Identifying causes of adverse events detected by an automated trigger tool through in-depth analysis.

PubMed

Muething, S E; Conway, P H; Kloppenborg, E; Lesko, A; Schoettker, P J; Seid, M; Kotagal, U

2010-10-01

To describe how in-depth analysis of adverse events can reveal underlying causes. Triggers for adverse events were developed using the hospital's computerised medical record (naloxone for opiate-related oversedation and administration of a glucose bolus while on insulin for insulin-related hypoglycaemia). Triggers were identified daily. Based on information from the medical record and interviews, a subject expert determined if an adverse drug event had occurred and then conducted a real-time analysis to identify event characteristics. Expert groups, consisting of frontline staff and specialist physicians, examined event characteristics and determined the apparent cause. 30 insulin-related hypoglycaemia events and 34 opiate-related oversedation events were identified by the triggers over 16 and 21 months, respectively. In the opinion of the experts, patients receiving continuous-infusion insulin and those receiving dextrose only via parenteral nutrition were at increased risk for insulin-related hypoglycaemia. Lack of standardisation in insulin-dosing decisions and variation regarding when and how much to adjust insulin doses in response to changing glucose levels were identified as common causes of the adverse events. Opiate-related oversedation events often occurred within 48 h of surgery. Variation in pain management in the operating room and post-anaesthesia care unit was identified by the experts as potential causes. Variations in practice, multiple services writing orders, multidrug regimens and variations in interpretation of patient assessments were also noted as potential contributing causes. Identification of adverse drug events through an automated trigger system, supplemented by in-depth analysis, can help identify targets for intervention and improvement.

Adverse effects of antioxidative vitamins.

PubMed

Rutkowski, Maciej; Grzegorczyk, Krzysztof

2012-06-01

High doses of synthetic antioxidative vitamins: A, E, C and β-carotene are often used on long-term basis in numerous preventive and therapeutic medical applications. Instead of expected health effects, the use of those vitamins may however lead to cases of hypervitaminosis and even to intoxication. The article points out main principles of safety which are to be observed during supplementation with antioxidative vitamins. Toxic effects resulting from erroneous administration of high doses of those substances on organs and systems of the organism are also discussed. Attention is drawn to interactions of antioxidative vitamins with concomitantly used drugs, as well as intensification of adverse effects caused by various exogenous chemical factors. Moreover, the article presents the evaluation of supplementation with these vitamins, which was performed in large studies.

Adverse drug reaction: rosuvastatin as a cause for ischaemic colitis in a 64-year-old woman

PubMed Central

Tan, Jackie; Pretorius, Casper Francois; Flanagan, Paul Vincent; Pais, Antonio

2012-01-01

Rosuvastatin (Crestor, AstraZeneca) is a commonly used drug for managing hypercholesterolaemia. It is a very safe medication with mostly acceptable side effects. Rare but serious side effects are not well known. A 64-year-old woman presented with bloody diarrhoea after starting rosuvastatin for hypercholesterolaemia. Stool microscopy and culture ruled out infective causes. Abdominal CT scan revealed normal calibre celiac axis and superior mesenteric artery. Colonoscopic biopsy revealed ischaemic colitis as the final histological diagnosis. The patient is in complete remission after ceasing the medication. Rosuvastatin causing ischaemic colitis should be considered a rare but serious adverse drug reaction. PMID:22744258

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

PubMed Central

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

2017-01-01

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

Topiramate-Induced Somnambulism in a Migraineur: A Probable Idiosyncratic Adverse Effect

PubMed Central

Mathew, Thomas; Sarma, G. R. K.; Nadig, Raghunandan; Varghese, Raji

2012-01-01

Somnambulism (sleepwalking) is a disorder of arousal that falls under “parasomnia” group and is more common in children. These phenomena occur as primary sleep events or secondary to systemic disease or can be drug induced. Medications that can cause sleepwalking include neuroleptics, hypnotics, lithium, amitriptyline, and β-blockers.1 This report presents an unusual adverse effect of topiramate on sleep in a patient with migraine. Citation: Mathew T; Sarma GRK; Nadig R; Varghese R. Topiramate-induced somnambulism in a migraineur: a probable idiosyncratic adverse effect. J Clin Sleep Med 2012;8(2):197-198. PMID:22505867

Adverse effects of concentrated green tea extracts.

PubMed

Schönthal, Axel H

2011-06-01

A myriad of health claims are being made in favor of the consumption of green tea. However, mostly due to the easy availability and greater than ever popularity of highly concentrated green tea extracts, sometimes combined with an attitude of more-is-better, certain health risks of green tea consumption have begun to emerge. Among such risks are the possibility of liver damage, the potential to interact with prescription drugs to alter their therapeutic efficacy, and the chance to cause harm when combined with other highly popular herbal remedies. This review will summarize documented examples of adverse effects of green tea in humans, and will discuss risks of copious consumption of highly concentrated green tea extracts as indicated by studies in animals. While there is no intention to minimize any of the scientifically established benefits of the use of green tea, the purpose of this review is to focus primarily on the potential for adverse effects and raise awareness of the rare, yet under-appreciated risks. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

PubMed

St Louis, Erik K; Louis, Erik K

2009-06-01

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

[Extrapyramidal toxicity caused by metoclopramide and clebopride: study of voluntary notifications of adverse effects to the Spanish Drug Surveillance System].

PubMed

Cuena Boy, R; Maciá Martínez, M A

1998-03-31

To clarify if there is any basis for the hypothesis that Clebopride leads to more extrapyramidal reactions than Metoclopramide. Observational, longitudinal, retrospective and comparative study of two series of cases. The entire Spanish healthcare system. Those notified to the Spanish Drug watch system as possibly having suffered an adverse reaction to Metoclopramide (n = 98) or Clebopride (n = 123) between 1/1/1990 and 10/6/1997. None. 84.3% of suspected adverse reactions to Clebopride and 51.6% of those to Metoclopramide had a non-hospital precedence (P < 0.001). In 48.0% of suspected adverse reactions to Metoclopramide and 72.4% of those to Clebopride, there was extrapyramidal toxicity (P = 0.021). There is a basis for the hypothesis that Clebopride causes more extrapyramidal reactions than Metoclopramide. It was reasonable to realize a study based on this hypothesis.

Adverse effects of dietary fructose.

PubMed

Gaby, Alan R

2005-12-01

The consumption of fructose, primarily from high-fructose corn syrup (HFCS), has increased considerably in the United States during the past several decades. Intake of HFCS may now exceed that of the other major caloric sweetener, sucrose. Some nutritionists believe fructose is a safer form of sugar than sucrose, particularly for people with diabetes mellitus, because it does not adversely affect blood-glucose regulation, at least in the short-term. However, fructose has potentially harmful effects on other aspects of metabolism. In particular, fructose is a potent reducing sugar that promotes the formation of toxic advanced glycation end-products, which appear to play a role in the aging process; in the pathogenesis of the vascular, renal, and ocular complications of diabetes; and in the development of atherosclerosis. Fructose has also been implicated as the main cause of symptoms in some patients with chronic diarrhea or other functional bowel disturbances. In addition, excessive fructose consumption may be responsible in part for the increasing prevalence of obesity, diabetes mellitus, and non-alcoholic fatty liver disease. Although the long-term effects of fructose consumption have not been adequately studied in humans, the available evidence suggests it may be more harmful than is generally recognized. The extent to which a person might be adversely affected by dietary fructose depends both on the amount consumed and on individual tolerance. With a few exceptions, the relatively small amounts of fructose that occur naturally in fruits and vegetables are unlikely to have deleterious effects, and this review is not meant to discourage the consumption of these healthful foods.

Potential adverse effects of oseltamivir in rats: males are more vulnerable than females.

PubMed

El-Sayed, Wael M; Al-Kahtani, Mohamed Ali

2011-09-01

Oseltamivir is the most widely used antiviral drug for the treatment and prophylaxis of influenza. However, not much is known about its adverse effects. The potential side effects were investigated in male and female rats (140-170 g). Oseltamivir was administered at 2.2 mg·kg(-1)·day(-1) for 5 days. For both genders, treatment with oseltamivir resulted in significant reductions in the hepatic activities of glutathione reductase, glutathione peroxidase, and glutathione S-transferase. Also for both genders, oseltamivir produced modest reductions in the hepatic activities of UDP-glucuronosyltransferase, quinone oxidoreductase, thioredoxin reductase, CYP1A1/2, and CYP3A, as well as hepatic glutathione content. For both genders, neither the kidney functions nor protein profile was affected by oseltamivir. Oseltamivir also caused significant elevation in serum levels of both triacylglycerols and LDL-cholesterol and in the activity of γ-glutamyl transpeptidase, in both genders. For male animals only, oseltamivir treatment elevated the serum level of total cholesterol as well as the activity of serum alanine aminotransferase, and reduced the hepatic activities of superoxide dismutase and catalase. Oseltamivir caused oxidative stress and acute toxicity in the liver, and disrupted the cholesterol and lipid metabolism but was less likely to cause serious drug interactions. There was a sexual differentiation in these adverse effects, with adverse effects being more evident in male rats.

Adverse Effects Associated With Newer Diabetes Therapies.

PubMed

Akiyode, Oluwaranti F; Adesoye, Adebola A

2017-04-01

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

Drug metabolism and transport gene polymorphisms and efavirenz adverse effects in Brazilian HIV-positive individuals.

PubMed

de Almeida, Tailah Bernardo; de Azevedo, Marcelo Costa Velho Mendes; Pinto, Jorge Francisco da Cunha; Ferry, Fernando Rafael de Almeida; da Silva, Guilherme Almeida Rosa; de Castro, Izana Junqueira; Baker, Paxton; Tanuri, Amilcar; Haas, David W; Cardoso, Cynthia C

2018-06-03

There are limited data regarding efavirenz pharmacogenetics in admixed populations. The Brazilian population is highly admixed. In a Brazilian cohort, we sought to characterize associations between efavirenz adverse effects (all-cause and CNS) and polymorphisms in seven genes known or suspected to affect efavirenz metabolism and transport. We studied 225 HIV-positive individuals who had been prescribed efavirenz-containing regimens at a hospital in Rio de Janeiro, Brazil. Eighty-nine cases had efavirenz adverse effects, including 43 with CNS adverse effects, while 136 controls had no adverse effect of any antiretroviral after treatment for at least 6 months. A total of 67 candidate polymorphisms in ABCB1, CYP2A6, CYP2B6, CYP3A4, CYP3A5, NR1I2 and NR1I3 genes were selected for association analysis. Admixture was assessed using 28 ancestry-informative polymorphisms previously validated for the Brazilian population. Associations were evaluated with logistic regression models adjusted for sex and genetic ancestry. There was extensive African, European and Native American admixture in the cohort. Increased all-cause adverse effects were associated with the CYP2B6 genotype combination 15582CC-516TT-983TT (OR = 7.26, P = 0.003) and with the CYP2B6 slow metabolizer group 516TT or 516GT-983CT (OR = 3.10, P = 0.04). CNS adverse effects were nominally associated with CYP3A4 rs4646437 (OR = 4.63, P = 0.014), but not after adjusting for multiple comparisons. In a highly admixed Brazilian cohort, the CYP2B6 slow metabolizer genotype was associated with an increased risk of efavirenz adverse effects.

Warnings of adverse side effects can backfire over time.

PubMed

Steinhart, Yael; Carmon, Ziv; Trope, Yaacov

2013-09-01

Warnings that a promoted product can have adverse side effects (e.g., smoking cigarettes can cause cancer) should dampen the product's allure. We predicted that with temporal distance (e.g., when an ad relates to future consumption or was viewed some time earlier), this common type of warning can have a worrisome alternative consequence: It can ironically boost the product's appeal. Building on construal-level theory, we argue that this is because temporal distance evokes high-level construal, which deemphasizes side effects and emphasizes message trustworthiness. In four studies, we demonstrated this phenomenon. For example, participants could buy cigarettes or artificial sweeteners after viewing an ad promoting the product. Immediately afterward, the quantity that participants bought predictably decreased if the ad they saw included a warning about adverse side effects. With temporal distance (product to be delivered 3 months later, or 2 weeks after the ad was viewed), however, participants who had seen an ad noting the benefits of the product but warning of risky side effects bought more than those who had seen an ad noting only benefits.

Adverse effects associated with photodynamic therapy (PDT) of port-wine stain (PWS) birthmarks.

PubMed

Yuan, Kai-Hua; Gao, Jian-Hua; Huang, Zheng

2012-12-01

Several Chinese studies suggest that Hemoporfin-mediated photodynamic therapy (PDT) is an alternative treatment for port-wine stain (PWS) birthmarks. To evaluate treatment responses and adverse effects associated with Hemoporfin PDT for the treatment of PWS and their management. The medical records of 700 patients who underwent PDT treatment in our center were retrospectively examined. Treatment-related reactions and adverse effects were reviewed. Different types of PWS lesions and different individuals showed different immediate responses (e.g. swelling, color change, pain). To certain extents these reactions were a useful indicator of the treatment endpoint. Edema and scabbing were the most common post-treatment responses. Short-term (e.g. blister, eczematous dermatitis, cutaneous photosensitivity) and long-term (e.g. pigmentation change, scar formation) adverse effects were generally caused by the phototoxicity associated with the combination of photosensitizer and light exposure. Although PDT is a safe treatment alternative for PWS birthmarks, treatment parameters must be selected for each individual patient and cutaneous changes must be monitored during light irradiation to minimize the risk of adverse effects. Over estimation of required light dosage or failure to recognize cutaneous changes associated with adverse effects can increase the risk of a poor outcome. Copyright © 2012 Elsevier B.V. All rights reserved.

Adverse Reactions to Hallucinogenic Drugs.

ERIC Educational Resources Information Center

Meyer, Roger E. , Ed.

This reports a conference of psychologists, psychiatrists, geneticists and others concerned with the biological and psychological effects of lysergic acid diethylamide and other hallucinogenic drugs. Clinical data are presented on adverse drug reactions. The difficulty of determining the causes of adverse reactions is discussed, as are different…

Review shows that early foetal alcohol exposure may cause adverse effects even when the mother consumes low levels.

PubMed

Sarman, Ihsan

2018-06-01

Studies are increasingly focusing on the effects of prenatal alcohol exposure (PAE) on child health. The aim of this review was to provide paediatricians with new insights to help them communicate key messages about avoiding alcohol during pregnancy. Inspired by the 7th International Conference on Fetal Alcohol Spectrum Disorder, which focused on integrating research, policy and practice, we studied English language papers published since 2010 on how early PAE triggered epigenetic mechanisms that had an impact on the development of some chronic diseases. We also report the findings of a human study using three-dimensional photography of the face to explore associations between PAE and craniofacial phenotyping. Animal models with different alcohol exposure patterns show that early PAE may lead to long-term chronic effects, due to developmental programming for some adult diseases in cardiovascular, metabolic and renal systems. The study with three-dimensional photographing is very promising in helping paediatricians to understand how even small amounts of PAE can affect craniofacial phenotyping. Even low levels of PAE can cause adverse foetal effects and not just in the brain. It is not currently possible to determine a safe period and level when alcohol consumption would not affect the foetus. ©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

[Hydroxymethyluracil in the correction of adverse effects caused by chemotherapy of malignant neoplasms].

PubMed

Sakaeva, D D

2004-01-01

Hydroxymethyluracil (HMU) in a dose of 1.5-3 g/day produces a stimulant effect upon leukopoiesis and granulocytopoiesis in cases of toxic neutropenia caused by chemotherapy. In the same dose range, HMU produces immunostimulant action in patients with immune deficit caused by oncopathology and chemotherapy.

DETERMINING THE CAUSES OF ADVERSE EFFECTS IN NEAR COASTAL ECOSYSTEMS: FROM TOXICITY IDENTIFICATION EVALUATIONS TO WATERSHED DIAGNOTICS

EPA Science Inventory

Several approaches are available for evaluating adverse effects in near coastal ecosystems. These range from performing toxicity tests with individual organisms on water column and sediment samples to conducting macrofaunal compositional analyses on pelagic and benthic communiti...

The adverse health effects of chronic cannabis use.

PubMed

Hall, Wayne; Degenhardt, Louisa

2014-01-01

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

36 CFR 800.6 - Resolution of adverse effects.

Code of Federal Regulations, 2010 CFR

2010-07-01

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

36 CFR 800.5 - Assessment of adverse effects.

Code of Federal Regulations, 2010 CFR

2010-07-01

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

Rare and very rare adverse effects of clozapine

PubMed Central

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

2015-01-01

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

MECHANISMS BY WHICH ULTRAFINE, FINE, AND COARSE PARTICLES CAUSE ADVERSE HEALTH EFFECTS

EPA Science Inventory

A small number of recent studies suggest that different size particles may cause different health effects. There are clearly differences in the chemical makeup of coarse, fine, and ultrafine particles, and this different chemistry may well drive different health responses. The ...

Adverse health effects of non-medical cannabis use.

PubMed

Hall, Wayne; Degenhardt, Louisa

2009-10-17

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

Adverse effects of oral amiodarone therapy.

PubMed

Sinha, P R; Dube, S; Sujata; Gupta, P R; Avasthey, P; Somani, P N

1992-04-01

Oral amiodarone was administered to 38 patients (25 males, 13 females) with mean age of 43.6 years. Ventricular and supraventricular arrhythmias were present in 30 and 8 patients respectively. Amiodarone was given as 400-1200 mg/day for 1-2 weeks as loading dose and then it was maintained as 100-600 mg/day. The mean duration of therapy was 12.4 months. Adverse effects were noted in 21 (55.3%) cases. The commonest adverse effects observed were asymptomatic corneal microdeposits followed by gastrointestinal, cardiac, neurological and cutaneous disturbances. The drug was withdrawn in 2 (5.3%) patients because of nausea and vomiting. One patient died of pulmonary infiltrations. It is concluded that adverse effects are common with amiodarone but are tolerated well, making this drug an excellent choice for treatment of cardiac arrhythmias.

Treatment of Functional Abdominal Pain With Antidepressants: Benefits, Adverse Effects, and the Gastroenterologist's Role.

PubMed

Zar-Kessler, Claire A M; Belkind-Gerson, Jaime; Bender, Suzanne; Kuo, Braden M

2017-07-01

Pediatric functional abdominal pain is often treated with tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). The aim is investigating antidepressant use for treatment efficacy, correlation of response to psychiatric factors, and impact of adverse effects in regard to physicians' prescribing patterns. Retrospective review (2005-2013) children (5-21 years old) with functional abdominal pain treated with SSRI or TCA. Of the 531 cases with functional abdominal pain, 192 initiated SSRIs or TCAs while followed by gastroenterology. Charts reviewed for symptoms, adverse effects, and response: decreased pain or increased daily functioning. Sixty-three of 84 (75%) SSRI patients improved, 56 of 92 (61%) TCA patients improved (P = 0.03). Logistic regression controlling for psychiatric factors: SSRI remained significant over TCA (P = 0.04). Thirty-two of 67 (48%) patients with constipation received TCAs and 26 of 45 (58%) patients with diarrhea received SSRIs (P = 0.64). Three SSRI patients reported gastrointestinal effects, all diarrheal-type symptoms, and 2 TCA patients reported gastrointestinal effects, both constipation, in all it led to discontinuation. Thirteen (29%) of diarrheal-type patients reported adverse effects causing discontinuation as compared to 7 (8%) in the constipation group (P = .01). Twenty-one (25%) SSRI patients reported adverse effects with 5 (6%) mood disturbances. Twenty (22%) TCA patients reported adverse effects, 13 (14%) with mood disturbances (P = .07). Overall, 12 (14%) SSRI patients discontinued medication due to adverse effects, whereas 16 (17%) TCA patients (P = 0.24) did. Patients had significantly greater response to SSRIs than TCAs, remaining significant after controlling for psychiatric factors. Little significance is given to patient's associated gastrointestinal symptoms, frequently resulting in adverse effects and termination of medication.

40 CFR 350.21 - Adverse health effects.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 29 2012-07-01 2012-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify the...

40 CFR 350.21 - Adverse health effects.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 29 2013-07-01 2013-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify the...

40 CFR 350.21 - Adverse health effects.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 28 2011-07-01 2011-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify the...

40 CFR 350.21 - Adverse health effects.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 27 2010-07-01 2010-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify the...

40 CFR 350.21 - Adverse health effects.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 28 2014-07-01 2014-07-01 false Adverse health effects. 350.21 Section... RIGHT-TO-KNOW INFORMATION: AND TRADE SECRET DISCLOSURES TO HEALTH PROFESSIONALS Trade Secrecy Claims § 350.21 Adverse health effects. The Governor or State emergency response commission shall identify the...

A rare adverse effect of metronidazole: nervous system symptoms.

PubMed

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

2013-06-01

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

Topiramate-induced somnambulism in a migraineur: a probable idiosyncratic adverse effect.

PubMed

Mathew, Thomas; Sarma, G R K; Nadig, Raghunandan; Varghese, Raji

2012-04-15

Somnambulism (sleepwalking) is a disorder of arousal that falls under "parasomnia" group and is more common in children. These phenomena occur as primary sleep events or secondary to systemic disease or can be drug induced. Medications that can cause sleepwalking include neuroleptics, hypnotics, lithium, amitriptyline, and β-blockers. This report presents an unusual adverse effect of topiramate on sleep in a patient with migraine.

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

PubMed

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

2008-08-01

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

Adverse medical complications: an under-reported contributory cause of death in New York City.

PubMed

Gill, J R; Ely, S F; Toriello, A; Hirsch, C S

2014-04-01

The current death certification system in the USA fails to accurately track deaths due to adverse medical events. The aim of this study was to demonstrate the under-reporting of deaths due to adverse medical events due to limitations in the current death certification/reporting system, and the benefits of using the term 'therapeutic complication' as the manner of death. Retrospective review and comparison of death certificates and vital statistical coding. The manner of death is certified as a therapeutic complication when death is caused by predictable complications of appropriate therapy, and would not have occurred but for the medical intervention. Based on medical examiner records, complications that caused or contributed to deaths over a five-year period were examined retrospectively. These fatalities were compared with deaths coded as medical and surgical complications by the New York City Bureau of Vital Statistics. The Medical Examiner's Office certified 2471 deaths as therapeutic complications and 312 deaths as accidents occurring in healthcare facilities. In contrast, the New York City Bureau of Vital Statistics reported 188 deaths due to complications of medical and surgical care. Use of the term 'therapeutic complication' as the manner of death identified nearly 14 times more deaths than were reported by the New York City Bureau of Vital Statistics. If these therapeutic complications and medical accidents were considered as a 'disease', they would rank as the 10th leading cause of death in New York City, surpassing homicides and suicides in some years. Nationwide policy shifts that use the term 'therapeutic complication' would improve the capture and reporting of these deaths, thus allowing better identification of fatal adverse medical events in order to focus on and assess preventative strategies. Copyright © 2013 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

Rebound effect of modern drugs: serious adverse event unknown by health professionals.

PubMed

Teixeira, Marcus Zulian

2013-01-01

Supported in the Hippocratic aphorism primum non nocere, the bioethical principle of non-maleficence pray that the medical act cause the least damage or injury to the health of the patient, leaving it to the doctor to assess the risks of a particular therapy through knowledge of possible adverse events of drugs. Among these, the rebound effect represents a common side effect to numerous classes of modern drugs, may cause serious and fatal disorders in patients. This review aims to clarify the health professionals on clinical and epidemiological aspects of rebound phenomenon. A qualitative, exploratory and bibliographic review was held in the PubMed database using the keywords 'rebound', 'withdrawal', 'paradoxical', 'acetylsalicylic acid', 'anti-inflammatory', 'bronchodilator', 'antidepressant', 'statin', 'proton pump inhibitor' and 'bisphosphonate'. The rebound effect occurs after discontinuation of numerous classes of drugs that act contrary to the disease disorders, exacerbating them at levels above those prior to treatment. Regardless of the disease, the drug and duration of treatment, the phenomenon manifests itself in a small proportion of susceptible individuals. However, it may cause serious and fatal adverse events should be considered a public health problem in view of the enormous consumption of drugs by population. Bringing together a growing and unquestionable body of evidence, the physician needs to have knowledge of the consequences of the rebound effect and how to minimize it, increasing safety in the management of modern drugs. On the other hand, this rebound can be used in a curative way, broadening the spectrum of the modern therapeutics. Copyright © 2012 Elsevier Editora Ltda. All rights reserved.

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

PubMed

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

2017-09-01

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

[Management of adverse drug effects].

PubMed

Schlienger, R G

2000-09-01

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

Adverse effects of methotrexate in three psoriatic arthritis patients.

PubMed

Maejima, Hideki; Watarai, Akira; Nakano, Toshiaki; Katayama, Chieko; Nishiyama, Hiromi; Katsuoka, Kensei

2014-04-01

Methotrexate, a folic acid analogue with anti-proliferative and anti-inflammatory effects, is commonly used to treat patients with severe destructive psoriatic arthritis and has considerable efficacy. Combined anti-tumor necrosis factor and MTX therapy result in less treatment discontinuation due to adverse events. Despite its efficacy, MTX may result in adverse effects including hepatic, pulmonary, and renal toxicity as well as lymphoproliferative disorders and predisposition to infection. We herein report rare adverse effects of MTX treatment, specifically asymptomatic pulmonary tuberculosis, renal cell carcinoma, and lateral uveitis, in three psoriatic arthritis patients treated with MTX. MTX is an important drug for the treatment for psoriatic arthritis patient, but an awareness of the possible adverse effects is needed.

Characterization of scientific studies usually cited as evidence of adverse effects of GM food/feed.

PubMed

Sánchez, Miguel A; Parrott, Wayne A

2017-10-01

GM crops are the most studied crops in history. Approximately 5% of the safety studies on them show adverse effects that are a cause for concern and tend to be featured in media reports. Although these reports are based on just a handful of GM events, they are used to cast doubt on all GM crops. Furthermore, they tend to come from just a few laboratories and are published in less important journals. Importantly, a close examination of these reports invariably shows methodological flaws that invalidate any conclusions of adverse effects. Twenty years after commercial cultivation of GM crops began, a bona fide report of an adverse health effect due to a commercialized modification in a crop has yet to be reported. © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Adverse Effects of Electronic Cigarette Use: A Concept Mapping Approach

PubMed Central

Nasim, Aashir; Rosas, Scott

2016-01-01

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

[Vasopressin intravenous infusion causes dose dependent adverse cardiovascular effects in anesthetized dogs.

PubMed

Martins, Luiz Cláudio; Sabha, Maricene; Paganelli, Maria Ondina; Coelho, Otávio Rizzi; Ferreira-Melo, Silvia Elaine; Moreira, Marcos Mello; Cavalho, Adriana Camargo de; Araujo, Sebastião; Moreno Junior, Heitor

2010-01-15

BACKGROUND: Arginine vasopressin (AVP) has been broadly used in the management of vasodilatory shock. However, there are many concerns regarding its clinical use, especially in high doses, as it can be associated with adverse cardiovascular events. OBJECTIVE: To investigate the cardiovascular effects of AVP in continuous IV infusion on hemodynamic parameters in dogs. METHODS: Sixteen healthy mongrel dogs, anesthetized with pentobarbital were intravascularly catheterized, and randomly assigned to: control (saline-placebo; n=8) and AVP (n=8) groups. The study group was infused with AVP for three consecutive 10-minute periods at logarithmically increasing doses (0.01; 0.1 and 1.0U/kg/min), at them 20-min intervals. Heart rate (HR) and intravascular pressures were continuously recorded. Cardiac output was measured by the thermodilution method. RESULTS: No significant hemodynamic effects were observed during 0.01U/kg/min of AVP infusion, but at higher doses (0.1 and 1.0U/kg/min) a progressive increase in mean arterial pressure (MAP) and systemic vascular resistance index (SVRI) were observed, with a significant decrease in HR and the cardiac index (CI). A significant increase in the pulmonary vascular resistance index (PVRI) was also observed with the 1.0U/kg/min dose, mainly due to the decrease in the CI. CONCLUSION: AVP, when administered at doses between 0.1 and 1.0U/kg/min, induced significant increases in MAP and SVRI, with negative inotropic and chronotropic effects in healthy animals. Although these doses are ten to thousand times greater than those routinely used for the management of vasodilatory shock, our data confirm that AVP might be used carefully and under strict hemodynamic monitoring in clinical practice, especially if doses higher than 0.01 U/kg/min are needed. Martins, LC et al.

Statin-Associated Muscle-Related Adverse Effects: A Case Series of 354 Patients

PubMed Central

Cham, Stephanie; Evans, Marcella A.; Denenberg, Julie O.; Golomb, Beatrice A.

2016-01-01

Study Objective To characterize the properties and natural history of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin)-associated muscle-related adverse effects (MAEs). Design Patient-targeted postmarketing adverse-effect surveillance approach coupling survey design with an open-ended narrative. Setting University-affiliated health care system. Subjects Three hundred fifty-four patients (age range 34–86 yrs) who self-reported muscle-related problems associated with statin therapy. Measurements and Main Results Patients with perceived statin-associated MAEs completed a survey assessing statin drugs and dosages; characteristics of the MAEs; time course of onset, resolution, or recurrence; and impact on quality of life (QOL). Cases were assessed for putative drug adverse-effect causality by using the Naranjo adverse drug reaction probability scale criteria and were evaluated for inclusion in groups for which mortality benefit with statins has been shown. Patients reported muscle pain (93%), fatigue (88%), and weakness (85%). Three hundred patients (85%) met literature criteria for probable or definite drug adverse-effect causality. Ninety-four percent of atorvastatin usages (240/255) generated MAEs versus 61% of lovastatin usages (38/62, p<0.0001). Higher potency statins reproduced MAEs in 100% of 39 rechallenges versus 73% (29/40) with lower potency rechallenges (p<0.01). Time course of onset after statin initiation varied (median 14 wks); some MAEs occurred after long-term symptom-free use. Recurrence with rechallenge had a significantly shorter latency to onset (median 2 wks). The MAEs adversely affected all assessed functional and QOL domains. Most patients with probable or definite MAEs were in categories for which available randomized controlled trial evidence shows no trend to all-cause mortality benefit with statin therapy. Conclusion This study complements available information on the properties and natural history of statin

Statin-associated muscle-related adverse effects: a case series of 354 patients.

PubMed

Cham, Stephanie; Evans, Marcella A; Denenberg, Julie O; Golomb, Beatrice A

2010-06-01

To characterize the properties and natural history of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor (statin)-associated muscle-related adverse effects (MAEs). Patient-targeted postmarketing adverse-effect surveillance approach coupling survey design with an open-ended narrative. University-affiliated health care system. Three hundred fifty-four patients (age range 34-86 yrs) who self-reported muscle-related problems associated with statin therapy. Patients with perceived statin-associated MAEs completed a survey assessing statin drugs and dosages; characteristics of the MAEs; time course of onset, resolution, or recurrence; and impact on quality of life (QOL). Cases were assessed for putative drug adverse-effect causality by using the Naranjo adverse drug reaction probability scale criteria and were evaluated for inclusion in groups for which mortality benefit with statins has been shown. Patients reported muscle pain (93%), fatigue (88%), and weakness (85%). Three hundred patients (85%) met literature criteria for probable or definite drug adverse-effect causality. Ninety-four percent of atorvastatin usages (240/255) generated MAEs versus 61% of lovastatin usages (38/62, p<0.0001). Higher potency statins reproduced MAEs in 100% of 39 rechallenges versus 73% (29/40) with lower potency rechallenges (p<0.01). Time course of onset after statin initiation varied (median 14 wks); some MAEs occurred after long-term symptom-free use. Recurrence with rechallenge had a significantly shorter latency to onset (median 2 wks). The MAEs adversely affected all assessed functional and QOL domains. Most patients with probable or definite MAEs were in categories for which available randomized controlled trial evidence shows no trend to all-cause mortality benefit with statin therapy. This study complements available information on the properties and natural history of statin-associated MAEs, affirming dose dependence and strong QOL impact. The data indicating a dose

Adverse testicular effects of Botox® in mature rats

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

Breikaa, Randa M.; Mosli, Hisham A.; Nagy, Ayman A.

Botox® injections are taking a consistently increasing place in urology. Intracremasteric injections, particularly, have been applied for cryptorchidism and painful testicular spasms. Studies outlining their safety for this use are, however, scanty. Thus, the present study aimed at evaluating possible testicular toxicity of Botox® injections and their effect on male fertility. Mature rats were given intracremasteric Botox® injections (10, 20 and 40 U/kg) three times in a two-week interval. Changes in body and testes weights were examined and gonadosomatic index compared to control group. Semen quality, sperm parameters, fructose, protein, cholesterol and triglycerides contents were assessed. Effects on normal testicularmore » function were investigated by measuring testosterone levels and changes in enzyme activities (lactate dehydrogenase-X and acid phosphatase). To draw a complete picture, changes in oxidative and inflammatory states were examined, in addition to the extent of connective tissue deposition between seminiferous tubules. In an attempt to have more accurate information about possible spermatotoxic effects of Botox®, flowcytometric analysis and histopathological examination were carried out. Botox®-injected rats showed altered testicular physiology and function. Seminiferous tubules were separated by dense fibers, especially with the highest dose. Flowcytometric analysis showed a decrease in mature sperms and histopathology confirmed the findings. The oxidative state was, however, comparable to control group. This study is the first to show that intracremasteric injections of Botox® induce adverse testicular effects evidenced by inhibited spermatogenesis and initiation of histopathological changes. In conclusion, decreased fertility may be a serious problem Botox® injections could cause. - Highlights: • Botox® injections are the trend nowadays, for both medical and non-medical uses. • They were recently suggested for cryptorchidism and

[Adverse muscle effects of a podofyllotoxin-containing cytotoxic drug product with simvastatin].

PubMed

Kaipiainen-Seppänen, Oili; Savolainen, Elina; Elfving, Pia; Kononoff, Aulikki

2009-01-01

With the ageing population, drug interactions pose an increasing challenge to health professionals. We describe four patients, for whom concurrent administration of a podofyllotoxin-containing cytotoxic drug product and simvastatin caused severe adverse effects on muscles, including muscle pain, soreness or fatigue or weakness, and in some patients also disintegration of muscle tissue, i.e. rhabdomyolysis. The metabolism of both drugs proceeds via the common CYP3A4 enzyme pathway.

The effects of early life adversity on the immune system.

PubMed

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

2017-08-01

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

Adverse Effects of Common Drugs: Dietary Supplements.

PubMed

Felix, Todd Matthew; Karpa, Kelly Dowhower; Lewis, Peter R

2015-09-01

Dietary supplement-induced adverse effects often resolve quickly after discontinuation of the offending product, especially in younger patients. The potential for unwanted outcomes can be amplified in elderly patients or those taking multiple prescription drugs, especially where interactions exist with drugs metabolized by cytochrome P450 enzymes. Attributing injury or illness to a specific supplement can be challenging, especially in light of multi-ingredient products, product variability, and variability in reporting, as well as the vast underreporting of adverse drug reactions. Clinicians prescribing a new drug or evaluating a patient with a new symptom complex should inquire about use of herbal and dietary supplements as part of a comprehensive evaluation. Clinicians should report suspected supplement-related adverse effects to the local or state health department, as well as the Food and Drug Administration's MedWatch program (available at https://www.safetyreporting.hhs.gov). Clinicians should consider discussing suspected adverse effects involving drugs, herbal products, or dietary supplements with their community- and hospital-based pharmacists, and explore patient management options with medical or clinical toxicology subspecialists. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

Modelling the adverse effects associated with ecstasy use.

PubMed

Fisk, John E; Murphy, Philip N; Montgomery, Catharine; Hadjiefthyvoulou, Florentia

2011-04-01

Ecstasy, the street name for 3,4-meththylenedioxymethamphetamine, has been associated with a range of psychiatric symptoms and impaired psychological health in both problem and recreational users. The purpose of the present paper is to determine how these impairments are related to the history of polydrug use, and the conditions under which individuals ingest ecstasy. Associations between the variables of interest were investigated utilizing negative binomial regression. Liverpool and Preston in the North West of England. A convenience sample of 159 recreational ecstasy/polydrug users (80 males, 79 females). The sample was composed primarily of undergraduates. The dependent variable was the number of reported ecstasy-related adverse effects. Independent variables included quantitative aspects of ecstasy and other drug use, and the various beliefs and behaviours associated with ecstasy use. The number of adverse effects was associated positively with life-time exposure to ecstasy and negatively with period of abstinence from the drug. Adverse effects were more common among those who consumed ecstasy and alcohol concurrently, but were unrelated to other aspects of polydrug use. They were unaffected by whether the user took precautions when using the drug, and only weakly related to prior beliefs concerning the effects of ecstasy. Greater life-time exposure to ecstasy and consuming the drug concurrently with alcohol increase the likelihood of experiencing adverse effects, including paranoia, poor general health, irritability, confusion and moodiness. Adverse effects decrease with the period of abstinence from the drug. © 2010 The Authors, Addiction © 2010 Society for the Study of Addiction.

Adverse effects of outdoor pollution in the elderly.

PubMed

Simoni, Marzia; Baldacci, Sandra; Maio, Sara; Cerrai, Sonia; Sarno, Giuseppe; Viegi, Giovanni

2015-01-01

With fewer newborns and people living longer, older people are making up an increasing fraction of the total population. Epidemiological evidence shows that older-age-related health problems affect a wide and expanding proportion of the world population. One of the major epidemiological trends of this century is the rise of chronic diseases that affect more elderly than younger people. A total of 3.7 million premature deaths worldwide in 2012 are attributable to outdoor air pollution; the susceptibility to adverse effects of air pollution is expected to differ widely between people and within the same person, and also over time. Frailty history, a measure of multi-system decline, modifies cumulative associations between air pollution and lung function. Moreover, pre-existing diseases may determine susceptibility. In the elderly, due to comorbidity, exposure to air pollutants may even be fatal. Rapid and not-well-planned urbanization is associated with high level of ambient air pollution, mainly caused by vehicular exhausts. In general, there is sufficient evidence of the adverse effects related to short-term exposure, while fewer studies have addressed the longer-term health effects. Increased pollution exposures have been associated with increased mortality, hospital admissions/emergency-room visits, mainly due to exacerbations of chronic diseases or to respiratory tract infections (e.g., pneumonia). These effects may also be modulated by ambient temperature and many studies show that the elderly are mostly vulnerable to heat waves. The association between heat and mortality in the elderly is well-documented, while less is known regarding the associations with hospital admissions. Chronic exposure to elevated levels of air pollution has been related to the incidence of chronic obstructive pulmonary disease (COPD), chronic bronchitis (CB), asthma, and emphysema. There is also growing evidence suggesting adverse effects on lung function related to long-term exposure

[Local adverse reactions associated with parenteral administration of drugs].

PubMed

Bjånes, Tormod Karlsen

2011-03-04

Parenteral administration of drugs may cause adverse reactions which in severe cases outweigh the intended therapeutic effects. This paper outlines local adverse reactions associated with various routes of parenteral administration. Different measures for prevention and management of such reactions are presented.

Adverse effects of public health interventions: a conceptual framework.

PubMed

Lorenc, Theo; Oliver, Kathryn

2014-03-01

Public health interventions may have a range of adverse effects. However, there is limited guidance as to how evaluations should address the possibility of adverse effects. This discussion paper briefly presents a framework for thinking about the potential harms of public health interventions, focusing on the following categories: direct harms; psychological harms; equity harms; group and social harms; and opportunity harms. We conclude that the possibility of adverse effects needs to be taken into account by those implementing and evaluating interventions, and requires a broad perspective on the potential impacts of public health strategies.

Adverse Effects of Nonsystemic Steroids (Inhaled, Intranasal, and Cutaneous): a Review of the Literature and Suggested Monitoring Tool.

PubMed

Gupta, Ratika; Fonacier, Luz S

2016-06-01

Inhaled, intranasal, and cutaneous steroids are prescribed by physicians for a plethora of disease processes including asthma and rhinitis. While the high efficacy of this class of medication is well known, the wide range of adverse effects, both local and systemic, is not well elucidated. It is imperative to monitor total steroid burden in its varied forms as well as tracking for possible side effects that may be caused by a high cumulative dose of steroids. This review article highlights the adverse effects of different steroid modalities as well as suggests a monitoring tool to determine steroid totality and side effects.

Adverse Effects of Plasma Transfusion

PubMed Central

Pandey, Suchitra; Vyas, Girish N.

2012-01-01

Plasma utilization has increased over the last two decades, and there is a growing concern that many plasma transfusions are inappropriate. Plasma transfusion is not without risk, and certain complications are more likely with plasma than other blood components. Clinical and laboratory investigations of the patients suffering reactions following infusion of fresh frozen plasma (FFP) define the etiology and pathogenesis of the panoply of adverse effects. We review here the pathogenesis, diagnosis, and management of the risks associated with plasma transfusion. Risks commonly associated with FFP include: (1) transfusion related acute lung injury; (2) transfusion associated circulatory overload, and (3) allergic/anaphylactic reactions. Other less common risks include (1) transmission of infections, (2) febrile non-hemolytic transfusion reactions, (3) RBC allo-immunization, and (4) hemolytic transfusion reactions. The affect of pathogen inactivation/reduction methods on these risks are also discussed. Fortunately, a majority of the adverse effects are not lethal and are adequately treated in clinical practice. PMID:22578374

Effect of monthly vitamin D3 supplementation in healthy adults on adverse effects of earthquakes: randomised controlled trial

PubMed Central

Florkowski, Christopher M; Chambers, Stephen T; Priest, Patricia C; Stewart, Alistair W; Jennings, Lance C; Livesey, John H; Camargo, Carlos A; Scragg, Robert; Murdoch, David R

2014-01-01

Objective To determine whether supplementation with vitamin D improves resilience to the adverse effects of earthquakes. Design Opportunistic addition to an established randomised double blind placebo controlled trial. Setting Christchurch, New Zealand, where a prolonged series of catastrophic earthquakes beginning on 4 September 2010 occurred, which caused widespread destruction, fatalities, and extensive psychological damage. Participants 322 healthy adults (241 women; 81 men) aged 18-67 who were already participating in the vitamin D and acute respiratory infections study (VIDARIS) between February 2010 and November 2011. Intervention Participants were randomised to receive an oral dose of either 200 000 IU vitamin D3 monthly for two months then 100 000 IU monthly (n=161) or placebo (n=161) for a total of 18 months. Main outcome measure This is a post hoc analysis from the previously published VIDARIS trial. The primary endpoint in the current analysis was the self reported effects and overall adverse impact of the Christchurch earthquakes as assessed by questionnaire four months after the most destructive earthquake on 22 February 2011, which was used as the index event. The secondary end point was the number of “psychological” adverse events that participants reported at their usual monthly appointments as part of the original VIDARIS trial. Results 308 participants completed the earthquake impact questionnaire (n=152 in the vitamin D group and 156 in the placebo group). There was no significant difference in the number of self reported adverse effects between those receiving vitamin D supplementation and those receiving placebo. There was also no difference in the overall adverse impact score between treatment groups (χ2 P=0.44). The exception was that those in the vitamin D group experienced more adverse effects on family relationships (22% v 13%; χ2 P=0.03). The number of psychological adverse events—such as fatigue, stress, anxiety, and insomnia�

Effect of monthly vitamin D3 supplementation in healthy adults on adverse effects of earthquakes: randomised controlled trial.

PubMed

Slow, Sandy; Florkowski, Christopher M; Chambers, Stephen T; Priest, Patricia C; Stewart, Alistair W; Jennings, Lance C; Livesey, John H; Camargo, Carlos A; Scragg, Robert; Murdoch, David R

2014-12-15

To determine whether supplementation with vitamin D improves resilience to the adverse effects of earthquakes. Opportunistic addition to an established randomised double blind placebo controlled trial. Christchurch, New Zealand, where a prolonged series of catastrophic earthquakes beginning on 4 September 2010 occurred, which caused widespread destruction, fatalities, and extensive psychological damage. 322 healthy adults (241 women; 81 men) aged 18-67 who were already participating in the vitamin D and acute respiratory infections study (VIDARIS) between February 2010 and November 2011. Participants were randomised to receive an oral dose of either 200,000 IU vitamin D3 monthly for two months then 100,000 IU monthly (n=161) or placebo (n=161) for a total of 18 months. This is a post hoc analysis from the previously published VIDARIS trial. The primary endpoint in the current analysis was the self reported effects and overall adverse impact of the Christchurch earthquakes as assessed by questionnaire four months after the most destructive earthquake on 22 February 2011, which was used as the index event. The secondary end point was the number of "psychological" adverse events that participants reported at their usual monthly appointments as part of the original VIDARIS trial. 308 participants completed the earthquake impact questionnaire (n=152 in the vitamin D group and 156 in the placebo group). There was no significant difference in the number of self reported adverse effects between those receiving vitamin D supplementation and those receiving placebo. There was also no difference in the overall adverse impact score between treatment groups (χ(2) P=0.44). The exception was that those in the vitamin D group experienced more adverse effects on family relationships (22% v 13%; χ(2) P=0.03). The number of psychological adverse events-such as fatigue, stress, anxiety, and insomnia-that participants reported at their usual monthly appointments was significantly

Effectiveness of adverse effects search filters: drugs versus medical devices.

PubMed

Farrah, Kelly; Mierzwinski-Urban, Monika; Cimon, Karen

2016-07-01

The study tested the performance of adverse effects search filters when searching for safety information on medical devices, procedures, and diagnostic tests in MEDLINE and Embase. The sensitivity of 3 filters was determined using a sample of 631 references from 131 rapid reviews related to the safety of health technologies. The references were divided into 2 sets by type of intervention: drugs and nondrug health technologies. Keyword and indexing analysis were performed on references from the nondrug testing set that 1 or more of the filters did not retrieve. For all 3 filters, sensitivity was lower for nondrug health technologies (ranging from 53%-87%) than for drugs (88%-93%) in both databases. When tested on the nondrug health technologies set, sensitivity was lower in Embase (ranging from 53%-81%) than in MEDLINE (67%-87%) for all filters. Of the nondrug records that 1 or more of the filters missed, 39% of the missed MEDLINE records and 18% of the missed Embase records did not contain any indexing terms related to adverse events. Analyzing the titles and abstracts of nondrug records that were missed by any 1 filter, the most commonly used keywords related to adverse effects were: risk, complications, mortality, contamination, hemorrhage, and failure. In this study, adverse effects filters were less effective at finding information about the safety of medical devices, procedures, and tests compared to information about the safety of drugs.

Identification and Characterization of Adverse Effects in 21st Century Toxicology

EPA Science Inventory

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

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

PubMed

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

2009-12-01

To identify methodological research on the incorporation of adverse effects in economic models and to review current practice. Major electronic databases (Cochrane Methodology Register, Health Economic Evaluations Database, NHS Economic Evaluation Database, EconLit, EMBASE, Health Management Information Consortium, IDEAS, MEDLINE and Science Citation Index) were searched from inception to September 2007. Health technology assessment (HTA) reports commissioned by the National Institute for Health Research (NIHR) HTA programme and published between 2004 and 2007 were also reviewed. The reviews of methodological research on the inclusion of adverse effects in decision models and of current practice were carried out according to standard methods. Data were summarised in a narrative synthesis. Of the 719 potentially relevant references in the methodological research review, five met the inclusion criteria; however, they contained little information of direct relevance to the incorporation of adverse effects in models. Of the 194 HTA monographs published from 2004 to 2007, 80 were reviewed, covering a range of research and therapeutic areas. In total, 85% of the reports included adverse effects in the clinical effectiveness review and 54% of the decision models included adverse effects in the model; 49% included adverse effects in the clinical review and model. The link between adverse effects in the clinical review and model was generally weak; only 3/80 (< 4%) used the results of a meta-analysis from the systematic review of clinical effectiveness and none used only data from the review without further manipulation. Of the models including adverse effects, 67% used a clinical adverse effects parameter, 79% used a cost of adverse effects parameter, 86% used one of these and 60% used both. Most models (83%) used utilities, but only two (2.5%) used solely utilities to incorporate adverse effects and were explicit that the utility captured relevant adverse effects; 53% of

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

PubMed Central

2014-01-01

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

Adverse effects of outdoor pollution in the elderly

PubMed Central

Baldacci, Sandra; Maio, Sara; Cerrai, Sonia; Sarno, Giuseppe; Viegi, Giovanni

2015-01-01

With fewer newborns and people living longer, older people are making up an increasing fraction of the total population. Epidemiological evidence shows that older-age-related health problems affect a wide and expanding proportion of the world population. One of the major epidemiological trends of this century is the rise of chronic diseases that affect more elderly than younger people. A total of 3.7 million premature deaths worldwide in 2012 are attributable to outdoor air pollution; the susceptibility to adverse effects of air pollution is expected to differ widely between people and within the same person, and also over time. Frailty history, a measure of multi-system decline, modifies cumulative associations between air pollution and lung function. Moreover, pre-existing diseases may determine susceptibility. In the elderly, due to comorbidity, exposure to air pollutants may even be fatal. Rapid and not-well-planned urbanization is associated with high level of ambient air pollution, mainly caused by vehicular exhausts. In general, there is sufficient evidence of the adverse effects related to short-term exposure, while fewer studies have addressed the longer-term health effects. Increased pollution exposures have been associated with increased mortality, hospital admissions/emergency-room visits, mainly due to exacerbations of chronic diseases or to respiratory tract infections (e.g., pneumonia). These effects may also be modulated by ambient temperature and many studies show that the elderly are mostly vulnerable to heat waves. The association between heat and mortality in the elderly is well-documented, while less is known regarding the associations with hospital admissions. Chronic exposure to elevated levels of air pollution has been related to the incidence of chronic obstructive pulmonary disease (COPD), chronic bronchitis (CB), asthma, and emphysema. There is also growing evidence suggesting adverse effects on lung function related to long-term exposure

Mitigation of Adverse Effects Caused by Shock Wave Boundary Layer Interactions Through Optimal Wall Shaping

NASA Technical Reports Server (NTRS)

Liou, May-Fun; Lee, Byung Joon

2013-01-01

It is known that the adverse effects of shock wave boundary layer interactions in high speed inlets include reduced total pressure recovery and highly distorted flow at the aerodynamic interface plane (AIP). This paper presents a design method for flow control which creates perturbations in geometry. These perturbations are tailored to change the flow structures in order to minimize shock wave boundary layer interactions (SWBLI) inside supersonic inlets. Optimizing the shape of two dimensional micro-size bumps is shown to be a very effective flow control method for two-dimensional SWBLI. In investigating the three dimensional SWBLI, a square duct is employed as a baseline. To investigate the mechanism whereby the geometric elements of the baseline, i.e. the bottom wall, the sidewall and the corner, exert influence on the flow's aerodynamic characteristics, each element is studied and optimized separately. It is found that arrays of micro-size bumps on the bottom wall of the duct have little effect in improving total pressure recovery though they are useful in suppressing the incipient separation in three-dimensional problems. Shaping sidewall geometry is effective in re-distributing flow on the side wall and results in a less distorted flow at the exit. Subsequently, a near 50% reduction in distortion is achieved. A simple change in corner geometry resulted in a 2.4% improvement in total pressure recovery.

