Public health implications of smokeless tobacco use as a harm reduction strategy.

PubMed

Savitz, David A; Meyer, Roger E; Tanzer, Jason M; Mirvish, Sidney S; Lewin, Freddi

2006-11-01

Harm reduction strategies involve promoting a product that has adverse health consequences as a substitute for one that has more severe adverse health consequences. Smokeless tobacco low in nitrosamine content offers potential benefits in reducing smoking prevalence rates. Possible harm arises from the potential for such products to serve as a gateway to more harmful tobacco products, public misinterpretation of "less harmful" as "safe," distraction from the public health goal of tobacco elimination, and ethical issues involved in advising those marketing these harmful products. We offer a research agenda to provide a stronger basis for evaluating the risks and benefits of smokeless tobacco as a means of reducing the adverse health effects of tobacco.

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

EPA Science Inventory

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

Evaluation of whole mount in situ hybridization as a tool for pathway-based toxicological research in early-life stage fathead minnows (poster)

EPA Science Inventory

Early-life stage fish can be more sensitive to chemical exposure than mature, adult fish. Therefore, defining adverse outcome pathways (AOPs) relevant to early-life stages is critical for linking perturbations of key events during fish development to potential adverse outcomes of...

Prescribing Errors Involving Medication Dosage Forms

PubMed Central

Lesar, Timothy S

2002-01-01

CONTEXT Prescribing errors involving medication dose formulations have been reported to occur frequently in hospitals. No systematic evaluations of the characteristics of errors related to medication dosage formulation have been performed. OBJECTIVE To quantify the characteristics, frequency, and potential adverse patient effects of prescribing errors involving medication dosage forms . DESIGN Evaluation of all detected medication prescribing errors involving or related to medication dosage forms in a 631-bed tertiary care teaching hospital. MAIN OUTCOME MEASURES Type, frequency, and potential for adverse effects of prescribing errors involving or related to medication dosage forms. RESULTS A total of 1,115 clinically significant prescribing errors involving medication dosage forms were detected during the 60-month study period. The annual number of detected errors increased throughout the study period. Detailed analysis of the 402 errors detected during the last 16 months of the study demonstrated the most common errors to be: failure to specify controlled release formulation (total of 280 cases; 69.7%) both when prescribing using the brand name (148 cases; 36.8%) and when prescribing using the generic name (132 cases; 32.8%); and prescribing controlled delivery formulations to be administered per tube (48 cases; 11.9%). The potential for adverse patient outcome was rated as potentially “fatal or severe” in 3 cases (0.7%), and “serious” in 49 cases (12.2%). Errors most commonly involved cardiovascular agents (208 cases; 51.7%). CONCLUSIONS Hospitalized patients are at risk for adverse outcomes due to prescribing errors related to inappropriate use of medication dosage forms. This information should be considered in the development of strategies to prevent adverse patient outcomes resulting from such errors. PMID:12213138

Use of the false discovery rate for evaluating clinical safety data.

PubMed

Mehrotra, Devan V; Heyse, Joseph F

2004-06-01

Clinical adverse experience (AE) data are routinely evaluated using between group P values for every AE encountered within each of several body systems. If the P values are reported and interpreted without multiplicity considerations, there is a potential for an excess of false positive findings. Procedures based on confidence interval estimates of treatment effects have the same potential for false positive findings as P value methods. Excess false positive findings can needlessly complicate the safety profile of a safe drug or vaccine. Accordingly, we propose a novel method for addressing multiplicity in the evaluation of adverse experience data arising in clinical trial settings. The method involves a two-step application of adjusted P values based on the Benjamini and Hochberg false discovery rate (FDR). Data from three moderate to large vaccine trials are used to illustrate our proposed 'Double FDR' approach, and to reinforce the potential impact of failing to account for multiplicity. This work was in collaboration with the late Professor John W. Tukey who coined the term 'Double FDR'.

Pharmacology of the Phosphate Binder, Lanthanum Carbonate

PubMed Central

Damment, Stephen JP

2011-01-01

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

ADESSA: A Real-Time Decision Support Service for Delivery of Semantically Coded Adverse Drug Event Data

PubMed Central

Duke, Jon D.; Friedlin, Jeff

2010-01-01

Evaluating medications for potential adverse events is a time-consuming process, typically involving manual lookup of information by physicians. This process can be expedited by CDS systems that support dynamic retrieval and filtering of adverse drug events (ADE’s), but such systems require a source of semantically-coded ADE data. We created a two-component system that addresses this need. First we created a natural language processing application which extracts adverse events from Structured Product Labels and generates a standardized ADE knowledge base. We then built a decision support service that consumes a Continuity of Care Document and returns a list of patient-specific ADE’s. Our database currently contains 534,125 ADE’s from 5602 product labels. An NLP evaluation of 9529 ADE’s showed recall of 93% and precision of 95%. On a trial set of 30 CCD’s, the system provided adverse event data for 88% of drugs and returned these results in an average of 620ms. PMID:21346964

Mining Adverse Events of Dietary Supplements from Product Labels by Topic Modeling.

PubMed

Wang, Yefeng; Gunashekar, Divya R; Adam, Terrence J; Zhang, Rui

2017-01-01

The adverse events of the dietary supplements should be subject to scrutiny due to their growing clinical application and consumption among U.S. adults. An effective method for mining and grouping the adverse events of the dietary supplements is to evaluate product labeling for the rapidly increasing number of new products available in the market. In this study, the adverse events information was extracted from the product labels stored in the Dietary Supplement Label Data-base (DSLD) and analyzed by topic modeling techniques, specifically Latent Dirichlet Allocation (LDA). Among the 50 topics generated by LDA, eight topics were manually evaluated, with topic relatedness ranging from 58.8% to 100% on the product level, and 57.1% to 100% on the ingredient level. Five out of these eight topics were coherent groupings of the dietary supplements based on their adverse events. The results demonstrated that LDA is able to group supplements with similar adverse events based on the dietary supplement labels. Such information can be potentially used by consumers to more safely use dietary supplements.

Mining Adverse Events of Dietary Supplements from Product Labels by Topic Modeling

PubMed Central

Wang, Yefeng; Gunashekar, Divya R.; Adam, Terrence J.; Zhang, Rui

2018-01-01

The adverse events of the dietary supplements should be subject to scrutiny due to their growing clinical application and consumption among U.S. adults. An effective method for mining and grouping the adverse events of the dietary supplements is to evaluate product labeling for the rapidly increasing number of new products available in the market. In this study, the adverse events information was extracted from the product labels stored in the Dietary Supplement Label Database (DSLD) and analyzed by topic modeling techniques, specifically Latent Dirichlet Allocation (LDA). Among the 50 topics generated by LDA, eight topics were manually evaluated, with topic relatedness ranging from 58.8% to 100% on the product level, and 57.1% to 100% on the ingredient level. Five out of these eight topics were coherent groupings of the dietary supplements based on their adverse events. The results demonstrated that LDA is able to group supplements with similar adverse events based on the dietary supplement labels. Such information can be potentially used by consumers to more safely use dietary supplements. PMID:29295169

Field Evaluation of an Avian Risk Assessment Model

EPA Science Inventory

We conducted two laboratory subacute dietary toxicity tests and one outdoor subacute dietary toxicity test to determine the effectiveness of the U.S. Environmental Protection Agency's deterministic risk assessment model for evaluating the potential of adverse effects to birds in ...

Methods for evaluating potential sources of chloride in surface waters and groundwaters of the conterminous United States

USGS Publications Warehouse

Granato, Gregory E.; DeSimone, Leslie A.; Barbaro, Jeffrey R.; Jeznach, Lillian C.

2015-09-04

Scientists, engineers, regulators, and decisionmakers need information about potential sources of chloride, water and solute budgets, and methods for collecting water-quality data to help identify potential sources. This information is needed to evaluate potential sources of chloride in areas where chloride may have adverse ecological effects or may degrade water supplies used for drinking water, agriculture, or industry. Knowledge of potential sources will help decisionmakers identify the best mitigation measures to reduce the total background chloride load, thereby reducing the potential for water-quality exceedances that occur because of superposition on rising background concentrations. Also, knowledge of potential sources may help decisionmakers identify the potential for the presence of contaminants that have toxic, carcinogenic, mutagenic, or endocrine-disrupting effects at concentrations that are lower by orders of magnitude than the chloride concentrations in the source water. This report is a comprehensive synthesis of relevant information, but it is not the result of an exhaustive search for literature on each topic. The potential adverse effects of chloride on infrastructure and the environment are not discussed in this report because these issues have been extensively documented elsewhere.

TOXCAST: A TOOL FOR THE PRIORITIZATION OF CHEMICALS FOR TOXICOLOGICAL EVALUATION

EPA Science Inventory

Due to various legislatiave mandates, the US EPA is faced with evaluating the potential of tens of thousands of chemicals (e.g., high production volume chemicals, pestididal inerts, and drinking water contaminants) to cause adverse human health & environmental effects.

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

PubMed

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

2016-11-01

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

A Comprehensive Framework for the Evaluation of Engineered Nanomaterials

EPA Science Inventory

Engineered nanomaterials (ENM) are a fundamental and growing component of the global economy, and are projected to reach an annual economic impact in the hundreds of billions of dollars. Currently, their growing use far outpaces our ability to evaluate potential for adverse impac...

A Comprehensive Framework for Evaluation of Engineered Nanomaterials- NS2017

EPA Science Inventory

Engineered nanomaterials (ENM) are a fundamental and growing component of the global economy, and are projected to reach an annual economic impact in the hundreds of billions of dollars. Currently, their growing use far outpaces our ability to evaluate potential for adverse impac...

Safety in the operating room during orthopedic trauma surgery-incidence of adverse events related to technical equipment and logistics.

PubMed

van Delft, E A K; Schepers, T; Bonjer, H J; Kerkhoffs, G M M J; Goslings, J C; Schep, N W L

2018-04-01

Safety in the operating room is widely debated. Adverse events during surgery are potentially dangerous for the patient and staff. The incidence of adverse events during orthopedic trauma surgery is unknown. Therefore, we performed a study to quantify the incidence of these adverse events. Primary objective was to determine the incidence of adverse events related to technical equipment and logistics. The secondary objective was to evaluate the consequences of these adverse events. We completed a cross-sectional observational study to assess the incidence, consequences and preventability of adverse events related to technical equipment and logistics during orthopedic trauma surgery. During a 10 week period, all orthopedic trauma operations were evaluated by an observer. Six types of procedures were differentiated: osteosynthesis; arthroscopy; removal of hardware; joint replacement; bone grafting and other. Adverse events were divided in six categories: staff dependent factors; patient dependent factors; anaesthesia; imaging equipment; operation room equipment and instruments and implants. Adverse events were defined as any factor affecting the surgical procedure in a negative way. Hundred-fifty operative procedures were included. In 54% of the procedures, at least one adverse event occurred. In total, 147 adverse events occurred, with a range of 1-5 per procedure. Most adverse events occurred during joint replacement procedures. Thirty-seven percent of the incidents concerned defect, incorrect connected or absent instruments. In 36% of the procedures adverse events resulted in a prolonged operation time with a median prolongation of 10.0 min. In more than half of orthopedic trauma surgical procedures adverse events related to technical equipment and logistics occurred, most of them could easily be prevented. These adverse events could endanger the safety of the patient and staff and should therefore be reduced. 4.

EVALUATION OF THE POTENTIAL CARCINOGENICITY OF ELECTROMAGNETIC FIELDS (EXTERNAL REVIEW DRAFT)

EPA Science Inventory

The U.S. Environmental Protection Agency (EPA or Agency) is posting on this web site a draft document related to the potential adverse human health effects resulting from exposure to electromagnetic fields (EMF). This document was never finalized after EPA activities were discon...

