold up-regulation of the core RNAi genes Ago-2 and Dcr-2 as well as a peak of 20 nt small RNAs were observed. Interestingly, vsRNAs of the same size were detected at lower rates in persistently infected larvae. Collectively, our data provide an initial assessment of the relative significance of persistent infection of silkworm larvae on the host response following pathogenic infection with CPV, while they also highlight the relative importance of RNAi as an antiviral mechanism. PMID:25816294

Risks and benefits of consumption of Great Lakes fish.

PubMed

Turyk, Mary E; Bhavsar, Satyendra P; Bowerman, William; Boysen, Eric; Clark, Milton; Diamond, Miriam; Mergler, Donna; Pantazopoulos, Peter; Schantz, Susan; Carpenter, David O

2012-01-01

Beneficial effects of fish consumption on early cognitive development and cardiovascular health have been attributed to the omega-3 fatty acids in fish and fish oils, but toxic chemicals in fish may adversely affect these health outcomes. Risk-benefit assessments of fish consumption have frequently focused on methylmercury and omega-3 fatty acids, not persistent pollutants such as polychlorinated biphenyls, and none have evaluated Great Lakes fish consumption. The risks and benefits of fish consumption have been established primarily for marine fish. Here, we examine whether sufficient data are available to evaluate the risks and benefits of eating freshwater fish from the Great Lakes. We used a scoping review to integrate information from multiple state, provincial, and federal agency sources regarding the contaminants and omega-3 fatty acids in Great Lakes fish and fish consumers, consumption rates and fish consumption advisories, and health effects of contaminants and omega-3 fatty acids. Great Lakes fish contain persistent contaminants--many of which have documented adverse health effects--that accumulate in humans consuming them. In contrast, data are sparse on omega-3 fatty acids in the fish and their consumers. Moreover, few studies have documented the social and cultural benefits of Great Lakes fish consumption, particularly for subsistence fishers and native communities. At this time, federal and state/provincial governments provide fish consumption advisories based solely on risk. Our knowledge of Great Lakes fish has critical gaps, particularly regarding the benefits of consumption. A risk-benefit analysis requires more information than is currently available on the concentration of omega-3 fatty acids in Great Lakes fish and their absorption by fish eaters in addition to more information on the social, cultural, and health consequences of changes in the amount of fish consumed.

Risks and Benefits of Consumption of Great Lakes Fish

PubMed Central

Bhavsar, Satyendra P.; Bowerman, William; Boysen, Eric; Clark, Milton; Diamond, Miriam; Mergler, Donna; Pantazopoulos, Peter; Schantz, Susan; Carpenter, David O.

2011-01-01

Background: Beneficial effects of fish consumption on early cognitive development and cardiovascular health have been attributed to the omega-3 fatty acids in fish and fish oils, but toxic chemicals in fish may adversely affect these health outcomes. Risk–benefit assessments of fish consumption have frequently focused on methylmercury and omega-3 fatty acids, not persistent pollutants such as polychlorinated biphenyls, and none have evaluated Great Lakes fish consumption. Objectives: The risks and benefits of fish consumption have been established primarily for marine fish. Here, we examine whether sufficient data are available to evaluate the risks and benefits of eating freshwater fish from the Great Lakes. Methods: We used a scoping review to integrate information from multiple state, provincial, and federal agency sources regarding the contaminants and omega-3 fatty acids in Great Lakes fish and fish consumers, consumption rates and fish consumption advisories, and health effects of contaminants and omega-3 fatty acids. Data synthesis: Great Lakes fish contain persistent contaminants—many of which have documented adverse health effects —that accumulate in humans consuming them. In contrast, data are sparse on omega-3 fatty acids in the fish and their consumers. Moreover, few studies have documented the social and cultural benefits of Great Lakes fish consumption, particularly for subsistence fishers and native communities. At this time, federal and state/provincial governments provide fish consumption advisories based solely on risk. Conclusions: Our knowledge of Great Lakes fish has critical gaps, particularly regarding the benefits of consumption. A risk–benefit analysis requires more information than is currently available on the concentration of omega-3 fatty acids in Great Lakes fish and their absorption by fish eaters in addition to more information on the social, cultural, and health consequences of changes in the amount of fish consumed. PMID:21947562

Born into adversity: psychological distress in two birth cohorts of second-generation Irish children growing up in Britain.

PubMed

Das-Munshi, J; Clark, C; Dewey, M E; Leavey, G; Stansfeld, S A; Prince, M J

2014-03-01

Worldwide, the Irish diaspora experience health inequalities persisting across generations. The present study sought to establish the prevalence of psychological morbidity in the children of migrant parents from Ireland, and reasons for differences. Data from two British birth cohorts were used for analysis. Each surveyed 17 000 babies born in one week in 1958 and 1970 and followed up through childhood. Validated scales assessed psychological health. Relative to the rest of the cohort, second-generation Irish children grew up in material hardship and showed greater psychological problems at ages 7, 11 (1958 cohort) and 16 (both cohorts). Adjusting for material adversity and maternal psychological distress markedly reduced differences. Relative to non-Irish parents, Irish-born parents were more likely to report chronic health problems (odds ratio [OR]: 1.29; 95% confidence interval [CI]: 1.08-1.54), and Irish-born mothers were more likely to be psychologically distressed (OR: 1.44; 95% CI: 1.13-1.84, when child was 10). Effect sizes diminished once material adversity was taken into account. Second-generation Irish children experienced high levels of psychological morbidity, but this was accounted for through adverse material circumstances in childhood and psychological distress in parents. Public health initiatives focusing on settlement experiences may reduce health inequalities in migrant children.

Transgender stigma and health: A critical review of stigma determinants, mechanisms, and interventions.

PubMed

White Hughto, Jaclyn M; Reisner, Sari L; Pachankis, John E

2015-12-01

Transgender people in the United States experience widespread prejudice, discrimination, violence, and other forms of stigma. This critical review aims to integrate the literature on stigma towards transgender people in the U.S. This review demonstrates that transgender stigma limits opportunities and access to resources in a number of critical domains (e.g., employment, healthcare), persistently affecting the physical and mental health of transgender people. The applied social ecological model employed here elucidates that transgender stigma operates at multiple levels (i.e., individual, interpersonal, structural) to impact health. Stigma prevention and coping interventions hold promise for reducing stigma and its adverse health-related effects in transgender populations. Additional research is needed to document the causal relationship between stigma and adverse health as well as the mediators and moderators of stigma in US transgender populations. Multi-level interventions to prevent stigma towards transgender people are warranted. Copyright © 2015 Elsevier Ltd. All rights reserved.

Transgender Stigma and Health: A Critical Review of Stigma Determinants, Mechanisms, and Interventions

PubMed Central

White Hughto, Jaclyn M.; Reisner, Sari L.; Pachankis, John E.

2015-01-01

Rationale Transgender people in the United States experience widespread prejudice, discrimination, violence, and other forms of stigma. Objective This critical review aims to integrate the literature on stigma towards transgender people in the US. Results This review demonstrates that transgender stigma limits opportunities and access to resources in a number of critical domains (e.g., employment, healthcare), persistently affecting the physical and mental health of transgender people. The applied social ecological model employed here elucidates that transgender stigma operates at multiple levels (i.e., individual, interpersonal, structural) to impact health. Stigma prevention and coping interventions hold promise for reducing stigma and its adverse health-related effects in transgender populations. Conclusion Additional research is needed to document the causal relationship between stigma and adverse health as well as the mediators and moderators of stigma in US transgender populations. Multi-level interventions to prevent stigma towards transgender people are warranted. PMID:26599625

Offenders in emerging adulthood: School maladjustment, childhood adversities, and prediction of aggressive antisocial behaviors.

PubMed

Wallinius, Märta; Delfin, Carl; Billstedt, Eva; Nilsson, Thomas; Anckarsäter, Henrik; Hofvander, Björn

2016-10-01

Early psychosocial adversities and maladjustment, such as childhood maltreatment and school adjustment problems, have been linked to an increased risk of aggressive antisocial behaviors. Yet, clinical studies of subjects at the highest risk of persistence in such behaviors are rare, especially during the life-changing transition years of emerging adulthood. This study describes early predictors of aggressive antisocial behaviors in a large, nationally representative cohort of Swedish, male violent offenders in emerging adulthood (age range = 18-25 years; N = 270). First, data on psychosocial background characteristics and aggressive antisocial behaviors (including age at onset) are provided. Second, early predictors of aggressive antisocial behaviors are tested in bivariate and multivariate interactive models. The offenders demonstrated a diversity of early onset adversities and disruptive behaviors, in line with established risk factors for subsequent criminality and adverse outcomes in a variety of life domains. Severe school adjustment problems, especially bullying others and early onset truancy, were important and interrelated predictors of aggressive antisocial behaviors over the lifetime, whereas childhood adversities such as parental substance or alcohol abuse and repeated exposure to violence at home during childhood were interrelated predictors of aggressive antisocial behaviors, albeit with less statistical importance. The findings stress the importance of early identification of individuals in the risk zone of developing severe and persistent aggressive antisocial behaviors and of early preventive interventions directed toward families with high-risk profiles. The findings also provide initial guidelines on which psychosocial background risk factors that need to be considered first-hand in early interventions. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Effectiveness of betahistine (48 mg/day) in patients with vestibular vertigo during routine practice: The VIRTUOSO study

PubMed Central

Parfenov, Vladimir A.; Golyk, Volodymyr A.; Matsnev, Eduard I.; Morozova, Svetlana V.; Melnikov, Oleg A.; Antonenko, Ludmila M.; Sigaleva, Elena E.; Situkho, Maksym I.; Asaulenko, Olena I.; Popovych, Vasyl I.; Zamergrad, Maxim V.

2017-01-01

Background Vestibular vertigo is associated with substantially reduced quality of life. Betahistine is effective in improving vertigo-associated symptoms, with longer treatment periods leading to greater improvements; however, it is not known whether these effects persist after treatment cessation. Methods VIRTUOSO was a prospective, multinational, non-comparative, post-marketing observational programme investigating the effectiveness of betahistine (48 mg/day) and the course of vertigo after the discontinuation of treatment. Patients with vestibular vertigo who were prescribed 48 mg/day betahistine were enrolled in Russia and Ukraine. Treatment duration was up to 2 months, and patients were followed up for 2 months after discontinuation of betahistine. Efficacy endpoints included clinical response (assessed by change in vertigo severity), monthly attack frequency, and physician and patient grading of overall clinical response and improvement of vertigo-associated symptoms. Results Overall, 309 patients were enrolled and 305 completed the study. Clinical response was rated as good, very good or excellent in 74.1% of patients at end of treatment, with vertigo severity significantly decreased from baseline (p < 0.001). Monthly vertigo attack frequency decreased significantly during the 2 months of treatment (p < 0.001 from baseline) and further decreased during the 2-month follow-up (p < 0.001 from end of treatment). Overall, clinical response was graded as good or excellent by 94.4% of physicians and 95.4% of patients. Clinical improvement was considered either good or excellent by 82.6–90.5% of physicians and patients for nausea, vomiting and faintness. Only one adverse event was reported, with no serious adverse events. Conclusion Our findings suggest that betahistine (48 mg/day) therapy is effective in treating vertigo in routine clinical settings. The observed effects persisted for 2 months after treatment cessation, suggesting that betahistine may facilitate lasting vestibular compensation. PMID:28358888

Health effects and toxicity mechanisms of rare earth elements-Knowledge gaps and research prospects.

PubMed

Pagano, Giovanni; Guida, Marco; Tommasi, Franca; Oral, Rahime

2015-05-01

In the recent decades, rare earth elements (REE) have undergone a steady spread in several industrial and medical applications, and in agriculture. Relatively scarce information has been acquired to date on REE-associated biological effects, from studies of bioaccumulation and of bioassays on animal, plant and models; a few case reports have focused on human health effects following occupational REE exposures, in the present lack of epidemiological studies of occupationally exposed groups. The literature is mostly confined to reports on few REE, namely cerium and lanthanum, whereas substantial information gaps persist on the health effects of other REE. An established action mechanism in REE-associated health effects relates to modulating oxidative stress, analogous to the recognized redox mechanisms observed for other transition elements. Adverse outcomes of REE exposures include a number of endpoints, such as growth inhibition, cytogenetic effects, and organ-specific toxicity. An apparent controversy regarding REE-associated health effects relates to opposed data pointing to either favorable or adverse effects of REE exposures. Several studies have demonstrated that REE, like a number of other xenobiotics, follow hormetic concentration-related trends, implying stimulatory or protective effects at low levels, then adverse effects at higher concentrations. Another major role for REE-associated effects should be focused on pH-dependent REE speciation and hence toxicity. Few reports have demonstrated that environmental acidification enhances REE toxicity; these data may assume particular relevance in REE-polluted acidic soils and in REE mining areas characterized by concomitant REE and acid pollution. The likely environmental threats arising from REE exposures deserve a new line of research efforts. Copyright © 2015 Elsevier Inc. All rights reserved.

Twelve-month trajectories of depressive and anxiety symptoms and associations with traumatic exposure and ongoing adversities: a latent trajectory analysis of a community cohort exposed to severe conflict in Sri Lanka

PubMed Central

Tay, A K; Jayasuriya, R; Jayasuriya, D; Silove, D

2017-01-01

We conducted a 12-month follow-up of a population sample of adults from districts (Mannar, Killinochi, Mullaitivu and Jaffna) exposed to high levels of mass conflict in Sri Lanka, the aim of the present analysis being to identify trajectories of depression and anxiety symptoms and their associations with exposure to psychological trauma and ongoing living adversities. The cohort of 1275 adults (response 86%) followed-up in 2015 was a structured subsample drawn from the baseline nationally representative survey conducted in 2014 across 25 districts in Sri Lanka. Interviews were conducted using electronic tablets by field workers applying contextually adapted indices of trauma exposure, ongoing adversities and symptoms of depression and anxiety. Latent transition analysis revealed a three-class longitudinal model from which four composite trajectories were derived, comprising a persistent symptom trajectory (n=555, 43.5%), an incident or new onset trajectory (n=170, 13.3%), a recovery trajectory (n=299, 23.5%) and a persistently low-symptom trajectory (n=251, 19.7%). Factors associated with both the persistent symptom and incident trajectories were female gender, past trauma exposure and lack of access to health services. Loss of a job was uniquely associated with the persisting trajectory at follow-up. The recovery trajectory comprised a higher proportion of men, older persons and those without risk factors. Our findings assist in translating epidemiologic data into public policy and practice by indicating the importance of stable employment and the provision of healthcare as key factors that may act to reduce anxiety and depressive symptoms in the post-conflict phase. The findings also confirm that women are at high risk of mental distress. Brief screening for trauma exposure in populations with high levels of exposure to mass conflict may assist in defining those at risk of ongoing symptoms of anxiety and depression. PMID:28786977

Persistent impacts to the deep soft-bottom benthos one year after the Deepwater Horizon event.

PubMed

Montagna, Paul A; Baguley, Jeffrey G; Cooksey, Cynthia; Hyland, Jeffrey L

2017-03-01

In fall 2010, several months after the Deepwater Horizon blowout was capped, zones of moderate and severe impacts to deep-sea, soft-bottom benthos were identified that together extended over an area of 172 km 2 . A subset of stations sampled in 2010 was resampled in May and June 2011, 10 to 11 months after the event, to determine whether the identified adverse effects were persisting. The design compared 20 stations from the combined moderate and severe impact zone to 12 stations in the reference zone that were sampled in both years. There were no statistically significant differences in contaminant concentrations between the impact and nonimpact zones from 2010 to 2011, which indicates contaminants persisted after 1 y. Whereas there were some signs of recovery in 2011 (particularly for the meiofauna abundance and diversity), there was evidence of persistent, statistically significant impacts to both macrofauna and meiofauna community structure. Macrofaunal taxa richness and diversity in 2011 were still 22.8% and 35.9% less, respectively, in the entire impact zone than in the surrounding nonimpact area, and meiofaunal richness was 28.5% less in the entire impact zone than in the surrounding area. The persistence of significant biodiversity losses and community structure change nearly 1 y after the wellhead was capped indicates that full recovery had yet to have occurred in 2011. Integr Environ Assess Manag 2017;13:342-351. © 2016 SETAC. © 2016 SETAC.

The challenge of compliance and persistence: focus on ulcerative colitis.

PubMed

Kane, Sunanda V; Brixner, Diana; Rubin, David T; Sewitch, Maida J

2008-01-01

Non-adherence to therapy is a widespread problem, with typical adherence rates for prescribed medications being approximately 50%. An estimated 20% to 50% of patients with ulcerative colitis (UC) do not take their medications as prescribed, resulting in higher disease-recurrence rates and potentially higher health care costs. To characterize the problem of non-adherence in UC, to review the many factors affecting compliance and persistence in this population, and to discuss practical strategies to improve adherence in these patients. Adherence to and persistence with medication are complex and multifactorial behaviors. Factors shown to affect adherence in UC patients include disease extent and duration, cost of medications, fear of adverse effects, individual psychosocial variables, and the patient-physician relationship. In contrast, recent data do not support an important role for treatment-related factors such as daily dose, regimen, and formulation in influencing adherence in this population, particularly with longer duration of use. Strategies to improve adherence should involve the patient, the provider, and the health care delivery system. For UC patients, knowledge and discussion of the rationale for supporting persistence, such as recent data regarding agents that have a potential chemoprotective benefit, may encourage persistence, even during periods of quiescence. The patient-physician relationship is critical in encouraging adherence, particularly with respect to education, open communication, and agreement regarding the value of the assigned treatment. Health care delivery systems can improve adherence by encouraging the participation of multidisciplinary teams, providing reporting and tracking systems, and eliminating financial barriers where possible.

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.

Family carers' experience of caring for an older parent with severe and persistent mental illness.

PubMed

McCann, Terence V; Bamberg, John; McCann, Flora

2015-06-01

While the burden of caring for older people with chronic medical illness and dementia has been well documented, considerably less is known about how carers develop the strength and resilience to sustain this important role with older family members with mental illness. The aim of the study was to understand the lived experience of primary caregivers of older people with severe and persistent mental illness, and to explore what, if anything, helps to sustain them in their caring role. An interpretative phenomenological analysis approach was adopted, and qualitative interviews were used with 30 primary caregivers. Two overarching themes, and related subthemes, were abstracted from the data. First, caring is a difficult and demanding responsibility. It affects carers adversely, emotionally, physically, socially, and financially, and their lifestyle in general. This is reflected in three subthemes: (i) physically and emotionally draining; (ii) grieving about the loss; (iii) and adverse effects on lifestyle and social relationships. Second, carers develop resilience in caring, which helps sustain them in their role, as illustrated in three subthemes: (i) caring as purposeful and satisfying; (ii) harnessing social support from others; and (iii) purposefully maintaining their own well-being. Community mental health nurses have a key role in assessing carers' needs and supporting them in their caring role. © 2015 Australian College of Mental Health Nurses Inc.

Particulate matter beyond mass: recent health evidence on the role of fractions, chemical constituents and sources of emission

PubMed Central

Héroux, Marie-Eve; Gerlofs-Nijland, Miriam E.; Kelly, Frank J.

2013-01-01

Particulate matter (PM) is regulated in various parts of the world based on specific size cut offs, often expressed as 10 or 2.5 µm mass median aerodynamic diameter. This pollutant is deemed one of the most dangerous to health and moreover, problems persist with high ambient concentrations. Continuing pressure to re-evaluate ambient air quality standards stems from research that not only has identified effects at low levels of PM but which also has revealed that reductions in certain components, sources and size fractions may best protect public health. Considerable amount of published information have emerged from toxicological research in recent years. Accumulating evidence has identified additional air quality metrics (e.g. black carbon, secondary organic and inorganic aerosols) that may be valuable in evaluating the health risks of, for example, primary combustion particles from traffic emissions, which are not fully taken into account with PM2.5 mass. Most of the evidence accumulated so far is for an adverse effect on health of carbonaceous material from traffic. Traffic-generated dust, including road, brake and tire wear, also contribute to the adverse effects on health. Exposure durations from a few minutes up to a year have been linked with adverse effects. The new evidence collected supports the scientific conclusions of the World Health Organization Air Quality Guidelines and also provides scientific arguments for taking decisive actions to improve air quality and reduce the global burden of disease associated with air pollution. PMID:24304307

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

Not Available

One objective of the study is to assess the effects of all currently known deviations from normal of medical, physiological, and biochemical parameters which appear to be due to zero gravity (zero-g) environment and to acceleration and deceleration to be experienced, as outlined in the reference Solar Power Satellite (SPS) design, by space worker. Study results include identification of possible health or safety effects on space workers - either immediate or delayed - due to the zero gravity environment and acceleration and deceleration; estimation of the probability that an individual will be adversely affected; description of the possible consequence tomore » work efficiently in persons adversely affected; and description of the possible/probable consequences to immediate and future health of individuals exposed to this environment. A research plan, which addresses the uncertainties in current knowledge regarding the health and safety hazards to exposed SPS space workers, is presented. Although most adverse affects experienced during space flight soon disappeared upon return to the Earth's environment, there remains a definite concern for the long-term effects to SPS space workers who might spend as much as half their time in space during a possible five-year career period. The proposed 90-day up/90 day down cycle, coupled with the fact that most of the effects of weightlessness may persist throughout the flight along with the realization that recovery may occupy much of the terrestrial stay, may keep the SPS workers in a deviant physical condition or state of flux for 60 to 100% of their five-year career. (JGB)« less

Particulate matter beyond mass: recent health evidence on the role of fractions, chemical constituents and sources of emission.

PubMed

Cassee, Flemming R; Héroux, Marie-Eve; Gerlofs-Nijland, Miriam E; Kelly, Frank J

2013-12-01

Particulate matter (PM) is regulated in various parts of the world based on specific size cut offs, often expressed as 10 or 2.5 µm mass median aerodynamic diameter. This pollutant is deemed one of the most dangerous to health and moreover, problems persist with high ambient concentrations. Continuing pressure to re-evaluate ambient air quality standards stems from research that not only has identified effects at low levels of PM but which also has revealed that reductions in certain components, sources and size fractions may best protect public health. Considerable amount of published information have emerged from toxicological research in recent years. Accumulating evidence has identified additional air quality metrics (e.g. black carbon, secondary organic and inorganic aerosols) that may be valuable in evaluating the health risks of, for example, primary combustion particles from traffic emissions, which are not fully taken into account with PM2.5 mass. Most of the evidence accumulated so far is for an adverse effect on health of carbonaceous material from traffic. Traffic-generated dust, including road, brake and tire wear, also contribute to the adverse effects on health. Exposure durations from a few minutes up to a year have been linked with adverse effects. The new evidence collected supports the scientific conclusions of the World Health Organization Air Quality Guidelines and also provides scientific arguments for taking decisive actions to improve air quality and reduce the global burden of disease associated with air pollution.

Respiratory Toxicity of Lunar Highland Dust

NASA Technical Reports Server (NTRS)

James, John T.; Lam, Chiu-wing; Wallace, William T.

2009-01-01

Lunar dust exposures occurred during the Apollo missions while the crew was on the lunar surface and especially when microgravity conditions were attained during rendezvous in lunar orbit. Crews reported that the dust was irritating to the eyes and in some cases respiratory symptoms were elicited. NASA s vision for lunar exploration includes stays of 6 months on the lunar surface hence the health effects of periodic exposure to lunar dust need to be assessed. NASA has performed this assessment with a series of in vitro and in vivo tests on authentic lunar dust. Our approach is to "calibrate" the intrinsic toxicity of lunar dust by comparison to a nontoxic dust (TiO2) and a highly toxic dust (quartz) using intratrachael instillation of the dusts in mice. A battery of indices of toxicity is assessed at various time points after the instillations. Cultures of selected cells are exposed to test dusts to assess the adverse effects on the cells. Finally, chemical systems are used to assess the nature of the reactivity of various dusts and to determine the persistence of reactivity under various environmental conditions that are relevant to a space habitat. Similar systems are used to assess the dissolution of the dust. From these studies we will be able to set a defensible inhalation exposure standard for aged dust and predict whether we need a separate standard for reactive dust. Presently-available data suggest that aged lunar highland dust is slightly toxic, that it can adversely affect cultured cells, and that the surface reactivity induced by grinding the dust persists for a few hours after activation.

Safety, Efficacy, and Persistence of Long-Term Mirabegron Treatment for Overactive Bladder in the Daily Clinical Setting: Interim (1-Year) Report from a Japanese Post-Marketing Surveillance Study.

PubMed

Kato, Daisuke; Tabuchi, Hiromi; Uno, Satoshi

2017-08-01

To report interim 1-year results from a 3-year surveillance study evaluating safety, efficacy, and persistence of long-term mirabegron for overactive bladder (OAB). Patients starting treatment with mirabegron for urinary urgency, daytime frequency, and urgency incontinence associated with OAB were registered and followed up for 3 years. Data were collected on adverse drug reactions (ADR), changes in OAB symptoms, changes in Overactive Bladder Symptom Score (OABSS), and treatment discontinuations. Treatment persistence rates were calculated by Kaplan-Meier analysis. Eighty-one ADR were observed in 72/1139 patients (6.3%) through 1 year of mirabegron treatment, with the incidence highest during the first month. No significant change in residual urine volume was observed at any observation point up to 1 year of mirabegron treatment. Mirabegron was deemed "effective" in 883/1091 patients (80.9%) at 1 year/discontinuation. Total OABSS was decreased with statistical significance at 3 months, 6 months, and 1 year, or at discontinuation (P < 0.001 at each time point). Kaplan-Meier treatment persistence rates were 84.8% at 3 months, 77.6% at 6 months, and 66.0% at 1 year. Treatment persistence rates were similar for male and female patients but significantly higher for patients aged ≥65 years (67.3%; n = 908) compared with those aged <65 years (59.8%; n = 231; log-rank test: P = 0.032). Long-term OAB treatment with mirabegron was well-tolerated, with effectiveness maintained through 1 year. Mirabegron treatment persistence was higher than has been previously reported, and was greater in patients aged ≥65 years compared with those aged <65 years. © 2017 John Wiley & Sons Australia, Ltd.

Alcohol intake alters immune responses and promotes CNS viral persistence in mice.

PubMed

Loftis, Jennifer M; Taylor, Jonathan; Raué, Hans-Peter; Slifka, Mark K; Huang, Elaine

2016-10-01

Chronic hepatitis C virus (HCV) infection leads to progressive liver disease and is associated with a variety of extrahepatic effects, including central nervous system (CNS) damage and neuropsychiatric impairments. Alcohol abuse can exacerbate these adverse effects on brain and behavior, but the molecular mechanisms are not well understood. This study investigated the role of alcohol in regulating viral persistence and CNS immunopathology in mice infected with lymphocytic choriomeningitis virus (LCMV), a model for HCV infections in humans. Female and male BALB/c mice (n=94) were exposed to alcohol (ethanol; EtOH) and water (or water only) using a two-bottle choice paradigm, followed one week later by infection with either LCMV clone 13 (causes chronic infection similar to chronic HCV), LCMV Armstrong (causes acute infection), or vehicle. Mice were monitored for 60days post-infection and continued to receive 24-h access to EtOH and water. Animals infected with LCMV clone 13 drank more EtOH, as compared to those with an acute or no viral infection. Six weeks after infection with LCMV clone 13, mice with EtOH exposure evidenced higher serum viral titers, as compared to mice without EtOH exposure. EtOH intake was also associated with reductions in virus-specific CD8(+) T cell frequencies (particularly CD11a(hi) subsets) and evidence of persistent CNS viremia in chronically infected mice. These findings support the hypothesis that EtOH use and chronic viral infection can result in combined toxic effects accelerating CNS damage and neuropsychiatric dysfunction and suggest that examining the role of EtOH in regulating viral persistence and CNS immunopathology in mice infected with LCMV can lead to a more comprehensive understanding of comorbid alcohol use disorder and chronic viral infection. Published by Elsevier B.V.

Adverse Health Effects Associated with Living in a Former Methamphetamine Drug Laboratory - Victoria, Australia, 2015.

PubMed

Wright, Jackie; Kenneally, Michaela E; Edwards, John W; Walker, G Stewart

2017-01-06

The manufacture of methamphetamine in clandestine drug laboratories occurs in various locations, including residential houses and apartments. Unlike the controlled manufacture of chemicals and drugs, clandestine manufacture results in the uncontrolled storage, use, generation, and disposal of a wide range of chemicals and the deposit of methamphetamine drug residues on indoor surfaces (1). These residues have been found at high levels on porous and nonporous surfaces and have been shown to persist for months to years (1). Persons exposed to these environments often have poorly defined exposures and health effects. It is commonly assumed that these levels of exposure are low compared with those related to illicit drug use or therapeutic use of amphetamine-based drugs for managing behavioral issues such as attention deficit hyperactivity disorder (2). In 2015, a family that was unknowingly exposed to methamphetamine residues in a house in Australia was found to have adverse health effects and elevated methamphetamine levels in hair samples, highlighting the potential for public health risks for persons who might live in methamphetamine-contaminated dwellings. This case study highlights the importance of the identification and effective decontamination of former clandestine drug laboratories.

POSSIBLE ESTUARY ASSOCIATED SYNDROME: SYMPTOMS, VISION & TREATMENT.

EPA Science Inventory

Evidence suggests that the estuarine dinoflagellate, Pfiesteria piscicida, and/or morphologically related organisms (Pf-MRO) may release a toxin(s) which kills fish and adversely affects human health. The North Carolina study investigated the potential for persistent health effec...

Solid waste containing persistent organic pollutants in Serbia: From precautionary measures to the final treatment (case study).

PubMed

Stevanovic-Carapina, Hristina; Milic, Jelena; Curcic, Marijana; Randjelovic, Jasminka; Krinulovic, Katarina; Jovovic, Aleksandar; Brnjas, Zvonko

2016-07-01

Sustainable solid waste management needs more dedicated attention in respect of environmental and human health protection. Solid waste containing persistent organic pollutants is of special concern, since persistent organic pollutants are persistent, toxic and of high risk to human health and the environment. The objective of this investigation was to identify critical points in the Serbian system of solid waste and persistent organic pollutants management, to assure the life cycle management of persistent organic pollutants and products containing these chemicals, including prevention and final destruction. Data were collected from the Serbian competent authorities, and led us to identify preventive actions for solid waste management that should reduce or minimise release of persistent organic pollutants into the environment, and to propose actions necessary for persistent organic pollutants solid waste. The adverse impact of persistent organic pollutants is multidimensional. Owing to the lack of treatment or disposal plants for hazardous waste in Serbia, the only option at the moment to manage persistent organic pollutants waste is to keep it in temporary storage and when conditions are created (primarily financial), such waste should be exported for destruction in hazardous waste incinerators. Meanwhile, it needs to be assured that any persistent organic pollutants management activity does not negatively impact recycling flows or disturb progress towards a more circular economy in Serbia. © The Author(s) 2016.

MODELING BLACK-WHITE PRETERM BIRTH DISPARITY: ECOLOGIC AND MULTILEVEL MODELS

EPA Science Inventory

INTRODUCTION. The disparity between black and white women's adverse birth outcomes has been subject to much investigation, yet the factors underlying its persistence remain elusive, which has encouraged research on neighborhood-level influences. This work considers two main que...

Persistent erectile dysfunction in men exposed to the 5α-reductase inhibitors, finasteride, or dutasteride

PubMed Central

Yarnold, Paul R.; Cashy, John; Brannigan, Robert E.; Nardone, Beatrice; Micali, Giuseppe; West, Dennis Paul

2017-01-01

Importance Case reports describe persistent erectile dysfunction (PED) associated with exposure to 5α-reductase inhibitors (5α-RIs). Clinical trial reports and the manufacturers’ full prescribing information (FPI) for finasteride and dutasteride state that risk of sexual adverse effects is not increased by longer duration of 5α-RI exposure and that sexual adverse effects of 5α-RIs resolve in men who discontinue exposure. Objective Our chief objective was to assess whether longer duration of 5α-RI exposure increases risk of PED, independent of age and other known risk factors. Men with shorter 5α-RI exposure served as a comparison control group for those with longer exposure. Design We used a single-group study design and classification tree analysis (CTA) to model PED (lasting ≥90 days after stopping 5α-RI). Covariates included subject attributes, diseases, and drug exposures associated with sexual dysfunction. Setting Our data source was the electronic medical record data repository for Northwestern Medicine. Subjects The analysis cohorts comprised all men exposed to finasteride or dutasteride or combination products containing one of these drugs, and the subgroup of men 16–42 years old and exposed to finasteride ≤1.25 mg/day. Main outcome and measures Our main outcome measure was diagnosis of PED beginning after first 5α-RI exposure, continuing for at least 90 days after stopping 5α-RI, and with contemporaneous treatment with a phosphodiesterase-5 inhibitor (PDE5I). Other outcome measures were erectile dysfunction (ED) and low libido. PED was determined by manual review of medical narratives for all subjects with ED. Risk of an adverse effect was expressed as number needed to harm (NNH). Results Among men with 5α-RI exposure, 167 of 11,909 (1.4%) developed PED (persistence median 1,348 days after stopping 5α-RI, interquartile range (IQR) 631.5–2320.5 days); the multivariable model predicting PED had four variables: prostate disease, duration of 5α-RI exposure, age, and nonsteroidal anti-inflammatory drug (NSAID) use. Of 530 men with new ED, 167 (31.5%) had new PED. Men without prostate disease who combined NSAID use with >208.5 days of 5α-RI exposure had 4.8-fold higher risk of PED than men with shorter exposure (NNH 59.8, all p < 0.002). Among men 16–42 years old and exposed to finasteride ≤1.25 mg/day, 34 of 4,284 (0.8%) developed PED (persistence median 1,534 days, IQR 651–2,351 days); the multivariable model predicting PED had one variable: duration of 5α-RI exposure. Of 103 young men with new ED, 34 (33%) had new PED. Young men with >205 days of finasteride exposure had 4.9-fold higher risk of PED (NNH 108.2, p < 0.004) than men with shorter exposure. Conclusion and relevance Risk of PED was higher in men with longer exposure to 5α-RIs. Among young men, longer exposure to finasteride posed a greater risk of PED than all other assessed risk factors. PMID:28289563

Resetting the bar: Establishing baselines for persistent contaminants after Hurricane Sandy in the coastal environments of New Jersey and New York, USA

USGS Publications Warehouse

Reilly, Timothy J.; Focazio, Michael J.; Simmons, Dale L.

2016-01-01

In the immediate aftermath of natural disasters, public health officials and other first responders engage in many activities to protect the public and ecosystems in the affected area. These activities include critical tasks designed to minimize adverse consequences resulting from chemical and microbial contaminant exposures, such as acute disease incidence and transmission. However, once these urgent priorities have been met and situations requiring immediate attention have been stabilized, questions regarding the potential longer term threats to humans and ecosystems associated with persistent contaminant exposures remain. Research conducted to address these questions is frequently challenged by the lack of available baseline contaminant information collected before the event for comparison and perspective. In addition, deployments of field crews and collection of environmental samples typically occur days, weeks, or months after the event. Consequently, during and in the aftermath of disasters, public health agencies commonly advise the public to disinfect water, avoid contact with disturbed infrastructure (such as sewer lines), and (or) refrain from use of recreational waters, with the general focus on acute health threats; however, the persisting effects of such releases on local recreational waters, fisheries, and other estuarine habitats are often undetermined.

Assessment of zero gravity effects on space worker health and safety

NASA Technical Reports Server (NTRS)

1980-01-01

One objective of the study is to assess the effects of all currently known deviations from normal of medical, physiological, and biochemical parameters which appear to be due to zero gravity (zero-g) environment and to acceleration and deceleration to be experienced, as outlined in the references Solar Power Satellites (SPS) design, by space worker. Study results include identification of possible health or safety effects on space workers either immediate or delayed due to the zero gravity environment and acceleration and deceleration; estimation of the probability that an individual will be adversely affected; description of the possible consequence to work efficiency in persons adversely affected; and description of the possible/probable consequences to immediate and future health of individuals exposed to this environment. A research plan, which addresses the uncertainties in current knowledge regarding the health and safety hazards to exposed SPS space workers, is presented. Although most adverse affects experienced during space flight soon disappeared upon return to the Earth's environment, there remains a definite concern for the long-term effects to SPS space workers who might spend as much as half their time in space during a possible five year career period. The proposed 90 day up/90 day down cycle, coupled with the fact that most of the effects of weightlessness may persist throughout the flight along with the realization that recovery may occupy much of the terrestrial stay, may keep the SPS workers in a deviant physical condition or state of flux for 60 to 100% of their five year career.

A Markov chain model to evaluate the effect of CYP3A5 and ABCB1 polymorphisms on adverse events associated with tacrolimus in pediatric renal transplantation.

PubMed

Sy, Sherwin K B; Heuberger, Jules; Shilbayeh, Sireen; Conrado, Daniela J; Derendorf, Hartmut

2013-10-01

The SNP A6986G of the CYP3A5 gene (*3) results in a non-functional protein due to a splicing defect whereas the C3435T was associated with variable expression of the ABCB1 gene, due to protein instability. Part of the large interindividual variability in tacrolimus efficacy and toxicity can be accounted for by these genetic factors. Seventy-two individuals were examined for A6986G and C3435T polymorphism using a PCR-RFLP-based technique to estimate genotype and allele frequencies in the Jordanian population. The association of age, hematocrit, platelet count, CYP3A5, and ABCB1 polymorphisms with tacrolimus dose- and body-weight-normalized levels in the subset of 38 pediatric renal transplant patients was evaluated. A Markov model was used to evaluate the time-dependent probability of an adverse event occurrence by CYP3A5 phenotypes and ABCB1 genotypes. The time-dependent probability of adverse event was about double in CYP3A5 non-expressors compared to the expressors for the first 12 months of therapy. The CYP3A5 non-expressors had higher corresponding normalized tacrolimus levels compared to the expressors in the first 3 months. The correlation trend between probability of adverse events and normalized tacrolimus concentrations for the two CYP3A5 phenotypes persisted for the first 9 months of therapy. The differences among ABCB1 genotypes in terms of adverse events and normalized tacrolimus levels were only observed in the first 3 months of therapy. The information on CYP3A5 genotypes and tacrolimus dose requirement is important in designing effective programs toward management of tacrolimus side effects particularly for the initial dose when tacrolimus blood levels are not available for therapeutic drug monitoring.

The moderating impact of childhood adversity profiles and conflict on psychological health and suicidal behaviour in the Northern Ireland population.

PubMed

McLafferty, Margaret; O'Neill, Siobhan; Murphy, Sam; Armour, Cherie; Ferry, Finola; Bunting, Brendan

2018-04-01

Childhood adversities are key etiological factors in the onset and persistence of psychopathology. In Northern Ireland the Troubles also impacted on the population's psychological health. This study used data from the Northern Ireland Study of Health and Stress a collaborative epidemiological study which used the WMH-CIDI to assess mental health disorders in a nationally representative sample (Part 2, n = 1986). The aims of the study were to assess co-occurrences of childhood adversities and investigate the impact of adversity profiles and conflict experience on psychopathology and suicidal behaviour. Latent Class Analysis uncovered 3 discrete childhood adversity profiles, a low, medium, and high risk class. Individuals from higher risk adversity profiles displayed significantly increased odds of having psychological problems, with conflict exposure also impacting on psychopathology. However, the study revealed that the impact of conflict exposure on suicidal behaviour was moderated by latent class membership and that some adversity may actually be protective. The findings highlight the need to consider that, while adversity can have a negative impact on psychopathology, a lack of adversity early in life may hinder some people from developing adequate coping strategies. Further research is required to identify adversity patterns and other interacting factors that are protective. Copyright © 2018 Elsevier B.V. All rights reserved.

Minocycline successfully treats exaggerated granulomatous hypersensitivity reaction to Mw immunotherapy.

PubMed

Vinay, Keshavamurthy; Narang, Tarun; Saikia, Uma N; Kumaran, Muthu Sendhil; Dogra, Sunil

2017-03-01

Mycobacterium W (Mw) vaccine has been found to be effective in the treatment of leprosy and warts. Despite increasing use of Mw immunotherapy, data on its safety is limited. We report a series of eight patients who developed persisting injection site granulomatous reaction following Mw immunotherapy and were successfully treated with minocycline. Eight patients with persistent nodular swelling at the site of Mw injections were identified. Seven of them had received Mw immunotherapy for cutaneous warts and one for verrucous epidermal nevus. The lesions were firm, erythematous, succulent, non-tender nodules confined to the sites of Mw vaccine injections. In 6 of these patients nodules also involved the previously injected areas. Skin biopsy from all patients showed eosinophil rich inflammation admixed with histiocytes and lymphocytes. In addition granulomas were seen in all with septal and nodular panniculitis in four patients. Broken and granular acid-fast bacilli were identified in two cases. All patients were treated with oral minocycline 100 mg/day for a mean of 9 weeks and showed good clinical response. Granulomatous reaction is a rare but significant adverse effect of Mw immunotherapy at cosmetically and functionally imperative sites. Oral minocycline appears to be effective therapy in this situation. © 2016 Wiley Periodicals, Inc.

Nanoparticulate carbon black in cigarette smoke induces DNA cleavage and Th17-mediated emphysema

PubMed Central

You, Ran; Lu, Wen; Shan, Ming; Berlin, Jacob M; Samuel, Errol LG; Marcano, Daniela C; Sun, Zhengzong; Sikkema, William KA; Yuan, Xiaoyi; Song, Lizhen; Hendrix, Amanda Y; Tour, James M; Corry, David B; Kheradmand, Farrah

2015-01-01

Chronic inhalation of cigarette smoke is the major cause of sterile inflammation and pulmonary emphysema. The effect of carbon black (CB), a universal constituent of smoke derived from the incomplete combustion of organic material, in smokers and non-smokers is less known. In this study, we show that insoluble nanoparticulate carbon black (nCB) accumulates in human myeloid dendritic cells (mDCs) from emphysematous lung and in CD11c+ lung antigen presenting cells (APC) of mice exposed to smoke. Likewise, nCB intranasal administration induced emphysema in mouse lungs. Delivered by smoking or intranasally, nCB persisted indefinitely in mouse lung, activated lung APCs, and promoted T helper 17 cell differentiation through double-stranded DNA break (DSB) and ASC-mediated inflammasome assembly in phagocytes. Increasing the polarity or size of CB mitigated many adverse effects. Thus, nCB causes sterile inflammation, DSB, and emphysema and explains adverse health outcomes seen in smokers while implicating the dangers of nCB exposure in non-smokers. DOI: http://dx.doi.org/10.7554/eLife.09623.001 PMID:26437452

Surgical ablation of atrial fibrillation during mitral-valve surgery.

PubMed

Gillinov, A Marc; Gelijns, Annetine C; Parides, Michael K; DeRose, Joseph J; Moskowitz, Alan J; Voisine, Pierre; Ailawadi, Gorav; Bouchard, Denis; Smith, Peter K; Mack, Michael J; Acker, Michael A; Mullen, John C; Rose, Eric A; Chang, Helena L; Puskas, John D; Couderc, Jean-Philippe; Gardner, Timothy J; Varghese, Robin; Horvath, Keith A; Bolling, Steven F; Michler, Robert E; Geller, Nancy L; Ascheim, Deborah D; Miller, Marissa A; Bagiella, Emilia; Moquete, Ellen G; Williams, Paula; Taddei-Peters, Wendy C; O'Gara, Patrick T; Blackstone, Eugene H; Argenziano, Michael

2015-04-09

Among patients undergoing mitral-valve surgery, 30 to 50% present with atrial fibrillation, which is associated with reduced survival and increased risk of stroke. Surgical ablation of atrial fibrillation has been widely adopted, but evidence regarding its safety and effectiveness is limited. We randomly assigned 260 patients with persistent or long-standing persistent atrial fibrillation who required mitral-valve surgery to undergo either surgical ablation (ablation group) or no ablation (control group) during the mitral-valve operation. Patients in the ablation group underwent further randomization to pulmonary-vein isolation or a biatrial maze procedure. All patients underwent closure of the left atrial appendage. The primary end point was freedom from atrial fibrillation at both 6 months and 12 months (as assessed by means of 3-day Holter monitoring). More patients in the ablation group than in the control group were free from atrial fibrillation at both 6 and 12 months (63.2% vs. 29.4%, P<0.001). There was no significant difference in the rate of freedom from atrial fibrillation between patients who underwent pulmonary-vein isolation and those who underwent the biatrial maze procedure (61.0% and 66.0%, respectively; P=0.60). One-year mortality was 6.8% in the ablation group and 8.7% in the control group (hazard ratio with ablation, 0.76; 95% confidence interval, 0.32 to 1.84; P=0.55). Ablation was associated with more implantations of a permanent pacemaker than was no ablation (21.5 vs. 8.1 per 100 patient-years, P=0.01). There were no significant between-group differences in major cardiac or cerebrovascular adverse events, overall serious adverse events, or hospital readmissions. The addition of atrial fibrillation ablation to mitral-valve surgery significantly increased the rate of freedom from atrial fibrillation at 1 year among patients with persistent or long-standing persistent atrial fibrillation, but the risk of implantation of a permanent pacemaker was also increased. (Funded by the National Institutes of Health and the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00903370.).

Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases

PubMed Central

Gasser, Peter; Holstein, Dominique; Michel, Yvonne; Doblin, Rick; Yazar-Klosinski, Berra; Passie, Torsten; Brenneisen, Rudolf

2014-01-01

Abstract A double-blind, randomized, active placebo-controlled pilot study was conducted to examine safety and efficacy of lysergic acid diethylamide (LSD)-assisted psychotherapy in 12 patients with anxiety associated with life-threatening diseases. Treatment included drug-free psychotherapy sessions supplemented by two LSD-assisted psychotherapy sessions 2 to 3 weeks apart. The participants received either 200 μg of LSD (n = 8) or 20 μg of LSD with an open-label crossover to 200 μg of LSD after the initial blinded treatment was unmasked (n = 4). At the 2-month follow-up, positive trends were found via the State-Trait Anxiety Inventory (STAI) in reductions in trait anxiety (p = 0.033) with an effect size of 1.1, and state anxiety was significantly reduced (p = 0.021) with an effect size of 1.2, with no acute or chronic adverse effects persisting beyond 1 day after treatment or treatment-related serious adverse events. STAI reductions were sustained for 12 months. These results indicate that when administered safely in a methodologically rigorous medically supervised psychotherapeutic setting, LSD can reduce anxiety, suggesting that larger controlled studies are warranted. PMID:24594678

Safety and efficacy of lysergic acid diethylamide-assisted psychotherapy for anxiety associated with life-threatening diseases.

PubMed

Gasser, Peter; Holstein, Dominique; Michel, Yvonne; Doblin, Rick; Yazar-Klosinski, Berra; Passie, Torsten; Brenneisen, Rudolf

2014-07-01

A double-blind, randomized, active placebo-controlled pilot study was conducted to examine safety and efficacy of lysergic acid diethylamide (LSD)-assisted psychotherapy in 12 patients with anxiety associated with life-threatening diseases. Treatment included drug-free psychotherapy sessions supplemented by two LSD-assisted psychotherapy sessions 2 to 3 weeks apart. The participants received either 200 μg of LSD (n = 8) or 20 μg of LSD with an open-label crossover to 200 μg of LSD after the initial blinded treatment was unmasked (n = 4). At the 2-month follow-up, positive trends were found via the State-Trait Anxiety Inventory (STAI) in reductions in trait anxiety (p = 0.033) with an effect size of 1.1, and state anxiety was significantly reduced (p = 0.021) with an effect size of 1.2, with no acute or chronic adverse effects persisting beyond 1 day after treatment or treatment-related serious adverse events. STAI reductions were sustained for 12 months. These results indicate that when administered safely in a methodologically rigorous medically supervised psychotherapeutic setting, LSD can reduce anxiety, suggesting that larger controlled studies are warranted.

Using energy budgets to combine ecology and toxicology in a mammalian sentinel species

NASA Astrophysics Data System (ADS)

Desforges, Jean-Pierre W.; Sonne, Christian; Dietz, Rune

2017-04-01

Process-driven modelling approaches can resolve many of the shortcomings of traditional descriptive and non-mechanistic toxicology. We developed a simple dynamic energy budget (DEB) model for the mink (Mustela vison), a sentinel species in mammalian toxicology, which coupled animal physiology, ecology and toxicology, in order to mechanistically investigate the accumulation and adverse effects of lifelong dietary exposure to persistent environmental toxicants, most notably polychlorinated biphenyls (PCBs). Our novel mammalian DEB model accurately predicted, based on energy allocations to the interconnected metabolic processes of growth, development, maintenance and reproduction, lifelong patterns in mink growth, reproductive performance and dietary accumulation of PCBs as reported in the literature. Our model results were consistent with empirical data from captive and free-ranging studies in mink and other wildlife and suggest that PCB exposure can have significant population-level impacts resulting from targeted effects on fetal toxicity, kit mortality and growth and development. Our approach provides a simple and cross-species framework to explore the mechanistic interactions of physiological processes and ecotoxicology, thus allowing for a deeper understanding and interpretation of stressor-induced adverse effects at all levels of biological organization.

What is the role of steroids in pneumonia therapy?

PubMed

Póvoa, Pedro; Salluh, Jorge I F

2012-04-01

This review evaluates the potential benefits as well as adverse effects from adjunctive therapy with systemic steroids in patients with pneumonia: either mild-to-moderate or severe, community-acquired or hospital-acquired, of bacterial or of viral origin (in particular H1N1 viral infection). Steroids potentially modulate the marked and persistent activation of the immune system in pneumonia. However, several recent randomized controlled trials and large prospective observational studies have repeatedly shown that steroids had no impact on survival, the clinical event of interest, but in severe pneumonia some studies pointed to potential harmful effect. In addition, adverse effects, namely hyperglycemia, superinfections, as well as increased length-of-stay, were frequent findings in the steroid-treated patients. According to the current evidence, there are no data to support the well tolerated use of systemic steroids as a standard of care in pneumonia, neither in mild-to-moderate and severe, nor in bacterial and viral infection. Clinical and basic research should work together to improve trial designs to identify reliable surrogate markers of outcome, in particular of mortality. This may improve the patient selection and facilitate the identification of subgroups that can benefit from adjunctive steroid therapy.

The feasibility, perceived satisfaction, and value of using synchronous webinars to educate clinical research professionals on reporting adverse events in clinical trials: a report from the Children's Oncology Group.

PubMed

Borgerson, Dawn; Dino, Jennifer

2012-01-01

Clinical research professionals are faced with decreased funding and increased workloads; innovative methods of professional development programs are necessary to accommodate these factors. This study evaluated the feasibility, perceived satisfaction, and value of using webinars to educate clinical research professionals on reporting adverse events commonly experienced in pediatric oncology clinical trials. The setting incorporated synchronous web-based educational technology. Constructivist learning provides the theoretical framework for this study. Participants evaluated the professional development program at 2 time points: (a) at the conclusion and (b) 4 to 6 weeks afterward, using survey method. Synchronous webinars were both economical and effective in educating clinical research professionals across institutional sites. Participants reported exceptionally high levels of satisfaction with the accessibility, scope, quality, and interactivity of the professional development program. The vast majority of participants reported that the education would assist with reporting adverse events in pediatric oncology clinical trials and this perception persisted into clinical practice. Although the results of this study were intended to guide future educational efforts of the Children's Oncology Group, they may also apply to other cooperative groups.

Job loss, unemployment, work stress, job satisfaction, and the persistence of posttraumatic stress disorder one year after the September 11 attacks.

PubMed

Nandi, Arijit; Galea, Sandro; Tracy, Melissa; Ahern, Jennifer; Resnick, Heidi; Gershon, Robyn; Vlahov, David

2004-10-01

The influence of unemployment and adverse work conditions on the course of psychopathology after a mass disaster is unclear. We recruited a representative sample of adults living in the New York City metropolitan area six months after the September 11 attacks and completed follow-up interviews on 71% of the baseline sample six months later (N = 1939). At follow-up, posttraumatic stress disorder (PTSD) persisted in 42.7% of the 149 cases with PTSD at baseline. In multivariable models, unemployment at any time since baseline predicted PTSD persistence in the entire cohort (P = 0.02) and among persons employed at follow-up (P = 0.02). High levels of perceived work stress predicted PTSD persistence among persons employed at follow-up (P = 0.02). Persons unemployed in the aftermath of a disaster may be at risk for poor mental health in the long-term.