[Adverse ocular effects of vaccinations].

PubMed

Ness, T; Hengel, H

2016-07-01

Vaccinations are very effective measures for prevention of infections but are also associated with a long list of possible side effects. Adverse ocular effects following vaccination have been rarely reported or considered to be related to vaccinations. Conjunctivitis is a frequent sequel of various vaccinations. Oculorespiratory syndrome and serum sickness syndrome are considered to be related to influenza vaccinations. The risk of reactivation or initiation of autoimmune diseases (e. g. uveitis) cannot be excluded but has not yet been proven. Overall the benefit of vaccination outweighs the possible but very low risk of ocular side effects.

Prevalence and detection of neuropsychiatric adverse effects during hepatitis C treatment.

PubMed

Masip, Montserrat; Tuneu, Laura; Pagès, Neus; Torras, Xavier; Gallego, Adolfo; Guardiola, Josep Maria; Faus, María José; Mangues, Maria Antònia

2015-12-01

Current treatment combinations for chronic hepatitis C virus infection still include pegylated interferon and ribavirin despite the new therapeutic options available. Interferon-based treatments are associated with a high incidence of adverse effects. Central nervous system events are among the most frequent adverse drug reactions and their influence on treatment adherence and effectiveness is controversial. The aim of the study was to evaluate neuropsychiatric adverse effects of interferon-based treatment for chronic hepatitis C in standard multidisciplinary clinical practice. Risk factors for these adverse effects and their impact on adherence and sustained viral response were also evaluated. Setting Ambulatory care pharmacy in coordination with the liver unit and the infectious diseases unit at a 650-bed tertiary university hospital. We included all consecutive patients with chronic hepatitis C who completed treatment with pegylated interferon and ribavirin between 2005 and 2013. All patients underwent a multidisciplinary follow-up during treatment. Neuropsychiatric adverse effects were evaluated in relation to severity, management and outcome. The presence of anxiety and depression was evaluated by means of specific tests. A total of 717 treatments in 679 patients were included. During treatment, we detected 1679 neuropsychiatric adverse effects in 618 patients (86.2 %), generating 1737 clinical interventions. Fifty-seven (3.3 %) neuropsychiatric adverse effects were severe and 2 (0.1 %) were life-threatening (suicidal attempts). Most neuropsychiatric adverse effects (1555 events, 92.6 %) resolved without sequelae. Psychiatric medication was required in 289 patients (40.3 %). Sustained viral response was achieved in 400 cases (55.8 %) and was associated with adherence (OR = 1.942, 95 % CI = 1.235-3.052, p = 0.004). A multivariate analysis did not show any relationship between neuropsychiatric adverse effects and treatment adherence or sustained viral response

Medications and Adverse Voice Effects.

PubMed

Nemr, Kátia; Di Carlos Silva, Ariana; Rodrigues, Danilo de Albuquerque; Zenari, Marcia Simões

2017-08-16

To identify the medications used by patients with dysphonia, describe the voice symptoms reported on initial speech-language pathology (SLP) examination, evaluate the possible direct and indirect effects of medications on voice production, and determine the association between direct and indirect adverse voice effects and self-reported voice symptoms, hydration and smoking habits, comorbidities, vocal assessment, and type and degree of dysphonia. This is a retrospective cross-sectional study. Fifty-five patients were evaluated and the vocal signs and symptoms indicated in the Dysphonia Risk Protocol were considered, as well as data on hydration, smoking and medication use. We analyzed the associations between type of side effect and self-reported vocal signs/symptoms, hydration, smoking, comorbidities, type of dysphonia, and auditory-perceptual and acoustic parameters. Sixty percent were women, the mean age was 51.8 years, 29 symptoms were reported on the screening, and 73 active ingredients were identified with 8.2% directly and 91.8% indirectly affecting vocal function. There were associations between the use of drugs with direct adverse voice effects, self-reported symptoms, general degree of vocal deviation, and pitch deviation. The symptoms of dry throat and shortness of breath were associated with the direct vocal side effect of the medicine, as well as the general degree of vocal deviation and the greater pitch deviation. Shortness of breath when speaking was also associated with the greatest degree of vocal deviation. Copyright © 2017 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

40 CFR 174.71 - Submission of information regarding adverse effects.

Code of Federal Regulations, 2011 CFR

2011-07-01

... any information regarding adverse effects on human health or the environment alleged to have been... information. (b) Adverse effects on human health or the environment for purposes of plant-incorporated... (CONTINUED) PESTICIDE PROGRAMS PROCEDURES AND REQUIREMENTS FOR PLANT-INCORPORATED PROTECTANTS Monitoring and...

40 CFR 174.71 - Submission of information regarding adverse effects.

Code of Federal Regulations, 2014 CFR

2014-07-01

... any information regarding adverse effects on human health or the environment alleged to have been... information. (b) Adverse effects on human health or the environment for purposes of plant-incorporated... (CONTINUED) PESTICIDE PROGRAMS PROCEDURES AND REQUIREMENTS FOR PLANT-INCORPORATED PROTECTANTS Monitoring and...

40 CFR 174.71 - Submission of information regarding adverse effects.

Code of Federal Regulations, 2012 CFR

2012-07-01

... any information regarding adverse effects on human health or the environment alleged to have been... information. (b) Adverse effects on human health or the environment for purposes of plant-incorporated... (CONTINUED) PESTICIDE PROGRAMS PROCEDURES AND REQUIREMENTS FOR PLANT-INCORPORATED PROTECTANTS Monitoring and...

40 CFR 174.71 - Submission of information regarding adverse effects.

Code of Federal Regulations, 2010 CFR

2010-07-01

... any information regarding adverse effects on human health or the environment alleged to have been... information. (b) Adverse effects on human health or the environment for purposes of plant-incorporated... (CONTINUED) PESTICIDE PROGRAMS PROCEDURES AND REQUIREMENTS FOR PLANT-INCORPORATED PROTECTANTS Monitoring and...

40 CFR 174.71 - Submission of information regarding adverse effects.

Code of Federal Regulations, 2013 CFR

2013-07-01

... any information regarding adverse effects on human health or the environment alleged to have been... information. (b) Adverse effects on human health or the environment for purposes of plant-incorporated... (CONTINUED) PESTICIDE PROGRAMS PROCEDURES AND REQUIREMENTS FOR PLANT-INCORPORATED PROTECTANTS Monitoring and...

Adverse reactions associated with acetylcysteine.

PubMed

Sandilands, E A; Bateman, D N

2009-02-01

Paracetamol (acetaminophen) is one of the most common agents deliberately ingested in self-poisoning episodes and a leading cause of acute liver failure in the western world. Acetylcysteine is widely acknowledged as the antidote of choice for paracetamol poisoning, but its use is not without risk. Adverse reactions, often leading to treatment delay, are frequently associated with both intravenous and oral acetylcysteine and are a common source of concern among treating physicians. A systematic literature review investigating the incidence, clinical features, and mechanisms of adverse effects associated with acetylcysteine. A variety of adverse reactions to acetylcysteine have been described ranging from nausea to death, most of the latter due to incorrect dosing. The pattern of reactions differs with oral and intravenous dosing, but reported frequency is at least as high with oral as intravenous. The reactions to the intravenous preparation result in similar clinical features to true anaphylaxis, including rash, pruritus, angioedema, bronchospasm, and rarely hypotension, but are caused by nonimmunological mechanisms. The precise nature of this reaction remains unclear. Histamine now seems to be an important mediator of the response, and there is evidence of variability in patient susceptibility, with females, and those with a history of asthma or atopy are particularly susceptible. Quantity of paracetamol ingestion, measured through serum paracetamol concentration, is also important as higher paracetamol concentrations protect patients against anaphylactoid effects. Most anaphylactoid reactions occur at the start of acetylcysteine treatment when concentrations are highest. Acetylcysteine also affects clotting factor activity, and this affects the interpretation of minor disturbances in the International Normalized Ratio in the context of paracetamol overdose. This review discusses the incidence, clinical features, underlying pathophysiological mechanisms, and

Doping with anabolic androgenic steroids (AAS): Adverse effects on non-reproductive organs and functions.

PubMed

Nieschlag, Eberhard; Vorona, Elena

2015-09-01

Since the 1970s anabolic androgenic steroids (AAS) have been abused at ever increasing rates in competitive athletics, in recreational sports and in bodybuilding. Exceedingly high doses are often consumed over long periods, in particular by bodybuilders, causing acute or chronic adverse side effects frequently complicated by additional polypharmacy. This review summarizes side effects on non-reproductive organs and functions; effects on male and female reproduction have been recently reviewed in a parallel paper. Among the most striking AAS side effects are increases in haematocrit and coagulation causing thromboembolism, intracardiac thrombosis and stroke as well as other cardiac disturbances including arrhythmias, cardiomyopathies and possibly sudden death. 17α-alkylated AAS are liver toxic leading to cholestasis, peliosis, adenomas and carcinomas. Hyperbilirubinaemia can cause cholemic nephrosis and kidney failure. AAS abuse may induce exaggerated self-confidence, reckless behavior, aggressiveness and psychotic symptoms. AAS withdrawal may be accompanied by depression and suicidal intentions. Since AAS abuse is not or only reluctantly admitted physicians should be aware of the multitude of serious side effects when confronted with unclear symptoms.

Protective Effect of Ethanolic Extract of Grape Pomace against the Adverse Effects of Cypermethrin on Weanling Female Rats

PubMed Central

Mossa, Abdel-Tawab H.; Ibrahim, Faten M.; Mohafrash, Samia M. M.; Abou Baker, Doha H.; El Gengaihi, Souad

2015-01-01

The adverse effect of cypermethrin on the liver and kidney of weanling female rats and the protective effect of ethanolic extract of grape pomace were investigated in the present study. Weanling female rats were given cypermethrin oral at a dose of 25 mg kg−1 body weight for 28 consecutive days. An additional two Cyp-trated groups received extract at a dose of 100 and 200 mg kg−1 body weight, respectively, throughout the experimental duration. Three groups more served as extract and control groups. Administration of Cyp resulted in a significant increase in serum marker enzymes, for example, aminotransferases (AST and ALT), alkaline phosphatase (ALP), and gamma-glutamyl transferase (GGT), and increases the level of urea nitrogen and creatinine. In contrast, Cyp caused significant decrease in levels of total protein and albumin and caused histopathological alterations in liver and kidneys of female rats. Coadministration of the extract to Cyp-treated female rats restored most of these biochemical parameters to within normal levels especially at high dose of extract. However, extract administration to Cyp-treated rats resulted in overall improvement in liver and kidney damage. This study demonstrated the adverse biohistological effects of Cyp on the liver and kidney of weanling female rats. The grape pomace extract administration prevented the toxic effect of Cyp on the above serum parameters. The present study concludes that grape pomace extract has significant antioxidant and hepatorenal protective activity. PMID:26265923

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

PubMed

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

2016-01-01

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

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

PubMed Central

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

2015-01-01

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

Influence of total face, facial and nasal masks on short-term adverse effects during noninvasive ventilation.

PubMed

Holanda, Marcelo Alcantara; Reis, Ricardo Coelho; Winkeler, Georgia Freire Paiva; Fortaleza, Simone Castelo Branco; Lima, José Wellington de Oliveira; Pereira, Eanes Delgado Barros

2009-02-01

Failure of noninvasive ventilation (NIV) has been associated with short-term adverse effects related to the use of masks. The aim of this study was to compare the incidence, type and intensity of adverse effects, as well as the comfort, of total face masks (TFMs), facial masks (FMs) and nasal masks (NMs) during NIV. This was a randomized crossover trial involving 24 healthy volunteers submitted to six sessions of NIV in bilevel positive airway pressure mode using the TFM, FM and NM masks at low and moderate-to-high pressure levels. A written questionnaire was applied in order to evaluate eleven specific adverse effects related to the use of the masks. Comfort was assessed using a visual analog scale. The CO2 exhaled into the ventilator circuit was measured between the mask and the exhalation port. The performance of the TFM was similar to that of the NM and FM in terms of comfort scores. Higher pressure levels reduced comfort and increased adverse effects, regardless of the mask type. When the TFM was used, there were fewer air leaks and less pain at the nose bridge, although there was greater oronasal dryness and claustrophobia. Air leaks were most pronounced when the FM was used. The partial pressure of exhaled CO2 entering the ventilator circuit was zero for the TFM. The short-term adverse effects caused by NIV interfaces are related to mask type and pressure settings. The TFM is a reliable alternative to the NM and FM. Rebreathing of CO2 from the circuit is less likely to occur when a TFM is used.

Cognition- and Dementia-Related Adverse Effects With Sacubitril-Valsartan: Analysis of the FDA Adverse Event Report System Database.

PubMed

Perlman, Amichai; Hirsh Raccah, Bruria; Matok, Ilan; Muszkat, Mordechai

2018-05-07

Because neprilysin is involved in the degradation of amyloid-beta, there is concern that the angiotensin-neprilysin inhibitor sacubitril-valsartan could increase the risk for dementia. We analyzed adverse event cases submitted to the Food and Drug Administration Adverse Event Report System from July 2015 to March 2017. Cognition- and dementia-related adverse event cases were defined with the use of broad and narrow structured medical queries. During the period evaluated, 9,004 adverse event reports (out of a total of 2,249,479) involved the use of sacubitril-valsartan. Based on the broad definition, sacubitril-valsartan was associated with cognition- and dementia-related adverse events in 459 reports (5.1%), but this was lower than the proportion of these reports among other medications (6.6%, reporting odds ratio [ROR] 0.72, 95% confidence interval [CI] 0.65-0.79). Restricting the comparison to cases with age >60 years and with the use of a comparator group with heart failure resulted in no association between sacubitril-valsartan and dementia-related adverse events, with the use of both the broad and the narrow definitions (ROR 0.87, 95% CI 0.76-1.02, and ROR 1.06, 95% CI 0.4-3.16, respectively). Sacubitril-valsartan is not associated with a disproportionately high rate of short-term dementia-related adverse effect reports. Long-term studies assessing cognitive outcomes are required to better establish the medication's cognition effects. Copyright © 2018 Elsevier Inc. All rights reserved.

Adverse effect profile of lidocaine injections for occipital nerve block in occipital neuralgia.

PubMed

Sahai-Srivastava, Soma; Subhani, Dawood

2010-12-01

To determine whether there are differences in the adverse effect profile between 1, 2 and 5% Lidocaine when used for occipital nerve blocks (ONB) in patients with occipital neuralgia. Occipital neuralgia is an uncommon cause of headaches. Little is known regarding the safety of Lidocaine injections for treatment in larger series of patients. Retrospective chart analysis of all ONB was performed at our headache clinic during a 6-year period on occipital neuralgia patients. 89 consecutive patients with occipital neuralgia underwent a total of 315 ONB. All the patients fulfilled the IHS criteria for Occipital Neuralgia. Demographic data were collected including age, gender, and ethnicity. The average age of this cohort was 53.25 years, and the majority of patients were females 69 (78%). Ethnicity of patients was diverse, with Caucasian 48(54%), Hispanics 31(35%), and others 10 (11%). 69 patients had 1%, 18 patients had 2% and 29 patient were given 5% Lidocaine. All Lidocaine injections were given with 20 mg Depo-medrol and the same injection technique and location were used for all the procedures. Eight patients (9%)had adverse effects to the Lidocaine and Depo-medrol injections, of which 5 received 5% and 3 received 1% Lidocaine. Majority of patients who had adverse effects were female 7(87%), and had received bilateral blocks (75%). ONB is a safe procedure with 1% Lidocaine; however, caution should be exerted with 5% in elderly patients, 70 or older, especially when administering bilateral injections.

Long-term adverse effects of neonatal exposure to bisphenol A on the murine female reproductive tract.

PubMed

Newbold, Retha R; Jefferson, Wendy N; Padilla-Banks, Elizabeth

2007-01-01

The developing fetus is uniquely sensitive to perturbation by chemicals with hormone-like activity. The adverse effects of prenatal diethylstilbestrol (DES) exposure are a classic example. Since concern has been mounting regarding the human health and environmental effects of bisphenol A (BPA), a high-production-volume chemical with estrogenic activity used in the synthesis of plastics, we investigated its long-term effects in an experimental animal model that was previously shown useful in studying the adverse effects of developmental exposure to DES. Outbred female CD-1 mice were treated on days 1-5 with subcutaneous injections of BPA (10, 100 or 1000 microg/kg/day) dissolved in corn oil or corn oil alone (Control). At 18 months, ovaries and reproductive tract tissues were examined. There was a statistically significant increase in cystic ovaries and cystic endometrial hyperplasia (CEH) in the BPA-100 group as compared to Controls. Progressive proliferative lesion (PPL) of the oviduct and cystic mesonephric (Wolffian) duct remnants were also seen in all of the BPA groups. More severe pathologies of the uterus following neonatal BPA treatment included adenomyosis, leiomyomas, atypical hyperplasia, and stromal polyps. These data suggest that BPA causes long-term adverse effects if exposure occurs during critical periods of differentiation.

Long-term Adverse Effects of Neonatal Exposure to Bisphenol A on the Murine Female Reproductive Tract

PubMed Central

Newbold, Retha R.; Jefferson, Wendy N.; Banks, Elizabeth Padilla

2007-01-01

The developing fetus is uniquely sensitive to perturbation by chemicals with hormone-like activity. The adverse effects of prenatal diethylstilbestrol (DES) exposure are a classic example. Since concern has been mounting regarding the human health and environmental effects of bisphenol A (BPA), a high-production-volume chemical with estrogenic activity used in the synthesis of plastics, we investigated its long-term effects in an experimental animal model that was previously shown useful in studying the adverse effects of developmental exposure to DES. Outbred female CD-1 mice were treated on days 1-5 with subcutaneous injections of BPA (10, 100 or 1000 μg/kg/day) dissolved in corn oil or corn oil alone (Control). At 18 months, ovaries and reproductive tract tissues were examined. There was a statistically significant increase in cystic ovaries and cystic endometrial hyperplasia (CEH) in the BPA-100 group as compared to Controls. Progressive proliferative lesion (PPL) of the oviduct and cystic mesonephric (Wolffian) duct remnants were also seen in all of the BPA groups. More severe pathologies of the uterus following neonatal BPA treatment included adenomyosis, leiomyomas, atypical hyperplasia, and stromal polyps. These data suggest that BPA causes long-term adverse effects if exposure occurs during critical periods of differentiation. PMID:17804194

Functional correlates of the therapeutic and adverse effects evoked by thalamic stimulation for essential tremor

PubMed Central

Gibson, William S.; Jo, Hang Joon; Testini, Paola; Cho, Shinho; Felmlee, Joel P.; Welker, Kirk M.; Klassen, Bryan T.; Min, Hoon-Ki

2016-01-01

Deep brain stimulation is an established neurosurgical therapy for movement disorders including essential tremor and Parkinson’s disease. While typically highly effective, deep brain stimulation can sometimes yield suboptimal therapeutic benefit and can cause adverse effects. In this study, we tested the hypothesis that intraoperative functional magnetic resonance imaging could be used to detect deep brain stimulation-evoked changes in functional and effective connectivity that would correlate with the therapeutic and adverse effects of stimulation. Ten patients receiving deep brain stimulation of the ventralis intermedius thalamic nucleus for essential tremor underwent functional magnetic resonance imaging during stimulation applied at a series of stimulation localizations, followed by evaluation of deep brain stimulation-evoked therapeutic and adverse effects. Correlations between the therapeutic effectiveness of deep brain stimulation (3 months postoperatively) and deep brain stimulation-evoked changes in functional and effective connectivity were assessed using region of interest-based correlation analysis and dynamic causal modelling, respectively. Further, we investigated whether brain regions might exist in which activation resulting from deep brain stimulation might correlate with the presence of paraesthesias, the most common deep brain stimulation-evoked adverse effect. Thalamic deep brain stimulation resulted in activation within established nodes of the tremor circuit: sensorimotor cortex, thalamus, contralateral cerebellar cortex and deep cerebellar nuclei (FDR q < 0.05). Stimulation-evoked activation in all these regions of interest, as well as activation within the supplementary motor area, brainstem, and inferior frontal gyrus, exhibited significant correlations with the long-term therapeutic effectiveness of deep brain stimulation (P < 0.05), with the strongest correlation (P < 0.001) observed within the contralateral cerebellum. Dynamic causal

Alcohol and cannabis: Comparing their adverse health effects and regulatory regimes.

PubMed

Hall, Wayne

2017-04-01

The claim that the adverse health effects of cannabis are much less serious than those of alcohol has been central to the case for cannabis legalisation. Regulators in US states that have legalised cannabis have adopted regulatory models based on alcohol. This paper critically examines the claim about adverse health effects and the wisdom of regulating cannabis like alcohol. First, it compares what we know about the adverse health effects of alcohol and cannabis. Second, it discusses the uncertainties about the long term health effects of sustained daily cannabis use. Third, it speculates about how the adverse health effects of cannabis may change after legalisation. Fourth, it questions the assumption that alcohol provides the best regulatory model for a legal cannabis market. Fifth, it outlines the major challenges in regulating cannabis under the liberal alcohol-like regulatory regimes now being introduced. Copyright © 2016 Elsevier B.V. All rights reserved.

A strategy for regulatory action when new adverse effects of a licensed product emerge.

PubMed

Aronson, Jeffrey K; Price, Deirdre; Ferner, Robin E

2009-01-01

Regulatory agencies grant product licences (marketing authorizations) for medicinal products in the light of evidence that the balance between benefit and harm in the population is favourable. Here we consider a framework for allowing regulatory agencies to make rational decisions when reviewing product licences in the light of new information about harms that change that balance. The regulator can revoke the product licence, restrict the product's availability or change the 'label' in different ways. We examine the features of the adverse effect that may be relevant in making the decision: namely, individual differences in susceptibility; the possibility of monitoring; and the availability of protective strategies. The balance of benefit and harm, and the time-course and dose relation of the adverse effect play important roles in the decision-making process. We set out how these factors can help determine the logical response to new information on the balance between benefit and harm, and provide a series of relevant examples. We believe that when regulatory agencies have to decide how to amend the product licence of a drug when new serious adverse effects cause concern, they would find it useful to adopt a framework of this kind, using different strategies for different cases. Our proposed framework could also be useful in risk management planning during drug development.

Evaluation of the adverse effects of subcutaneous carprofen over six days in healthy cats.

PubMed

Steagall, P V M; Moutinho, F Q; Mantovani, F B; Passarelli, D; Thomassian, A

2009-02-01

This study evaluated the adverse effects of carprofen in seven healthy cats. Values for CBC, biochemical profiles and platelet aggregation were measured before and at seven days after SID treatment with subcutaneous carprofen: 4 mg/kg (day 1), 2mg/kg (day 2 and 3) and 1mg/kg (day 4 and 6) (CG) or 0.35 ml of saline (SG) for six days in a randomized, blinded, cross-over study with a four-week washout period. No treatment was given on day 5. Endoscopy of the GI tract was performed pre-treatment and on day 7 post-treatment. There were no significant changes in hematological profiles, biochemical profiles and endoscopy grading scores within nor between groups, except for lower albumin values at baseline than on day 7 (CG), and globulin and ALP values were higher at baseline than on day 7 in CG and SG. SC administration of carprofen over six days did not cause any adverse effects on gastrointestinal, hematological, or serum biochemical variables.

Search strategies to identify information on adverse effects: a systematic review

PubMed Central

Golder, Su; Loke, Yoon

2009-01-01

Objectives: The review evaluated studies of electronic database search strategies designed to retrieve adverse effects data for systematic reviews. Methods: Studies of adverse effects were located in ten databases as well as by checking references, hand-searching, searching citations, and contacting experts. Two reviewers screened the retrieved records for potentially relevant papers. Results: Five thousand three hundred thirteen citations were retrieved, yielding 19 studies designed to develop or evaluate adverse effect filters, of which 3 met the inclusion criteria. All 3 studies identified highly sensitive search strategies capable of retrieving over 95% of relevant records. However, 1 study did not evaluate precision, while the level of precision in the other 2 studies ranged from 0.8% to 2.8%. Methodological issues in these papers included the relatively small number of records, absence of a validation set of records for testing, and limited evaluation of precision. Conclusions: The results indicate the difficulty of achieving highly sensitive searches for information on adverse effects with a reasonable level of precision. Researchers who intend to locate studies on adverse effects should allow for the amount of resources and time required to conduct a highly sensitive search. PMID:19404498

"Freshman's week": characteristics associated with participation and experiencing adverse effects.

PubMed

Erevik, E K; Pallesen, S; Vedaa, Ø; Andreassen, C S; Torsheim, T

2018-05-29

"Freshman's week" (FW) is a Norwegian initiation ritual to higher education. Previous research has suggested that FW-participation is associated with better social adjustment to the student setting, as well as heavy alcohol use both during and after the event. In this study, we aimed to identify characteristics associated with participation in FW and characteristics associated with experiencing adverse effects of alcohol use during FW. Students in the city of Bergen, Norway participated in a survey during fall 2015, shortly after FW. The current sample consisted of the first-year students (N = 4, 401, estimated response rate: 49%). The sample's mean age was 24 years (range: 17-73 years), 65% were females, and the majority were born in Norway (93%). Logistic regressions were conducted to identify characteristics associated with participation in FW and experiencing adverse effects. A total of 64% of the first-year students reported participation in FW, and 27% of these reported experiencing at least one adverse alcohol-related effect during FW. Participation in FW was positively associated with being single (OR = 1.29), extroversion (OR = 1.18), and alcohol use (OR = 1.28), and inversely associated with age (OR = 0.70), and having children (OR = 0.36). Several characteristics (e.g., alcohol use (OR = 1.84), extroversion (OR = 0.60), symptoms of depression (OR = 1.60)) were associated with an increased risk of experiencing adverse effects of alcohol use during participation. The current results suggest that initiatives for increasing the participation rate in FW, reducing alcohol use during FW, and decreasing the occurrence of adverse alcohol effects during FW are warranted. Aiming to reduce the focus on alcohol use during FW, and seeking to make FW more available and enjoyable for students with other priorities, students who do not match the stereotype of the typical first-year student, and less sociable students, might both

Efficacy of Rasayana Avaleha as adjuvant to radiotherapy and chemotherapy in reducing adverse effects.

PubMed

Vyas, Purvi; Thakar, A B; Baghel, M S; Sisodia, Arvind; Deole, Yogesh

2010-10-01

Cancer is the most dreadful disease affecting mankind. The available treatments such as chemotherapy and radiotherapy have cytotoxic effects, which are hazardous to the normal cells of the patient, causing many unnecessary effects. This further leads to complications of the therapy, impaired health, and deterioration of quality of life, resulting in mandatory stoppage of the treatment. In the present study, the efficacy of an Ayurvedic formulation, Rasayana Avaleha, has been evaluated as an adjuvant medication to modern radiotherapy and chemotherapy. A total of 36 cancer patients were registered in this trial and were divided into two groups, group A and group B. In group A, the patients were treated with radiotherapy and chemotherapy along with adjuvant Rasayana Avaleha (RT + CT + RA), while in group B only radiotherapy and chemotherapy (RT + CT) were given, as the control group. After assessing the results, it was observed that Rasayana Avaleha gave better results in controlling the adverse effect of chemotherapy and radiotherapy in comparison with the control group. Therefore, Rasayana Avaleha has proved to be an effective adjuvant therapy in protecting patients from the adverse effects of chemotherapy and radiotherapy.

Surveillance of adverse effects during a vaccination campaign against meningitis C.

PubMed

Laribière, Anne; Miremont-Salamé, Ghada; Reyre, Hadrien; Abouelfath, Abdelilah; Liège, Ludovic; Moore, Nicholas; Haramburu, Françoise

2005-12-01

To describe adverse events occurring after mass vaccination with conjugate and nonconjugate vaccines and to assess the incidence of serious adverse effects. A mass immunisation campaign against meningococcal C disease was conducted in two French administrative areas, Landes and Pyrénées atlantiques, for 2 months (from October to December 2002). Adverse events were reported by families and physicians by means of a specific reporting form returned to the pharmacovigilance centre 15 days after vaccination. The target population was 260,630 individuals aged between 2 months and 24 years. About 179,000 children and young adults were vaccinated. A total of 92,711 report forms were received by the pharmacovigilance centre, and 12,695 subjects presented at least one adverse event. The most frequently involved systems/disorders were application site disorders (48.4%), whole-body general disorders (21.8%), central and peripheral nervous system disorders (14.6%), and gastrointestinal system disorders (4.7%). Most of these adverse events were transient and not serious. There were 13 serious adverse events: one each of syncope, fever, headache with fever, neuralgia, serum sickness, arthritis, purpura, facial paralysis, multiple sclerosis, lipoma, and meningism, and two cases of bronchospasm. No significant difference was found in rates of adverse event reports between both vaccines. The estimated incidence of serious adverse effect reports was 7 per 100,000. This campaign was the second immunisation campaign undertaken in France involving both physicians and families as reporters. Although unlabeled adverse effects were identified during this campaign, they were mostly nonserious and have been known to occur with other vaccines.

Causes and Adverse Impact of Physician Burnout: A Systematic Review.

PubMed

Azam, Kamran; Khan, Anwar; Alam, Muhammad Toqeer

2017-08-01

To review the significant causes and effects of physician burnout in published literature. Asystematic review was conducted for searching published literature on the causes and effects of burnout in three online databases. Inclusion and exclusion criteria were developed for final selection of papers. The selected papers were critically appraised and thematic analysis was done to identify major themes related to physician burnout. Thirty-one papers were finally selected among the 2,828 identified studies. The thematic analysis revealed demographic factors, e.g. age, gender, marital status, specialty and job position; and organizational factors, e.g. workload, interpersonal demands, job insecurity and lack of resources, as significant causes of burnout. The consequences of burnout included individual and organizational effects. The individual effects of burnout included physical health problems; while organizational effects included poor job performance, low organizational commitment, and turnover intentions. Burnout is a recognized workplace hazard in the healthcare sector. The individual characteristics of physicians and working environment within hospitals are contributory factors of burnout. Therefore, proactive interventions should be taken at individual and institutional levels for preventing physician burnout by improving the personal lifestyle of physician and working environment in hospitals.

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

PubMed

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

2003-06-01

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

Adverse mood effects of combined oral contraceptives in relation to personality traits.

PubMed

Borgström, Anna; Odlind, Viveca; Ekselius, Lisa; Sundström-Poromaa, Inger

2008-12-01

Mood symptoms, such as depressed mood, anxiety and increased irritability, remain one of the major reasons for discontinuation of combined oral contraceptive (COC) pills. The aim of this study was to compare personality traits in women with ongoing or previous use of COCs and different experiences from these compounds with respect to adverse mood symptoms. Thirty women currently on COCs with no reports of adverse mood symptoms, 28 women currently on COCs and experiencing mood-related side effects, 27 women who had discontinued COC use for reasons other than adverse mood symptoms and 33 women who had discontinued COC use due to adverse mood effects were included. All participants were asked to fill out the Swedish universities Scales of Personality (SSP) to assess different personality traits. The women who were experiencing mood-related side effects on their current COC use exhibited higher scores on the somatic anxiety and stress susceptibility traits as compared to the women who did not experience any mood-related side effects from their current COCs. Women who had discontinued COC treatment because of adverse mood effects had higher scores of detachment and mistrust compared to women who had discontinued COC for reasons unrelated to mood effects. Higher scores on specific personality traits such as somatic anxiety and stress susceptibility are found in women with ongoing experience of adverse mood symptoms from COC. Higher scores of mistrust and detachment are more common among women who have discontinued COC treatment due to adverse mood effects.

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

PubMed

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

2018-01-01

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

Oral adverse effects due to the use of Nevirapine.

PubMed

Moura, Mariela Dutra Gontijo; Senna, Maria Inês Barreiros; Madureira, Davidson Fróis; Fonseca, Linaena Merícy Silva; Mesquita, Ricardo Alves

2008-01-01

The aim of this article is to present the clinical characteristics and management of an oral adverse effect stemming from the use of the antiretroviral medication Nevirapine (NVP). NVP is a non-nucleoside reverse transcriptase inhibitor used in the treatment of Human Immunodeficiency Virus (HIV) infection. A 29-year-old black man, HIV-infected since 1996, began highly active antiretroviral therapy (HAART) with zidovudine, lamivudine, and indinavir. From 1996 to 2002 several medications were changed due to their adverse effects: indinavir (renal colic and fever), nelfinavir (cutaneous rash), and efavirenz (nausea and temporary memory loss). When the patient presented to our service he was taking NVP, zidovudine, and lamivudine. A whitish plaque in the lips and bilateral buccal mucosa, burning, taste disturbance, and xerostomia were observed. The discontinuation of HAART led to the complete resolution of signs and symptoms. The patient has received follow-up treatment for three years and five months without local or systemic effects observed. Unfortunately, the clinical features of the oral adverse effect from NVP are not well known. This paper contributed to the identification of possible reactions in the oral cavity due to antiretroviral medication. Although HAART is very important in the treatment of HIV, its side effects are responsible for patients' non-adherence to medications. While more studies are needed to better understand the mechanism of action after suspending HAART, the complete resolution of the signs and symptoms was observed. Therefore, physicians and dentists alike must understand how to identify and prevent these adverse effects in order to further improve HIV patient treatments.

Clinical outcomes and adverse effect monitoring in allergic rhinitis.

PubMed

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

2005-03-01

The subjective recording in diary cards of symptoms of itch, sneeze, nose running, and blockage, with the use of a rating scale to indicate the level of severity, is usual for clinical trials in allergic rhinitis. The primary outcome measure is usually a composite score that enables a single total symptoms score endpoint. It is appreciated, however, that rhinitis has a greater effect on the individual than is reflected purely by the recording of anterior nasal symptoms. Nasal obstruction is troublesome and may lead to sleep disturbance in addition to impaired daytime concentration and daytime sleepiness. These impairments affect school and work performance. Individuals with rhinitis find it socially embarrassing to be seen sneezing, sniffing, or blowing their nose. To capture these and other aspects of the disease-specific health-related quality of life, questionnaires such as the Rhinoconjunctivitis Quality of Life Questionnaire have been developed and validated for clinical trial use. The adoption of health-related quality of life questionnaires into clinical trials broadens the information obtained regarding the effect of the therapeutic intervention and helps focus on issues relevant to the individual patient. It must be appreciated that it is not only the disease that may adversely affect health-related quality of life; administered therapy, although intended to be beneficial, may also cause health impairment. Adverse-event monitoring is thus essential in clinical trials. The first-generation H 1 -histamines, because of their effect on central H 1 -receptors, are classically associated with central nervous system (CNS) effects such as sedation. Although this is not always perceived by the patient, it is clearly evident with objective performance testing, and positron emission tomography scanning has directly demonstrated the central H 1 -receptor occupancy. The second-generation H 1 -antihistamines have reduced central H 1 -receptor occupancy and considerably

Adverse effects of neuromuscular blockers and their antagonists.

PubMed

Naguib, M; Magboul, M M

1998-02-01

Among all the drugs used for general anaesthesia, neuromuscular blockers appear to play a prominent role in the incidence of severe adverse reactions. It now seems likely that most serious adverse drug reactions occurring during anaesthesia are immunological in type. The frequency of life-threatening anaphylactic or anaphylactoid reactions occurring during anaesthesia has been estimated to be between 1 in 1000 and 1 in 25,000 anaesthetic procedures, with the neuromuscular blockers being involved in 80% of cases. The mortality from such serious reactions is reported to be in the range of 3.4 to 6%. The highly immunogenic drug, suxamethonium chloride (succinylcholine), was found to be the most hazardous agent. Drug-specific immunoglobulin E antibodies to suxamethonium chloride and other neuromuscular blockers have been demonstrated. This sensitivity to neuromuscular blockers seems to be a long-lasting phenomenon. During anaesthesia, the clinical features of an allergic reaction are often masked. Tachycardia and circulatory collapse may be the only signs of an allergic reaction, and they are easily misdiagnosed. Bronchospasm is reported to be present in about 40% of cases. Successful management of these patients includes stabilisation during the acute reaction and avoidance of future reactions. The latter is based on the identification of the causative drug and potentially cross-reacting compounds. The use of suxamethonium chloride is associated with many other adverse effects, such as fasciculations, myalgia, potassium release, changes in the heart rate, increases in intragastric and intraocular pressures, and malignant hyperthermia. Because of the dangers of hyperkalaemic cardiac arrest after suxamethonium chloride administration in children with unrecognised muscular dystrophy, there have now been moves to limit the use of this drug in children. Although neuromuscular blockers are designed to specifically block nicotinic cholinergic receptors at the neuromuscular

Adverse effects of neuromuscular blockers and their antagonists.

PubMed

Naguib, M; Magboul, M M

1998-06-01

Among all the drugs used for general anesthesia, neuromuscular blockers appear to play a prominent role in the incidence of severe adverse reactions. It now seems likely that most serious adverse drug reactions occurring during anesthesia are immunological in type. The frequency of life-threatening anaphylactic or anaphylactoid reactions occurring during anesthesia has been estimated to be between 1 in 1000 and 1 in 25,000 anesthetic procedures, with the neuromuscular blockers being involved in 80% of cases. The mortality from such serious reactions is reported to be in the range of 3.4 to 6%. The highly immunogenic drug, suxamethonium chloride (succinylcholine), was found to be the most hazardous agent. Drug-specific immunoglobulin E antibodies to suxamethonium chloride and other neuromuscular blockers have been demonstrated. This sensitivity to neuromuscular blockers seems to be a long-lasting phenomenon. During anesthesia, the clinical features of an allergic reaction are often masked. Tachycardia and circulatory collapse may be the only signs of an allergic reaction, and they are easily misdiagnosed. Bronchospasm is reported to be present in about 40% of cases. Successful management of these patients includes stabilisation during the acute reaction and avoidance of future reactions. The latter is based on the identification of the causative drug and potentially cross-reacting compounds. The use of suxamethonium chloride is associated with many other adverse effects, such as fasciculations, myalgia, potassium release, changes in the heart rate, increases in intragastric and intraocular pressures, and malignant hyperthermia. Because of the dangers of hyperkalemic cardiac arrest suxamethonium chloride administration in children with unrecognised muscular dystrophy, there have now been moves to limit the use of this drug in children. Although neuromuscular blockers are designed to specifically block nicotinic cholinergic receptors at the neuromuscular junction

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.

Energy Drink Consumption: Beneficial and Adverse Health Effects.

PubMed

Alsunni, Ahmed Abdulrahman

2015-10-01

Consumption of energy drinks has been increasing dramatically in the last two decades, particularly amongst adolescents and young adults. Energy drinks are aggressively marketed with the claim that these products give an energy boost to improve physical and cognitive performance. However, studies supporting these claims are limited. In fact, several adverse health effects have been related to energy drink; this has raised the question of whether these beverages are safe. This review was carried out to identify and discuss the published articles that examined the beneficial and adverse health effects related to energy drink. It is concluded that although energy drink may have beneficial effects on physical performance, these products also have possible detrimental health consequences. Marketing of energy drinks should be limited or forbidden until independent research confirms their safety, particularly among adolescents.

Probable Nootropicinduced Psychiatric Adverse Effects: A Series of Four Cases

PubMed Central

Ajaltouni, Jean

2015-01-01

The misuse of nootropics—any substance that may alter, improve, or augment cognitive performance, mainly through the stimulation or inhibition of certain neurotransmitters—may potentially be dangerous and deleterious to the human brain, and certain individuals with a history of mental or substance use disorders might be particularly vulnerable to their adverse effects. We describe four cases of probable nootropic-induced psychiatric adverse effects to illustrate this theory. To the best of our knowledge this has not been previously reported in the formal medical literature. We briefly describe the most common classes of nootropics, including their postulated or proven methods of actions, their desired effects, and their adverse side effects, and provide a brief discussion of the cases. Our objective is to raise awareness among physicians in general and psychiatrists and addiction specialists in particular of the potentially dangerous phenomenon of unsupervised nootropic use among young adults who may be especially vulnerable to nootropics’ negative effects. PMID:27222762

Adverse effects of anticancer agents that target the VEGF pathway.

PubMed

Chen, Helen X; Cleck, Jessica N

2009-08-01

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

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

PubMed

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

2014-06-01

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

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

PubMed

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

2014-06-12

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

Long-term mucocutaneous adverse effects of imatinib in Indian chronic myeloid leukemia patients.

PubMed

Vinay, Keshavamurthy; Yanamandra, Uday; Dogra, Sunil; Handa, Sanjeev; Suri, Vikas; Kumari, Savita; Khadwal, Alka; Prakash, Gaurav; Lad, Deepesh; Varma, Subhash; Malhotra, Pankaj

2018-03-01

Short-term mucocutaneous adverse effects are well documented with imatinib. However, studies on long-term adverse effects and in the ethnic population are lacking. To study the long-term mucocutaneous adverse effects of imatinib and factors predicting these adverse effects. In this cross-sectional study, consenting adult chronic myeloid leukemia patients on imatinib for more than 250 days were recruited. The details of imatinib treatment were retrieved from hematology clinic records. Four hundred and thirty-eight patients who were on imatinib for a mean duration of 1820 days were recruited. A mean number of 1.42 ± 0.98 cutaneous adverse effects were seen per patient. Melasma-like pigmentation, periorbital edema, oral lichenoid reaction, cutaneous hypopigmentation, and vesicobullous eruptions were seen in 236 (53.9%), 81 (18.5%), 70 (16%), 42 (9.6%), and 12 (2.7%) patients, respectively. Drug-induced cutaneous eruptions (9.1%) and cutaneous hypopigmentation (9.6%) were seen less frequently. Cutaneous hyperpigmentation was more likely seen in younger patients (P = 0.001) and females (P < 0.001). On multivariate analysis, female gender was a significant risk factor for developing cutaneous hyperpigmentation and periorbital edema. Cutaneous hyperpigmentation and periorbital edema are common long-term adverse effects of imatinib in Indian patients. Female gender is a significant risk factor for the development of both these adverse effects. © 2017 The International Society of Dermatology.

Do Carpets Impair Indoor Air Quality and Cause Adverse Health Outcomes: A Review.

PubMed

Becher, Rune; Øvrevik, Johan; Schwarze, Per E; Nilsen, Steinar; Hongslo, Jan K; Bakke, Jan Vilhelm

2018-01-23

Several earlier studies have shown the presence of more dust and allergens in carpets compared with non-carpeted floors. At the same time, adverse effects of carpeted floors on perceived indoor air quality as well as worsening of symptoms in individuals with asthma and allergies were reported. Avoiding extensive carpet use in offices, schools, kindergartens and bedrooms has therefore been recommended by several health authorities. More recently, carpet producers have argued that former assessments were obsolete and that modern rugs are unproblematic, even for those with asthma and allergies. To investigate whether the recommendation to be cautious with the use of carpets is still valid, or whether there are new data supporting that carpet flooring do not present a problem for indoor air quality and health, we have reviewed the literature on this matter. We have not found updated peer reviewed evidence that carpeted floor is unproblematic for the indoor environment. On the contrary, also more recent data support that carpets may act as a repository for pollutants which may become resuspended upon activity in the carpeted area. Also, the use of carpets is still linked to perception of reduced indoor air quality as well as adverse health effects as previously reported. To our knowledge, there are no publications that report on deposition of pollutants and adverse health outcomes associated with modern rugs. However, due to the three-dimensional structure of carpets, any carpet will to some extent act like a sink. Thus, continued caution should still be exercised when considering the use of wall-to-wall carpeted floors in schools, kindergartens and offices, as well as in children's bedrooms unless special needs indicate that carpets are preferable.

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

PubMed

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

2017-05-23

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

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

PubMed Central

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

2017-01-01

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

10 CFR 1017.10 - Adverse effect test.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Adverse effect test. 1017.10 Section 1017.10 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) IDENTIFICATION AND PROTECTION OF UNCLASSIFIED CONTROLLED NUCLEAR INFORMATION Initially Determining What Information Is Unclassified Controlled Nuclear Information § 1017.10...

10 CFR 1017.10 - Adverse effect test.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false Adverse effect test. 1017.10 Section 1017.10 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) IDENTIFICATION AND PROTECTION OF UNCLASSIFIED CONTROLLED NUCLEAR INFORMATION Initially Determining What Information Is Unclassified Controlled Nuclear Information § 1017.10...

Endocrine and Metabolic Adverse Effects of Psychotropic Medications in Children and Adolescents

ERIC Educational Resources Information Center

Correll, Christoph U.; Carlson, Harold E.

2006-01-01

Objective: Despite increasing use of psychotropic medications in children and adolescents, data regarding their efficacy and safety are limited. Endocrine and metabolic adverse effects are among the most concerning adverse effects of commonly used psychotropic medications. Method: Selective review of endocrine and metabolic effects of psychotropic…

Prevention and management of statin adverse effects: A practical approach for pharmacists.

PubMed

Barry, Arden R; Beach, Jessica E; Pearson, Glen J

2018-01-01

Statin-associated adverse effects, primarily muscle-related symptoms, occur in up to approximately one-third of patients in clinical practice. Recently, a Canadian Consensus Working Group outlined 6 key principles to assess and manage patients with goal-inhibiting statin intolerance, defined as a syndrome characterized by symptoms or biomarker abnormalities that prevent the long-term use of and adherence to indicated statin therapy, which includes a trial of at least 2 statins and precludes reversible causes of statin adverse effects. These principles ensure patients are appropriately receiving a statin and aware of both the benefits and risks of therapy. As well, they address factors that may increase the risk of statin-associated myopathy. A thorough assessment of patients' clinical and laboratory history should be performed in any patient presenting with muscle symptoms on statin therapy, followed by a systematic dechallenge/rechallenge approach. In practice, most patients with statin intolerance due to muscle symptoms will be able to tolerate another statin. This is of particular importance because of the relative paucity of compelling evidence demonstrating a cardiovascular benefit with nonstatin therapies. Pharmacists are ideally situated to provide patient education, recommend changes to therapy and monitor patients with goal-inhibiting statin intolerance.

Herbal products and the liver: a review of adverse effects and mechanisms.

PubMed

Seeff, Leonard B; Bonkovsky, Herbert L; Navarro, Victor J; Wang, Guqi

2015-03-01

Herbal products have been used for centuries among indigenous people to treat symptoms and illnesses. Recently, their use in Western countries has grown significantly, rivaling that of prescription medications. Currently, herbal products are used mainly for weight loss and bodybuilding purposes but also to improve well-being and symptoms of chronic diseases. Many people believe that because they are natural, they must be effective and safe; however, these beliefs are erroneous. Few herbal products have been studied in well-designed controlled trials of patients with liver or other diseases, despite testimony to the contrary. Moreover, current highly effective antiviral drugs make efforts to treat hepatitis C with herbal products redundant. Herbal products are no safer than conventional drugs and have caused liver injury severe enough to require transplantation or cause death. Furthermore, their efficacy, safety, and claims are not assessed by regulatory agencies, and there is uncertainty about their reported and unreported contents. We review the history of commonly used herbal products, as well as their purported efficacies and mechanisms and their adverse effects. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Identifying genomic and developmental causes of adverse drug reactions in children

PubMed Central

Becker, Mara L; Leeder, J Steven

2011-01-01

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

Adverse hematological effects of hexavalent chromium: an overview

PubMed Central

2016-01-01

Workers of tanneries, welding industries, factories manufacturing chromate containing paints are exposed to hexavalent chromium that increases the risk of developing serious adverse health effects. This review elucidates the mode of action of hexavalent chromium on blood and its adverse effects. Both leukocyte and erythrocyte counts of blood sharply decreased in Swiss mice after two weeks of intraperitoneal treatment with Cr (VI), with the erythrocytes transforming into echinocytes. The hexavalent chromium in the blood is readily reduced to trivalent form and the reductive capacity of erythrocytes is much greater than that of plasma. Excess Cr (VI), not reduced in plasma, may enter erythrocytes and lymphocytes and in rodents it induces microcytic anemia. The toxic effects of chromium (VI) include mitochondrial injury and DNA damage of blood cells that leads to carcinogenicity. Excess Cr (VI) increases cytosolic Ca2+ activity and ATP depletion thereby inducing eryptosis. Se, vitamin C, and quercetin are assumed to have some protective effect against hexavalent chromium induced hematological disorders. PMID:28652847

Adverse hematological effects of hexavalent chromium: an overview.