Dynamic role and importance of surrogate species for assessing potential adverse environmental impacts of genetically engineered insect-resistant plants on non-target organisms

USDA-ARS?s Scientific Manuscript database

Surrogate species have a long history of use in research and regulatory settings to understand the potentially harmful effects of toxic substances including pesticides. More recently, surrogate species have been used to evaluate the potential effects of proteins contained in genetically engineered ...

Current limitations and recommendations to improve testing for the environmental assessment of endocrine active substances

USGS Publications Warehouse

Coady, Katherine K.; Biever, Ronald C.; Denslow, Nancy D.; Gross, Melanie; Guiney, Patrick D.; Holbech, Henrik; Karouna-Renier, Natalie K.; Katsiadaki, Ioanna; Krueger, Hank; Levine, Steven L.; Maack, Gerd; Williams, Mike; Wolf, Jeffrey C.; Ankley, Gerald T.

2017-01-01

In the present study, existing regulatory frameworks and test systems for assessing potential endocrine active chemicals are described, and associated challenges are discussed, along with proposed approaches to address these challenges. Regulatory frameworks vary somewhat across geographies, but all basically evaluate whether a chemical possesses endocrine activity and whether this activity can result in adverse outcomes either to humans or to the environment. Current test systems include in silico, in vitro, and in vivo techniques focused on detecting potential endocrine activity, and in vivo tests that collect apical data to detect possible adverse effects. These test systems are currently designed to robustly assess endocrine activity and/or adverse effects in the estrogen, androgen, and thyroid hormone signaling pathways; however, there are some limitations of current test systems for evaluating endocrine hazard and risk. These limitations include a lack of certainty regarding: 1) adequately sensitive species and life stages; 2) mechanistic endpoints that are diagnostic for endocrine pathways of concern; and 3) the linkage between mechanistic responses and apical, adverse outcomes. Furthermore, some existing test methods are resource intensive with regard to time, cost, and use of animals. However, based on recent experiences, there are opportunities to improve approaches to and guidance for existing test methods and to reduce uncertainty. For example, in vitro high-throughput screening could be used to prioritize chemicals for testing and provide insights as to the most appropriate assays for characterizing hazard and risk. Other recommendations include adding endpoints for elucidating connections between mechanistic effects and adverse outcomes, identifying potentially sensitive taxa for which test methods currently do not exist, and addressing key endocrine pathways of possible concern in addition to those associated with estrogen, androgen, and thyroid signaling. 

Evaluating the Environmental Health and Safety Impact of Engineered Nanomaterials

EPA Science Inventory

Engineered nanomaterials (ENM) are a fundamental and growing component of the global economy, and are projected to reach an annual economic impact in the hundreds of billions of dollars. Their spreading use far outpaces our ability to evaluate potential for adverse impacts on env...

Probiotic and synbiotic safety in infants under two years of age.

PubMed

van den Nieuwboer, M; Claassen, E; Morelli, L; Guarner, F; Brummer, R J

2014-03-01

In this study, we systematically evaluated safety aspects in clinical trials with probiotics and synbiotics in young infants (0-2 years of age). This study is an update of earlier reports and covers the recent literature from 2008-2013. The safety evaluation is performed along the Common Terminology Clinical Adverse Events (CTCAE) version 4.0 scale, hereby also providing guidance for future studies. Safety aspects are represented and related to number of participants per probiotic strain/culture, study duration, dosage, clinical condition and selected afflictions. The results show a deficiency in the precise reporting and classification of adverse events in most studies. Analysis of 57 clinical trials with probiotics and synbiotics in combination with eight follow-up studies indicate that probiotic administration to infants between 0 and 24 months is safe with regard to the evaluated strains in infants with a particular health status or susceptibility. Most adverse events and serious adverse events were considered unrelated to the study product, and there were no major safety concerns. Almost all studies concluded that none of the adverse effects were related to the study product; the study products are generally well tolerated. Finally, inconsistent, imprecise and potentially incomplete reporting as well as the variation in probiotic strains, dosages, administration regimes, study populations and reported outcomes, greatly limit the generalizability of conclusions and argue convincingly for obligatory and standardised behaviour on adverse events (CTCAE) reporting in 'food' studies.

Calcium lignosulphonate: re-evaluation of relevant endpoints to re-confirm validity and NOAEL of a 90-day feeding study in rats.

PubMed

Thiel, Anette; Braun, William; Cary, Maurice G; Engelhardt, Jeffery A; Goodman, Dawn G; Hall, William C; Romeike, Annette; Ward, Jerrold M

2013-08-01

A 90-day feeding study in Han/Wistar rats with calcium lignosulphonate was evaluated by the EFSA. The study was considered to be inadequate due to potentially impaired health status of the animals based upon a high incidence of minimal lymphoid hyperplasia in mesenteric/mandibular lymph nodes and Peyer's patches, and minimal lymphoid cell infiltration in the liver in all animals. The EFSA Panel further disagreed with the conclusion that the treatment-related observation of foamy histiocytosis in mesenteric lymph nodes was non-adverse and asked whether this observation would progress to something more adverse over time. A PWG was convened to assess the sections of lymph nodes, Peyer's patches and liver. In addition, all lymphoid tissues were re-examined. The clinical pathology and animal colony health screening data were re-evaluated. The question whether the foamy histiocytosis could progress to an adverse finding with increasing exposure duration was addressed by read-across. In conclusion, the animals on the 90-day feeding study were in good health, the study was adequate for safety evaluation, and the foamy histiocytes in the mesenteric lymph nodes were not considered adverse, but rather an adaptive response that was considered unlikely to progress to an adverse condition with time. The NOAEL was re-affirmed to be 2000 mg/kgbw/d. Copyright © 2013 Elsevier Inc. All rights reserved.

Current limitations and recommendations to improve testing ...

EPA Pesticide Factsheets

In this paper existing regulatory frameworks and test systems for assessing potential endocrine-active chemicals are described, and associated challenges discussed, along with proposed approaches to address these challenges. Regulatory frameworks vary somewhat across organizations, but all basically evaluate whether a chemical possesses endocrine activity and whether this activity can result in adverse outcomes either to humans or the environment. Current test systems include in silico, in vitro and in vivo techniques focused on detecting potential endocrine activity, and in vivo tests that collect apical data to detect possible adverse effects. These test systems are currently designed to robustly assess endocrine activity and/or adverse effects in the estrogen, androgen, and thyroid hormonal pathways; however, there are some limitations of current test systems for evaluating endocrine hazard and risk. These limitations include a lack of certainty regarding: 1)adequately sensitive species and life-stages, 2) mechanistic endpoints that are diagnostic for endocrine pathways of concern, and 3) the linkage between mechanistic responses and apical, adverse outcomes. Furthermore, some existing test methods are resource intensive in regard to time, cost, and use of animals. However, based on recent experiences, there are opportunities to improve approaches to, and guidance for existing test methods, and to reduce uncertainty. For example, in vitro high throughput

A research framework for pharmacovigilance in health social media: Identification and evaluation of patient adverse drug event reports.

PubMed

Liu, Xiao; Chen, Hsinchun

2015-12-01

Social media offer insights of patients' medical problems such as drug side effects and treatment failures. Patient reports of adverse drug events from social media have great potential to improve current practice of pharmacovigilance. However, extracting patient adverse drug event reports from social media continues to be an important challenge for health informatics research. In this study, we develop a research framework with advanced natural language processing techniques for integrated and high-performance patient reported adverse drug event extraction. The framework consists of medical entity extraction for recognizing patient discussions of drug and events, adverse drug event extraction with shortest dependency path kernel based statistical learning method and semantic filtering with information from medical knowledge bases, and report source classification to tease out noise. To evaluate the proposed framework, a series of experiments were conducted on a test bed encompassing about postings from major diabetes and heart disease forums in the United States. The results reveal that each component of the framework significantly contributes to its overall effectiveness. Our framework significantly outperforms prior work. Published by Elsevier Inc.

Operational Area Environmental Evaluations

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

Bailey-White, Brenda Eileen; Nagy, Michael David; Wagner, Katrina Marie

The Operational Area Environmental Evaluation update provides a description of activities that have the potential to adversely affect natural and cultural resources, including soil, air, water, biological, ecological, and historical resources. The environmental sensitivity of an area is evaluated and summarized, which may facilitate informed management decisions as to where development may be prohibited, restricted, or subject to additional requirements.

NTP-CERHR Expert Panel Report on the Reproductive and Developmental Toxicity of Bisphenol A

EPA Science Inventory

The National Toxicology Program (NTP)1 established the NTP Center for the Evaluation of Risks to Human Reproduction (CERHR) in June 1998. The purpose of the CERHR is to provide timely, unbiased, scientifically sound evaluations of the potential for adverse effects on reproduction...

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

PubMed

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

2013-06-01

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

Cognitive Function

EPA Science Inventory

Because chemicals can adversely affect cognitive function in humans, considerable effort has been made to characterize their effects using animal models. Information from such models will be necessary to: evaluate whether chemicals identified as potentially neurotoxic by screenin...

Identification of adverse events in ground transport emergency medical services.

PubMed

Patterson, P Daniel; Weaver, Matthew D; Abebe, Kaleab; Martin-Gill, Chris; Roth, Ronald N; Suyama, Joseph; Guyette, Francis X; Rittenberger, Jon C; Krackhardt, David; Arnold, Robert; Yealy, Donald M; Lave, Judith

2012-01-01

The purpose of this study was to develop a method to define and rate the severity of adverse events (AEs) in emergency medical services (EMS) safety research. They used a modified Delphi technique to develop a consensus definition of an AE. The consensus definition was as follows: "An adverse event in EMS is a harmful or potentially harmful event occurring during the continuum of EMS care that is potentially preventable and thus independent of the progression of the patient's condition." Physicians reviewed 250 charts from 3 EMS agencies for AEs. The authors examined physician agreement using κ, Fleiss's κ, and corresponding 95% confidence intervals (CIs). Overall physician agreement on presence of an AE per chart was fair (κ = 0.24; 95% CI = 0.19, 0.29). These findings should serve as a basis for refining and implementing an AE evaluation instrument.

Surrogate species selection for assessing potential adverse environmental impacts of genetically engineered insect-resistant plants on non-target organisms.

PubMed

Carstens, Keri; Cayabyab, Bonifacio; De Schrijver, Adinda; Gadaleta, Patricia G; Hellmich, Richard L; Romeis, Jörg; Storer, Nicholas; Valicente, Fernando H; Wach, Michael

2014-01-01

Most regulatory authorities require that developers of genetically engineered insect-resistant (GEIR) crops evaluate the potential for these crops to have adverse impacts on valued non-target organisms (NTOs), i.e., organisms not intended to be controlled by the trait. In many cases, impacts to NTOs are assessed using surrogate species, and it is critical that the data derived from surrogates accurately predict any adverse impacts likely to be observed from the use of the crop in the agricultural context. The key is to select surrogate species that best represent the valued NTOs in the location where the crop is going to be introduced, but this selection process poses numerous challenges for the developers of GE crops who will perform the tests, as well as for the ecologists and regulators who will interpret the test results. These issues were the subject of a conference "Surrogate Species Selection for Assessing Potential Adverse Environmental Impacts of Genetically Engineered Plants on Non-Target Organisms" convened by the Center for Environmental Risk Assessment, ILSI Research Foundation. This report summarizes the proceedings of the conference, including the presentations, discussions and the points of consensus agreed to by the participants.

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

PubMed

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

2003-08-01

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

Development of an automated assessment tool for MedWatch reports in the FDA adverse event reporting system.