A Discordant Monozygotic Twin Design Shows Blunted Cortisol Reactivity Among Bullied Children

PubMed Central

Ouellet-Morin, Isabelle; Danese, Andrea; Bowes, Lucy; Shakoor, Sania; Ambler, Antony; Pariante, Carmine M.; Papadopoulos, Andrew S.; Caspi, Avshalom; Moffitt, Terrie E.; Arseneault, Louise

2013-01-01

Objective Childhood adverse experiences are known to engender persistent changes in stress-related systems and brain structures involved in mood, cognition, and behavior in animal models. Uncertainty remains about the causal effect of early stressful experiences on physiological response to stress in human beings, as the impact of these experiences has rarely been investigated while controlling for both genetic and shared environmental influences. Method We tested whether bullying victimization, a repeated adverse experience in childhood, influences cortisol responses to a psychosocial stress test (PST) using a discordant monozygotic (MZ) twin design. Thirty pairs (43.3% males) of 12-year-old MZ twins discordant for bullying victimization were identified in the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative 1994–1995 cohort of families with twins. Results Bullied and nonbullied MZ twins showed distinct patterns of cortisol secretion after the PST. Specifically, bullied twins exhibited a blunted cortisol response compared with their nonbullied MZ co-twins, who showed the expected increase. This difference in cortisol response to stress could not be attributed to children's genetic makeup, their familial environments, pre-existing and concomitant individual factors, or the perception of stress and emotional response to the PST. Conclusion Results from this natural experiment provide support for a causal effect of adverse childhood experiences on the neuroendocrine response to stress. PMID:21621141

The impact of severe mental disorders and psychotropic medications on sexual health and its implications for clinical management

PubMed Central

Montejo, Angel L.; Montejo, Laura; Baldwin, David S.

2018-01-01

Sexual dysfunction often accompanies severe psychiatric illness and can be due to both the mental disorder itself and the use of psychotropic treatments. Many sexual symptoms resolve as the mental state improves, but treatment‐related sexual adverse events tend to persist over time, and are unfortunately under‐recognized by clinicians and scarcely investigated in clinical trials. Treatment‐emergent sexual dysfunction adversely affects quality of life and may contribute to reduce treatment adherence. There are important differences between the various compounds in the incidence of adverse sexual effects, associated with differences in mechanisms of action. Antidepressants with a predominantly serotonergic activity, antipsychotics likely to induce hyperprolactinaemia, and mood stabilizers with hormonal effects are often linked to moderate or severe sexual dysfunction, including decreased libido, delayed orgasm, anorgasmia, and sexual arousal difficulties. Severe mental disorders can interfere with sexual function and satisfaction, while patients wish to preserve a previously satisfactory sexual activity. In many patients, a lack of intimate relationships and chronic deterioration in mental and physical health can be accompanied by either a poor sexual life or a more frequent risky sexual behaviour than in the general population. Here we describe the influence of psychosis and antipsychotic medications, of depression and antidepressant drugs, and of bipolar disorder and mood stabilizers on sexual health, and the optimal management of patients with severe psychiatric illness and sexual dysfunction. PMID:29352532

Parental depression and child outcomes – is marital conflict the missing link?

PubMed Central

Hanington, L; Heron, J; Stein, A; Ramchandani, P

2012-01-01

Background Both maternal and paternal depression during the perinatal period are associated with adverse effects on child outcomes. Attention has started to focus on the mechanisms mediating these relationships. Marital conflict may play a role in this context. Methods In a large cohort study, the Avon Longitudinal Study of Parents and Children (n= 14 541 pregnancies), we aimed to (i) investigate the relative influences of parental postnatal depression and marital conflict on child outcomes and to attempt to determine the pathway(s) of risk; (ii) investigate the impact of two types of antenatal stress (parental depression and marital conflict) on child outcomes; and (iii) determine the relative contributions of antenatal and postnatal risk. Parents completed the Edinburgh Postnatal Depression Scale and a marital conflict scale during the second trimester and at 8 months postnatally. Child outcomes were assessed at 42 months using the Rutter revised pre-school scales. Results Marital conflict partially mediated the relationship between postnatal depression in both mothers and fathers and child outcomes, and acted as an independent risk for adverse outcomes. Parental depression (maternal and paternal) and marital conflict in the antenatal period were both associated with adverse effects which persisted even when postnatal stresses were taken into account. Conclusions These findings, if replicated, suggest that screening and intervention programmes targeted at parental depression and marital problems should be considered antenatally, as well as postnatally. PMID:21771000

Patterns and predictors of ADHD persistence into adulthood: Results from the National Comorbidity Survey Replication

PubMed Central

Kessler, Ronald C.; Adler, Lenard A.; Barkley, Russell; Biederman, Joseph; Conners, C. Keith; Faraone, Stephen V.; Greenhill, Laurence L.; Jaeger, Savina; Secnik, Kristina; Spencer, Thomas; Üstün, T. Bedirhan; Zaslavsky, Alan M.

2010-01-01

BACKGROUND Despite growing interest in adult ADHD, little is known about predictors of persistence of childhood cases into adulthood. METHODS A retrospective assessment of childhood ADHD, childhood risk factors, and a screen for adult ADHD were included in a sample of 3197 18–44 year old respondents in the National Comorbidity Survey Replication (NCS-R). Blinded adult ADHD clinical reappraisal interviews were administered to a sub-sample of respondents. Multiple imputation (MI) was used to estimate adult persistence of childhood ADHD. Logistic regression was used to study retrospectively reported childhood predictors of persistence. Potential predictors included socio-demographics, childhood ADHD severity, childhood adversity, traumatic life experiences, and comorbid DSM-IV child-adolescent disorders (anxiety, mood, impulse-control, and substance disorders). RESULTS 36.3% of respondents with retrospectively assessed childhood ADHD were classified by blinded clinical interviews as meeting DSM-IV criteria for current ADHD. Childhood ADHD severity and childhood treatment significantly predicted persistence. Controlling for severity and excluding treatment, none of the other variables significantly predicted persistence even though they were significantly associated with childhood ADHD. CONCLUSIONS No modifiable risk factors were found for adult persistence of ADHD. Further research, ideally based on prospective general population samples, is needed to search for modifiable determinants of adult persistence of ADHD. PMID:15950019

Childhood and later life stressors and increased inflammatory gene expression at older ages.

PubMed

Levine, M E; Cole, S W; Weir, D R; Crimmins, E M

2015-04-01

Adverse experiences in early life have the ability to "get under the skin" and affect future health. This study examined the relative influence of adversities during childhood and adulthood in accounting for individual differences in pro-inflammatory gene expression in late life. Using a pilot-sample from the Health and Retirement Study (N = 114) aged from 51 to 95, OLS regression models were run to determine the association between a composite score from three proinflammatory gene expression levels (PTGS2, ILIB, and IL8) and 1) childhood trauma, 2) childhood SES, 3) childhood health, 4) adult traumas, and 5) low SES in adulthood. Our results showed that only childhood trauma was found to be associated with increased inflammatory transcription in late life. Furthermore, examination of interaction effects showed that childhood trauma exacerbated the influence of low SES in adulthood on elevated levels of inflammatory gene expression-signifying that having low SES in adulthood was most damaging for persons who had experienced traumatic events during their childhood. Overall our study suggests that traumas experienced during childhood may alter the stress response, leading to more sensitive reactivity throughout the lifespan. As a result, individuals who experienced greater adversity in early life may be at higher risk of late life health outcomes, particularly if adulthood adversity related to SES persists. Copyright © 2015. Published by Elsevier Ltd.

Are psychological interventions effective for the management of neck pain and whiplash-associated disorders? A systematic review by the Ontario Protocol for Traffic Injury Management (OPTIMa) Collaboration.

PubMed

Shearer, Heather M; Carroll, Linda J; Wong, Jessica J; Côté, Pierre; Varatharajan, Sharanya; Southerst, Danielle; Sutton, Deborah A; Randhawa, Kristi A; Yu, Hainan; Mior, Silvano A; van der Velde, Gabrielle M; Nordin, Margareta C; Stupar, Maja; Taylor-Vaisey, Anne L

2016-12-01

In 2008, the lack of published evidence prevented the Bone and Joint Decade 2000-2010 Task Force on Neck Pain and Its Associated Disorders (Neck Pain Task Force [NPTF]) from commenting on the effectiveness of psychological interventions for the management of neck pain. This study aimed to update findings of the NPTF and evaluate the effectiveness of psychological interventions for the management of neck pain and associated disorders (NAD) or whiplash-associated disorders (WAD). This study used systematic review and best-evidence synthesis. Randomized controlled trials, cohort studies, and case-control studies comparing psychological interventions to other non-invasive interventions or no intervention were the samples used in this study. The outcome measures are (1) self-rated recovery; (2) functional recovery; (3) clinical outcomes; (4) administrative outcomes; and (5) adverse effects. We searched six databases from 1990 to 2015. Randomized controlled trials, cohort studies, and case-control studies meeting our selection criteria were eligible for critical appraisal. Random pairs of independent reviewers used the Scottish Intercollegiate Guidelines Network criteria to critically appraise eligible studies. Studies with a low risk of bias were synthesized following best evidence synthesis principles. This study was funded by the Ontario Ministry of Finance. We screened 1,919 articles, 19 were eligible for critical appraisal and 10 were judged to have low risk of bias. We found no clear evidence supporting relaxation training or cognitive behavioral therapy (CBT) for persistent grades I-III NAD for reducing pain intensity or disability. Similarly, we did not find evidence to support the effectiveness of biofeedback or relaxation training for persistent grade II WAD, and there is conflicting evidence for the use of CBT in this population. However, adding a progressive goal attainment program to functional restoration physiotherapy may benefit patients with persistent grades I-III WAD. Furthermore, Jyoti meditation may help reduce neck pain intensity and bothersomeness in patients with persistent NAD. We did not find evidence for or against the use of psychological interventions in patients with recent onset NAD or WAD. We found evidence that a progressive goal attainment program may be helpful for the management of persistent WAD and that Jyoti meditation may benefit patients with persistent NAD. The limited evidence of effectiveness for psychological interventions may be due to several factors, such as interventions that are ineffective, poorly conceptualized, or poorly implemented. Further methodologically rigorous research is needed. Copyright © 2015 Elsevier Inc. All rights reserved.

Bone morphogenetic protein 7 and autologous bone graft in revision surgery for non-union after lumbar interbody fusion.

PubMed

Werle, Stephan; AbuNahleh, Kais; Boehm, Heinrich

2016-08-01

Potential adverse and unknown long-term effects as well as additional costs limit the use of BMPs (Bone morphogenetic proteins) in primary fusion procedures. However, the proven osteoinductive properties render BMPs attractive for the attempt to reach fusion of symptomatic non-unions. The aim of this study is to evaluate the fusion rate and potential disadvantages of eptotermin alfa (rhBMP-7) used with autologous bone graft in revision procedures for lumbar pseudoarthrosis. At our institution, rhBMP-7 has been used to improve fusion rates in revision surgery for symptomatic pseudoarthrosis during the past 10 years. Eighty-four fusion procedures using rhBMP-7 between 08/2003 and 07/2011 were revisions due to symptomatic lumbar pseudoarthrosis. The surgical approach was posterior in three and combined anterior-posterior in 71 patients. Of those, 74 patients had either reached fusion or had follow-up of at least 39.5 months (range 21-80 months) in the case of pseudoarthrosis. These 74 patients have been included in a retrospective follow-up study. In 60 patients (81.1 %) the rhBMP-7 procedure was successful. In 14 patients, pseudoarthrosis persisted or fusion was questionable. Of those patients 12 accounted for persisting L5-S1 non-union. Persisting non-unions were found in 26.7 % of the study after four or more segment instrumentations compared to the 16.9 % after mono-, bi-, or three-segment instrumentation, and in four of 14 patients with spondylodesis of three or more levels above a pseudoarthrotic lumbosacral junction. Adverse effects related to the use of eptotermin alfa were rare in this group with symptomatic ectopic bone formation in one patient. Using rhBMP-7 with autologous bone graft in revisions for lumbar pseudoarthrosis via an anterior approach is safe and can lead to fusion even under unfavorable biomechanical conditions. However, successful outcome depends on the individual constellation. Treatment of non-unions of the lumbosacral junction remains especially difficult in cases with solid fusions above those pseudoarthrotic levels. 4; retrospective follow-up study.

Multiple Endocrine Disrupting Effects in Rats Perinatally Exposed to Butylparaben.

PubMed

Boberg, J; Axelstad, M; Svingen, T; Mandrup, K; Christiansen, S; Vinggaard, A M; Hass, U

2016-07-01

Parabens comprise a group of preservatives commonly added to cosmetics, lotions, and other consumer products. Butylparaben has estrogenic and antiandrogenic properties and is known to reduce sperm counts in rats following perinatal exposure. Whether butylparaben exposure can affect other endocrine sensitive endpoints, however, remains largely unknown. In this study, time-mated Wistar rats (n = 18) were orally exposed to 0, 10, 100, or 500 mg/kg bw/d of butylparaben from gestation day 7 to pup day 22. Several endocrine-sensitive endpoints were adversely affected. In the 2 highest dose groups, the anogenital distance of newborn male and female offspring was significantly reduced, and in prepubertal females, ovary weights were reduced and mammary gland outgrowth was increased. In male offspring, sperm count was significantly reduced at all doses from 10 mg/kg bw/d. Testicular CYP19a1 (aromatase) expression was reduced in prepubertal, but not adult animals exposed to butylparaben. In adult testes, Nr5a1 expression was reduced at all doses, indicating persistent disruption of steroidogenesis. Prostate histology was altered at prepuberty and adult prostate weights were reduced in the high dose group. Thus, butylparaben exerted endocrine disrupting effects on both male and female offspring. The observed adverse developmental effect on sperm count at the lowest dose is highly relevant to risk assessment, as this is the lowest observed adverse effect level in a study on perinatal exposure to butylparaben. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The Adverse Effects of Environmental Noise Exposure on Oxidative Stress and Cardiovascular Risk

PubMed Central

Sørensen, Mette; Schmidt, Frank; Schmidt, Erwin; Steven, Sebastian; Kröller-Schön, Swenja; Daiber, Andreas

2018-01-01

Abstract Epidemiological studies have provided evidence that traffic noise exposure is linked to cardiovascular diseases such as arterial hypertension, myocardial infarction, and stroke. Noise is a nonspecific stressor that activates the autonomous nervous system and endocrine signaling. According to the noise reaction model introduced by Babisch and colleagues, chronic low levels of noise can cause so-called nonauditory effects, such as disturbances of activity, sleep, and communication, which can trigger a number of emotional responses, including annoyance and subsequent stress. Chronic stress in turn is associated with cardiovascular risk factors, comprising increased blood pressure and dyslipidemia, increased blood viscosity and blood glucose, and activation of blood clotting factors, in animal models and humans. Persistent chronic noise exposure increases the risk of cardiometabolic diseases, including arterial hypertension, coronary artery disease, diabetes mellitus type 2, and stroke. Recently, we demonstrated that aircraft noise exposure during nighttime can induce endothelial dysfunction in healthy subjects and is even more pronounced in coronary artery disease patients. Importantly, impaired endothelial function was ameliorated by acute oral treatment with the antioxidant vitamin C, suggesting that excessive production of reactive oxygen species contributes to this phenomenon. More recently, we introduced a novel animal model of aircraft noise exposure characterizing the underlying molecular mechanisms leading to noise-dependent adverse oxidative stress-related effects on the vasculature. With the present review, we want to provide an overview of epidemiological, translational clinical, and preclinical noise research addressing the nonauditory, adverse effects of noise exposure with focus on oxidative stress. Antioxid. Redox Signal. 28, 873–908. PMID:29350061

Early life persistent vitamin D deficiency exacerbates arrhythmias and autonomic imbalance following acrolein exposure in mice.

EPA Science Inventory

Epidemiological and animal data have conclusively linked adverse cardiovascular outcomes to air pollution exposure. As such, cardiovascular function is maintained by adequate levels of certain essential micronutrients like vitamin D. Unfortunately, vitamin D deficiency (VDD) has ...

Management of Chronic Hypotony following Bilateral Uveitis in a Patient Treated with Pembrolizumab for Cutaneous Metastatic Melanoma.

PubMed

Reid, Gerard; Lorigan, Paul; Heimann, Heinrich; Hovan, Marta

2018-04-19

To describe the presentation and management of severe ocular adverse events following treatment with pembrolizumab for cutaneous metastatic melanoma. Interventional case report. A 73-year-old Caucasian man receiving pembrolizumab treatment for metastatic melanoma presented with panuveitis and subsequent profound hypotony, choroidal effusions, and optic disk swelling bilaterally. Oral prednisolone controlled intraocular inflammation. However, bilateral hypotony persisted which was managed over a 12-month period with ocular viscoelastic device injections into the anterior chamber of both eyes. There was also phacoemulsification with pars plana vitrectomy (PPV) and silicone oil (SO) tamponade performed on the left eye only. Intraocular pressure (IOP) stabilized (>6 mmHg) with best-corrected visual acuity of 6/60. We report a severe adverse event from pembrolizumab therapy resulting in uveitis and persistent hypotony. Repeat injections of high viscosity OVD achieved an increase in IOP up to 12 months. This technique may be a useful adjuvant or alternative to PPV and SO.

Mortality risk from comorbidities independent of triple-negative breast cancer status: NCI-SEER-based cohort analysis.

PubMed

Swede, Helen; Sarwar, Amna; Magge, Anil; Braithwaite, Dejana; Cook, Linda S; Gregorio, David I; Jones, Beth A; R Hoag, Jessica; Gonsalves, Lou; L Salner, Andrew; Zarfos, Kristen; Andemariam, Biree; Stevens, Richard G; G Dugan, Alicia; Pensa, Mellisa; A Brockmeyer, Jessica

2016-05-01

A comparatively high prevalence of comorbidities among African-American/Blacks (AA/B) has been implicated in disparate survival in breast cancer. There is a scarcity of data, however, if this effect persists when accounting for the adverse triple-negative breast cancer (TNBC) subtype which occurs at threefold the rate in AA/B compared to white breast cancer patients. We reviewed charts of 214 white and 202 AA/B breast cancer patients in the NCI-SEER Connecticut Tumor Registry who were diagnosed in 2000-2007. We employed the Charlson Co-Morbidity Index (CCI), a weighted 17-item tool to predict risk of death in cancer populations. Cox survival analyses estimated hazard ratios (HRs) for all-cause mortality in relation to TNBC and CCI adjusting for clinicopathological factors. Among patients with SEER local stage, TNBC increased the risk of death (HR 2.18, 95 % CI 1.14-4.16), which was attenuated when the CCI score was added to the model (Adj. HR 1.50, 95 % CI 0.74-3.01). Conversely, the adverse impact of the CCI score persisted when controlling for TNBC (Adj. HR 1.49, 95 % CI 1.29-1.71; per one point increase). Similar patterns were observed in SEER regional stage, but estimated HRs were lower. AA/B patients with a CCI score of ≥3 had a significantly higher risk of death compared to AA/B patients without comorbidities (Adj. HR 5.65, 95 % CI 2.90-11.02). A lower and nonsignificant effect was observed for whites with a CCI of ≥3 (Adj. HR 1.90, 95 % CI 0.68-5.29). comorbidities at diagnosis increase risk of death independent of TNBC, and AA/B patients may be disproportionately at risk.

Exposure from the Chernobyl accident had adverse effects on erythrocytes, leukocytes, and, platelets in children in the Narodichesky region, Ukraine: A 6-year follow-up study

PubMed Central

Stepanova, Eugenia; Karmaus, Wilfried; Naboka, Marina; Vdovenko, Vitaliy; Mousseau, Tim; Shestopalov, Viacheslav M; Vena, John; Svendsen, Erik; Underhill, Dwight; Pastides, Harris

2008-01-01

Background After the Chernobyl nuclear accident on April 26, 1986, all children in the contaminated territory of the Narodichesky region, Zhitomir Oblast, Ukraine, were obliged to participate in a yearly medical examination. We present the results from these examinations for the years 1993 to 1998. Since the hematopoietic system is an important target, we investigated the association between residential soil density of 137Caesium (137Cs) and hemoglobin concentration, and erythrocyte, platelet, and leukocyte counts in 1,251 children, using 4,989 repeated measurements taken from 1993 to 1998. Methods Soil contamination measurements from 38 settlements were used as exposures. Blood counts were conducted using the same auto-analyzer in all investigations for all years. We used linear mixed models to compensate for the repeated measurements of each child over the six year period. We estimated the adjusted means for all markers, controlling for potential confounders. Results Data show a statistically significant reduction in red and white blood cell counts, platelet counts and hemoglobin with increasing residential 137Cs soil contamination. Over the six-year observation period, hematologic markers did improve. In children with the higher exposure who were born before the accident, this improvement was more pronounced for platelet counts, and less for red blood cells and hemoglobin. There was no exposure×time interaction for white blood cell counts and not in 702 children who were born after the accident. The initial exposure gradient persisted in this sub-sample of children. Conclusion The study is the first longitudinal analysis from a large cohort of children after the Chernobyl accident. The findings suggest persistent adverse hematological effects associated with residential 137Cs exposure. PMID:18513393

Persistent Threats by Persistent Pollutants: Chemical Nature, Concerns and Future Policy Regarding PCBs-What Are We Heading For?

PubMed

Hens, Bart; Hens, Luc

2017-12-21

Polychlorinated biphenyl (PCB)-contaminated sites around the world affect human health for many years, showing long latency periods of health effects. The impact of the different PCB congeners on human health should not be underestimated, as they are ubiquitous, stable molecules and reactive in biological tissues, leading to neurological, endocrine, genetic, and systemic adverse effects in the human body. Moreover, bioaccumulation of these compounds in fatty tissues of animals (e.g., fish and mammals) and in soils/sediments, results in chronic exposure to these substances. Efficient destruction methods are important to decontaminate polluted sites worldwide. This paper provides an in-depth overview of (i) the history and accidents with PCBs in the 20th century, (ii) the mechanisms that are responsible for the hazardous effects of PCBs, and (iii) the current policy regarding PCB control and decontamination. Contemporary impacts on human health of historical incidents are discussed next to an up to date overview of the health effects caused by PCBs and their mechanisms. Methods to decontaminate sites are reviewed. Steps which lead to a policy of banning the production and distribution of PCBs are overviewed in a context of preventing future accidents and harm to the environment and human health.

Persistent Threats by Persistent Pollutants: Chemical Nature, Concerns and Future Policy Regarding PCBs—What Are We Heading For?

PubMed Central

Hens, Luc

2017-01-01

Polychlorinated biphenyl (PCB)-contaminated sites around the world affect human health for many years, showing long latency periods of health effects. The impact of the different PCB congeners on human health should not be underestimated, as they are ubiquitous, stable molecules and reactive in biological tissues, leading to neurological, endocrine, genetic, and systemic adverse effects in the human body. Moreover, bioaccumulation of these compounds in fatty tissues of animals (e.g., fish and mammals) and in soils/sediments, results in chronic exposure to these substances. Efficient destruction methods are important to decontaminate polluted sites worldwide. This paper provides an in-depth overview of (i) the history and accidents with PCBs in the 20th century, (ii) the mechanisms that are responsible for the hazardous effects of PCBs, and (iii) the current policy regarding PCB control and decontamination. Contemporary impacts on human health of historical incidents are discussed next to an up to date overview of the health effects caused by PCBs and their mechanisms. Methods to decontaminate sites are reviewed. Steps which lead to a policy of banning the production and distribution of PCBs are overviewed in a context of preventing future accidents and harm to the environment and human health. PMID:29267240

Adversity, emotion recognition, and empathic concern in high-risk youth

PubMed Central

Quas, Jodi A.; 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. PMID:28738074

HISTORICAL SERIES OF PATIENTS WITH VISCERAL LEISHMANIASIS TREATED WITH MEGLUMINE ANTIMONIATE IN A HOSPITAL FOR TROPICAL DISEASES, MACEIÓ-AL, BRAZIL

PubMed Central

Silveira, Lindon Johoson Diniz; Rocha, Thiago José Matos; Ribeiro, Sandra Aparecida; Pedrosa, Célia Maria Silva

2015-01-01

Introduction: Visceral leishmaniasis is an endemic protozoan found in Brazil. It is characterized by fever, pallor, hepatosplenomegaly, lymphadenopathy, and progressive weakness in the patient. It may lead to death if untreated. The drug of choice for treatment is meglumine antimoniate (Glucantime®). The aim of this study was to evaluate patients with visceral leishmaniasis according to criteria used for diagnosis, possible reactions to Glucantime® and blood pressure measured before and after treatment. Methods: 89 patients admitted to the Teaching Hospital Dr. Hélvio Auto (HEHA) in Maceió-AL, in the period from May 2006 to December 2009 were evaluated. Data were collected on age, sex, origin, method of diagnosis, adverse effects of drugs, duration of hospitalization, duration of treatment and dosage up to the onset of adverse effects. Results: There was a predominance of child male patients, aged between one and five years old, from the interior of the State of Alagoas. Parasitological diagnosis was made by bone marrow aspirate; three (3.37%) patients died, 12 (13.48%) had adverse reactions and treatment was changed to amphotericin B, and 74 (83.14%) were cured. Changes that led to replacing Glucantime® were persistent fever, jaundice, rash, bleeding and cyanosis. Conclusion: During the study, 89 patients hospitalized for VL were analyzed: 74 were healed, 12 were replaced by amphotericin B treatment and three died. Most of them were under five years old, male and came from the interior. The dosage and duration of treatment with Glucantime® were consistent with that advocated by the Ministry of Health. Persistence of fever, jaundice, rash, cyanosis and bleeding were the reactions that led the physician to modify treatment. No change was observed in blood pressure before and after treatment. This study demonstrated the work of a hospital, a reference in the treatment of leishmaniasis, which has many patients demanding its services in this area. It demonstrates that this disease is still important today, and needs to be addressed properly to prevent injury and death due to the disease. PMID:25651324

Historical series of patients with visceral leishmaniasis treated with meglumine antimoniate in a hospital for tropical diseases, Maceió-AL, Brazil.

PubMed

Silveira, Lindon Johoson Diniz; Rocha, Thiago José Matos; Ribeiro, Sandra Aparecida; Pedrosa, Célia Maria Silva

2015-01-01

Visceral leishmaniasis is an endemic protozoan found in Brazil. It is characterized by fever, pallor, hepatosplenomegaly, lymphadenopathy, and progressive weakness in the patient. It may lead to death if untreated. The drug of choice for treatment is meglumine antimoniate (Glucantime). The aim of this study was to evaluate patients with visceral leishmaniasis according to criteria used for diagnosis, possible reactions to Glucantime and blood pressure measured before and after treatment. 89 patients admitted to the Teaching Hospital Dr. Hélvio Auto (HEHA) in Maceió-AL, in the period from May 2006 to December 2009 were evaluated. Data were collected on age, sex, origin, method of diagnosis, adverse effects of drugs, duration of hospitalization, duration of treatment and dosage up to the onset of adverse effects. There was a predominance of child male patients, aged between one and five years old, from the interior of the State of Alagoas. Parasitological diagnosis was made by bone marrow aspirate; three (3.37%) patients died, 12 (13.48%) had adverse reactions and treatment was changed to amphotericin B, and 74 (83.14%) were cured. Changes that led to replacing Glucantime were persistent fever, jaundice, rash, bleeding and cyanosis. During the study, 89 patients hospitalized for VL were analyzed: 74 were healed, 12 were replaced by amphotericin B treatment and three died. Most of them were under five years old, male and came from the interior. The dosage and duration of treatment with Glucantime were consistent with that advocated by the Ministry of Health. Persistence of fever, jaundice, rash, cyanosis and bleeding were the reactions that led the physician to modify treatment. No change was observed in blood pressure before and after treatment. This study demonstrated the work of a hospital, a reference in the treatment of leishmaniasis, which has many patients demanding its services in this area. It demonstrates that this disease is still important today, and needs to be addressed properly to prevent injury and death due to the disease.

Cycloserine Induced Late Onset Psychosis and Ethambutol Induced Peripheral Neuropathy Associated with MDR-TB Treatment in an Indian Patient- A Rare Case Report

PubMed Central

Holla, Sadhana; Bhandarypanambur, Rajeshkrishna; Kamalkishore, Meenakumari; Janardhanan, Manju

2015-01-01

Adverse reactions and toxicity inevitably accompany all treatment courses for drug-resistant TB. Our case underscores the importance of awareness regarding neuropsychiatric adverse reactions due to MDR-TB therapy and reversible nature of it. Cycloserine induced psychosis is most life threatening complication and sometimes could be fatal. A 42-year-old male on MDR-TB therapy got admitted for his persistent psychotic complaints like hallucinations, delusions and suicidal ideations, despite being treated with quetiapine/olanzapine. Eventually patient was rehabilitated, cycloserine was stopped and psychotic events regressed slowly. Other culprit drugs like ethambutol and levofloxacin causing psychosis was ruled out because there was no relapse of psychotic events despite being continued with these drugs. He also complained of tingling, numbness, swaying, pain and weakness. On examination, he had distal motor weakness in lower limbs, tandem gait positive, altered position sense, and tenderness over toes and positive Romberg’s sign with ataxia. He was diagnosed to have drug induced sensorimotor peripheral neuropathy. All these symptoms persisted after stopping cycloserine and patient continued to have neuropathy with ethambutol and ethionamide. Considering the nature of neuropathy which was mild, mixed sensorimotor and resolved completely after 2-3 weeks of stopping, it was more in favour of ethambutol. However, we could not rule out the possibility of ethionamide or (ethionamide + ethambutol) causing neuropathy or both could have accelerated the neurotoxic effects of cycloserine which remained elusive. PMID:25859468

Cycloserine Induced Late Onset Psychosis and Ethambutol Induced Peripheral Neuropathy Associated with MDR-TB Treatment in an Indian Patient- A Rare Case Report.

PubMed

Holla, Sadhana; Amberkar, Mohan Babu; Bhandarypanambur, Rajeshkrishna; Kamalkishore, Meenakumari; Janardhanan, Manju

2015-02-01

Adverse reactions and toxicity inevitably accompany all treatment courses for drug-resistant TB. Our case underscores the importance of awareness regarding neuropsychiatric adverse reactions due to MDR-TB therapy and reversible nature of it. Cycloserine induced psychosis is most life threatening complication and sometimes could be fatal. A 42-year-old male on MDR-TB therapy got admitted for his persistent psychotic complaints like hallucinations, delusions and suicidal ideations, despite being treated with quetiapine/olanzapine. Eventually patient was rehabilitated, cycloserine was stopped and psychotic events regressed slowly. Other culprit drugs like ethambutol and levofloxacin causing psychosis was ruled out because there was no relapse of psychotic events despite being continued with these drugs. He also complained of tingling, numbness, swaying, pain and weakness. On examination, he had distal motor weakness in lower limbs, tandem gait positive, altered position sense, and tenderness over toes and positive Romberg's sign with ataxia. He was diagnosed to have drug induced sensorimotor peripheral neuropathy. All these symptoms persisted after stopping cycloserine and patient continued to have neuropathy with ethambutol and ethionamide. Considering the nature of neuropathy which was mild, mixed sensorimotor and resolved completely after 2-3 weeks of stopping, it was more in favour of ethambutol. However, we could not rule out the possibility of ethionamide or (ethionamide + ethambutol) causing neuropathy or both could have accelerated the neurotoxic effects of cycloserine which remained elusive.

Integrating nano- and microparticles in practical decontamination processes for water and sediments in a green technology approach

NASA Astrophysics Data System (ADS)

Eggen, Trine; Soran, Maria-Loredana

2015-12-01

Historically, pollution has been associated with heavy metals and hydrophobic persistent organic pollutants (POPs). This has changed. Today, legacy or emerging contaminants cover a vast number of compounds including industrial man-made chemicals, pesticides and pharmaceuticals in addition to inorganic elements and nanomaterials. These compounds are transferred to the environment via wastewater effluents and leachates and via sludge/biosolids such as fertilizers or soil amendments. Compared to previous POPs, today's legacy and emerging contaminants cover a broader spectrum of structures and properties, including a high number of persistent medium to highly water. For most emerging contaminants, neither the environmental transfer and residue nor the short- and long ecotoxicological and human adverse effects are known. Thus, it's time for precautionary acting and to replace conventional treatment processes originally designed for removal of organic matter and nutrients with processes suitable for removal of hazardous chemicals with a wide range of properties before entering water and terrestrial recipients.

Athlete's foot and fungally infected toenails

PubMed Central

Crawford, Fay; Hart, Rachel; Bell-Syer, Sally E M; Torgerson, David J; Young, Philip; Russell, Ian

2001-01-01

Definition Athlete's foot is a cutaneous fungal infection that causes the skin to itch, flake, and fissure. Nail involvement is characterised by ungual thickening and discoloration. Incidence/prevalence In the United Kingdom, athlete's foot is present in about 15% of the general population,1 and 1.2 million people have fungally infected toenails.2 Aetiology/risk factors Swimming pool users and industrial workers may have increased risk of fungal foot infection. However, one survey found fungal foot infection in only 8.5% of swimmers, with the highest incidence (20%) in men aged 16 years and over.1 Prognosis Fungal infections of the foot are not life threatening in people with normal immunity, but in some people they cause persistent symptoms. Other people seem to be oblivious of persistent infection. The infection can spread to other parts of the body and to other people. Aims To control symptoms and prevent recurrence, with minimal adverse effects. Outcomes Rates of fungal eradication, shown by negative microscopy and culture, and resolution of clinical signs and symptoms at follow up. PMID:11157535

Postnatal investigation of prenatally induced effects on the vertebral column of rats reduces the uncertainty of classification of anomalies.

PubMed

Chahoud, I; Talsness, C E; Walter, A; Grote, K

2015-12-01

Classification of substances as teratogenic is based on the observation of external, visceral and skeletal anomalies. Characterization of anomalies as variation or malformation is contingent upon their postnatal persistence and adversity to health. Lack of information thereof may result in inconsistent or incorrect classification. The aim of this work is the examination of vertebral skeletal anomalies regarding their postnatal fate on PNDs 7 and 21. The anomalies unossified, asymmetric ossification, bipartite ossification, hemicentric, as well as misshapen, did not persist up to PND21 and should be classified as a variation. The finding, cervical vertebra centrum dumbbell-shaped, should be categorized as a malformation due to its continued presence on PND 21. Lumbar centrum supernumerary sinister/dexter/sinister+dexter should also be classified as a malformation. This study demonstrates that postnatal examination is useful and substantially improves the ability to perform a scientifically sound classification of an anomaly compared to investigations terminated on GD 21. Copyright © 2015 Elsevier Inc. All rights reserved.

Farming and the fate of wild nature.

PubMed

Green, Rhys E; Cornell, Stephen J; Scharlemann, Jörn P W; Balmford, Andrew

2005-01-28

World food demand is expected to more than double by 2050. Decisions about how to meet this challenge will have profound effects on wild species and habitats. We show that farming is already the greatest extinction threat to birds (the best known taxon), and its adverse impacts look set to increase, especially in developing countries. Two competing solutions have been proposed: wildlife-friendly farming (which boosts densities of wild populations on farmland but may decrease agricultural yields) and land sparing (which minimizes demand for farmland by increasing yield). We present a model that identifies how to resolve the trade-off between these approaches. This shows that the best type of farming for species persistence depends on the demand for agricultural products and on how the population densities of different species on farmland change with agricultural yield. Empirical data on such density-yield functions are sparse, but evidence from a range of taxa in developing countries suggests that high-yield farming may allow more species to persist.

Association between childhood adversities and long-term suicidality among South Africans from the results of the South African Stress and Health study: a cross-sectional study.

PubMed

Bruwer, Belinda; Govender, Ravi; Bishop, Melanie; Williams, David R; Stein, Dan J; Seedat, Soraya

2014-06-11

Suicide and suicidal behaviours are significant public health problems and a leading cause of death worldwide and in South Africa. We examined the association between childhood adversities and suicidal behaviour over the life course. A national probability sample of 4351 South African adult participants (aged 18 years and older) in the South African Stress and Health (SASH) study was interviewed as part of the World Mental Health Surveys initiative. Respondents provided sociodemographic and diagnostic information, as well as an account of suicide-related thoughts and behaviours. Suicidality or suicidal behaviour were defined as were defined as suicide attempts and suicidal ideation in the total sample, and suicide plans and attempts among ideators. Childhood adversities included physical abuse, sexual abuse, parental death, parental divorce, other parental loss, family violence, physical illness and financial adversity. The association between suicidality and childhood adversities was examined using discrete-time survival models. More than a third of the respondents with suicidal behaviour experienced at least one childhood adversity, with physical abuse, parental death and parental divorce being the most prevalent adversities. Physical abuse, sexual abuse and parental divorce were identified as significant risk markers for lifetime suicide attempts, while physical abuse and parental divorce were significantly correlated with suicidal ideation. Two or more childhood adversities were associated with a twofold higher risk of lifetime suicide attempts. Sexual abuse (OR 9.3), parental divorce (OR 3.1) and childhood physical abuse (OR 2.2) had the strongest associations with lifetime suicide attempts. The effect of childhood adversities on suicidal tendencies varied over the life course. For example, sexual abuse was significantly associated with suicide attempts during childhood and teen years, but not during young and later adulthood. Childhood adversities, especially sexual abuse, physical abuse and parental divorce, are important risk factors for the onset and persistence of suicidal behaviour, with this risk being greatest in childhood and adolescence. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The Modern Design of Experiments for Configuration Aerodynamics: A Case Study

NASA Technical Reports Server (NTRS)

DeLoach, Richard

2006-01-01

The effects of slowly varying and persisting covariate effects on the accuracy and precision of experimental result is reviewed, as is the rationale for run-order randomization as a quality assurance tactic employed in the Modern Design of Experiments (MDOE) to defend against such effects. Considerable analytical complexity is introduced by restrictions on randomization in configuration aerodynamics tests because they involve hard-to-change configuration variables that cannot be randomized conveniently. Tradeoffs are examined between quality and productivity associated with varying degrees of rigor in accounting for such randomization restrictions. Certain characteristics of a configuration aerodynamics test are considered that may justify a relaxed accounting for randomization restrictions to achieve a significant reduction in analytical complexity with a comparably negligible adverse impact on the validity of the experimental results.

[Effects of air pollution on human health and their importance in Mexico City].

PubMed

Vallejo, Maite; Jáuregui-Renaud, Kathrine; Hermosillo, Antonio G; Márquez, Manlio F; Cárdenas, Manuel

2003-01-01

The impact of air pollution on human health is a complicated problem. In this review, we describe the main health effects of exposure to ozone, carbon monoxide, sulfur dioxide, nitrogen dioxide, lead and particulate matter. Geographical characteristics of the metropolitan area of Mexico City that favor pollutant persistence with adverse effects on the population are described; the use of the Indice Metropolitano de la Calidad del Aire (IMECA), current norms, and present programs to diminish this problem are discussed. Evidence shows that through these actions, air quality has improved. However, some pollutants such as ozone and particulate matter, still exceed the standard. To further improve air quality in the city, existing programs should continue and multidisciplinary research, both basic and applied, is required.

Developmental Deltamethrin Exposure Causes Persistent Changes in Dopaminergic Gene Expression, Neurochemistry, and Locomotor Activity in Zebrafish.

PubMed

Kung, Tiffany S; Richardson, Jason R; Cooper, Keith R; White, Lori A

2015-08-01

Pyrethroids are commonly used insecticides that are considered to pose little risk to human health. However, there is an increasing concern that children are more susceptible to the adverse effects of pesticides. We used the zebrafish model to test the hypothesis that developmental exposure to low doses of the pyrethroid deltamethrin results in persistent alterations in dopaminergic gene expression, neurochemistry, and locomotor activity. Zebrafish embryos were treated with deltamethrin (0.25-0.50 μg/l), at concentrations below the LOAEL, during the embryonic period [3-72 h postfertilization (hpf)], after which transferred to fresh water until the larval stage (2-weeks postfertilization). Deltamethrin exposure resulted in decreased transcript levels of the D1 dopamine (DA) receptor (drd1) and increased levels of tyrosine hydroxylase at 72 hpf. The reduction in drd1 transcripts persisted to the larval stage and was associated with decreased D2 dopamine receptor transcripts. Larval fish, exposed developmentally to deltamethrin, had increased levels of homovanillic acid, a DA metabolite. Since the DA system is involved in locomotor activity, we measured the swim activity of larval fish following a transition to darkness. Developmental exposure to deltamethrin significantly increased larval swim activity which was attenuated by concomitant knockdown of the DA transporter. Acute exposure to methylphenidate, a DA transporter inhibitor, increased swim activity in control larva, while reducing swim activity in larva developmentally exposed to deltamethrin. Developmental exposure to deltamethrin causes locomotor deficits in larval zebrafish, which is likely mediated by dopaminergic dysfunction. This highlights the need to understand the persistent effects of low-dose neurotoxicant exposure during development. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Developmental Deltamethrin Exposure Causes Persistent Changes in Dopaminergic Gene Expression, Neurochemistry, and Locomotor Activity in Zebrafish

PubMed Central

Kung, Tiffany S.; Richardson, Jason R.; Cooper, Keith R.; White, Lori A.

2015-01-01

Pyrethroids are commonly used insecticides that are considered to pose little risk to human health. However, there is an increasing concern that children are more susceptible to the adverse effects of pesticides. We used the zebrafish model to test the hypothesis that developmental exposure to low doses of the pyrethroid deltamethrin results in persistent alterations in dopaminergic gene expression, neurochemistry, and locomotor activity. Zebrafish embryos were treated with deltamethrin (0.25–0.50 μg/l), at concentrations below the LOAEL, during the embryonic period [3–72 h postfertilization (hpf)], after which transferred to fresh water until the larval stage (2-weeks postfertilization). Deltamethrin exposure resulted in decreased transcript levels of the D1 dopamine (DA) receptor (drd1) and increased levels of tyrosine hydroxylase at 72 hpf. The reduction in drd1 transcripts persisted to the larval stage and was associated with decreased D2 dopamine receptor transcripts. Larval fish, exposed developmentally to deltamethrin, had increased levels of homovanillic acid, a DA metabolite. Since the DA system is involved in locomotor activity, we measured the swim activity of larval fish following a transition to darkness. Developmental exposure to deltamethrin significantly increased larval swim activity which was attenuated by concomitant knockdown of the DA transporter. Acute exposure to methylphenidate, a DA transporter inhibitor, increased swim activity in control larva, while reducing swim activity in larva developmentally exposed to deltamethrin. Developmental exposure to deltamethrin causes locomotor deficits in larval zebrafish, which is likely mediated by dopaminergic dysfunction. This highlights the need to understand the persistent effects of low-dose neurotoxicant exposure during development. PMID:25912032

The natural history of gastro-oesophageal reflux symptoms in the community and its effects on survival: a longitudinal 10-year follow-up study.

PubMed

Ford, A C; Forman, D; Bailey, A G; Axon, A T R; Moayyedi, P

2013-02-01

Gastro-oesophageal reflux symptoms (GERS) are common in the community. However, few studies have examined their long-term natural history, or impact on survival. To examine these issues in individuals recruited into a community-based screening programme for Helicobacter pylori in 1994. Data on mortality and cause of death at 10 years were obtained from the Office for National Statistics. Baseline demographic data, lifestyle factors, gastrointestinal symptoms and quality of life were recorded at study entry. The effect of all these factors on persistent and new-onset GERS, and 10-year mortality, were examined using univariate and multivariate analysis, with results expressed as odds ratios (ORs) or hazard ratios (HR) with 99% confidence intervals (CI). Of 3967 individuals providing complete GERS data at baseline and 10 years, 549 (13.8%) had GERS at baseline. Of these, 183 (33.3%) had persistent symptoms. Among 3418 individuals asymptomatic at baseline, approximately 0.8% per year developed new-onset GERS. No predictors of persistent GERS were identified. New-onset symptoms were associated with lower quality of life or presence of irritable bowel syndrome (IBS) at baseline, and higher body mass index (BMI) at 10 years. There were 8331 (99.1%) of 8407 subjects providing complete GERS data at baseline, 1289 (15.5%) of whom were symptomatic. Presence of GERS at baseline did not affect survival (HR: 0.84; 99% CI: 0.44-1.59). Gastro-oesophageal reflux symptoms persisted in one-third of individuals, whilst new-onset gastro-oesophageal reflux symptoms were associated with poor quality of life, irritable bowel syndrome and higher body mass index. Gastro-oesophageal reflux symptoms did not impact adversely on survival. © 2012 Blackwell Publishing Ltd.

A trial of radiofrequency ablation for anal intraepithelial neoplasia.

PubMed

Goldstone, Robert N; Hasan, Shirin R; Drury, Steven; Darragh, Teresa M; van Zante, Annemieke; Goldstone, Stephen E

2017-03-01

Radiofrequency ablation (RFA) effectively treats esophageal high-grade dysplasia, but its efficacy in treating anal canal high-grade squamous intraepithelial lesions (HSILs) is unsubstantiated. This prospective study assessed the safety and efficacy of applying hemi-circumferential RFA to anal canal HSIL. Twenty-one HIV-negative participants with HSIL occupying ≤ half the anal canal circumference were treated with hemi-circumferential anal canal RFA. Participants were assessed every 3 months for 12 months with high-resolution anoscopy; recurrence in the treatment zone was re-treated with focal RFA. Twenty-one participants with a mean of 1.7 lesions (range 1-4) enrolled and completed the trial. Six (29 %) participants had recurrent HSIL within the treated hemi-circumference within 1 year. Four participants (19 %) had persistence of an index lesion at 3 months. One (2.9 %) index HSIL persisted again at 12 months. No participants had more than two RFA treatments. KM curve-predicted HSIL-free survival within the treatment zone at 1 year was 76 % (95 % CI 52-89 %). Comparing the first 7 and last 14 participants, the predicted 1-year HSIL-free survivals are 43 % (95 % CI 10-73 %) and 93 % (95 % CI 59-99 %), respectively (p = 0.008), suggesting a learning curve with the treating physician. Multivariable analysis showed decreased recurrence in the last 14 participants (HR 0.02; 95 % CI 0.001-0.63) while increasing BMI increased recurrence (HR 1.43, 95 % CI 1.01-2.01). No participants had device or procedure-related serious adverse events, anal stricture, or heavy bleeding. Hemi-circumferential RFA yielded a high rate of anal HSIL eradication in HIV-negative patients at 1 year with minimal adverse events. Lesion persistence was probably related to incomplete initial ablation.

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

Inhibition of bladder overactivity by a combination of tibial neuromodulation and tramadol treatment in cats

PubMed Central

Zhang, Fan; Mally, Abhijith D.; Ogagan, P. Dafe; Shen, Bing; Wang, Jicheng; Roppolo, James R.; de Groat, William C.

2012-01-01

Our recent study in cats revealed that inhibition of bladder overactivity by tibial nerve stimulation (TNS) depends on the activation of opioid receptors. TNS is a minimally invasive treatment for overactive bladder (OAB), but its efficacy is low. Tramadol (an opioid receptor agonist) is effective in treating OAB but elicits significant adverse effects. This study was to determine if a low dose of tramadol (expected to produce fewer adverse effects) can enhance the TNS inhibition of bladder overactivity. Bladder overactivity was induced in α-chloralose-anesthetized cats by an intravesical infusion of 0.25% acetic acid (AA) during repeated cystometrograms (CMGs). TNS (5 Hz) at two to four times the threshold intensity for inducing toe movement was applied during CMGs before and after tramadol (0.3–7 mg/kg iv) to examine the interaction between the two treatments. AA irritation significantly reduced bladder capacity to 24.8 ± 3.3% of the capacity measured during saline infusion. TNS alone reversibly inhibited bladder overactivity and significantly increased bladder capacity to 50–60% of the saline control capacity. Tramadol administered alone in low doses (0.3–1 mg/kg) did not significantly change bladder capacity, whereas larger doses (3–7 mg/kg) increased bladder capacity (50–60%). TNS in combination with tramadol (3–7 mg/kg) completely reversed the effect of AA. Tramadol also unmasked a prolonged (>2 h) TNS inhibition of bladder overactivity that persisted after termination of the stimulation. The results suggest a novel treatment strategy for OAB by combining tibial neuromodulation with a low dose of tramadol, which is minimally invasive with a potentially high efficacy and fewer adverse effects. PMID:22496406

Local infiltration analgesia: a 2-year follow-up of patients undergoing total hip arthroplasty.

PubMed

Kuchálik, Ján; Magnuson, Anders; Lundin, Anders; Gupta, Anil

2017-12-01

Local infiltration analgesia (LIA) is commonly used for postoperative pain management following total hip arthroplasty (THA). However, the long-term effects of the component drugs are unclear. The aim of our study was to investigate functional outcome, quality of life, chronic post-surgical pain, and adverse events in patients within 2 years of undergoing THA. The study was a secondary analysis of data from a previous larger study. Eighty patients were randomized to receive either intrathecal morphine (Group ITM) or local infiltration analgesia (Group LIA) for pain management in a double-blind study. The parameters measured were patient-assessed functional outcome [using the Hip dysfunction and Osteo-arthritis Outcome Score (HOOS) questionnaire], health-related quality of life [using the European Quality of Life-5 dimensions (EQ-5D) questionnaire and the 36-Item Short Form Health Survey (SF-36) score], and pain using the numeric rating score (NRS), with persistent post-surgical pain having a NRS of > 3 or a HOOS pain sub-score of > 30. All complications and adverse events were investigated during the first 2 years after primary surgery. Pain intensity and rescue analgesic consumption were similar between the groups after hospital discharge. No differences were found in HOOS or SF-36 score between the groups up to 6 months after surgery. A significant group × time interaction was seen in the EQ 5D form in favor of the LIA group. No between-group difference in persistent post-surgical pain was found at 3 or 6 months, or in adverse events up to 2 years after surgery. Analysis of functional outcome, quality of life, and post-discharge surgical pain did not reveal significant differences between patients receiving LIA and those receiving ITM. LIA was found to be a safe technique for THA during the long-term follow-up. However, it should be noted that these conclusions are based on a limited number of patients.

Simulated Space Radiation and Weightlessness: Vascular-Bone Coupling Mechanisms to Preserve Skeletal Health

NASA Technical Reports Server (NTRS)

Globus, R. K.; Alwood, J.; Tahimic, C.; Schreurs, A.-S.; Shirazi-Fard, Y.; Terada, M.; Zaragoza, J.; Truong, T.; Bruns, K.; Castillo, A.;

Let's talk about sex: gender norms and sexual health in English schools.

PubMed

Jamal, Farah; Bonell, Chris; Wooder, Kai; Blake, Simon

2015-03-01

The sexual health of young people in England is an urgent public health concern. While interventions to address young people's sexual health have focussed on knowledge, skills and contraception access, amazingly none in the UK has explicitly addressed the effects of the social hierarchies of gender and gendered behavioural ideals that shape young people's sexual expectations, attitudes and behaviour. The lack of attention to gender is a persistent gap in health research, practice and policy. A rigorous evaluation of such an intervention package would go some way to building an evidence base for challenging gender norms, which appear to be strongly associated with adverse sexual health outcomes.

[Hiatal hernia and reflux disease--long-term results following fundoplication and consequences in therapeutic failures].

PubMed

Ackermann, C; Margreth, L; Muller, C; Harder, F

1987-01-01

10 to 20 years (median 15.1 years) after fundoplication for primary reflux disease 257 patients were questioned about their symptoms. Data of 163 patients could be analyzed. 21.4% of the patients have persistent or recurrent reflux symptoms, about half of them (9.8%) need medical treatment. Adverse side-effects of the fundoplication are frequent: dysphagia in 28.2%, gas-bloat in 50.3%. Using the Visick criteria for classification we found Visick grade I and II for 75.5%, grade III for 17.2%, and IV for 7.4%. Diagnostic and therapeutic concepts in case of failed reflux control are discussed.