PubMed

Ray, Rina Rani

2016-06-01

Workers of tanneries, welding industries, factories manufacturing chromate containing paints are exposed to hexavalent chromium that increases the risk of developing serious adverse health effects. This review elucidates the mode of action of hexavalent chromium on blood and its adverse effects. Both leukocyte and erythrocyte counts of blood sharply decreased in Swiss mice after two weeks of intraperitoneal treatment with Cr (VI), with the erythrocytes transforming into echinocytes. The hexavalent chromium in the blood is readily reduced to trivalent form and the reductive capacity of erythrocytes is much greater than that of plasma. Excess Cr (VI), not reduced in plasma, may enter erythrocytes and lymphocytes and in rodents it induces microcytic anemia. The toxic effects of chromium (VI) include mitochondrial injury and DNA damage of blood cells that leads to carcinogenicity. Excess Cr (VI) increases cytosolic Ca 2+ activity and ATP depletion thereby inducing eryptosis. Se, vitamin C, and quercetin are assumed to have some protective effect against hexavalent chromium induced hematological disorders.

[Adverse Effect Predictions Based on Computational Toxicology Techniques and Large-scale Databases].

PubMed

Uesawa, Yoshihiro

2018-01-01

　Understanding the features of chemical structures related to the adverse effects of drugs is useful for identifying potential adverse effects of new drugs. This can be based on the limited information available from post-marketing surveillance, assessment of the potential toxicities of metabolites and illegal drugs with unclear characteristics, screening of lead compounds at the drug discovery stage, and identification of leads for the discovery of new pharmacological mechanisms. This present paper describes techniques used in computational toxicology to investigate the content of large-scale spontaneous report databases of adverse effects, and it is illustrated with examples. Furthermore, volcano plotting, a new visualization method for clarifying the relationships between drugs and adverse effects via comprehensive analyses, will be introduced. These analyses may produce a great amount of data that can be applied to drug repositioning.

Adverse Effects of Iodine-derived Intravenous Radiopaque Contrast Media.

PubMed

Matthews, Eric P

2015-01-01

Although the advent of nonionic low-osmolar contrast agents has reduced the probability of a reaction to radiopaque contrast media derived from tri-iodinated benzoic acid, reactions still occur. Radiologic technologists must understand and know how to manage adverse effects of contrast media. Prompt attention to patients who exhibit the early signs of an adverse reaction can help to ensure the reaction does not progress to become severe or life-threatening.

Learning from adverse incidents involving medical devices.

PubMed

Amoore, John; Ingram, Paula

While an adverse event involving a medical device is often ascribed to either user error or device failure, the causes are typically multifactorial. A number of incidents involving medical devices are explored using this approach to investigate the various causes of the incident and the protective barriers that minimised or prevented adverse consequences. User factors, including mistakes, omissions and lack of training, conspired with background factors--device controls and device design, storage conditions, hidden device damage and physical layout of equipment when in use--to cause the adverse events. Protective barriers that prevented or minimised the consequences included staff vigilance, operating procedures and alarms.

Evidence for a neural dual-process account for adverse effects of cognitive control.

PubMed

Zink, Nicolas; Stock, Ann-Kathrin; Colzato, Lorenza; Beste, Christian

2018-06-09

Advantageous effects of cognitive control are well-known, but cognitive control may also have adverse effects, for example when it suppresses the implicit processing of stimulus-response (S-R) bindings that could benefit task performance. Yet, the neurophysiological and functional neuroanatomical structures associated with adverse effects of cognitive control are poorly understood. We used an extreme group approach to compare individuals who exhibit adverse effects of cognitive control to individuals who do not by combining event-related potentials (ERPs), source localization, time-frequency analysis and network analysis methods. While neurophysiological correlates of cognitive control (i.e. N2, N450, theta power and theta-mediated neuronal network efficiency) and task-set updating (P3) both reflect control demands and implicit information processing, differences in the degree of adverse cognitive control effects are associated with two independent neural mechanisms: Individuals, who show adverse behavioral effects of cognitive control, show reduced small-world properties and thus reduced efficiency in theta-modulated networks when they fail to effectively process implicit information. In contrast to this, individuals who do not display adverse control effects show enhanced task-set updating mechanism when effectively processing implicit information, which is reflected by the P3 ERP component and associated with the temporo-parietal junction (TPJ, BA 40) and medial frontal gyrus (MFG; BA 8). These findings suggest that implicit S-R contingencies, which benefit response selection without cognitive control, are always 'picked up', but may fail to be integrated with task representations to guide response selection. This provides evidence for a neurophysiological and functional neuroanatomical "dual-process" account of adverse cognitive control effects.

Pretreatment Predictors of Adverse Radiation Effects After Radiosurgery for Arteriovenous Malformation

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

Hayhurst, Caroline; Monsalves, Eric; Prooijen, Monique van

Purpose: To identify vascular and dosimetric predictors of symptomatic T2 signal change and adverse radiation effects after radiosurgery for arteriovenous malformation, in order to define and validate preexisting risk models. Methods and Materials: A total of 125 patients with arteriovenous malformations (AVM) were treated at our institution between 2005 and 2009. Eighty-five patients have at least 12 months of clinical and radiological follow-up. Any new-onset headaches, new or worsening seizures, or neurological deficit were considered adverse events. Follow-up magnetic resonance images were assessed for new onset T2 signal change and the volume calculated. Pretreatment characteristics and dosimetric variables were analyzedmore » to identify predictors of adverse radiation effects. Results: There were 19 children and 66 adults in the study cohort, with a mean age of 34 (range 6-74). Twenty-three (27%) patients suffered adverse radiation effects (ARE), 9 patients with permanent neurological deficit (10.6%). Of these, 5 developed fixed visual field deficits. Target volume and 12 Gy volume were the most significant predictors of adverse radiation effects on univariate analysis (p < 0.001). Location and cortical eloquence were not significantly associated with the development of adverse events (p = 0.12). No additional vascular parameters were identified as predictive of ARE. There was a significant target volume threshold of 4 cm{sup 3}, above which the rate of ARE increased dramatically. Multivariate analysis target volume and the absence of prior hemorrhage are the only significant predictors of ARE. The volume of T2 signal change correlates to ARE, but only target volume is predictive of a higher volume of T2 signal change. Conclusions: Target volume and the absence of prior hemorrhage is the most accurate predictor of adverse radiation effects and complications after radiosurgery for AVMs. A high percentage of permanent visual field defects in this series

Do Carpets Impair Indoor Air Quality and Cause Adverse Health Outcomes: A Review

PubMed Central

Becher, Rune; Øvrevik, Johan; Schwarze, Per E.; Nilsen, Steinar; Hongslo, Jan K.; Bakke, Jan Vilhelm

2018-01-01

Several earlier studies have shown the presence of more dust and allergens in carpets compared with non-carpeted floors. At the same time, adverse effects of carpeted floors on perceived indoor air quality as well as worsening of symptoms in individuals with asthma and allergies were reported. Avoiding extensive carpet use in offices, schools, kindergartens and bedrooms has therefore been recommended by several health authorities. More recently, carpet producers have argued that former assessments were obsolete and that modern rugs are unproblematic, even for those with asthma and allergies. To investigate whether the recommendation to be cautious with the use of carpets is still valid, or whether there are new data supporting that carpet flooring do not present a problem for indoor air quality and health, we have reviewed the literature on this matter. We have not found updated peer reviewed evidence that carpeted floor is unproblematic for the indoor environment. On the contrary, also more recent data support that carpets may act as a repository for pollutants which may become resuspended upon activity in the carpeted area. Also, the use of carpets is still linked to perception of reduced indoor air quality as well as adverse health effects as previously reported. To our knowledge, there are no publications that report on deposition of pollutants and adverse health outcomes associated with modern rugs. However, due to the three-dimensional structure of carpets, any carpet will to some extent act like a sink. Thus, continued caution should still be exercised when considering the use of wall-to-wall carpeted floors in schools, kindergartens and offices, as well as in children’s bedrooms unless special needs indicate that carpets are preferable. PMID:29360764

Contribution of new technologies to characterization and prediction of adverse effects.

PubMed

Rouquié, David; Heneweer, Marjoke; Botham, Jane; Ketelslegers, Hans; Markell, Lauren; Pfister, Thomas; Steiling, Winfried; Strauss, Volker; Hennes, Christa

2015-02-01

Identification of the potential hazards of chemicals has traditionally relied on studies in laboratory animals where changes in clinical pathology and histopathology compared to untreated controls defined an adverse effect. In the past decades, increased consistency in the definition of adversity with chemically-induced effects in laboratory animals, as well as in the assessment of human relevance has been reached. More recently, a paradigm shift in toxicity testing has been proposed, mainly driven by concerns over animal welfare but also thanks to the development of new methods. Currently, in vitro approaches, toxicogenomic technologies and computational tools, are available to provide mechanistic insight in toxicological Mode of Action (MOA) of the adverse effects observed in laboratory animals. The vision described as Tox21c (Toxicity Testing in the 21st century) aims at predicting in vivo toxicity using a bottom-up-approach, starting with understanding of MOA based on in vitro data to ultimately predict adverse effects in humans. At present, a practical application of the Tox21c vision is still far away. While moving towards toxicity prediction based on in vitro data, a stepwise reduction of in vivo testing is foreseen by combining in vitro with in vivo tests. Furthermore, newly developed methods will also be increasingly applied, in conjunction with established methods in order to gain trust in these new methods. This confidence is based on a critical scientific prerequisite: the establishment of a causal link between data obtained with new technologies and adverse effects manifested in repeated-dose in vivo toxicity studies. It is proposed to apply the principles described in the WHO/IPCS framework of MOA to obtain this link. Finally, an international database of known MOAs obtained in laboratory animals using data-rich chemicals will facilitate regulatory acceptance and could further help in the validation of the toxicity pathway and adverse outcome pathway

Adversity in Preschool-Aged Children: Effects on Salivary Interleukin-1β

PubMed Central

Tyrka, Audrey R.; Parade, Stephanie H.; Valentine, Thomas R.; Eslinger, Nicole M.; Seifer, Ronald

2016-01-01

Exposure to early life adversity is linked to impaired affective, cognitive, and behavioral functioning and increases risk for various psychiatric and medical conditions. Stress-induced increases in pro-inflammatory cytokines may be a biological mechanism of these effects. Few studies have examined cytokine levels in children experiencing early life adversity, and very little research has investigated cytokines or other markers of inflammation in saliva. In the present study, we examined salivary IL-1β and C-reactive protein (CRP) levels in relation to stress exposure in 40 children aged 3 to 5 years who were enrolled in a larger study of early life adversity. Childhood maltreatment status was assessed via review of child welfare records, and contextual stress exposure, traumatic life event history, and symptoms of psychopathology were assessed via caregiver interviews at a home visit. In a subsequent visit, salivary IL-1β and CRP were obtained before and after participation in four emotion-eliciting tasks. Number of past month contextual stressors, lifetime contextual stressors, and traumatic life events each demonstrated a significant main effect on IL-1β. Baseline IL-1β was positively associated with each of the significant main-effect adversities. Post-challenge IL-1β displayed positive associations with each adversity variable, but were not significant. CRP was not significantly associated with any of the adversity variables. Given evidence suggesting involvement of IL-1β in the neuropathology of psychiatric conditions, these results may have important implications for developmental outcomes. PMID:25997772

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

PubMed

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

1997-01-15

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

Adverse Effects of Collagenase in the Treatment of Dupuytren Disease: A Systematic Review.

PubMed

Sanjuan-Cerveró, Rafael; Carrera-Hueso, Francisco J; Vazquez-Ferreiro, Pedro; Gomez-Herrero, Diego

2017-04-01

Collagenase clostridium histolyticum (CCH) has proven to be both safe and effective in the treatment of Dupuytren disease (DD). The medium-term outcomes are similar to those achieved with surgery, and most adverse effects are self-limiting and considered to be mild or moderate. Our objective was to conduct a systematic review of the adverse effects of CCH in DD since the release of the drug to evaluate the incidence, severity, classification, and definitions of these effects. We analyzed the literature in terms of modifications to the original treatment protocol and grouped adverse effects according to their pathophysiological origin. We included 28 clinical studies and five case reports or case series analyzing 4456 patients with a mean age of 63.6 years. Mean follow-up was 7.07 months (range 3-24); the mean number of patients per study was 148 (range 5-1082). The studies did not classify the adverse effects they reported into groups. The most common effects were peripheral edema (54.4%), bruising (42.9%), and upper limb pain (28.3%). Significant biases were observed for use of terminology, demarcation of sites of involvement, severity criteria, and assessment methods. A simpler and clearer consensus-based classification system would enable better evaluation and comparison of the adverse effects of CCH in the treatment of DD. Consideration of inflammatory phenomena as part of the drug's mechanism of action would significantly reduce overall rates of adverse effects.

Disease-specific adverse events following nonlive vaccines: a paradoxical placebo effect or a nocebo phenomenon?

PubMed

Okaïs, Claire; Gay, Constance; Seon, Fabrice; Buchaille, Lydie; Chary, Emilie; Soubeyrand, Benoît

2011-08-26

Vaccines can cause adverse reactions (AR), i.e. adverse events following immunization (AEFIs) due to the vaccine, such as local reactions or fever. In addition, live attenuated vaccines which replicate in vaccinees can cause disease-specific AR, e.g. measles-like rash following measles vaccination. However, nonlive vaccines because they are inactivated and they do not replicate in vaccinees, are not likely to cause disease-specific AR. The aim of the study was to assess whether safety signals could be generated by an undescribed bias in spontaneous reporting of disease-specific AEFIs with nonlive vaccines. All AEFIs of Sanofi Pasteur MSD vaccines spontaneously reported in France from January 2000 to June 2010, coded according to MedDRA terms and collected in the company's pharmacovigilance database were analyzed. Vaccine-event pairs of interest were selected a priori. The disproportionality reporting rate methodology was used, comparing the proportion of a given event reported following a given vaccine to its proportion reported following all other studied vaccines. The Reporting Odds Ratio (ROR) was used for signals detection for each vaccine-event pair selected. A total of 33,275 AEFIs were analyzed. The calculated ROR showed a statistically disproportionate reporting rate and generated false safety signals for almost all the pairs tested. Three nonlive vaccine pairs were striking: gynaecological symptoms and the quadrivalent human papillomavirus (qHPV) vaccine; trismus and tetanus vaccines; hepatobiliary disorders and hepatitis B vaccines. In conclusion we have identified a new vaccine AE spontaneous reporting bias: "disease-specific adverse events following nonlive vaccines", showing that vaccinees and healthcare professionals tend to report preferentially the symptoms of the disease against which the nonlive vaccine was administered. We suggest that bias is subordinate to a paradoxical placebo effect and/or a nocebo phenomenon. Copyright © 2011 Elsevier Ltd

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

PubMed Central

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

2010-01-01

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

Adverse effects of antiretroviral therapy for HIV infection.

PubMed

Montessori, Valentina; Press, Natasha; Harris, Marianne; Akagi, Linda; Montaner, Julio S G

2004-01-20

Long-term remission of HIV-1 disease can be readily achieved by combinations of antiretroviral agents. The suppression of plasma viral loads to less than the limit of quantification of the most sensitive commercially available assays (i.e., less than 50 copies/mL) and the coincident improvement in CD4 T cell counts is associated with resolution of established opportunistic infections and a decrease in the risk of new opportunistic infections. However, prolonged treatment with combination regimens can be difficult to sustain because of problems with adherence and toxic effects. All antiretroviral drugs can have both short-term and long-term adverse events. The risk of specific side effects varies from drug to drug, from drug class to drug class, and from patient to patient. A better understanding of the adverse effects of antiretroviral agents is of interest not only for HIV specialists as they try to optimize therapy, but also for other physicians who care for HIV-positive patients.

Adverse effects of antiretroviral therapy for HIV infection

PubMed Central

Montessori, Valentina; Press, Natasha; Harris, Marianne; Akagi, Linda; Montaner, Julio S.G.

2004-01-01

LONG-TERM REMISSION OF HIV-1 DISEASE CAN BE READILY ACHIEVED by combinations of antiretroviral agents. The suppression of plasma viral loads to less than the limit of quantification of the most sensitive commercially available assays (i.e., less than 50 copies/mL) and the coincident improvement in CD4 T cell counts is associated with resolution of established opportunistic infections and a decrease in the risk of new opportunistic infections. However, prolonged treatment with combination regimens can be difficult to sustain because of problems with adherence and toxic effects. All antiretroviral drugs can have both short-term and long-term adverse events. The risk of specific side effects varies from drug to drug, from drug class to drug class, and from patient to patient. A better understanding of the adverse effects of antiretroviral agents is of interest not only for HIV specialists as they try to optimize therapy, but also for other physicians who care for HIV-positive patients. PMID:14734438

Adverse CNS-effects of beta-adrenoceptor blockers.

PubMed

Gleiter, C H; Deckert, J

1996-11-01

In 1962 propranolol, the first beta adrenoceptor antagonist (beta blocker), was brought on to the market. There is now a host of different beta blockers available, and these compounds are among the most commonly prescribed groups of drugs. The efficacy of beta blockers has been proven predominantly for the treatment of cardiovascular diseases. Beta blockers are also used for certain types of CNS disorders, such as anxiety disorders, essential tremor and migraine. While low toxicity means that they have a favorable risk-benefit ratio, given the high intensity of use, it is essential to have a comprehensive knowledge of adverse events. Adverse events of beta blockers that can be related to the CNS are quite often neglected, even in textbooks of clinical pharmacology or review articles, and thus often misdiagnosed. The following article, therefore, after summarizing the use of beta blockers for CNS indications, critically reviews the literature on centrally mediated adverse events. General pharmacological features of beta blockers and their molecular basis of action will briefly be addressed to the extent that they are or may become relevant for central nervous pharmacotherapy and side-effects.

Potential adverse effects of omega-3 Fatty acids in dogs and cats.

PubMed

Lenox, C E; Bauer, J E

2013-01-01

Fish oil omega-3 fatty acids, mainly eicosapentaenoic acid and docosahexaenoic acid, are used in the management of several diseases in companion animal medicine, many of which are inflammatory in nature. This review describes metabolic differences among omega-3 fatty acids and outlines potential adverse effects that may occur with their supplementation in dogs and cats with a special focus on omega-3 fatty acids from fish oil. Important potential adverse effects of omega-3 fatty acid supplementation include altered platelet function, gastrointestinal adverse effects, detrimental effects on wound healing, lipid peroxidation, potential for nutrient excess and toxin exposure, weight gain, altered immune function, effects on glycemic control and insulin sensitivity, and nutrient-drug interactions. Copyright © 2013 by the American College of Veterinary Internal Medicine.

[THE EFFECT OF CLAIMS ABOUT MEDICAL ADVERSE EVENTS ON PATIENTS' SAFETY].

PubMed

Niv, Yaron

2018-04-01

In 1999 the Institute of Medicine (ION) declared that "to err in human" and that our goal is not to "blame and shame" but to investigate and establish processes that will prevent future mistakes. Shortage in manpower, physicians and nurses, may cause a disproportional burden of work and increase mistakes and adverse events. The complexity of patients requires a multidisciplinary team with many participants for achieving goals and saving lives. In the last 2 decades there was an exponential increase in the number of medical negligence claims and a similar increase in the sums given to the plaintiffs, in verdicts, mediation or compromises. The judges see before them the victims of these mistakes and their suffering, and look at the health system as a "deep pocket" for plaintiffs' compensation. Health institutes invest a lot of money and personnel to protect against claims instead of investing in systemic learning, manpower and equipment for preventing future adverse events. Fear of claims may cause excellent physicians to leave their profession leading to a possible shortage in experts in some important fields.

Countermeasures for space radiation induced adverse biologic effects

NASA Astrophysics Data System (ADS)

Kennedy, A. R.; Wan, X. S.

2011-11-01

Radiation exposure in space is expected to increase the risk of cancer and other adverse biological effects in astronauts. The types of space radiation of particular concern for astronaut health are protons and heavy ions known as high atomic number and high energy (HZE) particles. Recent studies have indicated that carcinogenesis induced by protons and HZE particles may be modifiable. We have been evaluating the effects of proton and HZE particle radiation in cultured human cells and animals for nearly a decade. Our results indicate that exposure to proton and HZE particle radiation increases oxidative stress, cytotoxicity, cataract development and malignant transformation in in vivo and/or in vitro experimental systems. We have also shown that these adverse biological effects can be prevented, at least partially, by treatment with antioxidants and some dietary supplements that are readily available and have favorable safety profiles. Some of the antioxidants and dietary supplements are effective in preventing radiation induced malignant transformation in vitro even when applied several days after the radiation exposure. Our recent progress is reviewed and discussed in the context of the relevant literature.

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

PubMed

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

2009-12-01

diagnostic codes for identification of AF and suspected adverse events is a source of potential investigator error. A direct cause-effect relationship between suspected adverse events/function tests and AF therapy cannot be confirmed based on the claims data available. The incidence of suspected adverse events and adverse event monitoring during AF rhythm-control and/or rate-control therapy is high. Costs associated with adverse events and adverse event monitoring are likely to add considerably to the overall burden of AF management.

Dietary supplementation with rice bran fermented with Lentinus edodes increases interferon-γ activity without causing adverse effects: a randomized, double-blind, placebo-controlled, parallel-group study.

PubMed

Choi, Ji-Young; Paik, Doo-Jin; Kwon, Dae Young; Park, Yongsoon

2014-04-22

The purpose of this study was to investigate the hypothesis that dietary supplementation with rice bran fermented with Lentinus edodes (rice bran exo-biopolymer, RBEP), a substance known to contain arabinoxylan, enhances natural killer (NK) cell activity and modulates cytokine production in healthy adults. This study was designed in a randomized, double-blind, placebo-controlled, and parallel-group format. Eighty healthy participants with white blood cell counts of 4,000-8,000 cells/μL were randomly assigned to take six capsules per day of either 3 g RBEP or 3 g placebo for 8 weeks. Three participants in the placebo group were excluded after initiation of the protocol; no severe adverse effects from RBEP supplementation were reported. NK cell activity of peripheral blood mononuclear cells was measured using nonradioactive cytotoxicity assay kits and serum cytokine concentrations included interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-4, IL-10, and IL-12 were measured by Bio-Plex cytokine assay kit. This study was registered with the Clinical Research Information Service (KCT0000536). Supplementation of RBEP significantly increased IFN-γ production compared with the placebo group (P = 0.012). However, RBEP supplementation did not affect either NK cell activity or cytokine levels, including IL-2, IL-4, IL-10, IL-12, and TNF-α, compared with the placebo group. The data obtained in this study indicate that RBEP supplementation increases IFN-γ secretion without causing significant adverse effects, and thus may be beneficial to healthy individuals. This new rice bran-derived product may therefore be potentially useful to include in the formulation of solid and liquid foods designed for treatment and prevention of pathological states associated with defective immune responses.

Adverse effects of orthodontic treatment: A clinical perspective

PubMed Central

Talic, Nabeel F.

2011-01-01

Orthodontic treatment is associated with a number of adverse effects, such as root resorption, pain, pulpal changes, periodontal disease, and temporomandibular dysfunction (TMD). Orthodontists should be aware of these effects and associated risk factors. Risk factors linked to root resorption include the duration of treatment, length, and shape of the root, trauma history, habits, and genetic predisposition. PMID:24151415

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

PubMed

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

2017-04-19

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

[L-carnitine treatment and fish odor syndrome: an unwaited adverse effect].

PubMed

Rocher, F; Caruba, C; Broly, F; Lebrun, C

2011-01-01

Levocarnitine treatment is usually well tolerated, with essentially dose-dependent diarrhea as the main induced adverse effect. We report a case of fish odor syndrome during levocarnitine treatment which resolved after levocarnitine discontinuation. This adverse effect seems to be correlated with excedent carnitine intake and might be expressed when the elimination pathway becomes saturated or in a situation of deficiency enzymatic metabolism. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Prediction of adverse drug reactions using decision tree modeling.

PubMed

Hammann, F; Gutmann, H; Vogt, N; Helma, C; Drewe, J

2010-07-01

Drug safety is of great importance to public health. The detrimental effects of drugs not only limit their application but also cause suffering in individual patients and evoke distrust of pharmacotherapy. For the purpose of identifying drugs that could be suspected of causing adverse reactions, we present a structure-activity relationship analysis of adverse drug reactions (ADRs) in the central nervous system (CNS), liver, and kidney, and also of allergic reactions, for a broad variety of drugs (n = 507) from the Swiss drug registry. Using decision tree induction, a machine learning method, we determined the chemical, physical, and structural properties of compounds that predispose them to causing ADRs. The models had high predictive accuracies (78.9-90.2%) for allergic, renal, CNS, and hepatic ADRs. We show the feasibility of predicting complex end-organ effects using simple models that involve no expensive computations and that can be used (i) in the selection of the compound during the drug discovery stage, (ii) to understand how drugs interact with the target organ systems, and (iii) for generating alerts in postmarketing drug surveillance and pharmacovigilance.

Real-World Adverse Effects of Capecitabine Toxicity in an Elderly Population.

PubMed

van Beek, Michiel W H; Roukens, Monique; Jacobs, Wilco C H; Timmer-Bonte, Johanna N H; Kramers, Cees

2018-06-22

Few studies have assessed the safety and effectiveness of the numerous available chemotherapeutic therapies for geriatric oncology patients. Most safety studies are conducted in large trials, and there is some uncertainty surrounding whether the results would be the same in typical daily use. This retrospective study aims to assess the adverse effects of real-world capecitabine use in elderly patients. We reviewed the records of patients treated with capecitabine in an oncology department of a University Clinic in Nijmegen, The Netherlands. We scored adverse effects such as hand-foot syndrome and diarrhea, and dosage adjustments and the reasons for them. In total, 132 patients were included, 69 of whom were aged 70 years or below (mean age: 57 years), while 63 were aged older than 70 years (mean age: 74 years). Patients aged over 70 years experienced more serious adverse effects than younger patients. Grade 2 or 3 hand-foot syndrome toxicity was experienced by 20.2% of patients aged younger than 70 years and by 34.9% of patients older than 70 years (p = 0.059). Grade 2, 3, or 4 diarrhea was experienced by 17.4% of the patients aged younger than 70 years but by 31.7% of the patients aged older than 70 years (p = 0.044). Dosage was adjusted for 27/69 patients in the younger group and 52/63 patients in the older group (p = 0.001). The difference in observed adverse effects cannot be the sole explanation for the high incidence of observed dose adjustments. A prospective follow-up study of elderly patients using capecitabine outside clinical trials is needed to evaluate the optimum balance between adverse effects and efficacy.

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

PubMed

Allen, Cheryl A; Ivester, Julius R

2017-12-01

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

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

PubMed

Krejci, Charlene B; Bissada, Nabil F

2012-01-01

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

Inadequacies of Physical Examination as a Cause of Medical Errors and Adverse Events: A Collection of Vignettes.

PubMed

Verghese, Abraham; Charlton, Blake; Kassirer, Jerome P; Ramsey, Meghan; Ioannidis, John P A

2015-12-01

Oversights in the physical examination are a type of medical error not easily studied by chart review. They may be a major contributor to missed or delayed diagnosis, unnecessary exposure to contrast and radiation, incorrect treatment, and other adverse consequences. Our purpose was to collect vignettes of physical examination oversights and to capture the diversity of their characteristics and consequences. A cross-sectional study using an 11-question qualitative survey for physicians was distributed electronically, with data collected from February to June of 2011. The participants were all physicians responding to e-mail or social media invitations to complete the survey. There were no limitations on geography, specialty, or practice setting. Of the 208 reported vignettes that met inclusion criteria, the oversight was caused by a failure to perform the physical examination in 63%; 14% reported that the correct physical examination sign was elicited but misinterpreted, whereas 11% reported that the relevant sign was missed or not sought. Consequence of the physical examination inadequacy included missed or delayed diagnosis in 76% of cases, incorrect diagnosis in 27%, unnecessary treatment in 18%, no or delayed treatment in 42%, unnecessary diagnostic cost in 25%, unnecessary exposure to radiation or contrast in 17%, and complications caused by treatments in 4%. The mode of the number of physicians missing the finding was 2, but many oversights were missed by many physicians. Most oversights took up to 5 days to identify, but 66 took longer. Special attention and skill in examining the skin and its appendages, as well as the abdomen, groin, and genitourinary area could reduce the reported oversights by half. Physical examination inadequacies are a preventable source of medical error, and adverse events are caused mostly by failure to perform the relevant examination. Copyright © 2015 Elsevier Inc. All rights reserved.

Adverse Effects of Grape Seed Extract Supplement: A Clinical Case and Long-Term Follow-Up.

PubMed

Berry, Andrew C; Nakshabendi, Rahman; Abidali, Hussein; Atchaneeyasakul, Kunakorn; Dholaria, Kevin; Johnson, Cassandra; Kishore, Varsha A; Baltz, Aaron C

2016-01-01

Grape seed extract (GSE) supplement use is becoming more popular today for its potential chemopreventive and chemotherapeutic role. We report a 49-year-old male who presented with recurrent nausea, vomiting, diarrhea, and acute weakness following GSE use. A thorough medical workup ensued and no causes were identified clinically, procedurally, or with imaging. Symptoms resolved after GSE discontinuation and the patient remained symptom-free 5 years later. This case illustrates the paucity of documented detailed clinical cases and lack of controlled trials detailing a thorough and reproducible adverse effect profile of GSE supplement.

Judgments of Cause and Blame: The Effects of Intentionality and Foreseeability

ERIC Educational Resources Information Center

Lagnado, David A.; Channon, Shelley

2008-01-01

What are the factors that influence everyday attributions of cause and blame? The current studies focus on sequences of events that lead to adverse outcomes, and examine people's cause and blame ratings for key events in these sequences. Experiment 1 manipulated the intentional status of candidate causes and their location in a causal chain.…

The Flavonoid 7,4'-Dihydroxyflavone Prevents Dexamethasone Paradoxical Adverse Effect on Eotaxin Production by Human Fibroblasts.

PubMed

Liu, Changda; Yang, Nan; Chen, Xiaoke; Tversky, Jody; Zhan, Jixun; Chehade, Mirna; Miller, Rachel L; Li, Xiu-Min

2017-03-01

Eotaxin/CCL-11 is a major chemoattractant that contributes to eosinophilic inflammation in asthma. Glucocorticoids inhibit inflammation, but long-time exposure may cause paradoxical adverse effects by augmenting eotaxin/CCL-11production. The aim of this study was to determine if 7,4'-dihydroxyflavone (7,4'-DHF), the eotaxin/CCL11 inhibitor isolated from Glycyrrhiza uralensis, reduces in vitro eotaxin production induced by long-time dexamethasone (Dex) exposure, and if so, to elucidate the mechanisms of this inhibition. Human lung fibroblast-1 cells were used to identify the potency of 7,4'-DHF compared with other compounds from G. uralensis, to compare 7,4'-DHF with Dex on eotaxin production following 24-h short-time culture and 72-h longer-time (LT) culture, and to determine the effects of the 7,4'-DHF on Dex LT culture augmented eotaxin production and molecule mechanisms. 7,4'-DHF was the most potent eotaxin/CCL-11 inhibitor among the ten compounds and provided continued suppression. In contrast to short-time culture, Dex LT culture increased constitutively, and IL-4/TNF-α stimulated eotaxin/CCL11 production by human lung fibroblast-1 cells. This adverse effect was abrogated by 7,4'-DHF co-culture. 7,4'-DHF significantly inhibited Dex LT culture augmentation of p-STAT6 and impaired HDAC2 expression. This study demonstrated that 7,4'-DHF has the ability to consistently suppress eotaxin production and prevent Dex-paradoxical adverse effects on eotaxin production. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

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

PubMed Central

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

2003-01-01

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

Cause-and-effect analysis of risk management files to assess patient care in the emergency department.

PubMed

White, Andrew A; Wright, Seth W; Blanco, Roberto; Lemonds, Brent; Sisco, Janice; Bledsoe, Sandy; Irwin, Cindy; Isenhour, Jennifer; Pichert, James W

2004-10-01

Identifying the etiologies of adverse outcomes is an important first step in improving patient safety and reducing malpractice risks. However, relatively little is known about the causes of emergency department-related adverse outcomes. The objective was to describe a method for identification of common causes of adverse outcomes in an emergency department. This methodology potentially can suggest ways to improve care and might provide a model for identification of factors associated with adverse outcomes. This was a retrospective analysis of 74 consecutive files opened by a malpractice insurer between 1995 and 2000. Each risk-management file was analyzed to identify potential causes of adverse outcomes. The main outcomes were rater-assigned codes for alleged problems with care (e.g., failures of communication or problems related to diagnosis). About 50% of cases were related to injuries or abdominal complaints. A contributing cause was found in 92% of cases, and most had more than one contributing cause. The most frequent contributing categories included failure to diagnose (45%), supervision problems (31%), communication problems (30%), patient behavior (24%), administrative problems (20%), and documentation (20%). Specific relating factors within these categories, such as lack of timely resident supervision and failure to follow policies and procedures, were identified. This project documented that an aggregate analysis of risk-management files has the potential to identify shared causes related to real or perceived adverse outcomes. Several potentially correctable systems problems were identified using this methodology. These simple, descriptive management tools may be useful in identifying issues for problem solving and can be easily learned by physicians and managers.

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

PubMed Central

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

2013-01-01

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

Efficacy and Adverse Effects of Atropine in Childhood Myopia: A Meta-analysis.

PubMed

Gong, Qianwen; Janowski, Miroslaw; Luo, Mi; Wei, Hong; Chen, Bingjie; Yang, Guoyuan; Liu, Longqian

2017-06-01

Some uncertainty about the clinical value and dosing of atropine for the treatment of myopia in children remains. To evaluate the efficacy vs the adverse effects of various doses of atropine in the therapy for myopia in children. Data were obtained from PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, from inception to April 30, 2016. The reference lists of published reviews and clinicaltrials.gov were searched for additional relevant studies. Key search terms included myopia, refractive errors, and atropine. Only studies published in English were included. Randomized clinical trials and cohort studies that enrolled patients younger than 18 years with myopia who received atropine in at least 1 treatment arm and that reported the annual rate of myopia progression and/or any adverse effects of atropine therapy were included in the analysis. Two reviewers independently abstracted the data. Heterogeneity was statistically quantified by Q, H, and I2 statistics, and a meta-analysis was performed using the random-effects model. The Cochrane Collaboration 6 aspects of bias and the Newcastle-Ottawa Scale were used to assess the risk for bias. The primary outcome was a difference in efficacy and the presence of adverse effects at different doses of atropine vs control conditions. The secondary outcomes included the differences in adverse effects between Asian and white patients. Nineteen unique studies involving 3137 unique children were included in the analysis. The weighted mean differences between the atropine and control groups in myopia progression were 0.50 diopters (D) per year (95% CI, 0.24-0.76 D per year) for low-dose atropine, 0.57 D per year (95% CI, 0.43-0.71 D per year) for moderate-dose atropine, and 0.62 D per year (95% CI, 0.45-0.79 D per year) for high-dose atropine (P < .001), which translated to a high effect size (Cohen d, 0.97, 1.76, and 1.94, respectively). All doses of atropine, therefore, were equally beneficial with

Adverse Health Effects of Betel Quid and the Risk of Oral and Pharyngeal Cancers

PubMed Central

Mahmood, Qaisar; Chiang, Tai-An

2017-01-01

Global reports estimate 600 million betel quid (BQ) chewers. BQ chewing has been demonstrated not only to be a risk factor for cancers of the oral cavity and pharynx and oral potentially malignant disorders (OPMD) but also to cause other cancers and adverse health effects. Herein, we summarized the international comparison data to aid in the understanding of the close relationship between the prevalence of BQ chewing, the occurrence of oral and pharyngeal cancers, and adverse health effects. Potential biomarkers of BQ carcinogens, such as areca nut, alkaloids, and 3-methylnitrosaminopropionitrile (MNPN), are closely associated with human health toxicology. Molecular mechanisms or pathways involving autophagy, hypoxia, COX-2, NF-κB activity, and stemness are known to be induced by BQ ingredients and are very closely related to the carcinogenesis of cancers of oral and pharynx. BQ abuse-related monoamine oxidase (MAO) gene was associated with the occurrence and progress of oral and pharyngeal cancers. In summary, our review article provides important insights into the potential roles of environmental BQ (specific alkaloid biomarkers and nitrosamine products MNPN) and genetic factors (MAO) and offers a basis for studies aiming to reduce or eliminate BQ-related OPMD and oral/pharyngeal cancer incidences in the future. PMID:29376073

The Effect of Cannabis on the Brain: Can it cause brain anomalies that lead to increased risk for Schizophrenia?

PubMed Central

DeLisi, Lynn E.

2015-01-01

Purpose of This Review This review explores what is known about cannabis’s association with schizophrenia, cannabis’s effects on the brain, and whether the brain changes known to be present in schizophrenia could be caused by cannabis and thus lead to a psychosis. Recent Findings The heavy use of cannabis is known to be associated with some adverse consequences, such as the occurrence of acute psychotic episodes and the development of chronic schizophrenia in some people even after its use has terminated. Recent studies have produced controversy about whether cannabis in heavy use can cause irreversible brain damage, particularly to adolescents and thus, whether a chronic psychosis could be a result of brain changes caused by cannabis. Summary From the evidence that exists, it appears that the above view is unlikely and that cannabis may even have benign effects on brain structure, not producing deleterious damage. However, its neurochemical interactions with the dopaminergic pathway may, particularly in genetically vulnerable individuals, have adverse consequences. PMID:18332661

Adverse Effects of Nutraceuticals and Dietary Supplements.

PubMed

Ronis, Martin J J; Pedersen, Kim B; Watt, James

2018-01-06

Over 70% of Americans take some form of dietary supplement every day, and the supplement industry is currently big business, with a gross of over $28 billion. However, unlike either foods or drugs, supplements do not need to be registered or approved by the US Food and Drug Administration (FDA) prior to production or sales. Under the Dietary Supplement Health and Education Act of 1994, the FDA is restricted to adverse report monitoring postmarketing. Despite widespread consumption, there is limited evidence of health benefits related to nutraceutical or supplement use in well-nourished adults. In contrast, a small number of these products have the potential to produce significant toxicity. In addition, patients often do not disclose supplement use to their physicians. Therefore, the risk of adverse drug-supplement interactions is significant. An overview of the major supplement and nutraceutical classes is presented here, together with known toxic effects and the potential for drug interactions.

Switching, Adverse Effects and Use of Over-the-Counter Analgesics among Users of Oral Anticoagulants: A Pharmacy-based Survey.

PubMed

Hellfritzsch, Maja; Hyllested, Lea Maria Rønneberg; Meegaard, Line; Wiberg-Hansen, Alexander; Grove, Erik Lerkevang; Pottegård, Anton

2017-07-01

Oral anticoagulants are widely used but information on important aspects in that respect is not available from medical registers or clinical databases. Therefore, we conducted a survey including patients filling a prescription for oral anticoagulants at two large Danish community pharmacies. We collected information concerning the patients' knowledge of their anticoagulant treatment including prior drug switching. Further, patients were asked about use of over-the-counter analgesics, adverse effects and how the treatment affected their everyday life. Among 335 eligible patients, 301 (90%) agreed to participate. Atrial fibrillation was the most common indication (65%), and most patients filled a prescription for a non-vitamin K antagonist oral anticoagulant (NOAC) (58%). Among the 12% (n = 35) of participants who had switched oral anticoagulant treatment, 69% had switched from a vitamin K antagonist (VKA) to a NOAC. Switching was most frequently caused by inconvenience (34%) and adverse effects (23%). Although half of all patients had recently bought over-the-counter analgesics, purchase of ibuprofen and aspirin was rare (6%). More VKA users than NOAC users felt limited in their everyday life because of anticoagulant treatment (18% versus 9%). Among non-incident NOAC users, 21% had experienced adverse effects during their current treatment. Based on first-hand information from a large sample of anticoagulant users, we conclude that the main drug-related issues leading to anticoagulant switching and perceived limitations in everyday life were inconvenience and adverse effects. This varied between drug groups. Further, use of NSAIDs obtained over the counter was rare. © 2017 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Adverse effects of nickel in transosseous wires and surgical implants: literature review.

PubMed

Nwashindi, A; Dim, E M

2014-01-01

Transosseous wires used in the management of fractures are stainless steel alloys which contain nickel 14.5%, chromium 17.6%, iron 62.5% and molybdenum 2.8%. Gradual disintegration of the transosseous wires release nickel into the blood leading to increase nickel concentration in the blood. Nickel has been found to have some adverse systemic effects on the body. The aim of this paper is to discuss the sources of Nickel in the body as well as the systemic adverse effects of Nickel as a degradation product of stainless steel surgical implants. A study of pertinent literature on nickel as a content of stainless steel alloy used in implant surgery was done, taking note also of other sources of nickel in the body, the toxicokinetics of nickel and the related adverse effects of this metal and its compound in humans. As outcome,the sources of human exposure to nickel,distribution and metabolism of nickel in the body, host responseto stainless steel wires and the adverse effects of nickel in the body are presented. It may be necessary to discourage the use of wires or implants containing nickel in the management of fractures.The need for removal of these implants after they have served their purposes is emphasized.

The lesser of two adverse reactions.

PubMed

Chakraborti, Chayan; Egan, John

2010-01-01

Fundamental to complex systems are interconnected processes involved in providing high-quality patient care. A case study and a root cause analysis (RCA) illustrate a patient safety effort with unintended consequences. A 38-year-old woman presented to the hospital for odynophagia and vomiting. The patient developed Mobitz type 2, second-degree heart block temporally associated with the administration of intravenous ondansetron. RESPONSE TO THE EVENT: An Ishikawa, or fishbone, diagram conducted to enumerate potential contributing factors indicated that a key factor appeared to be an institutional restriction against using intravenous (i.v.) promethazine, which resulted in ondansetron being the only readily available i.v. anti-emetic on formulary. The anesthesia department requested that i.v. promethazine be removed from all operating and recovery room automated medication dispensing machines. The pharmacy department, given the realization that individual departments were taking independent action regarding promethazine, discussed the matter with the medical director, who issued a memo banning the use of i.v. promethazine. An institutional ban on i.v. anti-emetics such as promethazine may have resulted in an increase in the use of ondansetron and contributed to this adverse reaction. The reason to restrict promethazine is not well reported in the literature. In limiting the use of promethazine for patient safety concerns, the inadvertent increase in adverse reactions of the alternative medication, ondansetron, may have been overlooked. The resultant RCA underscores the need for careful cataloguing of adverse medication effects. Stakeholders should anticipate as many "downstream effects" of quality and patient safety improvements as possible. Comprehensive reporting of adverse medication effects will augment the emerging science of patient safety.

Indoor air pollution: Acute adverse health effects and host susceptibility

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

Zummo, S.M.; Karol, M.H.

1996-01-01

Increased awareness of the poor quality of indoor air compared with outdoor air has resulted in a significant amount of research on the adverse health effects and mechanisms of action of indoor air pollutants. Common indoor air agents are identified, along with resultant adverse health effects, mechanisms of action, and likely susceptible populations. Indoor air pollutants range from biological agents (such as dust mites) to chemical irritants (such as nitrogen dioxide, carbon monoxide, sulfur dioxide, formaldehyde, and isocyanates). These agents may exert their effects through allergic as well as nonallergic mechanisms. While the public does not generally perceive poor indoormore » air quality as a significant health risk, increasing reports of illness related to indoor air and an expanding base of knowledge on the health effects of indoor air pollution are likely to continue pushing the issue to the forefront.« less

Adverse health effects and unhealthy behaviors among medical students using Facebook.

PubMed

Al-Dubai, Sami Abdo Radman; Ganasegeran, Kurubaran; Al-Shagga, Mustafa Ahmed Mahdi; Yadav, Hematram; Arokiasamy, John T

2013-01-01

Little is known about the relationships between adverse health effects and unhealthy behaviors among medical students using Facebook. The aim of this study was to determine the associations between adverse health effects and unhealthy behaviors with Facebook use. A cross-sectional study was conducted in a private university in Malaysia among 316 medical students. A self-administered questionnaire was used. It included questions on sociodemographics, pattern of Facebook use, social relationship, unhealthy behaviors, and health effects. Mean age was 20.5 (±2.7) years. All students had a Facebook account. The average daily Facebook surfing hours were 2.5 (±1.7). Significant associations were found between average hours of Facebook surfing and the following factors: isolation from family members and community, refusing to answer calls, musculoskeletal pain, headache, and eye irritation (P < 0.005). The average hours spent on Facebook were significantly associated with holding urination and defecation while online, surfing Facebook until midnight, and postponing, forgetting, or skipping meals (P < 0.005). The average hours spent on Facebook were associated with adverse health effects and unhealthy behaviors among medical students, as well as social isolation from the family and community.

Adverse Health Effects and Unhealthy Behaviors among Medical Students Using Facebook

PubMed Central

Al-Dubai, Sami Abdo Radman; Al-Shagga, Mustafa Ahmed Mahdi; Yadav, Hematram; Arokiasamy, John T.

2013-01-01

Little is known about the relationships between adverse health effects and unhealthy behaviors among medical students using Facebook. The aim of this study was to determine the associations between adverse health effects and unhealthy behaviors with Facebook use. A cross-sectional study was conducted in a private university in Malaysia among 316 medical students. A self-administered questionnaire was used. It included questions on sociodemographics, pattern of Facebook use, social relationship, unhealthy behaviors, and health effects. Mean age was 20.5 (±2.7) years. All students had a Facebook account. The average daily Facebook surfing hours were 2.5 (±1.7). Significant associations were found between average hours of Facebook surfing and the following factors: isolation from family members and community, refusing to answer calls, musculoskeletal pain, headache, and eye irritation (P < 0.005). The average hours spent on Facebook were significantly associated with holding urination and defecation while online, surfing Facebook until midnight, and postponing, forgetting, or skipping meals (P < 0.005). The average hours spent on Facebook were associated with adverse health effects and unhealthy behaviors among medical students, as well as social isolation from the family and community. PMID:24453859

The development of search filters for adverse effects of surgical interventions in medline and Embase.

PubMed

Golder, Su; Wright, Kath; Loke, Yoon Kong

2018-06-01

Search filter development for adverse effects has tended to focus on retrieving studies of drug interventions. However, a different approach is required for surgical interventions. To develop and validate search filters for medline and Embase for the adverse effects of surgical interventions. Systematic reviews of surgical interventions where the primary focus was to evaluate adverse effect(s) were sought. The included studies within these reviews were divided randomly into a development set, evaluation set and validation set. Using word frequency analysis we constructed a sensitivity maximising search strategy and this was tested in the evaluation and validation set. Three hundred and fifty eight papers were included from 19 surgical intervention reviews. Three hundred and fifty two papers were available on medline and 348 were available on Embase. Generic adverse effects search strategies in medline and Embase could achieve approximately 90% relative recall. Recall could be further improved with the addition of specific adverse effects terms to the search strategies. We have derived and validated a novel search filter that has reasonable performance for identifying adverse effects of surgical interventions in medline and Embase. However, we appreciate the limitations of our methods, and recommend further research on larger sample sizes and prospective systematic reviews. © 2018 The Authors Health Information and Libraries Journal published by John Wiley & Sons Ltd on behalf of Health Libraries Group.

[Changes of menstruation patterns and adverse effects during the treatment of LNG-IUS for symptomatic adenomyosis].

PubMed

Li, L; Leng, J H; Zhang, J J; Jia, S Z; Li, X Y; Shi, J H; Dai, Y; Zhang, J R; Li, T; Xu, X X; Liu, Z Z; You, S S; Chang, X Y; Lang, J H

2016-09-25

Objective: To investigate the changes of mestruation patterns and adverse effects during the treatment of levonorgestrel-releasing intrauterine system(LNG-IUS)for symptomatic adenomyosis in a prospective cohort study. Methods: From December, 2006 to December, 2014, patients of symptomatic adenomyosis diagnosed by transvaginal ultrasound in Peking Union Medical College Hospital were given LNG-IUS. Before and after placement of IUS, all patients' parameters were recorded, including carrying status of IUS, symptoms and scores of dysmenorrhea, menstruation scores, biochemical indicators, physical parameters, menstruation patterns and adverse effects. Risk factors for changes of menstruation patterns and adverse effects, and their impact on treatment effects were analyzed. Results: Totally 1 100 cases met inclusion criteria, with median age 36 years(range 20-44 years), median follow-up 35 months(range 1 -108 months). During follow-up changes of menstruation patterns increased significantly with amenorrhea and shortened-menstruation being the most common manifestations. On 3, 6, 12, 24, 36, 48 and 60 months after the placement of LNG-IUS, 0, 5.8%(43/744), 6.9%(47/682), 10.1%(60/595), 17.3%(87/502), 27.2%(104/383)and 29.6%(82/277)patients achieved amenorrhea respectively( P <0.01). Total and subclassification of adverse effects decreased significantly( P <0.01). Within 12 months and >12 months after placement, abdominal pain and body weight increasing ≥5 kg/year were the most common adverse effects. Changes of menstruation patterns, total and subclassifications of adverse effects were neither dependent on patient parameters, treatment modes and treatment effects, nor could predict future LNG-IUS carrying status(all P > 0.05). After taking out of LNG-IUS, most changes of menstruation and adverse effects disappeared. Conclusions: During the treatment of LNG-IUS for symptomatic adenomyosis, changes of menstruation patterns increase gradually with amenorrhea and shortened

A U.S. perspective on the adverse reactions from traditional Chinese medicines.