PubMed

Han, Lichy; Ball, Robert; Pamer, Carol A; Altman, Russ B; Proestel, Scott

2017-09-01

As the US Food and Drug Administration (FDA) receives over a million adverse event reports associated with medication use every year, a system is needed to aid FDA safety evaluators in identifying reports most likely to demonstrate causal relationships to the suspect medications. We combined text mining with machine learning to construct and evaluate such a system to identify medication-related adverse event reports. FDA safety evaluators assessed 326 reports for medication-related causality. We engineered features from these reports and constructed random forest, L1 regularized logistic regression, and support vector machine models. We evaluated model accuracy and further assessed utility by generating report rankings that represented a prioritized report review process. Our random forest model showed the best performance in report ranking and accuracy, with an area under the receiver operating characteristic curve of 0.66. The generated report ordering assigns reports with a higher probability of medication-related causality a higher rank and is significantly correlated to a perfect report ordering, with a Kendall's tau of 0.24 ( P  = .002). Our models produced prioritized report orderings that enable FDA safety evaluators to focus on reports that are more likely to contain valuable medication-related adverse event information. Applying our models to all FDA adverse event reports has the potential to streamline the manual review process and greatly reduce reviewer workload. Published by Oxford University Press on behalf of the American Medical Informatics Association 2017. This work is written by US Government employees and is in the public domain in the United States.

Using clinical trial data and linked administrative health data to reduce the risk of adverse events associated with the uptake of newly released drugs by older Australians: a model process.

PubMed

Whitstock, Margaret T; Pearce, Christopher M; Ridout, Stephen C; Eckermann, Elizabeth J

2011-05-21

The study was undertaken to evaluate the contribution of a process which uses clinical trial data plus linked de-identified administrative health data to forecast potential risk of adverse events associated with the use of newly released drugs by older Australian patients. The study uses publicly available data from the clinical trials of a newly released drug to ascertain which patient age groups, gender, comorbidities and co-medications were excluded in the trials. It then uses linked de-identified hospital morbidity and medications dispensing data to investigate the comorbidities and co-medications of patients who suffer from the target morbidity of the new drug and who are the likely target population for the drug. The clinical trial information and the linked morbidity and medication data are compared to assess which patient groups could potentially be at risk of an adverse event associated with use of the new drug. Applying the model in a retrospective real-world scenario identified that the majority of the sample group of Australian patients aged 65 years and over with the target morbidity of the newly released COX-2-selective NSAID rofecoxib also suffered from a major morbidity excluded in the trials of that drug, indicating a substantial potential risk of adverse events amongst those patients. This risk was borne out in post-release morbidity and mortality associated with use of that drug. Clinical trial data and linked administrative health data can together support a prospective assessment of patient groups who could be at risk of an adverse event if they are prescribed a newly released drug in the context of their age, gender, comorbidities and/or co-medications. Communication of this independent risk information to prescribers has the potential to reduce adverse events in the period after the release of the new drug, which is when the risk is greatest.Note: The terms 'adverse drug reaction' and 'adverse drug event' have come to be used interchangeably in the current literature. For consistency, the authors have chosen to use the wider term 'adverse drug event' (ADE).

Comparison of two questionnaires to assess gastrointestinal toxicity in dogs and cats treated with chemotherapy*.

PubMed

Malone, E K; Rassnick, K M; Bailey, D B; Kiselow, M A; Erb, H N

2011-09-01

Questionnaires completed by pet owners are widely used instruments to monitor adverse gastrointestinal (GI) effects in the owners' animals undergoing chemotherapy and for reporting toxicoses in clinical trials; however, no questionnaires have been formally evaluated. This study compares two questionnaire-based evaluations of adverse GI events: a basic, open-ended questionnaire and a detailed questionnaire modelled after the grading in the Veterinary Co-operative Oncology Group-Common Terminology Criteria for Adverse Events (VCOG-CTCAE). Owners completed both questionnaires after their dog or cat received moderately emetogenic chemotherapy. Results were used to derive toxicity grades for anorexia, vomiting and diarrhoea. We evaluated 123 pairs of questionnaires. Disagreement in grade of anorexia, vomiting and diarrhoea was found in 24, 7 and 13% of paired questionnaires, respectively (κ = 0.63, 0.83 and 0.71, respectively). Although 'good' to 'very good' agreement was found, the potential for only 'fair' agreement between questionnaire methods is of concern and suggests a need to adopt a standardized form. © 2011 Blackwell Publishing Ltd.

Human abuse liability evaluation of CNS stimulant drugs.

PubMed

Romach, Myroslava K; Schoedel, Kerri A; Sellers, Edward M

2014-12-01

Psychoactive drugs that increase alertness, attention and concentration and energy, while also elevating mood, heart rate and blood pressure are referred to as stimulants. Despite some overlapping similarities, stimulants cannot be easily categorized by their chemical structure, mechanism of action, receptor binding profile, effects on monoamine uptake, behavioral pharmacology (e.g., effects on locomotion, temperature, and blood pressure), therapeutic indication or efficacy. Because of their abuse liability, a pre-market assessment of abuse potential is required for drugs that show stimulant properties; this review article focuses on the clinical aspects of this evaluation. This includes clinical trial adverse events, evidence of diversion or tampering, overdoses and the results of a human abuse potential study. While there are different types of human experimental studies that can be employed to evaluate stimulant abuse potential (e.g., drug discrimination, self-administration), only the human abuse potential study and clinical trial adverse event data are required for drug approval. The principal advances that have improved human abuse potential studies include using study enrichment strategies (pharmacologic qualification), larger sample sizes, better selection of endpoints and measurement strategies and more carefully considered interpretation of data. Because of the methodological advances, comparisons of newer studies with historical data is problematic and may contribute to a biased regulatory framework for the evaluation of newer stimulant-like drugs, such as A2 antagonists. This article is part of the Special Issue entitled 'CNS Stimulants'. Copyright © 2014 Elsevier Ltd. All rights reserved.

The role of adverse events and related safety data in the pre-market evaluation of drug abuse potential.

PubMed

Mansbach, Robert S; Schoedel, Kerri A; Kittrelle, Jeffrey P; Sellers, Edward M

2010-12-01

The scientific and regulatory assessment of abuse and dependence potential of drugs involves a multi-layered evaluation of its properties related to chemistry, formulation, pharmacology, animal behavior and clinical response. In addition to the primary laboratory-based assessment in experienced drug users, data are also reviewed from studies in healthy volunteers and in the patient population. Much of the emphasis in these latter studies is placed on adverse events that are reported by the subject or observed by the investigator. Unlike other aspects of abuse potential assessment, the evaluation of abuse- and dependence-related events has not been the subject of scholarly research. The present commentary presents recommendations for several areas that would benefit from a consensus review to result in greater standardization for the analysis and presentation of abuse- and dependence-related data from clinical trials. These include special investigator training, a system of weighted primary and secondary terms, adjudication of individual events, case report management, organization of integrated safety data, and protocols for drug accountability. Such an effort would aid in implementing the evolving efforts of health authorities to guide drug developers in the collection and presentation of data needed for the regulation of drugs with the potential for abuse and dependence. Copyright © 2010 Elsevier Ireland 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.

Drought allocations using the Systems Impact Assessment Model: Klamath River

USGS Publications Warehouse

Flug, M.; Campbell, S.G.

2005-01-01

Water supply and allocation scenarios for the Klamath River, Ore. and Calif., were evaluated using the Systems Impact Assessment Model (SIAM), a decision support system developed by the U.S. Geological Survey. SIAM is a set of models with a graphical user interface that simulates water supply and delivery in a managed river system, water quality, and fish production. Simulation results are presented for drought conditions, one aspect of Klamath River water operations. The Klamath River Basin has experienced critically dry conditions in 1992, 1994, and 2001. Drought simulations are useful to estimate the impacts of specific legal or institutional flow constraints. In addition, simulations help to identify potential adverse water quality consequences including evaluating the potential for reducing adverse temperature impacts on anadromous fish. In all drought simulations, water supply was insufficient to fully meet upstream and downstream targets for endangered species.

MICRONUCLEUS STUDIES IN THE PERIPHERAL BLOOD AND BONE MARROW OF MICE TREATED WITH JET FUELS, JP-8 AND JET-A

EPA Science Inventory

The potential adverse effects of dermal and inhalation exposure of jet fuels are important for health hazard evaluation in humans. In an animal model, the genotoxic potential of jet fuels, JP-8 and Jet-A, was investigated. Mice were treated dermally with either a single or multip...

Evaluation of vaginal implant transmitters in elk (Cervus elaphus nelsoni).

Treesearch

Bruce K. Johnson; Terrance McCoy; Christopher O. Kochanny; Rachel C. Cook

2006-01-01

The effects of vaginal implant transmitters for tissue damage after 11 wk in 13 captive adult elk (Cervus elaphus nelsoni) and subsequent reproductive performance in 38 free-ranging elk were evaluated. Vaginal implant transmitters are designed to be shed at parturition and are used to locate birth sites of wild ungulates; however, potential adverse...

Surrogate species selection for assessing potential adverse environmental impacts of genetically engineered insect-resistant plants on non-target organisms

PubMed Central

Carstens, Keri; Cayabyab, Bonifacio; De Schrijver, Adinda; Gadaleta, Patricia G; Hellmich, Richard L; Romeis, Jörg; Storer, Nicholas; Valicente, Fernando H; Wach, Michael

2014-01-01

Most regulatory authorities require that developers of genetically engineered insect-resistant (GEIR) crops evaluate the potential for these crops to have adverse impacts on valued non-target organisms (NTOs), i.e., organisms not intended to be controlled by the trait. In many cases, impacts to NTOs are assessed using surrogate species, and it is critical that the data derived from surrogates accurately predict any adverse impacts likely to be observed from the use of the crop in the agricultural context. The key is to select surrogate species that best represent the valued NTOs in the location where the crop is going to be introduced, but this selection process poses numerous challenges for the developers of GE crops who will perform the tests, as well as for the ecologists and regulators who will interpret the test results. These issues were the subject of a conference “Surrogate Species Selection for Assessing Potential Adverse Environmental Impacts of Genetically Engineered Plants on Non-Target Organisms” convened by the Center for Environmental Risk Assessment, ILSI Research Foundation. This report summarizes the proceedings of the conference, including the presentations, discussions and the points of consensus agreed to by the participants. PMID:24637519

Adverse interactions between herbal and dietary substances and prescription medications: a clinical survey.

PubMed

Bush, Thomas M; Rayburn, Keith S; Holloway, Sandra W; Sanchez-Yamamoto, Deanna S; Allen, Blaine L; Lam, Tiffany; So, Brian K; Tran, De H; Greyber, Elizabeth R; Kantor, Sophia; Roth, Larry W

2007-01-01

Patients often combine prescription medications with herbal and dietary substances (herein referred to as herbal medicines). A variety of potential adverse herb-drug interactions exist based on the pharmacological properties of herbal and prescription medications. To determine the incidence of potential and observed adverse herb-drug interactions in patients using herbal medicines with prescription medications. Consecutive patients were questioned about their use of herbal medicines in 6 outpatient clinics. Patients reporting use of these products provided a list of their prescription medications, which were reviewed for any potential adverse herb-drug interactions using a comprehensive natural medicine database. Any potential adverse herb-drug interactions prompted a review of the patient's chart for evidence of an observed adverse herb-drug interaction. The rate of potential and observed adverse herb-drug interactions. Eight hundred four patients were surveyed, and 122 (15%) used herbal medicines. Eighty-five potential adverse herb-drug interactions were found in 49 patients (40% of herbal medicine users). Twelve possible adverse herb-drug interactions in 8 patients (7% of herbal medicine users) were observed. In all 12 cases, the severity scores were rated as mild, including 8 cases of hypoglycemia in diabetics taking nopal (prickly pear cactus). A substantial number of potential adverse herb-drug interactions were detected and a small number of adverse herb-drug interactions observed, particularly in diabetics taking nopal. Screening for herbal medicine usage in 804 patients did not uncover any serious adverse interactions with prescription medications.