Wet combing for the eradication of head lice.

PubMed

2013-03-01

Manual removal (using conditioner and comb or a wet comb) can be used in the treatment of head lice. Head lice infestation (Pediculosis humanus capitis) is a common problem. It is diagnosed by visualising the lice. As half of people infested with head lice will not scratch, all people in contact with a person affected with head lice should be manually checked for infestations. Wet combing is easily and safely performed at home, but persistence is needed. This article describes the process of head lice removal using a wet comb. It has NHMRC Level 2 evidence of efficacy and no serious adverse effects have been reported.

Persistence Factors of First-Generation Learners

ERIC Educational Resources Information Center

Braswell, Tawanda M.

2010-01-01

This dissertation utilized a qualitative narrative case study method to explore the unknown factors and elements of perseverance in spite of adversity and crisis. The study documented the lives of five African American women in order to describe, understand, and explain the central research question of how and why some first-generation learners…

CHANGES IN PROTEOMIC PROFILES OF CEREBELLUM AND HIPPOCAMPUS FOLLOWING EXPOSURE TO A DEVELOPMENTAL NEUROTOXICANT.

EPA Science Inventory

The vast literature on the group of chemicals known as polychlorinated biphenyls (PCBs) makes it a unique model to understand major issues related to environmental mixtures of persistent chemicals. At background levels of exposure, PCBs have been shown to adversely affect human h...

CHRONIC LYME DISEASE: SYMPTOMS, VISION AND A NEW APPROACH TO TREATMENT BASED ON A THEORY OF NEUROTOXIN-MEDIATED ILLNESS.

EPA Science Inventory

Evidence suggests that the estuarine dinoflagellate, Pfiesteria piscicida, and/or morphologically related organisms (Pf-MRO) may release a toxin(s) which kills fish and adversely affects human health. The North Carolina study investigated the potential for persistent health effec...

Peer Mentoring: Encouraging Persistence in Native American Postsecondary Students

ERIC Educational Resources Information Center

Lee, Susan D.

2013-01-01

Native Americans have endured historical and contemporary challenges that have adversely affected their achievement, including in the realm of postsecondary education. The difficulties have included, but are not limited to, the problems inherent in the process of assimilation into Caucasian culture, the repercussions of Indian Boarding Schools,…

Delayed Neurotoxicity Associated with Therapy for Children with Acute Lymphoblastic Leukemia

ERIC Educational Resources Information Center

Cole, Peter D.; Kamen, Barton A.

2006-01-01

Most children diagnosed today with acute lymphoblastic leukemia (ALL) will be cured. However, treatment entails risk of neurotoxicity, causing deficits in neurocognitive function that can persist in the years after treatment is completed. Many of the components of leukemia therapy can contribute to adverse neurologic sequelae, including…

Percutaneous Repair of Postoperative Mitral Regurgitation After Left Ventricular Assist Device Implant.

PubMed

Cork, David P; Adamson, Robert; Gollapudi, Raghava; Dembitsky, Walter; Jaski, Brian

2018-02-01

Mitral regurgitation commonly improves after implantation of a left ventricular assist device without concomitant valvular repair owing to the mechanical unloading of the left ventricle. However, the development (or persistence) of significant mitral regurgitation after implantation of a left ventricular assist device is associated with adverse clinical events. We present a case of a left ventricular assist device patient who successfully underwent a percutaneous MitraClip procedure for repair of persistent late postoperative mitral insufficiency with demonstrable clinical and hemodynamic improvement. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Adjuvant Ciprofloxacin for Persistent BK Polyomavirus Infection in Kidney Transplant Recipients

PubMed Central

Chandran, Sindhu; Vagefi, Parsia A.

2014-01-01

Background. BK virus (BKV) infection is a common complication following kidney transplantation. Immunosuppression reduction is the cornerstone of treatment while adjuvant drugs have been tried in small uncontrolled studies. We sought to examine our center's experience with the use of ciprofloxacin in patients with persistent BKV infection. Methods. Retrospective evaluation of the effect of a 30-day ciprofloxacin course (250 mg twice daily) on BKV infection in kidney transplant recipients who had been diagnosed with BK viruria ≥106 copies/mL and viremia ≥500 copies/mL and in whom the infection did not resolve after immunosuppression reduction and/or treatment with other adjuvant agents. BKV in plasma and urine was evaluated after 3 months following treatment with ciprofloxacin. Results. Nine kidney transplant recipients received ciprofloxacin at a median of 130 days following the initial reduction in immunosuppression. Three patients showed complete viral clearance and another 3 had a ≥50% decrease in plasma viral load. No serious adverse events secondary to ciprofloxacin were reported and no grafts were lost due to BKV up to 1 year after treatment. Conclusion. Ciprofloxacin may be a useful therapy for persistent BKV infection despite conventional treatment. Randomized trials are required to evaluate the potential benefit of this adjuvant therapy. PMID:25349720

Does physical activity during pregnancy adversely influence markers of the metabolic syndrome in adult offspring? A prospective study over two decades.

PubMed

Danielsen, Inge; Granström, Charlotta; Rytter, Dorte; Hammer Bech, Bodil; Brink Henriksen, Tine; Vaag, Allan Arthur; Olsen, Sjurdur Frodi

2013-08-01

It is unknown whether physical activity during pregnancy (PA) has long-term impact on the metabolic profile of the offspring. We investigated associations of PA with markers of the metabolic syndrome (MS) in 20y old offspring. Longitudinal study where 965 pregnant women during 1988-1989 had four dimensions of PA assessed by questionnaires in gestation week 30: PA at work; leisure time PA, daily amount of walking-biking and sport participation. The following MS markers were assessed in the offspring (n=439): body mass index (BMI), waist circumference, blood pressure, homeostasis model assessment insulin resistance as well as fasting plasma glucose, triglycerides, cholesterol (high-density lipoprotein (HDL), low-density lipoprotein and total cholesterol), insulin and leptin levels. Walking-biking PA in pregnancy is associated with unchanged or subtle, adverse changes of distinct MS markers among offspring including lower levels of HDL cholesterol (ratio 0.95 (95% CI 0.92 to 0.98) per 1 h increment in walking-biking), a higher diastolic blood pressure (difference 1.12 (95% CI 0.03 to 2.20) mm Hg/1 h increment) and a higher BMI (ratio 1.03 (95% CI 1.01 to 1.05) per 1 h increment). In separate analyses in males, these associations persisted and additional adverse associations were found for triglycerides, systolic blood pressure, waist circumference and leptin. No associations were detected with other measures of PA. The study did not substantiate any protective effects of PA in pregnancy. In contrast, data suggested that high amounts of daily walking-biking in pregnancy may have adverse effects on levels of HDL cholesterol, diastolic blood pressure and BMI in young adult offspring.

Eliminating health disparities in unintended pregnancy with long-acting reversible contraception (LARC).

PubMed

Parks, Caitlin; Peipert, Jeffrey F

2016-06-01

Significant public health disparities exist surrounding teen and unplanned pregnancy in the United States. Women of color and those with lower education and socioeconomic status are at much greater risk of unplanned pregnancy and the resulting adverse outcomes. Unplanned pregnancies reduce educational and career opportunities and may contribute to socioeconomic deprivation and widening income disparities. Long-acting reversible contraception (LARC), including intrauterine devices and implants, offer the opportunity to change the default from drifting into parenthood to planned conception. LARC methods are forgettable; once placed, they offer highly effective, long-term pregnancy prevention. Increasing evidence in the medical literature demonstrates the population benefits of use of these methods. However, barriers to more widespread use of LARC methods persist and include educational, access, and cost barriers. With increasing insurance coverage under the Affordable Care Act and more widespread, no-cost coverage of methods, more and more women are choosing intrauterine devices and the contraceptive implant. Increasing the use of highly effective contraceptive methods may provide one solution to the persistent problem of the health disparities of unplanned and teen pregnancies in the United States and improve women's and children's health. Copyright © 2016 Elsevier Inc. All rights reserved.

Cancer-related fatigue--mechanisms, risk factors, and treatments.

PubMed

Bower, Julienne E

2014-10-01

Fatigue is one of the most common adverse effects of cancer that might persist for years after treatment completion in otherwise healthy survivors. Cancer-related fatigue causes disruption in all aspects of quality of life and might be a risk factor of reduced survival. The prevalence and course of fatigue in patients with cancer have been well characterized and there is growing understanding of the underlying biological mechanisms. Inflammation seems to have a key role in fatigue before, during, and after cancer-treatment. However, there is a considerable variability in the presentation of cancer-related fatigue, much of which is not explained by disease-related or treatment-related characteristics, suggesting that host factors might be important in the development and persistence of this symptom. Indeed, longitudinal studies have identified genetic, biological, psychosocial, and behavioural risk factors associated with cancer-related fatigue. Although no current gold-standard treatment for fatigue is available, a variety of intervention approaches have shown beneficial effects in randomized controlled trials, including physical activity, psychosocial, mind-body, and pharmacological treatments. This Review describes the mechanisms, risk factors, and possible interventions for cancer-related fatigue, focusing on recent longitudinal studies and randomized trials that have targeted fatigued patients.

A 2-night, 3-period, crossover study of ramelteon's efficacy and safety in older adults with chronic insomnia.

PubMed

Roth, Thomas; Seiden, David; Wang-Weigand, Sherry; Zhang, Jeffrey

2007-05-01

To assess the efficacy and safety of ramelteon, a selective melatonin MT1/MT2-receptor agonist, for insomnia treatment in older adults. In a randomized, 9-week, 3-period crossover trial conducted at 17 sleep centers, older adults (N = 100) with chronic primary insomnia (37 men, 63 women; mean age [range], 70.7 [65-83] years) were administered placebo, ramelteon 4 mg, and ramelteon 8 mg in three treatment phases for two consecutive nights. Each phase was separated by 5- to 12-day washout periods. Sleep was monitored via polysomnography. Subjective sleep parameters, using a Postsleep Questionnaire, were recorded, and residual pharmacologic effects were assessed. Statistically significant reductions in latency to persistent sleep were observed with both ramelteon 4 mg and 8 mg compared to placebo (28.7 min vs. 38.4 min, p < 0.001; 30.8 min vs. 38.4 min, p = 0.005, respectively). Total sleep time (p = 0.036 and p = 0.007, respectively) and sleep efficiency (p = 0.037 and p = 0.007, respectively) were also significantly improved with ramelteon 4 mg and 8 mg compared to placebo. Statistically significant reductions in subjective sleep latency on a Postsleep Questionnaire were reported with ramelteon 4 mg versus placebo (p = 0.037), but not ramelteon 8 mg (p = 0.120); no significant differences on other subjective sleep assessments were reported. A lack of power limits interpretation of self-reported sleep parameters. Incidences of adverse events considered treatment related were placebo (7%), ramelteon 4 mg (11%), and ramelteon 8 mg (5%). No residual pharmacologic effects were observed via Digit Symbol Substitution Test, memory recall tests (immediate and delayed), visual analog scales (feelings and mood), and Postsleep Questionnaire (level of alertness and ability to concentrate). In older adults with chronic primary insomnia, ramelteon produced significant reductions in latency to persistent sleep and increases in total sleep time and sleep efficacy, and showed no evidence of adverse next-day psychomotor or cognitive effects.

Peripheral Nerve Blocks for the Treatment of Headache in Older Adults: A Retrospective Study.

PubMed

Hascalovici, Jacob R; Robbins, Matthew S

2017-01-01

The objective of this study is to provide demographical and clinical descriptions of patients age 65 years old and older who were treated with peripheral nerve blocks (PNBs) at our institution and evaluate the safety and efficacy of this treatment. Headache disorders are common, disabling chronic neurological diseases that often persist with advancing age. Geriatric headache management poses unique therapeutic challenges because of considerations of comorbidity, drug interactions, and adverse effects. Peripheral nerve blocks are commonly used for acute and short-term prophylactic treatment for headache disorders and may be a safer alternative to standard pharmacotherapy in this demographic. We performed a single center, retrospective chart review of patients at least 65 years of age who received peripheral nerve blocks for headache management over a 6 year period. Sixty-four patients were mostly female (78%) with an average age of 71 years (range 65-94). Representative headache diagnoses were chronic migraine 50%, episodic migraine 12.5%, trigeminal autonomic cephalalgia 9.4%, and occipital neuralgia 7.8%. Average number of headache days/month was 23. Common comorbidities were hypertension 48%, hyperlipidemia 42%, arthritis 27%, depression 47%, and anxiety 33%. Eighty-nine percent were prescribed at least 1 medication fulfilling the Beers criteria. The average number of peripheral nerve blocks per patient was 4. Peripheral nerve blocks were felt to be effective in 73% for all headaches, 81% for chronic migraine, 75% for episodic migraine, 67% for chronic tension type headache, 67% for new daily persistent headache, and 60% for occipital neuralgia. There were no adverse events related to PNBs reported. PNBs might be a safe and effective alternative headache management strategy for older adults. Medical and psychiatric comorbidities, medication overuse, and Beers list medication rates were extraordinarily high, giving credence to the use of peripherally administered therapies in the geriatric population that may be better tolerated and safer. © 2016 American Headache Society.

Biological Stress Systems, Adverse Life Events, and the Improvement of Chronic Multisite Musculoskeletal Pain Across a 6-Year Follow-Up.

PubMed

Generaal, Ellen; Vogelzangs, Nicole; Macfarlane, Gary J; Geenen, Rinie; Smit, Johannes H; de Geus, Eco J C N; Dekker, Joost; Penninx, Brenda W J H

2017-02-01

Dysfunction of biological stress systems and adverse life events, independently and in interaction, have been hypothesized to predict chronic pain persistence. Conversely, these factors may hamper the improvement of chronic pain. Longitudinal evidence is currently lacking. We examined whether: 1) function of biological stress systems, 2) adverse life events, and 3) their combination predict the improvement of chronic multisite musculoskeletal pain. Subjects of the Netherlands Study of Depression and Anxiety (NESDA) with chronic multisite musculoskeletal pain at baseline (N = 665) were followed-up 2, 4, and 6 years later. The Chronic Pain Grade Questionnaire was used to determine improvement (not meeting the criteria) of chronic multisite musculoskeletal pain at follow-up. Baseline assessment of biological stress systems included function of hypothalamic-pituitary-adrenal axis (1-hour cortisol awakening response, evening level, and post dexamethasone level), the immune system (basal and lipopolysaccharide-stimulated inflammatory markers), the autonomic nervous system (heart rate, pre-ejection period, SD of the normal-to-normal interval, and respiratory sinus arrhythmia). The number of adverse life events were assessed at baseline and 2-year follow-up using the List of Threatening Events Questionnaire. We showed that hypothalamic-pituitary-adrenal axis, immune system, and autonomic nervous system functioning and adverse life events were not associated with the improvement of chronic multisite musculoskeletal pain, either as a main effect or in interaction. This longitudinal study could not confirm that biological stress system dysfunction and adverse life events affect the course of chronic multisite musculoskeletal pain. Biological stress systems and adverse life events are not associated with the improvement of chronic multisite musculoskeletal pain over 6 years of follow-up. Other determinants should thus be considered in future research to identify in which persons pain symptoms will improve. Copyright © 2016 American Pain Society. Published by Elsevier Inc. All rights reserved.

Systematic review: colitis associated with anti-CTLA-4 therapy.

PubMed

Gupta, A; De Felice, K M; Loftus, E V; Khanna, S

2015-08-01

Cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) has an important role in T-cell regulation, proliferation and tolerance. Anti-CTLA-4 agents, such as ipilimumab and tremelimumab, have been shown to prolong overall survival in patients with metastatic melanoma, and their use is being investigated in the treatment of other malignancies. Their novel immunostimulatory mechanism, however, predisposes patients to immune-related adverse effects, of which gastrointestinal effects such as diarrhoea and colitis are the most common. To discuss the existing literature and summarise the epidemiology, pathogenesis and clinical features of anti-CTLA-4-associated colitis, and to present a management algorithm for it. We searched PubMed for studies published through October 2014 using the terms 'anti-CTLA,' 'ipilimumab,' 'tremelimumab,' 'colitis,' 'gastrointestinal,' 'immune-related adverse effect,' 'immunotherapy,' 'melanoma,' and 'diarrhoea.' Watery diarrhoea is commonly associated with anti-CTLA-4 therapy (27-54%), and symptoms occur within a few days to weeks of therapy. Diffuse acute and chronic colitis are the most common findings on endoscopy (8-22%). Concomitant infectious causes of diarrhoea must be evaluated. Most cases may be successfully managed with discontinuation of anti-CTLA-4 and conservative therapy. Those with persistent grade 2 and grade 3/4 diarrhoea should undergo endoscopic evaluation and require corticosteroid therapy. Corticosteroid-resistant cases may respond to anti-tumour necrosis factor-alpha therapy such as infliximab. Surgery is reserved for patients with bowel perforation or failure of medical therapy. Given the increasing use of anti-CTLA-4 therapy, clinicians must be aware of related adverse events and their management. © 2015 John Wiley & Sons Ltd.

Early exposure to thirdhand cigarette smoke affects body mass and the development of immunity in mice

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

Hang, Bo; Snijders, Antoine M.; Huang, Yurong

Thirdhand smoke (THS) is the fraction of cigarette smoke that persists in indoor environments after smoking. We investigated the effects of neonatal and adult THS exposure on bodyweight and blood cell populations in C57BL/6 J mice. At the end of neonatal exposure, THS-treated male and female mice had significantly lower bodyweight than their respective control mice. However, five weeks after neonatal exposure ended, THS-treated mice weighed the same as controls. In contrast, adult THS exposure did not change bodyweight of mice. On the other hand, both neonatal and adult THS exposure had profound effects on the hematopoietic system. Fourteen weeksmore » after neonatal THS exposure ended, eosinophil number and platelet volume were significantly higher, while hematocrit, mean cell volume, and platelet counts were significantly lower compared to control. Similarly, adult THS exposure also decreased platelet counts and increased neutrophil counts. Moreover, both neonatal and adult THS exposure caused a significant increase in percentage of B-cells and significantly decreased percentage of myeloid cells. Our results demonstrate that neonatal THS exposure decreases bodyweight and that THS exposure induces persistent changes in the hematopoietic system independent of age at exposure. These results also suggest that THS exposure may have adverse effects on human health.« less

Early exposure to thirdhand cigarette smoke affects body mass and the development of immunity in mice

DOE PAGES

Hang, Bo; Snijders, Antoine M.; Huang, Yurong; ...

2017-02-03

Thirdhand smoke (THS) is the fraction of cigarette smoke that persists in indoor environments after smoking. We investigated the effects of neonatal and adult THS exposure on bodyweight and blood cell populations in C57BL/6 J mice. At the end of neonatal exposure, THS-treated male and female mice had significantly lower bodyweight than their respective control mice. However, five weeks after neonatal exposure ended, THS-treated mice weighed the same as controls. In contrast, adult THS exposure did not change bodyweight of mice. On the other hand, both neonatal and adult THS exposure had profound effects on the hematopoietic system. Fourteen weeksmore » after neonatal THS exposure ended, eosinophil number and platelet volume were significantly higher, while hematocrit, mean cell volume, and platelet counts were significantly lower compared to control. Similarly, adult THS exposure also decreased platelet counts and increased neutrophil counts. Moreover, both neonatal and adult THS exposure caused a significant increase in percentage of B-cells and significantly decreased percentage of myeloid cells. Our results demonstrate that neonatal THS exposure decreases bodyweight and that THS exposure induces persistent changes in the hematopoietic system independent of age at exposure. These results also suggest that THS exposure may have adverse effects on human health.« less

Five-year Antibody Persistence and Safety After a Single Dose of Combined Haemophilus influenzae Type B Neisseria meningitidis Serogroup C-Tetanus Toxoid Conjugate Vaccine in Haemophilus influenzae Type B-primed Toddlers.

PubMed

Booy, Robert; Nolan, Terry; Reynolds, Graham; Richmond, Peter; Nissen, Michael; Marshall, Helen; Stoney, Tanya; Van Der Wielen, Marie; Kolhe, Devayani; Miller, Jacqueline M

2015-12-01

Antibody persistence is evaluated in healthy Australian children 4 and 5 years postvaccination with a single dose of combined Haemophilus influenzae type b-Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine (Hib-MenC-TT) compared with separately administered Hib-TT and MenC-CRM197 vaccines (Hib + MCC). This is another follow-up of a phase III, open, randomized, controlled study (NCT00326118), in which 433 Hib-primed but MenC naïve toddlers aged 12-18 months were randomized 3:1 to receive Hib-MenC-TT or Hib + MCC vaccines. Protection against (1) MenC was measured by serum bactericidal antibody assay using rabbit complement (rSBA) and (2) Hib was measured by enzyme-linked immunosorbent assay of antibodies to polyribosylribitol phosphate (anti-PRP). Study children were assessed for any potentially vaccine-related serious adverse events at each persistence study visit. The according-to-protocol cohorts for persistence at years 4 and 5 included 282 and 263 children, respectively. The percentages of children with rSBA-MenC titers ≥1:8 at years 4 and 5 were 12.5% and 19.0%, respectively, in the Hib-MenC group; and 12.3% and 25.0% in the Hib + MCC group. All children in each group had anti-PRP concentrations ≥0.15 μg/mL at year 5. Exploratory analyses suggested no potential differences between groups in rSBA-MenC or anti-PRP antibody persistence. No vaccine-related serious adverse events were reported. Antibody persistence was similar for years 4 and 5 after Hib-MenC-TT or Hib + MCC vaccination, with the majority of children retaining anti-PRP antibody concentrations ≥0.15 μg/mL at both timepoints. The percentage of children retaining rSBA-MenC titers ≥1:8 was low (≤25%), suggesting that a MenC booster dose may be warranted before adolescence.

Patterns of poverty exposure and children's trajectories of externalizing and internalizing behaviors.

PubMed

Comeau, Jinette; Boyle, Michael H

2018-04-01

Using data from the Child Supplement of the National Longitudinal Survey of Youth, we compare trajectories of externalizing and internalizing behaviors among children exposed to five patterns of poverty from birth to age 14: always or never poor - stable patterns; a single transition into or out of poverty, or repeated fluctuations in and out of poverty - changing patterns. We also examine how low maternal education and single parenthood interact with these poverty exposures to compound their adverse effects. Finally, we compare the magnitude of effects associated with the patterns of poverty exposure, as well as their interactions with low maternal education and single parenthood, on trajectories of externalizing and internalizing behaviors to determine if they are significantly different. Results reveal that initial levels and rates of change in children's trajectories of externalizing and internalizing behaviors are similar across the three changing patterns of poverty exposure, leading us to combine them into a single group representing intermittent poverty. Initial disparities between children who are never poor and their counterparts who are always or intermittently poor are constant over time for internalizing behaviors and grow in magnitude for externalizing behaviors. The cumulative negative effect of poverty exposure over time is stronger for externalizing vs. internalizing behaviors. Low maternal education compounds the adverse effects of persistent poverty, an effect that is similar for externalizing and internalizing behaviors.

Job sharing at a children's hospital: evaluation by medical staff.

PubMed

Valentine, J P; Martin, C J

1996-01-13

To evaluate job sharing for registrars at Princess Margaret Hospital for Children, Perth, by seeking responses from members of the relevant medical teams. A questionnaire was sent to all 126 medical staff within the hospital (and three managers in medical administration) asking their views on job sharing for registrars. Whether job sharing should continue, who should do it, at what stage of training, and the effects on patient care. Among the 77 respondents (60%) there was broad support for the continuation of job sharing at the hospital: only 5 of 37 consultants and 2 of 19 non-job sharing registrars rejected the idea (with a further 4 consultants uncertain). 43% Of the consultants who had worked with job sharing registrars thought continuity of care was adversely affected. The committee for physician training of the Royal Australasian College of Physicians emphasises that advanced training should be flexible, with a wide range of opportunities for individuals to plan an appropriate training programme in line with their personal goals. This study has shown that job sharing for registrars at Princess Margaret Hospital for Children allows this choice. Action on concerns over any adverse effects on patient care should resolve any persisting disquiet.

Topiramate induced peripheral neuropathy: A case report and review of literature.

PubMed

Hamed, Sherifa Ahmed

2017-12-16

Drug-induced peripheral neuropathy had been rarely reported as an adverse effect of some antiepileptic drugs (AEDs) at high cumulative doses or even within the therapeutic drug doses or levels. We describe clinical and diagnostic features of a patient with peripheral neuropathy as an adverse effect of chronic topiramate (TPM) therapy. A 37-year-old woman was presented for the control of active epilepsy (2010). She was resistant to some AEDs as mono- or combined therapies (carbamazepine, sodium valproate, levetiracetam, oxcarbazepine and lamotrigine). She has the diagnosis of frontal lobe epilepsy with secondary generalization and has a brother, sister and son with active epilepsies. She became seizure free on TPM (2013-2017) but is complaining of persistent distal lower extremities paresthesia in a stocking distribution. Neurological examination revealed presence of diminished Achilles tendon reflexes, stocking hypesthesia and delayed distal latencies, reduced conduction velocities and amplitudes of action potentials of posterior tibial and sural nerves, indicating demyelinating and axonal peripheral neuropathy of the lower extremities. After exclusion of the possible causes of peripheral neuropathy, chronic TPM therapy is suggested as the most probable cause of patient's neuropathy. This is the first case report of topiramate induced peripheral neuropathy in the literature.

Fourth-line rescue therapy with rifabutin in patients with three Helicobacter pylori eradication failures.

PubMed

Gisbert, J P; Castro-Fernandez, M; Perez-Aisa, A; Cosme, A; Molina-Infante, J; Rodrigo, L; Modolell, I; Cabriada, J L; Gisbert, J L; Lamas, E; Marcos, E; Calvet, X

2012-04-01

In some cases, Helicobacter pylori infection persists even after three eradication treatments. To evaluate the efficacy of an empirical fourth-line rescue regimen with rifabutin in patients with three eradication failures. Multicentre, prospective study. In whom the following three treatments had consecutively failed: first (PPI + clarithromycin + amoxicillin); second (PPI + bismuth + tetracycline + metronidazole); third (PPI + amoxicillin + levofloxacin). A fourth regimen with rifabutin (150 mg b.d.), amoxicillin (1 g b.d.) and a PPI (standard dose b.d.) was prescribed for 10 days. Eradication was confirmed by (13) C-urea breath test 4-8 weeks after therapy. Compliance and tolerance: Compliance was determined through questioning and recovery of empty medication envelopes. Adverse effects were evaluated using a questionnaire. One-hundred patients (mean age 50 years, 39% men, 31% peptic ulcer/69% functional dyspepsia) were included. Eight patients did not take the medication correctly (in six cases due to adverse effects). Per-protocol and intention-to-treat eradication rates were 52% (95% CI = 41-63%) and 50% (40-60%). Adverse effects were reported in 30 (30%) patients: nausea/vomiting (13 patients), asthenia/anorexia (8), abdominal pain (7), diarrhoea (5), fever (4), metallic taste (4), myalgia (4), hypertransaminasemia (2), leucopenia (<1,500 neutrophils) (2), thrombopenia (<150,000 platelets) (2), headache (1) and aphthous stomatitis (1). Myelotoxicity resolved spontaneously in all cases. Even after three previous H. pylori eradication failures, an empirical fourth-line rescue treatment with rifabutin may be effective in approximately 50% of the cases. Therefore, rifabutin-based rescue therapy constitutes a valid strategy after multiple previous eradication failures with key antibiotics, such as clarithromycin, metronidazole, tetracycline and levofloxacin. © 2012 Blackwell Publishing Ltd.

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.

LEARNING TO BE BAD: ADVERSE SOCIAL CONDITIONS, SOCIAL SCHEMAS, AND CRIME

PubMed Central

Simons, Ronald L.; Burt, Callie Harbin

2011-01-01

In this paper we develop and test a new approach to explain the link between social factors and individual offending. We argue that seemingly disparate family, peer, and community conditions lead to crime because the lessons communicated by these events are similar and promote social schemas involving a hostile view of people and relationships, a preference for immediate rewards, and a cynical view of conventional norms. Further, we posit that these three schemas are interconnected and combine to form a criminogenic knowledge structure that gives rise to situational interpretations legitimating criminal behavior. Structural equation modeling with a sample of roughly 700 hundred African American teens provided strong support for the model. The findings indicated that persistent exposure to adverse conditions such as community crime, discrimination, harsh parenting, deviant peers and low neighborhood collective efficacy increased commitment to the three social schemas. The three schemas were highly intercorrelated and combined to form a latent construct that strongly predicted increases in crime. Further, in large measure the effect of the various adverse conditions on increases in crime was indirect through their impact on this latent construct. We discuss the extent to which the social schematic model presented in the paper might be used to integrate concepts and findings from several of the major theories of criminal behavior. PMID:21760641

Inhaled Corticosteroids in Lung Diseases

PubMed Central

Raissy, Hengameh H.; Kelly, H. William; Harkins, Michelle

2013-01-01

Inhaled corticosteroids (ICSs) are used extensively in the treatment of asthma and chronic obstructive pulmonary disease (COPD) due to their broad antiinflammatory effects. They improve lung function, symptoms, and quality of life and reduce exacerbations in both conditions but do not alter the progression of disease. They decrease mortality in asthma but not COPD. The available ICSs vary in their therapeutic index and potency. Although ICSs are used in all age groups, younger and smaller children may be at a greater risk for adverse systemic effects because they can receive higher mg/kg doses of ICSs compared with older children. Most of the benefit from ICSs occurs in the low to medium dose range. Minimal additional improvement is seen with higher doses, although some patients may benefit from higher doses. Although ICSs are the preferred agents for managing persistent asthma in all ages, their benefit in COPD is more controversial. When used appropriately, ICSs have few adverse events at low to medium doses, but risk increases with high-dose ICSs. Although several new drugs are being developed and evaluated, it is unlikely that any of these new medications will replace ICSs as the preferred initial long-term controller therapy for asthma, but more effective initial controller therapy could be developed for COPD. PMID:23370915

A review of the epidemiologic literature on the role of environmental arsenic exposure and cardiovascular diseases

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

Wang, C.-H.; Hsiao, C.K.; Chen, C.-L.

2007-08-01

Cardiovascular disease is the leading cause of mortality worldwide. Arsenic is a ubiquitous metalloid in the crust of the earth. Chronic arsenic poisoning is becoming an emerging epidemic in Asia. Epidemiological studies have shown that chronic arsenic poisoning through ingestion of arsenic-contaminated water is associated with various cardiovascular diseases in dose-response relationships. These cardiovascular disorders include carotid atherosclerosis detected by ultrasonography, impaired microcirculation, prolonged QT interval and increased QT dispersion in electrocardiography, and clinical outcomes such as hypertension, blackfoot disease (a unique peripheral vascular disease endemic in southwestern Taiwan), coronary artery disease and cerebral infarction. Chronic arsenic poisoning is anmore » independent risk factor for cardiovascular disease. The adverse cardiovascular effects of long-term arsenic exposure may be persistent and/or irreversible. Arsenic-induced cardiovascular diseases in human population may result from the interaction among genetic, environment and nutritional factors. The major adverse cardiovascular effect of chronic arsenic poisoning has been established qualitatively and quantitatively in the high arsenic exposure areas, but the low-dose effect of arsenic on cardiovascular diseases remains to be explored. Cardiovascular death is the major cause of mortality worldwide, and a small increased risk may imply a large quantity of excess mortality.« less

Patient perspectives on low level light therapy and laser therapies for rosacea-associated persistent facial redness.

PubMed

McGinley, Meagan; Alinia, Hossein; Kuo, Sandy; Huang, Karen E; Feldman, Steven R

2014-12-13

There are no definitive treatments of facial redness for rosacea. All treatments aim to alleviate symptoms. Patients' perspectives of two emerging modalities, Low level light therapy and laser treatments are not well characterized. The purpose is to further understand rosacea patients unmet needs about these modalities, Methods: The publicly accessible, online rosacea forum was accessed at august 2013. Stratified random sampling method has done to identify a 10% sample of total 27,051 posts. The Posts were published in the "Laser and IPL therapy" and "Low level light therapy" forums were qualitatively analyzed. Patients discussed a variety of topics, but most commonly discussed effectiveness (34.2%), treatment education (19.3%), and adverse effects (18%). Relationship with the health care provider (9.9%), cost (8.1%), execution of treatments (8.1%) and convenience of treatments (2.5%) were less commonly discussed, but contributed to patients' decisions about utilizing laser and light therapies. Online forums are utilized to fulfill patients' desire for educational, empathic and collaborative relationship. Patients' adherence to laser and light therapies will likely increase if costs are reduced, reduction in redness is consistent with their expectations, and if physicians empower them through education on device choices and managing adverse effects.

Phosphodiesterase 4 inhibitors in chronic obstructive pulmonary disease: a new approach to oral treatment

PubMed Central

Currie, Graeme P; Butler, Claire A; Anderson, Wendy J; Skinner, Chris

2008-01-01

Chronic obstructive pulmonary disease represents a major global health care burden for both primary and secondary care providers and is the most common respiratory condition necessitating hospital admission. Short-acting bronchodilators play a vital role in immediate relief of symptoms, while inhaled long-acting bronchodilators and inhaled corticosteroids are advocated for regular use in individuals with persistent symptoms and exacerbations. Theophylline is a nonspecific phosphodiesterase inhibitor and is usually reserved for patients with ongoing symptoms despite optimum inhaled bronchodilator treatment or when difficulty is encountered with inhaler devices. However, it is often not widely used mainly due to frequency of dose-related adverse effects, numerous drug interactions and narrow therapeutic index. This in turn has lead to the development of more selective phosphodiesterase inhibitors in an attempt to create a drug which patients can use with beneficial effects but without the problems associated with theophylline. Current data do indicate that phosphodiesterase 4 inhibitors confer some benefits in chronic obstructive pulmonary disease when compared to placebo in terms of lung function, quality of life and exacerbations. They are also generally well tolerated. Further studies are required to determine fully their long-term beneficial and adverse effect profiles and ultimately where they might comfortably sit in management algorithms. PMID:18341675

Adverse environments and children's creativity development: transforming the notion of "success in adversity" in China.

PubMed

Cheng, Li; Tan, Mei; Liu, Zhengkui

2015-01-01

China has been undergoing great social change due to its new focus on urbanization and globalization. Such change has had a tremendous adverse impact on the living conditions of millions of young children, simultaneously generating new interest in children's creativity development. The intersection of these two issues has important implications for China's future as it brings together one of China's core cultural values-"success in adversity"-the importance of creativity, and very real social and economic needs. "Success in adversity" reflects the strongly held belief that individuals who suffer adverse environments can rise to excellence and success through persistence, effort, and creativity. In this article, we briefly explore the historical sources of this belief and how it is closely related to the Chinese conception of creativity. We then present some studies on the creativity of some of China's migrant children. Findings show that while migrant children as a group may not generally exhibit higher creativity than their urban peers as hypothesized, indications of resilience and creative potential suggest that the notion of success in adversity may contribute to the positive development of China's migrant children more substantially when it is informed by research and augmented by research-supported policy. © 2015 Wiley Periodicals, Inc.

[Treatment of Persistent Somatoform Pain Disorder by Floating Needle Therapy and Duloxetine].

PubMed

Ren, Wan-wen; Zhou, Zhi-ying; Xu, Mi-mi; Long, Sen; Tang, Guang-zheng; Mao, Hong-jing; Chen, Shu-lin

2016-02-01

To evaluate clinical effect and safety of floating needle therapy and duloxetine in treating patients with persistent somatoform pain disorder (PSPD). Totally 108 PSPD patients were randomly assigned to the floating needle treatment group, the duloxetine treatment group, and the placebo treatment group, 36 in each group. Patients in the floating needle treatment group received floating needle therapy and placebo. Those in the duloxetine treatment group received duloxetine and simulated floating needle therapy. Those in the placebo treatment group received the placebo and simulated floating needle therapy. All treatment lasted for six weeks. Efficacy and adverse reactions were evaluated using Simple McGill pain scale (SF-MPQ) and Treatment Emergent Symptom Scale (TESS) before treatment and immediately after treatment, as well as at the end of 1st, 2nd, 4th, and 6th week of treatment, respectively. Hamilton Depression Scale (HAMD, 17 items), Hamilton Anxiety Scale (HAMA) were assessed before treatment and at the end of 1st, 2nd, 4th, and 6th week of treatment, respectively. Patients in the floating needle treatment group and the duloxetine treatment group with the total reducing score rate of SF-MPQ in Pain Rating index (PRI) ≥ 50% after 6 weeks' treatment were involved in the follow-up study. (1) Compared with the same group before treatment, SF-MPQ score, HAMD score and HAMA total scores all decreased in all the three groups at the end of 1st, 2nd, 4th, and 6th week of treatment (P < 0.05, P < 0.01). Besides , each item of SF-MPQ significantly decreased immediately after treatment in the floating needle treatment group (P < 0.01). Compared with the placebo treatment group, SF-MPQ, HAMD, and HAMA total score in the floating needle treatment group significantly decreased after 1, 2, 4, and 6 weeks of treatment (P < 0.05, P < 0.01). SF-MPQ score, HAMD score and HAMA total score in the duloxetine treatment group also significantly decreased after 2, 4, and 6 weeks of treatment (P < 0.05, P < 0.01). (2) There were 3 patients (8.3%) who had adverse reactions in the floating needle treatment group, 17 (50.0%) in the duloxetine treatment group, and 7 (21.2%) in the placebo treatment group. Compared with the placebo treatment group, the incidence of adverse reaction increased in the duloxetine treatment group (χ² = 6.04, P < 0.05). Besides, it was higher in the duloxetine treatment group than in the floating needle treatment group (χ² = 14.9, P < 0.05). (3) There were 19 patients in the floating needle treatment group and 17 patients in the duloxetine treatment group involved in the follow-up study. Compared with 6 weeks after treatment, no significant difference was observed at 3 and 6 months after treatment in the score of SF-MPQ, HAMD, and HAMA in the floating needle treatment group and the duloxetine treatment group. No significant difference was observed between the two groups (P > 0.05). There were 5 patients (29.4%) who had adverse reactions in the duloxetine treatment group, and no adverse reactions were observed in the floating needle treatment group. The adverse reaction rate was significantly different between the two groups (χ² = 4.26, P < 0.05). Floating needle therapy and duloxetine were effective in treatment of patients with PSPD. However, floating needle therapy could relieve pain more rapidly than duloxetine, with obviously less adverse reactions.

Aroclor-1254, a developmental neurotoxicant, alters energy metabolism-and intracellular signaling-associated protein networks in rat cerebellum and hippocampus

EPA Science Inventory

The vast literature on the mode of action of polychlorinated biphenyls (PCBs) indicates that PCBs are a unique model for understanding the mechanisms of toxicity of environmental mixtures of persistent chemicals. PCBs have been shown to adversely affect psychomotor function and l...

In Situ Field-Based Metabolomics for Evaluating the Impacts of Exposure to Chemicals of Emerging Concern Relative to Other Stressors

EPA Science Inventory

Significant attention is being devoted to the potential impacts on ecosystems from exposure to chemicals of emerging concern (CECs; including pharmaceuticals, personal-care products, etc.). Many of these are persistent, distributed globally, and have been shown to cause adverse i...

A randomized controlled trial to prevent childhood obesity through early childhood feeding and parenting guidance: Rationale and design of study

USDA-ARS?s Scientific Manuscript database

Early and rapid growth in infants is strongly associated with early development and persistence of obesity in young children. Substantial research has linked child obesity/overweight to increased risks for serious health outcomes, which include adverse physical, psychological, behavioral, or social ...

Teachers' Perceptions of Bullying: Hindsight Bias in Relation to Victim Responses

ERIC Educational Resources Information Center

Sherman, Karen J.

2012-01-01

Bullying, a common, persistent, and detrimental occurrence in schools, adversely affects the social, emotional, behavioral, and psychological well-being of children and youth. Independent variables that have been studied among children and youth involved in bullying in school settings are delineated, ways that bullying has been assessed and…

Concrete Roses: Examining the Resilience of Academically Successful Latino Students

ERIC Educational Resources Information Center

Alfaro, Daisy Denise

2013-01-01

This study focuses on the academic resilience exhibited by urban, low-income, first college generation Latino students, as they navigated numerous risk factors and persisted from early education to law school. In order to uncover the protective factors that allowed resilient Latino students to overcome adversity within the K-20 educational…

Prenatal Tobacco Exposure: Developmental Outcomes in the Neonatal Period

ERIC Educational Resources Information Center

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

2011-01-01

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

What influences persistence with medicines? A multinational discrete choice experiment of 2549 patients.

PubMed

Holmes, Emily A F; Morrison, Valerie L; Hughes, Dyfrig A

2016-08-01

The aim was to examine patients' stated preferences to persist with medicines and to explore the influence of psychosocial and sociocognitive factors. Community-dwelling, hypertensive patients recruited from nine European countries were invited to complete a discrete choice experiment (DCE) with attributes for treatment benefits, mild yet common adverse drug reactions (ADRs), rare but potentially life-threatening ADRs and dosing frequency. Patients responded to the binary choice of which medicine would they be most likely to continue taking. Data were analyzed using a random effects logit model. Two thousand five hundred and forty-nine patients from Austria (n = 321), Belgium (n = 175), England (n = 315), Germany (n = 266), Greece (n = 288), Hungary (n = 322), the Netherlands (n = 231), Poland (n = 312) and Wales (n = 319) completed the DCE. All attributes significantly influenced patients' stated preference to persist with medications (P < 0.05). Patients were willing to accept decreases in treatment benefits of 50.6 percentage points (95% CI 46.1, 57.9) for a very rare (as opposed to rare) risk of severe ADR, 28.3 percentage points (95% CI 25.2, 33.1) for a once daily instead of twice daily dosing and 0.74 percentage points (95% CI 0.67, 0.85) for a 1% point reduction in mild ADRs. Models accounting for psychosocial and sociocognitive characteristics were significantly different from the base case. Patients' intention to persist with treatment was associated with their willingness to trade potential benefits, harms and dosing frequency. Psychosocial and sociocognitive factors influenced the extent of trading. The utility model may have value in assessing patients' likelihood of persisting with medicines and to tailor treatment to maximize persistence. © 2016 The British Pharmacological Society.

Biosafety of parenteral Brucella abortus RB51 vaccine in bison calves

USGS Publications Warehouse

Roffe, T.J.; Olsen, S.C.; Gidlewski, T.; Jensen, A.E.; Palmer, M.V.; Huber, R.

1999-01-01

Vaccination is considered among the primary management tools for reducing brucellosis prevalence in Greater Yellowstone Area (GYA) ungulates. Before their use, however, vaccine safety and efficacy must be demonstrated. Twenty-seven female bison (Bison bison) calves (approx 5 months old) were vaccinated with Brucella abortus Strain RB51 (1.5 x 1010 colony forming units [CFU], subcutaneously) as part of routine management. We assessed the persistence, pathology, shedding, and transmission associated with RB51 by serial necropsy, bacteriology, histopathology, and serology of 20 of these 27 vaccinated calves, and RB51 serology of 10 nonvaccinated, commingling adult females. With the exception of 1 calf, RB51 dot-blot titers at necropsy were <1:80. Strain RB51 was cultured from lymph nodes in 4 of 4 calves at 14 weeks postvaccination (PV), 4 of 4 calves at 18 weeks PV, 1 of 4 calves at 22 weeks PV, 3 of 4 at 26 weeks PV, and 0 of 4 calves at 30 weeks PV. No gross lesions were observed. Mild histologic changes occurred only in a few draining lymph nodes early in sampling. Adverse clinical effects were not observed in vaccinates. Swabs from nasopharynx, conjunctiva, rectum, and vagina were uniformly culture negative for RB51. Strain RB51 dot-blot assays of bison cows were negative at a 1:20 dilution at 26 weeks PV. Our results suggest that RB51 persists longer in bison calves than in domestic cattle and is systemically distributed within lymphatic tissues. However, bison apparently clear the RB51 vaccine strain without shedding, transmission, or significant adverse reactions.

Optimism and recovery after acute coronary syndrome: a clinical cohort study.

PubMed

Ronaldson, Amy; Molloy, Gerard J; Wikman, Anna; Poole, Lydia; Kaski, Juan-Carlos; Steptoe, Andrew

2015-04-01

Optimism is associated with reduced cardiovascular mortality, but its impact on recovery after acute coronary syndrome (ACS) is poorly understood. We hypothesized that greater optimism would lead to more effective physical and emotional adaptation after ACS and would buffer the impact of persistent depressive symptoms on clinical outcomes. This prospective observational clinical study took place in an urban general hospital and involved 369 patients admitted with a documented ACS. Optimism was assessed with a standardized questionnaire. The main outcomes were physical health status, depressive symptoms, smoking, physical activity, and fruit and vegetable consumption measured 12 months after ACS, and composite major adverse cardiac events (cardiovascular death, readmission with reinfarction or unstable angina, and coronary artery bypass graft surgery) assessed over an average of 45.7 months. We found that optimism predicted better physical health status 12 months after ACS independently of baseline physical health, age, sex, ethnicity, social deprivation, and clinical risk factors (B = 0.65, 95% confidence interval [CI] = 0.10-1.20). Greater optimism also predicted reduced risk of depressive symptoms (odds ratio = 0.82, 95% CI = 0.74-0.90), more smoking cessation, and more fruit and vegetable consumption at 12 months. Persistent depressive symptoms 12 months after ACS predicted major adverse cardiac events over subsequent years (odds ratio = 2.56, 95% CI = 1.16-5.67), but only among individuals low in optimism (optimism × depression interaction; p = .014). Optimism predicts better physical and emotional health after ACS. Measuring optimism may help identify individuals at risk. Pessimistic outlooks can be modified, potentially leading to improved recovery after major cardiac events.

[Documented effects of SSRI preparations in anxiety].

PubMed

Allgulander, C

1998-05-20

The article consists in a review of the clinical evidence for treating anxiety disorders with selective serotonin re-uptake inhibitors (SSRIs). Sufficient documentation now exists to support the use of SSRIs in treating panic and obsessive-compulsive disorders, and in Sweden moclobemide is now approved for use in treating social phobia, and buspirone for use in treating generalised anxiety disorder. Further documentation of the treatment of post-traumatic stress disorder with SSRIs is probably to be expected. Benzodiazepines remain the most commonly used anxiolytics. Although persistent adverse sexual reactions, and withdrawal symptoms upon abrupt termination of medication, are notable side effects of SSRIs, patients become measurably more self-confident and focused, and manage risks more adequately. This underscores the need of further research into the interrelationship of personality traits and anxiety symptoms.

Ecological risk assessment of TBT in Ise Bay.

PubMed

Yamamoto, Joji; Yonezawa, Yoshitaka; Nakata, Kisaburo; Horiguchi, Fumio

2009-02-01

An ecological risk assessment of tributyltin (TBT) in Ise Bay was conducted using the margin of exposure (MOE) method. The assessment endpoint was defined to protect the survival, growth and reproduction of marine organisms. Sources of TBT in this study were assumed to be commercial vessels in harbors and navigation routes. Concentrations of TBT in Ise Bay were estimated using a three-dimensional hydrodynamic model, an ecosystem model and a chemical fate model. Estimated MOEs for marine organisms for 1990 and 2008 were approximately 0.1-2.0 and over 100 respectively, indicating a declining temporal trend in the probability of adverse effects. The chemical fate model predicts a much longer persistence of TBT in sediments than in the water column. Therefore, it is necessary to monitor the harmful effects of TBT on benthic organisms.

Disorder-induced transitions in resonantly driven Floquet topological insulators

NASA Astrophysics Data System (ADS)

Titum, Paraj; Lindner, Netanel H.; Refael, Gil

2017-08-01

We investigate the effects of disorder in Floquet topological insulators (FTIs) occurring in semiconductor quantum wells. Such FTIs are induced by resonantly driving a transition between the valence and conduction bands. We show that when disorder is added, the topological nature of such FTIs persists as long as there is a mobility gap at the resonant quasienergy. For strong enough disorder, this gap closes and all the states become localized as the system undergoes a transition to a trivial insulator. Interestingly, the effects of disorder are not necessarily adverse: we show that in the same quantum well, disorder can also induce a transition from a trivial to a topological system, thereby establishing a Floquet topological Anderson insulator (FTAI). We identify the conditions on the driving field necessary for observing such a transition.

Effects of exposure to oil spills on human health: Updated review.

PubMed

Laffon, Blanca; Pásaro, Eduardo; Valdiglesias, Vanessa

2016-01-01

Oil spills may involve health risks for people participating in the cleanup operations and coastal inhabitants, given the toxicological properties of the oil components. In spite of this, only after a few major oil spills (crude oil or fuel oil no. 6) have studies on effects of exposure to diverse aspects of human health been performed. Previously, Aguilera et al. (2010) examined all documents published to that date dealing with any type of human health outcome in populations exposed to oil spills. The aim of the present review was to compile all new information available and determine whether evidence reported supports the existence of an association between exposure and adverse human health risks. Studies were classified in three groups according to type of health outcome addressed: (i) effects on mental health, (ii) physical/physiological effects, and (iii) genotoxic, immunotoxic, and endocrine toxicity. New studies published on oil-spill-exposed populations-coastal residents in the vicinity of the spills or participants in cleanup operations-provide additional support to previous evidence on adverse health effects related to exposure regarding different parameters in all three categories considered. Some of the observed effects even indicated that several symptoms may persist for some years after exposure. Hence, (1) health protection in these individuals should be a matter of concern; and (2) health risk assessment needs to be carried out not only at the time of exposure but also for prolong periods following exposure, to enable early detection of any potential exposure-related harmful effects.

The role of natural and UV-induced skin pigmentation on low-fluence IPL-induced side effects: a randomized controlled trial.

PubMed

Thaysen-Petersen, Daniel; Lin, Jennifer Y; Nash, Jf; Beerwerth, Frank; Wulf, Hans C; Philipsen, Peter A; Haedersdal, Merete

2014-02-01

The risk of adverse skin effects following light-based hair removal is greater in pigmented skin based on the theory of selective photothermolysis. Thus sunlight-induced pigment i.e., facultative pigmentation, increases the risk of adverse skin effects, perhaps disproportionately. The aim of this study was to evaluate the influence of constitutive and facultative skin pigmentation on low-fluence intense pulsed light (IPL)-induced adverse skin effects. Twenty-one subjects with Fitzpatrick skin type II-IV were enrolled. Two buttock blocks were randomized to receive 0 or 8 solar simulated ultraviolet radiation (UVR) exposures of consecutively increasing Standard Erythema Doses (2-4 SED). Each block was subdivided into four sites, randomized to receive IPL of 0, 7, 8, or 10 J/cm(2) , once a week for 3 weeks. Biopsies were taken 16-24 hours after the first IPL exposure and subjects were seen 1 and 4 weeks after the last IPL exposure. Outcome measures were: (i) skin reactions, (ii) pain, (iii) mRNA expression of pigment-markers microphthalmia-associated transcription factor (MITF) and pro-opiomelanocortin (POMC), and (iv) clinical appearance of biopsy wounds. Skin pigmentation increased after UVR (baseline median 13.8%, after UVR 28.1%, P = 0.0001) in all skin types. Subjects reported low pain intensities (median 1.5, scale 0-10) and experienced transient erythema immediately after IPL exposure. No persistent erythema, blisters, crusting, textual, or pigment changes were observed. The risk of erythema and pain intensities increased with IPL dose and skin pigmentation (P < 0.03). There was no difference in pain or skin reactions in skin with similar degree of natural and facultative pigmentation (P ≥ 0.104). Expression of cellular pigment-markers was not influenced by IPL exposure, neither in constitutive nor in facultative pigmented skin. Clinical appearance of biopsy wounds was unaffected by IPL exposure. The prevalence and intensity of low-fluence IPL-induced adverse skin effects depended on IPL dose and skin pigmentation regardless of the origin, i.e., constitutive versus UV induced. © 2013 Wiley Periodicals, Inc.