PubMed

Ko, Richard J

2004-03-01

Traditional Chinese medicines (TCM) are popular in the United States and Asian and non-Asian consumers are using the product for disease treatment and health prevention. As more people are using TCM products, there are increased reports on adverse reactions. This review will focus on adverse reactions due to TCM as reported in the literature. The review is based on MedLine search of literatures using keywords including: herbs, herbal, traditional Chinese medicines with toxicity, adverse effects, death, drug interaction and pharmacokinetic. In addition, specific searches were performed using the above keywords with the common name and the scientific name of the plant product. The causes of adverse reactions associated with TCM are diverse. They include variability in active/toxic ingredients due to growing conditions, use of inherent toxic herbs causing toxicity, overdose of herbs, drug-herb interactions especially with pharmaceuticals that have narrow therapeutic index, coexisting diseases, and idiosyncratic reactions like allergy, hepatitis and anaphylaxis. Other adverse reactions can be due to manufacturing and quality problems causing adulteration, misidentification, substitution of one herb with another, variability in the amount of active ingredients, use of pharmaceuticals without identifying on the labels, improper processing and preparation, and contamination. To minimize the adverse reactions from TCM and protect the public, there must be adequate laws and regulations to ensure that products are manufactured with the highest standards. Manufacturers should be licensed by regulatory agency and manufactured under good manufacturing practice. TCM products must be evaluated for their safety before marketing. Proper labeling and good surveillance systems shall ensure the protection of the consumers.

The no-observed-adverse-effect-level in drug safety evaluations: use, issues, and definition(s).

PubMed

Dorato, Michael A; Engelhardt, Jeffery A

2005-08-01

The no-observed-adverse-effect-level (NOAEL) is an important part of the non-clinical risk assessment. It is a professional opinion based on the design of the study, indication of the drug, expected pharmacology, and spectrum of off-target effects. There is no consistent standard definition of NOAEL. This is based, in part, on the varied definitions of what constitutes an adverse effect. Toxicologists, either investigating or reviewing, have not been consistent in defining an effect as either adverse or acceptable. The common definition of NOAEL, "the highest experimental point that is without adverse effect," serves us well in general discussions. It does not, however, address the interpretation of risk based on toxicologically relevant effects, nor does it consider the progression of effect with respect to duration and/or dose. This paper will discuss the issues and application of a functional definition of the NOAEL in toxicology evaluations.

Bicalutamide-induced hepatotoxicity: A rare adverse effect.

PubMed

Hussain, Salwa; Haidar, Abdallah; Bloom, Robert E; Zayouna, Nafea; Piper, Michael H; Jafri, Syed-Mohammed R

2014-01-01

Male, 81 FINAL DIAGNOSIS: Prostate cancer Symptoms: Anorexia • dark urine • joundice • letargy Casodex Clinical Procedure: - Specialty: Oncology. Adverse events of drug therapy. Bicalutamide is a nonsteroidal anti-androgen used extensively during the initiation of androgen deprivation therapy with a luteinizing hormone-releasing hormone (LHRH) agonist to reduce the symptoms of tumor flare in patients with metastatic prostate neoplasm. It can cause gynecomastia, hot flashes, fatigue, and decreased libido through competitive androgen receptor blockade. Although not as common, acute drug-induced liver injury is also possible with bicalutamide therapy. Typically, this results in transient derangement of liver function and patients remain asymptomatic. We share our experience with a case of symptomatic acute hepatotoxicity secondary to the use of bicalutamide and use this opportunity to present a brief review of existing literature. An 81-year-old African American male with metastatic prostate neoplasm presented with nonspecific symptoms along with jaundice of 1-day duration. He was started on a trial of bicalutamide 3 weeks prior to presentation. On physical examination, scleral icterus was noted. Workup revealed acutely elevated liver transaminases (>5 times the upper limit of normal), alkaline phosphatase, conjugated hyperbilirubinemia, and coagulopathy. Other etiologies, including viruses, common toxins, drugs, autoimmune, and copper-induced hepatitis, were considered. Bicalutamide was discontinued and the patient was managed with supportive care. He showed improvement of clinical and laboratory abnormalities within days. While rare, clinically significant and potentially life-threatening liver injury can result from use of bicalutamide. Prompt recognition and discontinuation of bicalutamide is necessary to avoid serious complications from this adverse reaction.

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

Adverse Childhood Experiences, Commitment Offense, and Race/Ethnicity: Are the Effects Crime-, Race-, and Ethnicity-Specific?

PubMed

DeLisi, Matt; Alcala, Justin; Kusow, Abdi; Hochstetler, Andy; Heirigs, Mark H; Caudill, Jonathan W; Trulson, Chad R; Baglivio, Michael T

2017-03-22

Adverse childhood experiences are associated with an array of health, psychiatric, and behavioral problems including antisocial behavior. Criminologists have recently utilized adverse childhood experiences as an organizing research framework and shown that adverse childhood experiences are associated with delinquency, violence, and more chronic/severe criminal careers. However, much less is known about adverse childhood experiences vis-à-vis specific forms of crime and whether the effects vary across race and ethnicity. Using a sample of 2520 male confined juvenile delinquents, the current study used epidemiological tables of odds (both unadjusted and adjusted for onset, total adjudications, and total out of home placements) to evaluate the significance of the number of adverse childhood experiences on commitment for homicide, sexual assault, and serious persons/property offending. The effects of adverse childhood experiences vary considerably across racial and ethnic groups and across offense types. Adverse childhood experiences are strongly and positively associated with sexual offending, but negatively associated with homicide and serious person/property offending. Differential effects of adverse childhood experiences were also seen among African Americans, Hispanics, and whites. Suggestions for future research to clarify the mechanisms by which adverse childhood experiences manifest in specific forms of criminal behavior are offered.

Evaluation of adverse effects of long-term orally administered carprofen in dogs.

PubMed

Raekallio, Marja R; Hielm-Björkman, Anna K; Kejonen, Johanna; Salonen, Hanna M; Sankari, Satu M

2006-03-15

To evaluate the adverse effects of carprofen in dogs after oral administration for 2 months. Prospective, randomized, blinded, placebo-controlled clinical trial. 22 dogs with osteoarthritis in the hip or elbow joint. 13 dogs received orally administered carprofen daily for 2 months, and 9 dogs received a placebo for 2 months. Dogs were weighed, and serum and urine samples were collected before initiation of treatment and 4 and 8 weeks after initiation of treatment. Serum concentrations of total protein, albumin, urea, and creatinine and serum activities of alkaline phosphatase (ALP) and alanine aminotransferase (ALT) were measured. Urinary ALP-to-creatinine, gamma-glutamyltransferase (GGT)-to-creatinine, and protein-to-creatinine ratios were calculated. Dogs were observed by owners for adverse effects. Serum protein and albumin concentrations were lower in treated dogs than in those that received placebo at 4 weeks, but not at 8 weeks. No changes were observed in serum urea or creatinine concentrations; ALP or ALT activity; or urinary ALP-to-creatinine, GGT-to-creatinine, or protein-to-creatinine ratios. Dogs' weights did not change. Severity of vomiting, diarrhea, and skin reactions did not differ between groups, but appetite was better in dogs receiving carprofen than in dogs in the placebo group. It is possible that the transient decreases in serum protein and albumin concentrations in dogs that received carprofen were caused by altered mucosal permeability of the gastrointestinal tract because no indications of renal or hepatic toxicity were observed. Carprofen appeared to be well tolerated by dogs after 2 months of administration.

[Management of adverse effects with antituberculosis chemotherapy].

PubMed

Tsuyuguchi, Kazunari; Wada, Masako

2011-02-01

Tuberculosis has now become a curable disease with chemotherapy. So it is natural that the present issues in tuberculosis management are focused on how to complete standard chemotherapy. In this context, management of adverse effects constitutes an essential part of antituberculosis chemotherapy, as well as directly observed therapy. In this symposium, discussions were held about three major subjects on this issue. First, hepatotoxicity develops frequently and has sometimes fatal outcome, which makes it the most problematic adverse effect. "Management of hepatotoxicity during antituberculosis chemotherapy" was published by the Japanese Society for Tuberculosis (JST) in 2006. Dr. Shinsho Yoshiba evaluated this recommendation and pointed out that the criteria for discontinuation of drug based on AST, ALT and bilirubin levels is too sensitive and the concept of predicting fulminant hepatic failure (FHF) is lacking. He stressed the importance of monitoring serum prothrombin time for predicting FHF. Next, allergic drug reaction such as fever or skin rash often causes distress, although rarely fatal. As isoniazid (INH) and rifampicin (RFP) are key drugs for the cure, readministration of these drugs is often attempted by desensitization therapy. "Recommendation about desensitization therapy of antituberculosis drugs" was also published by JST in 1997. Dr. Yoshihiro Kobashi reported high success rates of 79 percent for INH and 75 percent for RFP according to this recommendation. He also reported correlated factor with the success, such as the longer period from the discontinuation to the desensitization therapy and lower doses of drugs at starting desensitization. Finally, we sometimes experience transient worsening of radiographical findings and general symptoms during antituberculosis chemotherapy. This is presumed to be due to allergic reaction to dead bacilli without requiring discontinuation of the drug. Differential diagnosis includes drug-induced pneumonia requring

Energy drink usage among university students in a Caribbean country: Patterns of use and adverse effects.

PubMed

Reid, Sandra D; Ramsarran, Jonathan; Brathwaite, Rachel; Lyman, Sarika; Baker, Ariane; Cornish, D'Andra C; Ganga, Stefan; Mohammed, Zahrid; Sookdeo, Avinash T; Thapelo, Cathrine K

2015-06-01

There has been little inquiry addressing whether or not concerns about adverse effects of energy drink usage are relevant in the Caribbean. This survey investigated energy drink usage and adverse consequences among tertiary level students in Trinidad and Tobago. A cross-sectional survey of 1994 students from eight institutions was conducted using a de novo questionnaire based on findings from a focus group of students. Chi-squared analyses and logistic regression were used to assess relationships between energy drink usage, adverse effects and other factors affecting energy drink use, and to verify predictors of energy drink use. Prevalence of use was 86%; 38% were current users. Males were more likely to use, used more frequently and at an earlier age. Energy drinks were used most commonly to increase energy (50%), combat sleepiness (45%) and enhance academic performance (40%), and occurred during sports (23%) and mixed with alcohol (22.2%). The majority (79.6%) consumed one energy drink per sitting; 62.2% experienced adverse effects, most commonly restlessness (22%), jolt and crash (17.1%) and tachycardia (16.6%). Awareness of adverse effects was associated with no use (p=0.004), but adverse effects were not a deterrent to continued use. Energy drink usage is prevalent among students. The use is not excessive, but associated with high rates of adverse effects and occurs in potentially dangerous situations like during exercise and with alcohol. There is a need to educate students about the potential adverse effects of energy drinks. Copyright © 2014 Ministry of Health, Saudi Arabia. Published by Elsevier Ltd. All rights reserved.

Energy drinks and their adverse health effects: A systematic review of the current evidence.

PubMed

Ali, Fahad; Rehman, Hiba; Babayan, Zaruhi; Stapleton, Dwight; Joshi, Divya-Devi

2015-04-01

With the rising consumption of so-called energy drinks over the last few years, there has been a growing body of literature describing significant adverse health events after the ingestion of these beverages. To gain further insight about the clinical spectrum of these adverse events, we conducted a literature review. Using PubMed and Google-Scholar, we searched the literature from January 1980 through May 2014 for articles on the adverse health effects of energy drinks. A total of 2097 publications were found. We then excluded molecular and industry-related studies, popular media reports, and case reports of isolated caffeine toxicity, yielding 43 reports. Energy drink consumption is a health issue primarily of the adolescent and young adult male population. It is linked to increased substance abuse and risk-taking behaviors. The most common adverse events affect the cardiovascular and neurological systems. The most common ingredient in energy drinks is caffeine, and it is believed that the adverse events are related to its effects, as well as potentiating effects of other stimulants in these drinks. Education, regulation, and further studies are required.

Influence of the ventilatory mode on acute adverse effects and facial thermography after noninvasive ventilation

PubMed Central

Pontes, Suzy Maria Montenegro; Melo, Luiz Henrique de Paula; Maia, Nathalia Parente de Sousa; Nogueira, Andrea da Nóbrega Cirino; Vasconcelos, Thiago Brasileiro; Pereira, Eanes Delgado Barros; Bastos, Vasco Pinheiro Diógenes; Holanda, Marcelo Alcantara

2017-01-01

ABSTRACT Objective: To compare the incidence and intensity of acute adverse effects and the variation in the temperature of facial skin by thermography after the use of noninvasive ventilation (NIV). Methods: We included 20 healthy volunteers receiving NIV via oronasal mask for 1 h. The volunteers were randomly divided into two groups according to the ventilatory mode: bilevel positive airway pressure (BiPAP) or continuous positive airway pressure (CPAP). Facial thermography was performed in order to determine the temperature of the face where it was in contact with the mask and of the nasal dorsum at various time points. After removal of the mask, the volunteers completed a questionnaire about adverse effects of NIV. Results: The incidence and intensity of acute adverse effects were higher in the individuals receiving BiPAP than in those receiving CPAP (16.1% vs. 5.6%). Thermographic analysis showed a significant cooling of the facial skin in the two regions of interest immediately after removal of the mask. The more intense acute adverse effects occurred predominantly among the participants in whom the decrease in the mean temperature of the nasal dorsum was lower (14.4% vs. 7.2%). The thermographic visual analysis of the zones of cooling and heating on the face identified areas of hypoperfusion or reactive hyperemia. Conclusions: The use of BiPAP mode was associated with a higher incidence and intensity of NIV-related acute adverse effects. There was an association between acute adverse effects and less cooling of the nasal dorsum immediately after removal of the mask. Cutaneous thermography can be an additional tool to detect adverse effects that the use of NIV has on facial skin. PMID:28538774

The adverse health effects of synthetic cannabinoids with emphasis on psychosis-like effects.

PubMed

van Amsterdam, Jan; Brunt, Tibor; van den Brink, Wim

2015-03-01

Cannabis use is associated with an increased risk of psychosis in vulnerable individuals. Cannabis containing high levels of the partial cannabinoid receptor subtype 1 (CB1) agonist tetrahydrocannabinol (THC) is associated with the induction of psychosis in susceptible subjects and with the development of schizophrenia, whereas the use of cannabis variants with relatively high levels of cannabidiol (CBD) is associated with fewer psychotic experiences. Synthetic cannabinoid receptor agonists (SCRAs) are full agonists and often more potent than THC. Moreover, in contrast to natural cannabis, SCRAs preparations contain no CBD so that these drugs may have a higher psychosis-inducing potential than cannabis. This paper reviews the general toxicity profile and the adverse effects of SCRAs with special emphasis on their psychosis-inducing risk. The review shows that, compared with the use of natural cannabis, the use of SCRAs may cause more frequent and more severe unwanted negative effects, especially in younger, inexperienced users. Psychosis and psychosis-like conditions seem to occur relatively often following the use of SCRAs, presumably due to their high potency and the absence of CBD in the preparations. Studies on the relative risk of SCRAs compared with natural cannabis to induce or evoke psychosis are urgently needed. © The Author(s) 2015.

Assessing adverse effects of intra-articular botulinum toxin A in healthy Beagle dogs: A placebo-controlled, blinded, randomized trial.

PubMed

Heikkilä, Helka M; Jokinen, Tarja S; Syrjä, Pernilla; Junnila, Jouni; Hielm-Björkman, Anna; Laitinen-Vapaavuori, Outi

2018-01-01

To investigate the clinical, cytological, and histopathological adverse effects of intra-articularly injected botulinum toxin A in dogs and to study whether the toxin spreads from the joint after the injection. A longitudinal, placebo-controlled, randomized clinical trial was conducted with six healthy laboratory Beagle dogs. Stifle joints were randomized to receive either 30 IU of onabotulinum toxin A or placebo in a 1:1 ratio. Adverse effects and spread of the toxin were examined by evaluating dynamic and static weight-bearing of the injected limbs, by assessing painless range of motion and pain on palpation of joints, and by performing synovial fluid analysis, neurological examination, and electrophysiological recordings at different examination time-points in a 12-week period after the injections. The dogs were then euthanized and autopsy and histopathological examination of joint structures and adjacent muscles and nerves were performed. Intra-articular botulinum toxin A did not cause local weakness or injection site pain. Instead, static weight-bearing and painless range of motion of stifle joints decreased in the placebo limbs. No clinically significant abnormalities associated with intra-articular botulinum toxin A were detected in the neurological examinations. Electrophysiological recordings showed low compound muscle action potentials in two dogs in the botulinum toxin A-injected limb. No significant changes were detected in the synovial fluid. Autopsy and histopathological examination of the joint and adjacent muscles and nerves did not reveal histopathological adverse effects of the toxin. Intra-articular botulinum toxin A does not produce significant clinical, cytological, or histopathological adverse effects in healthy dogs. Based on the electrophysiological recordings, the toxin may spread from the joint, but its clinical impact seems to be low.

Endocrine Disruptors: Adverse Health Effects Mediated by EGFR?

PubMed

Stolz, Ailine; Schönfelder, Gilbert; Schneider, Marlon R

2018-02-01

Although endocrine disruptors represent a serious concern to human health, the underlying molecular mechanisms leading to diseases such as cancer remain poorly understood. Recent work has uncovered the epidermal growth factor receptor (EGFR) as a possible mediator of these adverse health effects, with important implications for the role of endocrine disruptors in human diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Are there more adverse effects with lingual orthodontics?

PubMed

Madurantakam, Parthasarathy; Kumar, Satish

2017-12-22

Data sourcesPubMed, Embase, Cochrane Library and LILACS database, review of references cited in included articles and a manual search of leading orthodontic journals. No language restrictions were imposed in the search. Study authors were contacted when necessary.Study selectionRandomised controlled trials (RCTs) and controlled clinical trials (CCTs) in healthy patients that directly compared the adverse effects following treatment using buccal and lingual appliances. Studies involving single arch or dual arch appliances were considered. Studies on patients with systemic diseases, animal studies and in vitro studies were excluded. The primary outcomes of interest to the authors were a list of adverse effects: pain, caries, eating and speech difficulties and oral hygiene.Data extraction and synthesisTwo authors reviewed the titles and abstracts of all studies identified through the search without blinding to names of authors or publication dates. Selected articles from searches were evaluated independently by two authors against established inclusion criteria, disagreements were resolved by consensus or by consulting a third author. Two authors independently assessed the risk of bias using the Cochrane Collaboration's tool (randomised trials) and the Newcastle-Ottawa Scale for non-randomised studies. The level of agreement between the authors was assessed using the Cohen kappa statistic. A meta-analysis was performed to provide pooled effect estimate (expressed as odds ratio) as well as 95% confidence interval. The outcomes of interest were pain, caries, eating difficulties, speech difficulties and deficient oral hygiene. Heterogeneity was quantified using I2 statistic and potential causes explored. Publication bias was assessed using a funnel plot.ResultsEight articles were included; three RCTs and five CCTs. One RCT was considered to be at high risk of bias, one moderate risk and one low risk. Of the non-randomised studies, four were low risk and one was high risk

A signal detection method for temporal variation of adverse effect with vaccine adverse event reporting system data.

PubMed

Cai, Yi; Du, Jingcheng; Huang, Jing; Ellenberg, Susan S; Hennessy, Sean; Tao, Cui; Chen, Yong

2017-07-05

To identify safety signals by manual review of individual report in large surveillance databases is time consuming; such an approach is very unlikely to reveal complex relationships between medications and adverse events. Since the late 1990s, efforts have been made to develop data mining tools to systematically and automatically search for safety signals in surveillance databases. Influenza vaccines present special challenges to safety surveillance because the vaccine changes every year in response to the influenza strains predicted to be prevalent that year. Therefore, it may be expected that reporting rates of adverse events following flu vaccines (number of reports for a specific vaccine-event combination/number of reports for all vaccine-event combinations) may vary substantially across reporting years. Current surveillance methods seldom consider these variations in signal detection, and reports from different years are typically collapsed together to conduct safety analyses. However, merging reports from different years ignores the potential heterogeneity of reporting rates across years and may miss important safety signals. Reports of adverse events between years 1990 to 2013 were extracted from the Vaccine Adverse Event Reporting System (VAERS) database and formatted into a three-dimensional data array with types of vaccine, groups of adverse events and reporting time as the three dimensions. We propose a random effects model to test the heterogeneity of reporting rates for a given vaccine-event combination across reporting years. The proposed method provides a rigorous statistical procedure to detect differences of reporting rates among years. We also introduce a new visualization tool to summarize the result of the proposed method when applied to multiple vaccine-adverse event combinations. We applied the proposed method to detect safety signals of FLU3, an influenza vaccine containing three flu strains, in the VAERS database. We showed that it had high

Adverse Childhood Experiences, Commitment Offense, and Race/Ethnicity: Are the Effects Crime-, Race-, and Ethnicity-Specific?

PubMed Central

DeLisi, Matt; Alcala, Justin; Kusow, Abdi; Hochstetler, Andy; Heirigs, Mark H.; Caudill, Jonathan W.; Trulson, Chad R.; Baglivio, Michael T.

2017-01-01

Adverse childhood experiences are associated with an array of health, psychiatric, and behavioral problems including antisocial behavior. Criminologists have recently utilized adverse childhood experiences as an organizing research framework and shown that adverse childhood experiences are associated with delinquency, violence, and more chronic/severe criminal careers. However, much less is known about adverse childhood experiences vis-à-vis specific forms of crime and whether the effects vary across race and ethnicity. Using a sample of 2520 male confined juvenile delinquents, the current study used epidemiological tables of odds (both unadjusted and adjusted for onset, total adjudications, and total out of home placements) to evaluate the significance of the number of adverse childhood experiences on commitment for homicide, sexual assault, and serious persons/property offending. The effects of adverse childhood experiences vary considerably across racial and ethnic groups and across offense types. Adverse childhood experiences are strongly and positively associated with sexual offending, but negatively associated with homicide and serious person/property offending. Differential effects of adverse childhood experiences were also seen among African Americans, Hispanics, and whites. Suggestions for future research to clarify the mechanisms by which adverse childhood experiences manifest in specific forms of criminal behavior are offered. PMID:28327508

Rodenticide incidents of exposure and adverse effects on non-raptor birds

USGS Publications Warehouse

Vyas, Nimish B.

2017-01-01

Interest in the adverse effects of rodenticides on birds has focused primarily on raptors. However, non-raptor birds are also poisoned (rodenticide exposure resulting in adverse effects including mortality) by rodenticides through consumption of the rodenticide bait and contaminated prey. A literature search for rodenticide incidents (evidence of exposure to a rodenticide, adverse effects, or exposure to placebo baits) involving non-raptor birds returned 641 records spanning the years 1931 to 2016. The incidents included 17 orders, 58 families, and 190 non-raptor bird species. Nineteen anticoagulant and non-anticoagulant rodenticide active ingredients were associated with the incidents. The number of incidents and species detected were compared by surveillance method. An incident was considered to have been reported through passive surveillance if it was voluntarily reported to the authorities whereas the report of an incident found through field work that was conducted with the objective of documenting adverse effects on birds was determined to be from active surveillance. More incidents were reported from passive surveillance than with active surveillance but a significantly greater number of species were detected in proportion to the number of incidents found through active surveillance than with passive surveillance (z = 7.61, p < 0.01). Results suggest that reliance on only one surveillance method can underestimate the number of incidents that have occurred and the number of species that are affected. Although rodenticides are used worldwide, incident records were found from only 15 countries. Therefore, awareness of the breadth of species diversity of non-raptor bird poisonings from rodenticides may increase incident reportings and can strengthen the predictions of harm characterized by risk assessments.

[Use of intravenous iron infusion in a gastroenterology day hospital: Indications, dosage and adverse effects].

PubMed

Dosal, Angelina; Calvet, Xavier; Moreno, Laura; López, María; Figuerola, Ariadna; Ruíz, Miquel Angel; Suárez, David; Gené, Emili; Miquel, Mireia; Villoria, Albert

2010-01-01

There are no data in the literature on the use of intravenous iron infusion in gastroenterology day hospitals. To determine the indications, dosage and tolerance of intravenous iron infusion in outpatients attending a gastroenterology day hospital. We retrospectively reviewed the medical records of patients who received intravenous iron infusion between August 2007 and July 2008. The indications, dosage, transfusion requirements, adverse effects and patients' clinical and laboratory data were recorded. During the study period, 111 patients (41% women, with a mean age of 63.8 ± 18 years) received intravenous iron infusions. The main causes of anemia indicating iron administration were portal hypertensive gastropathy (n=55), inflammatory bowel disease (n=22) and intestinal angiodysplasia (n=12). The patients received a total of 557 iron infusions with a mean dose of 1033 mg iron per patient. There were no adverse effects. Despite the treatment, 46 patients required transfusion. Iron and transfusion requirements and mortality were significantly higher in patients with liver cirrhosis than in the remainder of the study group. Intravenous iron therapy is frequently used in the gastroenterology day hospital. Most infusions were administered in patients with chronic iron loss. Patients with liver cirrhosis had the most severe anemia and underlying disease and the highest mortality.

Mechanisms and assessment of statin-related muscular adverse effects

PubMed Central

Moßhammer, Dirk; Schaeffeler, Elke; Schwab, Matthias; Mörike, Klaus

2014-01-01

Statin-associated muscular adverse effects cover a wide range of symptoms, including asymptomatic increase of creatine kinase serum activity and life-threatening rhabdomyolysis. Different underlying pathomechanisms have been proposed. However, a unifying concept of the pathogenesis of statin-related muscular adverse effects has not emerged so far. In this review, we attempt to categorize these mechanisms along three levels. Firstly, among pharmacokinetic factors, it has been shown for some statins that inhibition of cytochrome P450-mediated hepatic biotransformation and hepatic uptake by transporter proteins contribute to an increase of systemic statin concentrations. Secondly, at the myocyte membrane level, cell membrane uptake transporters affect intracellular statin concentrations. Thirdly, at the intracellular level, inhibition of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase results in decreased intracellular concentrations of downstream metabolites (e.g. selenoproteins, ubiquinone, cholesterol) and alteration of gene expression (e.g. ryanodine receptor 3, glycine amidinotransferase). We also review current recommendations for prescribers. PMID:25069381

Adverse health effects of high-effort/low-reward conditions.

PubMed

Siegrist, J

1996-01-01

In addition to the person-environment fit model (J. R. French, R. D. Caplan, & R. V. Harrison, 1982) and the demand-control model (R. A. Karasek & T. Theorell, 1990), a third theoretical concept is proposed to assess adverse health effects of stressful experience at work: the effort-reward imbalance model. The focus of this model is on reciprocity of exchange in occupational life where high-cost/low-gain conditions are considered particularly stressful. Variables measuring low reward in terms of low status control (e.g., lack of promotion prospects, job insecurity) in association with high extrinsic (e.g., work pressure) or intrinsic (personal coping pattern, e.g., high need for control) effort independently predict new cardiovascular events in a prospective study on blue-collar men. Furthermore, these variables partly explain prevalence of cardiovascular risk factors (hypertension, atherogenic lipids) in 2 independent studies. Studying adverse health effects of high-effort/low-reward conditions seems well justified, especially in view of recent developments of the labor market.

The Development of Countermeasures for Space Radiation Induced Adverse Health Effects

NASA Astrophysics Data System (ADS)

Kennedy, Ann

human trials necessary to demonstrate "efficacy" for a beneficial effect on the long term adverse health effects of radiation, such as the development of cancer, cataracts, etc., is expected to take particularly long periods of time. To avoid the long time delay in the development of new drugs as countermeasures for radiation induced adverse health effects, the NSBRI Center for Acute Radiation Research (CARR) is currently focused on the use of drugs that have already been approved for human use by the FDA. Currently there are no approved countermeasures for external radiation exposure by the US Army or by NASA. The appropriate medications for symptoms of the Acute Radiation Syndrome (ARS) due to exposure to solar particle event (SPE) radiation are unknown, but there are medications appropriate for ARS symptoms caused by exposure to conventional ra-diation. The Armed Forces Radiobiology Research Institute (AFRRI) has medical guidelines for ARS medications (http://www.afrri.usuhs.mil/outreach/guidance.htm#policies), as does the US Dept. of Health and Human Services (the REMM (Radiation Event Medical Manage-ment) site (http://www.remm.nlm.gov). Supportive care when ARS symptoms develop include the administration of antimicrobial agents (which can include systemic antibiotics [especially those directed at gram-negative bacteria]), antiemetic agents, antidiarrheal agents, fluids, elec-trolytes, analgesic agents and topical burn creams (Waselenko, J.K. et al. Ann. Intern. Med. 140: 1037, 2004). For nausea and vomiting, serotonin receptor antagonists (5HT3 receptor antagonists) are very effective prophylaxis. There are two drugs that have been approved by the FDA (Zofran and Kytril) for radiation induced nausea and vomiting. Kytril (granisetron) is preferred by the US Army and is currently maintained in the US National Stockpile. Both of these drugs are known to stop retching and vomiting when given either before or after irradi-ation, even when vomiting and/or retching are

Global Association of Cold Spells and Adverse Health Effects: A Systematic Review and Meta-Analysis

PubMed Central

Ryti, Niilo R.I.; Guo, Yuming; Jaakkola, Jouni J.K.

2015-01-01

Background There is substantial evidence that mortality increases in low temperatures. Less is known about the role of prolonged cold periods denoted as cold spells. Objective We conducted the first systematic review and meta-analysis to summarize the evidence on the adverse health effects of cold spells in varying climates. Data sources and extraction Four databases (Ovid Medline, PubMed, Scopus, Web of Science) were searched for all years and languages available. “Cold spell” was defined as an event below a temperature threshold lasting for a minimum duration of 2 days. Of 1,527 identified articles, 26 satisfied our eligibility criteria for the systematic review, and 9 were eligible for meta-analyses. The articles were grouped by the three main study questions into Overall-effect Group, Added-effect Group, and Temperature-change-effect Group. Data synthesis Based on random-effects models in the meta-analyses, cold spells were associated with increased mortality from all or all nonaccidental causes (summary rate ratio = 1.10; 95% CI: 1.04, 1.17 based on 9 estimates from five studies), cardiovascular diseases (1.11; 95% CI: 1.03, 1.19; 12 estimates from eight studies), and respiratory diseases (1.21; 95% CI: 0.97, 1.51; 8 estimates from four studies). Estimated associations were stronger for people ≥ 65 years of age (1.06; 95% CI: 1.00, 1.12) than for people 0–64 years of age (1.01; 95% CI: 1.00, 1.03). Study-specific effect estimates from a limited number of studies suggested an increased morbidity related to cold spells, but it was not possible to quantitatively summarize the evidence. Conclusions Cold spells are associated with increased mortality rates in populations around the world. The body of evidence suggests that cold spells also have other adverse health effects. There was substantial heterogeneity among the studies, which should be taken into account in the interpretation of the results. Citation Ryti NR, Guo Y, Jaakkola JJ. 2016. Global

Global Association of Cold Spells and Adverse Health Effects: A Systematic Review and Meta-Analysis.

PubMed

Ryti, Niilo R I; Guo, Yuming; Jaakkola, Jouni J K

2016-01-01

There is substantial evidence that mortality increases in low temperatures. Less is known about the role of prolonged cold periods denoted as cold spells. We conducted the first systematic review and meta-analysis to summarize the evidence on the adverse health effects of cold spells in varying climates. Four databases (Ovid Medline, PubMed, Scopus, Web of Science) were searched for all years and languages available. "Cold spell" was defined as an event below a temperature threshold lasting for a minimum duration of 2 days. Of 1,527 identified articles, 26 satisfied our eligibility criteria for the systematic review, and 9 were eligible for meta-analyses. The articles were grouped by the three main study questions into Overall-effect Group, Added-effect Group, and Temperature-change-effect Group. Based on random-effects models in the meta-analyses, cold spells were associated with increased mortality from all or all nonaccidental causes (summary rate ratio = 1.10; 95% CI: 1.04, 1.17 based on 9 estimates from five studies), cardiovascular diseases (1.11; 95% CI: 1.03, 1.19; 12 estimates from eight studies), and respiratory diseases (1.21; 95% CI: 0.97, 1.51; 8 estimates from four studies). Estimated associations were stronger for people ≥ 65 years of age (1.06; 95% CI: 1.00, 1.12) than for people 0-64 years of age (1.01; 95% CI: 1.00, 1.03). Study-specific effect estimates from a limited number of studies suggested an increased morbidity related to cold spells, but it was not possible to quantitatively summarize the evidence. Cold spells are associated with increased mortality rates in populations around the world. The body of evidence suggests that cold spells also have other adverse health effects. There was substantial heterogeneity among the studies, which should be taken into account in the interpretation of the results. Ryti NR, Guo Y, Jaakkola JJ. 2016. Global association of cold spells and adverse health effects: a systematic review and meta

Adverse Effects and Surgical Complications in Pediatric Patients Undergoing Vagal Nerve Stimulation for Drug-Resistant Epilepsy.

PubMed

Trezza, A; Landi, A; Grioni, D; Pirillo, D; Fiori, L; Giussani, C; Sganzerla, E P

2017-01-01

Vagal nerve stimulation (VNS) is an effective treatment for drug-resistant epilepsy that is not suitable for resective surgery, both in adults and in children. Few reports describe the adverse effects and complications of VNS. The aim of our study was to present a series of 33 pediatric patients who underwent VNS for drug-resistant epilepsy and to discuss the adverse effects and complications through a review of the literature.The adverse effects of VNS are usually transient and are dependent on stimulation of the vagus and its efferent fibers; surgical complications of the procedure may be challenging and patients sometimes require further surgery; generally these complications affect VNS efficacy; in addition, hardware complications also have to be taken into account.In our experience and according to the literature, adverse effects and surgical and hardware complications are uncommon and can usually be managed definitely. Careful selection of patients, particularly from a respiratory and cardiac point of view, has to be done before surgery to limit the incidence of some adverse effects.

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

EPA Pesticide Factsheets

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

Deferasirox, an oral iron chelator, prevents hepatocarcinogenesis and adverse effects of sorafenib.

PubMed

Yamamoto, Naoki; Yamasaki, Takahiro; Takami, Taro; Uchida, Koichi; Fujisawa, Koichi; Matsumoto, Toshihiko; Saeki, Issei; Terai, Shuji; Sakaida, Isao

2016-05-01

Although sorafenib is expected to have a chemopreventive effect on hepatocellular carcinoma (HCC) recurrence, there are limitations to its use because of adverse effects, including effects on liver function. We have reported that the iron chelator, deferoxamine can prevent liver fibrosis and preneoplastic lesions. We investigated the influence of administering a new oral iron chelator, deferasirox (DFX), on the effects of sorafenib. We used the choline-deficient l-amino acid-defined (CDAA) diet-induced rat liver fibrosis and HCC model. We divided rats into four groups: CDAA diet only (control group), CDAA diet with sorafenib (sorafenib group), CDAA diet with DFX (DFX group), and CDAA diet with DFX and sorafenib (DFX + sorafenib group). Liver fibrosis and development of preneoplastic lesions were assessed. In addition, we assessed adverse effects such as changes in body and liver weight, skin damage (eruption, dryness, and hair loss), which is defined as hand-foot skin syndrome, in the sorafenib and DFX + sorafenib groups. The combination of DFX + sorafenib markedly prevented liver fibrosis and preneoplastic lesions better than the other treatments. Furthermore, the combination therapy significantly decreased adverse effects compared with the sorafenib group. In conclusion, the combination therapy with DFX and sorafenib may be a useful adjuvant therapy to prevent recurrence after curative treatment of HCC.

The adverse effects of oral desmopressin lyophilisate (MELT): personal experience on enuretic children

PubMed Central

Franceschini, Giulia; Mercurio, Serena; Del Vescovo, Ester; Ianniello, Francesca; Petitti, Tommasangelo

2018-01-01

Objective The aim of this study was to evaluate adverse effects of oral desmopressin lyophilisate (MELT) in enuretic children. Material and methods We enrolled 260 children with nocturnal enuresis (NE) referred to the Pediatric Service, ‘Campus Bio-Medico’ University of Rome, from April 2014 to April 2017 in the study, of these 23 were excluded. The study was characterized by 2 phases. During Phase 1 a careful patient’s medical history was obtained and physical examination was performed. After 3 months of treatment with MELT (Minirin/DDAVP®) at the dose of 120 mcg a day, a micturition diary was kept, adherence to therapy and any possible adverse effects were checked during the Phase 2. The study was carried out in compliance with the Helsinki Declaration. Results Among 237 patients included in the study 11 male and 6 female (n=17; 7.2%) patients with a mean age 10.06±2.49 years, reported 22 adverse effects, with an absolute risk of 7.17%. In particular, 5 neurological symptoms, 3 gastrointestinal effects, 4 sleep disturbances, 8 psycho-behavioral disorders, 2 symptoms of fatigue were reported. Conclusion In our study MELT with its higher bioavailability guaranteed lower frequency of adverse effects which resolved spontaneously and rapidly. The MELT formulation actually represents the first line and safe treatment for the NE. PMID:29484228

36 CFR 800.7 - Failure to resolve adverse effects.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 36 Parks, Forests, and Public Property 3 2012-07-01 2012-07-01 false Failure to resolve adverse effects. 800.7 Section 800.7 Parks, Forests, and Public Property ADVISORY COUNCIL ON HISTORIC PRESERVATION... concerning the undertaking and assist the Council in arranging an onsite inspection and an opportunity for...

Potential Adverse Cardiovascular Effects From Excessive Endurance Exercise

PubMed Central

O'Keefe, James H.; Patil, Harshal R.; Lavie, Carl J.; Magalski, Anthony; Vogel, Robert A.; McCullough, Peter A.

2012-01-01

A routine of regular exercise is highly effective for prevention and treatment of many common chronic diseases and improves cardiovascular (CV) health and longevity. However, long-term excessive endurance exercise may induce pathologic structural remodeling of the heart and large arteries. Emerging data suggest that chronic training for and competing in extreme endurance events such as marathons, ultramarathons, ironman distance triathlons, and very long distance bicycle races, can cause transient acute volume overload of the atria and right ventricle, with transient reductions in right ventricular ejection fraction and elevations of cardiac biomarkers, all of which return to normal within 1 week. Over months to years of repetitive injury, this process, in some individuals, may lead to patchy myocardial fibrosis, particularly in the atria, interventricular septum, and right ventricle, creating a substrate for atrial and ventricular arrhythmias. Additionally, long-term excessive sustained exercise may be associated with coronary artery calcification, diastolic dysfunction, and large-artery wall stiffening. However, this concept is still hypothetical and there is some inconsistency in the reported findings. Furthermore, lifelong vigorous exercisers generally have low mortality rates and excellent functional capacity. Notwithstanding, the hypothesis that long-term excessive endurance exercise may induce adverse CV remodeling warrants further investigation to identify at-risk individuals and formulate physical fitness regimens for conferring optimal CV health and longevity. PMID:22677079

Adverse effects of the anabolic steroid, boldenone undecylenate, on reproductive functions of male rabbits

PubMed Central

Oda, Samah S; El-Ashmawy, Ibrahim M

2012-01-01

Summary This study was conducted to evaluate the adverse effects of the anabolic steroid, boldenone undecylenate (BOL) on reproductive functions of male rabbits. Thirty white New Zealand mature male rabbits were divided into three groups (10 rabbits each). Group A rabbits served as a control group. Group B rabbits received 4.4 mg/kg body weight (bwt) BOL 5% oily solution. Group C rabbits received 8.8 mg/kg bwt BOL. Rabbits were injected intramuscularly twice weekly for two months. BOL had no significant effect on the bwt and bwt gain. Testes and epididymis weights were decreased significantly in the BOL-treated groups. BOL caused significant reduction in serum testosterone level, seminal volume, sperm motility, and sperm count. No abnormalities were detected in the sperm morphology of the BOL-treated groups. Histopathological alterations in the testes and epididymis were marked in the group C rabbits. These results indicate that administration of BOL exerts a significant harmful effect on the reproductive functions of male rabbits. PMID:22583130

RotaTeq vaccine adverse events and policy considerations.

PubMed

Geier, David A; King, Paul G; Sykes, Lisa K; Geier, Mark R

2008-03-01

Rotavirus is the leading cause of severe gastroenteritis in children <5 years-old worldwide. On February 3, 2006, the US Food and Drug Administration licensed RotaTeq (Merck and Co.), a bioengineered combination of five human-bovine hybridized reassortment rotaviruses. In August of 2006, the Advisory Committee on Immunization Practices recommended RotaTeq for routine vaccination of US infants administered orally at the ages 2, 4, and 6 months. An evaluation of data reported to VAERS following the first five quarters of post-marketing surveillance of RotaTeq was undertaken. Trends in adverse events reported following RotaTeq and cost-effectiveness calculations of RotaTeq in the context of the disease burden of rotavirus in the US were examined. From February 3, 2006 through July 31, 2007, a total of 160 (of the 165 reported) intussusception and 11 (of the 16 reported) Kawasaki disease adverse event reports were identified when RotaTeq was administered or co-administered with other vaccines. Time-trend analyses showed that there were significant increases in the total number of intussusception and Kawasaki disease adverse events entered into VAERS in comparison to previous years. These observations, coupled with limited rotavirus disease burden, cost-effectiveness, and potential contact viral transmission concerns, raise serious questions regarding the use of RotaTeq in the US. Healthcare providers should diligently report adverse events following RotaTeq vaccination to VAERS, and those who have experienced a vaccine-associated adverse event should be made aware that they may be eligible for compensation from the no-fault National Vaccine Injury Compensation Program (NVICP).

Assessing adverse effects of intra-articular botulinum toxin A in healthy Beagle dogs: A placebo-controlled, blinded, randomized trial

PubMed Central

Jokinen, Tarja S.; Syrjä, Pernilla; Junnila, Jouni; Hielm-Björkman, Anna; Laitinen-Vapaavuori, Outi

2018-01-01

Objective To investigate the clinical, cytological, and histopathological adverse effects of intra-articularly injected botulinum toxin A in dogs and to study whether the toxin spreads from the joint after the injection. Methods A longitudinal, placebo-controlled, randomized clinical trial was conducted with six healthy laboratory Beagle dogs. Stifle joints were randomized to receive either 30 IU of onabotulinum toxin A or placebo in a 1:1 ratio. Adverse effects and spread of the toxin were examined by evaluating dynamic and static weight-bearing of the injected limbs, by assessing painless range of motion and pain on palpation of joints, and by performing synovial fluid analysis, neurological examination, and electrophysiological recordings at different examination time-points in a 12-week period after the injections. The dogs were then euthanized and autopsy and histopathological examination of joint structures and adjacent muscles and nerves were performed. Results Intra-articular botulinum toxin A did not cause local weakness or injection site pain. Instead, static weight-bearing and painless range of motion of stifle joints decreased in the placebo limbs. No clinically significant abnormalities associated with intra-articular botulinum toxin A were detected in the neurological examinations. Electrophysiological recordings showed low compound muscle action potentials in two dogs in the botulinum toxin A-injected limb. No significant changes were detected in the synovial fluid. Autopsy and histopathological examination of the joint and adjacent muscles and nerves did not reveal histopathological adverse effects of the toxin. Conclusion Intra-articular botulinum toxin A does not produce significant clinical, cytological, or histopathological adverse effects in healthy dogs. Based on the electrophysiological recordings, the toxin may spread from the joint, but its clinical impact seems to be low. PMID:29320549

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.

Social work and adverse childhood experiences research: implications for practice and health policy.

PubMed

Larkin, Heather; Felitti, Vincent J; Anda, Robert F

2014-01-01

Medical research on "adverse childhood experiences" (ACEs) reveals a compelling relationship between the extent of childhood adversity, adult health risk behaviors, and principal causes of death in the United States. This article provides a selective review of the ACE Study and related social science research to describe how effective social work practice that prevents ACEs and mobilizes resilience and recovery from childhood adversity could support the achievement of national health policy goals. This article applies a biopsychosocial perspective, with an emphasis on mind-body coping processes to demonstrate that social work responses to adverse childhood experiences may contribute to improvement in overall health. Consistent with this framework, the article sets forth prevention and intervention response strategies with individuals, families, communities, and the larger society. Economic research on human capital development is reviewed that suggests significant cost savings may result from effective implementation of these strategies.

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

Childhood adversity, adult socioeconomic status and risk of work disability: a prospective cohort study.

PubMed

Halonen, Jaana I; Kivimäki, Mika; Vahtera, Jussi; Pentti, Jaana; Virtanen, Marianna; Ervasti, Jenni; Oksanen, Tuula; Lallukka, Tea

2017-09-01

To examine the combined effects of childhood adversities and low adult socioeconomic status (SES) on the risk of future work disability. Included were 34 384 employed Finnish Public Sector study participants who responded to questions about childhood adversities (none vs any adversity, eg, parental divorce or financial difficulties) in 2008, and whose adult SES in 2008 was available. We categorised exposure into four groups: neither (reference), childhood adversity only, low SES only or both. Participants were followed from 2009 until the first period of register-based work disability (sickness absence >9 days or disability pension) due to any cause, musculoskeletal or mental disorders; retirement; death or end of follow-up (December 2011). We ran Cox proportional hazard models adjusted for behavioural, health-related and work-related covariates, and calculated synergy indices for the combined effects. When compared with those with neither exposure, HR for work disability from any cause was increased among participants with childhood adversity, with low SES, and those with both exposures. The highest hazard was observed in those with both exposures: HR 2.53, 95% CI 2.29 to 2.79 for musculoskeletal disability, 1.55, 95% CI 1.36 to 1.78 for disability due to mental disorders and 1.29, 95% CI 1.20 to 1.39 for disability due to other reasons. The synergy indices did not indicate synergistic effects. These findings indicate that childhood psychosocial adversity and low adult SES are additive risk factors for work disability. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Renal-related adverse effects of intravenous contrast media in computed tomography

PubMed Central

Leow, Kheng Song; Wu, Yi Wei; Tan, Cher Heng

2015-01-01

Renal-related adverse effects of intravascular contrast media (CM) include contrast-induced nephropathy in computed tomography and angiography. While large retrospective studies have been published, the exact pathogenesis of this condition is still unknown. We review the main international guidelines, including the American College of Radiology white paper and the guidelines of European Society of Urogenital Radiology, Royal College of Radiologists and Canadian Association of Radiologists, as well as their references, regarding this subject. We present a simplified, concise approach to renal-related adverse effects of CM, taking into consideration the basis for each recommendation in these published guidelines. This will allow the reader to better understand the rationale behind appropriate patient preparation for cross-sectional imaging. PMID:25917468

The efficacy and adverse effects of dicobalt edetate in cyanide poisoning.

PubMed

Marrs, Timothy Clive; Thompson, John Paul

2016-09-01

Dicobalt edetate is one of a number of cobalt compounds that have been studied in the treatment of cyanide poisoning, their efficacy being based upon the fact that cyanide combines with cobalt to form relatively non-toxic complexes. Inorganic cobalt salts are quite toxic (cyanide and cobalt antagonise one another's toxicity) and complexes such as dicobalt edetate were studied with the aim of identifying compounds that were less acutely toxic, but which retained the antidotal properties of cobalt salts. The proprietary preparation, Kelocyanor™, contains free cobalt and glucose as well as dicobalt edetate. The aim of this study was to evaluate the published evidence for the efficacy and adverse effects of dicobalt edetate. A Pubmed search was undertaken for the period 1961-September 2015. The search terms were "dicobalt edetate", "cobalt edetate" and "Kelocyanor", which produced 24 relevant citations. A review of the references in four relevant books (L'intoxication cyanhydrique et son traitement, Clinical and Experimental Toxicology of Cyanides, Antidotes for Poisoning by Cyanide and Antidotes) produced three further relevant papers, making a total of 27 papers. Efficacy of dicobalt edetate: There is evidence from animal pharmacodynamic studies that dicobalt edetate is an effective cyanide antidote in experimental animals. Some 39 cases of human poisoning treated with dicobalt edetate have been reported, but in only nine cases were blood cyanide concentrations measured, although administration of dicobalt edetate procured survival in four of the seven patients with concentrations in the lethal range (>3.0 mg/L). It is unlikely that death in any of the adequately documented fatal cases was attributable to treatment failure with dicobalt edetate, as it is probable that they all had suffered anoxic brain damage before treatment could be initiated. Furthermore, in one case, acute gold toxicity contributed substantially to death. Adverse effects of dicobalt edetate

Ranitidine-Associated Sleep Disturbance: Case Report and Review of H2 Antihistamine-Related Central Nervous System Adverse Effects.