BIG DARBY CREEK WATERSHED

EPA Science Inventory

What is an ecological risk assessment?

Middle Platte River Watershed

EPA Science Inventory

What is an ecological risk assessment?

An ecological risk assessment evaluates the potential adverse effects of human activities on the plants and animals that make up ecosystems. The risk assessment process provides a way to develop, organize and present sc...

DETERMINING INHALATION RISK -- TOOLS FOR ASSESSING HAZARD.

EPA Science Inventory

The Clean Air Act focuses on reduction of the potential for specific air pollutants to cause adverse health effects. Implementation of standards to control release of the 188 hazardous air pollutants (HAPs) requires the Environmental Protection Agency (EPA) to evaluate the healt...

Clinical roundtable monograph. New alternatives in CLL therapy: managing adverse events.

PubMed

Chanan-Khan, Asher; Kipps, Thomas; Stilgenbauer, Stephan

2010-08-01

Chronic lymphocytic leukemia (CLL) is a B-cell leukemia mainly affecting older adults. Historically, CLL has been regarded as an incurable disease, and treatment has been confined to cytotoxic chemotherapy regimens. However, prognosis for patients treated with these agents remained poor, prompting the development of new, targeted agents. The introduction of rituximab, a CD20-targeted monoclonal antibody, revolutionized the treatment for this disease. Rituximab in combination with fludarabine improved response rates and length of progression-free survival. The success of rituximab in this setting has prompted the development of many more investigational agents for CLL, including other antibody agents. However, as with any medication, the potential benefit achieved with CLL therapies is mitigated by the safety risk for the patient. These agents have been associated with adverse events such as immunosuppression, reactivation of cytomegalovirus, and infusion-related reactions that can occur with antibody administration. Adverse events can greatly affect the patient’s quality of life and ability to tolerate therapy. Management of adverse events is a critical component of the overall treatment strategy for CLL, particularly in elderly patients. In this clinical roundtable monograph, 3 expert physicians discuss the latest clinical studies evaluating the treatment of CLL, focusing on the adverse events associated with each agent and the potential interventions that can be used to manage their occurrence.

[Pharmaceutical care of patients with rheumatoid and psoriatic arthritis receiving etanercept].

PubMed

Romero Crespo, I; Antón Torres, R; Borrás Blasco, J; Navarro Ruiz, A

2005-01-01

To evaluate a pharmaceutical care protocol for patients with rheumatoid arthritis (RA) or psoriatic arthritis who begin treatment with etanercept with the objective of identifying potential medication-related problems and implementing therapeutic measures to improve the way this drug is used. An observational, prospective, 3-month study of patients with RA receiving etanercept therapy from March to December 2003 was conducted and a pharmaceutical care protocol was set up. During the first visit, a pharmacotherapeutic record was initiated for each patient, including socio-demographic data, personal history, diagnosis, DMARDs (disease-modifying anti-rheumatic drugs) previously received, and concomitant therapies for other underlying conditions. Patients were briefed on dosage, administration route, and potential adverse events both orally and in writing. Correct drug administration and preservation were verified during the second visit, where potential adverse effects were identified, treatment adherence was confirmed, and, if needed, potential drug interactions with other ongoing medications were disclosed. During the third visit, adherence was assessed, adverse events were recorded, and patients evaluated their response to treatment. Fifty patients were included, 40 with a diagnosis of rheumatoid arthritis (80%) and 10 diagnosed with psoriatic arthritis (20%). In all, 72% had received previous treatment with methotrexate (MTX), 40% with leflunomide, 20% with infliximab, 56% with corticoids, 2% with analgesics, 56% with NSAIDs, and 30% with other DMARDs. No significant drug interactions were found. Regarding adherence to treatment, 7.7% of patients skipped one or more doses, with travelling being the most common reason. Adverse events reported included: injection site reaction (27%), headache (7.7%) and nausea (7.7%). At 3 months after treatment onset, a reduction of MTX doses was seen in 18% of patients, of leflunomide dosage in 8%, of corticoids in 18%, of analgesic usage in 6%, and of NSAIDs in 8% of patients. In agreement with these results, 92% of patients reported having experienced improvment.

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

PubMed

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

2009-12-01

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

No impact of DvSnf7 RNA on honey bee (Apis mellifera L.) adults and larvae in dietary feeding tests.

PubMed

Tan, Jianguo; Levine, Steven L; Bachman, Pamela M; Jensen, Peter D; Mueller, Geoffrey M; Uffman, Joshua P; Meng, Chen; Song, Zihong; Richards, Kathy B; Beevers, Michael H

2016-02-01

The honey bee (Apis mellifera L.) is the most important managed pollinator species worldwide and plays a critical role in the pollination of a diverse range of economically important crops. This species is important to agriculture and historically has been used as a surrogate species for pollinators to evaluate the potential adverse effects for conventional, biological, and microbial pesticides, as well as for genetically engineered plants that produce pesticidal products. As part of the ecological risk assessment of MON 87411 maize, which expresses a double-stranded RNA targeting the Snf7 ortholog (DvSnf7) in western corn rootworm (Diabrotica virgifera virgifera), dietary feeding studies with honey bee larvae and adults were conducted. Based on the mode of action of the DvSnf7 RNA in western corn rootworm, the present studies were designed to be of sufficient duration to evaluate the potential for adverse effects on larval survival and development through emergence and adult survival to a significant portion of the adult stage. Testing was conducted at concentrations of DvSnf7 RNA that greatly exceeded environmentally relevant exposure levels based on expression levels in maize pollen. No adverse effects were observed in either larval or adult honey bees at these high exposure levels, providing a large margin of safety between environmental exposure levels and no-observed-adverse-effect levels. © 2015 The Authors. Environmental Toxicology and Chemistry Published by Wiley Periodicals, Inc. on behalf of SETAC.

Evaluation of two high through-put (HTP) androgen receptor based assays: Utility of data for prioritization for further testing versus prediction of adverse effects.

EPA Science Inventory

The androgen signaling pathway plays a critical role in sexual differentiation during development in mammals and is one of the better understood pathways in human development. Thus it was chosen as a model pathway to evaluate the potential of HTP in vitro assays as risk assessmen...

Weight of evidence evaluation of a network of adverse ...

EPA Pesticide Factsheets

Ongoing honey bee colony losses are of significant international concern because of the essential role these insects play in pollinating many high nutrient crops, such as fruits, vegetables, and nuts. Both chemical and non-chemical stressors have been implicated as possible contributors to colony failure, however, the potential role(s) of commonly-used neonicotinoid insecticides has emerged as particularly concerning. Neonicotinoids act on the nicotinic acetylcholine receptors (nAChRs) in the central nervous system to eliminate target pest insects. However, mounting evidence indicates that these neonicotinoids also may adversely affect beneficial pollinators, such as the honey bee, via impairments on learning and memory, and ultimately foraging success. The specific 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. The objective of this review was to develop adverse outcome pathways (AOPs) as a means to evaluate the biological plausibility and empirical evidence supporting (or refuting) the linkage between activation of the physiological target site, the nAChR, and colony level consequences. Development of 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 norm

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

Walking in fully immersive virtual environments: an evaluation of potential adverse effects in older adults and individuals with Parkinson's disease.

PubMed

Kim, Aram; Darakjian, Nora; Finley, James M

2017-02-21

Virtual reality (VR) has recently been explored as a tool for neurorehabilitation to enable individuals with Parkinson's disease (PD) to practice challenging skills in a safe environment. Current technological advances have enabled the use of affordable, fully immersive head-mounted displays (HMDs) for potential therapeutic applications. However, while previous studies have used HMDs in individuals with PD, these were only used for short bouts of walking. Clinical applications of VR for gait training would likely involve an extended exposure to the virtual environment, which has the potential to cause individuals with PD to experience simulator-related adverse effects due to their age or pathology. Thus, our objective was to evaluate the safety of using an HMD for longer bouts of walking in fully immersive VR for older adults and individuals with PD. Thirty-three participants (11 healthy young, 11 healthy older adults, and 11 individuals with PD) were recruited for this study. Participants walked for 20 min while viewing a virtual city scene through an HMD (Oculus Rift DK2). Safety was evaluated using the mini-BESTest, measures of center of pressure (CoP) excursion, and questionnaires addressing symptoms of simulator sickness (SSQ) and measures of stress and arousal. Most participants successfully completed all trials without any discomfort. There were no significant changes for any of our groups in symptoms of simulator sickness or measures of static and dynamic balance after exposure to the virtual environment. Surprisingly, measures of stress decreased in all groups while the PD group also increased the level of arousal after exposure. Older adults and individuals with PD were able to successfully use immersive VR during walking without adverse effects. This provides systematic evidence supporting the safety of immersive VR for gait training in these populations.

MEETING IN VANCOUVER, B.C.: MICRONUCLEUS STUDIES IN THE PERIPHERAL BLOOD AND BONE MARROW OF MICE TREATED WITH JET FUELS, JP-8 AND JET-A

EPA Science Inventory

The potential adverse effects of dermal and inhalation exposure of jet fuels are important for health hazard evaluation in humans. In an animal model, the genotoxic potential of jet fuels, JP-8 and Jet-A, was investigated. Mice were treated dermally with either a single or multip...

QSAR EVALUATION OF ER BINDING AFFINITY OF CHEMICALS AND METABOLITES

EPA Science Inventory

Chemicals in commerce are assessed for a variety of potential adverse effects. As governments around the globe strive to meet the challenge of assessing chemicals as endocrine disruptors, the need for hypothesis-driven strategies to prioritize chemicals for testing has risen to t...

Defining a Computational Framework for the Assessment of Taxonomic Applicability

EPA Science Inventory

The Adverse Outcome Pathway (AOP) framework describes the effects of environmental stressors across multiple scales of biological organization and function. This includes an evaluation of the potential for each key event to occur across a broad range of species in order to determ...

15 CFR 923.25 - Shoreline erosion/mitigation planning.

Code of Federal Regulations, 2014 CFR

2014-01-01

... (Continued) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE OCEAN AND COASTAL... effects of, and studying and evaluating ways to control, or lessen the impact of, shoreline erosion, including potential impacts of sea level rise, and to restore areas adversely affected by such erosion. This...

15 CFR 923.25 - Shoreline erosion/mitigation planning.

Code of Federal Regulations, 2012 CFR

2012-01-01

... (Continued) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE OCEAN AND COASTAL... effects of, and studying and evaluating ways to control, or lessen the impact of, shoreline erosion, including potential impacts of sea level rise, and to restore areas adversely affected by such erosion. This...

15 CFR 923.25 - Shoreline erosion/mitigation planning.

Code of Federal Regulations, 2013 CFR

2013-01-01

... (Continued) NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE OCEAN AND COASTAL... effects of, and studying and evaluating ways to control, or lessen the impact of, shoreline erosion, including potential impacts of sea level rise, and to restore areas adversely affected by such erosion. This...

Simultaneous analysis of thirteen endogenous steroid hormones by liquid chromatography tandem mass spectrometry with atmospheric pressure photoionization

EPA Science Inventory

Exposure to endocrine active chemicals can lead to perturbations of the hypothalamic-pituitary-gonadal (HPG) axis, ultimately leading to adverse reproductive effects. To evaluate potential reproductive effects, many aquatic toxicity assessments still rely on radioimmunoassay (RIA...