Life Span Studies of ADHD-Conceptual Challenges and Predictors of Persistence and Outcome.

PubMed

Caye, Arthur; Swanson, James; Thapar, Anita; Sibley, Margaret; Arseneault, Louise; Hechtman, Lily; Arnold, L Eugene; Niclasen, Janni; Moffitt, Terrie; Rohde, Luis Augusto

2016-12-01

There is a renewed interest in better conceptualizing trajectories of attention-deficit/hyperactivity disorder (ADHD) from childhood to adulthood, driven by an increased recognition of long-term impairment and potential persistence beyond childhood and adolescence. This review addresses the following major issues relevant to the course of ADHD in light of current evidence from longitudinal studies: (1) conceptual and methodological issues related to measurement of persistence of ADHD, (2) estimates of persistence rate from childhood to adulthood and its predictors, (3) long-term negative outcomes of childhood ADHD and their early predictors, and (4) the recently proposed new adult-onset ADHD. Estimates of persistence vary widely in the literature, and diagnostic criteria, sample characteristics, and information source are the most important factors explaining variability among studies. Evidence indicates that ADHD severity, comorbid conduct disorder and major depressive disorder, and treatment for ADHD are the main predictors of ADHD persistence from childhood to adulthood. Comorbid conduct disorder and ADHD severity in childhood are the most important predictors of adverse outcomes in adulthood among children with ADHD. Three recent population studies suggested the existence of a significant proportion of individuals who report onset of ADHD symptoms and impairments after childhood. Finally, we highlight areas for improvement to increase our understanding of ADHD across the life span.

Life Span Studies of ADHD—Conceptual Challenges and Predictors of Persistence and Outcome

PubMed Central

Caye, Arthur; Swanson, James; Thapar, Anita; Sibley, Margaret; Arseneault, Louise; Hechtman, Lily; Arnold, L. Eugene; Niclasen, Janni; Moffitt, Terrie

2018-01-01

There is a renewed interest in better conceptualizing trajectories of attention-deficit/hyperactivity disorder (ADHD) from childhood to adulthood, driven by an increased recognition of long-term impairment and potential persistence beyond childhood and adolescence. This review addresses the following major issues relevant to the course of ADHD in light of current evidence from longitudinal studies: (1) conceptual and methodological issues related to measurement of persistence of ADHD, (2) estimates of persistence rate from childhood to adulthood and its predictors, (3) long-term negative outcomes of childhood ADHD and their early predictors, and (4) the recently proposed new adult-onset ADHD. Estimates of persistence vary widely in the literature, and diagnostic criteria, sample characteristics, and information source are the most important factors explaining variability among studies. Evidence indicates that ADHD severity, comorbid conduct disorder and major depressive disorder, and treatment for ADHD are the main predictors of ADHD persistence from childhood to adulthood. Comorbid conduct disorder and ADHD severity in childhood are the most important predictors of adverse outcomes in adulthood among children with ADHD. Three recent population studies suggested the existence of a significant proportion of individuals who report onset of ADHD symptoms and impairments after childhood. Finally, we highlight areas for improvement to increase our understanding of ADHD across the life span. PMID:27783340

Cost-Effectiveness of Intensive versus Standard Blood-Pressure Control.

PubMed

Bress, Adam P; Bellows, Brandon K; King, Jordan B; Hess, Rachel; Beddhu, Srinivasan; Zhang, Zugui; Berlowitz, Dan R; Conroy, Molly B; Fine, Larry; Oparil, Suzanne; Morisky, Donald E; Kazis, Lewis E; Ruiz-Negrón, Natalia; Powell, Jamie; Tamariz, Leonardo; Whittle, Jeff; Wright, Jackson T; Supiano, Mark A; Cheung, Alfred K; Weintraub, William S; Moran, Andrew E

2017-08-24

In the Systolic Blood Pressure Intervention Trial (SPRINT), adults at high risk for cardiovascular disease who received intensive systolic blood-pressure control (target, <120 mm Hg) had significantly lower rates of death and cardiovascular disease events than did those who received standard control (target, <140 mm Hg). On the basis of these data, we wanted to determine the lifetime health benefits and health care costs associated with intensive control versus standard control. We used a microsimulation model to apply SPRINT treatment effects and health care costs from national sources to a hypothetical cohort of SPRINT-eligible adults. The model projected lifetime costs of treatment and monitoring in patients with hypertension, cardiovascular disease events and subsequent treatment costs, treatment-related risks of serious adverse events and subsequent costs, and quality-adjusted life-years (QALYs) for intensive control versus standard control of systolic blood pressure. We determined that the mean number of QALYs would be 0.27 higher among patients who received intensive control than among those who received standard control and would cost approximately $47,000 more per QALY gained if there were a reduction in adherence and treatment effects after 5 years; the cost would be approximately $28,000 more per QALY gained if the treatment effects persisted for the remaining lifetime of the patient. Most simulation results indicated that intensive treatment would be cost-effective (51 to 79% below the willingness-to-pay threshold of $50,000 per QALY and 76 to 93% below the threshold of $100,000 per QALY), regardless of whether treatment effects were reduced after 5 years or persisted for the remaining lifetime. In this simulation study, intensive systolic blood-pressure control prevented cardiovascular disease events and prolonged life and did so at levels below common willingness-to-pay thresholds per QALY, regardless of whether benefits were reduced after 5 years or persisted for the patient's remaining lifetime. (Funded by the National Heart, Lung, and Blood Institute and others; SPRINT ClinicalTrials.gov number, NCT01206062 .).

Safety, Effectiveness, and Treatment Persistence of Golimumab in Elderly Patients with Rheumatoid Arthritis in Real-World Clinical Practice in Japan.

PubMed

Okazaki, Masateru; Kobayashi, Hisanori; Shimizu, Hirohito; Ishii, Yutaka; Yajima, Tsutomu; Kanbori, Masayoshi

2018-06-01

Golimumab has been proven as an effective treatment for rheumatoid arthritis in clinical trials. However, there is a scarcity of data regarding its use in elderly patients in a real-world setting. This study aims to evaluate the safety, effectiveness, and treatment persistence of golimumab in elderly Japanese patients (≥ 75 years) with rheumatoid arthritis. This study was a post hoc analysis of post-marketing surveillance data on 5137 Japanese patients with active rheumatoid arthritis who received golimumab for 24 weeks. The study population was divided into two age groups (younger: < 75 years and elderly: ≥ 75 years), and the safety, effectiveness, and treatment persistence of golimumab were assessed. Also, the reasons for discontinuing golimumab treatment were analyzed by multi-logistic regression. During golimumab treatment over 24 weeks, younger and elderly groups exhibited comparable improvement of disease activity as measured by EULAR response criteria with similar overall rates of adverse events. However, the survival curve of golimumab for elderly patients was significantly different from that for younger patients due largely to the discontinuation at 4 weeks. The most common reason for discontinuation in elderly patients was patient choice, while it was disease progression in younger patients. Analysis of elderly patients who discontinued treatment by their own decision identified EULAR good response as a factor associated with continuation of golimumab treatment whereas no predictive factor associated with discontinuation was identified. The safety and effectiveness of golimumab treatment in elderly Japanese patients aged 75 years or older were comparable to those in younger patients in real-world clinical practice. Analysis of the survival curves suggested that continuous use of golimumab might further improve clinical benefit of golimumab in elderly patients, underpinning the importance of effective communication between physicians and elderly patients based on the treat-to-target strategy. Janssen Pharmaceutical K.K. and Mitsubishi Tanabe Pharma Corporation.

Biological mechanisms underlying the role of physical fitness in health and resilience

PubMed Central

Silverman, Marni N.; Deuster, Patricia A.

2014-01-01

Physical fitness, achieved through regular exercise and/or spontaneous physical activity, confers resilience by inducing positive psychological and physiological benefits, blunting stress reactivity, protecting against potentially adverse behavioural and metabolic consequences of stressful events and preventing many chronic diseases. In this review, we discuss the biological mechanisms underlying the beneficial effects of physical fitness on mental and physical health. Physical fitness appears to buffer against stress-related disease owing to its blunting/optimizing effects on hormonal stress responsive systems, such as the hypothalamic–pituitary–adrenal axis and the sympathetic nervous system. This blunting appears to contribute to reduced emotional, physiological and metabolic reactivity as well as increased positive mood and well-being. Another mechanism whereby regular exercise and/or physical fitness may confer resilience is through minimizing excessive inflammation. Chronic psychological stress, physical inactivity and abdominal adiposity have been associated with persistent, systemic, low-grade inflammation and exert adverse effects on mental and physical health. The anti-inflammatory effects of regular exercise/activity can promote behavioural and metabolic resilience, and protect against various chronic diseases associated with systemic inflammation. Moreover, exercise may benefit the brain by enhancing growth factor expression and neural plasticity, thereby contributing to improved mood and cognition. In summary, the mechanisms whereby physical fitness promotes increased resilience and well-being and positive psychological and physical health are diverse and complex. PMID:25285199

Bench-to-bedside review: Antidotal treatment of sulfonylurea-induced hypoglycaemia with octreotide

PubMed Central

Lheureux, Philippe ER; Zahir, Soheil; Penaloza, Andrea; Gris, Mireille

2005-01-01

The major potential adverse effect of use of sulfonylurea agents (SUAs) is a hyperinsulinaemic state that causes hypoglycaemia. It may be observed during chronic therapeutic dosing, even with very low doses of a SUA, and especially in older patients. It may also result from accidental or intentional poisoning in both diabetic and nondiabetic patients. The traditional approach to SUA-induced hypoglycaemia includes administration of glucose, and glucagon or diazoxide in those who remain hypoglycaemic despite repeated or continuous glucose supplementation. However, these antidotal approaches are associated with several shortcomings, including further exacerbation of insulin release by glucose and glucagon, leading only to a temporary beneficial effect and later relapse into hypoglycaemia, as well as the adverse effects of both glucagon and diazoxide. Octreotide inhibits the secretion of several neuropeptides, including insulin, and has successfully been used to control life-threatening hypoglycaemia caused by insulinoma or persistent hyperinsulinaemic hypoglycaemia of infancy. Therefore, this agent should in theory also be useful to decrease glucose requirements and the number of hypoglycaemic episodes in patients with SUA-induced hypoglycaemia. This has apparently been confirmed by experimental data, one retrospective study based on chart review, and several anecdotal case reports. There is thus a need for further prospective studies, which should be adequately powered, randomized and controlled, to confirm the probable beneficial effect of octreotide in this setting. PMID:16356235

The Effects of High-Intensity versus Low-Intensity Resistance Training on Leg Extensor Power and Recovery of Knee Function after ACL-Reconstruction

PubMed Central

Aue Sobol, Nanna; Andersen, Lars L.; Kiel, Peter; Løfholm, Peter; Magnusson, S. Peter; Krogsgaard, Michael R.

2014-01-01

Objective. Persistent weakness is a common problem after anterior cruciate ligament- (ACL-) reconstruction. This study investigated the effects of high-intensity (HRT) versus low-intensity (LRT) resistance training on leg extensor power and recovery of knee function after ACL-reconstruction. Methods. 31 males and 19 females were randomized to HRT (n = 24) or LRT (n = 26) from week 8–20 after ACL-reconstruction. Leg extensor power, joint laxity, and self-reported knee function were measured before and 7, 14, and 20 weeks after surgery. Hop tests were assessed before and after 20 weeks. Results. Power in the injured leg was 90% (95% CI 86–94%) of the noninjured leg, decreasing to 64% (95% CI 60–69%) 7 weeks after surgery. During the resistance training phase there was a significant group by time interaction for power (P = 0.020). Power was regained more with HRT compared to LRT at week 14 (84% versus 73% of noninjured leg, resp.; P = 0.027) and at week 20 (98% versus 83% of noninjured leg, resp.; P = 0.006) without adverse effects on joint laxity. No other between-group differences were found. Conclusion. High-intensity resistance training during rehabilitation after ACL-reconstruction can improve muscle power without adverse effects on joint laxity. PMID:24877078

Adverse Childhood Experiences and Alcohol Consumption in Midlife and Early Old-Age

PubMed Central

Leung, Jessica Pui Kei; Britton, Annie; Bell, Steven

2016-01-01

Aims To examine the individual and cumulative effects of adverse childhood experiences (ACEs) on alcohol consumption in midlife and early old-age, and the role of ACEs in 10-year drinking trajectories across midlife. Methods Data were from the Whitehall II study, a longitudinal British civil service-based cohort study (N = 7870, 69.5% male). Multinomial logistic regression was used to examine the individual and cumulative effects of ACEs on weekly alcohol consumption. Mixed-effect multilevel modelling was used to explore the relationship between ACEs and change in alcohol consumption longitudinally. Results Participants who were exposed to parental arguments/fights in childhood were 1.24 (95% CI 1.06, 1.45) times more likely to drink at hazardous levels in midlife (mean age 56 years) after controlling for covariates and other ACEs. For each additional exposure to an ACE, the risk of hazardous drinking versus moderate drinking was increased by 1.12 (95% CI 1.03, 1.21) after adjusting for sex, age, adult socio-economic status, ethnicity and marital status. No associations between ACEs and increased risk of hazardous drinking in early old-age (mean age 66 years) were found. In longitudinal analyses, ACEs did not significantly influence 10-year drinking trajectories across midlife. Conclusion The effect of exposure to parental arguments on hazardous drinking persists into midlife. PMID:26553290

Biological mechanisms underlying the role of physical fitness in health and resilience.

PubMed

Silverman, Marni N; Deuster, Patricia A

2014-10-06

Physical fitness, achieved through regular exercise and/or spontaneous physical activity, confers resilience by inducing positive psychological and physiological benefits, blunting stress reactivity, protecting against potentially adverse behavioural and metabolic consequences of stressful events and preventing many chronic diseases. In this review, we discuss the biological mechanisms underlying the beneficial effects of physical fitness on mental and physical health. Physical fitness appears to buffer against stress-related disease owing to its blunting/optimizing effects on hormonal stress responsive systems, such as the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. This blunting appears to contribute to reduced emotional, physiological and metabolic reactivity as well as increased positive mood and well-being. Another mechanism whereby regular exercise and/or physical fitness may confer resilience is through minimizing excessive inflammation. Chronic psychological stress, physical inactivity and abdominal adiposity have been associated with persistent, systemic, low-grade inflammation and exert adverse effects on mental and physical health. The anti-inflammatory effects of regular exercise/activity can promote behavioural and metabolic resilience, and protect against various chronic diseases associated with systemic inflammation. Moreover, exercise may benefit the brain by enhancing growth factor expression and neural plasticity, thereby contributing to improved mood and cognition. In summary, the mechanisms whereby physical fitness promotes increased resilience and well-being and positive psychological and physical health are diverse and complex.

The social context of food insecurity among persons living with HIV/AIDS in rural Uganda

PubMed Central

Tsai, Alexander C.; Bangsberg, David R.; Emenyonu, Nneka; Senkungu, Jude K.; Martin, Jeffrey N.; Weiser, Sheri D.

2011-01-01

HIV/AIDS and food insecurity are two of the leading causes of morbidity and mortality in sub-Saharan Africa, with each heightening the vulnerability to, and worsening the severity of, the other. Less research has focused on the social determinants of food insecurity in resource-limited settings, including social support and HIV-related stigma. In this study, we analyzed data from a cohort of 456 persons from the Uganda AIDS Rural Treatment Outcomes study, an ongoing prospective cohort of persons living with HIV/AIDS (PLWHA) initiating HIV antiretroviral therapy in Mbarara, Uganda. Quarterly data were collected by structured interviews. The primary outcome, food insecurity, was measured with the Household Food Insecurity Access Scale. Key covariates of interest included social support, internalized HIV-related stigma, HIV-related enacted stigma, and disclosure of HIV serostatus. Severe food insecurity was highly prevalent overall (38%) and more prevalent among women than among men. Social support, HIV disclosure, and internalized HIV-related stigma were associated with food insecurity; these associations persisted after adjusting for household wealth, employment status, and other previously identified correlates of food insecurity. The adverse effects of internalized stigma persisted in a lagged specification, and the beneficial effect of social support further persisted after the inclusion of fixed effects. International organizations have increasingly advocated for addressing food insecurity as part of HIV/AIDS programming to improve morbidity and mortality. This study provides quantitative evidence on social determinants of food insecurity among PLWHA in resource-limited settings and suggests points of intervention. These findings also indicate that structural interventions to improve social support and/or decrease HIV-related stigma may also improve the food security of PLWHA. PMID:22019367

A comparison of water quality criteria for the Great Lakes based on human and wildlife health

USGS Publications Warehouse

Ludwig, James P.; Giesy, John P.; Summer, Cheryl L.; Bowerman, William; Aulerich, Richard J.; Bursian, Steven J.; Auman, Heidi J.; Jones, Paul D.; Williams, Lisa L.; Tillitt, Donald E.; Gilbertson, Michael

1993-01-01

Water quality criteria (WQC) can be derived in several ways. The usual techniques involve hazard and risk assessment procedures. For non-persistent, non-biomagnified compounds and elements, WQC are experimentally derived from their acute and chronic toxicity to aquatic organisms. For those persistent chlorinated hydrocarbons (PCHs) that are bioaccumulated and biomagnified, these traditional techniques have not been effective, partly because effects higher in the food web were not considered. Polychlorinated biphenyls (PCBs) are the bioaccumulative synthetic chemicals of primary toxicological significance to the Great Lakes biota which have caused widespread injury to wildlife. In the Laurentian Great Lakes, the primary emphasis of hazard assessments has been on the potential for adverse effects in humans who eat fish. The primary regulatory endpoint of traditional hazard and risk assessments underlying current WQC are the probabilities of additional cancers occurring in the human population. The analysis presented here indicates that this is not adequate to restore sensitive wildlife species that are highly exposed to PCBs, especially those that have suffered serious population declines. Because WQC are legal instruments, the methods of deriving WQC have large implications for remediation, litigation, and damage assessments. Here WQC are derived for six species based on the responses of wildlife in the field or produced by feeding fish to surrogate species, rather than projecting a potential of increased cancer rates in humans. If the most sensitive wildlife species are restored and protected for very sensitive reproductive endpoints, then all components of the ecosystem, including human health, should be more adequately protected. The management of Great Lakes wildlife requires an understanding of the injury and causal relationships to persistent toxic substances.

The social context of food insecurity among persons living with HIV/AIDS in rural Uganda.

PubMed

Tsai, Alexander C; Bangsberg, David R; Emenyonu, Nneka; Senkungu, Jude K; Martin, Jeffrey N; Weiser, Sheri D

2011-12-01

HIV/AIDS and food insecurity are two of the leading causes of morbidity and mortality in sub-Saharan Africa, with each heightening the vulnerability to, and worsening the severity of, the other. Less research has focused on the social determinants of food insecurity in resource-limited settings, including social support and HIV-related stigma. In this study, we analyzed data from a cohort of 456 persons from the Uganda AIDS Rural Treatment Outcomes study, an ongoing prospective cohort of persons living with HIV/AIDS (PLWHA) initiating HIV antiretroviral therapy in Mbarara, Uganda. Quarterly data were collected by structured interviews. The primary outcome, food insecurity, was measured with the Household Food Insecurity Access Scale. Key covariates of interest included social support, internalized HIV-related stigma, HIV-related enacted stigma, and disclosure of HIV serostatus. Severe food insecurity was highly prevalent overall (38%) and more prevalent among women than among men. Social support, HIV disclosure, and internalized HIV-related stigma were associated with food insecurity; these associations persisted after adjusting for household wealth, employment status, and other previously identified correlates of food insecurity. The adverse effects of internalized stigma persisted in a lagged specification, and the beneficial effect of social support further persisted after the inclusion of fixed effects. International organizations have increasingly advocated for addressing food insecurity as part of HIV/AIDS programming to improve morbidity and mortality. This study provides quantitative evidence on social determinants of food insecurity among PLWHA in resource-limited settings and suggests points of intervention. These findings also indicate that structural interventions to improve social support and/or decrease HIV-related stigma may also improve the food security of PLWHA. Copyright © 2011 Elsevier Ltd. All rights reserved.

Recurrent persistent hypophosphatemia in a male-to-female transgender patient with anorexia nervosa: Case report.

PubMed

Beaty, L; Trees, N; Mehler, P

2017-05-01

Refeeding hypophosphatemia remains a serious and common complication during the early phases of nutritional rehabilitation and weight restoration for patients with anorexia nervosa. Typically, the risk of refeeding hypophosphatemia diminishes after the first 1-2 weeks of the refeeding process and thus, frequent monitoring serum phosphorus levels becomes less important as refeeding proceeds. Herein, we describe a case of persistent recurrent hypophosphatemia in a male-to-female transgender patient with severe anorexia nervosa. As transgender patients become increasingly seen in the realm of eating disorders, it is worth noting this phenomenon to mitigate adverse events. © 2017 Wiley Periodicals, Inc.

Endoscopic Bronchial Occlusion with Silicon Spigots for the Treatment of an Alveolar-pleural Fistula during Anti-tuberculosis Therapy for Tuberculous Empyema.

PubMed

Nishihara, Takashi; Hayama, Manabu; Okamoto, Norio; Tanaka, Ayako; Nishida, Takuji; Shiroyama, Takayuki; Tamiya, Motohiro; Morishita, Naoko; Suzuki, Hidekazu; Matsuoka, Hiroto; Hirashima, Tomonori

2016-01-01

A prolonged air leak caused by pulmonary tuberculosis is difficult to treat, and little is known about optimal treatment strategies. We herein report the case of a 60-year-old man who demonstrated tuberculous empyema with a fistula. An air leak from a tuberculous cavity in his left upper lobe persisted for approximately 4 months; surgical repair could not be performed due to a poor physical status and undernourishment. However, the air leak was successfully treated with endobronchial occlusion using two silicone spigots in left B3b and B4, without any adverse effects or aggravation of the infection.

Prevalence of Adverse Childhood Experiences in Low-Income Latino Immigrant and Nonimmigrant Children.

PubMed

Loria, Hilda; Caughy, Margaret

2018-01-01

To estimate the prevalence of adverse childhood experiences in low-income Latino children and examine differences in the prevalence of adverse childhood experiences by immigrant generational status. This is a secondary data analysis of the 2011-2012 National Survey of Children's Health, a telephone survey of parents/caregivers of a nationally representative sample of US children. The study sample was limited to Latino children in households with an annual income ≤200% of the federal poverty level (FPL) whose parents responded to a 9-item inventory of adverse childhood experiences. Descriptive statistics estimated the prevalence of adverse childhood experiences and examined differences in prevalence by immigrant generational status. Of 22 297 children, 29% (n = 6483) were Latino (9% first generation, 57% second generation, 30% third or higher generation); 25% (n = 1692) of all Latino children were exposed to 2 or more adverse childhood experiences. Latino immigrant children had a lower prevalence (13%; n = 801) compared with nonimmigrant Latino children (40%; n = 772). The most common adverse childhood experiences were financial hardship and parent divorce/separation. The total number and mean number of adverse childhood experiences differed by child generational status, and the differences persisted after stratification by age and FPL. The prevalence of exposure to adverse childhood experiences was highest among third- or higher-generation nonimmigrant children and lowest among second-generation immigrant children. The prevalence of adverse childhood experiences in low-income Latino children is similar to the prevalence for all US children; however, the prevalence is significantly higher in nonimmigrant children. Targeted screening to address adverse childhood experiences, policy changes, and guidance regarding care practices to address adverse childhood experiences in Latino children are needed. Copyright © 2017 Elsevier Inc. All rights reserved.

Levocetirizine in persistent allergic rhinitis: continuous or on-demand use? A pilot study.

PubMed

Canonica, Giorgio Walter; Fumagalli, Federica; Guerra, Laura; Baiardini, Ilaria; Compalati, Enrico; Rogkakou, Anthi; Massacane, Pierangela; Gamalero, Cinzia; Riccio, Anna Maria; Scordamaglia, Antonio; Passalacqua, Giovanni

2008-10-01

Allergic rhinitis is a high-prevalence disease that affects quality of life (QOL), sleep quality and productivity of patients. According to the ARIA initiative, it is classified as intermittent and persistent, the latter being the most troublesome. The aim of this randomized, open-label, 6-month, pilot study was to determine whether levocetirizine 5 mg administered continuously once daily in the morning was better than levocetirizine 5 mg on-demand in symptomatic subjects with persistent allergic rhinitis. Total and individual symptom scores were recorded in a diary card throughout the study. QOL, quality of sleep, nasal cytology, rate of drug intake, and safety were also assessed at pre-defined time-points. In all, adult patients (31 in each group) were enrolled, of whom 22 dropped out. Both treatment regimens considerably decreased the total and individual symptoms scores from baseline and achieved similar levels up to week 14. Continuous treatment was generally better than on-demand from week 15 onwards, reaching statistical significance from weeks 17 to 21 (from week 19 to 21 for nasal pruritus). Both regimens substantially improved QOL and sleep quality. Both treatments were well tolerated, although the on-demand group reported more adverse events. The present open label study in 62 patients indicates that levocetirizine 5 mg reliably controls persistent rhinitis over a period of 6 months, and shows a trend to be more effective in controlling the symptoms of rhinitis, improving QOL and decreasing nasal inflammation, when administered as long-term continuous therapy rather than as on-demand therapy.

Evaluation of persistent hydrophobic organic compounds in the Columbia River Basin using semipermeable-membrane devices

USGS Publications Warehouse

McCarthy, K.A.; Gale, R.W.

2001-01-01

Persistent hydrophobic organic compounds are of concern in the Columbia River because they have been correlated with adverse effects on wildlife. We analysed samples from nine main-stem and six tributary sites throughout the Columbia River Basin (Washington and Oregon) for polychlorinated dibenzo-p-dioxins, dibenzofurans, polychlorinated biphenyls, organochlorine pesticides, and priority-pollutant polycyclic aromatic hydrocarbons. Because these compounds may have important biological consequences at aqueous concentrations well below the detection limits associated with conventional sampling methods, we used semipermeable-membrane devices to sample water and achieved parts-per-quintillion detection limits. All of these compound classes were prevalent within the basin, but concentrations of many analytes were highest in the vicinity of Portland-Vancouver, indicating that the Willamette subbasin-and perhaps the urban area in particular-is an important source of these compounds. Data collected during basin low-flow conditions in 1997 and again during basin high-flow conditions in 1998 indicate that in-stream processes such as dilution by relatively clean inflow, and flow through island hyporheic zones may be important mechanisms for attenuating dissolved concentrations of hydrophobic compounds.

Hypersomnolence and Sleep-related Complaints in Metropolitan, Urban, and Rural Georgia

PubMed Central

Decker, Michael J.; Lin, Jin-Mann S.; Tabassum, Humyra

2009-01-01

Persistent daytime hypersomnolence is associated with significant morbidity and mortality, but its prevalence in the population has been poorly documented. This study sought to characterize the prevalence of persistent daytime hypersomnolence, difficulties initiating and maintaining sleep, unrefreshing sleep, snoring, and the presence of physician-diagnosed sleep disorders in metropolitan, urban, and rural US Georgia populations. Between September 2004 and July 2005, a total of 6,530 randomly selected well and unwell adults, identified by screening interviews of 10,837 households (contacted by random digit dialing), completed a detailed phone interview. Sixteen percent reported persistent problems staying awake during the day; 26% reported persistent problems falling asleep at night; 31% experienced problems sleeping through the night; 34% were bothered by unrefreshing sleep; and 33% reported that they snored. In spite of the high occurrence of reported persistent sleep problems, only 10% of the survey participants reported having been diagnosed with a sleep disorder. These study findings highlight the need for increased public and clinician awareness with respect to proactively indentifying signs and symptoms of sleep disorders, a better understanding of their adverse impact upon morbidity and mortality, and their negative impact upon socioeconomic and academic potential. PMID:19066308

Effect of potassium perfluorooctanesulfonate, perfluorooctanoate and octanesulfonate on the phase transition of dipalmitoylphosphatidylcholine (DPPC) bilayers

PubMed Central

Xie, W.; Kania-Korwel, I.; Bummer, P. M.; Lehmler, H.-J.

2007-01-01

Summary Perfluorooctanesulfonic acid (PFOS) is a persistent environmental pollutant that may cause adverse effects by inhibiting pulmonary surfactant. To gain further insights in this potential mechanism of toxicity, we investigated the interaction of PFOS potassium salt with dipalmitoylphosphatidylcholine (DPPC) – the major component of pulmonary surfactant – using steady-state fluorescence anisotropy spectroscopy and DSC (differential scanning calorimetry). In addition, we investigated the interactions of two structurally related compounds, perfluorooctanoic acid (PFOA) and octanesulfonic acid (OS) potassium salt, with DPPC. In the fluorescence experiments a linear depression of the main phase transition temperature of DPPC (Tm) and an increased peak width was observed with increasing concentration of all three compounds, both using 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene p-toluenesulfonate (TMA-DPH) as fluorescent probes. PFOS caused an effect on Tm and peak width at much lower concentrations because of its increased tendency to partition onto DPPC bilayers, i.e., the partition coefficients decrease in the K(PFOS) > K(PFOA) ≫ K(OS). Similar to the fluorescence anisotropy measurements, all three compounds caused a linear depression in the onset of the main phase transition temperature and a significant peak broadening in the DSC experiments, with PFOS having the most pronounced effect of the peak width. The effect of PFOS and other fluorinated surfactants on DPPC in both mono- and bilayers may be one mechanism by which these compounds causes adverse biological effects. PMID:17349969

Biomarkers for Adverse Pregnancy Outcomes in Rheumatic Diseases.

PubMed

Soh, May Ching; Nelson-Piercy, Catherine

2017-05-01

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

Changes in Food Selectivity in Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Bandini, Linda G.; Curtin, Carol; Phillips, Sarah; Anderson, Sarah E.; Maslin, Melissa; Must, Aviva

2017-01-01

Food selectivity is a common problem in children with autism spectrum disorder (ASD) and has an adverse impact on nutrient adequacy and family mealtimes. Despite recent research in this area, few studies have addressed whether food selectivity present in children with ASD persists into adolescence. In this study, we assessed food selectivity in 18…

Academic Resilience and Achievement: Self-Motivational Resources That Guide Faculty Participation in Instructional Technology Training at a Mexican University

ERIC Educational Resources Information Center

Montero-Hernandez, Virginia; Levin, John; Diaz-Castillo, Maribel

2014-01-01

This study uses narrative analysis to understand the ways in which Mexican university faculty members used their self-motivational resources to persist in an instructional technology training program within adverse work conditions. The methodology included interviews and participant observation. Findings suggest that faculty's academic resilience…

Acrolein-induced arrhythmias and autonomic imbalance due to early life persistent vitamin D deficiency in mice is mediated by the putative anti-aging factor klotho.

EPA Science Inventory

Although epidemiological, human and animal data have conclusively linked air pollution exposure to adverse cardiovascular outcomes, the severity of responses depends on a number of intrinsic (diet, underlying disease, etc) and extrinsic (e.g. co-stressors) factors. As such, cardi...

Toxic stress and child refugees.

PubMed

Murray, John S

2018-01-01

The purpose of this article was to describe the phenomenon of toxic stress and its impact on the physical and mental health of child refugees. Almost two decades ago, researchers found that recurring adverse childhood events (ACEs; e.g., physical, psychological, and sexual abuse, neglect, and household dysfunction such as substance abuse, mental illness, and criminal behavior) were associated with a significant increase in serious illnesses during adulthood. Illnesses include heart, lung, and liver disease, cancer, and bone fractures. The scientists reported that experiencing four or more ACEs during childhood significantly increases the risk for toxic stress. Toxic stress is defined as the exposure to extreme, frequent, and persistent adverse events without the presence of a supportive caretaker. There is a paucity of literature related to toxic stress and child refugees. However, it has been clearly established that the prolonged brutal and traumatizing war in Syria is having a profound impact on the physical and mental health of child refugees at a distressing rate. Prevention of toxic stress should be a primary goal of all pediatric healthcare professionals working with child refugees. While this seems daunting given the population, and the seemingly insurmountable stressors they experience, some basic interventions should be considered. Providing basic anticipatory guidance to parents and caregivers of child refugees, to encourage positive parenting and strengthening support networks, will be highly effective in developing the requisite buffers that mitigate the effects of stress and avoid toxic stress. Efforts should also be focused on addressing caregiver stress and improving their ability to provide safe, reliable, and nurturing care that will help to mitigate any stress response experienced by a child. It is critical that greater awareness be placed on the effects of toxic stress on child refugees who are exposed to significant adverse events early in life. © 2017 Wiley Periodicals, Inc.

Efficacy of Rhizophora mangle aqueous bark extract (RMABE) in the treatment of aphthous ulcers: a pilot study.

PubMed

de Armas, Elizabeth; Sarracent, Yamina; Marrero, Eva; Fernández, Octavio; Branford-White, Christopher

2005-11-01

Rhizophora mangle aqueous bark extract (RMABE) (CIKRON-H), has been used as antiseptic and skin wound healing promoter. The present study was a randomised, single-blinded, placebo control trial conducted to asses the efficacy of RMABE in treating oral aphthous ulcers. Patients (n = 32) with aphthous ulcers were randomised to received placebo solution or RMABE topically, once a day, from Monday to Friday, until they healed. The efficacy of the treatment was evaluated by physician clinical observations (time to heal, change in condition), the quality of the patient's life and the tolerability through recording adverse effects. No demographic differences were noted between the two groups at base-line. Seven days after treatment, 12 of the 17 patients in the RMABE group (71%) were completely healed of their aphthous ulcers, with repaired mucosa and no symptoms of ulcers, compared with one in 15 patients in the placebo group (7%) (p < 0.0001). The time taken for the signs and symptoms of ulcers to diminish was also higher in the placebo than in RMABE-treatment group (erythema: placebo 10.54 +/- 1.24, RMABE 4.94 +/- 0.72 days, p = 0.0003; ardour: placebo 7.00 +/- 0.76, RMABE 2.93 +/- 0.49 days, p = 0.0001; and pain: placebo 7.43 +/- 1.21, RMABE 2.92 +/- 0.23 days, p = 0.0011). No subject showed any sign of adverse effects. These observations demonstrate that the R. mangle aqueous bark extract reduced the time to repair mucosal tissue, erythema, ardour and pain persistence. There was no evidence any adverse effects. This is the first time that the R. mangle extract has been reported to have mouth mucosa healing properties.

Late Administration of a Palladium Lipoic Acid Complex (POLY-MVA) Modifies Cardiac Mitochondria but Not Functional or Structural Manifestations of Radiation-Induced Heart Disease in a Rat Model

PubMed Central

Sridharan, Vijayalakshmi; Seawright, John W.; Antonawich, Francis J.; Garnett, Merrill; Cao, Maohua; Singh, Preeti; Boerma, Marjan

2017-01-01

Exposure of the heart to ionizing radiation can cause adverse myocardial remodeling. In small animal models, local heart irradiation causes persistent alterations in cardiac mitochondrial function and swelling. POLY-MVA is a dietary supplement that contains a palladium lipoic acid complex that targets mitochondrial complex I and has been demonstrated to have greater redox potential than lipoic acid alone. POLY-MVA improves mitochondrial function and anti-oxidant enzyme activity in the aged rat heart. In this study, we tested whether POLY-MVA can mitigate cardiac effects of ionizing radiation. Adult male rats were exposed to local heart X rays with a daily dose of 9 Gy for 5 consecutive days. Eighteen weeks after irradiation, POLY-MVA was administered orally at 1 ml/kg bodyweight per day during weekdays, for 6 weeks. Alterations in cardiac function as measured with echocardiography coincided with enhanced mitochondrial swelling, a reduction in mitochondrial expression of complex II, manifestations of adverse remodeling such as a reduction in myocardial microvessel density and an increase in collagen deposition and mast cell numbers. POLY-MVA enhanced left ventricular expression of superoxide dismutase 2, but only in sham-irradiated animals. In irradiated animals, POLY-MVA caused a reduction in markers of inflammatory infiltration, CD2 and CD68. Moreover, POLY-MVA mitigated the effects of radiation on mitochondria. Nonetheless, POLY-MVA did not mitigate adverse cardiac remodeling, suggesting that this tissue remodeling may not be alleviated by altering cardiac mitochondria alone. However, we cannot exclude the possibility that an earlier onset of POLY-MVA administration may have more profound effects on radiation-induced cardiac remodeling. PMID:28231026

Influence of radical prostatectomy for prostate cancer on work status and working life 3 years after surgery.

PubMed

Dahl, Sigrun; Loge, Jon Håvard; Berge, Viktor; Dahl, Alv Andreas; Cvancarova, Milada; Fosså, Sophie Dorothea

2015-06-01

The purpose of this study is to study the influence of radical prostatectomy (RP) for prostate cancer on work status and working life in men 3 years after surgery. In a prospective, questionnaire-based study on adverse effects after RP, 330 prostate cancer (PCa) patients who had been active in the workforce before RP described their work status 3 years after having surgery. We dichotomized their postoperative work status into "unchanged or increased" versus "reduced." The participants also reported whether their working life was influenced by the PCa trajectory to no, some, or a great extent. Univariate and multiple logistic regression models were established with sociodemographic and clinical characteristics as independent variables and "work status" or "influence of PCa trajectory on working life" as dependent variables. Twenty-five percent of the participants had retired. Of the remaining participants, approximately 20 % had a reduced work status, which in the multivariate analyses was significantly associated with increasing age. One third of the men still active in the workforce considered the PCa to negatively influence their working life. This was independently associated with bother related to urinary leakage, fatigue, and having undergone additional oncological therapy (pelvic radiotherapy and/or hormone treatment). Though RP does not affect work status in most men, approximately one third of them experience problems in their working life due to adverse effects related to RP and/or additional post-RP anti-cancer therapy. Most PCa survivors can expect to remain in the workforce for at least 3 years after RP, but for some, persistent adverse effects after RP and /or additional anti-cancer treatment negatively affect their working life. Pre-RP counseling of men within the workforce should cover possible post-RP changes concerning work status and working life.

The Psychiatric Consequences of Cannabinoids.

PubMed

De Aquino, Joao P; Sherif, Mohamed; Radhakrishnan, Rajiv; Cahill, John D; Ranganathan, Mohini; D'Souza, Deepak C

2018-04-17

With rising rates of cannabis use in the general population and an increasing number of US states legalizing both recreational and medical cannabis use, it is important to be informed about the adverse consequences of cannabinoids. This Commentary provides an overview of the psychiatric effects of plant-based and synthetic cannabinoids, differentiating acute effects from effects associated with persistent use. Cannabinoids produce multiphasic and dose-dependent effects on anxiety, mood, and perception, in addition to impairing cognition and psychomotor function. Generally, in healthy individuals, the acute negative psychiatric effects of cannabinoids are rated as milder in severity compared with those in individuals with pre-existing psychiatric disorders. With chronic exposure to cannabinoids, the probability of developing tolerance and dependence can increase. A problematic pattern of cannabis use can lead to clinically significant impairment and distress. Cessation of cannabis use in individuals who are tolerant and dependent can lead to a withdrawal syndrome. Studies report long-term cannabis exposure has been linked to psychiatric disorders, such as anxiety, psychotic and mood disorders. Limitations to the existing evidence notwithstanding, the plausibility of a causal relationship between cannabinoid exposure and persistent negative psychiatric outcomes, and the potential for long-term brain changes by regular exposure, especially for adolescents, are sufficient to warrant discussions with clinicians and the public. Implications for clinicians who certify, prescribe, or care for patients receiving cannabinoids are discussed, and a case is made for further research to better understand the impact of legalization on public mental health. Copyright © 2018. Published by Elsevier Inc.

Designing for resilience

NASA Astrophysics Data System (ADS)

Dwivedi, Anurag

2014-06-01

The motivation for this work comes from a desire to improve resilience of mission critical cyber enabled systems including those used in critical infrastructure domains such as cyber, power, water, fuel, financial, healthcare, agriculture, and manufacturing. Resilience can be defined as the ability of a system to persistently meet its performance requirements despite the occurrence of adverse events. Characterizing the resilience of a system requires a clear definition of the performance requirements of the system of interest and an ability to quantify the impact on performance by the adverse events of concern. A quantitative characterization of system resilience allows the resilience requirements to be included in the system design criteria. Resilience requirements of a system are derived from the service level agreements (SLAs), measures of effectiveness (MOEs), and measures of performance (MOPs) of the services or missions supported by the system. This paper describes a methodology for designing resilient systems. The components of the methodology include resilience characterization for threat models associated with various exposure modes, requirements mapping, subsystem ranking based on criticality, and selective implementation of mitigations to improve system resilience to a desired level.

Anesthetic Management of a Patient With Multiple Sclerosis

PubMed Central

Ohshita, Naohiro; Gamoh, Shoko; Kanazumi, Masahiko; Nakajima, Masahiro; Momota, Yoshihiro; Tsutsumi, Yasuo M.

2017-01-01

A 54-year-old woman diagnosed with multiple sclerosis (MS) at the age of 19 years was scheduled to undergo temporomandibular joint mobilization. She was currently in a remission phase from her MS but with persistent sequelae, including impaired eyesight and muscle weakness of the limbs. In addition, the blood vessels in her upper limbs were compromised by the formation of internal shunts secondary to vascular prosthesis replacements for plasma exchange therapy in MS. After a previous joint mobilization surgery, her temporomandibular joint developed adhesions with resultant trismus. One of the adverse effects of general anesthesia can be exacerbations of MS symptoms. Minimizing mental and physical stress caused by surgical and anesthetic procedures and maintenance of stable body temperature are important considerations. Awake intubation was performed under sedation with midazolam and fentanyl. After intubation, anesthesia was induced with propofol, remifentanil, and rocuronium. Maintenance of anesthesia was achieved with oxygen-N2O-sevoflurane, remifentanil, fentanyl, and rocuronium. In this case, no adverse events occurred intraoperatively. However, the patient experienced lingering weakness of the limbs in the postoperative period, and activities of daily living of the patient were affected. PMID:28604090

[Structural plasticity associated with drugs addiction].

PubMed

Zhu, Jie; Cao, Guo-fen; Dang, Yong-hui; Chen, Teng

2011-12-01

An essential feature of drug addiction is that an individual continues to use drug despite the threat of severely adverse physical or psychosocial consequences. Persistent changes in behavior and psychological function that occur as a function of drugs of abuse are thought to be due to the reorganization of synaptic connections (structural plasticity) in relevant brain circuits (especially the brains reward circuits). In this paper we summarized evidence that, indeed, exposure to amphetamine, cocaine, nicotine or morphine produced persistent changes in the structure of dendrites and dendritic spines on cells in relevant brain regions. We also approached the potential molecular mechanisms of these changes. It is suggested that structural plasticity associated with exposure to drugs of abuse reflects a reorganization of patterns of synaptic connectivity in these neural systems, a reorganization that alters their operation, thus contributing to some of the persistent sequela associated with drug use-including addiction.

Long-term overexpression of human granulocyte colony-stimulating factor in transgenic mice: persistent neutrophilia with no increased mortality for more than one year.

PubMed

Serizawa, I; Amano, K; Ishii, H; Ichikawa, T; Kusaka, M; Taguchi, T; Kiyokawa, N; Fujimoto, J

2000-06-01

To investigate possible adverse consequences of persistent neutrophil overproduction, mice transgenic for human granulocyte colony-stimulating factor (hG-CSF) were studied for more than 1 year. They showed marked granulocytopoiesis and neutrophilia. Continuous medullary and extramedullary granulocytopoiesis resulted in marked changes in bone and liver. In the liver, haemorrhage and focal necrosis and a few haemangiosarcomas were present, presumably caused by the destructive granulocytopoiesis. Despite the high incidence of lung infiltration by mature neutrophils, lung lesions rarely appeared. Although there was a persistent increase in neutrophils, mortality of the mice did not differ from that of non-transgenic littermates at least within 1 year after birth. Factors other than overproduction of G-CSF and extensive neutrophilia could be required for the development of neutrophil-mediated acute and chronic tissue damage. Copyright 2000 Academic Press.

Genital anomalies in boys and the environment.

PubMed

Main, Katharina M; Skakkebaek, Niels E; Virtanen, Helena E; Toppari, Jorma

2010-04-01

The prevalence of male reproductive disorders, such as testicular cancer and impaired semen quality, is increasing in many, albeit not all, countries. These disorders are aetiologically linked with congenital cryptorchidism and hypospadias by common factors leading to perinatal disruption of normal testis differentiation, the testicular dysgenesis syndrome (TDS). There is recent evidence that also the prevalence of genital malformations is increasing and the rapid pace of increase suggests that lifestyle factors and exposure to environmental chemicals with endocrine disrupting properties may play a role. Recent prospective studies have established links between perinatal exposure to persistent halogenated compounds and cryptorchidism, as well as between phthalates and anti-androgenic effects in newborns. Maternal alcohol consumption, mild gestational diabetes and nicotine substitutes were also identified as potential risk factors for cryptorchidism. It may be the cocktail effect of many simultaneous exposures that result in adverse effects, especially during foetal life and infancy. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Helicobacter pylori vaccine: from past to future.

PubMed

Agarwal, Kanishtha; Agarwal, Shvetank

2008-02-01

Helicobacter pylori infection is highly prevalent worldwide and is an important cause of gastritis, peptic ulcer disease, gastric mucosa-associated lymphoid tissue lymphoma (MALToma), and gastric adenocarcinoma. Infection is usually acquired during childhood and tends to persist unless treated. Because eradication requires treatment with multidrug regimens, prevention of initial infection by a suitable vaccine is attractive. Although immunization with H pylori protein subunits has been encouraging in animals, similar vaccine trials in humans have shown adjuvant-related adverse effects and only moderate effectiveness. Newer immunization approaches (use of DNA, live vectors, bacterial ghosts, and microspheres) are being developed. Several questions about when and whom to vaccinate will need to be appropriately answered, and a cost-effective vaccine production and delivery strategy will have to be useful for developing countries. For this review, we searched MEDLINE using the Medical Subject Heading (MeSH) terms Helicobacter pylori and vaccines for articles in English from 1990 to 2007.

Halogenated flame retardants: do the fire safety benefits justify the risks?

PubMed

Shaw, Susan D; Blum, Arlene; Weber, Roland; Kannan, Kurunthachalam; Rich, David; Lucas, Donald; Koshland, Catherine P; Dobraca, Dina; Hanson, Sarah; Birnbaum, Linda S

2010-01-01

Since the 1970s, an increasing number of regulations have expanded the use of brominated and chlorinated flame retardants. Many of these chemicals are now recognized as global contaminants and are associated with adverse health effects in animals and humans, including endocrine and thyroid disruption, immunotoxicity, reproductive toxicity, cancer, and adverse effects on fetal and child development and neurologic function. Some flame retardants such as polybrominated diphenyl ethers (PBDEs) have been banned or voluntarily phased out by manufacturers because of their environmental persistence and toxicity, only to be replaced by other organohalogens of unknown toxicity. Despite restrictions on further production in some countries, consumer products previously treated with banned retardants are still in use and continue to release toxic chemicals into the environment, and the worldwide use of organohalogen retardants continues to increase. This paper examines major uses and known toxic effects of commonly-used organohalogen flame retardants, replacements for those that have been phased out, their combustion by-products, and their effectiveness at reducing fire hazard. Policy and other solutions to maintain fire safety while reducing toxicity are suggested. The major conclusions are: (1) Flammability regulations can cause greater adverse environmental and health impacts than fire safety benefits. (2) The current options for end-of-life disposal of products treated with organohalogens retardants are problematic. (3) Life-cycle analyses evaluating benefits and risks should consider the health and environmental effects of the chemicals, as well as their fire safety impacts. (4) Most fire deaths and most fire injuries result from inhaling carbon monoxide, irritant gases, and soot. The incorporation of organohalogens can increase the yield of these toxic by-products during combustion. (5) Fire-safe cigarettes, fire-safe candles, child-resistant lighters, sprinklers, and smoke detectors can prevent fires without the potential adverse effects of flame retardant chemicals. (6) Alternatives to organohalogen flame retardant chemicals include using less flammable materials, design changes, and safer chemicals. To date, before evaluating their health and environmental impacts, many flame retardant chemicals have been produced and used, resulting in high levels of human exposure. As a growing literature continues to find adverse impacts from such chemicals, a more systematic approach to their regulation is needed. Before implementing new flammability standards, decision-makers should evaluate the potential fire safety benefit versus the health and environmental impacts of the chemicals, materials, or technologies likely to be used to meet the standard. Reducing the use of toxic or untested flame retardant chemicals in consumer products can protect human and animal health and the global environment without compromising fire safety.

Internet-mediated physiotherapy and pain coping skills training for people with persistent knee pain (IMPACT - knee pain): a randomised controlled trial protocol.

PubMed

Dobson, Fiona; Hinman, Rana S; French, Simon; Rini, Christine; Keefe, Francis; Nelligan, Rachel; Abbott, J Haxby; Bryant, Christina; Staples, Margaret P; Dalwood, Andrew; Bennell, Kim L

2014-08-13

Persistent knee pain in people over 50 years of age is often attributable to knee osteoarthritis (OA), a common joint condition that causes physical and psychological dysfunction. Exercise and pain coping skills training (PCST) can help reduce the impact of persistent knee pain, however, access to health professionals who deliver these services can be challenging. With increasing access to the Internet, remotely delivered Internet-based treatment approaches may provide alternatives for healthcare delivery. This pragmatic randomised controlled trial will investigate whether an Internet-delivered intervention that combines PCST and physiotherapist-guided exercise (PCST + Ex) is more effective than online educational material (educational control) in people with persistent knee pain. We will recruit 148 people over 50 years of age with self-reported persistent knee pain consistent with knee OA from the Australian community. Following completion of baseline questionnaires, participants will be randomly allocated to access a 3-month intervention of either (i) online educational material, or (ii) the same online material plus an 8-module (once per week) Internet-based PCST program and seven Internet-delivered physiotherapy sessions with a home exercise programs to be performed 3 times per week. Outcomes will be measured at baseline, 3 months and 9 months with the primary time point at 3 months. Primary outcomes are average knee pain on walking (11-point numeric rating scale) and self-reported physical function (Western Ontario and McMaster Universities Osteoarthritis Index subscale). Secondary outcomes include additional measures of knee pain, health-related quality-of-life, perceived global change in symptoms, and potential moderators and mediators of outcomes including self-efficacy for pain management and function, pain coping attempts and pain catastrophising. Other measures of adherence, adverse events, harms, use of health services/co-interventions, and process measures including appropriateness and satisfaction of the intervention, will be collected at 3, 6 and 9 months. The findings will help determine the effectiveness and acceptability of Internet access to a combination of interventions that are known to be beneficial to people with persistent knee pain. This study has the potential to guide clinical practice towards innovative modes of healthcare provision. Australian New Zealand Clinical Trials Registry reference: ACTRN12614000243617.

Initiation of Basal Insulin Analog Treatment for Type 2 Diabetes and Reasons Behind Patients' Treatment Persistence Behavior: Real-World Data from Germany.