PubMed

Werbel, Tyler; Cohen, Philip R

2018-04-03

Ranitidine is an H2 antihistamine used as an off-label therapy for recalcitrant verruca vulgaris. We describe a man who developed a sleep disturbance after initiating therapy with ranitidine and review similar adverse effects associated with other drugs in this class. The patient was a 40-year-old man with an eight-year history of a wart on his right plantar foot that was recalcitrant to several topical therapies. Adjunctive treatment with ranitidine 150 mg twice daily was initiated. He developed sleep disturbance with bizarre dreams and gastrointestinal symptoms. All symptoms resolved after discontinuation of the medication and recurred when he restarted the drug. PubMed was searched for the following terms: disturbance, dream, ranitidine, verruca, wart, and Zantac. The papers containing these terms and their references were reviewed. Sleep disturbance caused by ranitidine is an uncommon adverse event in patients receiving the drug. However, similar reactions have been observed with other H2 antihistamines such as cimetidine and famotidine. Clinicians should be aware that sleep disturbance secondary to ranitidine is a potential side effect of this medication.

The Italian Pharmacovigilance Program: An Observational Study of Adverse Effects of Natalizumab in Multiple Sclerosis Therapy.

PubMed

Giacoppo, Sabrina; Ruscica, Maria; Grimaldi, Luigi Maria; Bramanti, Placido; Mazzon, Emanuela

2017-09-02

BACKGROUND This study shows the results of a regional pharmacovigilance program on Natalizumab therapy in relapsing-remitting multiple sclerosis (RR-MS) patients after 3 years of experience. MATERIAL AND METHODS The primary objectives of this study were to estimate the incidence of expected and unexpected adverse effects correlated to Natalizumab therapy in a cohort of 88 RR-MS patients from Sicily, Italy, and to investigate the procedures adopted by the physicians to minimize the risk of developing severe adverse reactions correlated to Natalizumab therapy. Secondary objectives of this study were to evaluate the effectiveness of Natalizumab therapy for a careful examination of the risk/benefit ratio and to assess the actions undertaken in case of adverse reactions. RESULTS Among 88 RR-MS patients, 55.68% did not report any type of adverse reaction, 35.22% showed expected adverse reactions (58.70% slight, 22.58% moderate, and 19.35% severe), and 9.10% showed unexpected adverse effects (62.50% slight, 25.00% moderate, and 12.50% severe). Approximately 4.54% of the patients treated with Natalizumab interrupted the therapy. Overall, among all patients, 56.62% showed ameliorated condition, 32.53% had stable disease condition, and 10.85% worsened. CONCLUSIONS We provide a short overview of evidence, which may be useful to better characterize the efficacy and potential adverse effects correlated to Natalizumab therapy.

The Italian Pharmacovigilance Program: An Observational Study of Adverse Effects of Natalizumab in Multiple Sclerosis Therapy

PubMed Central

Giacoppo, Sabrina; Ruscica, Maria; Grimaldi, Luigi Maria; Bramanti, Placido; Mazzon, Emanuela

2017-01-01

Background This study shows the results of a regional pharmacovigilance program on Natalizumab therapy in relapsing-remitting multiple sclerosis (RR-MS) patients after 3 years of experience. Material/Methods The primary objectives of this study were to estimate the incidence of expected and unexpected adverse effects correlated to Natalizumab therapy in a cohort of 88 RR-MS patients from Sicily, Italy, and to investigate the procedures adopted by the physicians to minimize the risk of developing severe adverse reactions correlated to Natalizumab therapy. Secondary objectives of this study were to evaluate the effectiveness of Natalizumab therapy for a careful examination of the risk/benefit ratio and to assess the actions undertaken in case of adverse reactions. Results Among 88 RR-MS patients, 55.68% did not report any type of adverse reaction, 35.22% showed expected adverse reactions (58.70% slight, 22.58% moderate, and 19.35% severe), and 9.10% showed unexpected adverse effects (62.50% slight, 25.00% moderate, and 12.50% severe). Approximately 4.54% of the patients treated with Natalizumab interrupted the therapy. Overall, among all patients, 56.62% showed ameliorated condition, 32.53% had stable disease condition, and 10.85% worsened. Conclusions We provide a short overview of evidence, which may be useful to better characterize the efficacy and potential adverse effects correlated to Natalizumab therapy. PMID:28864818

Deferasirox, an oral iron chelator, prevents hepatocarcinogenesis and adverse effects of sorafenib

PubMed Central

Yamamoto, Naoki; Yamasaki, Takahiro; Takami, Taro; Uchida, Koichi; Fujisawa, Koichi; Matsumoto, Toshihiko; Saeki, Issei; Terai, Shuji; Sakaida, Isao

2016-01-01

Although sorafenib is expected to have a chemopreventive effect on hepatocellular carcinoma (HCC) recurrence, there are limitations to its use because of adverse effects, including effects on liver function. We have reported that the iron chelator, deferoxamine can prevent liver fibrosis and preneoplastic lesions. We investigated the influence of administering a new oral iron chelator, deferasirox (DFX), on the effects of sorafenib. We used the choline-deficient l-amino acid-defined (CDAA) diet-induced rat liver fibrosis and HCC model. We divided rats into four groups: CDAA diet only (control group), CDAA diet with sorafenib (sorafenib group), CDAA diet with DFX (DFX group), and CDAA diet with DFX and sorafenib (DFX + sorafenib group). Liver fibrosis and development of preneoplastic lesions were assessed. In addition, we assessed adverse effects such as changes in body and liver weight, skin damage (eruption, dryness, and hair loss), which is defined as hand-foot skin syndrome, in the sorafenib and DFX + sorafenib groups. The combination of DFX + sorafenib markedly prevented liver fibrosis and preneoplastic lesions better than the other treatments. Furthermore, the combination therapy significantly decreased adverse effects compared with the sorafenib group. In conclusion, the combination therapy with DFX and sorafenib may be a useful adjuvant therapy to prevent recurrence after curative treatment of HCC. PMID:27257345

Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS)

PubMed Central

Shimabukuro, Tom T.; Nguyen, Michael; Martin, David; DeStefano, Frank

2015-01-01

The Centers for Disease Control and Prevention (CDC) and the U.S. Food and Drug Administration (FDA) conduct post-licensure vaccine safety monitoring using the Vaccine Adverse Event Reporting System (VAERS), a spontaneous (or passive) reporting system. This means that after a vaccine is approved, CDC and FDA continue to monitor safety while it is distributed in the marketplace for use by collecting and analyzing spontaneous reports of adverse events that occur in persons following vaccination. Various methods and statistical techniques are used to analyze VAERS data, which CDC and FDA use to guide further safety evaluations and inform decisions around vaccine recommendations and regulatory action. VAERS data must be interpreted with caution due to the inherent limitations of passive surveillance. VAERS is primarily a safety signal detection and hypothesis generating system. Generally, VAERS data cannot be used to determine if a vaccine caused an adverse event. VAERS data interpreted alone or out of context can lead to erroneous conclusions about cause and effect as well as the risk of adverse events occurring following vaccination. CDC makes VAERS data available to the public and readily accessible online. We describe fundamental vaccine safety concepts, provide an overview of VAERS for healthcare professionals who provide vaccinations and might want to report or better understand a vaccine adverse event, and explain how CDC and FDA analyze VAERS data. We also describe strengths and limitations, and address common misconceptions about VAERS. Information in this review will be helpful for healthcare professionals counseling patients, parents, and others on vaccine safety and benefit-risk balance of vaccination. PMID:26209838

Mining adverse drug reactions from online healthcare forums using hidden Markov model.

PubMed

Sampathkumar, Hariprasad; Chen, Xue-wen; Luo, Bo

2014-10-23

Adverse Drug Reactions are one of the leading causes of injury or death among patients undergoing medical treatments. Not all Adverse Drug Reactions are identified before a drug is made available in the market. Current post-marketing drug surveillance methods, which are based purely on voluntary spontaneous reports, are unable to provide the early indications necessary to prevent the occurrence of such injuries or fatalities. The objective of this research is to extract reports of adverse drug side-effects from messages in online healthcare forums and use them as early indicators to assist in post-marketing drug surveillance. We treat the task of extracting adverse side-effects of drugs from healthcare forum messages as a sequence labeling problem and present a Hidden Markov Model(HMM) based Text Mining system that can be used to classify a message as containing drug side-effect information and then extract the adverse side-effect mentions from it. A manually annotated dataset from http://www.medications.com is used in the training and validation of the HMM based Text Mining system. A 10-fold cross-validation on the manually annotated dataset yielded on average an F-Score of 0.76 from the HMM Classifier, in comparison to 0.575 from the Baseline classifier. Without the Plain Text Filter component as a part of the Text Processing module, the F-Score of the HMM Classifier was reduced to 0.378 on average, while absence of the HTML Filter component was found to have no impact. Reducing the Drug names dictionary size by half, on average reduced the F-Score of the HMM Classifier to 0.359, while a similar reduction to the side-effects dictionary yielded an F-Score of 0.651 on average. Adverse side-effects mined from http://www.medications.com and http://www.steadyhealth.com were found to match the Adverse Drug Reactions on the Drug Package Labels of several drugs. In addition, some novel adverse side-effects, which can be potential Adverse Drug Reactions, were also

Juvenile Male Rats Exposed to a Low-Dose Mixture of Twenty-Seven Environmental Chemicals Display Adverse Health Effects

PubMed Central

Svingen, Terje; Mandrup, Karen; Skov, Kasper; Pedersen, Mikael; Frederiksen, Hanne; Frandsen, Henrik Lauritz; Vinggaard, Anne Marie

2016-01-01

Humans are exposed to a large number of environmental chemicals in their daily life, many of which are readily detectable in blood or urine. It remains uncertain if these chemicals can cause adverse health effects when present together at low doses. In this study we have tested whether a mixture of 27 chemicals administered orally to juvenile male rats for three months could leave a pathophysiological footprint. The mixture contained metals, perfluorinated compounds, PCB, dioxins, pesticides, heterocyclic amines, phthalate, PAHs and others, with a combined dose of 0.16 (Low dose), 0.47 (Mid dose) or 1.6 (High dose) mg/kg bw/day. The lowest dose was designed with the aim of obtaining plasma or urine concentrations in rats at levels approaching those observed in humans. Some single congeners were administered at doses representative of combined doses for chemical groups. With this baseline, we found effects on weight, histology and gene expression in the liver, as well as changes to the blood plasma metabolome in all exposure groups, including low-dose. Additional adverse effects were observed in the higher dosed groups, including enlarged kidneys and alterations to the metabolome. No significant effects on reproductive parameters were observed. PMID:27598887

Adverse drug effects in hospitalized elderly: Data from the Healthcare Cost and Utilization Project

PubMed Central

Shamliyan, Tatyana

2010-01-01

We aimed to analyze trends in hospital admissions due to adverse drug effects between the years 2000 to 2007 among the elderly using the National Inpatient Sample (NIS) of the Healthcare Cost and Utilization Project. We identified the discharges with the principal and all listed diagnoses related to adverse drug effects and associated hospital charges using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9) codes. Between 2000 and 2007, 321,057 patients over 65 years were discharged with a principal diagnosis related to an adverse drug effect. Hospital charges were $5,329,276,300 or $666,159,537 annual cost. The number of discharges and total hospital charges did not change over the examined years, while mean charge per discharge increased on average by $1064 ± 384 per year. Total hospital charges for drug-induced gastritis with hemorrhage increased the most by $11,206,555 per year among those 66–84 years old and by $8,646,456 per year among those older than 85 years. During 2007, 791,931 elderly had adverse treatment effects among all listed diagnoses with hospital charges of $937,795,690. Effective drug management interventions are needed to improve safety of treatments in the elderly. PMID:22291486

Safety of antipsychotics for the treatment of schizophrenia: a focus on the adverse effects of clozapine.

PubMed

De Berardis, Domenico; Rapini, Gabriella; Olivieri, Luigi; Di Nicola, Domenico; Tomasetti, Carmine; Valchera, Alessandro; Fornaro, Michele; Di Fabio, Fabio; Perna, Giampaolo; Di Nicola, Marco; Serafini, Gianluca; Carano, Alessandro; Pompili, Maurizio; Vellante, Federica; Orsolini, Laura; Martinotti, Giovanni; Di Giannantonio, Massimo

2018-05-01

Clozapine, a dibenzodiazepine developed in 1961, is a multireceptorial atypical antipsychotic approved for the treatment of resistant schizophrenia. Since its introduction, it has remained the drug of choice in treatment-resistant schizophrenia, despite a wide range of adverse effects, as it is a very effective drug in everyday clinical practice. However, clozapine is not considered as a top-of-the-line treatment because it may often be difficult for some patients to tolerate as some adverse effects can be particularly bothersome (i.e. sedation, weight gain, sialorrhea etc.) and it has some other potentially dangerous and life-threatening side effects (i.e. myocarditis, seizures, agranulocytosis or granulocytopenia, gastrointestinal hypomotility etc.). As poor treatment adherence in patients with resistant schizophrenia may increase the risk of a psychotic relapse, which may further lead to impaired social and cognitive functioning, psychiatric hospitalizations and increased treatment costs, clozapine adverse effects are a common reason for discontinuing this medication. Therefore, every effort should be made to monitor and minimize these adverse effects in order to improve their early detection and management. The aim of this paper is to briefly summarize and provide an update on major clozapine adverse effects, especially focusing on those that are severe and potentially life threatening, even if most of the latter are relatively uncommon.

DOSE CONCENTRATED COARSE PARTICULATE MATTER EXPOSURE PRODUCE ADVERSE HEALTH EFFECTS?

EPA Science Inventory

The potential for experiencing adverse health effects from particulate matter (PM) exposure is an important public health issue. Mortality associations have generally been shown to be stronger for fine PM (<2.5uM) produced by combustion processes (e.g. power plants, automobile...

Herbal remedies and their adverse effects in Tem tribe traditional medicine in Togo.

PubMed

Tchacondo, Tchadjobo; Karou, Simplice D; Batawila, Komlan; Agban, Amegninou; Ouro-Bang'na, Kawiwou; Anani, Kokou T; Gbeassor, Mensavi; de Souza, Comlan

2011-01-01

In Africa, up to 80% of the population relies on herbal concoctions for their primarily health care. In Togo, western Africa, Tem tribe is a population with old knowledge of medicinal plants, however, still very little is known about their medical practices. The present study was conducted to access for the apprehension of adverse effects of traditional remedies by Tem traditional healers (TH). Enquiry was performed by interviews with healers from August to October 2007 in Tchaoudjo prefecture (Togo). The study allowed us to interview 54 TH including 41(75.93%) males and 13(24.07%) females, who cited 102 recipes assumed to have adverse effects. The recipes were used alone to cure several diseases including haemorrhoids (22.55%), female sexual disorders and infertility (21.57%), gastrointestinal disorders (18.63%), and malaria (6.86%). A total of 34 plants belonging to 21 families were cited to be components of the recipes. Euphorbiaceae and Mimosaceae families were the most represented, however, Nauclea latifolia, Khaya senegalensis, Pseudocedrela kotschyi and Xeroderris stuhlmannii were the main components of recipes linked to adverse effects. A total of 20 adverse effects were linked to the administration of theses drugs, and among them; diarrhoea, abdominal pains, polyuria, general weakness and vomiting were the most frequently encountered. These findings were in accordance with several reports of the literature concerning medicinal plants, although they were based on empirical observations. Laboratory screenings are needed to access for the effectiveness as well as the possible toxic effects of the recipes.

Assessment of the health effects of chemicals in humans: II. Construction of an adverse effects database for QSAR modeling.

PubMed

Matthews, Edwin J; Kruhlak, Naomi L; Weaver, James L; Benz, R Daniel; Contrera, Joseph F

2004-12-01

The FDA's Spontaneous Reporting System (SRS) database contains over 1.5 million adverse drug reaction (ADR) reports for 8620 drugs/biologics that are listed for 1191 Coding Symbols for Thesaurus of Adverse Reaction (COSTAR) terms of adverse effects. We have linked the trade names of the drugs to 1861 generic names and retrieved molecular structures for each chemical to obtain a set of 1515 organic chemicals that are suitable for modeling with commercially available QSAR software packages. ADR report data for 631 of these compounds were extracted and pooled for the first five years that each drug was marketed. Patient exposure was estimated during this period using pharmaceutical shipping units obtained from IMS Health. Significant drug effects were identified using a Reporting Index (RI), where RI = (# ADR reports / # shipping units) x 1,000,000. MCASE/MC4PC software was used to identify the optimal conditions for defining a significant adverse effect finding. Results suggest that a significant effect in our database is characterized by > or = 4 ADR reports and > or = 20,000 shipping units during five years of marketing, and an RI > or = 4.0. Furthermore, for a test chemical to be evaluated as active it must contain a statistically significant molecular structural alert, called a decision alert, in two or more toxicologically related endpoints. We also report the use of a composite module, which pools observations from two or more toxicologically related COSTAR term endpoints to provide signal enhancement for detecting adverse effects.

Neurological Adverse Effects in Patients of Advanced Colorectal Carcinoma Treated with Different Schedules of FOLFOX

PubMed Central

Najam, Rahila; Mateen, Ahmed

2013-01-01

The study is designed to assess the frequency and severity of few dose limiting neurological adverse effects of four different schedules of FOLFOX. Patients with histologically confirmed advanced colorectal carcinoma (CRC) were included in the study. Toxicity was graded according to CTC v 2.0. The frequency of grade 3 and 4 adverse effects was comparatively assessed in each treatment arm. The difference in the pattern of toxicity between the treatment schedule was evaluated. The most frequent adverse symptom of neurological adverse effect was grade 1 paresthesia in the patients treated with FOLFOX4 schedule. Grade 4 peripheral neuropathy was reported in few patients of FOLFOX7 treatment arm. Frequency and onset of neurological adverse effects like paresthesia, dizziness, and hypoesthesia were significantly different (P < 0.05), whereas frequency and onset of peripheral neuropathy were highly significant (P < 0.01) in each treatment arm of FOLFOX. Peripheral neuropathy was associated with electrolyte imbalance and diabetes in few patients. Frequency of symptoms, for example, paresthesia, is associated with increased number of recurrent exposure to oxaliplatin (increased number of cycles) even at low doses (85 mg/m2), whereas severity of symptoms, for example, peripheral neuropathy, is associated with higher dose (130 mg/m2) after few treatment cycles. PMID:24187619

Judgments of cause and blame: the effects of intentionality and foreseeability.

PubMed

Lagnado, David A; Channon, Shelley

2008-09-01

What are the factors that influence everyday attributions of cause and blame? The current studies focus on sequences of events that lead to adverse outcomes, and examine people's cause and blame ratings for key events in these sequences. Experiment 1 manipulated the intentional status of candidate causes and their location in a causal chain. Participants rated intentional actions as more causal, and more blameworthy, than unintentional actions or physical events. There was also an overall effect of location, with later events assigned higher ratings than earlier events. Experiment 2 manipulated both intentionality and foreseeability. The preference for intentional actions was replicated, and there was a strong influence of foreseeability: actions were rated as more causal and more blameworthy when they were highly foreseeable. These findings are interpreted within two prominent theories of blame, [Shaver, K. G. (1985). The attribution of blame: Causality, responsibility, and blameworthiness. New York: Springer-Verlag] and [Alicke, M. D. (2000). Culpable control and the psychology of blame. Psychological Bulletin, 126, 556-574]. Overall, it is argued that the data are more consistent with Alicke's model of culpable control.

Adverse effects of homeopathy, what do we know? A systematic review and meta-analysis of randomized controlled trials.

PubMed

Stub, Trine; Musial, Frauke; Kristoffersen, Agnete A; Alræk, Terje; Liu, Jianping

2016-06-01

Homeopathy is a popular treatment modality among patient, however there is sparse research about adverse effects of homeopathy. A concept unique for homeopathy, is homeopathic aggravation that is understood as a transient worsening of the patients' symptoms before an expected improvement occurs. From a risk perspective it is vital that a distinction between homeopathic aggravations and adverse effects is established. There is a lack of systematic information on how frequent adverse effects and homeopathic aggravations are reported in studies. Therefore, a systematic review and meta-analysis were performed. Sixteen electronic databases were searched for Randomized Controlled Trials (RCTs). The searches were limited from the year 1995 to January 2011. Forty-one RCTs, with a total of 6.055 participants were included. A subtotal of 39 studies was included in the additional meta-analysis. A total of 28 trials (68%) reported adverse effects and five trials (12%) reported homeopathic aggravations. The meta-analysis (including six subgroup comparisons) demonstrated that no significant difference was found between homeopathy and control with OR 0.99, 95% CI 0.86-1.14, I(2)=54%. More than two third of the adverse effects were classified as grade 1 (68%) and two third were classified as grade 2 (25%) and grade 3 (6%) according to the Common Terminology Criteria for Adverse Effects. Homeopathic aggravation was classified as grade 1 (98%) and grade 3 (2%), suggesting that homeopathic aggravations were reported to be less severe than adverse effects. The methodological quality according to a method recommended in the Cochrane handbook for RCTs, was high. Adverse effects including the concept of homeopathic aggravations are commonly reported in trials. The meta-analysis demonstrated that the proportion of patients experiencing adverse effects to be similar for patients randomized to homeopathic treatment compared to patients randomized to placebo and conventional medicine

Maternal adverse effects of different antenatal magnesium sulphate regimens for improving maternal and infant outcomes: a systematic review

PubMed Central

2013-01-01

Background Antenatal magnesium sulphate, widely used in obstetrics to improve maternal and infant outcomes, may be associated with adverse effects for the mother sufficient for treatment cessation. This systematic review aimed to quantify maternal adverse effects attributed to treatment, assess how adverse effects vary according to different regimens, and explore women’s experiences with this treatment. Methods Bibliographic databases were searched from their inceptions to July 2012 for studies of any design that reported on maternal adverse effects associated with antenatal magnesium sulphate given to improve maternal or infant outcomes. Primary outcomes were life-threatening adverse effects of treatment (death, cardiac arrest, respiratory arrest). For randomised controlled trials, data were meta-analysed, and risk ratios (RR) pooled using fixed-effects or random-effects models. For non-randomised studies, data were tabulated by design, and presented as RR, odds ratios or percentages, and summarised narratively. Results A total of 143 publications were included (21 randomised trials, 15 non-randomised comparative studies, 32 case series and 75 reports of individual cases), of mixed methodological quality. Compared with placebo or no treatment, magnesium sulphate was not associated with an increased risk of maternal death, cardiac arrest or respiratory arrest. Magnesium sulphate significantly increased the risk of 'any adverse effects’ overall (RR 4.62, 95% CI 2.42-8.83; 4 trials, 13,322 women), and treatment cessation due to adverse effects (RR 2.77; 95% CI 2.32-3.30; 5 trials, 13,666 women). Few subgroup differences were observed (between indications for use and treatment regimens). In one trial, a lower dose regimen (2 g/3 hours) compared with a higher dose regimen (5 g/4 hours) significantly reduced treatment cessation (RR 0.05; 95% CI 0.01-0.39, 126 women). Adverse effect estimates from studies of other designs largely supported data from randomised

Effects of surface roughness on an adverse-pressure-gradient separating turbulent boundary layer

NASA Astrophysics Data System (ADS)

Wu, Wen; Piomelli, Ugo; Turbulence Simulation; Modelling Laboratory Team

2017-11-01

Separating turbulent boundary layers over smooth and rough flat plates are investigated by large-eddy simulations. A suction-blowing velocity distribution is imposed at the top boundary to produce an adverse-to-favourable pressure gradient and a closed separation bubble. Sandgrain roughness in the fully-rough regime is modelled by an immersed boundary method. In the rough-wall case, streamline detachment occurs earlier and the separation region is substantially larger due to the momentum deficit caused by the roughness. The adverse pressure gradient decreases the form drag and causes a thin reversed-flow region below the roughness crest, so that Cf = 0 does not coincide with the detachment of the flow from the surface. The wake regions behind roughness elements affect the intermittency of the near-wall flow, so that upstream of the detachment point the flow can be reversed half of the time, but its average is positive. The separated shear layer exhibits higher turbulent kinetic energy (TKE); the growth of the TKE there begins earlier relative to the separation point, and the peak TKE occurs close to the separation point. The momentum deficit caused by the roughness, again, plays a critical role in these changes. The authors acknowledge the support from Hydro-Québec and the NSERC Collaborative Research & Development program (CRDPJ 418786-11). The simulations were performed at CAC Queen't site. UP also thanks the support of Canada Research Chair Program.

CYP2C9 polymorphisms and phenytoin metabolism: implications for adverse effects.

PubMed

Franco, Valentina; Perucca, Emilio

2015-01-01

Phenytoin, a widely prescribed old-generation antiepileptic drug, requires careful individualization of dosage to compensate for its prominent pharmacokinetic variability. This article reviews the contribution of genetic polymorphisms affecting the activity of CYP2C9, the main enzyme responsible for phenytoin metabolism, to the variation in phenytoin clearance and susceptibility to adverse effects. Comprehensive and critical review of available evidence concerning the influence of CYP2C9 genetic polymorphism on phenytoin pharmacokinetic and safety profile. There is extensive evidence that CYP2C9 polymorphisms are an important determinant of the rate of phenytoin metabolism, although other factors including expression of other enzymes such as CYP2C19 and the influence of drug interactions, physiological and disease-related factors may also play a role. Patients carrying CYP2C9 genotypes associated with reduced phenytoin clearance are at greater risk of developing CNS adverse effects as well as serious cutaneous adverse reactions when given usual dosages of phenytoin. The clinical value and cost-effectiveness of CYP2C9 genotyping in improving the safety of phenytoin therapy, however, have not been clearly established and require formal testing in well-designed prospective studies.

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

PubMed

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

2017-06-01

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

Social Adversity and Antisocial Behavior: Mediating Effects of Autonomic Nervous System Activity.

PubMed

Fagan, Shawn E; Zhang, Wei; Gao, Yu

2017-11-01

The display of antisocial behaviors in children and adolescents has been of interest to criminologists and developmental psychologists for years. Exposure to social adversity is a well-documented predictor of antisocial behavior. Additionally, measures of autonomic nervous system (ANS) activity, including heart rate variability (HRV), pre-ejection period (PEP), and heart rate, have been associated with antisocial behaviors including rule-breaking and aggression. Social neuroscience research has begun to investigate how neurobiological underpinnings affect the relationship between social adversity and antisocial/psychopathic behavior in children and adolescents. This study investigated the potential mediating effects of ANS activity on the relationship between social adversity and antisocial behavior in a group of 7- to 10-year-old children from the community (N = 339; 48.2% male). Moderated multiple mediation analyses revealed that low resting heart rate, but not PEP or HRV, mediated the relationship between social adversity and antisocial behavior in males only. Social adversity but not ANS measures were associated with antisocial behavior in females. Findings have implications for understanding the neural influences that underlie antisocial behavior, illustrate the importance of the social environment regarding the expression of these behaviors, and highlight essential gender differences.

Safety of antipsychotics for the treatment of schizophrenia: a focus on the adverse effects of clozapine

PubMed Central

De Berardis, Domenico; Rapini, Gabriella; Olivieri, Luigi; Di Nicola, Domenico; Tomasetti, Carmine; Valchera, Alessandro; Fornaro, Michele; Di Fabio, Fabio; Perna, Giampaolo; Di Nicola, Marco; Serafini, Gianluca; Carano, Alessandro; Pompili, Maurizio; Vellante, Federica; Orsolini, Laura; Martinotti, Giovanni; Di Giannantonio, Massimo

2018-01-01

Clozapine, a dibenzodiazepine developed in 1961, is a multireceptorial atypical antipsychotic approved for the treatment of resistant schizophrenia. Since its introduction, it has remained the drug of choice in treatment-resistant schizophrenia, despite a wide range of adverse effects, as it is a very effective drug in everyday clinical practice. However, clozapine is not considered as a top-of-the-line treatment because it may often be difficult for some patients to tolerate as some adverse effects can be particularly bothersome (i.e. sedation, weight gain, sialorrhea etc.) and it has some other potentially dangerous and life-threatening side effects (i.e. myocarditis, seizures, agranulocytosis or granulocytopenia, gastrointestinal hypomotility etc.). As poor treatment adherence in patients with resistant schizophrenia may increase the risk of a psychotic relapse, which may further lead to impaired social and cognitive functioning, psychiatric hospitalizations and increased treatment costs, clozapine adverse effects are a common reason for discontinuing this medication. Therefore, every effort should be made to monitor and minimize these adverse effects in order to improve their early detection and management. The aim of this paper is to briefly summarize and provide an update on major clozapine adverse effects, especially focusing on those that are severe and potentially life threatening, even if most of the latter are relatively uncommon. PMID:29796248

Effect of Early Adversity and Childhood Internalizing Symptoms on Brain Structure in Young Men.

PubMed

Jensen, Sarah K G; Dickie, Erin W; Schwartz, Deborah H; Evans, C John; Dumontheil, Iroise; Paus, Tomáš; Barker, Edward D

2015-10-01

Early adversity is an important risk factor that relates to internalizing symptoms and altered brain structure. To assess the direct effects of early adversity and child internalizing symptoms (ie, depression, anxiety) on cortical gray matter (GM) volume, as well as the extent to which early adversity associates with variation in cortical GM volume indirectly via increased levels of internalizing symptoms. A prospective investigation of associations between adversity within the first 6 years of life, internalizing symptoms during childhood and early adolescence, and altered brain structure in late adolescence (age, 18-21 years) was conducted in a community-based birth cohort in England (Avon Longitudinal Study of Parents and Children). Participants from the cohort included 494 mother-son pairs monitored since the mothers were pregnant (estimated date of delivery between April 1, 1991, and December 31, 1992). Data collection for the present study was conducted between April 1, 1991, and November 30, 2010; the neuroimaging data were collected between September 1, 2010, and November 30, 2012, and data analyses for the present study occurred between January 25, 2013, and February 15, 2015. Risk factors were adversity within the first 6 years of the child's life (including prenatal exposure) and the child's internalizing symptoms between age 7 and 13 years. Early childhood adversity. The main outcome was GM volume of cortical regions previously associated with major depression measured through T1-weighted magnetic resonance images collected in late adolescence. Among 494 young men included in this analysis, early adversity was directly associated with lower GM volumes in the anterior cingulate cortex (β = -.18; P = .01) and higher GM volume in the precuneus (β = .18; P = .009). Childhood internalizing symptoms were associated with lower GM volume in the right superior frontal gyrus (β = -.20; P = .002). Early adversity was also associated with higher

Kindling of Life Stress in Bipolar Disorder: Effects of Early Adversity.

PubMed

Shapero, Benjamin G; Weiss, Rachel B; Burke, Taylor A; Boland, Elaine M; Abramson, Lyn Y; Alloy, Lauren B

2017-05-01

Most theoretical frameworks regarding the role of life stress in bipolar disorders (BD) do not incorporate the possibility of a changing relationship between psychosocial context and episode initiation across the course of the disorder. The kindling hypothesis theorizes that over the longitudinal course of recurrent affective disorders, the relationship between major life stressors and episode initiation declines (Post, 1992). The present study aimed to test an extension of the kindling hypothesis in BD by examining the effect of early life adversity on the relationship between proximal life events and prospectively assessed mood episodes. Data from 145 bipolar participants (59.3% female, 75.2% Caucasian, and mean age of 20.19 years; SD = 1.75 years) were collected as part of the Temple-Wisconsin Longitudinal Investigation of Bipolar Spectrum Project (112 Bipolar II; 33 Cyclothymic disorder). Participants completed a self-report measure of early adversity at baseline and interview-assessed mood episodes and life events at regular 4-month follow-ups. Results indicate that early childhood adversity sensitized bipolar participants to the effects of recent stressors only for depressive episodes and not hypomanic episodes within BD. This was particularly the case with minor negative events. The current study extends prior research examining the kindling model in BD using a methodologically rigorous assessment of life stressors and mood episode occurrence. Clinicians should assess experiences of early adversity in individuals with BD as it may impact reactivity to developing depressive episodes in response to future stressors. Copyright © 2017. Published by Elsevier Ltd.

Inference of chemicals that cause biological effects in treated pulp and paper mill effluent using gene expression in caged fathead minnows

EPA Science Inventory

Analytical chemistry techniques can identify chemicals present in the waters of the Great Lakes areas of concern, however it remains a challenge to identify those chemicals or classes of chemicals that actually cause adverse effects. Use of caged fathead minnows (Pimephales prome...

Risk of adverse cardiovascular outcomes and all-cause mortality associated with concomitant use of clopidogrel and proton pump inhibitors in elderly patients.

PubMed

Mahabaleshwarkar, Rohan K; Yang, Yi; Datar, Manasi V; Bentley, John P; Strum, Matthew W; Banahan, Benjamin F; Null, Kyle D

2013-04-01

To examine the effect of concomitant use of clopidogrel and PPIs in a national sample of elderly Medicare beneficiaries (age ≥65 years). A nested case-control design was employed. A cohort of Medicare beneficiaries who initiated clopidogrel and did not have any gap of ≥30 days between clopidogrel fills between July 1, 2006 and December 31, 2008 was identified from a 5% national sample of Medicare claims data. Within this cohort, cases (beneficiaries who experienced any major cardiovascular event [MCE] [acute myocardial infarction, stroke, coronary artery bypass graft, or percutaneous coronary intervention] or all-cause mortality) and controls (beneficiaries who did not experience any MCE or all-cause mortality) were identified from inpatient and outpatient claims. Cases and controls were matched on age and the time to first clopidogrel fill. Conditional logistic regression was performed on the matched sample to evaluate the association between concomitant use of clopidogrel and PPIs and adverse health outcomes (MCEs and all-cause mortality). A total of 43,159 clopidogrel users were identified. Among them, 15,415 (35.7%) received clopidogrel and a PPI concomitantly at any time during the study period, 3502 (8.1%) experienced a MCE, 7306 (17.1%) died, and a total of 9908 (22.8%) experienced the primary composite outcome (any MCE or all-cause mortality) during follow-up. The odds ratio (OR) for the primary composite outcome was 1.26 (95% confidence interval [CI]: 1.18-1.35). Secondary analyses indicated that elderly patients using clopidogrel and a PPI concomitantly were more likely to experience all-cause mortality (OR: 1.40; 95% CI: 1.29-1.53) as compared to those receiving clopidogrel only, but not MCEs (OR: 1.06; 95% CI: 0.95-1.18). Concomitant use of clopidogrel and PPIs was associated with a slightly increased risk of all-cause mortality but not MCEs.

Adverse effects of the anabolic steroid, boldenone undecylenate, on reproductive functions of male rabbits.

PubMed

Oda, Samah S; El-Ashmawy, Ibrahim M

2012-06-01

This study was conducted to evaluate the adverse effects of the anabolic steroid, boldenone undecylenate (BOL) on reproductive functions of male rabbits. Thirty white New Zealand mature male rabbits were divided into three groups (10 rabbits each). Group A rabbits served as a control group. Group B rabbits received 4.4 mg/kg body weight (bwt) BOL 5% oily solution. Group C rabbits received 8.8 mg/kg bwt BOL. Rabbits were injected intramuscularly twice weekly for two months. BOL had no significant effect on the bwt and bwt gain. Testes and epididymis weights were decreased significantly in the BOL-treated groups. BOL caused significant reduction in serum testosterone level, seminal volume, sperm motility, and sperm count. No abnormalities were detected in the sperm morphology of the BOL-treated groups. Histopathological alterations in the testes and epididymis were marked in the group C rabbits. These results indicate that administration of BOL exerts a significant harmful effect on the reproductive functions of male rabbits. © 2012 The Authors. International Journal of Experimental Pathology © 2012 International Journal of Experimental Pathology.

Adverse effects of levamisole in cocaine users: a review and risk assessment.

PubMed

Brunt, Tibor Markus; van den Berg, Jorrit; Pennings, Ed; Venhuis, Bastiaan

2017-06-01

The immunomodulatory adjuvant and antihelminth levamisole is increasingly used as an adulterant in cocaine worldwide. An accumulating body of clinical and toxicological literature has appeared since 2010 describing neutropenia, agranulocytosis, leukoencephalopathy and vasculitis in cases associated with levamisole-adulterated cocaine. Mostly, neutropenia and agranulocytosis were reported, characterized by a decimation of neutrophils. A large proportion of cases also involved vasculopathy, characterized by pronounced black and purple skin purpura with cutaneous necrosis. Females are more susceptible for both agranulocytosis and vasculitis. Another complication reported with levamisole-adulterated cocaine is leukoencephalopathy, a disabling and potentially fatal neurological disorder caused by cerebral demyelination. In this review, all adverse effects associated with therapeutic levamisole and levamisole-adulterated cocaine are described. In addition, this review provides an update of the pharmacology of levamisole, its metabolism, including toxic metabolites and metabolites that are relevant for levamisole's addition to cocaine. Special emphasis is put on the immunopathology and the dose-effect relationship of chronic levamisole exposure. Finally, a risk assessment is provided based on the current level of levamisole adulteration in street cocaine, the dose range calculated per gram and the pattern of chronic exposure in heavy or dependent users.

Cimetidine: II. Adverse reactions and patterns of use.

PubMed

Freston, J W

1982-11-01

Numerous adverse reactions have been attributed to cimetidine, which is understandable in view of the attention and scrutiny the drug has received, its widespread use, and its systemic effects. The reported frequency of side effects has differed considerably but is surprisingly low in all studies. The drug has caused an array of central nervous system disturbances, gynecomastia, and, rarely, hepatotoxicity, interstitial nephritis, bradycardia, hypotension, and even cardiac arrest. The last complication has occurred with rapid-bolus intravenous injection. Blood dyscrasias have also been rare and usually associated with serious underlying disease or multiple drugs, making it difficult to establish cause and effect in most cases. The drug is used widely to treatment conditions for which it is not approved. Some of these conditions are now believed to respond to cimetidine (gastric ulcer); others are known not to respond (acute upper gastrointestinal bleeding and acute pancreatitis).

No-go decision: A newly identified adverse event in orthopaedic surgery - causes and medico-legal implications.

PubMed

Coudane, H; Benfrech, E; Lecoq, C; Zabee, L; Tracol, P; Danan, J L; Bruno, P Y; Lighezzolo Alnot, J

2018-06-01

No-go designates a decision not to perform surgery when it becomes apparent that safety and/or feasibility requirements are not met. No-go decisions can occur at any time between patient admission to a hospital department and immediately before the first incision. The primary objective of this study was to assess the causes of no-go decisions reported as healthcare-associated adverse events (HAAEs). Most no-go decisions in orthopaedic surgery are related to problems with medical devices. A preliminary retrospective study assessed HAAEs reported over the 1-year period from 1st October 2014 to 30th September 2015, using the risk-management tool ALARM. A prospective survey was then performed by emailing a 15-item questionnaire to the 1828 members of Orthorisq (the French orthopaedic surgeon accreditation agency). Responses were either yes/no or open. Statistical comparisons were performed, using the paired Wilcoxon signed-rank test to estimate p values. Among reported HAAEs, 5.6% were no-go decisions. Of the 101 reported no-go decisions, 43.5% and 45.2% were due to problems with managing implantable medical devices in the retrospective and prospective assessments, respectively. In over 85% of cases, surgery was cancelled or postponed. Over half the no-go decisions were associated with unnecessary anaesthesia. Checklist completion was performed in only half the cases and was not associated with no-go decisions (p>0.8). This study provides descriptive data on no-go decisions in orthopaedic surgery. Healthcare professionals use many methods to enhance patient safety by preventing adverse events or diminishing their impact. Errors in managing implantable medical devices are the leading cause of no-go decisions. The current checklist is not appropriate for managing implantable medical devices in orthopaedic surgery, in part because it does not include checking devices upon receipt. Before surgery, patients should be informed of the risk of a no-go decision, since

Do environmental effects on human emotions cause cardiovascular disorders?

PubMed

Rosenman, R H

1997-01-01

Environmental influences on human health include the effects of toxic materials and adverse ecological factors. Natural milieu stressors also affect emotions that may adversely affect cardiovascular function and precipitate or otherwise contribute to complications of cardiovascular diseases. However, although variously hypothesized, there is inadequate evidence that they directly contribute to the pathogenesis of sustained hypertension or coronary atherosclerosis.

The Potential Return on Public Investment in Detecting Adverse Drug Effects

PubMed Central

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

2017-01-01

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

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

Code of Federal Regulations, 2013 CFR

2013-04-01

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

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

Code of Federal Regulations, 2012 CFR

2012-04-01

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

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

Code of Federal Regulations, 2011 CFR

2011-04-01

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

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

Code of Federal Regulations, 2014 CFR

2014-04-01

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

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

Code of Federal Regulations, 2010 CFR

2010-04-01

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

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.

A Review of Adverse Effects of Road Traffic Noise on Human Health

NASA Astrophysics Data System (ADS)

Singh, Devi; Kumari, Neeraj; Sharma, Pooja

Noise pollution due to road traffic is a potential threat to human health. Since it is a global hazard, the rapid urbanization and exponential traffic growth have aggravated the problem. Population residing along the busy traffic lanes is continuously exposed to the sound levels which are above the permissible limits. This constant exposure to noise pollution is a cause of concern as it leads to several adverse impacts on human health. Traffic noise causes irritation and annoyance, sleep disturbances, cardiovascular disease, risk of stroke, diabetes, hypertension and loss of hearing. It results in decreased work performance. The present review highlights the serious health hazards of road traffic noise (RTN) which needs to be curbed. Preventive measures of noise pollution can help in combating noise-induced health hazards and increased work performance.

More effective assessment of adverse effects and comorbidities in epilepsy: results of a Phase II communication study.

PubMed

Stern, John M; Labiner, David M; Gilliam, Frank G; Penovich, Patricia E; Onofrey, Meaghan; Eagan, Corey A; Holmes, Gregory L

2011-11-01

Research was conducted to evaluate conversations about epilepsy between community-based neurologists and patients. Adverse effects of antiepileptic drugs and mood/behavioral issues were infrequently discussed, and neurologists and patients disagreed about these issues postvisit. Follow-up research was conducted to assess the impact of a previsit assessment tool on discussions of epilepsy. Twenty neurologists reviewed a tool incorporating questions from validated instruments (Adverse Events Profile [AEP] and Neurological Disorders Depression Inventory for Epilepsy [NDDI-E]). Naturally occurring interactions between neurologists and 60 patients were recorded. Neurologists and patients were interviewed separately. All components were transcribed and analyzed using sociolinguistics. Using the previsit assessment tool increased the number of discussions about adverse effects and mood/behavioral issues and increased neurologist-patient agreement about issues postvisit. Visit length did not increase significantly when the tool was used. Ten months after follow-up research, 50% of neurologists reported continuing to use the tool in everyday practice with patients with epilepsy. Copyright © 2011 Elsevier Inc. All rights reserved.

Interstitial lung disease caused by TS-1: a case of long-term drug retention as a fatal adverse reaction.

PubMed

Park, Joong-Min; Hwang, In Gyu; Suh, Suk-Won; Chi, Kyong-Choun

2011-12-01

TS-1 is an oral anti-cancer agent for gastric cancer with a high response rate and low toxicity. We report a case of long-term drug retention of TS-1 causing interstitial lung disease (ILD) as a fatal adverse reaction. A 65-year-old woman underwent a total gastrectomy with pathologic confirmation of gastric adenocarcinoma. She received 6 cycles of TS-1 and low-dose cisplatin for post-operative adjuvant chemotherapy followed by single-agent maintenance therapy with TS-1. After 8 months, the patient complained of a productive cough with sputum and mild dyspnea. A pulmonary evaluation revealed diffuse ILD in the lung fields, bilaterally. In spite of discontinuing chemotherapy and the administration of corticosteroids, the pulmonary symptoms did not improve, and the patient died of pulmonary failure. TS-1-induced ILD can be caused by long-term drug retention that alters the lung parenchyma irreversibly, the outcome of which can be life-threatening. Pulmonary evaluation for early detection of disease is recommended.

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

PubMed Central

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

2016-01-01

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

Prevalence of Adverse Effects Post-Brachytherapy on Women with Uterine Cervix Cancer in Durango, Mexico

NASA Astrophysics Data System (ADS)

Herrera, Higmar; Yañez, Elvia; Deras, Diana C.; Reyes, Francianella

2010-12-01

This work aimed at determining the local prevalence of adverse effects on women with CaCu that recieved LDR brachytherapy treatment at CECAN. The data was extracted from the patient's and medical physics' departement records. Non Gaussian statistics was used due to dose distribution characteristics. A total of 103 patients were studied with average age of 55±13 years and Ia-IV FIGO clinical clasification. The observed prevalence is higher than that reported by other studies. It was observed that patients with proctitis were prescribed a slightly higher dose than those without adverse effects (90% confidence). Patients with proctitis also presented higher age (95% confidence) when compared with the mean of the studied population. The inverse applies to the group with other adverse effects, its average age is lower than the mean (90% confidence).

Association of adverse drug effects with subjective well-being in patients with schizophrenia receiving stable doses of risperidone.

PubMed

Kim, Jong-Hoon; Kim, Min-Jung

2009-01-01

The purpose of the present study was to examine the association of adverse drug effects with subjective well-being in patients with schizophrenia receiving stable doses of risperidone. Thirty outpatients with schizophrenia receiving stable doses of risperidone were comprehensively evaluated for psychopathology, subjective well-being, and adverse drug effects. Subjective well-being was assessed using the Subjective Well-being Under Neuroleptics Scale (SWN). Adverse drug effects were evaluated using the Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS) and the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). In correlation analysis controlling for relevant variables, the SWN score had significant negative correlations with the following subscale scores of the LUNSERS: extrapyramidal side effect (EPS) (r = -0.54, P < 0.01), akathisia (r = -0.46, P < 0.05), and autonomic adverse effect (r = -0.44, P < 0.05). The SWN score also had a significant negative correlation with the global severity of EPS as measured by the DIEPSS (r = -0.44, P < 0.05). The results of our study suggest that adverse effects, particularly EPS and akathisia, are significantly associated with subjective well-being, implying the necessity to develop rational strategies to control these variables effectively. The results also suggest that EPS and akathisia continue to be major adverse effects associated with a low level of subjective well-being in patients receiving risperidone. Further studies are required to investigate the multidimensional factors associated with subjective well-being in patients receiving atypical antipsychotics and to determine their relative contributions.

Alert Regarding Cisplatin-induced Severe Adverse Events in Cancer Patients with Xeroderma Pigmentosum.

PubMed

Sumiyoshi, Makoto; Soda, Hiroshi; Sadanaga, Noriaki; Taniguchi, Hirokazu; Ikeda, Takaya; Maruta, Hiroshi; Dotsu, Yosuke; Ogawara, Daiki; Fukuda, Yuichi; Mukae, Hiroshi

2017-01-01

Xeroderma pigmentosum (XP) is a genetic disease in which DNA repair mechanisms are impaired. Cisplatin (CDDP) exerts cytotoxic effects by forming mainly intrastrand DNA cross-links, and sensitivity to CDDP depends on the DNA repair system. Several in vitro studies have suggested that treatment with CDDP may cause enhanced adverse events as well as anti-tumor activity in cancer patients with XP. This article is the first to describe two cancer patients with XP showing severe adverse events following CDDP-based chemotherapy. Physicians should pay attention when administering CDDP in cancer patients with XP.

Adverse effects of parental zinc deficiency on metal homeostasis and embryonic development in a zebrafish model.

PubMed

Beaver, Laura M; Nkrumah-Elie, Yasmeen M; Truong, Lisa; Barton, Carrie L; Knecht, Andrea L; Gonnerman, Greg D; Wong, Carmen P; Tanguay, Robert L; Ho, Emily

2017-05-01

The high prevalence of zinc deficiency is a global public health concern, and suboptimal maternal zinc consumption has been associated with adverse effects ranging from impaired glucose tolerance to low birthweights. The mechanisms that contribute to altered development and poor health in zinc deficient offspring are not completely understood. To address this gap, we utilized the Danio rerio model and investigated the impact of dietary zinc deficiency on adults and their developing progeny. Zinc deficient adult fish were significantly smaller in size, and had decreases in learning and fitness. We hypothesized that parental zinc deficiency would have an impact on their offspring's mineral homeostasis and embryonic development. Results from mineral analysis showed that parental zinc deficiency caused their progeny to be zinc deficient. Furthermore, parental dietary zinc deficiency had adverse consequences for their offspring including a significant increase in mortality and decreased physical activity. Zinc deficient embryos had altered expression of genes that regulate metal homeostasis including several zinc transporters (ZnT8, ZnT9) and the metal-regulatory transcription factor 1 (MTF-1). Zinc deficiency was also associated with decreased expression of genes related to diabetes and pancreatic development in the embryo (Insa, Pax4, Pdx1). Decreased expression of DNA methyltransferases (Dnmt4, Dnmt6) was also found in zinc deficient offspring, which suggests that zinc deficiency in parents may cause altered epigenetic profiles for their progeny. These data should inform future studies regarding zinc deficiency and pregnancy and suggest that supplementation of zinc deficient mothers prior to pregnancy may be beneficial. Published by Elsevier Inc.