Ginger for Prevention of Antituberculosis-induced Gastrointestinal Adverse Reactions Including Hepatotoxicity: A Randomized Pilot Clinical Trial.

PubMed

Emrani, Zahra; Shojaei, Esphandiar; Khalili, Hossein

2016-06-01

In this study, the potential benefits of ginger in preventing antituberculosis drug-induced gastrointestinal adverse reactions including hepatotoxicity have been evaluated in patients with tuberculosis. Patients in the ginger and placebo groups (30 patients in each group) received either 500 mg ginger (Zintoma)(®) or placebo one-half hour before each daily dose of antituberculosis drugs for 4 weeks. Patients' gastrointestinal complaints (nausea, vomiting, dyspepsia, and abdominal pain) and antituberculosis drug-induced hepatotoxicity were recorded during the study period. In this cohort, nausea was the most common antituberculosis drug-induced gastrointestinal adverse reactions. Forty eight (80%) patients experienced nausea. Nausea was more common in the placebo than the ginger group [27 (90%) vs 21 (70%), respectively, p = 0.05]. During the study period, 16 (26.7%) patients experienced antituberculosis drug-induced hepatotoxicity. Patients in the ginger group experienced less, but not statistically significant, antituberculosis drug-induced hepatotoxicity than the placebo group (16.7% vs 36.7%, respectively, p = 0.07). In conclusion, ginger may be a potential option for prevention of antituberculosis drug-induced gastrointestinal adverse reactions including hepatotoxicity. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Environmental assessment of the potential effects of aquifer thermal energy storage systems on microorganisms in groundwater

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

Hicks, R.J.; Stewart, D.L.

1988-03-01

The primary objective of this study was to evaluate the potential environmental effects (both adverse and beneficials) of aquifer thermal energy storage (ATES) technology pertaining to microbial communities indigenous to subsurface environments (i.e., aquifers) and the propagation, movement, and potential release of pathogenic microorganisms (specifically, Legionella) within ATES systems. Seasonal storage of thermal energy in aquifers shows great promise to reduce peak demand; reduce electric utility load problems; contribute to establishing favorable economics for district heating and cooling systems; and reduce pollution from extraction, refining, and combustion of fossil fuels. However, concerns that the widespread implementation of this technology maymore » have adverse effects on biological systems indigeneous to aquifers, as well as help to propagate and release pathogenic organisms that enter thee environments need to be resolved. 101 refs., 2 tabs.« less

FINDING POTENTIALLY UNSAFE NUTRITIONAL SUPPLEMENTS FROM USER REVIEWS WITH TOPIC MODELING.

PubMed

Sullivan, Ryan; Sarker, Abeed; O'Connor, Karen; Goodin, Amanda; Karlsrud, Mark; Gonzalez, Graciela

2016-01-01

Although dietary supplements are widely used and generally are considered safe, some supplements have been identified as causative agents for adverse reactions, some of which may even be fatal. The Food and Drug Administration (FDA) is responsible for monitoring supplements and ensuring that supplements are safe. However, current surveillance protocols are not always effective. Leveraging user-generated textual data, in the form of Amazon.com reviews for nutritional supplements, we use natural language processing techniques to develop a system for the monitoring of dietary supplements. We use topic modeling techniques, specifically a variation of Latent Dirichlet Allocation (LDA), and background knowledge in the form of an adverse reaction dictionary to score products based on their potential danger to the public. Our approach generates topics that semantically capture adverse reactions from a document set consisting of reviews posted by users of specific products, and based on these topics, we propose a scoring mechanism to categorize products as "high potential danger", "average potential danger" and "low potential danger." We evaluate our system by comparing the system categorization with human annotators, and we find that the our system agrees with the annotators 69.4% of the time. With these results, we demonstrate that our methods show promise and that our system represents a proof of concept as a viable low-cost, active approach for dietary supplement monitoring.

Potential immediate hypersensitivity reactions following immunization in preschool aged children in Victoria, Australia.

PubMed

Baxter, C-M; Clothier, H J; Perrett, K P

2018-04-06

Immediate hypersensitivity reactions (IHR) are rare but potentially serious adverse events following immunization (AEFI). Surveillance of Adverse Events following Vaccination in the Community (SAEFVIC) is an enhanced passive surveillance system that collects, analyses and reports information about AEFI in Victoria, Australia. We describe the incidence, timing and type of potential IHR following vaccination in preschool children reported over an 8-year period. A total of 2110 AEFI were reported in 1620 children, of which 23.5% (496) were classified as potential IHR. Of these, 37.1% (184) were suspected to be IgE-mediated, (including anaphylaxis, angioedema and/or urticaria) and 83.5% (414) occurred within 15 minutes of vaccination. The incidence of potential IHR was 5.4 per 100,000 doses, with that of suspected IgE-mediated IHR being 2.0 per 100,000 doses. The incidence of anaphylaxis was extremely low (0.13 per 100,000 doses) and is consistent with other published studies. Potential IHR following immunization should be reported to appropriate local pharmacovigilance systems and patients reviewed by specialists able to evaluate, investigate and manage future vaccinations.

THE SECOND GENERATION OF THE WASTE REDUCTION (WAR) ALGORITHM: A DECISION SUPPORT SYSTEM FOR GREENER CHEMICAL PROCESSES

EPA Science Inventory

chemical process designers using simulation software generate alternative designs for one process. One criterion for evaluating these designs is their potential for adverse environmental impacts due to waste generated, energy consumed, and possibilities for fugitive emissions. Co...

INTERPRETING SPONTANEOUS RENAL LESIONS IN SAFETY AND RISK ASSESSMENT

EPA Science Inventory

Interpreting Spontaneous Renal Lesions in Safety and Risk Assessment
Douglas C. Wolf, D.V.M., Ph.D.

Introduction

Risk assessment is a process whereby the potential adverse health effects from exposure to a xenobiotic are predicted after evaluation of the availab...

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.

Environmental Assessment for Construction of Base Training Area, Schriever Air Force Base, Colorado

DTIC Science & Technology

2010-12-01

FONSI) based upon the results of the Environmental Assessment (EA) to evaluate environmental issues and potential impacts associated with a proposal...SIGNIFICANT IMPACT (FONSI) FOR CONSTRUCTION OF BASE TRAINING AREA, SCHRIEVER AIR FORCE BASE, COLORADO An Environmental Assessment (EA) was...Proposed Action has the potential to result in adverse environmental impacts ; however, no significant impacts are anticipated as noted in Table 1 which

Combing signals from spontaneous reports and electronic health records for detection of adverse drug reactions

PubMed Central

Harpaz, Rave; Vilar, Santiago; DuMouchel, William; Salmasian, Hojjat; Haerian, Krystl; Shah, Nigam H; Chase, Herbert S; Friedman, Carol

2013-01-01

Objective Data-mining algorithms that can produce accurate signals of potentially novel adverse drug reactions (ADRs) are a central component of pharmacovigilance. We propose a signal-detection strategy that combines the adverse event reporting system (AERS) of the Food and Drug Administration and electronic health records (EHRs) by requiring signaling in both sources. We claim that this approach leads to improved accuracy of signal detection when the goal is to produce a highly selective ranked set of candidate ADRs. Materials and methods Our investigation was based on over 4 million AERS reports and information extracted from 1.2 million EHR narratives. Well-established methodologies were used to generate signals from each source. The study focused on ADRs related to three high-profile serious adverse reactions. A reference standard of over 600 established and plausible ADRs was created and used to evaluate the proposed approach against a comparator. Results The combined signaling system achieved a statistically significant large improvement over AERS (baseline) in the precision of top ranked signals. The average improvement ranged from 31% to almost threefold for different evaluation categories. Using this system, we identified a new association between the agent, rasburicase, and the adverse event, acute pancreatitis, which was supported by clinical review. Conclusions The results provide promising initial evidence that combining AERS with EHRs via the framework of replicated signaling can improve the accuracy of signal detection for certain operating scenarios. The use of additional EHR data is required to further evaluate the capacity and limits of this system and to extend the generalizability of these results. PMID:23118093

A Decision Support Framework for Evaluation of Engineered ...

EPA Pesticide Factsheets

Engineered nanomaterials (ENM) are currently being developed and applied at rates that far exceed our ability to evaluate their potential for environmental or human health risks. The gap between material development and capacity for assessment grows wider every day. Transformative approaches are required that enhance our ability to forecast potential exposure and adverse health risks based on limited information such as the physical and chemical parameters of ENM, their proposed uses, and functional assays reflective of key ENM - environmental interactions. We are developing a framework that encompasses the potential for release of nanomaterials across a product life cycle, environmental transport, transformations and fate, exposure to sensitive species, including humans, and the potential for causing adverse effects. Each component of the framework is conceive of as a sequential segmented model depicting the movement, transformations and actions of ENM through environmental or biological compartments, and along which targeted functional assays can be developed that are indicative of projected rates of ENM movement or action. The eventual goal is to allow simple predictive models to be built that incorporate the data from key functional assays and thereby allow rapid screening of the projected margin of exposure for proposed applications of ENM enabled products. In this way, cases where a substantially safe margin of exposure is forecast can be reduced in

Final Environmental Assessment Addressing Construction, Operation, and Maintenance of a Hot Cargo Pad at Kirtland Air Force Base, New Mexico

DTIC Science & Technology

2011-01-01

ground surface of the pad. The surface sludge at WP-26 is currently being removed, which would alleviate any potential adverse effects on the...removing and disposing of the top 5 inches of the ground surface , which is potentially contaminated sewage sludge, within WP-26 in a manner consistent...Construction, Operation, and Maintenance of a Hot Cargo Pad at Kirtland Air Force Base, New Mexico, to identifY and evaluate potential environmental effects

Is detection of adverse events affected by record review methodology? an evaluation of the "Harvard Medical Practice Study" method and the "Global Trigger Tool".

PubMed

Unbeck, Maria; Schildmeijer, Kristina; Henriksson, Peter; Jürgensen, Urban; Muren, Olav; Nilsson, Lena; Pukk Härenstam, Karin

2013-04-15

There has been a theoretical debate as to which retrospective record review method is the most valid, reliable, cost efficient and feasible for detecting adverse events. The aim of the present study was to evaluate the feasibility and capability of two common retrospective record review methods, the "Harvard Medical Practice Study" method and the "Global Trigger Tool" in detecting adverse events in adult orthopaedic inpatients. We performed a three-stage structured retrospective record review process in a random sample of 350 orthopaedic admissions during 2009 at a Swedish university hospital. Two teams comprised each of a registered nurse and two physicians were assigned, one to each method. All records were primarily reviewed by registered nurses. Records containing a potential adverse event were forwarded to physicians for review in stage 2. Physicians made an independent review regarding, for example, healthcare causation, preventability and severity. In the third review stage all adverse events that were found with the two methods together were compared and all discrepancies after review stage 2 were analysed. Events that had not been identified by one of the methods in the first two review stages were reviewed by the respective physicians. Altogether, 160 different adverse events were identified in 105 (30.0%) of the 350 records with both methods combined. The "Harvard Medical Practice Study" method identified 155 of the 160 (96.9%, 95% CI: 92.9-99.0) adverse events in 104 (29.7%) records compared with 137 (85.6%, 95% CI: 79.2-90.7) adverse events in 98 (28.0%) records using the "Global Trigger Tool". Adverse events "causing harm without permanent disability" accounted for most of the observed difference. The overall positive predictive value for criteria and triggers using the "Harvard Medical Practice Study" method and the "Global Trigger Tool" was 40.3% and 30.4%, respectively. More adverse events were identified using the "Harvard Medical Practice Study" method than using the "Global Trigger Tool". Differences in review methodology, perception of less severe adverse events and context knowledge may explain the observed difference between two expert review teams in the detection of adverse events.