PubMed

Moennig, Elisabeth; Perez-Nieves, Magaly; Hadjiyianni, Irene; Cao, Dachuang; Ivanova, Jasmina; Klask, Ralf

2018-05-01

Poor treatment persistence can affect the real-world effectiveness of insulin therapy. A cross-sectional online survey in 942 patients with type 2 diabetes from 7 different countries evaluated patient experience when initiating basal insulin and the reasons behind insulin persistence patterns. Here, we report the quantitative results for the subset of patients from Germany. Adults with type 2 diabetes who had initiated basal insulin during the last 3-24 months, identified from market-research panels, participated in the survey. Patients were asked if they had ≥7-day gaps in basal insulin treatment, and were then classified as "continuers" (no gap since starting insulin), "interrupters" (≥1 gap within the first 6 months after starting insulin and subsequently restarted insulin), or "discontinuers" (stopped insulin within the first 6 months after starting and had not restarted at the time of the survey). For each country, 50 participants were planned per persistence category. Enrollment ended if the target quota was reached or enrollment plateaued. Data were analyzed overall and separately for each persistence cohort. The 131 participants from Germany included 55 (42.0%) continuers, 50 (38.2%) interrupters and 26 (19.9%) discontinuers. The most common motivations to initiate basal insulin therapy were encouragement by physician or other healthcare provider (HCP; 54.2%) and expectation to improve glycemic control (42.0%). More than 95% of participants received training before and during insulin initiation (considered as helpful by 81.7%); most (67.2%) preferred in-person training. Continuers more frequently felt that insulin would help to manage diabetes and that their own views were considered when initiating insulin, they reported less concerns and challenges before and during insulin initiation than interrupters or discontinuers. The most common motivations to continue basal insulin were improved glycemic control (72.7%), improved physical well-being (49.1%), and instruction by physician or other HCP (45.5%). The most common reasons contributing to interruption/discontinuation were perceived weight gain (52.0%/50.0%), hypoglycemia (22.0%/38.5%), and potential adverse effects (30.0%/26.9%). Quality interactions between physicians or other HCPs and their patients before and during the initiation of basal insulin may help to manage patient expectations and to improve persistence to insulin therapy. © Georg Thieme Verlag KG Stuttgart · New York.

Childhood Adversity and Men’s Relationships in Adulthood: Life Course Processes and Racial Disadvantage

PubMed Central

Thomeer, Mieke Beth; Williams, Kristi; Thomas, Patricia A.; Liu, Hui

2016-01-01

Objectives: Prior U.S. population studies have found that childhood adversity influences the quality of relationships in adulthood, with emerging research suggesting that this association might be especially strong for black men. We theorize psychosocial and behavioral coping responses to early life adversity and how these responses may link early life adversity to strain in men’s relationships with their indeterminate partners and children across the life course, with attention to possible racial variation in these experiences and implications for later life well-being. Method: We analyze in-depth interviews with 15 black men and 15 white men. We use qualitative analysis techniques to connect childhood experiences to psychosocial processes in childhood and behavioral coping strategies associated with relationship experiences throughout adulthood. Results: Black men describe much stronger and more persistent childhood adversity than do white men. Findings further suggest that childhood adversity contributes to psychosocial processes (e.g., diminished sense of mastery) that may lead to ways of coping with adversity (e.g., self-medication) that are likely to contribute to relationship difficulties throughout the life span. Discussion: A life course perspective directs attention to the early life origins of cumulative patterns of social disadvantage, patterns that extend to later life. Our findings suggest psychosocial and behavioral pathways through which early life adversity may constrain and strain men’s relationships, possibly contributing to racial inequality in family relationships across the life span. PMID:26589348

Goshajinkigan for reducing chemotherapy-induced peripheral neuropathy: a systematic review and meta-analysis.

PubMed

Hoshino, Nobuaki; Ganeko, Riki; Hida, Koya; Sakai, Yoshiharu

2018-06-01

Chemotherapy-induced peripheral neuropathy (CIPN) is common and presents with persistent and challenging symptoms for which there is no effective means of prevention. This systematic review assessed the efficacy and safety of Goshajinkigan in the prevention of CIPN. A comprehensive literature search was conducted using Scopus, Ovid MEDLINE, the Cochrane Central Register of Controlled Trials, and ICHUSHI. Randomised controlled trials comparing Goshajinkigan with an alternative strategy for preventing CIPN were selected. Of five studies included in the review, Goshajinkigan did not reduce the risk of CIPN when the common terminology criteria for adverse events was used [risk ratio (RR) 0.94, 95% confidence interval (CI) 0.57-1.57 for grade ≥2 CIPN and RR 1.08, 95% CI 0.59-2.00 for grade ≥3 CIPN]. When the neurotoxicity criteria of Debiopharm was used, Goshajinkigan tended to decrease the risk of CIPN, but not significantly (RR 0.74, 95% CI 0.33-1.64 for grade ≥2 CIPN and RR 0.65, 95% CI 0.28-1.52 for grade ≥3 CIPN). Goshajinkigan tended to prevent persistence but not severity of CIPN. Higher quality trials using multiple measures are needed in the future to clarify the preventive effect of Goshajinkigan and to assess the various aspects of CIPN.

Mortality Risk from Co-Morbidities independent of Triple-Negative Breast Cancer Status: NCI SEER-based Cohort Analysis

PubMed Central

Swede, Helen; Sarwar, Amna; Magge, Anil; Braithwaite, Dejana; Cook, Linda S.; Gregorio, David I.; Jones, Beth A; Hoag, Jessica; Gonsalves, Lou; Salner, Andrew; Zarfos, Kristen; Andemariam, Biree; Stevens, Richard G; Dugan, Alicia; Pensa, Mellisa; Brockmeyer, Jessica

2017-01-01

Purpose A comparatively high prevalence of co-morbidities among African-American/Blacks (AA/B) has been implicated in disparate survival in breast cancer. There is a scarcity of data, however, if this effect persists when accounting for the adverse triple-negative breast cancer (TNBC) subtype which occurs at three-fold the rate in AA/B compared to white breast cancer patients. Methods We reviewed charts of 214 white and 202 AA/B breast cancer patients in the NCI-SEER Connecticut Tumor Registry who were diagnosed in 2000-07. We employed the Charlson Co-Morbidity Index (CCI), a weighted 17-item tool to predict risk of death in cancer populations. Cox Survival Analyses estimated hazard ratios (HR) for all-cause mortality in relation to TNBC and CCI adjusting for clinicopathological factors. Results Among patients with SEER-Local Stage, TNBC increased the risk of death (HR=2.18, 95% CI 1.14-4.16), which was attenuated when the CCI score was added to the model (Adj. HR=1.50, 95% CI 0.74-3.01). Conversely, the adverse impact of the CCI score persisted when controlling for TNBC (Adj. HR=1.49, 95% CI 1.29-1.71; per one point increase). Similar patterns were observed in SEER-Regional Stage but estimated HRs were lower. AA/B patients with a CCI score of ≥3 had a significantly higher risk of death compared to AA/B patients without comorbidities (Adj. HR=5.65, 95% CI 2.90-11.02). A lower and non-significant effect was observed for whites with a CCI of ≥3 (Adj. HR=1.90, 95% CI 0.68-5.29). Conclusions Co-morbidities at diagnosis increase risk of death independent of TNBC, and AA/B patients may be disproportionately at risk. PMID:27000206

The Use of Wet Cupping for Persistent Nonspecific Low Back Pain: Randomized Controlled Clinical Trial.

PubMed

AlBedah, Abdullah; Khalil, Mohamed; Elolemy, Ahmed; Hussein, Asim A; AlQaed, Meshari; Al Mudaiheem, Abdullah; Abutalib, Raid A; Bazaid, Faisal Mohamed; Bafail, Ahmad Saeed; Essa, AboBakr; Bakrain, Mohammed Yahia

2015-08-01

To evaluate the effectiveness and safety of wet cupping therapy as a single treatment for persistent nonspecific low back pain (PNSLBP). Randomized controlled trial comparing wet cupping versus no treatment in PNSLBP. Outpatient clinic in three secondary care hospitals in Saudi Arabia. Eighty eligible participants with PNSLBP for at least 3 months were randomly allocated to an intervention group (n=40) or to a control group (n=40). Six wet cupping sessions within 2 weeks, each of which were done at two bladder meridian (BL) acupuncture points among BL23, BL24, and BL25. Only acetaminophen was allowed as a rescue treatment in both groups. The Numeric Rating Scale (NRS), McGill Present Pain Intensity (PPI), and Oswestry Disability Questionnaire (ODQ) were used as outcome measures. Numbers of acetaminophen tablets taken were compared at 4 weeks from baseline. Adverse events were recorded. At the end of the intervention, statistically significant differences in the three outcome measures favoring the wet cupping group compared with the control group were seen: NRS score, 29.2 (95% confidence interval [CI], 24.6-33.8) versus 57.9 (95% CI, 53.3-62.6), respectively; PPI score, 1.17 (95% CI, 0.96-1.4) versus 2.3 (95% CI, 2.1- 2.7); and ODQ score, 19.6 (95% CI, 16.5-22.7) versus 35.4 (95% CI, 32.3-38.5) (p=0.0001). This improvement continued for another 2 weeks after the end of the intervention. Acetaminophen was used less in the wet cupping group, but this difference was not statistically significant. No adverse events were reported. Wet cupping is potentially effective in reducing pain and improving disability associated with PNSLBP at least for 2 weeks after the end of the wet cupping period. Placebo-controlled trials are needed.

The Use of Wet Cupping for Persistent Nonspecific Low Back Pain: Randomized Controlled Clinical Trial

PubMed Central

AlBedah, Abdullah; Elolemy, Ahmed; Hussein, Asim A.; AlQaed, Meshari; Al Mudaiheem, Abdullah; Abutalib, Raid A.; Bazaid, Faisal Mohamed; Bafail, Ahmad Saeed; Essa, AboBakr; Bakrain, Mohammed Yahia

2015-01-01

Abstract Objectives: To evaluate the effectiveness and safety of wet cupping therapy as a single treatment for persistent nonspecific low back pain (PNSLBP). Design: Randomized controlled trial comparing wet cupping versus no treatment in PNSLBP. Setting: Outpatient clinic in three secondary care hospitals in Saudi Arabia. Patients: Eighty eligible participants with PNSLBP for at least 3 months were randomly allocated to an intervention group (n=40) or to a control group (n=40). Interventions: Six wet cupping sessions within 2 weeks, each of which were done at two bladder meridian (BL) acupuncture points among BL23, BL24, and BL25. Only acetaminophen was allowed as a rescue treatment in both groups. Outcome measures: The Numeric Rating Scale (NRS), McGill Present Pain Intensity (PPI), and Oswestry Disability Questionnaire (ODQ) were used as outcome measures. Numbers of acetaminophen tablets taken were compared at 4 weeks from baseline. Adverse events were recorded. Results: At the end of the intervention, statistically significant differences in the three outcome measures favoring the wet cupping group compared with the control group were seen: NRS score, 29.2 (95% confidence interval [CI], 24.6–33.8) versus 57.9 (95% CI, 53.3–62.6), respectively; PPI score, 1.17 (95% CI, 0.96–1.4) versus 2.3 (95% CI, 2.1– 2.7); and ODQ score, 19.6 (95% CI, 16.5–22.7) versus 35.4 (95% CI, 32.3–38.5) (p=0.0001). This improvement continued for another 2 weeks after the end of the intervention. Acetaminophen was used less in the wet cupping group, but this difference was not statistically significant. No adverse events were reported. Conclusions: Wet cupping is potentially effective in reducing pain and improving disability associated with PNSLBP at least for 2 weeks after the end of the wet cupping period. Placebo-controlled trials are needed. PMID:26069973

Interaction between specific forms of childhood maltreatment and the serotonin transporter gene (5-HTT) in recurrent depressive disorder

PubMed Central

Fisher, Helen L.; Cohen-Woods, Sarah; Hosang, Georgina M.; Korszun, Ania; Owen, Mike; Craddock, Nick; Craig, Ian W.; Farmer, Anne E.; McGuffin, Peter; Uher, Rudolf

2013-01-01

Background There is inconsistent evidence of interaction between stressful events and a serotonin transporter promoter polymorphism (5-HTTLPR) in depression. Recent studies have indicated that the moderating effect of 5-HTTLPR may be strongest when adverse experiences have occurred in childhood and the depressive symptoms persist over time. However, it is unknown whether this gene-environment interaction is present for recurrent depressive disorder and different forms of maltreatment. Therefore, patients with recurrent clinically diagnosed depression and controls screened for absence of depression were utilised to examine the moderating effect of 5-HTTLPR on associations between specific forms of childhood adversity and recurrent depression. Method A sample of 227 recurrent unipolar depression cases and 228 never psychiatrically ill controls completed the Childhood Trauma Questionnaire to assess exposure to sexual, physical and emotional abuse, physical and emotional neglect in childhood. DNA extracted from blood or cheek swabs was genotyped for the short (s) and long (l) alleles of 5-HTTLPR. Results All forms of childhood maltreatment were reported as more severe by cases than controls. There was no direct association between 5-HTTLPR and depression. Significant interactions with additive and recessive 5-HTTLPR genetic models were found for overall severity of maltreatment, sexual abuse and to a lesser degree for physical neglect, but not other maltreatment types. Limitations The cross-sectional design limits causal inference. Retrospective report of childhood adversity may have reduced the accuracy of the findings. Conclusions This study provides support for the role of interplay between 5-HTTLPR and a specific early environmental risk in recurrent depressive disorder. PMID:22840631

Instrumental rotation for persistent fetal occiput posterior position: a way to decrease maternal and neonatal injury?

PubMed

Vidal, Fabien; Simon, Caroline; Cristini, Christelle; Arnaud, Catherine; Parant, Olivier

2013-01-01

To evaluate immediate perineal and neonatal morbidity associated with instrumental rotations performed with Thierry's spatulas for the management of persistent posterior occiput (OP) positions. Retrospective study including all persistent occiput posterior positions with vaginal OP delivery, from August 2006 to September 2007. Occiput anterior deliveries following successful instrumental rotation were included as well. We compared maternal and neonatal immediate outcomes between spontaneous deliveries, rotational and non rotational assisted deliveries, using χ(2) and Anova tests. 157 patients were enrolled, comprising 46 OP spontaneous deliveries, 58 assisted OP deliveries and 53 deliveries after rotational procedure. Instrumental rotation failed in 9 cases. Mean age and parity were significantly higher in the spontaneous delivery group, while labor duration was shorter. There were no significant differences in the rate of severe perineal tears and neonatal adverse outcomes between the 3 groups. Instrumental rotation using Thierry's spatulas was not associated with a reduced risk of maternal and neonatal morbidity for persistent OP deliveries. Further studies are required to define the true interest of such procedure in modern obstetrics.

Instrumental Rotation for Persistent Fetal Occiput Posterior Position: A Way to Decrease Maternal and Neonatal Injury?

PubMed Central

Vidal, Fabien; Simon, Caroline; Cristini, Christelle; Arnaud, Catherine; Parant, Olivier

2013-01-01

Objective To evaluate immediate perineal and neonatal morbidity associated with instrumental rotations performed with Thierry’s spatulas for the management of persistent posterior occiput (OP) positions. Methods Retrospective study including all persistent occiput posterior positions with vaginal OP delivery, from August 2006 to September 2007. Occiput anterior deliveries following successful instrumental rotation were included as well. We compared maternal and neonatal immediate outcomes between spontaneous deliveries, rotational and non rotational assisted deliveries, using χ2 and Anova tests. Results 157 patients were enrolled, comprising 46 OP spontaneous deliveries, 58 assisted OP deliveries and 53 deliveries after rotational procedure. Instrumental rotation failed in 9 cases. Mean age and parity were significantly higher in the spontaneous delivery group, while labor duration was shorter. There were no significant differences in the rate of severe perineal tears and neonatal adverse outcomes between the 3 groups. Conclusion Instrumental rotation using Thierry’s spatulas was not associated with a reduced risk of maternal and neonatal morbidity for persistent OP deliveries. Further studies are required to define the true interest of such procedure in modern obstetrics. PMID:24205122

A phase I trial of intraperitoneal GEN-1, an IL-12 plasmid formulated with PEG-PEI-cholesterol lipopolymer, administered with pegylated liposomal doxorubicin in patients with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancers: An NRG Oncology/Gynecologic Oncology Group study

PubMed Central

Thaker, Premal H.; Brady, William E.; Lankes, Heather A.; Odunsi, Kunle; Bradley, William H.; Moore, Kathleen N.; Muller, Carolyn Y.; Anwer, Khursheed; Schilder, Russell J.; Alvarez, Ronald D.; Fracasso, Paula M.

2017-01-01

Objective The study’s purpose was to assess safety and efficacy of escalating doses of weekly GEN-1 with pegylated liposomal doxorubicin (PLD) in patients with recurrent or persistent epithelial ovarian, fallopian tube or primary peritoneal cancers (EOC). Methods Patients had persistent or recurrent platinum-resistant EOC. The trial was a standard 3 + 3 phase I dose escalation design with patients receiving intravenous PLD 40 mg/m2 (dose level 1 and 2) or 50 mg/m2 (dose level 3) every 28 days and intraperitoneal GEN-1 at 24 mg/m2 (dose level 1) or 36 mg/m2 (dose level 2 and 3) on days 1, 8, 15, and 22 of a 28 day cycle. Cycles were repeated every 28 days until disease progression. Patients were monitored for toxicity, clinical efficacy, and evidence of systemic and intraperitoneal immunologic effect. Results Sixteen evaluable patients received a median of 4 cycles (range 1–8). No dose limiting toxicities were found. The adverse side effects were 4 grade 3 anemia, 2 grade 3 abdominal pain, 7 grade 3 neutropenia, and 2 grade 4 neutropenia. A clinical benefit of 57.1% (PR = 21.4%; SD = 35.7%) was found in the 14 patients with measurable disease. The highest number of partial responses (28.6%) and stable disease (57.1%) were found at dose level 3. The maximum tolerated dose was not reached. Increases in IL-12, IFN-γ, and TNF-α levels were found in peritoneal fluid following GEN-1 treatment. Conclusions GEN-1 in combination with PLD has encouraging clinical benefit and biological activity in recurrent or persistent EOC and warrants further investigation with escalating doses of GEN-1. PMID:28802766

Persistent activation of DNA damage signaling in response to complex mixtures of PAHs in air particulate matter

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

Jarvis, Ian W.H., E-mail: Ian.Jarvis@ki.se; Bergvall, Christoffer, E-mail: Christoffer.Bergvall@anchem.su.se; Bottai, Matteo, E-mail: Matteo.Bottai@ki.se

2013-02-01

Complex mixtures of polycyclic aromatic hydrocarbons (PAHs) are present in air particulate matter (PM) and have been associated with many adverse human health effects including cancer and respiratory disease. However, due to their complexity, the risk of exposure to mixtures is difficult to estimate. In the present study the effects of binary mixtures of benzo[a]pyrene (BP) and dibenzo[a,l]pyrene (DBP) and complex mixtures of PAHs in urban air PM extracts on DNA damage signaling was investigated. Applying a statistical model to the data we observed a more than additive response for binary mixtures of BP and DBP on activation of DNAmore » damage signaling. Persistent activation of checkpoint kinase 1 (Chk1) was observed at significantly lower BP equivalent concentrations in air PM extracts than BP alone. Activation of DNA damage signaling was also more persistent in air PM fractions containing PAHs with more than four aromatic rings suggesting larger PAHs contribute a greater risk to human health. Altogether our data suggests that human health risk assessment based on additivity such as toxicity equivalency factor scales may significantly underestimate the risk of exposure to complex mixtures of PAHs. The data confirms our previous findings with PAH-contaminated soil (Niziolek-Kierecka et al., 2012) and suggests a possible role for Chk1 Ser317 phosphorylation as a biological marker for future analyses of complex mixtures of PAHs. -- Highlights: ► Benzo[a]pyrene (BP), dibenzo[a,l]pyrene (DBP) and air PM PAH extracts were compared. ► Binary mixture of BP and DBP induced a more than additive DNA damage response. ► Air PM PAH extracts were more potent than toxicity equivalency factor estimates. ► Larger PAHs (> 4 rings) contribute more to the genotoxicity of PAHs in air PM. ► Chk1 is a sensitive marker for persistent activation of DNA damage signaling from PAH mixtures.« less

An integrated evaluation of the persistence and effects of 4-nonylphenol in an experimental littoral ecosystem

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

Liber, K.; Knuth, M.L.; Stay, F.S.

1999-03-01

A comprehensive littoral enclosure study was conducted to assess the persistence and distribution of 4-nonylphenol (NP) in a littoral ecosystem, and to evaluate the compound`s effects on resident aquatic biota. Enclosures with a mean ({+-} SD) surface area and volume of 31.4 {+-} 3.3 m{sup 2} and 32.0 {+-} 6.4 m{sup 3}, respectively, received eleven applications at 48-h intervals with one of four different rates of NP. This created a 20-d application period which was followed by a three to fourteen month observation period, depending on the endpoint measured. Mean {+-} SD NP concentrations in the water column measured 2more » h after each application averaged 5 {+-} 4, 23 {+-} 11, 76 {+-} 21, and 243 {+-} 41 {micro}g/L at nominal treatments of 3, 30, 100, and 300 {micro}g/L, respectively. Persistence in the water column was relatively short, with a dissipation half-life estimated at {le} 1.2 d. Persistence of NP in sediment and on macrophytes was substantially longer, with estimated half-lives of 28 to 104 d and 8 to 13 d, respectively. Zooplankton was the most sensitive group of organisms evaluated, with significant reductions in population abundances of some copepod taxa observed at the 23 {+-} 11-{micro}g/L treatment. Fish survival was affected at 243 {+-} 41 {micro}g/L. The most sensitive benthic macroinvertebrate taxon, Pisidium (Bivalvia) was affected at 76 {+-} 21 {micro}g/L, but most taxa were only affected at the 243 {+-} 41-{micro}g/L treatment. None of the assessed populations were affected at the 5 {+-} 4-{micro}g/L treatment. Macrophytes and periphyton were not adversely affected by any of the treatments. Overall community composition, assessed at the family level or higher, was not affected at or below the 23 {+-} 11-{micro}g/L treatment, but did exhibit substantial changes at the 243 {+-} 41-{micro}g/L treatment. Some minor changes were observed at the 76 {+-} 21-{micro}g/L treatment. The maximum acceptable toxicant concentration in the water column, based on protection of the most sensitive taxa in the test system, was estimated at {approximately} 10 {micro}g/L. Details on NP persistence and distribution within the enclosures, and detailed effects on zooplankton, benthic macroinvertebrates, and fish are described in four separate papers immediately following this overview.« less

Update on the use of trilostane in dogs.

PubMed

Lemetayer, Julie; Blois, Shauna

2018-04-01

Many articles published in the past few years have contributed to a better understanding of the use of trilostane in dogs. Trilostane is a competitive inhibitor of 3β-hydroxysteroid dehydrogenase, the enzyme essential for synthesis of cortisol and all other steroids. Trilostane is reported to be safe and effective in the treatment of pituitary-dependent hyperadrenocorticism (HAC), adrenal-dependent HAC, and alopecia X. While trilostane controls most of the clinical signs associated with HAC, abnormalities such as hypertension, hypercoagulability, and proteinuria may persist despite therapy. Because the duration of cortisol suppression after a dose of trilostane is often less than 12 hours, many dogs with HAC could benefit from low dose trilostane treatment every 12 hours. Many controversies regarding trilostane still exist. This review provides a comprehensive commentary on trilostane's indications, mode of action, dose, monitoring, efficacy, and adverse effects.

Effects of BPA and BPS exposure limited to early embryogenesis persist to impair non-associative learning in adults.

PubMed

Mersha, Mahlet D; Patel, Bansri M; Patel, Dipen; Richardson, Brittany N; Dhillon, Harbinder S

2015-09-17

Bisphenol-A (BPA) is a polymerizing agent used in plastic bottles and several routinely used consumer items. It is classified among endocrine disrupting chemicals suspected to cause adverse health effects in mammals ranging from infertility and cancer to behavioral disorders. Work with the invertebrate lab model Caenorhabditis elegans has shown that BPA affects germ cells by disrupting double-stranded DNA break repair mechanisms. The current study utilizes this model organism to provide insight into low-dose and long-term behavioral effects of BPA and bisphenol-S (BPS), a supposed safer replacement for BPA. Experiments presented in our report demonstrate that the effects of embryonic exposure to considerably low levels of BPA persist into adulthood, affecting neural functionality as assayed by measuring habituation to mechano-sensory stimuli in C. elegans. These results are noteworthy in that they are based on low-dose exposures, following the rationale that subtler effects that may not be morphologically apparent are likely to be discernible through behavioral changes. In addition, we report that embryonic exposure to BPS follows a pattern similar to BPA. Building upon previous observations using the C. elegans model, we have shown that exposure of embryos to BPA and BPS affects their behavior as adults. These long-term effects are in line with recommended alternate low-dose chemical safety testing approaches. Our observation that the effects of BPS are similar to BPA is not unexpected, considering their structural similarity. This, to our knowledge, is the first reported behavioral study on low-dose toxicity of any endocrine disrupting chemical in C. elegans.

Associations between childhood body size and seventeen adverse outcomes: analysis of 65,057 European women.

PubMed

Li, Jingmei; Eriksson, Mikael; He, Wei; Hall, Per; Czene, Kamila

2017-12-05

Large childhood body size has been consistently shown to be associated with decreased breast cancer risk. However, it is important to consider the effects of a large childhood body size on other adult diseases. It is not clear if the associations between childhood body size and adult diseases will persist if they later attain healthy weight. The associations between body size at age 7 and 17 adverse outcomes in adulthood were examined using Cox models in a Swedish study of 65,057 women. Large body size at age 7, when compared to small body size, was associated with decreased risk for breast cancer (HR [95% CI]: 0.81 [0.70-0.93]) and increased risks for anorexia (2.13 [1.63-2.77]) and bulimia (1.91 [1.35-2.70]). Neither adjusting for adult BMI nor restricting the dataset to lean adults (BMI < 25 kg/m 2 ) attenuated the associations. While large body size at age 7 by itself was positively associated with increased risks of diabetes (1.34 [1.16-1.55]), PCOS (1.69 [1.13-2.51]) and hypertension (before age 60), the associations were no longer significant after controlling for adult BMI. No clear associations were found with the remaining adverse outcomes (cervical, uterine, melanoma, colon cancer, depression, ovarian cyst, stroke, hyperlipidemia, heart failure, myocardial infarction, and angina pectoris).

Acute, subacute and long-term subjective effects of psilocybin in healthy humans: a pooled analysis of experimental studies.

PubMed

Studerus, Erich; Kometer, Michael; Hasler, Felix; Vollenweider, Franz X

2011-11-01

Psilocybin and related hallucinogenic compounds are increasingly used in human research. However, due to limited information about potential subjective side effects, the controlled medical use of these compounds has remained controversial. We therefore analysed acute, short- and long-term subjective effects of psilocybin in healthy humans by pooling raw data from eight double-blind placebo-controlled experimental studies conducted between 1999 and 2008. The analysis included 110 healthy subjects who had received 1-4 oral doses of psilocybin (45-315 µg/kg body weight). Although psilocybin dose-dependently induced profound changes in mood, perception, thought and self-experience, most subjects described the experience as pleasurable, enriching and non-threatening. Acute adverse drug reactions, characterized by strong dysphoria and/or anxiety/panic, occurred only in the two highest dose conditions in a relatively small proportion of subjects. All acute adverse drug reactions were successfully managed by providing interpersonal support and did not need psychopharmacological intervention. Follow-up questionnaires indicated no subsequent drug abuse, persisting perception disorders, prolonged psychosis or other long-term impairment of functioning in any of our subjects. The results suggest that the administration of moderate doses of psilocybin to healthy, high-functioning and well-prepared subjects in the context of a carefully monitored research environment is associated with an acceptable level of risk.

What has research over the past two decades revealed about the adverse health effects of recreational cannabis use?

PubMed

Hall, Wayne

2015-01-01

To examine changes in the evidence on the adverse health effects of cannabis since 1993. A comparison of the evidence in 1993 with the evidence and interpretation of the same health outcomes in 2013. Research in the past 20 years has shown that driving while cannabis-impaired approximately doubles car crash risk and that around one in 10 regular cannabis users develop dependence. Regular cannabis use in adolescence approximately doubles the risks of early school-leaving and of cognitive impairment and psychoses in adulthood. Regular cannabis use in adolescence is also associated strongly with the use of other illicit drugs. These associations persist after controlling for plausible confounding variables in longitudinal studies. This suggests that cannabis use is a contributory cause of these outcomes but some researchers still argue that these relationships are explained by shared causes or risk factors. Cannabis smoking probably increases cardiovascular disease risk in middle-aged adults but its effects on respiratory function and respiratory cancer remain unclear, because most cannabis smokers have smoked or still smoke tobacco. The epidemiological literature in the past 20 years shows that cannabis use increases the risk of accidents and can produce dependence, and that there are consistent associations between regular cannabis use and poor psychosocial outcomes and mental health in adulthood. © 2014 Society for the Study of Addiction.

Exploring alternative treatments for Helicobacter pylori infection

PubMed Central

Ayala, Guadalupe; Escobedo-Hinojosa, Wendy Itzel; de la Cruz-Herrera, Carlos Felipe; Romero, Irma

2014-01-01

Helicobacter pylori (H. pylori) is a successful pathogen that can persist in the stomach of an infected person for their entire life. It provokes chronic gastric inflammation that leads to the development of serious gastric diseases such as peptic ulcers, gastric cancer and Mucosa associated lymphoid tissue lymphoma. It is known that these ailments can be avoided if the infection by the bacteria can be prevented or eradicated. Currently, numerous antibiotic-based therapies are available. However, these therapies have several inherent problems, including the appearance of resistance to the antibiotics used and associated adverse effects, the risk of re-infection and the high cost of antibiotic therapy. The delay in developing a vaccine to prevent or eradicate the infection has furthered research into new therapeutic approaches. This review summarises the most relevant recent studies on vaccine development and new treatments using natural resources such as plants, probiotics and nutraceuticals. In addition, novel alternatives based on microorganisms, peptides, polysaccharides, and intragastric violet light irradiation are presented. Alternative therapies have not been effective in eradicating the bacteria but have been shown to maintain low bacterial levels. Nevertheless, some of them are useful in preventing the adverse effects of antibiotics, modulating the immune response, gastroprotection, and the general promotion of health. Therefore, those agents can be used as adjuvants of allopathic anti-H. pylori eradication therapy. PMID:24587621

Work characteristics, socioeconomic position and health: a systematic review of mediation and moderation effects in prospective studies

PubMed Central

Hoven, Hanno; Siegrist, Johannes

2013-01-01

Social inequalities in health persist in modern societies. The contribution of adverse work and employment conditions towards their explanation is analysed by two approaches, mediation and moderation. Yet the relative significance of each approach remains unclear in respective research. We set out to study this question by conducting a systematic literature review. We included all original papers based on prospective observational studies of employed cohorts that were published between January 1980 and October 2012 meeting our search criteria, by using major databases and by observing established quality criteria. 26 reports were included after quality assessment. 17 studies examined the mediation hypothesis and nine studies tested the moderation hypothesis. Moderate support was found for the mediation hypothesis where OR or HR of health according to socioeconomic position (SEP) were reduced in a majority of analyses after introducing work characteristics in multivariate models. Evidence in favour of the moderation hypothesis was found in some studies, demonstrating stronger effects of adverse work on health among people with low SEP. Despite some support in favour of the two hypotheses future research should aim at reducing the heterogeneity in defining and measuring core variables and at applying advanced statistical analyses. Policy recommendations would benefit from a higher degree of consistency of respective research evidence. PMID:23739492

Work characteristics, socioeconomic position and health: a systematic review of mediation and moderation effects in prospective studies.

PubMed

Hoven, Hanno; Siegrist, Johannes

2013-09-01

Social inequalities in health persist in modern societies. The contribution of adverse work and employment conditions towards their explanation is analysed by two approaches, mediation and moderation. Yet the relative significance of each approach remains unclear in respective research. We set out to study this question by conducting a systematic literature review. We included all original papers based on prospective observational studies of employed cohorts that were published between January 1980 and October 2012 meeting our search criteria, by using major databases and by observing established quality criteria. 26 reports were included after quality assessment. 17 studies examined the mediation hypothesis and nine studies tested the moderation hypothesis. Moderate support was found for the mediation hypothesis where OR or HR of health according to socioeconomic position (SEP) were reduced in a majority of analyses after introducing work characteristics in multivariate models. Evidence in favour of the moderation hypothesis was found in some studies, demonstrating stronger effects of adverse work on health among people with low SEP. Despite some support in favour of the two hypotheses future research should aim at reducing the heterogeneity in defining and measuring core variables and at applying advanced statistical analyses. Policy recommendations would benefit from a higher degree of consistency of respective research evidence.

Large-scale risk assessment of polycyclic aromatic hydrocarbons in shoreline sediments from Saudi Arabia: environmental legacy after twelve years of the Gulf war oil spill.

PubMed

Bejarano, Adriana C; Michel, Jacqueline

2010-05-01

A large-scale assessment of polycyclic aromatic hydrocarbons (PAHs) from the 1991 Gulf War oil spill was performed for 2002-2003 sediment samples (n = 1679) collected from habitats along the shoreline of Saudi Arabia. Benthic sediment toxicity was characterized using the Equilibrium Partitioning Sediment Benchmark Toxic Unit approach for 43 PAHs (ESBTU(FCV,43)). Samples were assigned to risk categories according to ESBTU(FCV,43) values: no-risk (< or = 1), low (>1 - < or = 2), low-medium (>2 - < or = 3), medium (>3 - < or = 5) and high-risk (>5). Sixty seven percent of samples had ESBTU(FCV,43) > 1 indicating potential adverse ecological effects. Sediments from the 0-30 cm layer from tidal flats, and the >30 - <60 cm layer from heavily oiled halophytes and mangroves had high frequency of high-risk samples. No-risk samples were characterized by chrysene enrichment and depletion of lighter molecular weight PAHs, while high-risk samples showed little oil weathering and PAH patterns similar to 1993 samples. North of Safaniya sediments were not likely to pose adverse ecological effects contrary to sediments south of Tanaqib. Landscape and geomorphology has played a role on the distribution and persistence in sediments of oil from the Gulf War. Copyright 2009 Elsevier Ltd. All rights reserved.

Age-Related Differences in Non-Persistence with Statin Treatment in Patients after a Transient Ischaemic Attack.

PubMed

Wawruch, Martin; Zatko, Dusan; Wimmer, Gejza; Luha, Jan; Wimmerova, Sona; Matalova, Petra; Kukumberg, Peter; Murin, Jan; Tesar, Tomas; Havelkova, Beata; Shah, Rashmi

2017-11-01

Non-persistence with secondary preventive measures, including medications such as statins, adversely affects the prospects of successful outcomes. This study was aimed at evaluating non-persistence with statin therapy in cohorts of young and elderly patients after a transient ischaemic attack (TIA) and identifying patient-associated characteristics that influence the risk for non-persistence. The study cohorts included 797 adult patients who were initiated on statin therapy following a TIA diagnosis between 1 January 2010 and 31 December 2010. Patients were followed up for 3 years and those with a treatment gap of at least a 6-month period were considered 'non-persistent'. In order to identify any age-related differences, all analyses were conducted in the entire study cohort (n = 797) as well as separately in the 'younger' (aged <65 years, n = 267) and the 'older' (aged ≥65 years, n = 530) patients. Non-persistence was significantly more common in younger patients compared to older patients (67.8% vs. 49.1%; p < 0.001). Factors that decreased the probability of non-persistence in younger and older patients included diabetes mellitus (hazard ratio [HR] = 0.72 and HR = 0.64, respectively) and hypercholesterolaemia (HR = 0.43 and HR = 0.62, respectively). Female gender (HR = 1.42) was associated with a higher and increasing number of medications taken (HR = 0.93), with lower probability for non-persistence in younger patients but not in the older patients. Our results indicate that certain patients with TIA require special counselling to improve persistence with statin therapy. These include younger patients, especially females and those not on polypharmacy, and both younger and older patients without diabetes mellitus or hypercholesterolaemia.

Effects of Increasing Hydrocortisone to 300 mg Per Day in the Treatment of Septic Shock: a Pilot Study.

PubMed

Hyvernat, Hervé; Barel, Rémy; Gentilhomme, Anne; Césari-Giordani, Jean François; Freche, Annie; Kaidomar, Michel; Goubaux, Bernard; Pradier, Christian; Dellamonica, Jean; Bernardin, Gilles

2016-11-01

The Surviving Sepsis Campaign guidelines recommend hydrocortisone in septic shock only when fluid resuscitation and vasopressors fail to restore hemodynamic stability. Hydrocortisone administration modalities are supported only by low-grade recommendations. Our main objective here was to determine differences in 28-day mortality between two low-dose hydrocortisone regimens for the treatment of septic shock. We performed a multicenter, prospective, randomized, double-blind, pilot study in four adult medical intensive care units. Patients presenting septic shock were rapidly administered one of two regimens of hydrocortisone, either a 50-mg intravenous bolus every 6 h during 7 days (200-mg group; n = 59) or a 100-mg initial bolus followed by a continuous infusion of 300 mg daily for 5 days (300-mg group; n = 63). Hydrocortisone was stopped abruptly at the end of treatment. There were no significant differences between the 200-mg and 300-mg groups as concerns 28-day mortality (respectively 52.5% vs. 44.4% [RR 0.84, 95% CI, 0.58-1.22, P = 0.47]), refractory shock incidence or delay from shock to vasopressor cessation. There were also no differences in adverse events between the groups. Shock relapse after hydrocortisone cessation was independent of hydrocortisone regimens, but it was associated with the persistence of infection and the use of etomidate. The resumption of hydrocortisone due to shock relapse was significantly more frequent in the 300-mg group. We found no differences in mortality or adverse events between the two hydrocortisone administration regimens. Shock relapse was significantly associated with the persistence of infection and the use of etomidate.

Cognitive Behavior Therapy as Augmentation for Sertraline in Treating Patients with Persistent Postural-Perceptual Dizziness.

PubMed

Yu, Yi-Chuan; Xue, Hui; Zhang, Ying-Xin; Zhou, Jiying

2018-01-01

Persistent postural-perceptual dizziness (PPPD) is a common vestibular disorder. This study was conducted to assess whether the addition of cognitive behavior therapy (CBT) could significantly improve the efficacy and acceptability of sertraline in treating PPPD. PPPD patients were recruited and randomly assigned to control and experiment groups. Patients in both groups received sertraline 50-200 mg/day, and only patients in the experiment group received CBT (twice a week, one hour per time). The treatment was continued for eight weeks. At baseline, week 2, week 4, and week 8, the 25-item Dizziness Handicap Inventory (DHI), Hamilton Anxiety Rating Scale (HARS), and Hamilton Depression Rating Scale (HDRS) were used to assess the self-perceived handicapping effects caused by PPPD, anxiety, and depressive symptoms, respectively. The dose of sertraline used and the adverse events in both groups were recorded and analyzed. In total, 91 PPPD patients were randomly assigned to the control group ( n = 45) and experiment group ( n = 46). After eight weeks of treatment, the average DHI scores, HDRS scores, and HARS scores were significantly decreased in both groups. But compared to the control group, the experiment group had significantly lower average DHI score, HDRS score, and HARS score at weeks 4 and 8. Moreover, the dose of sertraline used in the experiment group was significantly lower than that in the control group, and adverse events occurred more frequently in the control group than in the experiment group (48.9% versus 26.1%, p = 0.025). These results demonstrated that the addition of CBT could significantly improve the efficacy and acceptability of sertraline in treating PPPD and reduce the dose of sertraline used.

Outcome Assessments and Cost Avoidance of an Oral Chemotherapy Management Clinic.

PubMed

Wong, Siu-Fun; Bounthavong, Mark; Nguyen, Cham P; Chen, Timothy

2016-03-01

Increasing use of oral chemotherapy drugs increases the challenges for drug and patient management. An oral chemotherapy management clinic was developed to provide patients with oral chemotherapy management, concurrent medication (CM) education, and symptom management services. This evaluation aims to measure the need and effectiveness of this practice model due to scarce published data. This is a case series report of all patients referred to the oral chemotherapy management clinic. Data collected included patient demographics, depression scores, CMs, and types of intervention, including detection and management outcomes collected at baseline, 3-day, 7-day, and 3-month follow-ups. Persistence rate was monitored. Secondary analysis assessed potential cost avoidance. A total of 86 evaluated patients (32 men and 54 women, mean age of 63.4 years) did not show a high risk for medication nonadherence. The 3 most common cancer diagnoses were rectal, pancreatic, and breast, with capecitabine most prescribed. Patients had an average of 13.7 CMs. A total of 125 interventions (detection and management of adverse drug event detection, compliance, drug interactions, medication error, and symptom management) occurred in 201 visits, with more than 75% of interventions occurring within the first 14 days. A persistence rate was observed in 78% of 41 evaluable patients. The total estimated annual cost avoidance per 1.0 full time employee (FTE) was $125,761.93. This evaluation demonstrated the need for additional support for patients receiving oral chemotherapy within standard of care medical service. A comprehensive oral chemotherapy management referral service can optimize patient care delivery via early interventions for adverse drug events, drug interactions, and medication errors up to 3 months after initiation of treatment. Copyright © 2016 by the National Comprehensive Cancer Network.

Immunogenicity and Safety of a Booster Dose of a Live Attenuated Japanese Encephalitis Chimeric Vaccine Given 1 Year After Primary Immunization in Healthy Children in the Republic of Korea.

PubMed

Kim, Dong Soo; Jang, Gwang Cheon; Cha, Sung-Ho; Choi, Soo-Han; Kim, Hwang Min; Kim, Ji Hong; Kang, Jin Han; Kim, Jong-Hyun; Kim, Ki Hwan; Bang, Joon; Naimi, Zulaikha; Bouckenooghe, Alain; Bosch-Castells, Valérie; Houillon, Guy

2016-02-01

This study evaluated the effect of a booster vaccination of a new, live attenuated, Japanese encephalitis chimeric vaccine (JE-CV). Previously this vaccine has been used as a booster 12 months after priming with an inactivated vaccine and at >24 months after priming with the same JE-CV. This study evaluates the immunogenicity and safety of the JE-CV given at 12-24 months after JE-CV priming. Phase III, open-label study in the Republic of Korea in which 119 children previously vaccinated with JE-CV at 12-24 months of age received a JE-CV booster at 12-24 months after primary vaccination. JE neutralizing antibody titers were measured using >50% plaque reduction neutralization test prebooster and 1 month postbooster vaccination. Seroprotection (SP) was defined as ≥10 (1/dil). Safety was assessed for 28 days postvaccination by parental reports. Serious adverse events were monitored for 6 months postvaccination. Antibody persistence was high prebooster (SP rate 93.5%). There was a strong anamnestic response postbooster vaccination, with an SP rate of 100% and a >50-fold increase in geometric mean titer from the prebooster level. Both antibody persistence and the booster response were independent of whether the booster was given at 12-17 or 18-24 months. The safety profile was good and comparable with the primary vaccination; there were no vaccine-related serious adverse events and no deaths. This study confirms the suitability of a JE-CV booster vaccination at 12-24 months after a primary dose of the same vaccine given at 12-24 months of age in children in the Republic of Korea.

Optimism and Recovery After Acute Coronary Syndrome: A Clinical Cohort Study

PubMed Central

Ronaldson, Amy; Molloy, Gerard J.; Wikman, Anna; Poole, Lydia; Kaski, Juan-Carlos; Steptoe, Andrew

2015-01-01

ABSTRACT Objective Optimism is associated with reduced cardiovascular mortality, but its impact on recovery after acute coronary syndrome (ACS) is poorly understood. We hypothesized that greater optimism would lead to more effective physical and emotional adaptation after ACS and would buffer the impact of persistent depressive symptoms on clinical outcomes. Methods This prospective observational clinical study took place in an urban general hospital and involved 369 patients admitted with a documented ACS. Optimism was assessed with a standardized questionnaire. The main outcomes were physical health status, depressive symptoms, smoking, physical activity, and fruit and vegetable consumption measured 12 months after ACS, and composite major adverse cardiac events (cardiovascular death, readmission with reinfarction or unstable angina, and coronary artery bypass graft surgery) assessed over an average of 45.7 months. Results We found that optimism predicted better physical health status 12 months after ACS independently of baseline physical health, age, sex, ethnicity, social deprivation, and clinical risk factors (B = 0.65, 95% confidence interval [CI] = 0.10–1.20). Greater optimism also predicted reduced risk of depressive symptoms (odds ratio = 0.82, 95% CI = 0.74–0.90), more smoking cessation, and more fruit and vegetable consumption at 12 months. Persistent depressive symptoms 12 months after ACS predicted major adverse cardiac events over subsequent years (odds ratio = 2.56, 95% CI = 1.16–5.67), but only among individuals low in optimism (optimism × depression interaction; p = .014). Conclusions Optimism predicts better physical and emotional health after ACS. Measuring optimism may help identify individuals at risk. Pessimistic outlooks can be modified, potentially leading to improved recovery after major cardiac events. PMID:25738438

Predictors and Prognostic Value of Worsening Renal Function During Admission in HFpEF Versus HFrEF: Data From the KorAHF (Korean Acute Heart Failure) Registry.

PubMed

Kang, Jeehoon; Park, Jin Joo; Cho, Young-Jin; Oh, Il-Young; Park, Hyun-Ah; Lee, Sang Eun; Kim, Min-Seok; Cho, Hyun-Jai; Lee, Hae-Young; Choi, Jin Oh; Hwang, Kyung-Kuk; Kim, Kye Hun; Yoo, Byung-Su; Kang, Seok-Min; Baek, Sang Hong; Jeon, Eun-Seok; Kim, Jae-Joong; Cho, Myeong-Chan; Chae, Shung Chull; Oh, Byung-Hee; Choi, Dong-Ju

2018-03-13

Worsening renal function (WRF) is associated with adverse outcomes in patients with heart failure. We investigated the predictors and prognostic value of WRF during admission, in patients with preserved ejection fraction (HFpEF) versus those with reduced ejection fraction (HFrEF). A total of 5625 patients were enrolled in the KorAHF (Korean Acute Heart Failure) registry. WRF was defined as an absolute increase in creatinine of ≥0.3 mg/dL. Transient WRF was defined as recovery of creatinine at discharge, whereas persistent WRF was indicated by a nonrecovered creatinine level. HFpEF and HFrEF were defined as a left ventricle ejection fraction ≥50% and ≤40%, respectively. Among the total population, WRF occurred in 3101 patients (55.1%). By heart failure subgroup, WRF occurred more frequently in HFrEF (57.0% versus 51.3%; P <0.001 in HFrEF and HFpEF). Prevalence of WRF increased as creatinine clearance decreased in both heart failure subgroups. Among various predictors of WRF, chronic renal failure was the strongest predictor. WRF was an independent predictor of adverse in-hospital outcomes (HFrEF: odds ratio; 2.75; 95% confidence interval, 1.50-5.02; P =0.001; HFpEF: odds ratio, 9.48; 95% confidence interval, 1.19-75.89; P =0.034) and 1-year mortality (HFrEF: hazard ratio, 1.41; 95% confidence interval, 1.12-1.78; P =0.004 versus HFpEF: hazard ratio, 1.72; 95% confidence interval, 1.23-2.42; P =0.002). Transient WRF was a risk factor for 1-year mortality, whereas persistent WRF had no additive risk compared to transient WRF. In patients with acute heart failure patients, WRF is an independent predictor of adverse in-hospital and follow-up outcomes in both HFrEF and HFpEF, though with a different effect size. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01389843. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

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

PubMed

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

2013-06-10

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

Periodontitis: from microbial immune subversion to systemic inflammation

PubMed Central

Hajishengallis, George

2014-01-01

Periodontitis is a dysbiotic inflammatory disease with an adverse impact on systemic health. Recent studies have provided insights into the emergence and persistence of dysbiotic oral microbial communities, which can mediate inflammatory pathology at local as well as distant sites. This Review discusses mechanisms of microbial immune subversion that tip the balance from homeostasis to disease in oral or extraoral sites. PMID:25534621

Child Poverty Higher and More Persistent in Rural America. National Issue Brief Number 97

ERIC Educational Resources Information Center

Schaefer, Andrew; Mattingly, Marybeth; Johnson, Kenneth M.

2016-01-01

The negative consequences of growing up in a poor family are well known. Poor children are less likely to have timely immunizations, have lower academic achievement, are generally less engaged in school activities, and face higher delinquency rates in adolescent years. Each of these has adverse impacts on their health, earnings, and family status…

Making Meaning of Adversity: Experiences of Women Leaders in Higher Education

ERIC Educational Resources Information Center

Diehl, Amy B.

2013-01-01

Despite the fact that women now earn more bachelor's, master's and doctorates than men, a gender gap for women leaders persists in the field of higher education. Women hold only 26 percent of all college and university presidencies with a large variance by type of institution. Women lead 33 percent of associate's level institutions but only 22…

Longitudinal Study of Sustained-Release Dexamethasone Intravitreal Implant in Patients with Diabetic Macular Edema.

PubMed

Aknin, Isabelle; Melki, Laurent

2016-01-01

Observational studies are needed to confirm the long-term efficacy and safety of Ozurdex® intravitreal implant in real life. Among 29 patients with persistent diabetic macular edema (DME), of whom 14 (48%) patients did not have any previous treatments and 22 (76%) any previous antivascular endothelial growth factor (anti-VEGF) injections, significant visual acuity (VA) improvement was observed with a mean gain of 13.8 letters at month 6 (p < 0.0001), 12.7 letters at month 12 (p = 0.0032) and 16.5 letters at month 18 (p = 0.0313). During the follow-up, a total of 17 (59%) patients had a VA improvement of ≥15 letters. Significant central macular thickness decrease was observed with a mean reduction of 159.07 μm at month 6 (p < 0.0001), 181.8 μm at month 12 (p < 0.0001) and 236.17 μm at month 18 (p = 0.0313). No serious adverse events were reported. With a good efficacy and safety, manageable adverse events and an injection rate much lower compared to that of anti-VEGF, this study confirms the use of Ozurdex® for the treatment of persistent DME. © 2016 S. Karger AG, Basel.

Key scientific issues in developing drinking water guidelines for perfluoroalkyl acids: Contaminants of emerging concern.

PubMed

Post, Gloria B; Gleason, Jessie A; Cooper, Keith R

2017-12-01

Perfluoroalkyl acids (PFAAs), a group of synthetic organic chemicals with industrial and commercial uses, are of current concern because of increasing awareness of their presence in drinking water and their potential to cause adverse health effects. PFAAs are distinctive among persistent, bioaccumulative, and toxic (PBT) contaminants because they are water soluble and do not break down in the environment. This commentary discusses scientific and risk assessment issues that impact the development of drinking water guidelines for PFAAs, including choice of toxicological endpoints, uncertainty factors, and exposure assumptions used as their basis. In experimental animals, PFAAs cause toxicity to the liver, the immune, endocrine, and male reproductive systems, and the developing fetus and neonate. Low-dose effects include persistent delays in mammary gland development (perfluorooctanoic acid; PFOA) and suppression of immune response (perfluorooctane sulfonate; PFOS). In humans, even general population level exposures to some PFAAs are associated with health effects such as increased serum lipids and liver enzymes, decreased vaccine response, and decreased birth weight. Ongoing exposures to even relatively low drinking water concentrations of long-chain PFAAs substantially increase human body burdens, which remain elevated for many years after exposure ends. Notably, infants are a sensitive subpopulation for PFAA's developmental effects and receive higher exposures than adults from the same drinking water source. This information, as well as emerging data from future studies, should be considered in the development of health-protective and scientifically sound guidelines for PFAAs in drinking water.

Key scientific issues in developing drinking water guidelines for perfluoroalkyl acids: Contaminants of emerging concern

PubMed Central

Gleason, Jessie A.; Cooper, Keith R.

2017-01-01

Perfluoroalkyl acids (PFAAs), a group of synthetic organic chemicals with industrial and commercial uses, are of current concern because of increasing awareness of their presence in drinking water and their potential to cause adverse health effects. PFAAs are distinctive among persistent, bioaccumulative, and toxic (PBT) contaminants because they are water soluble and do not break down in the environment. This commentary discusses scientific and risk assessment issues that impact the development of drinking water guidelines for PFAAs, including choice of toxicological endpoints, uncertainty factors, and exposure assumptions used as their basis. In experimental animals, PFAAs cause toxicity to the liver, the immune, endocrine, and male reproductive systems, and the developing fetus and neonate. Low-dose effects include persistent delays in mammary gland development (perfluorooctanoic acid; PFOA) and suppression of immune response (perfluorooctane sulfonate; PFOS). In humans, even general population level exposures to some PFAAs are associated with health effects such as increased serum lipids and liver enzymes, decreased vaccine response, and decreased birth weight. Ongoing exposures to even relatively low drinking water concentrations of long-chain PFAAs substantially increase human body burdens, which remain elevated for many years after exposure ends. Notably, infants are a sensitive subpopulation for PFAA’s developmental effects and receive higher exposures than adults from the same drinking water source. This information, as well as emerging data from future studies, should be considered in the development of health-protective and scientifically sound guidelines for PFAAs in drinking water. PMID:29261653

Regional analgesia for improvement of long-term functional outcome after elective large joint replacement.