Adverse effects of parental zinc deficiency on metal homeostasis and embryonic development in a zebrafish model

PubMed Central

Beaver, Laura M.; Nkrumah-Elie, Yasmeen M.; Truong, Lisa; Barton, Carrie L.; Knecht, Andrea L.; Gonnerman, Greg D.; Wong, Carmen P.; Tanguay, Robert L.; Ho, Emily

2017-01-01

The high prevalence of zinc deficiency is a global public health concern, and suboptimal maternal zinc consumption has been associated with adverse effects ranging from impaired glucose tolerance to low birthweights. The mechanisms that contribute to altered development and poor health in zinc deficient offspring are not completely understood. To address this gap, we utilized the Danio rerio model and investigated the impact of dietary zinc deficiency on adults and their developing progeny. Zinc deficient adult fish were significantly smaller in size, and had decreases in learning and fitness. We hypothesized that parental zinc deficiency would have an impact on their offspring’s mineral homeostasis and embryonic development. Results from mineral analysis showed that parental zinc deficiency caused their progeny to be zinc deficient. Furthermore, parental dietary zinc deficiency had adverse consequences for their offspring including a significant increase in mortality and decreased physical activity. Zinc deficient embryos had altered expression of genes that regulate metal homeostasis including several zinc transporters (ZnT8, ZnT9) and the metal-regulatory transcription factor 1 (MTF-1). Zinc deficiency was also associated with decreased expression of genes related to diabetes and pancreatic development in the embryo (Insa, Pax4, Pdx1). Decreased expression of DNA methyltransferases (Dnmt4, Dnmt6) was also found in zinc deficient offspring, which suggests that zinc deficiency in parents may cause altered epigenetic profiles for their progeny. These data should inform future studies regarding zinc deficiency and pregnancy and suggest that supplementation of zinc deficient mothers prior to pregnancy may be beneficial. PMID:28268202

Cutaneous Adverse Effects of Neurologic Medications.

PubMed

Bahrani, Eman; Nunneley, Chloe E; Hsu, Sylvia; Kass, Joseph S

2016-03-01

Life-threatening and benign drug reactions occur frequently in the skin, affecting 8 % of the general population and 2-3 % of all hospitalized patients, emphasizing the need for physicians to effectively recognize and manage patients with drug-induced eruptions. Neurologic medications represent a vast array of drug classes with cutaneous side effects. Approximately 7 % of the United States (US) adult population is affected by adult-onset neurological disorders, reflecting a large number of patients on neurologic drug therapies. This review elucidates the cutaneous reactions associated with medications approved by the US Food and Drug Administration (FDA) to treat the following neurologic pathologies: Alzheimer disease, amyotrophic lateral sclerosis, epilepsy, Huntington disease, migraine, multiple sclerosis, Parkinson disease, and pseudobulbar affect. A search of the literature was performed using the specific FDA-approved drug or drug classes in combination with the terms 'dermatologic,' 'cutaneous,' 'skin,' or 'rash.' Both PubMed and the Cochrane Database of Systematic Reviews were utilized, with side effects ranging from those cited in randomized controlled trials to case reports. It behooves neurologists, dermatologists, and primary care physicians to be aware of the recorded cutaneous adverse reactions and their severity for proper management and potential need to withdraw the offending medication.

[Intestinal cleaning for colonoscopy in children: effectiveness, adherence and adverse effects of schemes differentiated by age].

PubMed

Miquel, Isabel; Arancibia, María Eugenia; Alliende, Francisco; Ríos, Gloria; Rodríguez, Lorena; Lucero, Yalda; Saelzer, Eric

2017-04-01

Adequate intestinal cleanliness is crucial to achieve optimal colonoscopy performance. Several bowel preparation (BP) schemes have been proposed, but there is still no consensus as regards which is the most suitable in paediatric patients. To describe the effectiveness, adherence, and adverse effects of BP protocols differentiated by age group in paediatric patients subjected to colonoscopy. Prospective, study that included patients < 18 years subjected to colonoscopy. BP protocols differentiated by age group were indicated as follows: < 6 m (glycerine suppository); 6 m-3y 11 m (poly-ethylene-glycol (PEG 3350 without electrolytes); 4y-9y 11 m (PEG 3350 without electrolytes + bisacodyl); 10 y-18 y (PEG 3350 with electrolytes). Demographic, clinical information, adherence and adverse effects were registered. Effectiveness was determined using a validated scale (Boston modified) during colonoscopy. A total of 159 patients were included, of which 87 (55%) were males, and with a median age of 4 years (range 1 m-17 years). Seventy eight percent of patients achieved successful BP. The higher effectiveness was observed in the groups of < 6 m (96%) and 10-18 y (91%). Constipation was significantly more frequent (29%) in the 4 yo-9 yo 11 m in which lower effectiveness was observed (69%). Good adherence was observed in 87% of patients. Adverse effects were observed in a third of patients, although they were mild and did not lead to the suspension of the BP. Satisfactory results were achieved with the BP schemes used, with a successful BP being obtained in 4 out of 5 patients. Results were different between groups, which is probably related to previous bowel transit and indicated medication.

Efficacy and adverse effects of medical marijuana for chronic noncancer pain

PubMed Central

Deshpande, Amol; Mailis-Gagnon, Angela; Zoheiry, Nivan; Lakha, Shehnaz Fatima

2015-01-01

Abstract Objective To determine if medical marijuana provides pain relief for patients with chronic noncancer pain (CNCP) and to determine the therapeutic dose, adverse effects, and specific indications. Data sources In April 2014, MEDLINE and EMBASE searches were conducted using the terms chronic noncancer pain, smoked marijuana or cannabinoids, placebo and pain relief, or side effects or adverse events. Study selection An article was selected for inclusion if it evaluated the effect of smoked or vaporized cannabinoids (nonsynthetic) for CNCP; it was designed as a controlled study involving a comparison group, either concurrently or historically; and it was published in English in a peer-review journal. Outcome data on pain, function, dose, and adverse effects were collected, if available. All articles that were only available in abstract form were excluded. Synthesis A total of 6 randomized controlled trials (N = 226 patients) were included in this review; 5 of them assessed the use of medical marijuana in neuropathic pain as an adjunct to other concomitant analgesics including opioids and anticonvulsants. The 5 trials were considered to be of high quality; however, all of them had challenges with masking. Data could not be pooled owing to heterogeneity in delta-9-tetrahydrocannabinol potency by dried weight, differing frequency and duration of treatment, and variability in assessing outcomes. All experimental sessions in the studies were of short duration (maximum of 5 days) and reported statistically significant pain relief with nonserious side effects. Conclusion There is evidence for the use of low-dose medical marijuana in refractory neuropathic pain in conjunction with traditional analgesics. However, trials were limited by short duration, variability in dosing and strength of delta-9-tetrahydrocannabinol, and lack of functional outcomes. Although well tolerated in the short term, the long-term effects of psychoactive and neurocognitive effects of medical

A systematic review of possible serious adverse health effects of nicotine replacement therapy.

PubMed

Lee, Peter N; Fariss, Marc W

2017-04-01

We conducted a systematic literature review to identify and critically evaluate studies of serious adverse health effects (SAHEs) in humans using nicotine replacement therapy (NRT) products. Serious adverse health effects refer to adverse events, leading to substantial disruption of the ability to conduct normal life functions. Strength of evidence evaluations and conclusions were also determined for the identified SAHEs. We evaluated 34 epidemiological studies and clinical trials, relating NRT use to cancer, reproduction/development, CVD, stroke and/or other SAHEs in patients, and four meta-analyses on effects in healthy populations. The overall evidence suffers from many limitations, the most significant being the short-term exposure (≤12 weeks) and follow-up to NRT product use in most of the studies, the common failure to account for changes in smoking behaviour following NRT use, and the sparse information on SAHEs by type of NRT product used. The only SAHE from NRT exposure we identified was an increase in respiratory congenital abnormalities reported in one study. Limited evidence indicated a lack of effect between NRT exposure and SAHEs for CVD and various reproduction/developmental endpoints. For cancer, stroke and other SAHEs, the evidence was inadequate to demonstrate any association with NRT use. Our conclusions agree with recent statements from authoritative bodies.

Mefloquine adverse effects with atypical facial lesions in an overweight patient.

PubMed

Descloux, Elodie; De Monbrison, Frédérique; Basselin, Cécile; Vial, Thierry; Peyron, François

2010-09-01

The recommended dosage of mefloquine to treat Plasmodium falciparum infection is 25 mg/kg, with no recommendation for dosage exceeding 1500 mg. We describe an original case of adverse reaction to mefloquine in an overweight patient. Case report. A 32-year-old woman weighing 139 kg presented with uncomplicated P. falciparum infection after returning from Cameroon. She received 3250 mg of mefloquine (i.e. 23 mg/kg) administered in four doses. On day 2, she developed neuropsychiatric disorders and facial lesions. Nasal mucocutaneous vesicles and bullae, depressive mood, mild thrombocytopenia and hepatic cytolysis were evidenced. Parasitemia was negative. Recovery was complete on day 17. High mefloquine serum levels were measured (8.030 mg/L on day 3, 6.880 mg/L on day 8, and 3.370 mg/L on day 17). The causal relationship between mefloquine and the occurrence of these adverse effects is probable. However, as no viral or bacteriological investigations were performed, the drug responsibility remains uncertain. Mefloquine-induced bullous and facial lesions reversible upon drug withdrawal have already been described. The associated neuropsychiatric symptoms were strongly suggestive of mefloquine adverse effects, as such events are more frequently observed in cases of overdosage. Our case emphasizes the difficulties of dosage adaptation in overweight patients. Copyright © 2010 Elsevier Ltd. All rights reserved.

Adverse effect versus quality control of the Fuenzalida-Palacios antirabies vaccine.

PubMed

Nogueira, Y L

1998-01-01

We evaluated the components of the Fuenzalida-Palacios antirabies vaccine, which is till used in most developing countries in human immunization for treatment and prophylaxis. This vaccine is prepared from newborn mouse brains at 1% concentration. Even though the vaccine is considered to have a low myelin content, it is not fully free of myelin or of other undesirable components that might trigger adverse effects after vaccination. The most severe effect is a post-vaccination neuroparalytic accident associated with Guillain-Barré syndrome. In the present study we demonstrate how the vaccines produced and distributed by different laboratories show different component patterns with different degrees of impurity and with varying protein concentrations, indicating that production processes can vary from one laboratory to another. These differences, which could be resolved using a better quality control process, may affect and impair immunization, with consequent risks and adverse effects after vaccination. We used crossed immunoelectrophoresis to evaluate and demonstrate the possibility of quality control in vaccine production, reducing the risk factors possibly involved in these immunizing products.

Possible adverse effects of frying with vegetable oils.

PubMed

Dobarganes, Carmen; Márquez-Ruiz, Gloria

2015-04-01

The question of whether heated fats in the diet may be detrimental to health is nowadays of the upmost concern, but finding an answer is not easy and requires careful consideration of different aspects of lipid oxidation. This review is divided into two sections. The first part deals with the nature of the new compounds formed at high temperature in the frying process as well as their occurrence in the diet while the second part focuses on their possible nutritional and physiological effects. Oxidation products present in abused frying fats and oils are the compounds most suspected of impairing the nutritional properties of the oils or involving adverse physiological effects. The recent studies on their health implications include those related to their fate and those focused on their effects in metabolic pathways and the most prevalent diseases.

Prevalence of Adverse Effects Post-Brachytherapy on Women with Uterine Cervix Cancer in Durango, Mexico

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

Herrera, Higmar; Yanez, Elvia; Deras, Diana C.

2010-12-07

This work aimed at determining the local prevalence of adverse effects on women with CaCu that recieved LDR brachytherapy treatment at CECAN. The data was extracted from the patient's and medical physics' departement records. Non Gaussian statistics was used due to dose distribution characteristics. A total of 103 patients were studied with average age of 55{+-}13 years and Ia-IV FIGO clinical clasification. The observed prevalence is higher than that reported by other studies. It was observed that patients with proctitis were prescribed a slightly higher dose than those without adverse effects (90% confidence). Patients with proctitis also presented higher agemore » (95% confidence) when compared with the mean of the studied population. The inverse applies to the group with other adverse effects, its average age is lower than the mean (90% confidence).« less

Management of common adverse effects in the era of highly active antiretroviral therapy in south east Ethiopia

PubMed Central

Abdella, Sadikalmahdi Hussen; Wabe, Nasir Tajure; Yesuf, Elias Ali

2011-01-01

Background: The combination of antiretroviral therapy is the corner stone of management of patients with human immune deficiency virus infection. Although antiretroviral therapy can reduce viral load to undetectable level, improve the immunity and prolong survival of patients, antiretroviral drugs are associated with many adverse effects that may be severe and affect patient adherence and quality of life. Aims: The aim of this study was to assess management strategies under taken in patient's experienced common adverse effects of highly active antiretroviral therapy in Goba Hospital antiretroviral clinic. Patients and Methods: A cross sectional study of patient record chart of patients who had follow-up during data collection period was done followed by patient interview. Data was filled on well structured questionnaire and analyzed using SPSS for window version 16.0. Results: The common adverse effects were Rash (48.8%), Peripheral neuropathy (36.9%) and Anemia (20.24%). The rate of management was 39.3%. Pyridoxine (36.8%) was commonly prescribed drug for management of Peripheral neuropathy. Chlorphenarimine gel and Iron gluconate were common drugs for management of Rash and Anemia respectively. Use of traditional healers (57.7%) was leading reason for non-management. Conclusion: Rate of management for common adverse effect is low. Education should be given on adverse effects for patients. PMID:22361495

A continuous GRASP to determine the relationship between drugs and adverse reactions

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

Hirsch, Michael J.; Meneses, Claudio N.; Pardalos, Panos M.

2007-11-05

Adverse drag reactions (ADRs) are estimated to be one of the leading causes of death. Many national and international agencies have set up databases of ADR reports for the express purpose of determining the relationship between drugs and adverse reactions that they cause. We formulate the drug-reaction relationship problem as a continuous optimization problem and utilize C-GRASP, a new continuous global optimization heuristic, to approximately determine the relationship between drugs and adverse reactions. Our approach is compared against others in the literature and is shown to find better solutions.

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

PubMed

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

2012-11-01

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

Systematic Review of Adverse Effects: A Further Step towards Modernization of Acupuncture in China

PubMed Central

Wu, Junyi; Hu, Yanmei; Zhu, Yin; Yin, Ping; Xu, Shifen

2015-01-01

As a further step towards the modernization of acupuncture, the objective of this review was to figure out the frequency and severity of adverse complications and events in acupuncture treatment reported from 1980 to 2013 in China. All first-hand case reports of acupuncture-related complications and adverse events that could be identified in the scientific literature were reviewed and classified according to the type of complication and adverse event, circumstance of the event, and long-term patient outcome. The selected case reports were published between 1980 and 2013 in 3 databases. Relevant papers were collected and analyzed by 2 reviewers. Over the 33 years, 182 incidents were identified in 133 relevant papers. Internal organ, tissue, or nerve injury is the main complications of acupuncture especially for pneumothorax and central nervous system injury. Adverse effects also included syncope, infections, hemorrhage, allergy, burn, aphonia, hysteria, cough, thirst, fever, somnolence, and broken needles. Qualifying training of acupuncturists should be systemized and the clinical acupuncture operations should be standardized in order to effectively prevent the occurrence of acupuncture accidents, enhance the influence of acupuncture, and further popularize acupuncture to the rest of the world. PMID:26339265

Confounding and Statistical Significance of Indirect Effects: Childhood Adversity, Education, Smoking, and Anxious and Depressive Symptomatology.

PubMed

Sheikh, Mashhood Ahmed

2017-01-01

The life course perspective, the risky families model, and stress-and-coping models provide the rationale for assessing the role of smoking as a mediator in the association between childhood adversity and anxious and depressive symptomatology (ADS) in adulthood. However, no previous study has assessed the independent mediating role of smoking in the association between childhood adversity and ADS in adulthood. Moreover, the importance of mediator-response confounding variables has rarely been demonstrated empirically in social and psychiatric epidemiology. The aim of this paper was to (i) assess the mediating role of smoking in adulthood in the association between childhood adversity and ADS in adulthood, and (ii) assess the change in estimates due to different mediator-response confounding factors (education, alcohol intake, and social support). The present analysis used data collected from 1994 to 2008 within the framework of the Tromsø Study ( N = 4,530), a representative prospective cohort study of men and women. Seven childhood adversities (low mother's education, low father's education, low financial conditions, exposure to passive smoke, psychological abuse, physical abuse, and substance abuse distress) were used to create a childhood adversity score. Smoking status was measured at a mean age of 54.7 years (Tromsø IV), and ADS in adulthood was measured at a mean age of 61.7 years (Tromsø V). Mediation analysis was used to assess the indirect effect and the proportion of mediated effect (%) of childhood adversity on ADS in adulthood via smoking in adulthood. The test-retest reliability of smoking was good (Kappa: 0.67, 95% CI: 0.63; 0.71) in this sample. Childhood adversity was associated with a 10% increased risk of smoking in adulthood (Relative risk: 1.10, 95% CI: 1.03; 1.18), and both childhood adversity and smoking in adulthood were associated with greater levels of ADS in adulthood ( p < 0.001). Smoking in adulthood did not significantly mediate the

Confounding and Statistical Significance of Indirect Effects: Childhood Adversity, Education, Smoking, and Anxious and Depressive Symptomatology

PubMed Central

Sheikh, Mashhood Ahmed

2017-01-01

The life course perspective, the risky families model, and stress-and-coping models provide the rationale for assessing the role of smoking as a mediator in the association between childhood adversity and anxious and depressive symptomatology (ADS) in adulthood. However, no previous study has assessed the independent mediating role of smoking in the association between childhood adversity and ADS in adulthood. Moreover, the importance of mediator-response confounding variables has rarely been demonstrated empirically in social and psychiatric epidemiology. The aim of this paper was to (i) assess the mediating role of smoking in adulthood in the association between childhood adversity and ADS in adulthood, and (ii) assess the change in estimates due to different mediator-response confounding factors (education, alcohol intake, and social support). The present analysis used data collected from 1994 to 2008 within the framework of the Tromsø Study (N = 4,530), a representative prospective cohort study of men and women. Seven childhood adversities (low mother's education, low father's education, low financial conditions, exposure to passive smoke, psychological abuse, physical abuse, and substance abuse distress) were used to create a childhood adversity score. Smoking status was measured at a mean age of 54.7 years (Tromsø IV), and ADS in adulthood was measured at a mean age of 61.7 years (Tromsø V). Mediation analysis was used to assess the indirect effect and the proportion of mediated effect (%) of childhood adversity on ADS in adulthood via smoking in adulthood. The test-retest reliability of smoking was good (Kappa: 0.67, 95% CI: 0.63; 0.71) in this sample. Childhood adversity was associated with a 10% increased risk of smoking in adulthood (Relative risk: 1.10, 95% CI: 1.03; 1.18), and both childhood adversity and smoking in adulthood were associated with greater levels of ADS in adulthood (p < 0.001). Smoking in adulthood did not significantly mediate the

Adverse effects of MWCNTs on life parameters, antioxidant systems, and activation of MAPK signaling pathways in the copepod Paracyclopina nana.

PubMed

Kim, Duck-Hyun; Puthumana, Jayesh; Kang, Hye-Min; Lee, Min-Chul; Jeong, Chang-Bum; Han, Jeonghoon; Hwang, Dae-Sik; Kim, Il-Chan; Lee, Jin Wuk; Lee, Jae-Seong

2016-10-01

Engineered multi-walled carbon nanotubes (MWCNTs) have received widespread applications in a broad variety of commercial products due to low production cost. Despite their significant commercial applications, CNTs are being discharged to aquatic ecosystem, leading a threat to aquatic life. Thus, we investigated the adverse effect of CNTs on the marine copepod Paracyclopina nana. Additional to the study on the uptake of CNTs and acute toxicity, adverse effects on life parameters (e.g. growth, fecundity, and size) were analyzed in response to various concentrations of CNTs. Also, as a measurement of cellular damage, oxidative stress-related markers were examined in a time-dependent manner. Moreover, activation of redox-sensitive mitogen-activated protein kinase (MAPK) signaling pathways along with the phosphorylation pattern of extracellular signal-regulated kinase (ERK), p38, and c-Jun-N-terminal kinases (JNK) were analyzed to obtain a better understanding of molecular mechanism of oxidative stress-induced toxicity in the copepod P. nana. As a result, significant inhibition on life parameters and evoked antioxidant systems were observed without ROS induction. In addition, CNTs activated MAPK signaling pathway via ERK, suggesting that phosphorylated ERK (p-ERK)-mediated adverse effects are the primary cause of in vitro and in vivo endpoints in response to CNTs exposure. Moreover, ROS-independent activation of MAPK signaling pathway was observed. These findings will provide a better understanding of the mode of action of CNTs on the copepod P. nana at cellular and molecular level and insight on possible ecotoxicological implications in the marine environment. Copyright © 2016 Elsevier B.V. All rights reserved.

Adulthood Stressors, History of Childhood Adversity, and Risk of Perpetration of Intimate Partner Violence

PubMed Central

Roberts, Andrea L.; McLaughlin, Katie A.; Conron, Kerith J.; Koenen, Karestan C.

2010-01-01

Background Over half a million U.S. women and more than 100,000 men are treated for injuries from intimate partner violence (IPV) annually, making IPV perpetration a major public health problem. However, little is known about causes of perpetration across the life course. Purpose This paper examines the role of “stress sensitization,” whereby adult stressors increase risk for IPV perpetration most strongly in people with a history of childhood adversity. Methods The study investigated a possible interaction effect between adulthood stressors and childhood adversities in risk of IPV perpetration, specifically, whether the difference in risk of IPV perpetration associated with past-year stressors varied by history of exposure to childhood adversity. Analyses were conducted in 2010 using de-identified data from 34,653 U.S. adults from the 2004–2005 follow-up wave of the National Epidemiologic Survey on Alcohol and Related Conditions. Results There was a significant stress sensitization effect. For men with high-level childhood adversity, past-year stressors were associated with an 8.8% increased risk of perpetrating compared to a 2.3% increased risk among men with low-level adversity. Women with high-level childhood adversity had a 14.3% increased risk compared with a 2.5% increased risk in the low-level adversity group. Conclusions Individuals with recent stressors and histories of childhood adversity are at particularly elevated risk of IPV perpetration; therefore, prevention efforts should target this population. Treatment programs for IPV perpetrators, which have not been effective in reducing risk of perpetrating, may benefit from further investigating the role of stress and stress reactivity in perpetration. PMID:21238860

[Adverse effects of seasonal flu vaccine and new influenza A (H1N1) vaccine in health care workers].

PubMed

Torruella, Joan Inglés; Soto, Rosa Gil; Valls, Rosa Carreras; Lozano, Judit Valverde; Carreras, Dolors Benito; Cunillera, Arnau Besora

2013-01-01

To assess and compare adverse effects of Seasonal Influenza Vaccine (SIV) and new Influenza A(H1N1) Vaccine (AIV) in health care workers. Multicenter cross-sectional study in health care workers from acute care hospitals, primary health care centers, social centers, mental health centers and a geriatric hospital participating in the 2009 vaccination campaign. Self-administered questionnaires were sent to all workers vaccinated with SIV and/or AIV. 527 valid questionnaires were collected out of 1123 sent to SIV vaccinated workers (46.9%), and 241 out of 461 sent to AIV vaccinated workers (52.%%). Participant workers include 527 vaccinated only with SIV, 117 first vaccinated with SIV and later with AIV (SIV+AIV), and 125 vaccinated only with AIV. Overall, 18.4% (95%CI 15.1-21.7) of workers vaccinated only with SIV reported adverse effects, as compared to 45.3% (95I 36.3-54.3) reporting adverse effects to AIV in the SIV+AIV group and 46.4% (95%CI 37.7-55.1) of workers vaccinated only with AIV. In all participants the most common adverseeffect was a local reaction. Women wre more reactive to both SIV and AIV than men. In all age groups SIV vaccination alone caused fewer reactions that either AIV only or the combination of SIV+AIV, with the exception of workers below 29 years of age. AIV was associated with more reactions than SIV, with no differences observed in relation to administration sequence. There were differences by sex and age, but reactions always occurred more commonly with AIV. Copyright belongs to the Societat Catalana de Seguretat i Medicina del Treball.

Effect of Two Different Methods of Initiating Atomoxetine on the Adverse Event Profile of Atomoxetine

ERIC Educational Resources Information Center

Greenhill, Laurence L.; Newcorn, Jeffrey H.; Gao, Haitao; Feldman, Peter D.

2007-01-01

Objective: To compare the effects of two different methods for initiating atomoxetine in terms of the incidence of early adverse events. Method: Data on atomoxetine treatment-emergent adverse events in youths, ages 6 to 18 years, were analyzed from five randomized, double-blind, placebo-controlled, acute-phase studies. Two studies involve…

Separate and cumulative effects of adverse childhood experiences in predicting adult health and health care utilization.

PubMed

Chartier, Mariette J; Walker, John R; Naimark, Barbara

2010-06-01

Objectives of this population-based study were: (1) to examine the relative contribution of childhood abuse and other adverse childhood experiences to poor adult health and increased health care utilization and (2) to examine the cumulative effects of adverse childhood experiences on adult health and health care utilization. Data from the Ontario Health Survey, a representative population sample (n=9,953) of respondents aged 15 years and older, were analyzed using logistic regression. Adverse childhood experiences examined were childhood physical and sexual abuse, parental marital conflict, poor parent-child relationship, low parental education and parental psychopathology. Most (72%) respondents reported at least one adverse childhood experience and a considerable proportion of respondents (37%) reported two or more of these experiences. In examining the bivariate models, childhood physical and sexual abuse had a stronger influence than other types of adverse childhood experiences. With the addition of other adverse childhood experiences in the model, the odds ratios for childhood abuse were attenuated but remained statistically significant for most health outcomes. This suggests that childhood abuse may have a unique adverse influence on the development of poor adult health. When an aggregate variable was created to explore the cumulative effects of adverse childhood experience, the odds were increased, with each additional experience, for reporting multiple health problems [odds ratio (OR): 1.22], poor self-rated health (OR: 1.18), pain (OR: 1.24), disability (OR: 1.24), general practitioner use (OR: 1.12), emergency room use (OR: 1.29) and health professional use (OR: 1.19). This study suggests that childhood abuse and other adverse childhood experiences are overlapping risk factors for long-term adult health problems and that the accumulation of these adverse experiences increases the risk of poor adult health. This study highlights the importance of the many

Cancer in working-age is not associated with childhood adversities.

PubMed

Korpimäki, Sonja K; Sumanen, Markku P T; Sillanmäki, Lauri H; Mattila, Kari J

2010-05-01

Early life events are studied as potential causes of cancer. The objective here was to study childhood adversities in the etiology of cancer. The material comprised a population based random sample of 25 898 individuals among the Finnish working-aged population. In 1998 they were requested through six questions in a postal questionnaire to recall their childhood adversities. The cases consisted of people with cancer diagnosed 2000-2006 and registered in the Finnish Cancer Registry (n = 384). The rest of the sample consisted of cancer-free controls. The most common adversities were prolonged financial difficulties, serious conflicts in the family and someone in the family having been seriously or chronically ill. The cancer patients reported more prolonged financial difficulties and someone seriously or chronically ill in the family. They reported less parental divorce than the controls. The associations were not statistically significant after adjusting for age, sex, education, and health behaviour. Nor was there a significant difference in the total number of childhood adversities between the study group and the controls. On the whole, these cancer patients had not experienced more childhood adversities than the controls. According to our findings, there is no cause to attribute development of cancer in working age to childhood adversities. This information may also give relief to other family members.

A joint ERS/ATS policy statement: what constitutes an adverse health effect of air pollution? An analytical framework.

PubMed

Thurston, George D; Kipen, Howard; Annesi-Maesano, Isabella; Balmes, John; Brook, Robert D; Cromar, Kevin; De Matteis, Sara; Forastiere, Francesco; Forsberg, Bertil; Frampton, Mark W; Grigg, Jonathan; Heederik, Dick; Kelly, Frank J; Kuenzli, Nino; Laumbach, Robert; Peters, Annette; Rajagopalan, Sanjay T; Rich, David; Ritz, Beate; Samet, Jonathan M; Sandstrom, Thomas; Sigsgaard, Torben; Sunyer, Jordi; Brunekreef, Bert

2017-01-01

The American Thoracic Society has previously published statements on what constitutes an adverse effect on health of air pollution in 1985 and 2000. We set out to update and broaden these past statements that focused primarily on effects on the respiratory system. Since then, many studies have documented effects of air pollution on other organ systems, such as on the cardiovascular and central nervous systems. In addition, many new biomarkers of effects have been developed and applied in air pollution studies.This current report seeks to integrate the latest science into a general framework for interpreting the adversity of the human health effects of air pollution. Rather than trying to provide a catalogue of what is and what is not an adverse effect of air pollution, we propose a set of considerations that can be applied in forming judgments of the adversity of not only currently documented, but also emerging and future effects of air pollution on human health. These considerations are illustrated by the inclusion of examples for different types of health effects of air pollution. Copyright ©ERS 2017.

A joint ERS/ATS policy statement: what constitutes an adverse health effect of air pollution? An analytical framework

PubMed Central

Thurston, George D.; Kipen, Howard; Annesi-Maesano, Isabella; Balmes, John; Brook, Robert D.; Cromar, Kevin; De Matteis, Sara; Forastiere, Francesco; Forsberg, Bertil; Frampton, Mark W.; Grigg, Jonathan; Heederik, Dick; Kelly, Frank J.; Kuenzli, Nino; Laumbach, Robert; Peters, Annette; Rajagopalan, Sanjay T.; Rich, David; Ritz, Beate; Samet, Jonathan M.; Sandstrom, Thomas; Sigsgaard, Torben; Sunyer, Jordi; Brunekreef, Bert

2017-01-01

The American Thoracic Society has previously published statements on what constitutes an adverse effect on health of air pollution in 1985 and 2000. We set out to update and broaden these past statements that focused primarily on effects on the respiratory system. Since then, many studies have documented effects of air pollution on other organ systems, such as on the cardiovascular and central nervous systems. In addition, many new biomarkers of effects have been developed and applied in air pollution studies. This current report seeks to integrate the latest science into a general framework for interpreting the adversity of the human health effects of air pollution. Rather than trying to provide a catalogue of what is and what is not an adverse effect of air pollution, we propose a set of considerations that can be applied in forming judgments of the adversity of not only currently documented, but also emerging and future effects of air pollution on human health. These considerations are illustrated by the inclusion of examples for different types of health effects of air pollution. PMID:28077473

[Analgesics in geriatric patients. Adverse side effects and interactions].

PubMed

Gosch, Markus

2015-07-01

Pain is a widespread symptom in clinical practice. Older adults and chronically ill patients are particularly affected. In multimorbid geriatric patients, pharmacological pain treatment is an extension of a previously existing multimedication. Besides the efficacy of pain treatment, drug side effects and drug-drug interactions have to be taken into account to minimize the health risk for these patients. Apart from the number of prescriptions, the age-related pharmacokinetic and pharmacodynamic changes significantly increase the risk among older adults. The use of non-steroidal anti-inflammatory drugs (NSAID) is widespread but NSAIDs have the highest risk of adverse drug reactions and drug interactions. In particular, the gastrointestinal, cardiovascular, renal and coagulation systems are affected. Apart from the known toxic effect on the liver (in high doses), paracetamol (acetaminophen) has similar risks although to a lesser degree. According to current data, metamizol is actually better than its reputation suggests. The risk of potential drug interactions seems to be low. Apart from the risk of sedation in combination with other drugs, tramadol and other opioids can induce the serotonin syndrome. Among older adults, especially in the case of polypharmacy, an individualized approach should be considered instead of sticking to the pain management recommended by the World Health Organization (WHO) in order to minimize drug-drug interactions and adverse drug reactions.

Tanning accelerators: prevalence, predictors of use, and adverse effects.

PubMed

Herrmann, Jennifer L; Cunningham, Rachel; Cantor, Alan; Elewski, Boni E; Elmets, Craig A

2015-01-01

Tanning accelerators are topical products used by indoor tanners to augment and hasten the tanning process. These products contain tyrosine, psoralens, and/or other chemicals. We sought to better define the population using accelerators, identify predictors of their use, and describe any related adverse effects. This cross-sectional study surveyed 200 indoor tanners about their tanning practices and accelerator use. Primary analysis compared accelerator users with nonusers with respect to questionnaire variables. Descriptive statistics and χ(2) contingency tables were applied to identify statistically significant variables. Of respondents, 53% used accelerators; 97% were female and 3% were male with a median age of 22 years (range: 19-67). Users were more likely to spray tan, tan frequently, and be addicted to tanning. Acne and rashes were more common in accelerator users. Adverse reactions to accelerators prevented their further use 31% of the time. A limited adult population was evaluated; exact accelerator ingredients were not examined. Tanning accelerator users are high-risk indoor tanners who tan more frequently and who are more likely addicted to tanning. Acne and rashes are more common with these products and act as only mild deterrents to continued use. Additional research should investigate accelerators' longer-term health effects. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Identifying and managing the adverse effects of immune checkpoint blockade

PubMed Central

Winer, Arthur; Bodor, J. Nicholas

2018-01-01

Immunotherapy has revolutionized the field of oncology. By inhibiting the cytotoxic T-lymphocyte-associated protein (CTLA-4) and programmed death-1 (PD-1) immune checkpoint pathways, multiple studies have demonstrated greatly improved survival in locally advanced and metastatic cancers including melanoma, renal, lung, gastric, and hepatocellular carcinoma. Trials in other malignancies are ongoing, and undoubtedly the number of drugs in this space will grow beyond the six currently approved by the Food and Drug Administration. However, by altering the immune response to fight cancer, a new class of side effects has emerged known as immune-related adverse events (irAEs). These adverse events are due to overactivation of the immune system in almost any organ of the body, and can occur at any point along a patient’s treatment course. irAEs such as endocrinopathies (thyroiditis), colitis, and pneumonitis may occur more commonly. However, other organs such as the liver, heart, or brain may also be affected by immune overactivation and any of these side effects may become life threatening. This review presents an approach to promptly recognize and manage these toxicities, to hopefully minimize morbidity and mortality from irAEs. PMID:29593893

Agricultural sources of contaminants of emerging concern and adverse health effects on freshwater fish

USGS Publications Warehouse

Tillitt, Donald E.; Buxton, Herbert T.

2011-01-01

Agricultural contaminants of emerging concern (CECs) are generally thought of as certain classes of chemicals associated with animal feeding and production facilities. Veterinary pharmaceuticals used in animal food production systems represent one of the largest groups of CECs. In our review, we discuss the extensive increase in use of antibiotics in animal feeding operations (AFOs) around the world. AFOs are a major consumer of antibiotics and other veterinary pharmaceuticals and over the past decade there has been growing information on the occurrence, release, and fate of CECs from animal food production operations, including the application of pharmaceutical-containing manure to agricultural fields and releases from waste lagoons. Concentrations of CECs in surface and ground water in proximity to AFOs correspond to their presence in the AFO wastes. In many cases, the environmental concentrations of agriculturally-derived CECs are below toxicity thresholds. Hormones and hormone replacement compounds are a notable exception, where chemical concentrations near AFOs can exceed concentrations known to cause adverse effects on endocrine-related functions in fish. In addition, some agricultural pesticides, once thought to be safe to non-target organisms, have demonstrated endocrine-related effects that may pose threats to fish populations in agricultural regions. That is, we have pesticides with emerging concerns, thus, the concern is emerging and not necessarily the chemical. In this light, one must consider certain agricultural pesticides to be included in the list of CECs. Even though agricultural pesticides are routinely evaluated in regulatory testing schemes which have been used for decades, the potential hazards of some pesticides have only recently been emerging. Emerging concerns of pesticides in fish include interference with hormone signaling pathways; additive (or more than additive) effects from pesticide mixtures; and adverse population-level effects at

Some effects of adverse weather conditions on performance of airplane antiskid braking systems

NASA Technical Reports Server (NTRS)

Horne, W. B.; Mccarty, J. L.; Tanner, J. A.

1976-01-01

The performance of current antiskid braking systems operating under adverse weather conditions was analyzed in an effort to both identify the causes of locked-wheel skids which sometimes occur when the runway is slippery and to find possible solutions to this operational problem. This analysis was made possible by the quantitative test data provided by recently completed landing research programs using fully instrumented flight test airplanes and was further supported by tests performed at the Langley aircraft landing loads and traction facility. The antiskid system logic for brake control and for both touchdown and locked-wheel protection is described and its response behavior in adverse weather is discussed in detail with the aid of available data. The analysis indicates that the operational performance of the antiskid logic circuits is highly dependent upon wheel spin-up acceleration and can be adversely affected by certain pilot braking inputs when accelerations are low. Normal antiskid performance is assured if the tire-to-runway traction is sufficient to provide high wheel spin-up accelerations or if the system is provided a continuous, accurate ground speed reference. The design of antiskid systems is complicated by the necessity for tradeoffs between tire braking and cornering capabilities, both of which are necessary to provide safe operations in the presence of cross winds, particularly under slippery runway conditions.

A cross-cultural longitudinal examination of the effect of cumulative adversity on the mental and physical health of older adults.

PubMed

Palgi, Yuval; Shrira, Amit

2016-03-01

Self-oriented adversity refers to traumatic events that primarily inflict the self, whereas other-oriented adversity refers to events that affect the self by primarily targeting others. The present study aimed to examine whether cultural background moderates the effects of self-oriented and other-oriented adversity on mental and physical health of older adults. Using longitudinal data from the Israeli component of the Survey of Health and Retirement, we focused on 370 Jews and 239 Arabs who reported their exposure to various adversities across the life span, and completed questionnaires regarding mental and physical health. Results showed that the effect of self-oriented adversity on health did not differ among Jews and Arabs. However, other-oriented adversity showed a stronger effect on Arabs' mental and physical health than on Jews' health. Our findings suggest that the accumulation of adverse events that affect the self by primarily targeting others may have a stronger impact in collectivist cultures than in individualist cultures. (c) 2016 APA, all rights reserved).

A Cross-Cultural Longitudinal Examination of the Effect of Cumulative Adversity on the Mental and Physical Health of Older Adults

PubMed Central

Palgi, Yuval; Shrira, Amit

2015-01-01

Self-oriented adversity refers to traumatic events that primarily inflict the self, whereas other-oriented adversity refers to events that affect the self by primarily targeting others. The present study aimed to examine whether cultural background moderates the effects of self-oriented and other-oriented adversity on mental and physical health of older adults. Using longitudinal data from the Israeli component of the Survey of Health and Retirement, we focused on 370 Jews and 239 Arabs who reported their exposure to various adversities across the lifespan, and completed questionnaires regarding mental and physical health. Results showed that the effect of self-oriented adversity on health did not differ among Jews and Arabs. However, other-oriented adversity showed a stronger effect on Arabs’ mental and physical health than on Jews’ health. Our findings suggest that the accumulation of adverse events that affect the self by primarily targeting others may have a stronger impact in collectivist cultures than in individualist cultures. PMID:25961862

Pathology effects at radiation doses below those causing increased mortality

NASA Technical Reports Server (NTRS)

Carnes, Bruce A.; Gavrilova, Natalia; Grahn, Douglas

2002-01-01

Mortality data from experiments conducted at the Argonne National Laboratory (ANL) on the long-term effects of external whole-body irradiation on B6CF(1) mice were used to investigate radiation-induced effects at intermediate doses of (60)Co gamma rays or fission-spectrum neutrons either delivered as a single exposure or protracted over 60 once-weekly exposures. Kaplan-Meier analyses were used to identify the lowest dose in the ANL data (within radiation quality, pattern of exposure, and sex) at which radiation-induced mortality caused by primary tumors could be detected (approximately 1-2 Gy for gamma rays and 10-15 cGy for neutrons). Doses at and below these levels were then examined for radiation-induced shifts in the spectrum of pathology detected at death. To do this, specific pathology events were pooled into larger assemblages based on whether they were cancer, cardiovascular disease or non-neoplastic diseases detected within the lungs and pleura, liver and biliary tract, reproductive organs, or urinary tract. Cancer and cardiovascular disease were further subdivided into categories based on whether they caused death, contributed to death, or were simply observed at death. Counts of how often events falling within each of these combined pathology categories occurred within a mouse were then used as predictor variables in logistic regression to determine whether irradiated mice could be distinguished from control mice. Increased pathology burdens were detected in irradiated mice at doses lower than those causing detectable shifts in mortality-22 cGy for gamma rays and 2 cGy for neutrons. These findings suggest that (1) models based on mortality data alone may underestimate radiation effects, (2) radiation may have adverse health consequences (i.e. elevated health risks) even when mortality risks are not detected, and (3) radiation-induced pathologies other than cancer do occur, and they involve multiple organ systems.

Adverse effects of gluten ingestion and advantages of gluten withdrawal in nonceliac autoimmune disease.

PubMed

Lerner, Aaron; Shoenfeld, Yehuda; Matthias, Torsten

2017-12-01

In light of the coincident surge in overall gluten intake and the incidence of autoimmune diseases, the possible biological adverse effects of gluten were explored. PubMed, MEDLINE, and the Cochrane Library databases were screened for reports published between 1964 and 2016 regarding the adverse effects of gluten as well as the effects of a gluten-free diet on autoimmune diseases. In vitro and in vivo studies describing gluten intake in animal models or cell lines and gluten-free diets in human autoimmune diseases were reviewed. Multiple detrimental aspects of gluten affect human health, including gluten-dependent digestive and extradigestive manifestations mediated by potentially immunological or toxic reactions that induce gastrointestinal inadequacy. Gluten affects the microbiome and increases intestinal permeability. It boosts oxidative stress and affects epigenetic behavior. It is also immunogenic, cytotoxic, and proinflammatory. Gluten intake increases apoptosis and decreases cell viability and differentiation. In certain nonceliac autoimmune diseases, gluten-free diets may help curtail the adverse effects of gluten. Additional in vivo studies are needed to unravel the puzzle of gluten effects in humans and to explore the potential beneficial effects of gluten-free diets in autoimmune diseases. © The Author(s) 2017. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The College Student and Marijuana: Research Findings Concerning Adverse Biological and Psychological Effects.

ERIC Educational Resources Information Center

Nicholi, Armand M., Jr.

1983-01-01

This paper focuses on current knowledge about adverse biological and psychological affects of marijuana use, with special reference to risks for college students. Short-term effects on intellectual functioning and perceptual-motor coordination and long-term effects on reproduction and motivation are highlighted. (PP)

ENVIRONMENTAL POLLUTANTS AND ADVERSE HUMAN HEALTH EFFECTS: HAZARD IDENTIFICATION USING INTERREGION COMPARISONS

EPA Science Inventory

Background: Associations between adverse health effects and environmental exposures are difficult to study, because exposures may be widespread, low-dose in nature, and common throughout the study population. Therefore, individual risk-factor epidemiology may not be the right to...

Could adverse effects and complications of selective laser trabeculoplasty be decreased by low-power laser therapy?

PubMed

Paiva, Alexandre de Carvalho Mendes; da Fonseca, Adenilson de Souza

2017-11-30

Selective laser trabeculoplasty (SLT) has been used for treatment of primary open-angle glaucoma, ocular hypertension, pigmenter and pseudoexfoliative glaucoma being considered a low-risk procedure. Therefore, transitory and permanent adverse effects have been reported, including corneal changes, subclinical edema, and reduction in endothelial cells and in central corneal thickness. Despite rarer, serious corneal complications after SLT can be permanent and lead to visual impairment, central corneal haze, opacity and narrowing. The mechanism involves increase of vasoactive and chemotactic cytokines causing inflammatory infiltrate, destruction of stromal collagen by fibroblasts and increase of matrix metalloproteinases type 2, which impair reepithelization. SLT also increases free radical production and reduces antioxidant enzymes, resulting in endothelium damages. Low-power laser therapy (LPLT) has been used in regenerative medicine based on its biostimulatory and anti-inflammatory effects. Biostimulation occurs through the interaction of laser photons with cytochrome C oxidase enzyme, which activates intracellular biochemical cascades causing synthesis of a number of molecules related to anti-inflammatory, regenerative effects, pain relief and reduction in edema. It has been showed that LPLT reduces gene expression related to pro-inflammatory cytokines and matrix metalloproteinases, and it increases expression of growth factors related to its proliferative and healing actions. Although radiations emitted by low-power lasers are considered safe and able to induce therapeutic effects, researches based on experimental models for glaucoma could bring important data if LPLT could be an alternative approach to improve acceptation for patients undergoing SLT.

[Adverse events in patients from a pediatric hospital.

PubMed

Ornelas-Aguirre, José Manuel; Arriaga-Dávila, José de Jesús; Domínguez-Serrano, María Isabel; Guzmán-Bihouet, Beatriz Filomena; Navarrete-Navarro, Susana

2013-01-01

Background: detection of adverse events is part of the safety management in hospitalized patients. The objective of this study was to describe the incidence of adverse events that occurred in a pediatric hospital. Methods: cross-sectional study of the adverse events occurred in a pediatric hospital from 2007 to 2009. Factors associated with their developmental causes were identified. The statistical analysis was descriptive and bivariate, with contingency tables to estimate the relationship between those factors. A p value = 0.05 was considered significant. Results: a total of 177 adverse events were registered. When they began, human factor occurred in 23 cases (13 %, OR = 1.41, p = 0.001), organizational factor was present in 71 cases (40 %, OR = 1.91, p = 0.236) and technical factor in 46 cases (26 %, OR = 0.87, p = 0.01). Blows or bruises from falls as a result of adverse events occurred in 71 cases (40 %, 95 % CI = 64-78). Conclusions: we found 1.84 events per 100 hospital discharges during the study period. The fall of patients ranked first of the adverse events identified.

Prenatal stress and development: beyond the single cause and effect paradigm.

PubMed

Hamlin, Heather J

2012-12-01

Our awareness of the causes of stress-induced developmental dysfunction has increased dramatically over the past decade, and it is becoming increasingly clear that a number of factors can have considerable impacts on the developing fetus. Although there is a tendency in investigations of developmental teratogens to attribute specific causes to adverse fetal outcomes, it is important we recognize that for most developmental dysfunctions it is unlikely a single cause, but yet a series of environmental insults combined with genetic predisposition that ultimately leads to a disease state. Nonetheless, a number of developmental teratogens, such as maternal psychological stress and chemical exposures, have been shown to increase the likelihood of developmental defects. These defects can manifest during development, leading to observable birth defects, or could become evident long after birth, even into adulthood. In addition, epigenetic mutations in the germline can alter the phenotype of successive generations through transgenerational inheritance, and in this way environmental factors can alter the developmental outcomes and disease predispositions of future generations. Understanding this complexity is essential to interpretations of causality in the studies of stress-induced developmental dysfunction and needs to be fully considered to more effectively interpret potential outcomes. Copyright © 2013 Wiley Periodicals, Inc.

40 CFR 172.57 - Submission of information regarding potential unreasonable adverse effects.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Submission of information regarding potential unreasonable adverse effects. 172.57 Section 172.57 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) PESTICIDE PROGRAMS EXPERIMENTAL USE PERMITS Notification for Certain...

Quality of life and adverse effects of olanzapine versus risperidone therapy in patients with schizophrenia.

PubMed

Chaves, Katarina Melo; Serrano-Blanco, Antoni; Ribeiro, Susana Barbosa; Soares, Luiz Alberto Lira; Guerra, Gerlane Coelho Bernardo; do Socorro Costa Feitosa Alves, Maria; de Araújo Júnior, Raimundo Fernandes; de Paula Soares Rachetti, Vanessa; Filgueira Júnior, Antônio; de Araújo, Aurigena Antunes

2013-03-01

This cross-sectional study aimed to compare the effects of treatment with an atypical antipsychotic drug (olanzapine or risperidone) on quality of life (QoL) and to document adverse effects in 115 patients diagnosed with schizophrenia who attended the ambulatory service of Hospital Dr. João Machado, Natal, Rio Grande do Norte, Brazil. Socioeconomic, sociodemographic, and clinical variables were compared. The QoL Scale validated for Brazil (QLS-BR) was used to evaluate QoL, and adverse effects were assessed using the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale. Data were analyzed using the χ(2) test and Student's t test, with a significance level of 5 %. Patients in both drug groups showed severe impairment in the occupational domain of the QLS-BR. Global QLS-BR scores indicated impairment among risperidone users and severe impairment among olanzapine users. The most significant side effects were associated with risperidone, including asthenia/lassitude/fatigue, somnolence/sedation, paresthesia, change in visual accommodation, increased salivation, diarrhea, orthostatic posture, palpitations/tachycardia, erythema, photosensitivity, weight loss, galactorrhea, decreased sexual desire, erectile/orgasmic dysfunction, vaginal dryness, headache, and physical dependence. QoL was impaired in patients using olanzapine and in those using risperidone. Risperidone use was associated with psychic, neurological, and autonomous adverse effects and other side effects.

[Pharmacotherapy of hyperthyreosis--adverse drug reactions].