Evaluation of 'SAEFVIC', A Pharmacovigilance Surveillance Scheme for the Spontaneous Reporting of Adverse Events Following Immunisation in Victoria, Australia.

PubMed

Clothier, Hazel J; Crawford, Nigel W; Russell, Melissa; Kelly, Heath; Buttery, Jim P

2017-06-01

Australia is traditionally an early adopter of vaccines, therefore comprehensive and effective post-licensure vaccine pharmacovigilance is critical to maintain confidence in immunisation, both nationally and internationally. With adverse event following immunisation (AEFI) surveillance the responsibility of Australian jurisdictions, Victoria operates an enhanced passive AEFI surveillance system integrated with clinical services, called 'SAEFVIC' (Surveillance of Adverse Events Following Vaccination In the Community). The aim of this study was to evaluate Victoria's current AEFI surveillance system 'SAEFVIC' and inform ongoing quality improvement of vaccine pharmacovigilance in Victoria and Australia. We conducted a retrospective structured desktop evaluation of AEFI reporting received by SAEFVIC from 2007 to 2014, to evaluate the system according to its stated objectives, i.e. to improve AEFI reporting; provide AEFI signal detection; and to maintain consumer confidence in vaccination. AEFI reporting has tripled since SAEFVIC commenced (incidence risk ratio [IRR] 3.04, 95% confidence interval [CI] 2.35-3.93), raising Victoria to be the lead jurisdiction by AEFI reporting volume and to rank third by population reporting rate nationally. The largest increase was observed in children. Data were utilised to investigate potential signal events and inform vaccine policy. Signal detection required clinical suspicion by surveillance nurses, or prior vaccine-specific concerns. Subsequent vaccination post-AEFI was documented for 56.2% (95% CI 54.1-58.4) of reports, and the proportion of children due or overdue for vaccination was 2.3% higher for those reporting AEFI compared with the general population. SAEFVIC has improved AEFI surveillance, facilitates signal investigation and validation, and supports consumer confidence in immunisation. Expansion of the system nationally has the potential to improve capacity and capability of vaccine pharmacovigilance, particularly through data consistency and jurisdictional comparability in Australia.

Safety and efficacy assessment of standardized herbal formula PM012

PubMed Central

2012-01-01

Background This study was conducted to evaluate the efficacy of the herbal formula PM012 on an Alzheimer's disease model, human presenilin 2 mutant transgenic mice (hPS2m), and also to evaluate the toxicity of PM012 in Sprague-Dawely rats after 4 or 26 weeks treatment with repeated oral administration. Methods Spatial learning and memory capacities of hPS2m transgenic mice were evaluated using the Morris Water Maze. Simultaneously, PM012 was repeatedly administered orally to male and female SD rats (15/sex/group) at doses of 0 (vehicle control), 500, 1,000 and 2,000 mg/kg/day for 4 or 26 weeks. To evaluate the recovery potential, 5 animals of each sex were assigned to vehicle control and 2,000 mg/kg/day groups during the 4-week recovery period. Results The results showed that PM012-treated hPS2m transgenic mice showed significantly reduced escape latency when compared with the hPS2m transgenic mice. The repeated oral administration of PM012 over 26 weeks in male and female rats induced an increase and increasing trend in thymus weight in the female treatment groups (main and recovery groups), but the change was judged to be toxicologically insignificant. In addition, the oral administration of the herbal medicine PM012 did not cause adverse effects as assessed by clinical signs, mortality, body weight, food and water consumption, ophthalmology, urinalysis, hematology, serum biochemistry, blood clotting time, organ weights and histopathology. The No Observed Adverse Effects Levels of PM012 was determined to be 2,000 mg/kg/day for both sexes, and the target organ was not identified. Conclusion These results suggest that PM012 has potential for use in the treatment of the Alzheimer's disease without serious adverse effects. PMID:22458507

Compassionate School Model: Creating Trauma Sensitive Schools

ERIC Educational Resources Information Center

Wilson, Mary A.

2013-01-01

Children who are victims of adverse childhood experiences may display behaviors in school that hinder their ability to develop socially and academically. The purpose of this research study was to determine the potential effectiveness of the Compassionate School training model. This study was a program evaluation that examined staff training…

Quantification of turfgrass buffer performance in reducing transport of pesticides in surface runoff

USDA-ARS?s Scientific Manuscript database

Pesticides are used to control pests in managed biological system such as agricultural crops and golf course turf. Off-site transport of pesticides with runoff and their potential to adversely affect non-target aquatic organisms has inspired the evaluation of management practices to minimize pestic...

REDOX DISRUPTING POTENTIAL OF TOXCAST CHEMICALS RANKED BY ACTIVITY IN MOUSE EMBRYONIC STEM CELLS

EPA Science Inventory

To gain insight regarding the adverse outcome pathways leading to developmental toxicity following exposure to chemicals, we evaluated ToxCast™ Phase I chemicals in an adherent mouse embryonic stem cell (mESC) assay and identified a redox sensitive pathway that correlated with al...

Redox Disrupting Potential of ToxCast™Chemicals Ranked by Activity in Mouse Embryonic Stem Cells

EPA Science Inventory

Little is known regarding the adverse outcome pathways responsible for developmental toxicity following exposure to chemicals. An evaluation of Toxoast™ Phase I chemicals in an adherent mouse embryonic stem cell (mESC) assay revealed a redox sensitive pathway that correlated with...

NITROGEN BOUNDING STUDY: METHODS FOR ESTIMATING THE RELATIVE EFFECTS OF SULFUR AND NITROGEN DEPOSITION ON SURFACE WATER CHEMISTRY

EPA Science Inventory

The leaching of atmospherically deposited nitrogen from forested watersheds may acidify lakes and streams. he Nitrogen Bounding Study evaluates the potential range of such adverse effects. he study estimates bounds on changes in regional-scale surface water acidification that mig...

Culture system noise seems not to affect growth and survival of rainbow trout

USDA-ARS?s Scientific Manuscript database

Intensive aquaculture systems, particularly recycle systems with all their pumps, blowers, and filters can be noisy, but the potential effects of this underwater noise on fish have not been evaluated. Earlier field and laboratory studies have shown that fish behavior and physiology can be adversely ...

Applying Adverse Outcome Pathways (AOPs) to support Integrated Approaches to Testing and Assessment (IATA workshop report)

EPA Science Inventory

Chemical regulation is challenged by the large number of chemicals requiring assessment for potential human health and environmental impacts. Current approaches are too resource intensive in terms of time, money and animal use to evaluate all chemicals under development or alread...

Current limitations and a path forward to improve testing for the environmental assessment of endocrine active substances-presentation

EPA Science Inventory

To assess the hazards and risks of possible endocrine active chemicals (EACs), there is a need for robust, validated test methods that detect perturbations of endocrine pathways and provide reliable information for evaluating potential adverse effects on apical endpoints. One iss...

Polybrominated diphenyl ether serum concentrations in a Californian population of children, their parents, and older adults: an exposure assessment study

EPA Science Inventory

BackgroundPolybrominated diphenyl ethers (PBDEs) are used as flame retardants in many household items. Given concerns over their potential adverse health effects, we identified predictors and evaluated temporal changes of PBDE serum concentrations.MethodsPBDE serum concentrations...

75 FR 36067 - Agency Information Collection Activities; Proposed Collection; Comment Request; Chemical-Specific...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-24

... section 8(a) to evaluate the potential for adverse human health and environmental effects caused by the... Office (7407M), Office of Pollution Prevention and Toxics (OPPT), Environmental Protection Agency, 1200... technical information contact: Karen Chu, Chemical Control Division (7405M), Office of Pollution Prevention...

Application of a framework for extrapolating chemical effects ...

EPA Pesticide Factsheets

Cross-species extrapolation of toxicity data from limited surrogate test organisms to all wildlife with potential of chemical exposure remains a key challenge in ecological risk assessment. A number of factors affect extrapolation, including the chemical exposure, pharmacokinetics, life-stage, and pathway similarities/differences. Here we propose a framework using a tiered approach for species extrapolation that enables a transparent weight-of-evidence driven evaluation of pathway conservation (or lack thereof) in the context of adverse outcome pathways. Adverse outcome pathways describe the linkages from a molecular initiating event, defined as the chemical-biomolecule interaction, through subsequent key events leading to an adverse outcome of regulatory concern (e.g., mortality, reproductive dysfunction). Tier 1 of the extrapolation framework employs in silico evaluations of sequence and structural conservation of molecules (e.g., receptors, enzymes) associated with molecular initiating events or upstream key events. Such evaluations make use of available empirical and sequence data to assess taxonomic relevance. Tier 2 uses in vitro bioassays, such as enzyme inhibition/activation, competitive receptor binding, and transcriptional activation assays to explore functional conservation of pathways across taxa. Finally, Tier 3 provides a comparative analysis of in vivo responses between species utilizing well-established model organisms to assess departure from

Corrosion Evaluation of Aircraft Depainting Chemicals

NASA Technical Reports Server (NTRS)

McGill, Preston; Torres, Pablo

1999-01-01

The National Aeronautics and Space Administration is participating in an interagency task agreement with the Environmental Protection Agency and the United States Air Force to evaluate alternative technologies for aerospace depainting operations that do not adversely affect the environment. An element of this study is directed towards the evaluation of environmentally advantaged chemical paint strippers, specifically, paint strippers that do not contain methylene chloride. Eight environmentally advantaged, or alternative, chemical paint strippers and two methylene chloride, or baseline, paint strippers were obtained from various manufacturers and incorporated into the depainting study. In addition to being evaluated on their ability to remove paint, the potential of these chemicals to promote corrosion and hydrogen embrittlement was evaluated. The corrosion and hydrogen embrittlement potential of the chemical paint strippers are presented in this report.

Safety and Tolerability of Hyperbaric Oxygen Therapy in Cats and Dogs.

PubMed

Birnie, Gemma L; Fry, Darren R; Best, Matthew P

2018-05-14

This prospective clinical trial was designed to evaluate the safety of hyperbaric oxygen therapy (HBOT) in a population of cats and dogs with a variety of naturally occurring diseases. Seventy-eight dogs and twelve cats with various naturally occurring disease conditions, who had the potential to benefit from HBOT, were enrolled in the study. These patients were treated with HBOT in a monoplace hyperbaric oxygen chamber at 2 air pressure absolute for a treatment length of either 45 min or 60 min. There were 230 hyperbaric oxygen treatments performed during the study period. No major adverse effects were observed. There were 76 minor adverse effects recorded, which were not considered to be of clinical significance. Hyperbaric oxygen therapy was well tolerated and there were no major adverse effects recorded during treatment.

Ocular Toxoplasmosis: Therapy-Related Adverse Drug Reactions and Their Management.