PubMed

Atchabahian, Arthur; Schwartz, Gary; Hall, Charles B; Lajam, Claudette M; Andreae, Michael H

2015-08-13

Regional analgesia is more effective than conventional analgesia for controlling pain and may facilitate rehabilitation after large joint replacement in the short term. It remains unclear if regional anaesthesia improves functional outcomes after joint replacement beyond three months after surgery. To assess the effects of regional anaesthesia and analgesia on long-term functional outcomes 3, 6 and 12 months after elective major joint (knee, shoulder and hip) replacement surgery. We performed an electronic search of several databases (CENTRAL, MEDLINE, EMBASE, CINAHL), and handsearched reference lists and conference abstracts. We updated our search in June 2015. We included randomized controlled trials (RCTs) comparing regional analgesia versus conventional analgesia in patients undergoing total shoulder, hip or knee replacement. We included studies that reported a functional outcome with a follow-up of at least three months after surgery. We used standard methodological procedures expected by Cochrane. We contacted study authors for additional information. We included six studies with 350 participants followed for at least three months. All of these studies enrolled participants undergoing total knee replacement. Studies were at least partially blinded. Three studies had a high risk of performance bias and one a high risk of attrition bias, but the risk of bias was otherwise unclear or low.Only one study assessed joint function using a global score. Due to heterogeneity in outcome and reporting, we could only pool three out of six RCTs, with range of motion assessed at three months after surgery used as a surrogate for joint function. All studies had a high risk of detection bias. Using the random-effects model, there was no statistically significant difference between the experimental and control groups (mean difference 3.99 degrees, 95% confidence interval (CI) - 2.23 to 10.21; P value = 0.21, 3 studies, 140 participants, very low quality evidence).We did not perform further analyses because immediate adverse effects were not part of the explicit outcomes of any of these typically small studies, and long-term adverse events after regional anaesthesia are rare.None of the included studies elicited or reported long-term adverse effects like persistent nerve damage. More high-quality studies are needed to establish the effects of regional analgesia on function after major joint replacement, as well as on the risk of adverse events (falls).

Care Pathways in Persistent Orofacial Pain: Qualitative Evidence from the DEEP Study.

PubMed

Breckons, M; Bissett, S M; Exley, C; Araujo-Soares, V; Durham, J

2017-01-01

Persistent orofacial pain is relatively common and known to have an adverse effect on quality of life. Previous studies suggest that the current care pathway may be problematic, but it is not well understood which health services patients access and what their experience is. The aim of this study was to explore care pathways and their impact from the perspective of patients. Qualitative interviews were conducted with a maximum variation sample of patients recruited from primary (community based) and secondary (specialist hospital based) care in the United Kingdom. Questions focused on the stages in their pathway and the impact of the care that they had received. Interviews were digitally recorded and transcribed verbatim, and analysis followed principles of the constant comparative method. NVivo 10 was used to help organize and analyze data. Twenty-two patients were interviewed at baseline, and 18 took part in a second interview at 12 mo. Three main themes emerged from the data: the "fluidity of the care pathway," in which patients described moving among health care providers in attempts to have their pain diagnosed and managed, occurring alongside a "failure to progress," where despite multiple appointments, patients described frustration at delays in obtaining a diagnosis and effective treatment for their pain. Throughout their care pathways, patients described the "effects of unmanaged pain," where the longer the pain went unmanaged, the greater its potential to negatively affect their lives. Findings of this study suggest that the current care pathway is inefficient and fails to meet patient needs. Future work needs to focus on working with stakeholder groups to redesign patient-centered care pathways. Knowledge Transfer Statement: Data from qualitative interviews conducted with patients with persistent orofacial pain suggest significant problems with the existing care pathway, consisting of delays to diagnosis, treatment, and referral. Patients describing their struggle to progress through the current care pathway highlighted the difficulties occurring while living with orofacial pain. This study suggests a need for a revised care pathway, which better meets the needs of people with persistent orofacial pain.

Pivotal Trial of the Efficacy and Safety of Oxymetazoline Cream 1.0% for the Treatment of Persistent Facial Erythema Associated With Rosacea: Findings from the Second REVEAL Trial.

PubMed

Baumann, Leslie; Goldberg, David J; Stein Gold, Linda; Tanghetti, Emil A; Lain, Edward; Kaufman, Joely; Weng, Emily; Berk, David R; Ahluwalia, Gurpreet

2018-03-01

Rosacea is a chronic dermatologic condition with limited treatment options, particularly for persistent erythema. This pivotal phase 3 study evaluated oxymetazoline, an a1A-adrenoceptor agonist, for the treatment of moderate to severe persistent erythema of rosacea. Eligible patients were randomly assigned 1:1 to receive oxymetazoline cream 1.0% or vehicle applied topically to the face once daily for 29 days. The primary efficacy outcome was ≥2-grade improvement from baseline on both Clinician Erythema Assessment (CEA) and Subject Self-Assessment for rosacea facial redness (SSA) (composite success) at 3, 6, 9, and 12 hours postdose on day 29. Digital image analysis of rosacea facial erythema was evaluated as a secondary efficacy outcome measure. Safety assessments included treatment-emergent adverse events (TEAEs) and dermal tolerability. Patients were followed for 28 days posttreatment to assess worsening of erythema (1-grade increase in severity from baseline on composite CEA/SSA in patients with moderate erythema at baseline; rebound effect). The study included 445 patients (mean age: 50.3 years; 78.7% female); most had moderate erythema at baseline (84.0% on CEA; 91.5% on SSA). The proportion of patients achieving the primary efficacy outcome was significantly greater with oxymetazoline versus vehicle (P=0.001). Similar results favoring oxymetazoline over vehicle were observed for the individual CEA and SSA scores (P less than 0.001 and P=0.011, respectively). Median reduction in rosacea facial erythema on day 29 as assessed by digital image analysis also favored oxymetazoline over vehicle (P less than 0.001). Safety results were similar between oxymetazoline and vehicle; discontinuations due to TEAEs were low (2.7% vs 0.5%). Following cessation of treatment, 2 (1.2%) patients in the oxymetazoline group and no patient in the vehicle group had rebound effect compared with their day 1 baseline score. Topical oxymetazoline applied to the face once daily for 29 days was effective, safe, and well tolerated in the treatment of moderate to severe persistent facial erythema of rosacea.

J Drugs Dermatol. 2018;17(3):290-298.

Effects of Adding an Internet-Based Pain Coping Skills Training Protocol to a Standardized Education and Exercise Program for People With Persistent Hip Pain (HOPE Trial): Randomized Controlled Trial Protocol

PubMed Central

Rini, Christine; Keefe, Francis; French, Simon; Nelligan, Rachel; Kasza, Jessica; Forbes, Andrew; Dobson, Fiona; Haxby Abbott, J.; Dalwood, Andrew; Vicenzino, Bill; Harris, Anthony; Hinman, Rana S.

2015-01-01

Background Persistent hip pain in older people is usually due to hip osteoarthritis (OA), a major cause of pain, disability, and psychological dysfunction. Objective The purpose of this study is to evaluate whether adding an Internet-based pain coping skills training (PCST) protocol to a standardized intervention of education followed by physical therapist–instructed home exercise leads to greater reductions in pain and improvements in function. Design An assessor-, therapist-, and participant-blinded randomized controlled trial will be conducted. Setting The study will be conducted in a community setting. Participants The participants will be 142 people over 50 years of age with self-reported hip pain consistent with hip OA. Intervention Participants will be randomly allocated to: (1) a control group receiving a 24-week standardized intervention comprising an 8-week Internet-based education package followed by 5 individual physical therapy exercise sessions plus home exercises (3 times weekly) or (2) a PCST group receiving an 8-week Internet-based PCST protocol in addition to the control intervention. Measurements Outcomes will be measured at baseline and 8, 24, and 52 weeks, with the primary time point at 24 weeks. Primary outcomes are hip pain on walking and self-reported physical function. Secondary outcomes include health-related quality-of-life, participant-perceived treatment response, self-efficacy for pain management and function, pain coping attempts, pain catastrophizing, and physical activity. Measurements of adherence, adverse events, use of health services, and process measures will be collected at 24 and 52 weeks. Cost-effectiveness will be assessed at 52 weeks. Limitations A self-reported diagnosis of persistent hip pain will be used. Conclusions The findings will help determine whether adding an Internet-based PCST protocol to standardized education and physical therapist–instructed home exercise is more effective than education and exercise alone for persistent hip pain. This study has the potential to guide clinical practice toward innovative modes of psychosocial health care provision. PMID:26023213

Effects of Adding an Internet-Based Pain Coping Skills Training Protocol to a Standardized Education and Exercise Program for People With Persistent Hip Pain (HOPE Trial): Randomized Controlled Trial Protocol.

PubMed

Bennell, Kim L; Rini, Christine; Keefe, Francis; French, Simon; Nelligan, Rachel; Kasza, Jessica; Forbes, Andrew; Dobson, Fiona; Abbott, J Haxby; Dalwood, Andrew; Vicenzino, Bill; Harris, Anthony; Hinman, Rana S

2015-10-01

Persistent hip pain in older people is usually due to hip osteoarthritis (OA), a major cause of pain, disability, and psychological dysfunction. The purpose of this study is to evaluate whether adding an Internet-based pain coping skills training (PCST) protocol to a standardized intervention of education followed by physical therapist-instructed home exercise leads to greater reductions in pain and improvements in function. An assessor-, therapist-, and participant-blinded randomized controlled trial will be conducted. The study will be conducted in a community setting. The participants will be 142 people over 50 years of age with self-reported hip pain consistent with hip OA. Participants will be randomly allocated to: (1) a control group receiving a 24-week standardized intervention comprising an 8-week Internet-based education package followed by 5 individual physical therapy exercise sessions plus home exercises (3 times weekly) or (2) a PCST group receiving an 8-week Internet-based PCST protocol in addition to the control intervention. Outcomes will be measured at baseline and 8, 24, and 52 weeks, with the primary time point at 24 weeks. Primary outcomes are hip pain on walking and self-reported physical function. Secondary outcomes include health-related quality-of-life, participant-perceived treatment response, self-efficacy for pain management and function, pain coping attempts, pain catastrophizing, and physical activity. Measurements of adherence, adverse events, use of health services, and process measures will be collected at 24 and 52 weeks. Cost-effectiveness will be assessed at 52 weeks. A self-reported diagnosis of persistent hip pain will be used. The findings will help determine whether adding an Internet-based PCST protocol to standardized education and physical therapist-instructed home exercise is more effective than education and exercise alone for persistent hip pain. This study has the potential to guide clinical practice toward innovative modes of psychosocial health care provision. © 2015 American Physical Therapy Association.

Single-walled carbon nanotubes disturbed the immune and metabolic regulation function 13-weeks after a single intratracheal instillation

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

Park, Eun-Jung, E-mail: pejtoxic@hanmail.net; Hong, Young-Shick; Lee, Byoung-Seok

2016-07-15

Due to their unique physicochemical properties, the potential health effects of single-walled carbon nanotubes (SWCNTs) have attracted continuous attention together with their extensive application. In this study, we aimed to identify local and systemic health effects following pulmonary persistence of SWCNTs. As expected, SWCNTs remained in the lung for 13 weeks after a single intratracheal instillation (50, 100, and 200 μg/kg). In the lung, the total number of cells and the percentages of lymphocytes and neutrophils significantly increased at 200 μg/kg compared to the control, and the Th1-polarized immune response was induced accompanying enhanced expression of tissue damage-related genes andmore » increased release of chemokines. Additionally, SWCNTs enhanced the expression of antigen presentation-related proteins on the surface of antigen-presenting cells, however, maturation of dendritic cells was inhibited by their persistence. As compared to the control, a significant increase in the percentage of neutrophils and a remarkable decrease of BUN and potassium level were observed in the blood of mice treated with the highest dose. This was accompanied by the down-regulation of the expression of antigen presentation-related proteins on splenocytes. Moreover, protein and glucose metabolism were disturbed with an up-regulation of fatty acid β-oxidation. Taken together, we conclude that SWCNTs may induce adverse health effects by disturbing immune and metabolic regulation functions in the body. Therefore, careful application of SWCNTs is necessary for the enforcement of safety in nano-industries. - Highlights: • We evaluated local and systemic health effects following persistence of SWCNTs. • SWCNTs remained in the lung for 13 weeks after a single intratracheal instillation. • Th1-polarized immune response was induced in the lung. • The expression of antigen presentation-related proteins was altered. • Immune and metabolic regulation function were disturbed.« less

[Concentrations of persistent toxic compounds in the Spanish population: a puzzle without pieces and the protection of public health].

PubMed

Porta, M; Kogevinas, M; Zumeta, E; Sunyer, J; Ribas-Fitó, N; Ruiz, Laura; Jariod, Manuel; Vioque, Jesús; Alguacil, Juan; Martín, Piedad; Malats, Núria; Ayude, Daniel

2002-01-01

The contamination by persistent toxic compounds (PTCs) of the general population is a fact of relevance from a public health perspective. It is also relevant to health care professionals, as well as for environmental, food, industrial and economic policies. Though in Spain information on food contamination by PTCs shows large time and geographic gaps, the scarcity of data is even more severe on the concentrations that PTCs have in people: a representative study of a general healthy population living in a wide geographic area has never been conducted in the country. However, the available studies indicate that around 80-100% of the population has detectable concentrations of DDE, PCBs, hexachlorbenzene or lindane. Studies on the effects that PTCs have upon humans are extremely infrequent in Spain. Yet, the international literature suggests that some PTCs may induce significant biological and clinical effects at doses below those traditionally deemed "safe". The mechanism of action of PTCs are not restricted to endocrine disruption. Assessing the clinical and social relevance of the more subtle and long-term effects of PTCs presents interesting challenges and opportunities. Spain and other European countries lack population indicators on the impact that environmental processes have on human health. Several government levels have a role to fulfill in the monitoring of biological levels of PTCs among persons in order to assess the risks of adverse health effects. Along with over a hundred other countries. Spain will soon try to implement the Stockholm treaty on persistent organic pollutants (POPs). This constitutes a new opportunity to develop more efficient policies to control PTC residues in food, humans and the environment. As part of the treaty implementation it is necessary to launch a Report on factors that influence body concentrations of PTCs in the Spain general population.

Gene Therapy in a Patient with Sickle Cell Disease.

PubMed

Ribeil, Jean-Antoine; Hacein-Bey-Abina, Salima; Payen, Emmanuel; Magnani, Alessandra; Semeraro, Michaela; Magrin, Elisa; Caccavelli, Laure; Neven, Benedicte; Bourget, Philippe; El Nemer, Wassim; Bartolucci, Pablo; Weber, Leslie; Puy, Hervé; Meritet, Jean-François; Grevent, David; Beuzard, Yves; Chrétien, Stany; Lefebvre, Thibaud; Ross, Robert W; Negre, Olivier; Veres, Gabor; Sandler, Laura; Soni, Sandeep; de Montalembert, Mariane; Blanche, Stéphane; Leboulch, Philippe; Cavazzana, Marina

2017-03-02

Sickle cell disease results from a homozygous missense mutation in the β-globin gene that causes polymerization of hemoglobin S. Gene therapy for patients with this disorder is complicated by the complex cellular abnormalities and challenges in achieving effective, persistent inhibition of polymerization of hemoglobin S. We describe our first patient treated with lentiviral vector-mediated addition of an antisickling β-globin gene into autologous hematopoietic stem cells. Adverse events were consistent with busulfan conditioning. Fifteen months after treatment, the level of therapeutic antisickling β-globin remained high (approximately 50% of β-like-globin chains) without recurrence of sickle crises and with correction of the biologic hallmarks of the disease. (Funded by Bluebird Bio and others; HGB-205 ClinicalTrials.gov number, NCT02151526 .).

Derivation of occupational exposure levels (OELs) of low-toxicity isometric biopersistent particles: How can the kinetic lung overload paradigm be used for improved inhalation toxicity study design and OEL-derivation?

PubMed

Pauluhn, Jürgen

2014-12-20

Convincing evidence suggests that poorly soluble low-toxicity particles (PSP) exert two unifying major modes of action (MoA), in which one appears to be deposition-related acute, whilst the other is retention-related and occurs with particle accumulation in the lung and associated persistent inflammation. Either MoA has its study- and cumulative dose-specific adverse outcome and metric. Modeling procedures were applied to better understand as to which extent protocol variables may predetermine any specific outcome of study. The results from modeled and empirical studies served as basis to derive OELs from modeled and empirically confirmed directions. This analysis demonstrates that the accumulated retained particle displacement volume was the most prominent unifying denominator linking the pulmonary retained volumetric particle dose to inflammogenicity and toxicity. However, conventional study design may not always be appropriate to unequivocally discriminate the surface thermodynamics-related acute adversity from the cumulative retention volume-related chronic adversity. Thus, in the absence of kinetically designed studies, it may become increasingly challenging to differentiate substance-specific deposition-related acute effects from the more chronic retained cumulative dose-related effects. It is concluded that the degree of dissolution of particles in the pulmonary environment seems to be generally underestimated with the possibility to attribute to toxicity due to decreased particle size and associated changes in thermodynamics and kinetics of dissolution. Accordingly, acute deposition-related outcomes become an important secondary variable within the pulmonary microenvironment. In turn, lung-overload related chronic adversities seem to be better described by the particle volume metric. This analysis supports the concept that 'self-validating', hypothesis-based computational study design delivers the highest level of unifying information required for the risk characterization of PSP. In demonstrating that the PSP under consideration is truly following the generic PSP-paradigm, this higher level of mechanistic information reduces the potential uncertainty involved with OEL derivation.

Methodology of AA CRASH: a prospective observational study evaluating the incidence and pathogenesis of adverse post-traumatic sequelae in African-Americans experiencing motor vehicle collision.

PubMed

Linnstaedt, Sarah D; Hu, JunMei; Liu, Andrea Y; Soward, April C; Bollen, Kenneth A; Wang, Henry E; Hendry, Phyllis L; Zimny, Erin; Lewandowski, Christopher; Velilla, Marc-Anthony; Damiron, Kathia; Pearson, Claire; Domeier, Robert; Kaushik, Sangeeta; Feldman, James; Rosenberg, Mark; Jones, Jeffrey; Swor, Robert; Rathlev, Niels; McLean, Samuel A

2016-09-06

A motor vehicle collision (MVC) is one of the most common life-threatening events experienced by individuals living in the USA. While most individuals recover following MVC, a significant proportion of individuals develop adverse post-traumatic sequelae such as post-traumatic stress disorder or persistent musculoskeletal pain. Adverse post-traumatic sequelae are common, morbid and costly public health problems in the USA and other industrialised countries. The pathogenesis of these disorders following MVC remains poorly understood. In the USA, available data suggest that African-Americans experience an increased burden of adverse post-traumatic sequelae after MVC compared to European Americans, but to date no studies examining the pathogenesis of these disorders among African-Americans experiencing MVC have been performed. The African-American CRASH (AA CRASH) study is an NIH-funded, multicentre, prospective study that enrols African-Americans (n=900) who present to the emergency department (ED) within 24 hours of MVC. Participants are enrolled at 13 ED sites in the USA. Individuals who are admitted to the hospital or who report a fracture or tissue injury are excluded. Participants complete a detailed ED interview that includes an assessment of crash history, current post-traumatic symptoms and health status prior to the MVC. Blood samples are also collected in the ED using PAXgene DNA and PAXgene RNA tubes. Serial mixed-mode assessments 6 weeks, 6 months and 1 year after MVC include an assessment of adverse sequelae, general health status and health service utilisation. The results from this study will provide insights into the incidence and pathogenesis of persistent pain and other post-traumatic sequelae in African-Americans experiencing MVC. AA CRASH has ethics approval in the USA, and the results will be published in a peer-reviewed journal. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

The value and safety of specific nasal provocation in the diagnosis of allergic rhinitis in mild persistent asthma under inhaled steroid therapy.

PubMed

Tuskan, Tansu Cengiz; Gemicioglu, Bilun; Ikitimur, Hande; Yilmaz, Nail; Tuskan, Kemal; Oz, Ferhan; Can, Gunay

2010-01-01

Although specific nasal provocation is an objective diagnostic test for allergic rhinitis, it can also increase the lower airway responsiveness in asthmatic patients. Our goal was to determine the value and safety of specific nasal provocation test for the diagnosis of allergic rhinitis in mild persistent asthmatic patients under low-dose inhaled steroid therapy. The study was performed on 32 mild persistent, stable, mite-sensitive allergic asthmatics (group 1), 9 mild persistent nonallergic asthmatics (group 2) and 9 healthy non-smokers (group 3). Nasal symptoms were noted, paranasal sinus computerized tomography (PNCT) and rhinoscopic evaluations were performed. Cases with pathologic-anatomic changes in PNCT and rhinoscopy were excluded. Symptom scoring, flow-volume, peak expiratory flow (PEF), serum and nasal lavage eosinophil cationic protein (ECP) and nasal lavage eosinophil counts were performed before mite specific nasal provocation test and at the 0th, 4th and 24th hours following the test. No adverse effects were observed in all diagnostic procedures. Total diagnostic value of nasal symptoms were found to be at 92%, while being 70% for rhinoscopy and 88% for specific nasal provocation test respectively in the diagnosis of allergic rhinitis in group 1. Statistically significant differences were found between basal nasal lavage eosinophil values (p < 0.001) and ECP levels (p < 0.05) when group 1 was compared with both group 2 and group 3. In the remaining measured values between three groups, no statistically significant differences were found. Specific nasal provocation test is a safe method for mild house dust mite allergic asthma cases under low-dose inhaled steroid therapy, but history of rhinitis might be sufficient for the diagnosis of allergic rhinitis.

Areal distribution and concentrations of contaminants of concern in surficial streambed and lakebed sediments, Lake Erie-Lake Saint Clair Drainages, 1990-97

USGS Publications Warehouse

Rheaume, S.J.; Button, D.T.; Myers, Donna N.; Hubbell, D.L.

2001-01-01

Concerns about elevated concentrations of contaminants such as polychlorinated biphenyls and mercury in aquatic bed sediments throughout the Great Lakes Basin have resulted in a need for better understanding of the scope and severity of the problem. Various organochlorine pesticides, polychlorinated biphenyls, trace metals, and polycyclic aromatic hydrocarbons are a concern because of their ability to persist and accumulate in aquatic sediments and their association with adverse aquatic biological effects. The areal distribution and concentrations in surficial bed sediments of 20 contaminants of concern with established bed-sediment-toxicity guidelines were examined in relation to their potential effects on freshwater aquatic biota. Contaminants at more than 800 sampling locations are characterized in this report. Surficial bed-sediment-quality data collected from 1990 to 1997 in the Lake Erie?Lake Saint Clair Drainages were evaluated to reflect recent conditions. In descending order, concentrations of total polycyclic aromatic hydrocarbons, phenanthrene, total polychlorinated biphenyls, chrysene, benz[a]anthracene, benzo[a]pyrene, cadmium, lead, zinc, arsenic, and mercury were the contaminants that most commonly exceeded levels associated with probable adverse effects on aquatic benthic organisms. The highest concentrations of most of these contaminants in aquatic bed sediments are confined to the 12 specific geographic Areas of Concern identified in the 1987 Revisions to the Great Lakes Water Quality Agreement of 1972. An exception is arsenic, which was detected at concentrations exceeding threshold effect levels at many locations outside Areas of Concern.

MODEL AND CELL MEMBRANE PARTITIONING OF PERFLUOROOCTANESULFONATE IS INDEPENDENT OF THE LIPID CHAIN LENGTH

PubMed Central

Xie, Wei; Ludewig, Gabriele; Wang, Kai; Lehmler, Hans-Joachim

2009-01-01

Perfluorooctanesulfonic acid (PFOS) is a persistent environmental pollutant that may cause adverse health effects in humans and animals by interacting with and disturbing of the normal properties of biological lipid assemblies. To gain further insights into these interactions, we investigated the effect of PFOS potassium salt on dimyristoyl- (DMPC), dipalmitoyl- (DPPC) and distearoylphosphatidylcholine (DSPC) model membranes using fluorescence anisotropy measurements and differential scanning calorimetry (DSC) and on the cell membrane of HL-60 human leukemia cells and freshly isolated rat alveolar macrophages using fluorescence anisotropy measurements. PFOS caused a concentration-dependent decrease of the main phase transition temperature (Tm) and an increased peak width (ΔTw) in both the fluorescence anisotropy and the DSC experiments, with a rank order DMPC > DPPC > DSPC. PFOS caused a fluidization of the gel phase of all phosphatidylcholines investigated, but had the opposite effect on the liquid crystalline phase. The apparent partition coefficients of PFOS between the phosphatidylcholine bilayer and the bulk aqueous phase were largely independent of the phosphatidylcholine chain length and ranged from 4.4 × 104 to 8.8 × 104. PFOS also significantly increased the fluidity of membranes of cells. These findings suggest that PFOS readily partitions into lipid assemblies, independent of their composition, and may cause adverse biological effects by altering their fluidity in a manner that depends on the membrane cooperativity and state (e.g., gel versus liquid crystalline phase) of the lipid assembly. PMID:19932010

Effectiveness, safety and cost of drug substitution in hypertension

PubMed Central

Johnston, Atholl; Stafylas, Panagiotis; Stergiou, George S

2010-01-01

Cost-containment measures in healthcare provision include the implementation of therapeutic and generic drug substitution strategies in patients whose condition is already well controlled with pharmacotherapy. Treatment for hypertension is frequently targeted for such measures. However, drug acquisition costs are only part of the cost-effectiveness equation, and a variety of other factors need to be taken into account when assessing the impact of switching antihypertensives. From the clinical perspective, considerations include maintenance of an appropriate medication dose during the switching process; drug equivalence in terms of clinical effectiveness; and safety issues, including the diverse adverse-event profiles of available alternative drugs, differences in the ‘inactive’ components of drug formulations and the quality of generic formulations. Patients' adherence to and persistence with therapy may be negatively influenced by switching, which will also impact on treatment effectiveness. From the economic perspective, the costs that are likely to be incurred by switching antihypertensives include those for additional clinic visits and laboratory tests, and for hospitalization if required to address problems arising from adverse events or poorly controlled hypertension. Indirect costs and the impact on patients' quality of life also require assessment. Substitution strategies for antihypertensives have not been tested in large outcome trials and there is little available clinical or economic evidence on which to base decisions to switch drugs. Although the cost of treatment should always be considered, careful assessment of the human and economic costs and benefits of antihypertensive drug substitution is required before this practice is recommended. PMID:20716230

Effectiveness, safety and cost of drug substitution in hypertension.

PubMed

Johnston, Atholl; Stafylas, Panagiotis; Stergiou, George S

2010-09-01

Cost-containment measures in healthcare provision include the implementation of therapeutic and generic drug substitution strategies in patients whose condition is already well controlled with pharmacotherapy. Treatment for hypertension is frequently targeted for such measures. However, drug acquisition costs are only part of the cost-effectiveness equation, and a variety of other factors need to be taken into account when assessing the impact of switching antihypertensives. From the clinical perspective, considerations include maintenance of an appropriate medication dose during the switching process; drug equivalence in terms of clinical effectiveness; and safety issues, including the diverse adverse-event profiles of available alternative drugs, differences in the 'inactive' components of drug formulations and the quality of generic formulations. Patients' adherence to and persistence with therapy may be negatively influenced by switching, which will also impact on treatment effectiveness. From the economic perspective, the costs that are likely to be incurred by switching antihypertensives include those for additional clinic visits and laboratory tests, and for hospitalization if required to address problems arising from adverse events or poorly controlled hypertension. Indirect costs and the impact on patients' quality of life also require assessment. Substitution strategies for antihypertensives have not been tested in large outcome trials and there is little available clinical or economic evidence on which to base decisions to switch drugs. Although the cost of treatment should always be considered, careful assessment of the human and economic costs and benefits of antihypertensive drug substitution is required before this practice is recommended.

POP emission inventories on different scales and their future trends

NASA Astrophysics Data System (ADS)

Theloke, Jochen; Breivik, Knut; Denier van der Gon, Hugo; Kugler, Ulrike; Li, Yi-Fan; Pacyna, Jozef; Panasiuk, Damian; Sundseth, Kyrre; Sweetman, Andy; Tao, Shu

2010-05-01

Persistent organic pollutants (POPs) are defined as organic substances that possess toxic characteristics; are persistent; bioaccumulate; are prone to long-range transboundary atmospheric transport and deposition; and are likely to cause significant adverse human health or environmental effects near to and distant from their sources. To reduce these adverse effects and for monitoring the effectiveness of existing international agreements, esp. UNECE-POP and UNEP protocols, concerning POPs the compilation of emission inventories is required. This presentation addresses emission inventories for POPs which are covered by existing protocols as well as candidate substances which are in focus for the revision of the international protocols. The following substances will be taken into account in this presentation: Dioxins and Furans (PCDD/F), PAHs, PCBs, Hexachlorbenzene (HCB), Pesticides (e.g. HCH, Dicofol and Endosulfan), Perfluoroctansulfonate (PFOS) and Polybrominated Diphenylethers (PBDEs), Hexachlorobutadiene (HCBD), Pentachlorobenzene (PeCB), Polychlorinated Naphthalenes (PCN), and Pentachlorophenols (PCPs). For all considered substances emission inventories exist with different qualities, from preliminary estimates to more complete inventories. These inventories are based on different methodologies (measurements, modelling, mass balance approaches, etc.), cover different regions (Europe, North America, Asia, China) and different spatial scales (regional, global) with different spatial resolutions. An overview will be given of the current state of the knowledge through a description of the main sources for the specific pollutants, the recent emission levels, a description of historical emission (incl. time series) and gridded data bases, if available. Furthermore, recommendations to improve POP emission inventories as well as major obstacles to achieve these improvements will be given. A further focus of this presentation will be an overview of future trends of specific POPs, e. g. PCB and PCDD/F until 2050, with special emphasis on the different approaches for compilation of future scenarios for specific substances. The following key questions concerning compilation of projections will be considered here: Do we have sufficient data on emissions and the trends in driving forces needed for making reasonable future projections? How might emission quantities and spatial distributions change over the next 20 to 50 years? How will different source categories change?

Perfluoroalkyl substances and fish consumption.

PubMed

Christensen, Krista Y; Raymond, Michelle; Blackowicz, Michael; Liu, Yangyang; Thompson, Brooke A; Anderson, Henry A; Turyk, Mary

2017-04-01

Perfluoroalkyl substances (PFAS) are an emerging class of contaminants. Certain PFAS are regulated or voluntarily limited due to concern about environmental persistence and adverse health effects, including thyroid disease and dyslipidemia. The major source of PFAS exposure in the general population is thought to be consumption of seafood. In this analysis we examine PFAS levels and their determinants, as well as associations between PFAS levels and self-reported fish and shellfish consumption, using a representative sample of the U.S. Data on PFAS levels and self-reported fish consumption over the past 30 days were collected from the 2007-2008, 2009-2010, 2011-2012, and 2013-2014 cycles of the National Health and Nutrition Examination Survey. Twelve different PFAS were measured in serum samples from participants. Ordinary least squares regression models were used to identify factors (demographic characteristics and fish consumption habits) associated with serum PFAS concentrations. Additional models were further adjusted for other potential exposures including military service and consumption of ready-to-eat and fast foods. Seven PFAS were detected in at least 30% of participants and were examined in subsequent analyses (PFDA, PFOA, PFOS, PFHxS, MPAH, PFNA, PFUA). The PFAS with the highest concentrations were PFOS, followed by PFOA, PFHxS and PFNA (medians of 8.3, 2.7, 1.5 and 1.0ng/mL). Fish consumption was generally low, with a median of 1.2 fish meals and 0.14 shellfish meals, reported over the past 30 days. After adjusting for demographic characteristics, total fish consumption was associated with reduced MPAH, and with elevated PFDE, PFNA and PFuDA. Shellfish consumption was associated with elevations of all PFAS examined except MPAH. Certain specific fish and shellfish types were also associated with specific PFAS. Adjustment for additional exposure variables resulted in little to no change in effect estimates for seafood variables. PFAS are emerging contaminants with widespread exposure, persistence, and potential for adverse health effects. In the general population, fish and shellfish consumption are associated with PFAS levels, which may indicate an avenue for education and outreach. Copyright © 2017 Elsevier Inc. All rights reserved.

The Pollution of the Oceans and Great Lakes by Persistent Organic Pollutants

NASA Astrophysics Data System (ADS)

Lohmann, R.; Muir, D.

2012-12-01

The presence of man-made organic chemicals across the Great Lakes and Oceans is widespread. Especially in the northern hemisphere, legacy persistent organic pollutants (POPs) such as polychlorinated biphenyls or DDT can be detected almost everywhere. Despite their ban several decades ago, concentrations are only declining slowly in the atmosphere, while time trends are not available for the waters of the world. While concentrations are often low (picogram per liter range), their bioaccumulation still causes adverse effects in top predators, including humans. Our results for legacy POPs highlight that oceans and the Great Lakes are by now re-releasing these compounds back to the atmosphere. More recently banned POPs include brominated flame retardants and perfluorinated compounds. Atmospheric concentrations are slowly declining, while their impacts on the aquatic environment will be felt for decades to come. Due to the paucity of aqueous data on POPs, we called for a global effort to monitor key POPs using passive samplers (AQUA-GAPS). Our recent cruise results show perfluorinated compounds to be present in all ocean basins, suggesting that they will remain for good. As of yet unknown are the presence and effects of additional hundreds to thousands industrial chemicals that are suspected of being persistent, bioaccumulative and toxic. Several of these have been identified as compounds of potential concern, but few have been investigated in the oceans. The solution to the pollution of POPs will have to rely on better chemical screening prior to high-volume production. The recent REACH legislation by the EU is a step in the right direction, but will not prevent the on-going release of man-made chemicals over the next few decades, many of which are already in use and will continue to be released over time.

4-Valent Human Papillomavirus (4vHPV) Vaccine in Preadolescents and Adolescents After 10 Years.

PubMed

Ferris, Daron G; Samakoses, Rudiwilai; Block, Stanley L; Lazcano-Ponce, Eduardo; Restrepo, Jaime Alberto; Mehlsen, Jesper; Chatterjee, Archana; Iversen, Ole-Erik; Joshi, Amita; Chu, Jian-Li; Krick, Andrea Likos; Saah, Alfred; Das, Rituparna

2017-12-01

We describe the final 10-year data for the long-term follow-up study of the 4-valent human papillomavirus (4vHPV) vaccine in preadolescents and adolescents. In the base study (V501-018), 1661 sexually inactive boys and girls received the 4vHPV vaccine (early vaccination group [EVG], managed for 9.9 years) or a placebo at day 1, month 2, and month 6. Thereafter, at month 30, the placebo group (catch-up vaccination group [CVG], managed for 7.4 years) received the 4vHPV vaccine by using the same dosing schedule. Long-term anti-HPV type 6, 11, 16, and 18 immune responses were assessed. Effectiveness was estimated by calculating the incidence rate of the primary endpoints (HPV types 6, 11, 16, and 18-related disease or persistent infection). For HPV types 6, 11, and 16, 89% to 96% of subjects remained seropositive through 10-years postvaccination. The preadolescents had 38% to 65% higher geometric mean titers at month 7, which remained 16% to 42% higher at 10 years compared with adolescents. No cases of HPV type 6, 11, 16, and 18-related diseases were observed. Ten subjects had a persistent infection of ≥6 months duration with vaccine-type HPV and 2 subjects had persistent infection for ≥12 months. No new serious adverse events were reported through 10 years. A 3-dose regimen of the 4vHPV vaccine was immunogenic, clinically effective, and generally well tolerated in preadolescents and adolescents during 10 years of follow-up. These long-term findings support efforts to vaccinate this population against HPV before exposure. Copyright © 2017 by the American Academy of Pediatrics.

Stressful life experiences in adolescence and cardiometabolic risk factors in young adulthood.

PubMed

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

2015-04-01

An increasing number of studies have provided evidence for the persistent influence of childhood/adolescent socioeconomic adversities on subsequent health outcomes. However, less is known about the distinct and additive influences of these early socioeconomic adversities and adolescents' own stressful life experiences on health outcomes in young adulthood. We used data from 11,030 adolescents who participated in the National Longitudinal Study of Adolescent Health at Waves 1, 3, and 4 and provided biomarker data at Wave 4. Three early socioeconomic adversities (community socioeconomic adversity, family economic hardship, and low parental education) were evaluated. Adolescents' stressful transition to young adulthood was captured by six specific precocious life events as follows: early sex, early marriage or cohabitation, early leaving home, early pregnancy, early employment, and truncated education. A summary measure of cardiovascular and metabolic disease risk was assessed using nine biomarkers. Univariate, bivariate, and multivariate regression analyses were employed. Early socioeconomic adversities and stressful life transition events were uniquely associated with elevated levels of cardiometabolic (CM) biomarkers and cumulative CM disease risk. For all of the biomarkers, young adults in high-adversity/stress groups were more likely to be in the high CM disease risk groups (>75th percentile) than in the low-adversity/stress groups. These findings provide support for the influence of multiple early socioeconomic adversities and adolescents' stressful life transitions on their CM disease risk as young adults. Increased efforts to prevent and mitigate these experiences may improve disease risks across a number of biomarkers. Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Early-Life Social Origins of Later-Life Body Weight: The Role of Socioeconomic Status and Health Behaviors over the Life Course

PubMed Central

Logan, Ellis Scott; Richman, Aliza

2014-01-01

Using the 1957-2004 data from the Wisconsin Longitudinal Study, we apply structural equation modeling to examine gender-specific effects of family socioeconomic status (SES) at age 18 on body weight at age 65. We further explore SES and health behaviors over the life course as mechanisms linking family background and later-life body weight. We find that early-life socioeconomic disadvantage is related to higher body weight at age 65 and a steeper weight increase between midlife and late life. These adverse effects are stronger among women than men. Significant mediators of the effect of parents' SES include adolescent body mass (especially among women) as well as exercise and SES in midlife. Yet, consistent with the critical period mechanism, the effect of early-life SES on late-life body weight persists net of all mediating variables. This study expands current understanding of life-course mechanisms that contribute to obesity and increase biological vulnerability to social disadvantage. PMID:24767590

Dioxin Toxicity In Vivo Results from an Increase in the Dioxin-Independent Transcriptional Activity of the Aryl Hydrocarbon Receptor

PubMed Central

Céspedes, Miguel Angel; Galindo, Maximo Ibo; Couso, Juan Pablo

2010-01-01

The Aryl hydrocarbon receptor (Ahr) is the nuclear receptor mediating the toxicity of dioxins -widespread and persistent pollutants whose toxic effects include tumor promotion, teratogenesis, wasting syndrome and chloracne. Elimination of Ahr in mice eliminates dioxin toxicity but also produces adverse effects, some seemingly unrelated to dioxin. Thus the relationship between the toxic and dioxin-independent functions of Ahr is not clear, which hampers understanding and treatment of dioxin toxicity. Here we develop a Drosophila model to show that dioxin actually increases the in vivo dioxin-independent activity of Ahr. This hyperactivation resembles the effects caused by an increase in the amount of its dimerisation partner Ahr nuclear translocator (Arnt) and entails an increased transcriptional potency of Ahr, in addition to the previously described effect on nuclear translocation. Thus the two apparently different functions of Ahr, dioxin-mediated and dioxin-independent, are in fact two different levels (hyperactivated and basal, respectively) of a single function. PMID:21079739

Therapeutic effects of arotinolol, a beta-adrenergic blocker, on tremor in MPTP-induced parkinsonian monkeys.

PubMed

Kuno, S; Mizuta, E; Nishida, J; Takechi, M

1992-10-01

The effect of arotinolol, a peripherally acting beta-adrenergic-blocking agent, on postural or kinetic tremor was studied in monkeys with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism. Male cynomolgus monkeys (Macaca fascicularis) were treated with three injections of MPTP hydrochloride (0.3 mg/kg, i.v.) at an interval of 3-4 days, followed by several injections of the same dose every 7 days. Four monkeys with persistent parkinsonian symptoms manifested for greater than 1 year were used. The animals developed mild to moderate degrees of postural or kinetic tremor, and their motor activity was reduced. Arotinolol (20-30 mg/kg, s.c.) significantly suppressed postural tremor in a dose-dependent manner. Propranolol (20-30 mg/kg) was also effective in suppressing the tremor. However, the application of propranolol induced emesis, whereas arotinolol had no adverse effects. These results suggest that arotinolol is a useful adjunct to dopaminergic therapy for tremor in Parkinson's disease.

Short-term exposure to JP-8 jet fuel results in long-term immunotoxicity.

PubMed

Harris, D T; Sakiestewa, D; Robledo, R F; Witten, M

1997-01-01

Chronic exposure to jet fuel has been shown to have adverse effects on human liver function, to cause emotional dysfunction, to cause abnormal electroencephalograms, to cause shortened attention spans, and to decrease sensorimotor speed. Due to the decision by the United States Air Force to implement the widespread use of JP-8 jet fuel in its operations, a thorough understanding of its potential effects upon exposed personnel is both critical and necessary. Exposure to potential environmental toxicants such as JP-8 may have significant effects on host systems beyond those readily visible (i.e., physiology, cardiology, respiratory, etc.); e.g., the immune system. Previous studies have shown that short-term, low concentration JP-8 exposure had significant effects on the immune system, which should have serious consequences for the exposed host in terms of susceptibility to infectious agents. If these alterations in immune function were long-lasting, it might also result in an increased likelihood of development and/or progression of cancer, as well as autoimmune disease. In the current study, mice were exposed for 1 h/day for 7 days to a moderate (1000 mg/m3) and a high (2500 mg/m3) concentration of aerosolized JP-8 jet fuel to stimulate occupational exposures. One to 28 days after the last exposure the mice were analyzed for effects of the exposure on their immune systems. It was observed that decrease in viable immune cell numbers and immune organ weights found at 24 h after exposure persisted for extended periods of time. Further, JP-8 exposure resulted in significantly decreased immune infection, as analyzed by mitogenesis assays, which persisted for up to 4 weeks post-exposure. Thus, short-term exposure of mice to JP-8 jet fuel caused significant toxicological effects on the immune system, which were long-lasting and persistent. It appears that the immune system may be the most sensitive indicator of toxicological damage due to JP-8 exposure. Such long-term changes in immune status may have significant effects on the health of the exposed individual.

Pre-treatment anxiety is associated with persistent chemotherapy-induced peripheral neuropathy in women treated with neoadjuvant chemotherapy for breast cancer.

PubMed

Lee, Kwang-Min; Jung, Dooyoung; Hwang, Heesung; Son, Kyung-Lak; Kim, Tae-Yong; Im, Seock-Ah; Lee, Kyung-Hun; Hahm, Bong-Jin

2018-05-01

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent adverse reaction caused by chemotherapeutic agents, especially the taxanes. CIPN can persist from months to years after completion of chemotherapy, decreasing quality of life for cancer survivors. The aim of this study was to explore the incidence and risk factors of persistent CIPN among women with breast cancer receiving neoadjuvant chemotherapy. In this prospective study, we recruited women with breast cancer receiving neoadjuvant chemotherapy, including four cycles of docetaxel. Participants reported neuropathic symptoms of tingling/numbness at baseline, at the end of chemotherapy treatment, and at 8 months after completion of chemotherapy. Candidate factors associated with CIPN were assessed before chemotherapy. Among 111 participants, 50 (45.0%) experienced CIPN during chemotherapy, and 21 (18.9%) reported persistent CIPN after chemotherapy. Univariate logistic regression analysis revealed that development of CIPN was significantly associated with pre-treatment numbness (odds ratio [OR], 4.02; 95% confidence interval [CI], 1.09-7.40; p = .033), and persistent CIPN was significantly associated with pre-treatment numbness (OR, 3.60; 95% CI, 1.12-11.61; p = .032) and pre-treatment anxiety (OR, 5.02; 95% CI, 1.84-13.70; p = .002). Multivariate analysis indicated that pre-treatment anxiety remained significantly associated with persistent CIPN (OR, 4.01; 95% CI, 1.25-12.87; p = .020). Our results suggested that pre-treatment anxiety might be related to a patient's risk for persistent CIPN in women with breast cancer undergoing neoadjuvant chemotherapy. Further research is required to investigate if interventions targeting pre-treatment anxiety could provide prevention and management for persistent CIPN. Copyright © 2018. Published by Elsevier Inc.

Long-term persistence with mirabegron in a real-world clinical setting.

PubMed

Wada, Naoki; Watanabe, Masaki; Banjo, Hiroko; Tsuchida, Miyu; Hori, Junichi; Tamaki, Gaku; Azumi, Makoto; Kita, Masafumi; Kakizaki, Hidehiro

2018-05-01

To examine the long-term persistence rate with mirabegron in a real-world clinical setting. We retrospectively collected the data of patients who were prescribed mirabegron. We investigated the persistence rate and the reason for the discontinuation. The analysis included patient's age, diagnosis, Overactive Bladder Symptom Score, prostatic volume, the prescription by specialists for lower urinary tract dysfunction, drug-naïve patients, replacement of antimuscarinics or add-on therapy to antimuscarinics. A total of 556 patients were included. Among them, 401 patients (72%) had overactive bladder and the other 155 (28%) were categorized as having other storage symptoms. During the observation period, 170 patients (42%) with overactive bladder discontinued mirabegron. The reasons for discontinuation in patients with overactive bladder included unmet expectation of treatment (45 patients, 26%), any adverse events (38 patients, 22%) or symptom improvement (37 patients, 22%). The persistence or discontinuation was not related with age, Overactive Bladder Symptom Score, prostatic volume or the prescription by specialists, while older male patients tended to continue mirabegron. The 3-year persistence rates in female and male overactive bladder patients were 46% and 51%, respectively, and these were better than those in patients with storage symptoms without urgency. In female overactive bladder patients, the persistence rate with mirabegron used as add-on therapy to antimuscarinics was higher than that in the drug-naïve patients on the Kaplan-Meier curve. The present study shows a relatively good long-term persistence rate with mirabegron in overactive bladder patients, notwithstanding the retrospective study in an academic hospital. The combined treatment with antimuscarinics could result in a good persistence rate with mirabegron. © 2018 The Japanese Urological Association.

Early Adverse Caregiving Experiences and Preschoolers' Current Attachment Affect Brain Responses during Facial Familiarity Processing: An ERP Study.

PubMed

Kungl, Melanie T; Bovenschen, Ina; Spangler, Gottfried

2017-01-01

When being placed into more benign environments like foster care, children from adverse rearing backgrounds are capable of forming attachment relationships to new caregivers within the first year of placement, while certain problematic social behaviors appear to be more persistent. Assuming that early averse experiences shape neural circuits underlying social behavior, neurophysiological studies on individual differences in early social-information processing have great informative value. More precisely, ERP studies have repeatedly shown face processing to be sensitive to experience especially regarding the caregiving background. However, studies on effects of early adverse caregiving experiences are restricted to children with a history of institutionalization. Also, no study has investigated effects of attachment security as a marker of the quality of the caregiver-child relationship. Thus, the current study asks how adverse caregiving experiences and attachment security to (new) caregivers affect early- and mid-latency ERPs sensitive to facial familiarity processing. Therefore, pre-school aged foster children during their second year within the foster home were compared to an age matched control group. Attachment was assessed using the AQS and neurophysiological data was collected during a passive viewing task presenting (foster) mother and stranger faces. Foster children were comparable to the control group with regard to attachment security. On a neurophysiological level, however, the foster group showed dampened N170 amplitudes for both face types. In both foster and control children, dampened N170 amplitudes were also found for stranger as compared to (foster) mother faces, and, for insecurely attached children as compared to securely attached children. This neural pattern may be viewed as a result of poorer social interactions earlier in life. Still, there was no effect on P1 amplitudes. Indicating heightened attentional processing, Nc amplitude responses to stranger faces were found to be enhanced in foster as compared to control children. Also, insecurely attached children allocated more attentional resources for the neural processing of mother faces. The study further confirms that early brain development is highly sensitive to the quality of caregiving. The findings are also relevant from a developmental perspective as miswiring of neural circuits may possibly play a critical role in children's psycho-social adjustment.

What Factors Promote Student Resilience on a Level 1 Distance Learning Module?

ERIC Educational Resources Information Center

Simons, Joan; Beaumont, Kythe; Holland, Lesley

2018-01-01

Resilience is understood to be the ability to adapt positively in the face of adversity. In relation to new students on a distance learning module, this can mean how they adapt and make sense of the demands of their chosen study to enable them to persist in their studies. This article reports a small-scale study involving semi-structured telephone…

Evidence for the Risks and Consequences of Adolescent Cannabis Exposure.

PubMed

Levine, Amir; Clemenza, Kelly; Rynn, Moira; Lieberman, Jeffrey

2017-03-01

This review of the scientific literature examines the potential adult sequelae of exposure to cannabis and related synthetic cannabinoids in adolescence. We examine the four neuropsychiatric outcomes that are likely most vulnerable to alteration by early cannabinoid use, as identified within both the clinical and preclinical research: cognition, emotional functioning, risk for psychosis, and addiction. A literature search was conducted through PubMed, PsychInfo, and Google Scholar with no publication date restrictions. The search terms used were "adolescent" and "adult," and either "cannabis," "marijuana," "delta-9-tetra-hydrocannabinol," or "cannabinoid," which was then crossed with one or more of the following terms: "deficit," "impairment," "alteration," "long-term," "persistent," "development," "maturation," and "pubescent." The majority of the clinical and preclinical data point to a strong correlation between adolescent cannabinoid exposure and persistent, adverse neuropsychiatric outcomes in adulthood. Although the literature supports the hypothesis that adolescent cannabis use is connected to impaired cognition and mental health in adults, it does not conclusively demonstrate that cannabis consumption alone is sufficient to cause these deficits in humans. The animal literature, however, clearly indicates that adolescent-onset exposure to cannabinoids can catalyze molecular processes that lead to persistent functional deficits in adulthood, deficits that are not found to follow adult-onset exposure and that model some of the adverse outcomes reported in humans among adult populations of early-onset cannabis users. Based on the data in the current literature, a strong association is found between early, frequent, and heavy adolescent cannabis exposure and poor cognitive and psychiatric outcomes in adulthood, yet definite conclusions cannot yet be made as to whether cannabis use alone has a negative impact on the human adolescent brain. Future research will require animal models and longitudinal studies to be carefully designed with a focus on integrating assessments of molecular, structural, and behavioral outcomes in order to elucidate the full range of potential adverse and long-term consequences of cannabinoid exposure in adolescence. Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Targeting acetylcholine receptor M3 prevents the progression of airway hyperreactivity in a mouse model of childhood asthma.

PubMed

Patel, Kruti R; Bai, Yan; Trieu, Kenneth G; Barrios, Juliana; Ai, Xingbin

2017-10-01

Asthma often progresses into adulthood from early-life episodes of adverse environmental exposures. However, how the injury to developing lungs contributes to the pathophysiology of persistent asthma remains poorly understood. In this study, we identified an age-related mechanism along the cholinergic nerve-airway smooth muscle (ASM) axis that underlies prolonged airway hyperreactivity (AHR) in mice. We showed that ASM continued to mature until ∼3 wk after birth. Coinciding with postnatal ASM maturation, there was a critical time window for the development of ASM hypercontractility after cholinergic stimulation. We found that allergen exposure in neonatal mice, but not in adult mice, elevated the level and activity of cholinergic nerves (termed neuroplasticity). We demonstrated that cholinergic neuroplasticity is necessary for the induction of persistent AHR after neonatal exposure during rescue assays in mice deficient in neuroplasticity. In addition, early intervention with cholinergic receptor muscarinic (ChRM)-3 blocker reversed the progression of AHR in the neonatal exposure model, whereas β2-adrenoceptor agonists had no such effect. Together, our findings demonstrate a functional relationship between cholinergic neuroplasticity and ASM contractile phenotypes that operates uniquely in early life to induce persistent AHR after allergen exposure. Targeting ChRM3 may have disease-modifying benefits in childhood asthma.-Patel, K. R., Bai, Y., Trieu, K. G., Barrios, J., Ai, X. Targeting acetylcholine receptor M3 prevents the progression of airway hyperreactivity in a mouse model of childhood asthma. © FASEB.