PubMed

Perger, Ludwig; Bürgi, Ulrich; Fattinger, Karin

2011-06-01

The antithyroid drugs mainly include thioimidazole (carbimazole, methimazole=thiamazole) and propylthiouracil. After absorption, carbimazole is rapidly metabolized to methimazole and thus switching between these two drugs should not be considered in case of side effects. Furthermore, in case of side effects, sometimes even cross reactions between thioimidazoles and propylthiouracil occur. Common and typical adverse reactions of antithyroid drugs include dose dependent hypothyroidism and thus thyroid function should be repeatedly checked while the patient is on antithyroid drugs. Furthermore, pruritus and rash may develop. In this case, one might try to switch from thioimidazoles to propylthiouracil or vice versa. Antithyroid drugs may cause mild dose dependent neutropenia or severe allergy-mediated agranulocytosis, which typically occurs during the first three months of treatment, has an incidence of 3 per 10,000 patients and cross reactivity between thioimidazoles to propylthiouracil may occur. Rarely, antithyroid drugs can cause aplastic anemia. Mainly propylthiouracil, but sometimes also methimazole may lead to an asymptomatic transient increase in liver enzymes or to severe, even lethal liver injury of cholestatic or hepatocellular pattern. Since propylthiouracil associated liver injury was observed increasingly among children and adolescent, it has been suggested to prefer thioimidazoles for these patients. Because of these potential serious adverse effects, physicians should advise patients to immediately seek medical help if they get a fever or sore throat or malaise, abdominal complaints or jaundice, respectively. Furthermore, arthralgias may develop in 1-5% of patients under both antithyroid drugs. Since arthralgias may be the first symptom of more serious immunologic side effects, it is recommended to stop the antithyroid drug in this case. Drug induced polyarthritis mainly develops during the first month of therapy, whereas ANCA-positive vasculitis is

Evaluation of the Quebec Healthy Enterprise Standard: Effect on Adverse Psychosocial Work Factors and Psychological Distress.

PubMed

Letellier, Marie-Claude; Duchaine, Caroline S; Aubé, Karine; Talbot, Denis; Mantha-Bélisle, Marie-Michèle; Sultan-Taïeb, Hélène; St-Hilaire, France; Biron, Caroline; Vézina, Michel; Brisson, Chantal

2018-02-28

Adverse psychosocial work factors are recognized as a significant source of psychological distress, resulting in a considerable socioeconomic burden. The impact of occupational health standards that aim to reduce these adverse work factors, such as the Quebec Healthy Enterprise Standard (QHES), is of great interest for public health. The aim of this study was to evaluate, for the first time, the effect of QHES interventions targeting adverse psychosocial work factors on the prevalence of these factors and of psychological distress among ten Quebec organizations. These outcomes were assessed by questionnaire using validated instruments before (T1, n = 2849) and 2-3 years following (T2, n = 2560) QHES implementation. Beneficial effects of interventions were observed for two adverse psychosocial work factors: low rewards (ratio of prevalence ratios (PRs) = 0.77, 95% CI = 0.66-0.91) and low social support at work (ratio of PRs = 0.89, 95% CI = 0.77-1.03). Moreover, beneficial effects of interventions were also observed on the prevalence of high psychological distress (ratio of PRs = 0.86, 95% CI = 0.75-0.998). Psychosocial interventions implemented in the context of this standard improved the psychosocial work environment and had beneficial effects on workers' mental health.

Evaluation of the Quebec Healthy Enterprise Standard: Effect on Adverse Psychosocial Work Factors and Psychological Distress

PubMed Central

Letellier, Marie-Claude; Duchaine, Caroline S.; Mantha-Bélisle, Marie-Michèle; Sultan-Taïeb, Hélène; St-Hilaire, France; Biron, Caroline; Vézina, Michel; Brisson, Chantal

2018-01-01

Adverse psychosocial work factors are recognized as a significant source of psychological distress, resulting in a considerable socioeconomic burden. The impact of occupational health standards that aim to reduce these adverse work factors, such as the Quebec Healthy Enterprise Standard (QHES), is of great interest for public health. The aim of this study was to evaluate, for the first time, the effect of QHES interventions targeting adverse psychosocial work factors on the prevalence of these factors and of psychological distress among ten Quebec organizations. These outcomes were assessed by questionnaire using validated instruments before (T1, n = 2849) and 2–3 years following (T2, n = 2560) QHES implementation. Beneficial effects of interventions were observed for two adverse psychosocial work factors: low rewards (ratio of prevalence ratios (PRs) = 0.77, 95% CI = 0.66–0.91) and low social support at work (ratio of PRs = 0.89, 95% CI = 0.77–1.03). Moreover, beneficial effects of interventions were also observed on the prevalence of high psychological distress (ratio of PRs = 0.86, 95% CI = 0.75–0.998). Psychosocial interventions implemented in the context of this standard improved the psychosocial work environment and had beneficial effects on workers’ mental health. PMID:29495632

Adverse effects of caffeinated energy drinks among youth and young adults in Canada: a Web-based survey

PubMed Central

Hammond, David; Reid, Jessica L.; Zukowski, Sara

2018-01-01

Background: Energy drink consumption has increased dramatically among young Canadians, with anecdotal evidence of adverse health effects. There is a lack of population-based studies to examine the prevalence of adverse events from energy drinks, particularly among young people. The current study sought to assess adverse events from energy drinks among a population-based sample of youth and young adults in Canada. Methods: An online survey was conducted in 2015 with a national sample of youth (aged 12-17 yr) and young adults (aged 18-24 yr) recruited from a consumer panel. Respondents reported prior consumption of energy drinks as well as adverse outcomes, concurrent activities associated with the outcomes and whether medical attention was sought or considered. Adverse events from coffee were also assessed for comparison. Weighted analyses are reported. Results: Of the 2055 respondents, 1516 (73.8%) reported having ever consumed an energy drink, and 1741 (84.7%) reported having ever consumed coffee (unweighted). Overall, 55.4% of respondents who had ever consumed an energy drink reported that they had experienced at least 1 adverse event, including fast heartbeat (24.7%), difficulty sleeping (24.1%), headache (18.3%), nausea/vomiting/diarrhea (5.1%), chest pain (3.6%) and seizures (0.2%); 3.1% had sought or had considered seeking medical help for an adverse event. The prevalence of reported adverse events was significantly greater among energy drink consumers than among coffee consumers (36.0%) (odds ratio [OR] 2.67 [95% confidence interval (CI) 2.01-2.56]), as was the proportion who reported seeking or considering seeking medical help for adverse events (3.1% v. 1.4%) (OR 2.18 [95% CI 1.39-3.41]). Interpretation: More than half of youth and young adults who had consumed energy drinks reported adverse outcomes, some serious enough to warrant seeking medical help. The adverse outcomes were consistent with the physiologic effects of caffeine but were significantly

Adverse effects of caffeinated energy drinks among youth and young adults in Canada: a Web-based survey.

PubMed

Hammond, David; Reid, Jessica L; Zukowski, Sara

2018-01-09

Energy drink consumption has increased dramatically among young Canadians, with anecdotal evidence of adverse health effects. There is a lack of population-based studies to examine the prevalence of adverse events from energy drinks, particularly among young people. The current study sought to assess adverse events from energy drinks among a population-based sample of youth and young adults in Canada. An online survey was conducted in 2015 with a national sample of youth (aged 12-17 yr) and young adults (aged 18-24 yr) recruited from a consumer panel. Respondents reported prior consumption of energy drinks as well as adverse outcomes, concurrent activities associated with the outcomes and whether medical attention was sought or considered. Adverse events from coffee were also assessed for comparison. Weighted analyses are reported. Of the 2055 respondents, 1516 (73.8%) reported having ever consumed an energy drink, and 1741 (84.7%) reported having ever consumed coffee (unweighted). Overall, 55.4% of respondents who had ever consumed an energy drink reported that they had experienced at least 1 adverse event, including fast heartbeat (24.7%), difficulty sleeping (24.1%), headache (18.3%), nausea/vomiting/diarrhea (5.1%), chest pain (3.6%) and seizures (0.2%); 3.1% had sought or had considered seeking medical help for an adverse event. The prevalence of reported adverse events was significantly greater among energy drink consumers than among coffee consumers (36.0%) (odds ratio [OR] 2.67 [95% confidence interval (CI) 2.01-2.56]), as was the proportion who reported seeking or considering seeking medical help for adverse events (3.1% v. 1.4%) (OR 2.18 [95% CI 1.39-3.41]). More than half of youth and young adults who had consumed energy drinks reported adverse outcomes, some serious enough to warrant seeking medical help. The adverse outcomes were consistent with the physiologic effects of caffeine but were significantly more prevalent than with other sources of

An in-flight simulation of approach and landing of a STOL transport with adverse ground effect

NASA Technical Reports Server (NTRS)

Ellis, D. R.

1976-01-01

The results of an in-flight simulation program undertaken to study the problems of landing a representative STOL transport in the presence of adverse ground effects are presented. Landings were performed with variations in ground effect magnitude, ground effect lag, and thrust response. Other variations covered the effects of augmented lift response, SAS-failures, turbulence, segmented approach, and flare warning. The basic STOL airplane required coordinated use of both stick and throttle for consistently acceptable landings, and the presence of adverse ground effects made the task significantly more difficult. Ground effect lag and good engine response gave noticeable improvement, as did augmented lift response.

[Adverse effects of hair care in users].

PubMed

Tennstedt, D; Herman, A; Lachapelle, J-M

2018-06-26

The panoply of products used by hair care professionals to wash, dye, shape and beautify hair is not entirely free from adverse events. Such effects consist mainly of irritation dermatitis and allergic contact eczema affecting the scalp, as well as the back and front of the neck, the forehead and periorbital areas, and the cheeks. The most frequently cited allergens include paraphenylenediamine (PPD) in hair dyes, glycerol monothioglycolate (GMTG) in acid perm lotions, and ammonium persulphate in hair lighteners (the latter substance being responsible primarily for contact urticaria). However, care should also be paid to other allergens such as cocamidopropyl betaine among surfactants, as well as certain components in hair formulations such as preservatives and fragrances (as well as minoxidil, frequently used by patients). Copyright © 2018. Published by Elsevier Masson SAS.

Exposure to Cobalt Causes Transcriptomic and Proteomic Changes in Two Rat Liver Derived Cell Lines

DTIC Science & Technology

2013-12-01

although contact with cobalt can cause dermatitis [16]. While cobalt is known to cause adverse health effects, the exact mechanism of action remains...animals and humans through various exposure routes. Cobalt can enter the body through respiration, ingestion, or contact with the skin. The adverse...concentration on the liver, kidney and heart in mice. Orthop Surg 2: 134–140. 16. Schwartz L PS (1945) Allergic dermatitis due to metallic cobalt. Journal

[Effect of electroacupuncture at Hegu (LI 4) and Sanyinjiao (SP 6) on short-term adverse effects of drug-induced abortion].

PubMed

Xu, Hong-Yan; Yang, Fang; Zhu, Jiang; He, Zhi-Ping; Yan, Chen

2007-02-01

To search for a therapeutic method for alleviating the short-term adverse effect of drug-induced abortion. Ninety cases of early pregnancy were divided into 3 groups randomly. Control group were treated with medicine, electroacupuncture group I with electroacupuncture at both Hegu (LI 4) and Sanyinjiao (SP 6) simultaneously within 30-60 min after the medicine was given, and electroacupuncture group II with electroacupuncture at Hegu (LI 4) and Sanyinjiao (SP 6) successively within 30-60 min after the medicine was administrated. After treatment, the short-term adverse effect in the electroacupuncture groups was more significantly alleviated as compared with the control group (P < 0.05), and alleviative degree of abdominal pain in the electroacupuncture group II was better than that in the electroacupuncture group I . Electroacupuncture at Hegu (LI 4) and Sanyinjiao (SP 6) can alleviate short-term adverse effects of drug-induced abortion, and first electroacupuncture at Hegu (LI 4) followed by Sanyinjiao (SP 6) can more significantly alleviate abdominal pain.

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.

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

PubMed

Vilar, Santiago; Hripcsak, George

2016-01-01

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

Potential Adverse Effects of Amphetamine Treatment on Brain and Behavior: A Review

PubMed Central

Berman, Steven M.; Kuczenski, Ronald; McCracken, James T.; London, Edythe D.

2009-01-01

Rationale Amphetamine stimulants have been used medically since early in the twentieth century, but they have a high abuse potential and can be neurotoxic. Although they have long been used effectively to treat attention deficit hyperactivity disorder (ADHD) in children and adolescents, amphetamines are now being prescribed increasingly as maintenance therapy for ADHD and narcolepsy in adults, considerably extending the period of potential exposure. Effects of prolonged stimulant treatment have not been fully explored, and understanding such effects is a research priority 1. Because the pharmacokinetics of amphetamines differ between children and adults, reevaluation of the potential for adverse effects of chronic treatment of adults is essential. Findings Despite information on the effects of stimulants in laboratory animals, profound species differences in susceptibility to stimulant-induced neurotoxicity underscore the need for systematic studies of prolonged human exposure. Early amphetamine treatment has been linked to slowing in height and weight growth in some children. Because the number of prescriptions for amphetamines has increased several-fold over the past decade, an amphetamine-containing formulation is the most commonly prescribed stimulant in North America, and it is noteworthy that amphetamines are also the most abused prescription medications. Although early treatment does not increase risk for substance abuse, few studies have tracked the compliance and usage profiles of individuals who began amphetamine treatment as adults. Overall, there is concern about risk for slowed growth in young patients who are dosed continuously, and for substance abuse in patients first medicated in late adolescence or adulthood. Although most adult patients also use amphetamines effectively and safely, occasional case reports indicate that prescription use can produce marked psychological adverse events, including stimulant-induced psychosis. Assessments of central

In Silico Prediction of Organ Level Toxicity: Linking Chemistry to Adverse Effects.

PubMed

Cronin, Mark T D; Enoch, Steven J; Mellor, Claire L; Przybylak, Katarzyna R; Richarz, Andrea-Nicole; Madden, Judith C

2017-07-01

In silico methods to predict toxicity include the use of (Quantitative) Structure-Activity Relationships ((Q)SARs) as well as grouping (category formation) allowing for read-across. A challenging area for in silico modelling is the prediction of chronic toxicity and the No Observed (Adverse) Effect Level (NO(A)EL) in particular. A proposed solution to the prediction of chronic toxicity is to consider organ level effects, as opposed to modelling the NO(A)EL itself. This review has focussed on the use of structural alerts to identify potential liver toxicants. In silico profilers, or groups of structural alerts, have been developed based on mechanisms of action and informed by current knowledge of Adverse Outcome Pathways. These profilers are robust and can be coded computationally to allow for prediction. However, they do not cover all mechanisms or modes of liver toxicity and recommendations for the improvement of these approaches are given.

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.

IDAAPM: integrated database of ADMET and adverse effects of predictive modeling based on FDA approved drug data.

PubMed

Legehar, Ashenafi; Xhaard, Henri; Ghemtio, Leo

2016-01-01

The disposition of a pharmaceutical compound within an organism, i.e. its Absorption, Distribution, Metabolism, Excretion, Toxicity (ADMET) properties and adverse effects, critically affects late stage failure of drug candidates and has led to the withdrawal of approved drugs. Computational methods are effective approaches to reduce the number of safety issues by analyzing possible links between chemical structures and ADMET or adverse effects, but this is limited by the size, quality, and heterogeneity of the data available from individual sources. Thus, large, clean and integrated databases of approved drug data, associated with fast and efficient predictive tools are desirable early in the drug discovery process. We have built a relational database (IDAAPM) to integrate available approved drug data such as drug approval information, ADMET and adverse effects, chemical structures and molecular descriptors, targets, bioactivity and related references. The database has been coupled with a searchable web interface and modern data analytics platform (KNIME) to allow data access, data transformation, initial analysis and further predictive modeling. Data were extracted from FDA resources and supplemented from other publicly available databases. Currently, the database contains information regarding about 19,226 FDA approval applications for 31,815 products (small molecules and biologics) with their approval history, 2505 active ingredients, together with as many ADMET properties, 1629 molecular structures, 2.5 million adverse effects and 36,963 experimental drug-target bioactivity data. IDAAPM is a unique resource that, in a single relational database, provides detailed information on FDA approved drugs including their ADMET properties and adverse effects, the corresponding targets with bioactivity data, coupled with a data analytics platform. It can be used to perform basic to complex drug-target ADMET or adverse effects analysis and predictive modeling. IDAAPM is

The Cumulative Effect of Health Adversities on Children's Later Academic Achievement.

PubMed

Quach, Jon; Nguyen, Cattram; O'Connor, Meredith; Wake, Melissa

We aimed to determine whether the accumulation of physical, psychosocial, and combined health adversities measured at age 8 to 9 years predicts worsening of academic scores cross-sectionally at 8 to 9 and longitudinally at 10 to 11 years. Design: Longitudinal data from Waves 3 and 4 in the Longitudinal Study of Australian Children (83% of 4983 retained). Exposures (8-9 years): Physical health adversities (yes/no; summed range, 0-5): overweight, special health care needs, chronic illness, PedsQL Physical, and global health. Psychosocial health adversities (yes/no; summed range, 0-4): parent- and teacher-reported behavior, PedsQL Psychosocial, sleep problems. Combined health adversities (range 0-9). Outcomes (8-9, and 10-11 years): National academic standardized test scores. Generalized estimating equations, accounting for multiple academic domains in each year and socioeconomic position and cognition. At 8 to 9 years, 23.9%, 9.9%, and 5.3% had 1, 2, or ≥3 physical health adversities, respectively, while 27.2%, 9.5%, and 4.9% had 1, 2, or ≥3 psychosocial health adversities. For each additional health adversity at 8 to 9 years, academic scores fell incrementally in year 3 and year 5 (both P < .001), with reductions of at least 0.4 SDs for ≥3 health adversities. Number was more important than type (physical, psychosocial) of adversity. The accumulation of health adversities predicts poorer academic achievement up to 2 years later. Interventions might need to address multiple domains to improve child academic outcomes and be delivered across the health-education interface. Copyright © 2017 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

Cinnamon: A systematic review of adverse events.

PubMed

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

2018-04-05

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

Nano-hydroxyapatite could Compensate the Adverse Effect of soft carbonated Drinks on Enamel.

PubMed

Rezvani, Mohammad B; Rouhollahi, Mohammad R; Andalib, Fahimeh; Hamze, Faeze

2016-08-01

Since one of the most important disadvantages of soft drinks includes their adverse effect on mineral content of enamel because of their low pH, this study examined the microhardness of enamel before and after exposure to a soft drink containing different concentrations of nano-hydroxyapatite (nano-HA) as an additive. Sixty caries free human premolars were mounted in epoxy resin. After polishing, the baseline micro-hardness was recorded three times for each specimen using a Vickers indenter at 50 gm load. Subsequently, the samples were divided into six groups, which were treated for 5 minutes at 9°C by a cola-based drink contacting 0, 0.5, 1, 5, and 10 wt.% of nano-HA while the control group was immersed in artificial saliva. Ultimately, the final microhardness was assessed three times again for each specimen. Paired t-test showed that in groups containing 0 and 0.5 wt.% of nano-HA, the microhardness was significantly reduced after treatment protocol (p = 0.00 and 0.01 respectively). Whereas in the other groups the microhardness was not significantly changed after treatment (p > 0.05). Pure cola-based drink has a pronounced adverse effect on enamel microhardness, while admixing it with nano-HA could act as a protective factor. Although soft beverages are hazardous to tooth structure, some additives could compensate their adverse effect.

Adverse Structural and Functional Effects of Marijuana on the Brain: Evidence Reviewed.

PubMed

Mandelbaum, David E; de la Monte, Suzanne M

2017-01-01

The growing use and legalization of cannabis are leading to increased exposures across all age groups, including in adolescence. The touting of its medicinal values stems from anecdotal reports related to treatment of a broad range of illnesses including epilepsy, multiple sclerosis, muscle spasms, arthritis, obesity, cancer, Alzheimer disease, Parkinson disease, post-traumatic stress, inflammatory bowel disease, and anxiety. However, anecdotal data and the high level of interest in this treatment must not obscure objective assessments of any potential and realized short- and long-term adverse effects of cannabis, particularly with respect to age of onset and chronicity of exposure. This critical review focuses on evidence-based research designed to assess both therapeutic benefits and harmful effects of cannabis exposure and is combined with an illustration of the neuropathologic findings in a fatal case of cannabis-induced psychosis. The literature and reported case provide strong evidence that chronic cannabis abuse causes cognitive impairment and damages the brain, particularly white matter, where cannabinoid 1 receptors abound. Contrary to popular perception, there are few objective data supporting preferential use of cannabis over conventional therapy for restoration of central nervous system structure and function in disease states such as multiple sclerosis, epilepsy, or schizophrenia. Additional research is needed to determine if subsets of individuals with various neurological and psychiatric diseases derive therapeutic benefits from cannabis. Copyright © 2016. Published by Elsevier Inc.

Separate and Cumulative Effects of Adverse Childhood Experiences in Predicting Adult Health and Health Care Utilization

ERIC Educational Resources Information Center

Chartier, Mariette J.; Walker, John R.; Naimark, Barbara

2010-01-01

Objectives: Objectives of this population-based study were: (1) to examine the relative contribution of childhood abuse and other adverse childhood experiences to poor adult health and increased health care utilization and (2) to examine the cumulative effects of adverse childhood experiences on adult health and health care utilization. Methods:…

[Sodium valproate as a cause of acute pancreatitis: a case report].

PubMed

Barreda, Luís; Rosas, Johana; Milian, William; Valdivia, Duilio; Targarona, Javier

2006-01-01

Valproic acid (VPA) is a commonly used medication approved by the U.S. FDA for the treatment of epilepsy, migraines and bipolar disorders. Adverse effects associated with VPA are typically benign, but there are more serious effects that are less frequent. These effects include hepatotoxicity, teratogenicity, possible polycystic ovaries with a potential sterile effect and acute pancreatitis. Even though acute pancreatitis is an adverse effect of very low frequency, it is very important due to the high mortality rate of patients with acute pancreatitis as a consequence of the use of valproic acid. In medical literature, by 2005, 80 cases of acute pancreatitis caused by valproic acid were reported, 33 of these cases were patients under the age of 18. This is a description of the clinical case of a 16 year old patient with necrotic pancreatitis caused by VPA, who was treated at the Acute Pancreatitis Unit of Edgardo Rebagliati Martins National Hospital.

Tuberculin skin testing: Spectrum of adverse reactions.

PubMed

Praveen, Ramar; Bahuguna, Amit; Dhadwal, Bhumesh Singh

2015-01-01

Tuberculin skin testing (TST) is one of the primary diagnostic modalities recommended by the World Health Organization (WHO) and the National Institute for Health and Care Excellence (NICE) study conducted in the United Kingdom (UK) for diagnosing tuberculosis (TB). Even after acceptance as a diagnostic modality and stern standardization, TST has its own flaws that include a spectrum of adverse reactions. We report a series of cases with a spectrum of adverse reactions occurring with a higher frequency than present in the available evidence. The study has some demerits such as being a retrospective one with interobserver variation and lack of histopathological confirmation. The observation is presented to accentuate the fact that adverse reactions are not a rarity and that further studies are required to establish the cause and exact incidence of the same.

Evaluation of a Novel System to Enhance Clinicians' Recognition of Preadmission Adverse Drug Reactions.

PubMed

Smith, Joshua C; Chen, Qingxia; Denny, Joshua C; Roden, Dan M; Johnson, Kevin B; Miller, Randolph A

2018-04-01

 Often unrecognized by providers, adverse drug reactions (ADRs) diminish patients' quality of life, cause preventable admissions and emergency department visits, and increase health care costs.  This article evaluates whether an automated system, the Adverse Drug Effect Recognizer (ADER), could assist clinicians in detecting and addressing inpatients' ongoing preadmission ADRs.  ADER uses natural language processing to extract patients' medications, findings, and past diagnoses from admission notes. It compares excerpted information to a database of known medication adverse effects and promptly warns clinicians about potential ongoing ADRs and potential confounders via alerts placed in patients' electronic health records (EHRs). A 3-month intervention trial evaluated ADER's impact on antihypertensive medication ordering behaviors. At the time of patient admission, ADER warned providers on the Internal Medicine wards of Vanderbilt University Hospital about potential ongoing preadmission antihypertensive medication ADRs. A retrospective control group, comprised similar physicians from a period prior to the intervention, received no alerts. The evaluation compared ordering behaviors for each group to determine if preadmission medications changed during hospitalization or at discharge. The study also analyzed intervention group participants' survey responses and user comments.  ADER identified potential preadmission ADRs for 30% of both groups. Compared with controls, intervention providers more often withheld or discontinued suspected ADR-causing medications during the inpatient stay ( p  < 0.001). Intervention providers who responded to alert-related surveys held or discontinued suspected ADR-causing medications more often at discharge ( p  < 0.001).  Results indicate that ADER helped physicians recognize ADRs and reduced ordering of suspected ADR-causing medications. In hospitals using EHRs, ADER-like systems could improve clinicians' recognition

More on the Cause-Effect Sequence

NASA Astrophysics Data System (ADS)

Janik, Jerzy A.

2007-06-01

Does every event have a cause? An answer is not simple. The notion of cause contains a particular being y acting on being x plus everything that may be called the boundary conditions. These may form necessary and suffcient conditions giving rise to a strong cause, or only necessary conditions, giving rise to a weak cause. These matters are discussed in this article with particular attention being paid to the argumentation of Thomas Aquinas known as prima via. Prima via is the analysis of a cause-effect sequence which leads (according to Thomas) to a First Cause (First Mover). It seems that the extrapolation of the cause-effect sequence to infinity is permissible from the logical point of view. But the possibility of weak causes seems to destroy the cause-effect "line". Here it is perhaps useful to "escape" to the metaphysical abstraction which looks at things sub ratione entitatis. If we ignore space and time (which is characteristic of this abstraction) we are led to believe that the IS of cause is finally unavoidable, which means that from the vantage point of this abstraction, i.e. from the point of view of IS, all causes are strong.

The association between cumulative adversity and mental health: considering dose and primary focus of adversity.

PubMed

Keinan, Giora; Shrira, Amit; Shmotkin, Dov

2012-09-01

The study addressed the dose-response model in the association of cumulative adversity with mental health. Data of 1,725 participants aged 50+ were drawn from the Israeli component of the Survey of Health, Ageing, and Retirement in Europe. Measures included an inventory of potentially traumatic events, distress (lifetime depression, depressive symptoms), and well-being (quality of life, optimism/hope). The maximal effect of cumulative trauma emerged in the contrast between 0-2 and 3+ events, where the higher number of events related to higher distress but also to higher well-being. While self-oriented adversity revealed no, or negative, association with well-being, other-oriented adversity revealed a positive association. The study suggests an experiential dose of cumulative adversity leading to a co-activation of distress and well-being. The source of this co-activation seems to be other-oriented adversity.

Drug-induced Epistaxis: An Often-Neglected Adverse Effect.

PubMed

Meirinho, Sara; Relvas, Ricardo; Alves, Gilberto

2018-02-12

Epistaxis is an active nose bleeding with a population occurrence of approximately 60%. Although epistaxis is a common clinical complaint, the majority of the cases are benign and caused by local induced factors (e.g., trauma and local inflammation). Nevertheless, it is also recognised that epistaxis can be induced after some drugs intake. Due to the increasing use of drugs or drug combinations that potentially may induce epistaxis, this review aims to alert healthcare professionals for this often neglected adverse drug effect and its possible complications. A comprehensive literature search was performed on PubMed and Google Scholar databases, considering the literature published from January 1985 to December 2015, using medical terms related to the scope of drug-induced epistaxis, nosebleeds and nasal blood supply. As expected, anticoagulant and antiplatelet drugs are the main pharmacotherapeutic agents associated with epistaxis, particularly warfarin, dabigatran, rivaroxaban and aspirin. However, it was reported that some selective serotonin reuptake inhibitors, intranasal corticosteroids, certain antibiotics and other drugs or drug associations can also be responsible by nosebleeds. Although most of these epistaxis episodes are mild to moderate, being spontaneously reversed or requiring only minor medical approaches to control it, there are also several case reports, as well as retrospective and prospective studies, documenting severe epistaxis episodes after specific medicines intake. In these cases some invasive medical interventions are demanded to manage the bleeding and avoid life-threatening consequences. This work provides an integrated and comprehensive review on drug-induced epistaxis bridging the gap in the current scientific literature addressing this topic. Therefore, the scientific information gathered and discussed will be valuable to raise awareness of doctors and pharmacists for this drug-related problem, as well as to promote their active

Emergency Department Visits for Adverse Events Related to Dietary Supplements.

PubMed

Geller, Andrew I; Shehab, Nadine; Weidle, Nina J; Lovegrove, Maribeth C; Wolpert, Beverly J; Timbo, Babgaleh B; Mozersky, Robert P; Budnitz, Daniel S

2015-10-15

Dietary supplements, such as herbal or complementary nutritional products and micronutrients (vitamins and minerals), are commonly used in the United States, yet national data on adverse effects are limited. We used nationally representative surveillance data from 63 emergency departments obtained from 2004 through 2013 to describe visits to U.S. emergency departments because of adverse events related to dietary supplements. On the basis of 3667 cases, we estimated that 23,005 (95% confidence interval [CI], 18,611 to 27,398) emergency department visits per year were attributed to adverse events related to dietary supplements. These visits resulted in an estimated 2154 hospitalizations (95% CI, 1342 to 2967) annually. Such visits frequently involved young adults between the ages of 20 and 34 years (28.0% of visits; 95% CI, 25.1 to 30.8) and unsupervised children (21.2% of visits; 95% CI, 18.4 to 24.0). After the exclusion of unsupervised ingestion of dietary supplements by children, 65.9% (95% CI, 63.2 to 68.5) of emergency department visits for single-supplement-related adverse events involved herbal or complementary nutritional products; 31.8% (95% CI, 29.2 to 34.3) involved micronutrients. Herbal or complementary nutritional products for weight loss (25.5%; 95% CI, 23.1 to 27.9) and increased energy (10.0%; 95% CI, 8.0 to 11.9) were commonly implicated. Weight-loss or energy products caused 71.8% (95% CI, 67.6 to 76.1) of supplement-related adverse events involving palpitations, chest pain, or tachycardia, and 58.0% (95% CI, 52.2 to 63.7) involved persons 20 to 34 years of age. Among adults 65 years of age or older, choking or pill-induced dysphagia or globus caused 37.6% (95% CI, 29.1 to 46.2) of all emergency department visits for supplement-related adverse events; micronutrients were implicated in 83.1% (95% CI, 73.3 to 92.9) of these visits. An estimated 23,000 emergency department visits in the United States every year are attributed to adverse events

Adverse effects as a consequence of being the subject of orthopaedic manual therapy training, a worldwide retrospective survey.

PubMed

Thoomes-de Graaf, M; Thoomes, E; Carlesso, L; Kerry, R; Rushton, A

2017-06-01

Physical therapists (PTs) use a range of manual therapy techniques developed to an advanced level through postgraduate orthopaedic manipulative physical therapy (OMPT) programmes. The aim of this study was to describe the adverse effects experienced by students after having techniques performed on them as part of their OMPT training. A descriptive online survey of current students and recent graduates (≤5 years)m of OMPT programmes across the 22 Member Organisations of the International Federation of Orthopaedic Manipulative Physical Therapists. The questionnaire was completed by 1640 respondents across 22 countries (1263 graduates, 377 students. Some 60% of respondents reported never having experienced adverse effects during their manual therapy training. Of the 40% who did, 66.4% reported neck pain, 50.9% headache and 32% low back pain. Most reports of neck pain started after a manipulation and/or mobilisation, of which 53.4% lasted ≤24 h, 38.1% > 24 h but <3 months and 13.7% still experienced neck pain to date. A small percentage of respondents (3.3%) reported knowing of a fellow student experiencing a major adverse effect. Mild to moderate adverse effects after practising manual therapy techniques are commonly reported, but usually resolve within 24 h. However, this survey has identified the reported occurrence of major adverse effects that warrant further investigation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Adverse cardiovascular, cerebrovascular, and peripheral vascular effects of marijuana inhalation: what cardiologists need to know.

PubMed

Thomas, Grace; Kloner, Robert A; Rezkalla, Shereif

2014-01-01

Marijuana is the most widely used illicit drug, with approximately 200 million users worldwide. Once illegal throughout the United States, cannabis is now legal for medicinal purposes in several states and for recreational use in 3 states. The current wave of decriminalization may lead to more widespread use, and it is important that cardiologists be made aware of the potential for marijuana-associated adverse cardiovascular effects that may begin to occur in the population at a greater frequency. In this report, the investigators focus on the known cardiovascular, cerebrovascular, and peripheral effects of marijuana inhalation. Temporal associations between marijuana use and serious adverse events, including myocardial infarction, sudden cardiac death, cardiomyopathy, stroke, transient ischemic attack, and cannabis arteritis have been described. In conclusion, the potential for increased use of marijuana in the changing legal landscape suggests the need for the community to intensify research regarding the safety of marijuana use and for cardiologists to maintain an awareness of the potential for adverse effects. Copyright © 2014 Elsevier Inc. All rights reserved.

Local adverse effects associated with the use of inhaled corticosteroids in patients with moderate or severe asthma*

PubMed Central

Pinto, Charleston Ribeiro; Almeida, Natalie Rios; Marques, Thamy Santana; Yamamura, Laira Lorena Lima; Costa, Lindemberg Assunção; Souza-Machado, Adelmir

2013-01-01

OBJECTIVE: To describe and characterize local adverse effects (in the oral cavity, pharynx, and larynx) associated with the use of inhaled corticosteroids (ICSs) in patients with moderate or severe asthma. METHODS: This was a cross-sectional study involving a convenience sample of 200 asthma patients followed in the Department of Pharmaceutical Care of the Bahia State Asthma and Allergic Rhinitis Control Program Referral Center, located in the city of Salvador, Brazil. The patients were ≥ 18 years of age and had been using ICSs regularly for at least 6 months. Local adverse effects (irritation, pain, dry throat, throat clearing, hoarseness, reduced vocal intensity, loss of voice, sensation of thirst, cough during ICS use, altered sense of taste, and presence of oral candidiasis) were assessed using a 30-day recall questionnaire. RESULTS: Of the 200 patients studied, 159 (79.5%) were women. The mean age was 50.7 ± 14.4 years. In this sample, 55 patients (27.5%) were using high doses of ICS, with a median treatment duration of 38 months. Regarding the symptoms, 163 patients (81.5%) reported at least one adverse effect, and 131 (65.5%) had a daily perception of at least one symptom. Vocal and pharyngeal symptoms were identified in 57 (28.5%) and 154 (77.0%) of the patients, respectively. The most commonly reported adverse effects were dry throat, throat clearing, sensation of thirst, and hoarseness. CONCLUSIONS: Self-reported adverse effects related to ICS use were common among the asthma patients evaluated here. PMID:24068261

Unintended adverse consequences of introducing electronic health records in residential aged care homes.

PubMed

Yu, Ping; Zhang, Yiting; Gong, Yang; Zhang, Jiajie

2013-09-01

burden, reduction of communication and the risks of lacking care follow-up, which may cause negative effects on aged care services. Further research can focus on investigating how the unintended adverse consequences can be mitigated or eliminated by understanding more about nursing staff's work as well as the information flow in RACH. This will help to improve the design, introduction and management of EHR systems in this setting. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Evidence for the adverse effect of starvation on bone quality: a review of the literature.

PubMed

Kueper, Janina; Beyth, Shaul; Liebergall, Meir; Kaplan, Leon; Schroeder, Josh E

2015-01-01

Malnutrition and starvation's possible adverse impacts on bone health and bone quality first came into the spotlight after the horrors of the Holocaust and the ghettos of World War II. Famine and food restrictions led to a mean caloric intake of 200-800 calories a day in the ghettos and concentration camps, resulting in catabolysis and starvation of the inhabitants and prisoners. Severely increased risks of fracture, poor bone mineral density, and decreased cortical strength were noted in several case series and descriptive reports addressing the medical issues of these individuals. A severe effect of severely diminished food intake and frequently concomitant calcium- and Vitamin D deficiencies was subsequently proven in both animal models and the most common cause of starvation in developed countries is anorexia nervosa. This review attempts to summarize the literature available on the impact of the metabolic response to Starvation on overall bone health and bone quality.

On the Causes of Effects

ERIC Educational Resources Information Center

Dawid, A. Philip; Faigman, David L.; Fienberg, Stephen E.

2015-01-01

We welcome Professor Pearl's comment on our original article, Dawid et al. Our focus there on the distinction between the "Effects of Causes" (EoC) and the "Causes of Effects" (CoE) concerned two fundamental problems, one a theoretical challenge in statistics and the other a practical challenge for trial courts. In this…

Unusual and Interesting Adverse Cutaneous Drug Reactions.

PubMed

Masatkar, Vaishali; Nagure, Ashok; Gupta, Lalit Kumar

2018-01-01

Any drug can cause any rash! Cutaneous adverse drug reactions (CADRs) are great mimickers and can be included in the differential diagnosis of any inflammatory dermatoses. Several drugs can cause rash of similar morphology and the same drug can cause rash of different morphology. While some common and specific drug reaction patterns are recognized easily by the clinicians, many a times unusual and interesting patterns can be induced by drug(s), thus leading to erroneous diagnosis and mistreatment. This review aims to familiarize clinicians with some rare, yet interesting patterns of CADR.

Unusual and Interesting Adverse Cutaneous Drug Reactions

PubMed Central

Masatkar, Vaishali; Nagure, Ashok; Gupta, Lalit Kumar

2018-01-01

Any drug can cause any rash! Cutaneous adverse drug reactions (CADRs) are great mimickers and can be included in the differential diagnosis of any inflammatory dermatoses. Several drugs can cause rash of similar morphology and the same drug can cause rash of different morphology. While some common and specific drug reaction patterns are recognized easily by the clinicians, many a times unusual and interesting patterns can be induced by drug(s), thus leading to erroneous diagnosis and mistreatment. This review aims to familiarize clinicians with some rare, yet interesting patterns of CADR. PMID:29692451

In Silico Prediction of Organ Level Toxicity: Linking Chemistry to Adverse Effects

PubMed Central

Cronin, Mark T.D.; Enoch, Steven J.; Mellor, Claire L.; Przybylak, Katarzyna R.; Richarz, Andrea-Nicole; Madden, Judith C.

2017-01-01

In silico methods to predict toxicity include the use of (Quantitative) Structure-Activity Relationships ((Q)SARs) as well as grouping (category formation) allowing for read-across. A challenging area for in silico modelling is the prediction of chronic toxicity and the No Observed (Adverse) Effect Level (NO(A)EL) in particular. A proposed solution to the prediction of chronic toxicity is to consider organ level effects, as opposed to modelling the NO(A)EL itself. This review has focussed on the use of structural alerts to identify potential liver toxicants. In silico profilers, or groups of structural alerts, have been developed based on mechanisms of action and informed by current knowledge of Adverse Outcome Pathways. These profilers are robust and can be coded computationally to allow for prediction. However, they do not cover all mechanisms or modes of liver toxicity and recommendations for the improvement of these approaches are given. PMID:28744348

Adversity, cannabis use and psychotic experiences: evidence of cumulative and synergistic effects.

PubMed

Morgan, Craig; Reininghaus, Ulrich; Reichenberg, Abraham; Frissa, Souci; Hotopf, Matthew; Hatch, Stephani L

2014-01-01

There is robust evidence that childhood adversity is associated with an increased risk of psychosis. There is, however, little research on intervening factors that might increase or decrease risk following childhood adversity. To investigate main effects of, and synergy between, childhood abuse and life events and cannabis use on odds of psychotic experiences. Data on psychotic experiences and childhood abuse, life events and cannabis use were collected from 1680 individuals as part of the South East London Community Health Study (SELCoH), a population-based household survey. There was strong evidence that childhood abuse and number of life events combined synergistically to increase odds of psychotic experiences beyond the effects of each individually. There was similar, but weaker, evidence for cannabis use (past year). Our findings are consistent with the hypothesis that childhood abuse creates an enduring vulnerability to psychosis that is realised in the event of exposure to further stressors and risk factors.

Adversity, cannabis use and psychotic experiences: evidence of cumulative and synergistic effects

PubMed Central

Morgan, Craig; Reininghaus, Ulrich; Reichenberg, Abraham; Frissa, Souci; Hotopf, Matthew; Hatch, Stephani L.

2014-01-01

Background There is robust evidence that childhood adversity is associated with an increased risk of psychosis. There is, however, little research on intervening factors that might increase or decrease risk following childhood adversity. Aims To investigate main effects of, and synergy between, childhood abuse and life events and cannabis use on odds of psychotic experiences. Method Data on psychotic experiences and childhood abuse, life events and cannabis use were collected from 1680 individuals as part of the South East London Community Health Study (SELCoH), a population-based household survey. Results There was strong evidence that childhood abuse and number of life events combined synergistically to increase odds of psychotic experiences beyond the effects of each individually. There was similar, but weaker, evidence for cannabis use (past year). Conclusions Our findings are consistent with the hypothesis that childhood abuse creates an enduring vulnerability to psychosis that is realised in the event of exposure to further stressors and risk factors. PMID:24627297

In silico design of novel proton-pump inhibitors with reduced adverse effects.

PubMed

Li, Xiaoyi; Kang, Hong; Liu, Wensheng; Singhal, Sarita; Jiao, Na; Wang, Yong; Zhu, Lixin; Zhu, Ruixin

2018-05-30

The development of new proton-pump inhibitors (PPIs) with less adverse effects by lowering the pKa values of nitrogen atoms in pyrimidine rings has been previously suggested by our group. In this work, we proposed that new PPIs should have the following features: (1) number of ring II = number of ring I + 1; (2) preferably five, six, or seven-membered heteroatomic ring for stability; and (3) 1 < pKa1 < 4. Six molecular scaffolds based on the aforementioned criteria were constructed, and R groups were extracted from compounds in extensive data sources. A virtual molecule dataset was established, and the pKa values of specific atoms on the molecules in the dataset were calculated to select the molecules with required pKa values. Drug-likeness screening was further conducted to obtain the candidates that significantly reduced the adverse effects of long-term PPI use. This study provided insights and tools for designing targeted molecules in silico that are suitable for practical applications.

Progressive gait ataxia following deep brain stimulation for essential tremor: adverse effect or lack of efficacy?

PubMed

Reich, Martin M; Brumberg, Joachim; Pozzi, Nicolò G; Marotta, Giorgio; Roothans, Jonas; Åström, Mattias; Musacchio, Thomas; Lopiano, Leonardo; Lanotte, Michele; Lehrke, Ralph; Buck, Andreas K; Volkmann, Jens; Isaias, Ioannis U

2016-11-01

syndrome caused by a maladaptive response to neurostimulation of the (sub)thalamic area. The metabolic signature of progressive gait ataxia is an activation of the cerebellar nodule, which may be caused by inadvertent current spread and antidromic stimulation of a cerebellar outflow pathway originating in the vermis. An anatomical candidate could be the ascending limb of the uncinate tract in the subthalamic area. Adjustments in programming and precise placement of the electrode may prevent this adverse effect and help fine-tuning deep brain stimulation to ameliorate tremor without negative cerebellar signs. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The applicability of animal health surveillance systems for post-market monitoring of potential adverse effects of genetically modified (GM) feed.

PubMed

Vince, L; Kleter, G A; Kostov, K; Pfeiffer, D U; Guitian, J

2018-04-20

A facultative post market monitoring of potential health impacts of genetically modified (GM) feedstuffs on livestock consuming these feeds after pre-market risk assessment is under ongoing consideration. Within the IPAFEED database, scientific studies on health effects beyond performance in livestock and the results of a systematic search for evidence of outcome effects due to GM feed are consolidated. These outcomes were reviewed and checked for consistency in order to identify plausible syndromes suitable for conducting surveillance. The 24 selected studies showed no consistent changes in any health parameter. There were no repeated studies in any species by GM crop type and animal species. As such, there is insufficient evidence to inform the design of surveillance systems for detecting known adverse effects. Animal health surveillance systems have been proposed for the post market monitoring of potential adverse effects in animals. Such systems were evaluated for their applicability to the detection of hypothetical adverse effects and their strengths and weaknesses to detect syndromes of concern are presented. For known adverse effects, applied controlled post-market studies may yield conclusive and high-quality evidence. For detecting unknown adverse effects, the use of existing surveillance systems may still be of interest. A simulation tool developed within the project can be adapted and applied to existing surveillance systems to explore their applicability to the detection of potential adverse effects of GM feed. Copyright © 2018. Published by Elsevier Ltd.

Honeybees Produce Millimolar Concentrations of Non-Neuronal Acetylcholine for Breeding: Possible Adverse Effects of Neonicotinoids.

PubMed

Wessler, Ignaz; Gärtner, Hedwig-Annabel; Michel-Schmidt, Rosmarie; Brochhausen, Christoph; Schmitz, Luise; Anspach, Laura; Grünewald, Bernd; Kirkpatrick, Charles James

2016-01-01

The worldwide use of neonicotinoid pesticides has caused concern on account of their involvement in the decline of bee populations, which are key pollinators in most ecosystems. Here we describe a role of non-neuronal acetylcholine (ACh) for breeding of Apis mellifera carnica and a so far unknown effect of neonicotinoids on non-target insects. Royal jelly or larval food are produced by the hypopharyngeal gland of nursing bees and contain unusually high ACh concentrations (4-8 mM). ACh is extremely well conserved in royal jelly or brood food because of the acidic pH of 4.0. This condition protects ACh from degradation thus ensuring delivery of intact ACh to larvae. Raising the pH to ≥5.5 and applying cholinesterase reduced the content of ACh substantially (by 75-90%) in larval food. When this manipulated brood was tested in artificial larval breeding experiments, the survival rate was higher with food supplemented by 100% with ACh (6 mM) than with food not supplemented with ACh. ACh release from the hypopharyngeal gland and its content in brood food declined by 80%, when honeybee colonies were exposed for 4 weeks to high concentrations of the neonicotinoids clothianidin (100 parts per billion [ppb]) or thiacloprid (8,800 ppb). Under these conditions the secretory cells of the gland were markedly damaged and brood development was severely compromised. Even field-relevant low concentrations of thiacloprid (200 ppb) or clothianidin (1 and 10 ppb) reduced ACh level in the brood food and showed initial adverse effects on brood development. Our findings indicate a hitherto unknown target of neonicotinoids to induce adverse effects on non-neuronal ACh which should be considered when re-assessing the environmental risks of these compounds. To our knowledge this is a new biological mechanism, and we suggest that, in addition to their well documented neurotoxic effects, neonicotinoids may contribute to honeybee colony losses consecutive to a reduction of the ACh content in

An Analysis of Adverse Events in the Rehabilitation Department: Using the Veterans Affairs Root Cause Analysis System.

PubMed

Hagley, Gregory W; Mills, Peter D; Shiner, Brian; Hemphill, Robin R

2018-04-01

Root cause analyses (RCA) are often completed in health care settings to determine causes of adverse events (AEs). RCAs result in action plans designed to mitigate future patient harm. National reviews of RCA reports have assessed the safety of numerous health care settings and suggested opportunities for improvement. However, few studies have assessed the safety of receiving care from physical therapists, occupational therapists, or speech and language pathology pathologists. The objective of this study was to determine the types of AEs, root causes, and action plans for risk mitigation that exist within the disciplines of rehabilitation medicine. This study is a retrospective, cross-sectional review. A national search of the Veterans Health Administration RCA database was conducted to identify reports describing AEs associated with physical therapy, occupational therapy, or speech and language pathology services between 2009 and May 2016. Twenty-five reports met the inclusion requirements. The reports were classified by the event type, root cause, action plans, and strength of action plans. Delays in care (32.0%) and falls (28.0%) were the most common type of AE. Three AEs resulted in death. RCA teams identified deficits regarding policy and procedures as the most common root cause. Eighty-eight percent of RCA reports included strong or intermediate action plans to mitigate risk. Strong action plans included standardizing emergency terminology and implementing a dedicated line to call for an emergency response. These data are self-reported and only AEs that are scored as a safety assessment code 3 in the system receive a full RCA, so there are likely AEs that were not captured in this study. In addition, the RCA reports are deidentified and so do not include all patient characteristics. As the Veterans Health Administration system services mostly men, the data might not generalize to non-Veterans Health Administration systems with a different patient mix. Care

Adverse events related to blood transfusion

PubMed Central

Sahu, Sandeep; Hemlata; Verma, Anupam

2014-01-01

The acute blood transfusion reactions are responsible for causing most serious adverse events. Awareness about various clinical features of acute and delayed transfusion reactions with an ability to assess the serious reactions on time can lead to a better prognosis. Evidence-based medicine has changed today's scenario of clinical practice to decrease adverse transfusion reactions. New evidence-based algorithms of transfusion and improved haemovigilance lead to avoidance of unnecessary transfusions perioperatively. The recognition of adverse events under anaesthesia is always challenging. The unnecessary blood transfusions can be avoided with better blood conservation techniques during surgery and with anaesthesia techniques that reduce blood loss. Better and newer blood screening methods have decreased the infectious complications to almost negligible levels. With universal leukoreduction of red blood cells (RBCs), selection of potential donors such as use of male donors only plasma and restriction of RBC storage, most of the non-infectious complications can be avoided. PMID:25535415

Novel Associations between FAAH Genetic Variants and Postoperative Central Opioid related Adverse Effects

PubMed Central

Sadhasivam, Senthilkumar; Zhang, Xue; Chidambaran, Vidya; Mavi, Jagroop; Pilipenko, Valentina; Mersha, Tesfaye B.; Meller, Jaroslaw; Kaufman, Kenneth M.; Martin, Lisa J.; McAuliffe, John

2014-01-01

Opioid effects are potentiated by cannabinoid agonists including anandamide, an endocannabinoid. Inter-individual variability in responses to opioids is a major clinical problem. Multiple deaths and anoxic brain injuries occur every year in due to opioid induced respiratory depression in surgical patients and drug abusers of opioids and cannabinoids. This study aimed to determine specific associations between genetic variants of fatty acid amide hydrolase (FAAH) and postoperative central opioid adverse effects in children undergoing tonsillectomy. This is a prospective genotype blinded observational study 259 healthy children between 6 and 15 years that received standard perioperative care with a standard anesthetic and an intraoperative dose of morphine were enrolled. Associations between frequent polymorphisms of FAAH and central postoperative opioid adverse effects including, respiratory depression (RD), postoperative nausea and vomiting (PONV) and prolonged stay in Post Anesthesia Recovery Room (PACU) due to RD and PONV were analyzed. Five specific FAAH SNPs had significant associations with more than 2 fold increased risk for refractory PONV (adjusted p<0.0018), and nominal associations (p<0.05) with RD and prolonged PACU stay in white children undergoing tonsillectomy. FAAH SNP, rs324420 is a missense mutation with altered FAAH function and it is linked with other FAAH SNPs associated with PONV and RD in our cohort; association between PONV and rs324420 was confirmed in our extended cohort with additional 66 white children. Specific FAAH polymorphisms are associated with refractory PONV, opioid-related respiratory depression, and prolonged PACU stay due to opioid adverse effects in white children undergoing tonsillectomy. PMID:25558980

Chronic effects of environmentally-relevant concentrations of lead in Pelophylax nigromaculata tadpoles: Threshold dose and adverse effects.