PubMed

Helfenstein, M; Zweifel, S; Barthelmes, D; Meier, F; Fehr, J; Böni, C

2017-04-01

Background There are different treatment options for ocular toxoplasmosis (OT). "Classic" therapy consists of pyrimethamine, sulfadiazine and folinic acid combined with systemic steroids and is still widely used. However, potentially severe side effects of this therapy have been reported. The aim of this retrospective study was to evaluate the incidence and types of adverse drug reactions in patients treated for OT. Clinical management of each adverse drug reaction was assessed. Patients and Methods In this retrospective analysis, we reviewed data of patients with OT, who were consecutively examined between December 2011 and December 2015 at the Department of Ophthalmology, University Hospital Zurich. Results In total, 49 patients had at least one episode of active OT. In 54 (83.0 %) of 65 treated episodes, the classic regimen was used. Of the 37 patients who received classic treatment, 9 (24.3 %) developed at least one adverse drug reaction which led to drug discontinuation, including elevated creatinine (5.4 %), elevated liver enzymes (5.4 %), vomiting (5.4 %), rash (5.4 %) and facial swelling (2.7 %). In 5 patients, treatment was switched to another drug, while in the other 4 patients, therapy was stopped. In these 9 patients, inflammation was well controlled 8 weeks after onset of therapy. No patient suffered from severe side effects, such as potentially life-threatening allergic reactions or pancytopenia. Conclusions In OT patients who were treated with classic therapy, adverse drug reactions are common. Therefore, clinical and laboratory monitoring is mandatory. Adverse drug reactions may require interdisciplinary management. Georg Thieme Verlag KG Stuttgart · New York.

Action of Phα1β, a peptide from the venom of the spider Phoneutria nigriventer, on the analgesic and adverse effects caused by morphine in mice.

PubMed

Tonello, Raquel; Rigo, Flávia; Gewehr, Camila; Trevisan, Gabriela; Pereira, Elizete Maria Rita; Gomez, Marcus Vinicius; Ferreira, Juliano

2014-06-01

Opioids are standard therapy for the treatment of pain; however, adverse effects limit their use. Voltage-gated calcium channel blockers may be used to increase opioid analgesia, but their effect on opioid-induced side effects is little known. Thus, the goal of this study was to evaluate the action of the peptide Phα1β, a voltage-gated calcium channel blocker, on the antinociceptive and adverse effects produced by morphine in mice. A single administration of morphine (3-10 mg/kg) was able to reduce heat nociception as well as decrease gastrointestinal transit. The antinociception caused by a single injection of morphine was slightly increased by an intrathecal injection of Phα1β (30 pmol/site). Repeated treatment with morphine caused tolerance, hyperalgesia, withdrawal syndrome, and constipation, and the Phα1β (.1-30 pmol/site, intrathecal) was able to reverse these effects. Finally, the effects produced by the native form of Phα1β were fully mimicked by a recombinant version of this peptide. Taken together, these data show that Phα1β was effective in potentiating the analgesia caused by a single dose of morphine as well as in reducing tolerance and the adverse effects induced by repeated administration of morphine, indicating its potential use as an adjuvant drug in combination with opioids. This article presents preclinical evidence for a useful adjuvant drug in opioid treatment. Phα1β, a peptide calcium channel blocker, could be used not only to potentiate morphine analgesia but also to reduce the adverse effects caused by repeated administration of morphine. Copyright © 2014. Published by Elsevier Inc.

Drug safety data mining with a tree-based scan statistic.

PubMed

Kulldorff, Martin; Dashevsky, Inna; Avery, Taliser R; Chan, Arnold K; Davis, Robert L; Graham, David; Platt, Richard; Andrade, Susan E; Boudreau, Denise; Gunter, Margaret J; Herrinton, Lisa J; Pawloski, Pamala A; Raebel, Marsha A; Roblin, Douglas; Brown, Jeffrey S

2013-05-01

In post-marketing drug safety surveillance, data mining can potentially detect rare but serious adverse events. Assessing an entire collection of drug-event pairs is traditionally performed on a predefined level of granularity. It is unknown a priori whether a drug causes a very specific or a set of related adverse events, such as mitral valve disorders, all valve disorders, or different types of heart disease. This methodological paper evaluates the tree-based scan statistic data mining method to enhance drug safety surveillance. We use a three-million-member electronic health records database from the HMO Research Network. Using the tree-based scan statistic, we assess the safety of selected antifungal and diabetes drugs, simultaneously evaluating overlapping diagnosis groups at different granularity levels, adjusting for multiple testing. Expected and observed adverse event counts were adjusted for age, sex, and health plan, producing a log likelihood ratio test statistic. Out of 732 evaluated disease groupings, 24 were statistically significant, divided among 10 non-overlapping disease categories. Five of the 10 signals are known adverse effects, four are likely due to confounding by indication, while one may warrant further investigation. The tree-based scan statistic can be successfully applied as a data mining tool in drug safety surveillance using observational data. The total number of statistical signals was modest and does not imply a causal relationship. Rather, data mining results should be used to generate candidate drug-event pairs for rigorous epidemiological studies to evaluate the individual and comparative safety profiles of drugs. Copyright © 2013 John Wiley & Sons, Ltd.

A Comprehensive Look at Polypharmacy and Medication Screening Tools for the Older Cancer Patient

PubMed Central

DeGregory, Kathlene A.; Morris, Amy L.; Ramsdale, Erika E.

2016-01-01

Inappropriate medication use and polypharmacy are extremely common among older adults. Numerous studies have discussed the importance of a comprehensive medication assessment in the general geriatric population. However, only a handful of studies have evaluated inappropriate medication use in the geriatric oncology patient. Almost a dozen medication screening tools exist for the older adult. Each available tool has the potential to improve aspects of the care of older cancer patients, but no single tool has been developed for this population. We extensively reviewed the literature (MEDLINE, PubMed) to evaluate and summarize the most relevant medication screening tools for older patients with cancer. Findings of this review support the use of several screening tools concurrently for the elderly patient with cancer. A deprescribing tool should be developed and included in a comprehensive geriatric oncology assessment. Finally, prospective studies are needed to evaluate such a tool to determine its feasibility and impact in older patients with cancer. Implications for Practice: The prevalence of polypharmacy increases with advancing age. Older adults are more susceptible to adverse effects of medications. “Prescribing cascades” are common, whereas “deprescribing” remains uncommon; thus, older patients tend to accumulate medications over time. Older patients with cancer are at high risk for adverse drug events, in part because of the complexity and intensity of cancer treatment. Additionally, a cancer diagnosis often alters assessments of life expectancy, clinical status, and competing risk. Screening for polypharmacy and potentially inappropriate medications could reduce the risk for adverse drug events, enhance quality of life, and reduce health care spending for older cancer patients. PMID:27151653

The Associations Between Air Pollution and Adverse Pregnancy Outcomes in China.

PubMed

Tan, Yafei; Yang, Rong; Zhao, Jinzhu; Cao, Zhongqiang; Chen, Yawen; Zhang, Bin

2017-01-01

Research on the potential impact of air pollution on the human's health has increased rapidly in recent years. Several studies have suggested that exposure to air pollutants during period of pregnancy which is a crucial time point of mother-fetus development may have long-term and serious impact on adverse pregnancy outcomes. There is lack of review to evaluate the existed epidemiologic evidence on the associations between air pollutants and adverse pregnancy outcomes in China, so we conducted a review to explore the current epidemiological evidence on the effects of air pollutants to pregnancy outcomes and possible mechanisms during the pregnancy process. We used keywords to systematically search all the English and Chinese literatures on studies that were conducted in China. Exposure to air pollutants during pregnancy had shown there were harmful effects for different birth outcomes: preterm birth, low birth weight, stillbirth, birth defects, infertility, and macrosomia fetus. Results on the effects of air pollutants on adverse pregnancy outcomes are small and inconsistent because they vary in their design and methodology. The existed available evidence is compatible with either a small negative effect of air pollutants on pregnancy outcomes or with no effect; therefore, further studies are needed to confirm and quantify the possible associations and potential biologic mechanisms between air pollutants and pregnancy outcomes.

[Adverse Event Trends Associated with Over-the-counter Combination Cold Remedy: Data Mining of the Japanese Adverse Drug Event Report Database].

PubMed

Sasaoka, Sayaka; Hatahira, Haruna; Hasegawa, Shiori; Motooka, Yumi; Fukuda, Akiho; Naganuma, Misa; Umetsu, Ryogo; Nakao, Satoshi; Shimauchi, Akari; Ueda, Natsumi; Hirade, Kouseki; Iguchi, Kazuhiro; Nakamura, Mitsuhiro

2018-01-01

 OTC combination cold remedies are widely used in Japan. In the present study, we aimed to evaluate the adverse event profiles of OTC combination cold remedy based on the components using the Japanese Adverse Drug Event Report (JADER) database. The JADER database contained 430587 reports between April 2004 and November 2016. 1084 adverse events associated with the use of OTC combination cold remedy were reported. Reporting odds ratio (ROR) was used to detect safety signals. The ROR values for "skin and subcutaneous tissue disorders", "hepatobiliary disorders", and "immune system disorders" stratified by system organ class of the Medical Dictionary for Regulatory Activities (MedDRA) were 9.82 (8.71-11.06), 2.63 (2.25-3.07), and 3.13 (2.63-3.74), respectively. OTC combination cold remedy containing acetaminophen exhibited a significantly higher reporting ratio for "hepatobiliary disorders" than OTC combination cold remedy without acetaminophen. We demonstrated the potential risk of OTC combination cold remedy in a real-life setting. Our results suggested that the monitoring of individuals using OTC combination cold remedy is important.

Evaluation of a predevelopment service delivery intervention: an application to improve clinical handovers.

PubMed

Yao, Guiqing Lily; Novielli, Nicola; Manaseki-Holland, Semira; Chen, Yen-Fu; van der Klink, Marcel; Barach, Paul; Chilton, Peter J; Lilford, Richard J

2012-12-01

We developed a method to estimate the expected cost-effectiveness of a service intervention at the design stage and 'road-tested' the method on an intervention to improve patient handover of care between hospital and community. The development of a nine-step evaluation framework: 1. Identification of multiple endpoints and arranging them into manageable groups; 2. Estimation of baseline overall and preventable risk; 3. Bayesian elicitation of expected effectiveness of the planned intervention; 4. Assigning utilities to groups of endpoints; 5. Costing the intervention; 6. Estimating health service costs associated with preventable adverse events; 7. Calculating health benefits; 8. Cost-effectiveness calculation; 9. Sensitivity and headroom analysis. Literature review suggested that adverse events follow 19% of patient discharges, and that one-third are preventable by improved handover (ie, 6.3% of all discharges). The intervention to improve handover would reduce the incidence of adverse events by 21% (ie, from 6.3% to 4.7%) according to the elicitation exercise. Potentially preventable adverse events were classified by severity and duration. Utilities were assigned to each category of adverse event. The costs associated with each category of event were obtained from the literature. The unit cost of the intervention was €16.6, which would yield a Quality Adjusted Life Year (QALY) gain per discharge of 0.010. The resulting cost saving was €14.3 per discharge. The intervention is cost-effective at approximately €214 per QALY under the base case, and remains cost-effective while the effectiveness is greater than 1.6%. We offer a usable framework to assist in ex ante health economic evaluations of health service interventions.