Effective Synthesis of Sulfate Metabolites of Chlorinated Phenols

PubMed Central

Lehmler, Hans-Joachim; He, Xianran; Li, Xueshu; Duffel, Michael W.; Parkin, Sean

2013-01-01

Chlorophenols are an important class of persistent environmental contaminants and have been implicated in a range of adverse health effects, including cancer. They are readily conjugated and excreted as the corresponding glucuronides and sulfates in the urine of humans and other species. Here we report the synthesis and characterization of a series of ten chlorophenol sulfates by sulfation of the corresponding chlorophenols with 2,2,2-trichloroethyl (TCE) chlorosulfate using N,N-dimethylaminopyridine (DMAP) as base. Deprotection of the chlorophenol diesters with zinc powder/ammonium formate yielded the respective chlorophenol sulfate ammonium salts in good yield. The molecular structure of three TCE-protected chlorophenol sulfate diesters and one chlorophenol sulfate monoester were confirmed by X-ray crystal structure analysis. The chlorophenol sulfates were stable for several months if stored at −20 °C and, thus, are useful for future toxicological, environmental and human biomonitoring studies. PMID:23906814

The Costs of Depression

PubMed Central

Kessler, Ronald C.

2011-01-01

Brief summary Data are reviewed on the societal costs of major depressive disorder (MDD). Early-onset MDD is found to predict difficulties in subsequent role transitions, including low educational attainment, high risk of teen child-bearing, marital disruption, and unstable employment. Among people with specific social and productive roles, MDD is found to predict significant decrements in role functioning (e.g., low marital quality, low work performance, low earnings). MDD is also associated with elevated risk of onset, persistence, and severity of a wide range of chronic physical disorders as well as with increased early mortality due to an even wider range of physical disorders and to suicide. Although effectiveness trials show that expanded MDD treatment can reverse many of these adverse effects, only a minority of people with MDD receives treatment and the quality of treatment is unacceptably low among the majority of those in treatment. PMID:22370487

Altered energy production, lowered antioxidant potential, and inflammatory processes mediate CNS damage associated with abuse of the psychostimulants MDMA and methamphetamine

PubMed Central

Downey, Luke A.; Loftis, Jennifer M.

2014-01-01

Central nervous system (CNS) damage associated with psychostimulant dependence may be an ongoing, degenerative process with adverse effects on neuropsychiatric function. However, the molecular mechanisms regarding how altered energy regulation affects immune response in the context of substance use disorders are not fully understood. This review summarizes the current evidence regarding the effects of psychostimulant [particularly 3,4-methylenedioxy-N-methylamphetamine (MDMA) and methamphetamine] exposure on brain energy regulation, immune response, and neuropsychiatric function. Importantly, the neuropsychiatric impairments (e.g., cognitive deficits, depression, and anxiety) that persist following abstinence are associated with poorer treatment outcomes – increased relapse rates, lower treatment retention rates, and reduced daily functioning. Qualifying the molecular changes within the CNS according to the exposure and use patterns of specifically abused substances should inform the development of new therapeutic approaches for addiction treatment. PMID:24485894

Household Structure and Children’s Educational Attainment: A Perspective on Coresidence with Grandparents

PubMed Central

Monserud, Maria A.; Elder, Glen H.

2013-01-01

Children from alternative households complete fewer years of schooling. Yet little is known about the implications of coresidence with grandparents for educational attainment. Using data from the National Longitudinal Study of Adolescent Health (N = 10,083), this study found that extended households with two biological parents were not detrimental to high school completion or college enrollment. Although coresidence with grandparents did not compensate for not living with two biological parents, it seemed to be beneficial for the educational attainment of youth from single-mother households. In contrast, skipped-generation households were associated with a persistent disadvantage for educational attainment. Limited socioeconomic resources partially accounted for the adverse effects of alternative households, whereas parenting quality did not explain these effects. Interactions of gender by household structure suggested that stepfather households could have negative consequences for high school completion and college enrollment only for girls. PMID:24415799

Altered energy production, lowered antioxidant potential, and inflammatory processes mediate CNS damage associated with abuse of the psychostimulants MDMA and methamphetamine.

PubMed

Downey, Luke A; Loftis, Jennifer M

2014-03-15

Central nervous system (CNS) damage associated with psychostimulant dependence may be an ongoing, degenerative process with adverse effects on neuropsychiatric function. However, the molecular mechanisms regarding how altered energy regulation affects immune response in the context of substance use disorders are not fully understood. This review summarizes the current evidence regarding the effects of psychostimulant [particularly 3,4-methylenedioxy-N-methylamphetamine (MDMA) and methamphetamine] exposure on brain energy regulation, immune response, and neuropsychiatric function. Importantly, the neuropsychiatric impairments (e.g., cognitive deficits, depression, and anxiety) that persist following abstinence are associated with poorer treatment outcomes - increased relapse rates, lower treatment retention rates, and reduced daily functioning. Qualifying the molecular changes within the CNS according to the exposure and use patterns of specifically abused substances should inform the development of new therapeutic approaches for addiction treatment. Published by Elsevier B.V.

New Evidence on the Persistence of Health Spending

PubMed Central

Hirth, Richard A.; Gibson, Teresa B.; Levy, Helen G.; Smith, Jeffrey A.; Calónico, Sebastian; Das, Anup

2015-01-01

Surprisingly little is known about long-term spending patterns in the under-65 population. Such information could inform efforts to improve coverage and control costs. Using the MarketScan claims database, we characterize the persistence of healthcare spending in the privately-insured, under-65 population. Over a six-year period, 69.8% of enrollees never had annual spending in the top 10% of the distribution and the bottom 50% of spenders accounted for less than 10% of spending. Those in the top 10% in 2003 were almost as likely (34.4%) to be in the top 10% five years later as one year later (43.4%). Many comorbid conditions retained much of their predictive power even five years later. The persistence at both ends of the spending distribution indicates the potential for adverse selection and cream-skimming and supports the use of disease-management, particularly for those with the conditions that remained strong predictors of high spending throughout the follow-up period. PMID:25701579

New evidence on the persistence of health spending.

PubMed

Hirth, Richard A; Gibson, Teresa B; Levy, Helen G; Smith, Jeffrey A; Calónico, Sebastian; Das, Anup

2015-06-01

Surprisingly little is known about long-term spending patterns in the under-65 population. Such information could inform efforts to improve coverage and control costs. Using the MarketScan claims database, we characterize the persistence of health care spending in the privately insured, under-65 population. Over a 6-year period, 69.8% of enrollees never had annual spending in the top 10% of the distribution and the bottom 50% of spenders accounted for less than 10% of spending. Those in the top 10% in 2003 were almost as likely (34.4%) to be in the top 10% five years later as one year later (43.4%). Many comorbid conditions retained much of their predictive power even 5 years later. The persistence at both ends of the spending distribution indicates the potential for adverse selection and cream skimming and supports the use of disease management, particularly for those with the conditions that remained strong predictors of high spending throughout the follow-up period. © The Author(s) 2015.

Overnight switching from oxcarbazepine to eslicarbazepine acetate: an observational study.

PubMed

Schmid, E; Kuchukhidze, G; Kirschner, M; Leitinger, M; Höfler, J; Rohracher, A; Kalss, G; Wendling, A-S; Steinhoff, B J; Trinka, E

2017-04-01

There are clinical situations where it might be appropriate to switch patients from immediate-release oxcarbazepine (OXC) to eslicarbazepine acetate (ESL). We investigated the effects of transitioning patients overnight from OXC to ESL. A retrospective, single-center study was conducted in which patients with drug-resistant focal epilepsy on a stable dose of immediate-release OXC for at least 4 weeks were switched overnight to ESL. Patients were switched because they experienced persistent seizures with OXC but were unable to tolerate increased OXC dosing due to adverse events. Tolerability was assessed using the Adverse Events Profile (AEP), quality of life was assessed using the Quality of Life in Epilepsy Inventory 10 (QOLIE-10), and alertness was assessed as reaction time using a subtest of the Test Battery for Attention Performance version 2.3. Assessments were performed immediately prior to and 5 days after switching from OXC to ESL (days 0 and 5, respectively). The analysis included 21 patients (12 women, 9 men; mean age 36 years). After switching from OXC to ESL, there were significant improvements in mean scores for AEP (P<.001), QOLIE-10 (P=.001), and alertness (P<.05). Adverse Events Profile total scores improved for 21/21 (100.0%) patients, QOLIE-10 total scores improved for 17/21 (81.0%) patients, and alertness scores improved for 16/21 (76.2%) patients. In this short-term, single-center study, an overnight switch from twice-daily OXC to once-daily ESL in patients with drug-resistant focal epilepsies resulted in improvements in side effects, quality of life, and alertness. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Interaction between specific forms of childhood maltreatment and the serotonin transporter gene (5-HTT) in recurrent depressive disorder.

PubMed

Fisher, Helen L; Cohen-Woods, Sarah; Hosang, Georgina M; Korszun, Ania; Owen, Mike; Craddock, Nick; Craig, Ian W; Farmer, Anne E; McGuffin, Peter; Uher, Rudolf

2013-02-15

There is inconsistent evidence of interaction between stressful events and a serotonin transporter promoter polymorphism (5-HTTLPR) in depression. Recent studies have indicated that the moderating effect of 5-HTTLPR may be strongest when adverse experiences have occurred in childhood and the depressive symptoms persist over time. However, it is unknown whether this gene-environment interaction is present for recurrent depressive disorder and different forms of maltreatment. Therefore, patients with recurrent clinically diagnosed depression and controls screened for the absence of depression were utilised to examine the moderating effect of 5-HTTLPR on associations between specific forms of childhood adversity and recurrent depression. A sample of 227 recurrent unipolar depression cases and 228 never psychiatrically ill controls completed the Childhood Trauma Questionnaire to assess exposure to sexual, physical and emotional abuse, physical and emotional neglect in childhood. DNA extracted from blood or cheek swabs was genotyped for the short (s) and long (l) alleles of 5-HTTLPR. All forms of childhood maltreatment were reported as more severe by cases than controls. There was no direct association between 5-HTTLPR and depression. Significant interactions with additive and recessive 5-HTTLPR genetic models were found for overall severity of maltreatment, sexual abuse and to a lesser degree for physical neglect, but not other maltreatment types. The cross-sectional design limits causal inference. Retrospective report of childhood adversity may have reduced the accuracy of the findings. This study provides support for the role of interplay between 5-HTTLPR and a specific early environmental risk in recurrent depressive disorder. Copyright © 2012 Elsevier B.V. All rights reserved.

Efficacy and tolerability of ramelteon in a double-blind, placebo-controlled, crossover study in Japanese patients with chronic primary insomnia.

PubMed

Kohsaka, Masako; Kanemura, Takashi; Taniguchi, Mitsutaka; Kuwahara, Hiroo; Mikami, Akira; Kamikawa, Kunihisa; Uno, Hideki; Ogawa, Atsushi; Murasaki, Mitsukuni; Sugita, Yoshiro

2011-10-01

The aim of this study was to evaluate the efficacy and safety of ramelteon 4, 8, 16 or 32 mg and placebo in Japanese patients with chronic insomnia using a randomized, double-blind, five-period crossover design. A total of 65 Japanese patients with chronic primary insomnia received ramelteon or placebo for two nights each in sleep laboratories. Changes in sleep parameters were assessed objectively by polysomnography and subjectively by postsleep questionnaires. Safety and tolerability was evaluated by assessment of the occurrence of adverse events, next-day residual effects and laboratory and ECG investigations. Ramelteon 8 and 32 mg significantly shortened the mean latency to persistent sleep in comparison with placebo, and there was a statistically significant trend for linear dose-response for this sleep parameter. Overall changes in sleep architecture were modest (<3% changes vs placebo), with increases in stage 1 and decreases in stage 3/4. Ramelteon was well tolerated, the most common adverse effect being somnolence, which was similar to placebo at doses up to 8 mg, but increased with higher doses. Next-day residual effects occurred no more frequently with ramelteon at any dose than with placebo. When compared with sleep latency data from a similarly-designed US study, there was no evidence of any ethnic differences in the efficacy of ramelteon between Japanese and US patients. Overall, ramelteon 8 mg showed the most favorable balance between sleep-promoting effects and tolerability. The unique efficacy profile of ramelteon, promoting sleep initiation without affecting other sleep parameters, may be due to its circadian shifting effect.

Predictors of persistent maternal depression trajectories in early childhood: results from the EDEN mother-child cohort study in France.

PubMed

van der Waerden, J; Galéra, C; Saurel-Cubizolles, M-J; Sutter-Dallay, A-L; Melchior, M

2015-07-01

Maternal depression in the pre- and postpartum period may set women on a course of chronic depressive symptoms. Little is known about predictors of persistently elevated depressive symptoms in mothers from pregnancy onwards. The aims of this study are to determine maternal depression trajectories from pregnancy to the child's fifth birthday and identify associated risk factors. Mothers (N = 1807) from the EDEN mother-child birth cohort study based in France (2003-2011) were followed from 24-28 weeks of pregnancy to their child's fifth birthday. Maternal depression trajectories were determined with a semi-parametric group-based modelling strategy. Sociodemographic, psychosocial and psychiatric predictors were explored for their association with trajectory class membership. Five trajectories of maternal symptoms of depression from pregnancy onwards were identified: no symptoms (60.2%); persistent intermediate-level depressive symptoms (25.2%); persistent high depressive symptoms (5.0%); high symptoms in pregnancy only (4.7%); high symptoms in the child's preschool period only (4.9%). Socio-demographic predictors associated with persistent depression were non-French origin; psychosocial predictors were childhood adversities, life events during pregnancy and work overinvestment; psychiatric predictors were previous mental health problems, psychological help, and high anxiety during pregnancy. Persistent depression in mothers of young children is associated to several risk factors present prior to or during pregnancy, notably anxiety. These characteristics precede depression trajectories and offer a possible entry point to enhance mother's mental health and reduce its burden on children.

The hypothalamus–pituitary–thyroid axis in teleosts and amphibians: Endocrine disruption and its consequences to natural populations

USGS Publications Warehouse

Carr, J.A.; Patino, Reynaldo

2011-01-01

Teleosts and pond-breeding amphibians may be exposed to a wide variety of anthropogenic, waterborne contaminants that affect the hypothalamus-pituitary-thyroid (HPT) axis. Because thyroid hormone is required for their normal development and reproduction, the potential impact of HPT-disrupting contaminants on natural teleost and amphibian populations raises special concern. There is laboratory evidence indicating that persistent organic pollutants, heavy metals, pharmaceutical and personal care products, agricultural chemicals, and aerospace products may alter HPT activity, development, and reproduction in teleosts and amphibians. However, at present there is no evidence to clearly link contaminant-induced HPT alterations to impairments in teleost or amphibian population health in the field. Also, with the exception of perchlorate for which laboratory studies have shown a direct link between HPT disruption and adverse impacts on development and reproductive physiology, little is known about if or how other HPT-disrupting contaminants affect organismal performance. Future field studies should focus on establishing temporal associations between the presence of HPT-disrupting chemicals, the occurrence of HPT alterations, and adverse effects on development and reproduction in natural populations; as well as determining how complex mixtures of HPT contaminants affect organismal and population health.

The hypothalamus-pituitary-thyroid axis in teleosts and amphibians: Endocrine disruption and its consequences to natural populations

USGS Publications Warehouse

Carr, J.A.; Patino, R.

2011-01-01

Teleosts and pond-breeding amphibians may be exposed to a wide variety of anthropogenic, waterborne contaminants that affect the hypothalamus-pituitary-thyroid (HPT) axis. Because thyroid hormone is required for their normal development and reproduction, the potential impact of HPT-disrupting contaminants on natural teleost and amphibian populations raises special concern. There is laboratory evidence indicating that persistent organic pollutants, heavy metals, pharmaceutical and personal care products, agricultural chemicals, and aerospace products may alter HPT activity, development, and reproduction in teleosts and amphibians. However, at present there is no evidence to clearly link contaminant-induced HPT alterations to impairments in teleost or amphibian population health in the field. Also, with the exception of perchlorate for which laboratory studies have shown a direct link between HPT disruption and adverse impacts on development and reproductive physiology, little is known about if or how other HPT-disrupting contaminants affect organismal performance. Future field studies should focus on establishing temporal associations between the presence of HPT-disrupting chemicals, the occurrence of HPT alterations, and adverse effects on development and reproduction in natural populations; as well as determining how complex mixtures of HPT contaminants affect organismal and population health. ?? 2010 Elsevier Inc.

Comprehensive review on toxicity of persistent organic pollutants from petroleum refinery waste and their degradation by microorganisms.

PubMed

Varjani, Sunita J; Gnansounou, Edgard; Pandey, Ashok

2017-12-01

Control and prevention of environmental pollution has become a worldwide issue of concern. Aromatic hydrocarbons including benzene, toluene, ethyl benzene, xylene (BTEX) and polyaromatic hydrocarbons (PAHs) are persistent organic pollutants (POPs), released into the environment mainly by exploration activities of petroleum industry. These pollutants are mutagenic, carcinogenic, immunotoxic and teratogenic to lower and higher forms of life i.e. microorganisms to humans. According to the International Agency for Research on Cancer (IARC) and United States Environmental Protection Agency (U.S. EPA), Benzo[a]pyrene (BaP) is carcinogenic in laboratory animals and humans. Aromatic hydrocarbons are highly lipid soluble and thus readily absorbed from environment in gastrointestinal tract of mammals. Treatment and remediation of petroleum refinery waste have been shown either to reduce or to eliminate genotoxicity of these pollutants. Bioremediation by using microorganisms to treat this waste is showing a promising technology as it is safe and cost-effective option among various technologies tested. The main aim of this review is to provide contemporary information on variety of aromatic hydrocarbons present in crude oil (with special focus to mono- and poly-aromatic hydrocarbons), exposure routes and their adverse effects on humans. This review also provides a synthesis of scientific literature on remediation technologies available for aromatic hydrocarbons, knowledge gaps and future research developments in this field. Copyright © 2017 Elsevier Ltd. All rights reserved.

Poorly controlled postoperative pain: prevalence, consequences, and prevention

PubMed Central

Gan, Tong J

2017-01-01

This review provides an overview of the clinical issue of poorly controlled postoperative pain and therapeutic approaches that may help to address this common unresolved health-care challenge. Postoperative pain is not adequately managed in greater than 80% of patients in the US, although rates vary depending on such factors as type of surgery performed, analgesic/anesthetic intervention used, and time elapsed after surgery. Poorly controlled acute postoperative pain is associated with increased morbidity, functional and quality-of-life impairment, delayed recovery time, prolonged duration of opioid use, and higher health-care costs. In addition, the presence and intensity of acute pain during or after surgery is predictive of the development of chronic pain. More effective analgesic/anesthetic measures in the perioperative period are needed to prevent the progression to persistent pain. Although clinical findings are inconsistent, some studies of local anesthetics and nonopioid analgesics have suggested potential benefits as preventive interventions. Conventional opioids remain the standard of care for the management of acute postoperative pain; however, the risk of opioid-related adverse events can limit optimal dosing for analgesia, leading to poorly controlled acute postoperative pain. Several new opioids have been developed that modulate μ-receptor activity by selectively engaging intracellular pathways associated with analgesia and not those associated with adverse events, creating a wider therapeutic window than unselective conventional opioids. In clinical studies, oliceridine (TRV130), a novel μ-receptor G-protein pathway-selective modulator, produced rapid postoperative analgesia with reduced prevalence of adverse events versus morphine. PMID:29026331

Poorly controlled postoperative pain: prevalence, consequences, and prevention.

PubMed

Gan, Tong J

2017-01-01

This review provides an overview of the clinical issue of poorly controlled postoperative pain and therapeutic approaches that may help to address this common unresolved health-care challenge. Postoperative pain is not adequately managed in greater than 80% of patients in the US, although rates vary depending on such factors as type of surgery performed, analgesic/anesthetic intervention used, and time elapsed after surgery. Poorly controlled acute postoperative pain is associated with increased morbidity, functional and quality-of-life impairment, delayed recovery time, prolonged duration of opioid use, and higher health-care costs. In addition, the presence and intensity of acute pain during or after surgery is predictive of the development of chronic pain. More effective analgesic/anesthetic measures in the perioperative period are needed to prevent the progression to persistent pain. Although clinical findings are inconsistent, some studies of local anesthetics and nonopioid analgesics have suggested potential benefits as preventive interventions. Conventional opioids remain the standard of care for the management of acute postoperative pain; however, the risk of opioid-related adverse events can limit optimal dosing for analgesia, leading to poorly controlled acute postoperative pain. Several new opioids have been developed that modulate μ-receptor activity by selectively engaging intracellular pathways associated with analgesia and not those associated with adverse events, creating a wider therapeutic window than unselective conventional opioids. In clinical studies, oliceridine (TRV130), a novel μ-receptor G-protein pathway-selective modulator, produced rapid postoperative analgesia with reduced prevalence of adverse events versus morphine.

Epigenetics and depression: return of the repressed.

PubMed

Dalton, Victoria S; Kolshus, Erik; McLoughlin, Declan M

2014-02-01

Epigenetics has recently emerged as a potential mechanism by which adverse environmental stimuli can result in persistent changes in gene expression. Epigenetic mechanisms function alongside the DNA sequence to modulate gene expression and ultimately influence protein production. The current review provides an introduction and overview of epigenetics with a particular focus on preclinical and clinical studies relevant to major depressive disorder (MDD). PubMed and Web of Science databases were interrogated from January 1995 up to December 2012 using combinations of search terms, including "epigenetic", "microRNA" and "DNA methylation" cross referenced with "depression", "early life stress" and "antidepressant". There is an association between adverse environmental stimuli, such as early life stress, and epigenetic modification of gene expression. Epigenetic changes have been reported in humans with MDD and may serve as biomarkers to improve diagnosis. Antidepressant treatments appear to reverse or initiate compensatory epigenetic alterations that may be relevant to their mechanism of action. As a narrative review, the current report was interpretive and qualitative in nature. Epigenetic modification of gene expression provides a mechanism for understanding the link between long-term effects of adverse life events and the changes in gene expression that are associated with depression. Although still a developing field, in the future, epigenetic modifications of gene expression may provide novel biomarkers to predict future susceptibility and/or onset of MDD, improve diagnosis, and aid in the development of epigenetics-based therapies for depression. © 2013 Published by Elsevier B.V.

Cognitive, motor, behavioural and academic performances of children born preterm: a meta-analysis and systematic review involving 64 061 children.

PubMed

Allotey, J; Zamora, J; Cheong-See, F; Kalidindi, M; Arroyo-Manzano, D; Asztalos, E; van der Post, Jam; Mol, B W; Moore, D; Birtles, D; Khan, K S; Thangaratinam, S

2018-01-01

Preterm birth may leave the brain vulnerable to dysfunction. Knowledge of future neurodevelopmental delay in children born with various degrees of prematurity is needed to inform practice and policy. To quantify the long-term cognitive, motor, behavioural and academic performance of children born with different degrees of prematurity compared with term-born children. PubMed and Embase were searched from January 1980 to December 2016 without language restrictions. Observational studies that reported neurodevelopmental outcomes from 2 years of age in children born preterm compared with a term-born cohort. We pooled individual estimates of standardised mean differences (SMD) and odds ratios (OR) with 95% confidence intervals using a random effects model. We included 74 studies (64 061 children). Preterm children had lower cognitive scores for FSIQ (SMD: -0.70; 95% CI: -0.73 to -0.66), PIQ (SMD: -0.67; 95% CI: -0.73 to -0.60) and VIQ (SMD: -0.53; 95% CI: -0.60 to -0.47). Lower scores for preterm children in motor skills, behaviour, reading, mathematics and spelling were observed at primary school age, and this persisted to secondary school age, except for mathematics. Gestational age at birth accounted for 38-48% of the observed IQ variance. ADHD was diagnosed twice as often in preterm children (OR: 1.6; 95% CI: 1.3-1.8), with a differential effect observed according to the severity of prematurity (I 2 = 49.4%, P = 0.03). Prematurity of any degree affects the cognitive performance of children born preterm. The poor neurodevelopment persists at various ages of follow up. Parents, educators, healthcare professionals and policy makers need to take into account the additional academic, emotional and behavioural needs of these children. Adverse effect of preterm birth on a child's neurodevelopment persists up to adulthood. © 2017 Royal College of Obstetricians and Gynaecologists.

Delayed coral recovery in a warming ocean.

PubMed

Osborne, Kate; Thompson, Angus A; Cheal, Alistair J; Emslie, Michael J; Johns, Kerryn A; Jonker, Michelle J; Logan, Murray; Miller, Ian R; Sweatman, Hugh P A

2017-09-01

Climate change threatens coral reefs across the world. Intense bleaching has caused dramatic coral mortality in many tropical regions in recent decades, but less obvious chronic effects of temperature and other stressors can be equally threatening to the long-term persistence of diverse coral-dominated reef systems. Coral reefs persist if coral recovery rates equal or exceed average rates of mortality. While mortality from acute destructive events is often obvious and easy to measure, estimating recovery rates and investigating the factors that influence them requires long-term commitment. Coastal development is increasing in many regions, and sea surface temperatures are also rising. The resulting chronic stresses have predictable, adverse effects on coral recovery, but the lack of consistent long-term data sets has prevented measurement of how much coral recovery rates are actually changing. Using long-term monitoring data from 47 reefs spread over 10 degrees of latitude on Australia's Great Barrier Reef (GBR), we used a modified Gompertz equation to estimate coral recovery rates following disturbance. We compared coral recovery rates in two periods: 7 years before and 7 years after an acute and widespread heat stress event on the GBR in 2002. From 2003 to 2009, there were few acute disturbances in the region, allowing us to attribute the observed shortfall in coral recovery rates to residual effects of acute heat stress plus other chronic stressors. Compared with the period before 2002, the recovery of fast-growing Acroporidae and of "Other" slower growing hard corals slowed after 2002, doubling the time taken for modest levels of recovery. If this persists, recovery times will be increasing at a time when acute disturbances are predicted to become more frequent and intense. Our study supports the need for management actions to protect reefs from locally generated stresses, as well as urgent global action to mitigate climate change. © 2017 John Wiley & Sons Ltd.

Short-term exposure with high concentrations of pristine microplastic particles leads to immobilisation of Daphnia magna.

PubMed

Rehse, Saskia; Kloas, Werner; Zarfl, Christiane

2016-06-01

Recent studies revealed that freshwaters are not only polluted by chemicals, but also by persistent synthetic material like microplastics (plastic particles <1 mm). Microplastics include a diverse range of characteristics, e.g. polymer type, size or shape, but also their tendency to sorb pollutants or release additives. Although there is rising concern about the pollution of freshwaters by microplastics, knowledge about their potential effects on organisms is limited. For a better understanding of their risks, it is crucial to unravel which characteristics influence their effects on organisms. Analysing effects by the mere particles is the first step before including more complex interactions e.g. with associated chemicals. The aim of this study was to analyse potential physical effects of microplastics on one representative organism for limnic zooplankton (Daphnia magna). We investigated whether microplastics can be ingested and whether their presence causes adverse effects after short-term exposure. Daphnids were exposed for up to 96 h to 1-μm and 100-μm polyethylene particles at concentrations between 12.5 and 400 mg L(-1). Ingestion of 1-μm particles led to immobilisation increasing with dose and time with an EC50 of 57.43 mg L(-1) after 96 h. 100-μm particles that could not be ingested by the daphnids had no observable effects. These results underline that, considering high concentrations, microplastic particles can already induce adverse effects in limnic zooplankton. Although it needs to be clarified if these concentrations can be found in the environment these results are a basis for future impact analysis, especially in combination with associated chemicals. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sodium benzoate for treatment of hepatic encephalopathy.

PubMed

Misel, Michael L; Gish, Robert G; Patton, Heather; Mendler, Michel

2013-04-01

Hepatic encephalopathy (HE) is a serious but usually reversible neuropsychiatric complication of cirrhosis, inborn errors of metabolism involving disorders of the urea cycle, and noncirrhotic portosystemic shunting that most commonly arises from a transjugular intrahepatic portosystemic shunting procedure. Symptoms can include alterations in cognitive function, neuromuscular activity, and consciousness, as well as sleep disorders and mood changes. HE is associated with significant morbidity and mortality and, if not properly treated, will lead to increased hospital admissions and healthcare costs. Although the standard therapies of lactulose and rifaximin (Xifaxan, Salix) are effective for most patients, these drugs may be associated with significant adverse effects and expense and, in some patients, inadequate therapeutic response. A need for adjunctive therapies exists. Drugs that target serum and tissue ammonia metabolism and elimination may be important adjuncts to drugs that reduce ammonia production and absorption from the gastrointestinal tract for patients with severe or persistent overt symptoms of HE. Sodium benzoate is an inexpensive adjunctive agent that can be used in addition to lactulose and rifaximin and may provide an option for some select patients with refractory HE who have failed to respond to standard therapies or who cannot afford them. Although sodium benzoate does not share the same adverse effect profiles of standard therapies for HE, its efficacy has not been well established. Given the significant dose-dependent sodium content of this therapy, it may not be appropriate for patients with significant fluid retention or kidney dysfunction.

Sodium Benzoate for Treatment of Hepatic Encephalopathy

PubMed Central

Misel, Michael L.; Patton, Heather; Mendler, Michel

2013-01-01

Hepatic encephalopathy (HE) is a serious but usually reversible neuropsychiatric complication of cirrhosis, inborn errors of metabolism involving disorders of the urea cycle, and noncirrhotic portosystemic shunting that most commonly arises from a transjugular intrahepatic portosystemic shunting procedure. Symptoms can include alterations in cognitive function, neuromuscular activity, and consciousness, as well as sleep disorders and mood changes. HE is associated with significant morbidity and mortality and, if not properly treated, will lead to increased hospital admissions and healthcare costs. Although the standard therapies of lactulose and rifaximin (Xifaxan, Salix) are effective for most patients, these drugs may be associated with significant adverse effects and expense and, in some patients, inadequate therapeutic response. A need for adjunctive therapies exists. Drugs that target serum and tissue ammonia metabolism and elimination may be important adjuncts to drugs that reduce ammonia production and absorption from the gastrointestinal tract for patients with severe or persistent overt symptoms of HE. Sodium benzoate is an inexpensive adjunctive agent that can be used in addition to lactulose and rifaximin and may provide an option for some select patients with refractory HE who have failed to respond to standard therapies or who cannot afford them. Although sodium benzoate does not share the same adverse effect profiles of standard therapies for HE, its efficacy has not been well established. Given the significant dose-dependent sodium content of this therapy, it may not be appropriate for patients with significant fluid retention or kidney dysfunction. PMID:24711766

Long-term safety and efficacy of stereotactic radiosurgery for vestibular schwannomas: evaluation of 440 patients more than 10 years after treatment with Gamma Knife surgery.

PubMed

Hasegawa, Toshinori; Kida, Yoshihisa; Kato, Takenori; Iizuka, Hiroshi; Kuramitsu, Shunichiro; Yamamoto, Takashi

2013-03-01

Object Little is known about long-term outcomes, including tumor control and adverse radiation effects, in patients harboring vestibular schwannomas (VSs) treated with stereotactic radiosurgery > 10 years previously. The aim of this study was to confirm whether Gamma Knife surgery (GKS) for VSs continues to be safe and effective > 10 years after treatment. Methods A total of 440 patients with VS (including neurofibromatosis Type 2) treated with GKS between May 1991 and December 2000 were evaluable. Of these, 347 patients (79%) underwent GKS as an initial treatment and 93 (21%) had undergone prior resection. Three hundred fifty-eight patients (81%) had a solid tumor and 82 (19%) had a cystic tumor. The median tumor volume was 2.8 cm(3) and the median marginal dose was 12.8 Gy. Results The median follow-up period was 12.5 years. The actuarial 5- and ≥ 10-year progression-free survival was 93% and 92%, respectively. No patient developed treatment failure > 10 years after treatment. According to multivariate analysis, significant factors related to worse progression-free survival included brainstem compression with a deviation of the fourth ventricle (p < 0.0001), marginal dose ≤ 13 Gy (p = 0.01), prior treatment (p = 0.02), and female sex (p = 0.02). Of 287 patients treated at a recent optimum dose of ≤ 13 Gy, 3 (1%) developed facial palsy, including 2 with transient palsy and 1 with persistent palsy after a second GKS, and 3 (1%) developed facial numbness, including 2 with transient and 1 with persistent facial numbness. The actuarial 10-year facial nerve preservation rate was 97% in the high marginal dose group (> 13 Gy) and 100% in the low marginal dose group (≤ 13 Gy). Ten patients (2.3%) developed delayed cyst formation. One patient alone developed malignant transformation, indicating an incidence of 0.3%. Conclusions In this study GKS was a safe and effective treatment for the majority of patients followed > 10 years after treatment. Special attention should be paid to cyst formation and malignant transformation as late adverse radiation effects, although they appeared to be rare. However, it is necessary to collect further long-term follow-up data before making conclusions about the long-term safety and efficacy of GKS, especially for young patients with VSs.

Factors affecting affect cardiovascular health in Indonesian HIV patients beginning ART.

PubMed

Karim, Birry; Wijaya, Ika Praseya; Rahmaniyah, Rizky; Ariyanto, Ibnu; Waters, Shelley; Estiasari, Riwanti; Price, Patricia

2017-08-31

We present a small longitudinal study of how demographic factors and persistent burdens of HIV and cytomegalovirus (CMV) influence cardiovascular health in young adults beginning ART in an inner-city clinic in Jakarta, Indonesia. ART-naïve HIV patients [n = 67; aged 31 (19 to 48) years] were enrolled in the JakCCANDO Project. Echocardiography and carotid Doppler ultrasonography were performed before ART (V0) and after 3, 6, and 12 months (V3-12). Antibodies reactive with CMV lysate or IE-1 protein were assessed at each timepoint and CMV DNA was identified at V0. Markers of adverse cardiovascular prognosis [left ventricular mass index, ejection fraction and carotid intimal media thickness (cIMT)] were similar to healthy controls, but increased at V12. Internal diameters of the carotid arteries and systolic blood pressure correlated with HIV disease severity at V0, but cardiac parameters and cIMT did not. E/A ratios (left ventricular diastolic function) were lower in patients with CMV DNA at V0, but this effect waned by V6. Levels of antibody reactive with CMV IE-1 correlated inversely with CD4 T cell counts at V0, and levels at V6-V12 correlated directly with the right cIMT. Overall the severity of HIV disease and the response to ART have only subtle effects on cardiovascular health in this young Asian population. CMV replication before ART may have a transient effect on cardiac health, whilst antibody reactive with CMV IE-1 may mark a high persistent CMV burden with cumulative effects on the carotid artery.

Early pregnancy termination with intravaginally administered sodium chloride solution-moistened misoprostol tablets: historical comparison with mifepristone and oral misoprostol.

PubMed

Jain, J K; Meckstroth, K R; Mishell, D R

1999-12-01

The purpose of this study was to compare the abortifacient effect of intravaginally administered moistened misoprostol tablets with that of the combination regimen of mifepristone and oral misoprostol. One hundred women at

Military duty: risk factor for preterm labor? A review.

PubMed

McNeary, A M; Lomenick, T S

2000-08-01

The female military population represents a high-risk group for preterm labor and other adverse pregnancy outcomes. As the number of women entering the armed forces continues to increase, concerns regarding the effects of military service on pregnancy must persist. Although active duty females have access to prenatal care and maintain consistent follow-up, previous research has noted a 5-fold increase in preterm labor compared with civilian working women. Hospitalization and loss of work attributable to pregnancy complications directly affect productivity and mission accomplishment; therefore, it is crucial to identify those at risk to institute measures that will prevent such occurrences and decrease time away from work. This article provides a review of the existing literature concerning preterm labor in military women, comparisons with the civilian population, and recommendations for future research.

[Trazodone in REM sleep behavior disorder].

PubMed

Chica-Urzola, Heydy Luz

2015-01-01

This case concerns an elderly man with a REM sleep behavior disorder, who was initially offered a pharmacological treatment with clonazepam, recommended by other articles, but with poor adherence due to its adverse reactions and persistence of symptoms. He was then offered a treatment with Trazodone was offered, achieving a complete remission of symptoms, with no reported side effects. It is clear that Trazodone has no known indication for this type of disorder; nevertheless, it was considered in this case because of its pharmacological profile, obtaining satisfactory results. Further research is needed in order to document thoroughly the mechanisms of action, efficacy and utility of this molecule in cases such as the one presented. Copyright © 2015 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Pharmacokinetics, pharmacodynamics and toxicology of theranostic nanoparticles

NASA Astrophysics Data System (ADS)

Kang, Homan; Mintri, Shrutika; Menon, Archita Venugopal; Lee, Hea Yeon; Choi, Hak Soo; Kim, Jonghan

2015-11-01

Nanoparticles (NPs) are considered a promising tool in both diagnosis and therapeutics. Theranostic NPs possess the combined properties of targeted imaging and drug delivery within a single entity. While the categorization of theranostic NPs is based on their structure and composition, the pharmacokinetics of NPs are significantly influenced by the physicochemical properties of theranostic NPs as well as the routes of administration. Consequently, altered pharmacokinetics modify the pharmacodynamic efficacy and toxicity of NPs. Although theranostic NPs hold great promise in nanomedicine and biomedical applications, a lack of understanding persists on the mechanisms of the biodistribution and adverse effects of NPs. To better understand the diagnostic and therapeutic functions of NPs, this review discusses the factors that influence the pharmacokinetics, pharmacodynamics and toxicology of theranostic NPs, along with several strategies for developing novel diagnostic and therapeutic modalities.

Changes in mercury exposure of marine birds breeding in the Gulf of Maine, 2008-2013.

PubMed

Stenhouse, Iain J; Adams, Evan M; Goyette, Jennifer L; Regan, Kevin J; Goodale, M Wing; Evers, David C

2018-03-01

Mercury is a potent contaminant that can disrupt an organism's behavior and physiology, ultimately affecting reproductive success. Over the last 100 years, environmental deposition of anthropogenic sourced mercury has increased globally, particularly in the U.S. Northeast region. Marine birds are considered effective bioindicators of ecosystem health, including persistent marine contaminants. Goodale et al. (2008) found that mercury exposure exceeded adverse effects levels in some marine bird species breeding across the Gulf of Maine. We re-examined mercury contamination in four species identified as effective bioindicators. Compared with the previous sampling effort, inshore-feeding species showed significant increases in mercury exposure, while one pelagic-feeding species remained stable. This suggests that a major shift may have occurred in methylmercury availability in inshore waters of the Gulf of Maine. Understanding environmental mercury trends in the Gulf of Maine, and its significance to marine birds and other taxa will require a dedicated, standardized, long-term monitoring scheme. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effects of ungulate disturbance and weather variation on Pediocactus winkleri: insights from long-term monitoring

USGS Publications Warehouse

Clark, Deborah J.; Clark, Thomas O.; Duniway, Michael C.; Flagg, Cody B.

2015-01-01

Population dynamics and effects of large ungulate disturbances on Winkler cactus (Pediocactus winkleri K.D. Heil) were documented annually over a 20-year time span at one plot within Capitol Reef National Park, Utah. This cactus species was federally listed as threatened in 1998. The study began in 1995 to gain a better understanding of life history aspects and threats to this species. Data were collected annually in early spring and included diameter, condition, reproductive structures, mortality, recruitment, and disturbance by large ungulates. We used odds ratio and probability model analyses to determine effects of large ungulate trampling and weather on these cacti. During the study, plot population declined by 18%, with trampling of cactus, low precipitation, and cold spring temperatures implicated as causal factors. Precipitation and temperature affected flowering, mortality, and recruitment. Large ungulate disturbances increased mortality and reduced the probability of flowering. These results suggest that large ungulate disturbances and recent climate regimes have had an adverse impact on long-term persistence of this cactus.

Priming effect of dengue and yellow fever vaccination on the immunogenicity, infectivity, and safety of a tetravalent dengue vaccine in humans.

PubMed

Qiao, Ming; Shaw, David; Forrat, Remi; Wartel-Tram, Anh; Lang, Jean

2011-10-01

A dengue vaccine effective against all four serotypes is urgently needed. However, safety and immunogenicity could be affected by prior exposure to flaviviruses. This open, controlled, phase IIa study was conducted in 35 healthy adults who had received monovalent, live attenuated Vero cell-derived dengue vaccine against dengue virus 1 (VDV1) or 2 (VDV2) or yellow fever (YF) vaccine 1 year before or who were flavivirus-naïve. All participants received one subcutaneous injection of tetravalent dengue vaccine (TDV) and were followed for 180 days. Previous vaccination did not increase reactogenicity, laboratory abnormalities, or incidence of vaccine viremia, but it did increase the neutralizing antibody response to dengue virus that persisted at day 180. There was no increase in YF antibodies in participants previously immunized with YF vaccine. Prior exposure to YF or monovalent dengue vaccines had no adverse effects on the safety or incidence of viremia associated with this TDV, but it increased immunogenicity.

Population-based HPV vaccination programmes are safe and effective: 2017 update and the impetus for achieving better global coverage.

PubMed

Brotherton, Julia M L; Bloem, Paul N

2018-02-01

Persistent oncogenic human papillomavirus (HPV) is the cause of cervical cancer, as well as cancers of the anus, penis, vulva, vagina and oropharynx. There is good evidence that prophylactic HPV vaccines are immunogenic and effective against targeted-type HPV infections and type-specific genital lesions, including high-grade cervical intraepithelial neoplasia (CIN), when administered prior to HPV infection. There is good evidence that HPV vaccines are safe in population usage, with the most frequent adverse event being injection-site reactions. There is evidence to support some cross-protection against non-targeted types occurring following the administration of HPV vaccines. There is limited evidence suggesting that HPV vaccines may be beneficial in preventing future disease in women treated for high-grade CIN. This chapter focuses on the accumulated evidence regarding the global use of the three licensed HPV vaccines including safety, immunogenicity, duration of protection, effectiveness, coverage to date and barriers to higher coverage. Copyright © 2018 Elsevier Ltd. All rights reserved.

Multicenter prospective study of treatment of Brucella melitensis brucellosis with doxycycline for 6 weeks plus streptomycin for 2 weeks.

PubMed Central

Cisneros, J M; Viciana, P; Colmenero, J; Pachón, J; Martinez, C; Alarcón, A

1990-01-01

The effectiveness of treating human brucellosis caused by Brucella melitensis with a 6-week course of doxcycline plus streptomycin for 2 of those weeks was analyzed by a multicenter prospective study of 139 patients. Subjects with central nervous system involvement, endocarditis, or spondylitis were excluded from the study. All but 5 of the 139 patients completed the full treatment schedule and became afebrile in the first week of therapy. Four patients suffered relapses during the follow-up period. Of the five patients who did not complete the treatment, two left because of adverse secondary effects (1.4%), another two left for noncomplicance with the treatment (1.4%), and the remaining patient was considered a therapeutic failure because his symptoms persisted after the first week of therapy (0.7%). We concluded that the combination of doxycycline and streptomycin is an effective treatment for the types of brucellosis included in our study. PMID:2193624

Long-Term Mortality Consequences of Childhood Family Context in Liaoning, China, 1749-1909

PubMed Central

Campbell, Cameron Dougall; Lee, James Z

2009-01-01

We examine the effects on adult and old age mortality of childhood living arrangements and other aspects of family context in early life. We focus on features of family context that have already been shown to be associated with infant or child mortality in historical and developing country populations. We apply discrete-time event-history analysis to longitudinal, individual-level household register data for a rural population in northeast China from the eighteenth and nineteenth centuries. Loss of a mother in childhood, a short preceding birth interval, and high maternal age were all associated with elevated mortality risks later in life. Such effects persist in a model with fixed effects that account for unobserved characteristics of the community and household. An important implication of these results is that in high mortality populations, features of early life family context that are associated with elevated infant and child mortality may also predict adverse mortality outcomes in adulthood. PMID:19278765

Neurobehavioral assessment of children and adolescents attending a developmental disabilities clinic.

PubMed

Brasić, James Robert; Barnett, Jacqueline Y; Kowalik, S; Tsaltas, Margaret Owen; Ahmad, Raheela

2004-12-01

Although the risk of the eventual development of tardive dyskinesia and other persistent adverse effects of neuroleptics is high, among adults with mental retardation and other developmental disabilities, neuroleptics may ameliorate dyskinesias, aggression, and inattention. The effects of traditional neuroleptics on a comparable population of children and adolescents with mental retardation and other developmental disabilities are unknown. The objective of this study was to develop an assessment battery to describe the effects of traditional neuroleptics on the behavior and movements of a small sample of children and adolescents with mental retardation and other developmental disabilities. 13 children and adolescents aged 6 to 16 years attending a developmental disabilities clinic were evaluated utilizing a Movement Assessment Battery to measure behavior and motions. Five subjects took traditional neuroleptic medications. Trained raters can reliably assess the movements and behaviors of children and adolescents with multiple handicaps. Children and adolescents with developmental disabilities may be vulnerable to experience functional impairment and akathisia, tics, and other dyskinesias when administered traditional neuroleptic medications.

“Shift-and-Persist” Strategies: Why Being Low in Socioeconomic Status isn’t Always Bad for Health

PubMed Central

Chen, Edith; Miller, Gregory E.

2012-01-01

Some individuals, despite facing recurrent, severe adversities in life such as low socioeconomic status (SES), are nonetheless able to maintain good physical health. This article explores why these individuals deviate from the expected association of low SES with poor health, and outlines a “shift-and-persist” model to explain the psychobiological mechanisms involved. This model proposes that in the midst of adversity, some children find role models who teach them to trust others, better regulate their emotions, and focus on their futures. Over a lifetime, these low SES children develop an approach to life that prioritizes shifting oneself (accepting stress for what it is and adapting the self to it) in combination with persisting (enduring life with strength by holding on to meaning and optimism). This combination of shift-and-persist strategies mitigates sympathetic-nervous-system and hypothalamic-pituitary-adrenocortical responses to the barrage of stressors that low SES individuals confront. This tendency vectors individuals off the trajectory to chronic disease by forestalling pathogenic sequelae of stress reactivity, like insulin resistance, high blood pressure, and systemic inflammation. We outline evidence for the model, and argue that efforts to identify resilience-promoting processes are important in this economic climate, given limited resources for improving the financial circumstances of disadvantaged individuals. PMID:23144651

Maternal and fetal response to fetal persistent infection with bovine viral diarrhea virus.

PubMed

Hansen, Thomas R; Smirnova, Natalia P; Van Campen, Hana; Shoemaker, Megan L; Ptitsyn, Andrey A; Bielefeldt-Ohmann, Helle

2010-10-01

Infection of naïve pregnant cows with non-cytopathic (ncp) bovine viral diarrhea virus (BVDV) results in transplacental infection of the fetus. Infection of the pregnant cow with ncp BVDV late in gestation (after day 150) results in transient infection (TI), as both the dam and fetus can mount an immune response to the virus. In contrast, if the fetus is infected with ncp BVDV early in gestation (before day 150), the fetal immune system is undeveloped and unable to recognize the virus as foreign. This results in induction of immune tolerance to the infecting BVDV strain and persistent infection (PI). Infection of naïve pregnant heifers with ncp BVDV2 on day 75 was hypothesized to induce differential gene expression in white blood cells of the dams and their fetuses, adversely affecting development and antiviral immune responses in PI fetuses. Gene expression differed in maternal blood cells in the presence of PI versus uninfected fetuses. PI adversely affected fetal development and antiviral responses, despite protective immune responses in the dam. Fetal PI with BVDV alters maternal immune function, compromises fetal growth and immune responses, and results in expression of maternal blood biomarkers that can be used to identify cows carrying PI fetuses.

The influence of progression of atrial fibrillation on quality of life: a report from the Euro Heart Survey.

PubMed

Dudink, Elton A M P; Erküner, Ömer; Berg, Jenny; Nieuwlaat, Robby; de Vos, Cees B; Weijs, Bob; Capucci, Alessandro; Camm, A John; Breithardt, Günter; Le Heuzey, Jean-Yves; Luermans, Justin G L M; Crijns, Harry J G M

2018-06-01

Progression of atrial fibrillation (AF) from paroxysmal to persistent forms is an active field of research. The influence of AF progression on health related quality of life (HRQoL) is currently unknown. We aimed to assess the influence of AF progression on HRQoL, and whether this association is mediated through symptoms, treatment, and major adverse events. In the Euro Heart Survey, 967 patients were included with paroxysmal AF who filled out EuroQoL-5D at baseline and at 1 year follow-up. Those who progressed (n = 132, 13.6%) developed more problems during follow-up than those who did not, on all EuroQoL-5D domains (increase in problems on mobility 20.5% vs. 11.4%; self-care 12.9% vs. 6.2%; usual activities 23.5% vs. 14.0%; pain/discomfort 20.5% vs. 13.7%; and anxiety/depression 22.7% vs. 15.7%; all P < 0.05), leading to a decrease in utility [baseline 0.744 ± 0.26, follow-up 0.674 ± 0.36; difference -0.07 (95% CI [-0.126,-0.013], P = 0.02)]. Multivariate analysis showed that the effect of progression on utility is mediated by a large effect of adverse events [stroke (-0.27 (95% CI [-0.43,-0.11]); P = 0.001], heart failure [-0.12 (95% CI [-0.20,-0.05]); P = 0.001], malignancy (-0.31 (95% CI [-0.56,-0.05]); P = 0.02] or implantation of an implantable cardiac defibrillator [-0.12 (95% CI [-0.23,-0.02]); P = 0.03)], as well as symptomatic AF [-0.04 (95% CI [-0.08,-0.01]); P = 0.008]. AF progression is associated with a decrease in HRQoL. However, multivariate analysis revealed that AF progression itself does not have a negative effect on HRQoL, but that this effect can be attributed to a minor effect of the associated symptoms and a major effect of associated adverse events.

Cypermethrin induced toxicities in fish and adverse health outcomes: Its prevention and control measure adaptation.

PubMed

Ullah, Sana; Zuberi, Amina; Alagawany, Mahmoud; Farag, Mayada Ragab; Dadar, Maryam; Karthik, Kumaragurubaran; Tiwari, Ruchi; Dhama, Kuldeep; Iqbal, Hafiz M N

2018-01-15

Pesticides are being widely employed in the modern agriculture, though in different quantities, across the globe. Although it is useful for crops yield enhancement, however, there are the serious environment, health and safety related concerns for aquatic and terrestrial living biomes that include humans, animals, and plants. Various in practice and emerging pesticides adversely affect the survival, development and biological systems stability. Several research efforts have been made to highlight the bio-safety and toxicological features of toxicants through risk assessment studies using different animal models, e.g., different fish species. Among several pesticides, cypermethrin is extensively used in agriculture and households, and the reported concentrations of this pesticide in different water bodies including rivers and streams, soil and even in rainwater are threatening. Consequently, cypermethrin is considered for risk assessment studies to know about its deep and different level of toxicological effects subject to its dose, exposure time and route. The cypermethrin existence/persistence in the environment is posing a severe threat to humans as well as another non-target terrestrial and aquatic organism. Herein, the toxic effects of pesticides, with special reference to cypermethrin, on fish, the mode of toxicity, concerns regarding public health and harmful impacts on human beings are comprehensively reviewed. The information is also given on their appropriate control and prevention strategies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Safety and efficacy of 2,790-nm laser resurfacing for chest photoaging.