PubMed

Huang, Min-Yi; Duan, Ren-Yan; Ji, Xiang

2014-06-01

Lead (Pb) is a common heavy metal in the natural environment, but its concentration has been increasing alongside widespread industrial and agricultural development in China. The dark-spotted frog Pelophylax (formerly Rana) nigromaculata (Anura: Ranidae) is distributed across East Asia and inhabits anthropogenic habitats such as farmland. Here, P. nigromaculata tadpoles (Gosner stage 19-46) were exposed to Pb at different concentrations (0, 40, 80, 160, 320, 640 and 1280µg/L) and Pb-induced survival, metamorphosis time, development, malformations, mobility and gonad structure were monitored. The results showed that above the threshold concentration of Pb, adverse effects were obvious. As the concentration of Pb increased, the adverse effects on different traits followed different patterns: the effects on hindlimb length, survival rate, metamorphosis rate, total malformation rate, swimming speed and jumping speed largely exhibited a linear pattern; the effects on snout-vent length, body mass and forelimb length largely exhibited a bimodal pattern. Sex ratio and gonadal histology were not affected by Pb, suggesting that Pb is not strongly estrogenic in P. nigromaculata. Copyright © 2014 Elsevier Inc. All rights reserved.

Adverse Effects of Plant Food Supplements Self-Reported by Consumers in the PlantLIBRA Survey Involving Six European Countries

PubMed Central

Restani, Patrizia; Di Lorenzo, Chiara; Garcia-Alvarez, Alicia; Badea, Mihaela; Ceschi, Alessandro; Egan, Bernadette; Dima, Lorena; Lüde, Saskia; Maggi, Franco M.; Marculescu, Angela; Milà-Villarroel, Raimon; Raats, Monique M.; Ribas-Barba, Lourdes; Uusitalo, Liisa; Serra-Majem, Lluís

2016-01-01

Background The use of food supplements containing botanicals is increasing in European markets. Although intended to maintain the health status, several cases of adverse effects to Plant Food Supplements (PFS) have been described. Objectives To describe the self-reported adverse effects collected during the European PlantLIBRA PFS Consumer Survey 2011–2012, with a critical evaluation of the plausibility of the symptomatology reported using data from the literature and from the PlantLIBRA Poisons Centers' survey. Subjects/Setting From the total sample of 2359 consumers involved in the consumers' survey, 82 subjects reported adverse effects due to a total of 87 PFS. Results Cases were self-reported, therefore causality was not classified on the basis of clinical evidence, but by using the frequency/strength of adverse effects described in scientific papers: 52 out of 87 cases were defined as possible (59.8%) and 4 as probable (4.6%). Considering the most frequently cited botanicals, eight cases were due to Valeriana officinalis (garden valerian); seven to Camellia sinensis (tea); six to Ginkgo biloba (Maidenhair tree) and Paullinia cupana (guarana). Most adverse events related to the gastrointestinal tract, nervous and cardiovascular systems. Conclusions Comparing the data from this study with those published in scientific papers and obtained by the PlantLIBRA Poisons Centers' survey, some important conclusions can be drawn: severe adverse effects to PFS are quite rare, although mild or moderate adverse symptoms can be present. Data reported in this paper can help health professionals (and in particular family doctors) to become aware of possible new problems associated with the increasing use of food supplements containing botanicals. PMID:26928206

Left ventricular global longitudinal strain predicts major adverse cardiac events and all-cause mortality in heart transplant patients.

PubMed

Clemmensen, Tor Skibsted; Eiskjær, Hans; Løgstrup, Brian Bridal; Ilkjær, Lars Bo; Poulsen, Steen Hvitfeldt

2017-05-01

Left ventricular global longitudinal strain (LVGLS) is a robust longitudinal myocardial deformation marker that is strongly affected by cardiac allograft vasculopathy (CAV), microvascular dysfunction, and acute cellular rejection (ACR). We evaluated graft deformation for risk stratification in long-term heart transplant (HTx) patients. The study included 196 patients who underwent HTx between 2011 and 2013. Patients underwent comprehensive echocardiography and coronary angiography. Previous rejection burden was assessed, and ACR grades were calculated. Patients were prospectively followed until February 24, 2016. Major adverse cardiac events (MACE), including coronary event, heart failure, treated rejection, and cardiovascular death, and all-cause mortality were recorded. During follow-up, 57 patients experienced MACE. Median follow-up was 1,035 (interquartile range [IQR] 856-1,124) days. Median time to first event was 534 (IQR 276-763) days. LVGLS was a strong predictor of MACE (hazard ratio [HR] 4.9, 95% confidence interval [CI] 2.7-8.9, p < 0.0001) in patients with and without CAV. LVGLS was a strong predictor of all-cause mortality (HR 4.9, 95% CI 2.2-10.8, p < 0.0001). Left ventricular ejection fraction (LVEF) also predicted MACE, but only in patients with CAV. No relationship between LVEF and all-cause mortality was seen. We obtained a strong MACE (HR 6.3, 95% CI 2.8-14.1, p < 0.0001) and all-cause mortality (HR 6.6, 95% CI 2.3-19.2, p < 0.0001) predictive model by combining LVGLS and restrictive left ventricular filling pattern (LVFP), which remained strong after adjustment for CAV, ACR score, hemoglobin, creatinine, and time since transplantation. Measurement of LVGLS strongly predicts MACE and mortality in long-term HTx patients. Predictive ability was seen in patients with and without CAV. A combined model of left ventricular systolic deformation by LVGLS and diastolic graft performance by LVFP was a stronger model for prediction of MACE and all-cause

Parent Report of Antidepressant, Anxiolytic, and Antipsychotic Medication Use in Individuals with Williams Syndrome: Effectiveness and Adverse Effects

ERIC Educational Resources Information Center

Martens, Marilee A.; Seyfer, Daisha L.; Andridge, Rebecca R.; Foster, Jessica E. A.; Chowdhury, Monali; McClure, Kelsey E.; Coury, Daniel L.

2012-01-01

Williams syndrome (WS) is a neurodevelopmental genetic disorder characterized in part by anxiety and behavioral difficulties. We examine the effectiveness and adverse effects of antidepressant, anxiolytic, and antipsychotic medications in individuals with WS. A total of 513 parents/caregivers completed a survey of psychotropic medication usage…

Putative kappa opioid heteromers as targets for developing analgesics free of adverse effects.

PubMed

Le Naour, Morgan; Lunzer, Mary M; Powers, Michael D; Kalyuzhny, Alexander E; Benneyworth, Michael A; Thomas, Mark J; Portoghese, Philip S

2014-08-14

It is now generally recognized that upon activation by an agonist, β-arrestin associates with G protein-coupled receptors and acts as a scaffold in creating a diverse signaling network that could lead to adverse effects. As an approach to reducing side effects associated with κ opioid agonists, a series of β-naltrexamides 3-10 was synthesized in an effort to selectively target putative κ opioid heteromers without recruiting β-arrestin upon activation. The most potent derivative 3 (INTA) strongly activated KOR-DOR and KOR-MOR heteromers in HEK293 cells. In vivo studies revealed 3 to produce potent antinociception, which, when taken together with antagonism data, was consistent with the activation of both heteromers. 3 was devoid of tolerance, dependence, and showed no aversive effect in the conditioned place preference assay. As immunofluorescence studies indicated no recruitment of β-arrestin2 to membranes in coexpressed KOR-DOR cells, this study suggests that targeting of specific putative heteromers has the potential to identify leads for analgesics devoid of adverse effects.

Cannabis: an overview of its adverse acute and chronic effects and their implications.

PubMed

Ford, Talitha C; Hayley, Amie C; Downey, Luke A; Parrott, Andrew C

2017-07-12

In many communities, cannabis is perceived as a low-risk drug, leading to political lobbying to decriminalise its use. However, acute and chronic cannabis use has been shown to be harmful to several aspects of psychological and physical health, such as mood states, psychiatric outcomes, neurocognition, driving and general health. Furthermore, cannabis is highly addictive, and the adverse effects of withdrawal can lead to regular use. These in turn have adverse implications for public safety and health expenditure. Although the cannabinoid cannabidiol (CBD) has been shown to have positive health outcomes with its antioxidant, anticonvulsant, anti-inflammatory and neuroprotective properties, high-potency cannabis is particularly damaging due to its high tetrahydrocannabinol (THC), low CDB concentration. It is this high-potency substance that is readily available recreationally. While pharmaceutical initiatives continue to investigate the medical benefits of CDB, "medicinal cannabis" still contains damaging levels of THC. Altogether, we argue there is insufficient evidence to support the safety of cannabis and its subsequent legalisation for recreational use. Furthermore, its use for medicinal purposes should be done with care. We argue that the public conversation for the legalisation of cannabis must include scientific evidence for its adverse effects. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Predicting the clinical efficacy and potential adverse effects of a humanized anticocaine monoclonal antibody

PubMed Central

Norman, Andrew B; Ball, William J

2012-01-01

The effects of a humanized monoclonal antibody (mAb) having high affinity and specificity for cocaine in animal models are reviewed. The mAb reduced the concentration of cocaine in the brain of mice after intravenous injection of cocaine. In addition, the mAb increased the concentration of cocaine required to reinstate cocaine self-administration. These effects may predict clinical efficacy of a passive immunotherapy for reducing the probability of cocaine-induced relapse. However, in the presence of the mAb, once cocaine self-administration was reinstated, the consumption rate of cocaine was increased. This effect is hypothesized to result from a pharmacokinetic/pharmacodynamic interaction. A humanized mAb should minimize adverse events related to the immunogenicity of the mAb protein, and the specificity for cocaine should avoid adverse events related to interactions with physiologically relevant endogenous proteins. PMID:22401638

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

PubMed Central

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

2015-01-01

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

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

PubMed

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

2017-12-01

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

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

PubMed Central

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

2013-01-01

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

Patterns of benzylpiperazine/trifluoromethylphenylpiperazine party pill use and adverse effects in a population sample in New Zealand.

PubMed

Wilkins, Chris; Sweetsur, Paul; Girling, Melissa

2008-11-01

A large legal market for party pills containing benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP) developed in New Zealand after 2004. The use of these party pills has been associated with adverse health effects. The purpose of this paper was to assess a general population sample of party pill users to investigate the relationship between (1) patterns of use of BZP/TFMPP party pills and concurrent use of other drug types, and (2) adverse side effects from BZP/TFMPP party pill use. A national household survey of the use of BZP/TFMPP party pills was conducted using a computer-assisted telephone interviewing (CATI) facility. The quantity of BZP and TFMPP in each brand of party pill was obtained from the National Poisons Centre. Multiple logistic regression analysis was used to identify independent predictors of having experienced adverse side effects from party pills. The mean quantity of BZP/TFMPP taken on an occasion of greatest use was 533 mg (median 400 mg, range 43-2500 mg). Being female, using cannabis and other drugs concurrently with BZP/TFMPP party pills, taking large quantities of party pills in a single session and taking 5-hydroxytryptophan (5-HTP) recovery pills at the same time as party pills were independent predictors of having experienced an adverse problem from party pills. Females may be at greater risk of experiencing problems from BZP/TFMPP party pills due to their smaller physical size. Taking 5-HTP 'recovery' pills with party pills may increase the risk of adverse effects as both substances increase users' levels of serotonin.

Adverse effect of diesel engine produced particulate matter on various stone types and concrete: a laboratory exposure experiment

NASA Astrophysics Data System (ADS)

Farkas, Orsolya; Szabados, György; Antal, Ákos; Török, Ákos

2015-04-01

The effect of particulate matter on construction materials have been studied under laboratory conditions. For testing the adverse effects of diesel soot and particulate matter on stone and concrete a small scale laboratory exposure chamber was constructed. Blocks of 9 different stone types and concrete was placed in the chamber and an exhaust pipe of diesel engine was diverted into the system. Tested stones included: porous limestone, cemented non-porous limestone, travertine, marble, rhyolite tuff, andesite and granite. The engine was operated for 10 hours and the produced particulate matter was diverted directly to the surface of the material specimens of 3 cm in diameter each. Working parameters of the engine were controlled; the composition of the exhaust gas, smoke value and temperature were continuously measured during the test. Test specimens were documented and analysed prior to exposure and after the exposure test. Parameters such colorimetric values, weight, surface properties, mineralogical compositions of the test specimens were recorded. The working temperature was in the order of 300°C-320°C. The gas concentration was in ppm as follows: 157 CO; 5.98 CO2, 34.3 THC; 463 NOx; 408 NO; 12.88 O2. Our tests have demonstrated that significant amount of particulate matter was deposited on construction materials even at a short period of time; however the exposure was very intense. It also indicates that that the interaction of particulate matter and aerosol compounds with construction materials in urban areas causes rapid decay and has an adverse effect not only on human health but also on built structures.

An unreported clindamycin adverse reaction: wrist monoarthritis.

PubMed

Alikhani, Ahmad; Salehifar, Ebrahim

2012-01-01

Clindamycin is a lincosamide antibiotic which is approved for the treatment of Anaerobic, Streptococcal and Staphylococcal infections. There has been an increased interest in the use of clindamycin since it achieves high intracellular levels in phagocytic cells, high levels in bone and appears to have an antitoxin effect against the toxin elaborating strains of streptococci and staphylococci. Clindamycin is considered as a bacteriostatic antibiotic, while it is bactericidal against some strains of Staphylococci, Streptococci and Anaerobes such as B. fragilis. Its major disadvantage is its propensity to cause antibiotic-associated diarrhea. In spite of expanded use of clindamycin in bone infections, the adverse reactions of this antibiotic are minor. Polyarthritis is a rare adverse effect of this antibiotic. In this case report, we studied a 75-year-old male patient with past history of drop attack and subdural hematoma who developed skull osteomyelitis after the surgery. After two weeks of intravenous antibiotic therapy, wound discharge was stopped and the patient was discharged from the hospital with the maintenance oral antibiotic therapy including clindamycin 300 mg q8 h, ciprofloxacin 500 mg q12 h and rifampin 600 mg fasting. Six days after the beginning of oral antibiotics, right wrist monoarthritis was developed. It was unresponsive to nonsteroidal anti-inflammatory drug and improved after decreased doses of clindamycin. As best as we know, monoarthritis was not reported with clindamycin previously.

Surveillance of adverse effects following vaccination and safety of immunization programs.

PubMed

Waldman, Eliseu Alves; Luhm, Karin Regina; Monteiro, Sandra Aparecida Moreira Gomes; Freitas, Fabiana Ramos Martin de

2011-02-01

The aim of the review was to analyze conceptual and operational aspects of systems for surveillance of adverse events following immunization. Articles available in electronic format were included, published between 1985 and 2009, selected from the PubMed/Medline databases using the key words "adverse events following vaccine surveillance", "post-marketing surveillance", "safety vaccine" and "Phase IV clinical trials". Articles focusing on specific adverse events were excluded. The major aspects underlying the Public Health importance of adverse events following vaccination, the instruments aimed at ensuring vaccine safety, and the purpose, attributes, types, data interpretation issues, limitations, and further challenges in adverse events following immunization were describe, as well as strategies to improve sensitivity. The review was concluded by discussing the challenges to be faced in coming years with respect to ensuring the safety and reliability of vaccination programs.

The Adverse Effects and Treatment Results of Smoking Cessation Pharmacotherapy During Fasting/Non-Fasting State.

PubMed

Iliaz, Sinem; Tural Onur, Seda; Uysal, Mehmet Atilla; Chousein, Efsun Gonca Uğur; Tanriverdi, Elif; Bagci, Belma Akbaba; Bahadir, Ayse; Hattatoglu, Didem Gorgun; Ortakoylu, Mediha Gonenc; Yurt, Sibel

2017-07-03

Cigarette smoking is one of the most common addictions worldwide. Muslim smokers reduce the number of cigarettes they smoke during Ramadan due to the long fasting hours. We aimed to share our experience in a smoking cessation clinic during Ramadan by analyzing the efficacy and adverse effects of once-daily dosing of bupropion or varenicline in a fasting group compared with conventional dosing in a non-fasting group. We analyzed 57 patients who attended our smoking cessation clinic during Ramadan of 2014 and 2015, and at least one follow-up visit. For the fasting patients, we prescribed bupropion or varenicline after dinner (once daily) as the maintenance therapy. We recorded demographic characteristics of the patients, fasting state, drugs taken for smoking cessation, and the dosage of the medication. At the first follow-up visit, adverse effects seen with the treatment were recorded. We conducted telephone interviews 6 months after the first visits of the patients to learn the current smoking status of the groups. Of the total 57 patients, 20 (35.1%) were fasting and 37 (64.9%) were not fasting. Fasting and non-fasting patients were similar for sex, age, smoking pack-years, marital status, educational status, and mean Fagerström scores (p >.05). Adverse effects and quit rates after 6 months of follow-up were similar between the fasting and non-fasting groups (p >.05). Although our sample size was small, we found no difference in the rates of adverse effects or smoking cessation using a single daily oral dose of bupropion or varenicline between a fasting group and a non-fasting group that received conventional dosing.

[Analysis on the adverse events of cupping therapy in the application].

PubMed

Zhou, Xin; Ruan, Jing-wen; Xing, Bing-feng

2014-10-01

The deep analysis has been done on the cases of adverse events and common injury of cupping therapy encountered in recent years in terms of manipulation and patient's constitution. The adverse events of cupping therapy are commonly caused by improper manipulation of medical practitioners, ignoring contraindication and patient's constitution. Clinical practitioners should use cupping therapy cautiously, follow strictly the rules of standard manipulation and medical core system, pay attention to the contraindication and take strict precautions against the occurrence of adverse events.

Characterizing "Adversity" of Pathology Findings in ...

EPA Pesticide Factsheets

The identification of adverse health effects has a central role in the development and risk/safety assessment of chemical entities and pharmaceuticals. There is currently a need for better alignment in the toxicologic pathology community regarding how nonclinical adversity is determined and characterized. The European Society of Toxicologic Pathology (ESTP) therefore coordinated a workshop in June 2015 to review available definitions of adversity, weigh determining and qualifying factors of adversity based on case examples, and recommend a practical approach to define and characterize adversity in toxicology reports. The international group of expert pathologists and toxicologists emphasized that a holistic, weight-of-evidence, case-specific approach should be followed for each adversity assessment. It was recommended that nonclinical adversity should typically be determined at a morphological level (most often the organ) in the pathology report and should refer specifically to the test species. Final adversity calls, integration of target pharmacology/pathway information, and consideration of human translation should generally be made in toxicology overview reports. Differences in interpretation and implications of adversity calls between (agro)chemical and pharmaceutical industries and among world regions were highlighted. The results of this workshop should serve a valuable prerequisite for future organ- or lesion-specific workshops planned by the ESTP. This

The Role of Mindfulness in Reducing the Adverse Effects of Childhood Stress and Trauma

PubMed Central

Ortiz, Robin; Sibinga, Erica M.

2017-01-01

Research suggests that many children are exposed to adverse experiences in childhood. Such adverse childhood exposures may result in stress and trauma, which are associated with increased morbidity and mortality into adulthood. In general populations and trauma-exposed adults, mindfulness interventions have demonstrated reduced depression and anxiety, reduced trauma-related symptoms, enhanced coping and mood, and improved quality of life. Studies in children and youth also demonstrate that mindfulness interventions improve mental, behavioral, and physical outcomes. Taken together, this research suggests that high-quality, structured mindfulness instruction may mitigate the negative effects of stress and trauma related to adverse childhood exposures, improving short- and long-term outcomes, and potentially reducing poor health outcomes in adulthood. Future work is needed to optimize implementation of youth-based mindfulness programs and to study long-term outcomes into adulthood. PMID:28264496

Evidence for the Adverse Effect of Starvation on Bone Quality: A Review of the Literature

PubMed Central

Kueper, Janina; Beyth, Shaul; Liebergall, Meir; Kaplan, Leon; Schroeder, Josh E.

2015-01-01

Malnutrition and starvation's possible adverse impacts on bone health and bone quality first came into the spotlight after the horrors of the Holocaust and the ghettos of World War II. Famine and food restrictions led to a mean caloric intake of 200–800 calories a day in the ghettos and concentration camps, resulting in catabolysis and starvation of the inhabitants and prisoners. Severely increased risks of fracture, poor bone mineral density, and decreased cortical strength were noted in several case series and descriptive reports addressing the medical issues of these individuals. A severe effect of severely diminished food intake and frequently concomitant calcium- and Vitamin D deficiencies was subsequently proven in both animal models and the most common cause of starvation in developed countries is anorexia nervosa. This review attempts to summarize the literature available on the impact of the metabolic response to Starvation on overall bone health and bone quality. PMID:25810719

"Competitive quenching": a mechanism by which perihydroxylated perylenequinone photosensitizers can prevent adverse phototoxic damage caused by verteporfin during photodynamic therapy.

PubMed

Lavie, Gad; Barliya, Tilda; Mandel, Mathilda; Blank, Michael; Ron, Yonina; Orenstein, Arie; Livnat, Tami; Friedman, Noga; Weiner, Lev; Sheves, Mordechai; Weinberger, Dov

2007-01-01

Incorporation of photodynamic therapy into clinical practice for induction of vascular photo-occlusion highlights the need to prevent adverse phototoxicity to sensitive juxtaposed tissues, particularly in the retina. We developed a system termed "competitive quenching" to prevent adverse phototoxic damage. It involves differential compartmentalization of a photoactivator to the intravascular compartment for photoexcitation and delivery of phototoxicity to targeted vessels. A different photodynamic agent is partitioned to the extravascular retinal space to quench reactive oxygen species generated by photosensitization, thereby protecting the adjacent retinal tissues from adverse phototoxicity. The absorption spectra of quenchers must span wavelengths that are shorter and excluded from the spectral range of photoexcitation light to prevent photoactivation of the quencher. Perihydroxylated perylenequinones were found to be suitable to function as "competitive quenchers" with the prototype hypericin identified as a potent quencher. Here we examined the mechanisms operative in competitive quenching and suggest that hypericin forms a complex with verteporfin, thereby quenching singlet oxygen formation. Furthermore, we show that hypericin, with six phenolic hydroxyls, protects retinal and endothelial hybridoma cells from phototoxicity more effectively than the dimethyl tetrahydroxy helianthrone structural analog with only four such phenolic hydroxyls. The findings suggest that hydroxyl numbers contribute to the efficacy of competitive quenching.

Childhood adversity moderates the effect of ADH1B on risk for alcohol-related phenotypes in Jewish Israeli drinkers.

PubMed

Meyers, Jacquelyn L; Shmulewitz, Dvora; Wall, Melanie M; Keyes, Katherine M; Aharonovich, Efrat; Spivak, Baruch; Weizman, Abraham; Frisch, Amos; Edenberg, Howard J; Gelernter, Joel; Grant, Bridget F; Hasin, Deborah

2015-01-01

Childhood adversity and genetic variant ADH1B-rs1229984 have each been shown to influence heavy alcohol consumption and disorders. However, little is known about how these factors jointly influence these outcomes. We assessed the main and additive interactive effects of childhood adversity (abuse, neglect and parental divorce) and the ADH1B-rs1229984 on the quantitative phenotypes 'maximum drinks in a day' (Maxdrinks) and DSM-Alcohol Use Disorder (AUD) severity, adjusting for demographic variables, in an Israeli sample of adult household residents (n = 1143) evaluated between 2007 and 2009. Childhood adversity and absence of the protective ADH1B-rs1229984 A allele were associated with greater mean Maxdrinks (mean differences: 1.50; 1.13, respectively) and AUD severity (mean ratios: 0.71; 0.27, respectively). In addition, childhood adversity moderated the ADH1B-rs1229984 effect on Maxdrinks (P < 0.01) and AUD severity (P < 0.05), in that there was a stronger effect of ADH1B-rs1229984 genotype on Maxdrinks and AUD severity among those who had experienced childhood adversity compared with those who had not. ADH1B-rs1229984 impacts alcohol metabolism. Therefore, among those at risk for greater consumption, e.g. those who experienced childhood adversity, ADH1B-rs1229984 appears to have a stronger effect on alcohol consumption and consequently on risk for AUD symptom severity. Evidence for the interaction of genetic vulnerability and early life adversity on alcohol-related phenotypes provides further insight into the complex relationships between genetic and environmental risk factors. © 2013 Society for the Study of Addiction.

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

PubMed Central

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

2006-01-01

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

Serious adverse events associated with yellow fever vaccine.

PubMed

de Menezes Martins, Reinaldo; Fernandes Leal, Maria da Luz; Homma, Akira

2015-01-01

Yellow fever vaccine was considered one of the safest vaccines, but in recent years it was found that it could rarely cause invasive and disseminated disease in some otherwise healthy individuals, with high lethality. After extensive studies, although some risk factors have been identified, the real cause of causes of this serious adverse event are largely unknown, but findings point to individual host factors. Meningoencephalitis, once considered to happen only in children less than 6 months of age, has also been identified in older children and adults, but with good prognosis. Efforts are being made to develop a safer yellow fever vaccine, and an inactivated vaccine or a vaccine prepared with the vaccine virus envelope produced in plants are being tested. Even with serious and rare adverse events, yellow fever vaccine is the best way to avoid yellow fever, a disease of high lethality and should be used routinely in endemic areas, and on people from non-endemic areas that could be exposed, according to a careful risk-benefit analysis.

The lack of knowledge about the voluntary reporting system of adverse drug reactions as a major cause of underreporting: direct survey among health professionals.

PubMed

Pérez García, Mariley; Figueras, Albert

2011-12-01

Underreporting suspected adverse drug reactions (ADRs) is one of the main problems that face the pharmacovigilance (PhV) systems based on yellow card schemes. To measure the knowledge level on the suspected ADR voluntary reporting system among physicians and pharmacists in Venezuela and to study its relationship with different variables. A population-based, anonymous, and self-administered questionnaire was addressed to health professionals along the national territory of Venezuela. An algorithm was developed to classify the knowledge level on the voluntary reporting system. Taken as a whole, the level of knowledge on the voluntary reporting system was "poor." Among the 515 participant physicians, 62.3% (95%CI = 58.0-66.5%) had a "poor" level of knowledge; PhV was associated with "control" of medicines use, and only 24.7% had ever reported a suspected ADR. "Medical specialty" was the only variable that showed a relationship with the knowledge level (p = 0.0041). Among the 78 participant pharmacists, 66.7% had a "poor" knowledge level (95%CI = 55.1-76.9%). The knowledge level on the voluntary reporting system among physicians and pharmacists in Venezuela is poor. These results strengthen the hypothesis that being unaware of the adverse effects of medicines and not knowing the existence of a PhV system is a major cause of underreporting. A careful study of the actual knowledge of PhV could be the basis to set up interventions specifically designed to overcome misleading concepts and to improve the reporting rate at a national level. Copyright © 2011 John Wiley & Sons, Ltd.

Adverse Effects of Daylight Saving Time on Adolescents' Sleep and Vigilance

PubMed Central

Medina, Diana; Ebben, Matthew; Milrad, Sara; Atkinson, Brianna; Krieger, Ana C.

2015-01-01

Study Objectives: Daylight saving time (DST) has been established with the intent to reduce energy expenditure, however unintentional effects on sleep and vigilance have not been consistently measured. The objective of this study was to test the hypothesis that DST adversely affects high school students' sleep and vigilance on the school days following its implementation. Methods: A natural experiment design was used to assess baseline and post-DST differences in objective and subjective measures of sleep and vigilance by actigraphy, sleep diary, sleepiness scale, and psychomotor vigilance testing (PVT). Students were tested during school days immediately preceding and following DST. Results: A total of 40 high school students were enrolled in this study; 35 completed the protocol. Sleep duration declined by an average of 32 minutes on the weeknights post-DST, reflecting a cumulative sleep loss of 2 h 42 min as compared to the baseline week (p = 0.001). This finding was confirmed by sleep diary analyses, reflecting an average sleep loss of 27 min/night (p = 0.004) post-DST. Vigilance significantly deteriorated, with a decline in PVT performance post-DST, resulting in longer reaction times (p < 0.001) and increased lapses (p < 0.001). Increased daytime sleepiness was also demonstrated (p < 0.001). Conclusions: The early March DST onset adversely affected sleep and vigilance in high school students resulting in increased daytime sleepiness. Larger scale evaluations of sleep impairments related to DST are needed to further quantify this problem in the population. If confirmed, measures to attenuate sleep loss post-DST should be implemented. Citation: Medina D, Ebben M, Milrad S, Atkinson B, Krieger AC. Adverse effects of daylight saving time on adolescents' sleep and vigilance. J Clin Sleep Med 2015;11(8):879–884. PMID:25979095

Adverse drug events in the oral cavity.

PubMed

Yuan, Anna; Woo, Sook-Bin

2015-01-01

Adverse reactions to medications are common and may have a variety of clinical presentations in the oral cavity. Targeted therapies and the new biologic agents have revolutionized the treatment of cancers, autoimmune diseases, and inflammatory and rheumatologic diseases but have also been associated with adverse events in the oral cavity. Some examples include osteonecrosis, seen with not only bisphosphonates but also antiangiogenic agents, and the distinctive ulcers caused by mammalian target of rapamycin inhibitors. As newer therapeutic agents are approved, it is likely that more adverse drug events will be encountered. This review describes the most common clinical presentations of oral mucosal reactions to medications, namely, xerostomia, lichenoid reactions, ulcers, bullous disorders, pigmentation, fibrovascular hyperplasia, white lesions, dysesthesia, osteonecrosis, infection, angioedema, and malignancy. Oral health care providers should be familiar with such events, as they will encounter them in their practice. Copyright © 2015 Elsevier Inc. All rights reserved.

WindVOiCe, a Self-Reporting Survey: Adverse Health Effects, Industrial Wind Turbines, and the Need for Vigilance Monitoring

ERIC Educational Resources Information Center

Krogh, Carmen M. E.; Gillis, Lorrie; Kouwen, Nicholas; Aramini, Jeff

2011-01-01

Industrial wind turbines have been operating in many parts of the globe. Anecdotal reports of perceived adverse health effects relating to industrial wind turbines have been published in the media and on the Internet. Based on these reports, indications were that some residents perceived they were experiencing adverse health effects. The purpose…

Adverse effects of e-cigarette exposures.

PubMed

Cantrell, F Lee

2014-06-01

In 2007, a new source of nicotine exposure was introduced to the United States market, the electronic cigarette (ECIG) or "e-cigarette". Since then, the USA ECIG market has been doubling annually. Despite their widespread popularity, there is a paucity of existing data regarding ECIG toxicity. We report the experience of a statewide poison system. The database of a statewide poison system was queried for human ECIG exposures from 2010 (when Poisindex code first generated) through 2012. Year, age, manner and route of exposure, estimate exposure amount, product concentration, if evaluated at healthcare facility and symptoms were recorded. A total of 35 cases were identified--4 in 2010, 12 in 2011, 19 in 2012. Age range 8 months-60 years. Reported symptoms were mild and transient. Five patients were evaluated in an emergency department and none were admitted. Product concentrations ranged from 4 to 30 mg of nicotine per ml. Poison centers are likely to see an increase in exposures to ECIG given their growing popularity. Our modest results suggest that adverse effects and accidental exposures to ECIG cartridges are unlikely to result in serious toxicity.

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

PubMed Central

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

2011-01-01

Background There is considerable debate as to the relative merits of using randomised controlled trial (RCT) data as opposed to observational data in systematic reviews of adverse effects. This meta-analysis of meta-analyses aimed to assess the level of agreement or disagreement in the estimates of harm derived from meta-analysis of RCTs as compared to meta-analysis of observational studies. Methods and Findings Searches were carried out in ten databases in addition to reference checking, contacting experts, citation searches, and hand-searching key journals, conference proceedings, and Web sites. Studies were included where a pooled relative measure of an adverse effect (odds ratio or risk ratio) from RCTs could be directly compared, using the ratio of odds ratios, with the pooled estimate for the same adverse effect arising from observational studies. Nineteen studies, yielding 58 meta-analyses, were identified for inclusion. The pooled ratio of odds ratios of RCTs compared to observational studies was estimated to be 1.03 (95% confidence interval 0.93–1.15). There was less discrepancy with larger studies. The symmetric funnel plot suggests that there is no consistent difference between risk estimates from meta-analysis of RCT data and those from meta-analysis of observational studies. In almost all instances, the estimates of harm from meta-analyses of the different study designs had 95% confidence intervals that overlapped (54/58, 93%). In terms of statistical significance, in nearly two-thirds (37/58, 64%), the results agreed (both studies showing a significant increase or significant decrease or both showing no significant difference). In only one meta-analysis about one adverse effect was there opposing statistical significance. Conclusions Empirical evidence from this overview indicates that there is no difference on average in the risk estimate of adverse effects of an intervention derived from meta-analyses of RCTs and meta-analyses of observational

Causes of highway road dust toxicity to an estuarine amphipod: Evaluating the effects of nicotine.

PubMed

Hiki, Kyoshiro; Nakajima, Fumiyuki; Tobino, Tomohiro

2017-02-01

Urban road dust can potentially have adverse effects on ecosystems if it is discharged into receiving waters. This study investigated the causes of highway road dust toxicity by performing sediment toxicity identification evaluation (TIE) tests with an estuarine amphipod, Grandidierella japonica. In addition to metals and polycyclic aromatic hydrocarbons, which are traditionally considered to be the major toxicants in road runoff, we focused on dissolved nicotine as a causative toxicant. The sediment TIE results suggested that organic contaminants contributed to the majority of toxicity, and that the contribution of unionized nicotine to the toxicity was the highest among the chemicals considered. However, additional mortality tests with 48-h pulsed nicotine exposure demonstrated that exposure to nicotine at the same concentration as the baseline level in TIE tests did not cause significant 10-day amphipod mortality. Thus, the road dust toxicity could not be explained only by unionized nicotine, thereby suggesting contributions from joint effects of the measured toxicants and the presence of other unmeasured factors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Biomarkers of adverse drug reactions.

PubMed

Carr, Daniel F; Pirmohamed, Munir

2018-02-01

Adverse drug reactions can be caused by a wide range of therapeutics. Adverse drug reactions affect many bodily organ systems and vary widely in severity. Milder adverse drug reactions often resolve quickly following withdrawal of the casual drug or sometimes after dose reduction. Some adverse drug reactions are severe and lead to significant organ/tissue injury which can be fatal. Adverse drug reactions also represent a financial burden to both healthcare providers and the pharmaceutical industry. Thus, a number of stakeholders would benefit from development of new, robust biomarkers for the prediction, diagnosis, and prognostication of adverse drug reactions. There has been significant recent progress in identifying predictive genomic biomarkers with the potential to be used in clinical settings to reduce the burden of adverse drug reactions. These have included biomarkers that can be used to alter drug dose (for example, Thiopurine methyltransferase (TPMT) and azathioprine dose) and drug choice. The latter have in particular included human leukocyte antigen (HLA) biomarkers which identify susceptibility to immune-mediated injuries to major organs such as skin, liver, and bone marrow from a variety of drugs. This review covers both the current state of the art with regard to genomic adverse drug reaction biomarkers. We also review circulating biomarkers that have the potential to be used for both diagnosis and prognosis, and have the added advantage of providing mechanistic information. In the future, we will not be relying on single biomarkers (genomic/non-genomic), but on multiple biomarker panels, integrated through the application of different omics technologies, which will provide information on predisposition, early diagnosis, prognosis, and mechanisms. Impact statement • Genetic and circulating biomarkers present significant opportunities to personalize patient therapy to minimize the risk of adverse drug reactions. ADRs are a significant heath issue

Adverse Psychiatric Effects Associated with Herbal Weight-Loss Products

PubMed Central

Coviello, Marialuce; Francesconi, Marta; Hough, Christina M.; De Stefano, Gianfranco; Bolzan Mariotti Posocco, Flaminia; Minichino, Amedeo; Corazza, Ornella

2015-01-01

Obesity and overeating are among the most prevalent health concerns worldwide and individuals are increasingly using performance and image-enhancing drugs (PIEDs) as an easy and fast way to control their weight. Among these, herbal weight-loss products (HWLPs) often attract users due to their health claims, assumed safety, easy availability, affordable price, extensive marketing, and the perceived lack of need for professional oversight. Reports suggest that certain HWLPs may lead to onset or exacerbation of psychiatric disturbances. Here we review the available evidence on psychiatric adverse effects of HWLPs due to their intrinsic toxicity and potential for interaction with psychiatric medications. PMID:26457296

The Neurobiology of Intervention and Prevention in Early Adversity.

PubMed

Fisher, Philip A; Beauchamp, Kate G; Roos, Leslie E; Noll, Laura K; Flannery, Jessica; Delker, Brianna C

2016-01-01

Early adverse experiences are well understood to affect development and well-being, placing individuals at risk for negative physical and mental health outcomes. A growing literature documents the effects of adversity on developing neurobiological systems. Fewer studies have examined stress neurobiology to understand how to mitigate the effects of early adversity. This review summarizes the research on three neurobiological systems relevant to interventions for populations experiencing high levels of early adversity: the hypothalamic-adrenal-pituitary axis, the prefrontal cortex regions involved in executive functioning, and the system involved in threat detection and response, particularly the amygdala. Also discussed is the emerging field of epigenetics and related interventions to mitigate early adversity. Further emphasized is the need for intervention research to integrate knowledge about the neurobiological effects of prenatal stressors (e.g., drug use, alcohol exposure) and early adversity. The review concludes with a discussion of the implications of this research topic for clinical psychology practice and public policy.

Predicting Nonauditory Adverse Radiation Effects Following Radiosurgery for Vestibular Schwannoma: A Volume and Dosimetric Analysis

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

Hayhurst, Caroline; Monsalves, Eric; Bernstein, Mark

2012-04-01

Purpose: To define clinical and dosimetric predictors of nonauditory adverse radiation effects after radiosurgery for vestibular schwannoma treated with a 12 Gy prescription dose. Methods: We retrospectively reviewed our experience of vestibular schwannoma patients treated between September 2005 and December 2009. Two hundred patients were treated at a 12 Gy prescription dose; 80 had complete clinical and radiological follow-up for at least 24 months (median, 28.5 months). All treatment plans were reviewed for target volume and dosimetry characteristics; gradient index; homogeneity index, defined as the maximum dose in the treatment volume divided by the prescription dose; conformity index; brainstem; andmore » trigeminal nerve dose. All adverse radiation effects (ARE) were recorded. Because the intent of our study was to focus on the nonauditory adverse effects, hearing outcome was not evaluated in this study. Results: Twenty-seven (33.8%) patients developed ARE, 5 (6%) developed hydrocephalus, 10 (12.5%) reported new ataxia, 17 (21%) developed trigeminal dysfunction, 3 (3.75%) had facial weakness, and 1 patient developed hemifacial spasm. The development of edema within the pons was significantly associated with ARE (p = 0.001). On multivariate analysis, only target volume is a significant predictor of ARE (p = 0.001). There is a target volume threshold of 5 cm3, above which ARE are more likely. The treatment plan dosimetric characteristics are not associated with ARE, although the maximum dose to the 5th nerve is a significant predictor of trigeminal dysfunction, with a threshold of 9 Gy. The overall 2-year tumor control rate was 96%. Conclusions: Target volume is the most important predictor of adverse radiation effects, and we identified the significant treatment volume threshold to be 5 cm3. We also established through our series that the maximum tolerable dose to the 5th nerve is 9 Gy.« less

The role of Mycoplasma and Ureaplasma in adverse pregnancy outcomes.

PubMed

Murtha, Amy P; Edwards, James M

2014-12-01

Genital mycoplasmas are frequently found in the vaginal flora across socioeconomic and ethnic groups and have been demonstrated to be involved in adverse perinatal outcomes. Both Mycoplasma and Ureaplasma spp cause inflammation potentially leading to spontaneous preterm birth and PPROM as well as postdelivery infectious complications and neonatal infections. Herein we have provided an overview of the existing literature and supportive evidence for genital mycoplasma's role in perinatal complications. Future research will need to focus on clearly delineating the species, allowing for discrimination of their effects. Copyright © 2014 Elsevier Inc. All rights reserved.

Influence of Japanese Regulatory Action on Denosumab-Related Hypocalcemia Using Japanese Adverse Drug Event Report Database.

PubMed

Takeyama, Mayu; Sai, Kimie; Imatoh, Takuya; Segawa, Katsunori; Hirasawa, Noriyasu; Saito, Yoshiro

2017-01-01

The anti-receptor activator of nuclear factor kappa-B ligand (RANKL) antibody, Denosumab (DEN), was approved in April 2012 in Japan, but a Dear Healthcare Professional Letter of Rapid Safety Communication was released in September, 2012 by the regulatory authority because of the severe hypocalcemia risks. Currently, the effectiveness of this regulatory action has not been evaluated and, therefore, this study aimed to assess its impact on DEN-induced hypocalcemia using the Japanese Adverse Drug Event Report database (JADER). The case reports from April 2012 to September 2014 were collected from the JADER, which included 151642 adverse events for the primary suspected drugs. The reporting odds ratio (ROR) of hypocalcemia as a signal of the target adverse event was analyzed for DEN and zoledronic acid (ZOL, a reference drug). Changes in RORs were compared between the pre- (Pre, April 2012 to September 2012) and post- (Post 1, October 2012 to September 2013 and Post 2, October 2013 to September 2014) periods of the regulatory action. A decrease in the hypocalcemia ROR was observed for DEN in the post-periods, especially Post 2. Multivariate logistic regression analysis showed a significant decrease in hypocalcemia signal in Post 1 (p=0.0306 vs. Pre) and Post 2 (p=0.0054 vs. Pre). ZOL caused no significant changes in ROR of hypocalcemia, and none of the drugs caused ROR changes in jaw osteonecrosis (a reference adverse event). This study suggests that the regulatory action against hypocalcemia in DEN effectively decreased hypocalcemia signal. Further studies using medical information databases are needed to confirm this result.

Pathways towards risk: syndemic conditions mediate the effect of adversity on HIV risk behaviors among young men who have sex with men (YMSM).

PubMed

Herrick, Amy; Stall, Ron; Egan, James; Schrager, Sheree; Kipke, Michele

2014-10-01

Research shows that young men who have sex with men (YMSM) engage in higher rates of health risk behaviors and experience higher rates of negative health outcomes than their peers. The purpose of this study is to determine if the effects of adversity on HIV risk are mediated by syndemics (co-occurring health problems). Participants were 470 ethnically diverse YMSM ages 18 to 24 recruited between 2005 and 2006 and surveyed every 6 months for 24 months. Regression analyses examined the impact of adversity on syndemics (emotional distress, substance use, and problematic alcohol use) and the effects of both adversity and syndemics on HIV risk behaviors over time. Gay-related discrimination and victimization-among other adversity variables-were significantly associated with syndemics and condomless sex (CS). Syndemics mediated the effects of adversity on CS in all models. Adverse events impact HIV risk taking among YMSM through syndemics. These findings suggest that prevention programs aimed at reducing adversity may reduce both the synergistic effect of multiple psychosocial health problems and HIV risk taking.

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

PubMed Central

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

2016-01-01

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

Severe unexpected adverse effects after permanent eye makeup and their management by Q-switched Nd:YAG laser.

PubMed

Goldman, Alberto; Wollina, Uwe

2014-01-01

Permanent makeup is a cosmetic tattoo that is used to enhance one's appearance, and which has become more popular among middle-aged and elderly women. A couple of benefits seem to be associated with permanent tattoos in the elderly: saving time (wake up with makeup); poor eyesight (difficult to apply makeup); and saving money. On the other hand, cosmetic tattoos bear the same risks as other tattoo procedures. We report on fading and unintended hyperpigmentation after tattooing on eyebrows and eyelids, and discuss the scientific and anatomical background behind the possible cause. Dermatochalasis may be a possible risk factor for excessive unwanted discolorations. Q-switched neodymium-doped yttrium aluminum garnet laser is an appropriate and safe therapeutic tool that can manage such adverse effects. Consumer protection warrants better information and education of the risks of cosmetic tattoos - in particular, for elderly women.

Expert panel evaluation of health information technology effects on adverse events.

PubMed

Abramson, Erika L; Kern, Lisa M; Brenner, Samantha; Hufstader, Meghan; Patel, Vaishali; Kaushal, Rainu

2014-08-01

Adverse events (AEs) among hospitalized patients occur frequently and result in significant sequelae. Federal policy is incentivizing health information technology (HIT) use, although research demonstrating safety benefits from HIT is mixed. Our objective was to evaluate the potential effects of HIT on reducing 21 different inpatient AEs. Identifying AEs most likely to be reduced by HIT can inform the design of future studies evaluating its effectiveness. We conducted a modified Delphi panel of national experts in HIT and safety. We conducted a focused literature review to inform the experts. Using a novel framework, experts rated each AE as 'definitely reduced by health IT,' 'possibly reduced by health IT' and 'not likely to be reduced by health IT'. From our panel discussion, experts identified six AEs as 'definitely reduced by health IT': (1) adverse drug events (ADEs) associated with digoxin; (2) ADE associated with IV heparin; (3) ADE associated with hypoglycaemic agents; (4) ADE associated with low molecular weight heparin and factor Xa inhibitor; (5) contrast nephropathy associated with catheter angiography; and (6) ADE hospital-acquired antibiotic-associated Clostridium difficile. Understanding the effects of HIT on patient outcomes will be essential to ensuring that the significant federal investment results in anticipated improvements. This study serves as an important early step in helping with the design of future work evaluating level of HIT infrastructure and rates of inpatient AEs. © 2014 John Wiley & Sons, Ltd.

Repeated exposure to intra-amniotic LPS partially protects against adverse effects of intravenous LPS in preterm lambs.

PubMed

Gisslen, Tate; Hillman, Noah H; Musk, Gabrielle C; Kemp, Matthew W; Kramer, Boris W; Senthamaraikannan, Paranthaman; Newnham, John P; Jobe, Alan H; Kallapur, Suhas G

2014-02-01

Histologic chorioamnionitis, frequently associated with preterm births and adverse outcomes, results in prolonged exposure of preterm fetuses to infectious agents and pro-inflammatory mediators, such as LPS. Endotoxin tolerance-type effects were demonstrated in fetal sheep following repetitive systemic or intra-amniotic (i.a.) exposures to LPS, suggesting that i.a. LPS exposure would cause endotoxin tolerance to a postnatal systemic dose of LPS in preterm sheep. In this study, randomized pregnant ewes received either two i.a. injections of LPS or saline prior to preterm delivery. Following operative delivery, the lambs were treated with surfactant, ventilated, and randomized to receive either i.v. LPS or saline at 30  min of age. Physiologic variables and indicators of systemic and lung inflammation were measured. Intravenous LPS decreased blood neutrophils and platelets values following i.a. saline compared to that after i.a. LPS. Intra-amniotic LPS prevented blood pressure from decreasing following the i.v. LPS, but also caused an increased oxygen index. Intra-amniotic LPS did not cause endotoxin tolerance as assessed by cytokine expression in the liver, lung or plasma, but increased myeloperoxidase-positive cells in the lung. The different compartments of exposure to LPS (i.a. vs i.v.) are unique to the fetal to newborn transition. Intra-amniotic LPS incompletely tolerized fetal lambs to postnatal i.v. LPS.

Is there evidence that recent consolidation in the health insurance industry has adversely affected premiums?