PubMed

Grunebaum, Lisa D; Murdock, Jennifer; Cofnas, Paul; Kaufman, Joely

2015-01-01

Chest photodamage is a common cosmetic complaint. Laser treatment of the chest may be higher risk than other areas. The objective of this study was to assess the safety and efficacy of 2,790-nm chest resurfacing for photodamage. Twelve patients with Fitzpatrick skin types I-III were enrolled in this university IRB-approved study. Photo documentation was obtained at baseline and each visit. A test spot with the 2,790-nm resurfacing laser was performed on the chest. Patients who did not have adverse effects from the test spot went on to have a full chest resurfacing procedure. Patients were instructed on standardized aftercare, including sunscreen. A 5-point healing and photodamage improvement scale was used to rate improvement by both investigators and the patients and was obtained at 2 weeks, 1 month, 2 months, and 3 months. One pass chest treatment with the 2,790-nm resurfacing laser at fluences greater than or equal to 3.0 mJ with 10% overlap leads to unacceptable rates of hyperpigmentation. Double pass chest treatment at fluences less than or equal to 2.5 mJ with 10% overlap leads to mild improvement in chest photodamage parameters without significant or persistent adverse effects. Laser treatment of aging/photodamaged chest skin remains a challenge due to the delicacy of chest skin. Mild improvement may be obtained with double pass resurfacing with the 2,790-nm wavelength.

Medical Compared With Surgical Abortion for Effective Pregnancy Termination in the First Trimester.

PubMed

Ireland, Luu Doan; Gatter, Mary; Chen, Angela Y

2015-07-01

To compare efficacy between medical and surgical abortion at 9 weeks of gestation or less. We performed a retrospective cohort study comparing efficacy of medical compared with surgical abortion before 64 days of gestation at Planned Parenthood, Los Angeles, from November 2010 to August 2013. Electronic medical records were reviewed for ongoing pregnancies after the initial abortion procedure. Data were also collected on complications occurring within the immediate postabortal period (8 weeks postabortal) including unanticipated aspiration and major adverse events (emergency department presentation, hospitalization, perforation, transfusion, infection). Chi square test and logistic regression were used to compare the primary outcomes between cohorts. Data were collected from 30,146 women with pregnancies seeking termination before 64 days of gestation. Sociodemographic and clinical characteristics were similar in the medication and surgical abortion groups. Efficacy of pregnancy termination was 99.6% for medication abortions and 99.8%% for surgical abortions (P<.001). The medication abortion group was more likely to undergo an unanticipated aspiration, for ongoing pregnancy or persistent pain, bleeding, or both (2.1% compared with 0.6%, respectively, odds ratio 1.6, 95% confidence interval 1.1-2.3). These rates were unchanged after controlling for gravidity, parity, and body mass index. There was no difference in major adverse events between the two groups. Medication abortion and surgical abortion before 64 days of gestation are both highly effective with low complication rates. II.

Early Adversity and Developmental Outcomes: Interaction Between Genetics, Epigenetics, and Social Experiences Across the Life Span.

PubMed

Champagne, Frances A

2010-09-01

Longitudinal studies in humans demonstrate the association between prenatal and postnatal experiences of adversity and long-term changes in neurodevelopment. These studies raise the question of how experiences become incorporated at a biological level to induce persistent changes in functioning. Laboratory studies using animal models and recent analyses in human cohorts implicate epigenetic mechanisms as a possible route through which these environmental effects are achieved. In particular, there is evidence that changes in DNA methylation are associated with early life experiences with consequences for gene expression and behavior. Despite the potential stability of DNA methylation, it is apparent that this epigenetic mark can be dynamically modified through pharmacological targeting and behavioral experiences. Developmental plasticity may also be achieved through modification of the juvenile environment. Although these juvenile experiences may lead to common endpoints, there is evidence suggesting that the effects of early and later life experiences may be achieved by different molecular pathways. This review discusses evidence for the role of epigenetic mechanisms in shaping developmental trajectories in response to early life experience as well as the potential plasticity that can occur beyond the perinatal period. These studies have implications for approaches to intervention and suggest the importance of considering individual differences in genetic and epigenetic vulnerability in developing treatment strategies. © The Author(s) 2010.

A 35-month profilometric and clinical evaluation of non-ablative remodeling using a 1540-nm Er:glass laser.

PubMed

Fournier, Nathalie; Lagarde, Jean Michel; Turlier, Virginie; Courrech, Laetitia; Mordon, Serge

2004-11-01

As remodeling is getting more popular with patients, long-term studies are becoming necessary. The aim of this 35-month clinical study was to evaluate the long-term benefits obtained using a 1540-nm Er:glass laser for non-ablative remodeling of perioral and periorbital rhytids. The role of maintenance treatments was also investigated. Eleven women with periorbital and perioral rhytids underwent a series of five treatments at 6-week intervals with an Er:glass laser. Five patients subsequently received two maintenance retreatments and six did not. The maintenance treatments were performed at 14 and 20 months. Silicone imprints were performed to measure anisotropy before treatment, at 6 months, at 14 months and at 35 months. Patient self-evaluation/questionnaire was also done to assess adverse effects and subjective clinical improvement. For all 11 patients, the percentage of anisotropy reduction was 41.21% at 6 months, 51.76% at 14 months and 29.87% at 35 months. No adverse effects were noted. Patient satisfaction was high at the end of the evaluation. Retreated patients were more satisfied than non-retreated ones. However, there was no difference in the anisotropy factor between the two groups. Treatment of facial rhytids with a non-ablative 1540-nm Er:glass laser system can produce benefits that persist over 2 years after the last treatment.

Adversity and Resilience Are Associated with Outcome after Mild Traumatic Brain Injury in Military Service Members.

PubMed

Reid, Matthew W; Cooper, Douglas B; Lu, Lisa H; Iverson, Grant L; Kennedy, Jan E

2018-05-15

The objective of this study was to assess the associations between resilience, adversity, post-concussion symptoms, and post-traumatic stress symptom reporting after mild traumatic brain injury (mTBI). We hypothesized that resilience would be associated with less symptom reporting, and adversity would be associated with greater symptom reporting. This was a cross-sectional study of retrospective data collected for an ongoing TBI repository. United States military service members who screened positive for mTBI during a primary care visit completed the Trauma History Screen (THS), Connor-Davidson Resilience Scale (CD-RISC), Neurobehavioral Symptom Inventory (NSI), and post-traumatic stress disorder (PTSD) Checklist-Civilian Version (PCL-C). Data collected from February 2015 to August 2016 were used for the present study. Only participants with complete data for the above measures were included, yielding a sample size of 165 participants. Adversity (THS) and resilience (CD-RISC) scores were each correlated significantly with post-concussion (NSI) and traumatic stress (PCL-C) total and subscale scores in the hypothesized direction. Interactions between adversity and resilience were absent for all measures except the NSI sensory subscale. Four traumatic event types were significantly associated positively with most NSI and PCL-C total and subscale scores, but the age at which traumatic events were first experienced showed few and mixed significant associations. In conclusion, resilience and adversity were significantly associated with symptom endorsement after mTBI. Screening for cumulative adversity may identify individuals at greater risk of developing persistent post-concussion symptoms and/or PTSD, and interventions that increase resilience may reduce symptom severity.

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

PubMed

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

2016-01-01

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

Human Myeloid-derived Suppressor Cells are Associated With Chronic Immune Suppression After Severe Sepsis/Septic Shock.

PubMed

Mathias, Brittany; Delmas, Amber L; Ozrazgat-Baslanti, Tezcan; Vanzant, Erin L; Szpila, Benjamin E; Mohr, Alicia M; Moore, Frederick A; Brakenridge, Scott C; Brumback, Babette A; Moldawer, Lyle L; Efron, Philip A

2017-04-01

We hypothesized that after sepsis in humans, MDSCs will be persistently increased, functionally immunosuppressive, and associated with adverse clinical outcomes. Cancer and sepsis have surprisingly similar immunologic responses and equally dismal long term consequences. In cancer, increased myeloid-derived suppressor cells (MDSCs) induce detrimental immunosuppression, but little is known about the role of MDSCs after sepsis. Blood was obtained from 74 patients within 12 hours of severe sepsis/septic shock (SS/SS), and at set intervals out to 28 days, and also in 18 healthy controls. MDSCs were phenotyped for cell surface receptor expression and enriched by cell sorting. Functional and genome-wide expression analyses were performed. Multiple logistic regression analysis was conducted to determine if increased MDSC appearance was associated with in-hospital and long-term outcomes. After SS/SS, CD33CD11bHLA-DR MDSCs were dramatically increased out to 28 days (P < 0.05). When co-cultured with MDSCs from SS/SS patients, antigen-driven T-cell proliferation and TH1/TH2 cytokine production were suppressed (P < 0.05). Additionally, septic MDSCs had suppressed HLA gene expression and up-regulated ARG1 expression (P < 0.05). Finally, SS/SS patients with persistent increased percentages of blood MDSCs had increased nosocomial infections, prolonged intensive care unit stays, and poor functional status at discharge (P < 0.05). After SS/SS in humans, circulating MDSCs are persistently increased, functionally immunosuppressive, and associated with adverse outcomes. This novel observation warrants further studies. As observed in cancer immunotherapy, MDSCs could be a novel component in multimodality immunotherapy targeting detrimental inflammation and immunosuppression after SS/SS to improve currently observed dismal long-term outcomes.

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

PubMed

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

2015-07-01

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

[Moderate and severe persistent allergic rhinitis treated with acupoint application therapy of the different intensity: a randomized controlled trial].

PubMed

Hu, Qimiao; Gu, Pengpeng; Jiang, Xia; Jiang, Fangqi; Zhuang, Jinfei; Zheng, Haisong; Yang, Guanhu; Jiang, Songhe

2017-11-12

To evaluate the clinical therapeutic effects and safety on moderate and severe persistent allergic rhinitis treated with acupoint application therapy of the different intensity during the dog days. One hundred and sixty patients of moderate and severe persistent allergic rhinitis were randomized into a No.1 treatment group, a No.2 treatment group, a No.3 treatment group and a placebo group, 40 cases in each one. The same acupoints were used in the four groups, named Dazhui (GV 14), Dingchuan (EX-B1), Feishu (BL 13), Pishu (BL 20), Mingmen (GV 4), Gaohuang (BL 43), Shenshu (BL 23) and Qihai (CV 6). In the three treatment groups, the fine powder of the ingredients ( semen brassicae , radix angeliceae , asarum sieboldii , rhizome corydalis ) of compound baijiezi formula was used. In the No.1 treatment group, the herbal paste (ginger-prepared paste) was prepared with ginger juice and the above herbal powder. In the No.2 and No.3 treatment groups, the herbal paste (honey-prepared paste) was prepared with honey with the above herbal powder. In the placebo group, the pseudo-herbal paste of the same appearance was prepared with millet powder and distilled water. The acupoint application was given for 2 h in the No.1 and No.2 groups and was for 6 h in the No.3 treatment group and the placebo group. The acupoint application therapy was given once every week during the dogdays, continuously for 5 weeks. The total nasal symptom score (TNSS), the score of the rhinoconjunctivitis quality of life questionnaire (RQLQ) and the count of blood eosinophils (EOS) were observed in the patients of the 4 groups before and after treatment. The clinical therapeutic effects were compared among the 4 groups. The incidences of the skin adverse reactions were observed in each treatment group. After treatment, the scores of TNSS and RQLQ were all reduced as compared with those before treatment in the three treatment groups ( P <0.05, P <0.01), in which, the improvements in the No.3 treatment group were better than those in the No.1 treatment group and the No.2 treatment group (both P <0.05). After treatment, the count of EOS was all reduced as compared with that before treatment in the three treatment groups (all P <0.05). The differences were not significant statistically among the three treatment groups (all P >0.05). The total effective rate was 85.0% (34/40) in the No.3 treatment group, better than 76.3% (29/38) in the No.1 treatment group, 71.8% (28/39) in the No.2 treatment group and 5.0% (2/40) in the placebo group ( P <0.05, P <0.01). The incidences of the skin adverse reaction in the No.3 treatment group and the No.2 treatment group were lower than those in the No.1 treatment group (both P <0.01). The acupoint application of the different intensity relieves the symptoms and improves the living quality in the patients of moderate and severe persistent allergic rhinitis. The stimulation of the ginger-prepared herbal paste is strong and induces skin blisters after 2 h herbal application. The stimulation of the honey-prepared herbal paste is moderate and does not induce blisters. The 6 h stimulation of the honey-prepared herbal paste is mild and the therapeutic effect is optimal.

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

PubMed Central

2013-01-01

Background Significant and persistent racial and income disparities in birth outcomes exist in the US. The analyses in this manuscript examine whether adverse birth outcome time trends and associations between area-level variables and adverse birth outcomes differ by urban–rural status. Methods Alabama births records were merged with ZIP code-level census measures of race, poverty, and rurality. B-splines were used to determine long-term preterm birth (PTB) and low birth weight (LBW) trends by rurality. Logistic regression models were used to examine differences in the relationships between ZIP code-level percent poverty or percent African-American with either PTB or LBW. Interactions with rurality were examined. Results Population dense areas had higher adverse birth outcome rates compared to other regions. For LBW, the disparity between population dense and other regions increased during the 1991–2005 time period, and the magnitude of the disparity was maintained through 2010. Overall PTB and LBW rates have decreased since 2006, except within isolated rural regions. The addition of individual-level socioeconomic or race risk factors greatly attenuated these geographical disparities, but isolated rural regions maintained increased odds of adverse birth outcomes. ZIP code-level percent poverty and percent African American both had significant relationships with adverse birth outcomes. Poverty associations remained significant in the most population-dense regions when models were adjusted for individual-level risk factors. Conclusions Population dense urban areas have heightened rates of adverse birth outcomes. High-poverty African American areas have higher odds of adverse birth outcomes in urban versus rural regions. These results suggest there are urban-specific social or environmental factors increasing risk for adverse birth outcomes in underserved communities. On the other hand, trends in PTBs and LBWs suggest interventions that have decreased adverse birth outcomes elsewhere may not be reaching isolated rural areas. PMID:23759062

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

PubMed

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

2017-02-01

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

Optogenetic activation of the central amygdala generates addiction-like preference for reward.

PubMed

Tom, Rebecca L; Ahuja, Aarit; Maniates, Hannah; Freeland, Charlotte M; Robinson, Mike J F

2018-05-23

Drug and behavioural addictions are characterized by an intense and focused pursuit of a single reward above all others. Pursuit of the addictive reward is often compulsively sought despite adverse consequences and better alternative outcomes. Here, we explored the ability of the central amygdala (CeA) to powerfully bias choice, causing specific rewards to be almost compulsively preferred. Rats were trained on an operant choice task in which they could choose to respond on either of the two levers to receive a sucrose reward, one of which was paired with optogenetic stimulation of the CeA using channelrhodopsin-2 (ChR2). Rats developed an almost exclusive preference for the laser-paired reward over the otherwise equal unpaired reward. We found that this preference for stimulation-paired reward persists even when a much larger sucrose reward is offered as an alternative (contingency management) or when this preferred reward is paired with adverse consequences such as progressively larger electric foot shock, time delays or effort requirements. We also report that when challenged with foot shock, a small proportion of these animals (≈20%) retained an exclusive laser-paired reward preference, whereas others began to seek the alternate reward when the shock reached high levels. Lastly, we confirmed that optogenetic CeA stimulation was not independently rewarding if delivered in the absence of a paired sucrose reward. These results suggest a role for the CeA in focusing motivation and desire to excessive levels, generating addiction-like behaviour that persists in the face of more rewarding alternatives and adverse consequences. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

[Benefits and risks for primary prevention with statins in the elderly].

PubMed

Joseph, Jean-Philippe; Afonso, Mélanie; Berdaï, Driss; Salles, Nathalie; Bénard, Antoine; Gay, Bernard; Bonnet, Fabrice

2015-12-01

Statins in primary prevention before 75 years old reduce cardiovascular events from 20 to 30% and mortality from 10% with acceptable side effects. We investigated whether these results persisted for patients aged 75 and older taking statin. Methodic review of large randomized clinical trials and meta-analyzes that included patients 75 years and older treated with statins in primary prevention. Since the 1990s, a score of randomized controlled trials studying statins versus placebo in primary prevention were published and studied in meta-analyses. Exclusion criteria, including persons older than 70 years, are often restrictive. The impact on all-cause mortality in the four main studies and meta-analyses in over 75 years has not been demonstrated. On the other hand, a recent meta-analyses of observational studies including subjects between 70 and 89 years treated with statins found that low total cholesterol was associated with a moderate decrease in cardiovascular mortality, with no decrease in all-cause mortality. Moreover, in a common context of comorbidities in this age group, statins may be responsible for many adverse effects, drug interactions and impaired quality of life. Given the lack of formal evidence of effectiveness in terms of all-cause mortality and a high level of adverse effects, the benefit/risk of primary prevention with statins is not established in the elderly. The economic weight of statin prescriptions and their possible impact on quality of life justify an economic analysis of discontinuing statin therapy for people 75 years and older. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Doxapram Treatment for Apnea of Prematurity: A Systematic Review.

PubMed

Vliegenthart, Roseanne J S; Ten Hove, Christine H; Onland, Wes; van Kaam, Anton H L C

2017-01-01

Apnea of prematurity (AOP) is a common complication of preterm birth, for which caffeine is the first treatment of choice. In case of persistent AOP, doxapram has been advocated as an additional therapy. To identify and appraise all existing evidence regarding efficacy and safety of doxapram use for AOP in infants born before 34 weeks of gestational age. All studies reporting on doxapram use for AOP were identified by searching electronic databases, references from relevant studies, and abstracts from the Societies for Pediatric Research. Two reviewers independently assessed study eligibility and quality, and extracted data on study design, patient characteristics, efficacy and safety outcomes. The randomized controlled trials showed less apnea during doxapram treatment when compared to placebo, but no difference in treatment effect when compared to theophylline. No serious adverse effects were reported. We identified 28 observational studies consisting mainly of cohort studies and case series (n = 1,994). There was considerable heterogeneity in study design and quality. Most studies reported a positive effect of doxapram on apnea rate. A few studies reported on long-term outcomes with conflicting results. A range of possible doxapram-related short-term adverse effects were reported, sometimes associated with the use of higher doses. Based on the limited number of studies and level of evidence, no firm conclusions on the efficacy and safety of doxapram in preterm infants can be drawn. For this reason, routine use cannot be recommended. A large multicenter randomized controlled trial is urgently needed to provide more conclusive evidence. © 2016 The Author(s) Published by S. Karger AG, Basel.

Neuromotor function in ship welders after cessation of manganese exposure.

PubMed

Wastensson, Gunilla; Sallsten, Gerd; Bast-Pettersen, Rita; Barregard, Lars

2012-08-01

The aim of the present study was to investigate whether previous long-term exposure to manganese (Mn) via inhalation of welding fumes can cause persistent impairment in neuromotor function even long after cessation of exposure. Quantitative tests of tremor, motor speed, manual dexterity, diadochokinesis, eye-hand coordination and postural stability were administered to 17 retired ship welders (mean age 69 years), with mean exposure time 28 years. The welders' exposure had ceased on average 18 years before the study. A cumulative exposure index (CEI) was calculated for each of the former welders. The welders were compared with 21 referents from the same shipyards (mean age was 66 years). Former welders performed less well than referents in the grooved pegboard test, and poorer performance was associated with CEI. The performance in most of the other neurobehavioral tests was similar between groups, but the welders tended to perform slightly better than the referents in tests demanding hand steadiness. The latter finding may be due to a training effect from their former working tasks or selection bias into or out of this occupation. In the present study of welders with previous welding fume exposure, former welders and referents performed similarly in most of the neurobehavioral tests. Previous adverse effects on the neuromotor system might have ceased, and decreased neuromotor function due to normal aging processes in both groups might have disguised any slight effect of previous Mn exposure. The poorer performance in the grooved pegboard test among welders may indicate an adverse effect on motor function of long-term exposure to Mn, but this finding has to be confirmed by other studies.

Adverse childhood experiences influence the detrimental effect of bipolar disorder and schizophrenia on cortico-limbic grey matter volumes.

PubMed

Poletti, Sara; Vai, Benedetta; Smeraldi, Enrico; Cavallaro, Roberto; Colombo, Cristina; Benedetti, Francesco

2016-01-01

Adverse childhood experiences (ACE) can lead to several negative consequences in adult life, are highly prevalent in psychiatric disorders where they associate with clinical and brain morphological features. Grey matter volume loss is a central characteristic of bipolar disorder (BD) and schizophrenia (SCZ). The aim of this study is to measure the effect of diagnosis and ACE on GM volume in a sample of patients with BD or SCZ compared with healthy controls (HC). We studied 206 depressed BD patients, 96 SCZ patients and 136 healthy subjects. GM volumes were estimated with 3.0 Tesla MRI and analyzed with VBM technique. The effect of diagnosis was investigated in the whole sample and separately exposed to high and low ACE subjects. An effect of diagnosis was observed in orbitofrontal cortex encompassing BA 47 and insula, and in the thalamus. HC had the highest volume and SCZ patients the lowest with BD patients showing an intermediate volume. This pattern persisted only in subjects with high ACE. No differences were observed for low ACE subjects. The three diagnostic groups differ for age and education, previous and current medications, and treatment periods. Our results underline the importance of ACE on the neural underpinnings of psychiatric psychopathology and suggest a major role of exposure to ACE for the GM deficits to reveal in clinical populations. Exposure to early stress is a crucial factor that must be taken in to account when searching for biomarkers of BD and SCZ. Copyright © 2015 Elsevier B.V. All rights reserved.

Health Effects of Air Pollution: A Historical Review and Present Status.

PubMed

Shima, Masayuki

2017-01-01

During the 1960s, the concentrations of air pollutants, particularly that of sulfur dioxide (SO 2 ), were extremely high in many industrial cities in Japan, and the prevalence of bronchial asthma and chronic bronchitis increased among residents living in the cities. To evaluate the effects of air pollution on respiratory diseases, many epidemiological studies were conducted, and the findings played an important role in the regulatory control of air pollution. After 1970, the concentration of SO 2 has decreased markedly, and its adverse health effects have been minimized. On the other hand, the increasing automobile traffic in Japan has caused considerable increases in concentrations of air pollutants, such as nitrogen oxides (NOx) and particulate matter (PM). The large-scale epidemiological studies conducted in Japan showed that traffic-related air pollution was associated with the development of asthma in school children and the persistence of asthmatic symptoms in preschool children. In recent years, however, the concentrations of NOx and PM have gradually decreased, since control measures based on the Automobile NOx/PM law were enforced in 2001. At present, the adverse health effects of airborne fine particulate matter (PM 2.5 ) and photochemical oxidants have become a major concern. These air pollutants consist of not only emissions from primary sources but also secondary formations in air, and have spread worldwide. Both short- and long-term exposure to these air pollutants are reported to increase the risk of respiratory and cardiovascular diseases in the population. Therefore, global efforts are necessary to reduce the health risk of these air pollutants.

Age at Arrival and Life Chances Among Childhood Immigrants.

PubMed

Hermansen, Are Skeie

2017-02-01

This study examines the causal relationship between childhood immigrants' age at arrival and their life chances as adults. I analyze panel data on siblings from Norwegian administrative registries, which enables me to disentangle the effect of age at arrival on adult socioeconomic outcomes from all fixed family-level conditions and endowments shared by siblings. Results from sibling fixed-effects models reveal a progressively stronger adverse influence of immigration at later stages of childhood on completed education, employment, adult earnings, occupational attainment, and social welfare assistance. The persistence of these relationships within families indicates that experiences related to the timing of childhood immigration have causal effects on later-life outcomes. These age-at-arrival effects are considerably stronger among children who arrive from geographically distant and economically less-developed origin regions than among children originating from developed countries. The age-at-arrival effects vary less by parental education and child gender. On the whole, the findings indicate that childhood immigration after an early-life formative period tends to constrain later human capital formation and economic opportunities over the life course.

Squill Oxymel, a traditional formulation from Drimia Maritima (L.) Stearn, as an add-on treatment in patients with moderate to severe persistent asthma: A pilot, triple-blind, randomized clinical trial.

PubMed

Nejatbakhsh, Fatemeh; Karegar-Borzi, Hossein; Amin, Gholamreza; Eslaminejad, Alireza; Hosseini, Mostafa; Bozorgi, Mahbubeh; Gharabaghi, Mehrnaz Asadi

2017-01-20

In Traditional Iranian Medicine (TIM), Squill (Drimia maritima (L.) Stearn) Oxymel was utilized in the treatment of asthma. Squill has been reported to exert anti-inflammatory, anti-oxidant, anti-cholinergic, and mucus secretion modulating effects. This study aimed to make a preliminary evaluation of the efficacy and safety of an add-on Squill Oxymel treatment in patients with moderate to severe persistent asthma. In a 6-week, triple-blind, randomized, placebo-controlled trial, 60 patients with stable moderate to severe persistent asthma were randomly allocated to receive either 10ml syrup of Squill Oxymel, simple oxymel, or a placebo 2 times a day, as an add-on to their routine treatment (inhaled corticosteroids and β2 agonists). Spirometry and plethysmography were performed on patients to evaluate the effect of the treatment at baseline and end of intervention. Forced Expiratory Volume in first second (FEV1) was considered the primary outcome. St. George's respiratory questionnaire (SGRQ) was also used for the subjective evaluation of patients' responses. Fifty-four patients completed the study. The results showed significant improvement in spirometry parameters, especially FEV1 (1.54±.38 vs. 2.11±.49l), in the Squill Oxymel group compared with the other groups. The increases in FEV1 liter, FEV1%, FEV1/FVC%, and MEF 25-75% during the intervention were significantly higher in the Squill Oxymel group than in the other groups (p<.001). However, the improvement of plethysmographic parameters showed no significant difference between the study groups (p>.05). The SGRQ scores (symptoms, activity, and total score) were significantly improved after intervention in both the Squill Oxymel and the simple honey oxymel groups (p<.001), but not in the placebo group. Nausea and vomiting was reported in 5 patients in Squill oxymel and simple oxymel groups. No other serious adverse event was observed. The results of the current study show preliminary evidence for the efficacy and safety of the add-on treatment of Squill Oxymel in patients with moderate to severe persistent asthma. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Changes in household food insecurity are related to changes in BMI and diet quality among Michigan Head Start preschoolers in a sex-specific manner.

PubMed

Jansen, Erica C; Kasper, Nicole; Lumeng, Julie C; Brophy Herb, Holly E; Horodynski, Mildred A; Miller, Alison L; Contreras, Dawn; Peterson, Karen E

2017-05-01

Children living in households that have recently become food insecure may be particularly vulnerable to adverse weight and dietary changes, but longitudinal studies examining these associations are lacking. Using data from 501 Head Start preschoolers from Michigan (48% male) who were followed during one school year as a part of a randomized obesity prevention trial, we examined changes in children's adiposity indices and dietary quality according to changes in household food insecurity. Household food insecurity change status was categorized as persistently food secure, became food secure, persistently food insecure, or became food insecure. Linear mixed effects models were used to estimate relative changes in BMI-for-age z scores (BAZ), triceps skinfolds-for-age z scores (TAZ), or diet quality (assessed with the 2010 Healthy Eating Index) over the school year according to food insecurity category. We found that girls from households that became food insecure over the year had a 0.21 unit higher gain in BAZ than girls from households that were persistently food secure, after adjustment for potential confounders (95% CI 0.02 to 0.39, P = 0.03). Girls from households that became food secure had improvements in dietary quality over the year compared to girls from persistently food insecure households (adjusted difference in Healthy Eating Index score change = 9.1 points; 95% CI 3.0 to 15.0; p = 0.003). There were no statistically significant associations with changes in TAZ. Among boys, there were no associations between changes in household food insecurity and changes in BAZ, TAZ, or dietary quality. In summary, we found that BMI and diet quality changes of Head Start preschool girls were correlated with short-term changes in household food insecurity. Continued research efforts should focus on identifying the most effective ways to promote the health of children in food insecure households, especially those who may have recently transitioned or are transitioning into food insecurity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Atlantic DIP: high prevalence of abnormal glucose tolerance post partum is reduced by breast-feeding in women with prior gestational diabetes mellitus.

PubMed

O'Reilly, Michael W; Avalos, Gloria; Dennedy, Michael C; O'Sullivan, Eoin P; Dunne, Fidelma

2011-12-01

Gestational diabetes (GDM) is associated with adverse fetal and maternal outcomes, and identifies women at risk of future type 2 diabetes mellitus (T2DM). Breast-feeding may improve post partum maternal glucose tolerance. Our objective was to identify the prevalence of post partum dysglycemia after GDM, to delineate associated factors and to examine the effect of lactation on post partum glucose tolerance. We compared post partum 75 g oral glucose tolerance test (OGTT) results from 300 women with GDM and 220 controls with normal gestational glucose tolerance (NGT) in five regional centers. Breast-feeding data was collected at time of OGTT. Methods Post partum OGTT results were classified as normal (fasting plasma glucose (FPG) <5.6 mmol/l, 2 h <7.8 mmol/l) and abnormal (impaired fasting glucose (IFG), FPG 5.6-6.9 mmol/l; impaired glucose tolerance (IGT), 2 h glucose 7.8-11 mmol/l; IFG+IGT; T2DM, FPG ≥7 mmol/l±2 h glucose ≥11.1 mmol/l). Binary logistic regression was used to identify factors predictive of persistent hyperglycemia. Five hundred and twenty women were tested; six (2.7%) with NGT in pregnancy had post partum dysglycemia compared with 57 (19%) with GDM in index pregnancy (P<0.001). Non-European ethnicity (odds ratio (OR) 3.40; 95% confidence interval (CI) 1.45-8.02, P=0.005), family history of T2DM (OR 2.14; 95% CI 1.06-4.32, P=0.034), and gestational insulin use (OR 2.62; 95% CI 1.17-5.87, P=0.019) were associated with persistent dysglycemia. The prevalence of persistent hyperglycemia was significantly lower in women who breast-fed vs bottle-fed post partum (8.2 vs 18.4%, P<0.001). Non-European ethnicity, gestational insulin use, family history of T2DM, and elevated body mass index were associated with persistent dysglycemia after GDM. Breast-feeding may confer beneficial metabolic effects after GDM and should be encouraged.

Regional analgesia for improvement of long-term functional outcome after elective large joint replacement

PubMed Central

Atchabahian, Arthur; Schwartz, Gary; Hall, Charles B; Lajam, Claudette M; Andreae, Michael H

2015-01-01

Background Regional analgesia is more effective than conventional analgesia for controlling pain and may facilitate rehabilitation after large joint replacement in the short term. It remains unclear if regional anaesthesia improves functional outcomes after joint replacement beyond three months after surgery. Objectives To assess the effects of regional anaesthesia and analgesia on long-term functional outcomes 3, 6 and 12 months after elective major joint (knee, shoulder and hip) replacement surgery. Search methods We performed an electronic search of several databases (CENTRAL, MEDLINE, EMBASE, CINAHL), and handsearched reference lists and conference abstracts. We updated our search in June 2015. Selection criteria We included randomized controlled trials (RCTs) comparing regional analgesia versus conventional analgesia in patients undergoing total shoulder, hip or knee replacement. We included studies that reported a functional outcome with a follow-up of at least three months after surgery. Data collection and analysis We used standard methodological procedures expected by Cochrane. We contacted study authors for additional information. Main results We included six studies with 350 participants followed for at least three months. All of these studies enrolled participants undergoing total knee replacement. Studies were at least partially blinded. Three studies had a high risk of performance bias and one a high risk of attrition bias, but the risk of bias was otherwise unclear or low. Only one study assessed joint function using a global score. Due to heterogeneity in outcome and reporting, we could only pool three out of six RCTs, with range of motion assessed at three months after surgery used as a surrogate for joint function. All studies had a high risk of detection bias. Using the random-effects model, there was no statistically significant difference between the experimental and control groups (mean difference 3.99 degrees, 95% confidence interval (CI) − 2.23 to 10.21; P value = 0.21, 3 studies, 140 participants, very low quality evidence). We did not perform further analyses because immediate adverse effects were not part of the explicit outcomes of any of these typically small studies, and long-term adverse events after regional anaesthesia are rare. None of the included studies elicited or reported long-term adverse effects like persistent nerve damage. Authors’ conclusions More high-quality studies are needed to establish the effects of regional analgesia on function after major joint replacement, as well as on the risk of adverse events (falls). PMID:26269416

Pediatric Patients Discharged from the Emergency Department with Abnormal Vital Signs.

PubMed

Winter, Josephine; Waxman, Michael J; Waterman, George; Ata, Ashar; Frisch, Adam; Collins, Kevin P; King, Christopher

2017-08-01

Children often present to the emergency department (ED) with minor conditions such as fever and have persistently abnormal vital signs. We hypothesized that a significant portion of children discharged from the ED would have abnormal vital signs and that those discharged with abnormal vital signs would experience very few adverse events. We performed a retrospective chart review encompassing a 44-month period of all pediatric patients (aged two months to 17 years) who were discharged from the ED with an abnormal pulse rate, respiratory rate, temperature, or oxygen saturation. We used a local quality assurance database to identify pre-defined adverse events after discharge in this population. Our primary aim was to determine the proportion of children discharged with abnormal vital signs and the frequency and nature of adverse events. Additionally, we performed a sub-analysis comparing the rate of adverse events in children discharged with normal vs. abnormal vital signs, as well as a standardized review of the nature of each adverse event. Of 33,185 children discharged during the study period, 5,540 (17%) of these patients had at least one abnormal vital sign. There were 24/5,540 (0.43%) adverse events in the children with at least one abnormal vital sign vs. 47/27,645 (0.17%) adverse events in the children with normal vital signs [relative risk = 2.5 (95% confidence interval, 1.6 to 2.4)].However, upon review of each adverse event we found only one case that was related to the index visit, was potentially preventable by a 23-hour hospital observation, and caused permanent disability. In our study population, 17% of the children were discharged with at least one abnormal vital sign, and there were very few adverse (0.43%) events associated with this practice. Heart rate was the most common abnormal vital sign leading to an adverse event. Severe adverse events that were potentially related to the abnormal vital sign(s) were exceedingly rare. Additional research is needed in broader populations to better determine the rate of adverse events and possible methods of avoiding them.

Botulinum Neurotoxin Type-A for the Treatment of Atypical Odontalgia.

PubMed

Cuadrado, María-Luz; García-Moreno, Héctor; Arias, José-Antonio; Pareja, Juan A

2016-09-01

Atypical odontalgia (AO), a subform of persistent idiopathic facial pain, is defined as a continuous toothache in which a thorough examination reveals no dental pathology. AO is believed to be a neuropathic condition, given that some cases are preceded by dental procedures. Different topical and systemic medications have been used for the treatment of AO, but their effect is often unsatisfactory. The authors aimed to assess the effect and safety of botulinum neurotoxin type-A (BoNTA) in a series of patients with AO. Four patients with refractory AO (2 males and 2 females, aged 31-72) were treated with local injections of BoNTA to the painful area. BoNTA was injected at various sites into the gums, and two patients had additional injections in the hard palate or the upper lip. The total dose of BoNTA for each procedure was 15-30 U, and the total number of injection points was 6-12. The follow-up ranged from 6 to 20 months. Two patients received two cycles of BoNTA, while the remaining patients received three and five cycles each, respectively. All patients obtained significant relief with complete or almost complete reduction of pain. The analgesic effect was apparent after a latency period of 3-14 days, and the effect persisted for 2-6 months. There were no adverse events reported from any of the interventions. The responses to BoNTA injections in this series agree with those previously observed in neuropathic pain. BoNTA injections may be a safe and effective option for the treatment of AO. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Biodegradation of fluorinated alkyl substances.

PubMed

Frömel, Tobias; Knepper, Thomas P

2010-01-01

The incorporation of fluorine into organic molecules entails both positive and adverse effects. Although fluorine imparts positive and unique properties such as water-and oil-repellency and chemical stability, adverse effects often pervade members of this compound class. A striking property of long perfluoroalkyl chains is their very pronounced environmental persistence. The present review is the first one designed to summarize recent accomplishments in the field of biodegradation of fluorine-containing surfactants, their metabolites, and structural analogs. The pronounced scientific and public interest in these chemicals has given impetus to undertake numerous degradation studies to assess the sources and origins of different fluorinated analog chemical known to exist in the environment. It was shown that biodegradation plays an important role in understanding how fluorinated substances reach the environment and, once they do, what their fate is. Today, PFOS and PFOA are ubiquitously detected as environmental contaminants. Their prominence as contaminants is mainly due to their extreme persistence, which is linked to their perfluoroalkyl chain length. It appears that desulfonation of a highly fluorinated surfactants can be achieved if an α-situated H atom, in relation to the sulfonate group, is present, at least under sulfur-limiting conditions. Molecules that are less heavily fluorinated can show very complex metabolic behavior, as is the case for fluorotelomer alcohols. These compounds are degraded via different but simultaneous pathways, which produce different stable metabolites, one of which is the respective perfluoroalkanoate (8:2-FTOH is transformed to PFOA). Preliminary screening tests indicate that fluorinated functional groups, such as the trifluoromethoxy group and the p-(trifluoromethyl)phenoxy group, may be useful implementations in novel, environmentally benign fluorosurfactants. More specifically, trifluoromethoxy groups constitute a substitute for those that have been used in the past; this functionality is degradable when it appears in structures that are normally subject to biodegradation. Other compounds tested did not meet this criterion. Interdisciplinary investigations on fluorinated surfactants are still very much needed and will certainly continue during the next many years. For instance, the role of fluorinated polymers in contributing small fluorinated molecules to the environmental burden still has not been fully understood.

The Relationship of Built Environment to Health-Related Behaviors and Health Outcomes in Elderly Community Residents in a Middle Income Country

PubMed Central

Blay, Sergio L.; Schulz, Amy J.; Mentz, Graciela

2015-01-01

Background Few studies have examined the impact of the built environment (BE) on health behaviours and health outcomes in middle income countries. This study examines associations between self-assessed characteristics of the home and neighbourhood environment and health-related behaviours and health outcomes in an elderly population in Brazil Design and methods In a community sample of 6963 community dwellers 60 years old and older living in the state of Rio Grande do Sul, Brazil, associations between self-reported BE conditions and health behaviours and health outcomes were assessed using a structured questionnaire. Multivariate analysis was conducted to investigate these associations while accounting for other relevant characteristics. Results We found significant positive associations between adverse BE conditions and pulmonary, urinary conditions, gastrointestinal, problems, headache and depression. There were mixed associations between adverse BE conditions and musculoskeletal and sensory conditions, inverse associations with metabolic disorders. and no associations with dermatologic problems and cancer. After accounting for health related behaviours, results suggest a modest association between adverse BE conditions and hypertension, with no significant associations with other indicators of cardiovascular conditions (heart problems, stroke, varicose veins). Conclusions The findings in this study suggest links between adverse conditions in the BE and health related behaviours in the hypothesized direction. Associations with the health conditions examined here are mixed. We find the strongest evidence for effects of adverse BE conditions for pulmonary and infectious conditions. Significant associations between the adverse BE indicators and health outcomes persist after accounting for health related behaviours, suggesting that BE conditions are linked to health pathways above and beyond the health related behaviours assessed in this study. Significance for public health The health outcomes for which we found most consistent evidence of associations with the built environment index (BEI) included respiratory conditions (bronchitis, pneumonia), urinary and renal conditions, gastrointestinal problems, headache, visual impairment and stroke. These health outcomes in the elderly may reflect exposures in the household environment associated with inadequate housing, such as mold, dust and damp. They may also be influenced by poor sanitary conditions, reflected in the absence of indoor plumbing and inadequate waste disposal facilities. Poor vision, headache and depression may all be associated with chronic exposure to poverty and stress, for which the measures of the household and neighborhood environmental conditions used in the BEI may be indicators. Assuring that the elderly in Brazil have access to adequate housing located in neighborhoods with access to basic sanitary conditions, water and lighting, will be increasingly important as the average age of Brazilians continues to increase, and increasing proportions of the population experience the adverse health effects associated with these conditions. PMID:26425497

The Relationship of Built Environment to Health-Related Behaviors and Health Outcomes in Elderly Community Residents in a Middle Income Country.

PubMed

Blay, Sergio L; Schulz, Amy J; Mentz, Graciela

2015-07-16

Few studies have examined the impact of the built environment (BE) on health behaviours and health outcomes in middle income countries. This study examines associations between self-assessed characteristics of the home and neighbourhood environment and health-related behaviours and health outcomes in an elderly population in Brazil. In a community sample of 6963 community dwellers 60 years old and older living in the state of Rio Grande do Sul, Brazil, associations between self-reported BE conditions and health behaviours and health outcomes were assessed using a structured questionnaire. Multivariate analysis was conducted to investigate these associations while accounting for other relevant characteristics. We found significant positive associations between adverse BE conditions and pulmonary, urinary conditions, gastrointestinal, problems, headache and depression. There were mixed associations between adverse BE conditions and musculoskeletal and sensory conditions, inverse associations with metabolic disorders. and no associations with dermatologic problems and cancer. After accounting for health related behaviours, results suggest a modest association between adverse BE conditions and hypertension, with no significant associations with other indicators of cardiovascular conditions (heart problems, stroke, varicose veins). The findings in this study suggest links between adverse conditions in the BE and health related behaviours in the hypothesized direction. Associations with the health conditions examined here are mixed. We find the strongest evidence for effects of adverse BE conditions for pulmonary and infectious conditions. Significant associations between the adverse BE indicators and health outcomes persist after accounting for health related behaviours, suggesting that BE conditions are linked to health pathways above and beyond the health related behaviours assessed in this study. Significance for public healthThe health outcomes for which we found most consistent evidence of associations with the built environment index (BEI) included respiratory conditions (bronchitis, pneumonia), urinary and renal conditions, gastrointestinal problems, headache, visual impairment and stroke. These health outcomes in the elderly may reflect exposures in the household environment associated with inadequate housing, such as mold, dust and damp. They may also be influenced by poor sanitary conditions, reflected in the absence of indoor plumbing and inadequate waste disposal facilities. Poor vision, headache and depression may all be associated with chronic exposure to poverty and stress, for which the measures of the household and neighborhood environmental conditions used in the BEI may be indicators. Assuring that the elderly in Brazil have access to adequate housing located in neighborhoods with access to basic sanitary conditions, water and lighting, will be increasingly important as the average age of Brazilians continues to increase, and increasing proportions of the population experience the adverse health effects associated with these conditions.

Long-term intravenous administration of carboxylated single-walled carbon nanotubes induces persistent accumulation in the lungs and pulmonary fibrosis via the nuclear factor-kappa B pathway.

PubMed

Qin, Yue; Li, Suning; Zhao, Gan; Fu, Xuanhao; Xie, Xueping; Huang, Yiyi; Cheng, Xiaojing; Wei, Jinbin; Liu, Huagang; Lai, Zefeng

2017-01-01

Numerous studies have demonstrated promising application of single-walled carbon nanotubes (SWNTs) in drug delivery, diagnosis, and targeted therapy. However, the adverse health effects resulting from intravenous injection of SWNTs are not completely understood. Studies have shown that levels of "pristine" or carboxylated carbon nanotubes are very high in mouse lungs after intravenous injection. We hypothesized that long-term and repeated intravenous administration of carboxylated SWNTs (c-SWNTs) can result in persistent accumulation and induce histopathologic changes in rat lungs. Here, c-SWNTs were administered repeatedly to rats via tail-vein injection for 90 days. Long-term intravenous injection of c-SWNTs caused sustained embolization in lung capillaries and granuloma formation. It also induced a persistent inflammatory response that was regulated by the nuclear factor-kappa B signaling pathway, and which resulted in pulmonary fibrogenesis. c-SWNTs trapped within lung capillaries traversed capillary walls and injured alveolar epithelial cells, thereby stimulating production of pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-1 beta) and pro-fibrotic growth factors (transforming growth factor-beta 1). Protein levels of type-I and type-III collagens, matrix metalloproteinase-2, and the tissue inhibitor of metalloproteinase-2 were upregulated after intravenous exposure to c-SWNTs as determined by immunohistochemical assays and Western blotting, which suggested collagen deposition and remodeling of the extracellular matrix. These data suggest that chronic and cumulative toxicity of nanomaterials to organs with abundant capillaries should be assessed if such nanomaterials are applied via intravenous administration.

Maternal Postnatal Depression and Anxiety and Their Association With Child Emotional Negativity and Behavior Problems at Two Years

PubMed Central

2017-01-01

Postnatal maternal depression is associated with poorer child emotional and behavioral functioning, but it is unclear whether this occurs following brief episodes or only with persistent depression. Little research has examined the relation between postnatal anxiety and child outcomes. The present study examined the role of postnatal major depressive disorder (MDD) and generalized anxiety disorder (GAD) symptom chronicity on children’s emotional and behavioral functioning at 24 months. Following postnatal screening mothers (n = 296) were identified as having MDD, GAD, MDD and GAD, or no disorder at 3 months postnatal; the average age was 32.3 (SD = 5.0), 91.9% self-identified as Caucasian, and 62.2% were married. Maternal disorder symptom severity was assessed by questionnaires and structured interview at 3, 6, 10, 14, and 24 months postpartum. At 24 months, child emotional negativity and behavior were assessed using questionnaires and by direct observation. Latent trait–state-occasion modeling was used to represent maternal disorder symptom chronicity; both stable trait and time-specific occasion portions of maternal symptomatology were examined in relation to child outcomes. Only the stable trait portion of maternal MDD and GAD symptom severity were related to maternal report of child behavior problems and higher levels of emotional negativity. Persistent maternal MDD, but not GAD, symptom severity was related to higher levels of child emotional negativity as measured observationally. These data suggest that children’s behavior problems and emotional negativity are adversely affected by persistent maternal depression, and possibly anxiety. This has implications for interventions to prevent negative effects of postnatal psychopathology on children. PMID:28026191

Influence of patient training on persistence, compliance, and tolerability of different dosing frequency regimens of bisphosphonate therapy: An observational study in Turkish patients with postmenopausal osteoporosis.

PubMed

Akarırmak, Ülkü; Koçyiğit, Hikmet; Eskiyurt, Nurten; Esmaeilzadeh, Sina; Kuru, Ömer; Yalçinkaya, Ebru Yılmaz; Peker, Özlen; Ekim, Ayşe Aydemir; Özgirgin, Neşe; Çalış, Mustafa; Rezvani, Aylin; Çevikol, Alev; Eyigör, Sibel; Şendur, Ömer Faruk; İrdesel, Jale

2016-08-01

In our study, we aimed to evaluate the influence of training on compliance and persistence with bisphosphonate treatment given on a weekly vs. monthly basis in postmenopausal osteoporosis patients. A total of 979 patients with postmenopausal osteoporosis (mean age: 63.2 ± 7.2 years) were included in this national, multicenter, prospective non-interventional observational cohort registry study. Patients were randomized into training (n = 492, 50.3%, mean age: 63.4 ± 7.2 years) and control (n = 487, 49.7%, mean age: 63.0 ± 7.1 years) groups. Patients in each intervention group were given weekly (44.9% and 44.6% for training and control subjects, respectively) or monthly (55.1% and 55.4%, respectively) bisphosphonate regimens. After the initial visit, patients were followed up at three-month intervals throughout 12 months of treatment for evaluation of persistence, compliance and adverse events. On average, 79.4% of the patients were persistent with the treatment with a mean of 350.4 days of duration during the 12-month follow-up period. The mean compliance in the compliant and fully compliant group remained at an average of 86.6%. No significant difference was detected between the training and control groups in terms of compliance and persistence. Significantly longer persistence (360.0 ± 89.0 vs. 345.0 ± 108.0 days; p = 0.035), higher percentage of persistent patients (83.4% vs. 74.2%; p = 0.012) and higher compliance rates (88.8% vs. 83.3%; p = 0.002) were noted in monthly regimen patients in comparison to those given weekly regimen. Our findings revealed remarkably high rates for persistence and compliance with bisphosphonate treatment in postmenopausal osteoporosis, with no impact of training on compliance and persistence rates. Longer persistence and better compliance rates were achieved with the monthly bisphosphonate regimen when compared to the weekly regimen. Copyright © 2016 Turkish Association of Orthopaedics and Traumatology. Production and hosting by Elsevier B.V. All rights reserved.

Effects of Hormone Therapy on Brain Volumes Changes of Postmenopausal Women Revealed by Optimally-Discriminative Voxel-Based Morphometry

PubMed Central

Zhang, Tianhao; Casanova, Ramon; Resnick, Susan M.; Manson, JoAnn E.; Baker, Laura D.; Padual, Claudia B.; Kuller, Lewis H.; Bryan, R. Nick; Espeland, Mark A.; Davatzikos, Christos

2016-01-01

Backgrounds The Women's Health Initiative Memory Study Magnetic Resonance Imaging (WHIMS-MRI) provides an opportunity to evaluate how menopausal hormone therapy (HT) affects the structure of older women’s brains. Our earlier work based on region of interest (ROI) analysis demonstrated potential structural changes underlying adverse effects of HT on cognition. However, the ROI-based analysis is limited in statistical power and precision, and cannot provide fine-grained mapping of whole-brain changes. Methods We aimed to identify local structural differences between HT and placebo groups from WHIMS-MRI in a whole-brain refined level, by using a novel method, named Optimally-Discriminative Voxel-Based Analysis (ODVBA). ODVBA is a recently proposed imaging pattern analysis approach for group comparisons utilizing a spatially adaptive analysis scheme to accurately locate areas of group differences, thereby providing superior sensitivity and specificity to detect the structural brain changes over conventional methods. Results Women assigned to HT treatments had significant Gray Matter (GM) losses compared to the placebo groups in the anterior cingulate and the adjacent medial frontal gyrus, and the orbitofrontal cortex, which persisted after multiple comparison corrections. There were no regions where HT was significantly associated with larger volumes compared to placebo, although a trend of marginal significance was found in the posterior cingulate cortical area. The CEE-Alone and CEE+MPA groups, although compared with different placebo controls, demonstrated similar effects according to the spatial patterns of structural changes. Conclusions HT had adverse effects on GM volumes and risk for cognitive impairment and dementia in older women. These findings advanced our understanding of the neurobiological underpinnings of HT effects. PMID:26974440

A Randomized Controlled Trial of Intranasal Ketamine in Major Depressive Disorder

PubMed Central

Lapidus, Kyle A.B.; Levitch, Cara F.; Perez, Andrew M.; Brallier, Jess W.; Parides, Michael K.; Soleimani, Laili; Feder, Adriana; Iosifescu, Dan V.; Charney, Dennis S.; Murrough, James W.

2014-01-01

Background The N-methyl-d-aspartate glutamate receptor antagonist ketamine, delivered via an intravenous route, has shown rapid antidepressant effects in patients with treatment-resistant depression. The current study was designed to test the safety, tolerability and efficacy of intranasal ketamine in patients with depression who had failed at least one prior antidepressant trial. Methods Twenty patients with major depression were randomized and 18 completed two treatment days with intranasal ketamine hydrochloride (50 mg) or saline solution in a randomized, double-blind, crossover study. The primary efficacy outcome measure was change in depression severity 24 hours following ketamine or placebo, measured using the Montgomery-Asberg Depression Rating Scale. Secondary outcomes included persistence of benefit, changes in self-reports of depression, changes in anxiety, and proportion of responders. Potential psychotomimetic, dissociative, hemodynamic, and general adverse effects associated with ketamine were also measured. Results Patients showed significant improvement in depressive symptoms at 24 hours following ketamine compared to placebo [t=4.39, p<0.001; estimated mean MADRS score difference of 7.6 ± 3.7 (95% CI: 3.9 – 11.3)]. Eight of 18 patients (44%) met response criteria 24 hours following ketamine administration, compared to 1 of 18 (6%) following placebo (p=0.033). Intranasal ketamine was well tolerated with minimal psychotomimetic or dissociative effects and was not associated with clinically significant changes in hemodynamic parameters. Conclusions This study provides the first controlled evidence for the rapid antidepressant effects of intranasal ketamine. Treatment was associated with minimal adverse effects. If replicated, these findings may lead to novel approaches to the pharmacologic treatment of patients with major depression. Trial Registration clinicaltrials.gov identifier NCT01304147 PMID:24821196

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.