Evaluation of a predevelopment service delivery intervention: an application to improve clinical handovers

PubMed Central

Yao, Guiqing Lily; Novielli, Nicola; Manaseki-Holland, Semira; Chen, Yen-Fu; van der Klink, Marcel; Barach, Paul; Chilton, Peter J; Lilford, Richard J

2012-01-01

Background We developed a method to estimate the expected cost-effectiveness of a service intervention at the design stage and ‘road-tested’ the method on an intervention to improve patient handover of care between hospital and community. Method The development of a nine-step evaluation framework: 1. Identification of multiple endpoints and arranging them into manageable groups; 2. Estimation of baseline overall and preventable risk; 3. Bayesian elicitation of expected effectiveness of the planned intervention; 4. Assigning utilities to groups of endpoints; 5. Costing the intervention; 6. Estimating health service costs associated with preventable adverse events; 7. Calculating health benefits; 8. Cost-effectiveness calculation; 9. Sensitivity and headroom analysis. Results     Literature review suggested that adverse events follow 19% of patient discharges, and that one-third are preventable by improved handover (ie, 6.3% of all discharges). The intervention to improve handover would reduce the incidence of adverse events by 21% (ie, from 6.3% to 4.7%) according to the elicitation exercise. Potentially preventable adverse events were classified by severity and duration. Utilities were assigned to each category of adverse event. The costs associated with each category of event were obtained from the literature. The unit cost of the intervention was €16.6, which would yield a Quality Adjusted Life Year (QALY) gain per discharge of 0.010. The resulting cost saving was €14.3 per discharge. The intervention is cost-effective at approximately €214 per QALY under the base case, and remains cost-effective while the effectiveness is greater than 1.6%. Conclusions We offer a usable framework to assist in ex ante health economic evaluations of health service interventions. PMID:22976505

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

Refining Video Game Use Questionnaires for Research and Clinical Application: Detection of Problematic Response Sets

ERIC Educational Resources Information Center

Faust, Kyle A.; Faust, David; Baker, Aaron M.; Meyer, Joseph F.

2012-01-01

Even when relatively infrequent, deviant response sets, such as defensive and careless responding, can have remarkably robust effects on individual and group data and thereby distort clinical evaluations and research outcomes. Given such potential adverse impacts and the widespread use of self-report measures when appraising addictions and…

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

EPA Science Inventory

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

Effect of surface application of ammonium thiosulfate on field-scale emissions of 1,3-dichloropropene

USDA-ARS?s Scientific Manuscript database

Soil fumigation is important for food production but has the potential to discharge toxic chemicals into the environment, which may adversely affect human and ecosystem health. A field experiment was conducted to evaluate the effect of applying ammonium thiosulfate fertilizer to the soil surface pr...

Cognitive Load Imposed by Ultrasound-Facilitated Teaching Does Not Adversely Affect Gross Anatomy Learning Outcomes

ERIC Educational Resources Information Center

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

2017-01-01

Ultrasonography is increasingly used in medical education, but its impact on learning outcomes is unclear. Adding ultrasound may facilitate learning, but may also potentially overwhelm novice learners. Based upon the framework of cognitive load theory, this study seeks to evaluate the relationship between cognitive load associated with using…

Novel surgical performance evaluation approximates Standardized Incidence Ratio with high accuracy at simple means.

PubMed

Gabbay, Itay E; Gabbay, Uri

2013-01-01

Excess adverse events may be attributable to poor surgical performance but also to case-mix, which is controlled through the Standardized Incidence Ratio (SIR). SIR calculations can be complicated, resource consuming, and unfeasible in some settings. This article suggests a novel method for SIR approximation. In order to evaluate a potential SIR surrogate measure we predefined acceptance criteria. We developed a new measure - Approximate Risk Index (ARI). "Number Needed for Event" (NNE) is the theoretical number of patients needed "to produce" one adverse event. ARI is defined as the quotient of the group of patients needed for no observed events Ge by total patients treated Ga. Our evaluation compared 2500 surgical units and over 3 million heterogeneous risk surgical patients that were induced through a computerized simulation. Surgical unit's data were computed for SIR and ARI to evaluate compliance with the predefined criteria. Approximation was evaluated by correlation analysis and performance prediction capability by Receiver Operating Characteristics (ROC) analysis. ARI strongly correlates with SIR (r(2) = 0.87, p < 0.05). ARI prediction of excessive risk revealed excellent ROC (Area Under the Curve > 0.9) 87% sensitivity and 91% specificity. ARI provides good approximation of SIR and excellent prediction capability. ARI is simple and cost-effective as it requires thorough risk evaluation of only the adverse events patients. ARI can provide a crucial screening and performance evaluation quality control tool. The ARI method may suit other clinical and epidemiological settings where relatively small fraction of the entire population is affected. Copyright © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

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.

Late biological effects of heavy charged particles: Cataracts, vascular injury and life shortening in mice

NASA Astrophysics Data System (ADS)

Ainsworth, E. J.; Jose, J. G.; Barker, M. E.; Alpen, E. L.

1980-07-01

Risks associated with extended habitation in a space environment, particularly hazards to space workers that might result from exposure to high energy heavy ion particles (HZE), were studied. Biological effects of HZE were investigated in mice to assess their potential adverse health hazards. The potential effects of HZE particles on the crystalline lens of the eye and the carcinogenic effects and blood vessel (vascular) damage from radiation were evaluated by a risk assessment. Animal experiments to evaluate dose response relationships for tumor induction/promotion and for vascular injury were introduced. Cataract productions and preliminary results on cacinogenic and vascular effects are presented for perspective.

Late biological effects of heavy charged particles: Cataracts, vascular injury and life shortening in mice

NASA Technical Reports Server (NTRS)

Ainsworth, E. J.; Jose, J. G.; Barker, M. E.; Alpen, E. L.

1980-01-01

Risks associated with extended habitation in a space environment, particularly hazards to space workers that might result from exposure to high energy heavy ion particles (HZE), were studied. Biological effects of HZE were investigated in mice to assess their potential adverse health hazards. The potential effects of HZE particles on the crystalline lens of the eye and the carcinogenic effects and blood vessel (vascular) damage from radiation were evaluated by a risk assessment. Animal experiments to evaluate dose response relationships for tumor induction/promotion and for vascular injury were introduced. Cataract productions and preliminary results on cacinogenic and vascular effects are presented for perspective.

Proposal of a New Adverse Event Classification by the Society of Interventional Radiology Standards of Practice Committee.

PubMed

Khalilzadeh, Omid; Baerlocher, Mark O; Shyn, Paul B; Connolly, Bairbre L; Devane, A Michael; Morris, Christopher S; Cohen, Alan M; Midia, Mehran; Thornton, Raymond H; Gross, Kathleen; Caplin, Drew M; Aeron, Gunjan; Misra, Sanjay; Patel, Nilesh H; Walker, T Gregory; Martinez-Salazar, Gloria; Silberzweig, James E; Nikolic, Boris

2017-10-01

To develop a new adverse event (AE) classification for the interventional radiology (IR) procedures and evaluate its clinical, research, and educational value compared with the existing Society of Interventional Radiology (SIR) classification via an SIR member survey. A new AE classification was developed by members of the Standards of Practice Committee of the SIR. Subsequently, a survey was created by a group of 18 members from the SIR Standards of Practice Committee and Service Lines. Twelve clinical AE case scenarios were generated that encompassed a broad spectrum of IR procedures and potential AEs. Survey questions were designed to evaluate the following domains: educational and research values, accountability for intraprocedural challenges, consistency of AE reporting, unambiguity, and potential for incorporation into existing quality-assurance framework. For each AE scenario, the survey participants were instructed to answer questions about the proposed and existing SIR classifications. SIR members were invited via online survey links, and 68 members participated among 140 surveyed. Answers on new and existing classifications were evaluated and compared statistically. Overall comparison between the two surveys was performed by generalized linear modeling. The proposed AE classification received superior evaluations in terms of consistency of reporting (P < .05) and potential for incorporation into existing quality-assurance framework (P < .05). Respondents gave a higher overall rating to the educational and research value of the new compared with the existing classification (P < .05). This study proposed an AE classification system that outperformed the existing SIR classification in the studied domains. Copyright © 2017 SIR. Published by Elsevier Inc. All rights reserved.

Estrogen Receptor Binding Affinity of Food Contact Material Components Estimated by QSAR.

PubMed

Sosnovcová, Jitka; Rucki, Marián; Bendová, Hana

2016-09-01

The presented work characterized components of food contact materials (FCM) with potential to bind to estrogen receptor (ER) and cause adverse effects in the human organism. The QSAR Toolbox, software application designed to identify and fill toxicological data gaps for chemical hazard assessment, was used. Estrogen receptors are much less of a lock-and-key interaction than highly specific ones. The ER is nonspecific enough to permit binding with a diverse array of chemical structures. There are three primary ER binding subpockets, each with different requirements for hydrogen bonding. More than 900 compounds approved as of FCM components were evaluated for their potential to bind on ER. All evaluated chemicals were subcategorized to five groups with respect to the binding potential to ER: very strong, strong, moderate, weak binder, and no binder to ER. In total 46 compounds were characterized as potential disturbers of estrogen receptor. Among the group of selected chemicals, compounds with high and even very high affinity to the ER binding subpockets were found. These compounds may act as gene activators and cause adverse effects in the organism, particularly during pregnancy and breast-feeding. It should be considered to carry out further in vitro or in vivo tests to confirm their potential to disturb the regulation of physiological processes in humans by abnormal ER signaling and subsequently remove these chemicals from the list of approved food contact materials. Copyright© by the National Institute of Public Health, Prague 2016

Can surveillance systems identify and avert adverse drug events? A prospective evaluation of a commercial application.

PubMed

Jha, Ashish K; Laguette, Julia; Seger, Andrew; Bates, David W

2008-01-01

Computerized monitors can effectively detect and potentially prevent adverse drug events (ADEs). Most monitors have been developed in large academic hospitals and are not readily usable in other settings. We assessed the ability of a commercial program to identify and prevent ADEs in a community hospital. and Measurement We prospectively evaluated the commercial application in a community-based hospital. We examined the frequency and types of alerts produced, how often they were associated with ADEs and potential ADEs, and the potential financial impact of monitoring for ADEs. Among 2,407 patients screened, the application generated 516 high priority alerts. We were able to review 266 alerts at the time they were generated and among these, 30 (11.3%) were considered substantially important to warrant contacting the physician caring for the patient. These 30 alerts were associated with 4 ADEs and 11 potential ADEs. In all 15 cases, the responsible physician was unaware of the event, leading to a change in clinical care in 14 cases. Overall, 23% of high priority alerts were associated with an ADE (95% confidence interval [CI] 12% to 34%) and another 15% were associated with a potential ADE (95% CI 6% to 24%). Active surveillance used approximately 1.5 hours of pharmacist time daily. A commercially available, computer-based ADE detection tool was effective at identifying ADEs. When used as part of an active surveillance program, it can have an impact on preventing or ameliorating ADEs.

Adverse drug events and medication problems in "Hospital at Home" patients.

PubMed

Mann, Elizabeth; Zepeda, Orlando; Soones, Tacara; Federman, Alex; Leff, Bruce; Siu, Albert; Boockvar, Kenneth

2018-03-26

"Hospital at Home(HaH)" programs provide an alternative to traditional hospitalization. However, the incidence of adverse drug events in these programs is unknown. This study describes adverse drug events and potential adverse drug events in a new HaH program. We examined the charts of the first 50 patients admitted. We found 45 potential adverse drug events and 14 adverse drug events from admission to 30 days after HaH discharge. None of the adverse drug events were severe. Some events, like problems with medication administration, may be unique to the hospital at home setting. Monitoring for adverse drug events is feasible and important for hospital at home programs.

A literature review: polypharmacy protocol for primary care.

PubMed

Skinner, Mary

2015-01-01

The purpose of this literature review is to critically evaluate published protocols on polypharmacy in adults ages 65 and older that are currently used in primary care settings that may potentially lead to fewer adverse drug events. A review of OVID, CINAHL, EBSCO, Cochrane Library, Medline, and PubMed databases was completed using the following key words: protocol, guideline, geriatrics, elderly, older adult, polypharmacy, and primary care. Inclusion criteria were: articles in medical, nursing, and pharmacology journals with an intervention, protocol, or guideline addressing polypharmacy that lead to fewer adverse drug events. Qualitative and quantitative studies were included. Exclusion criteria were: publications prior to the year 1992. A gap exists in the literature. No standardized protocol for addressing polypharmacy in the primary care setting was found. Mnemonics, algorithms, clinical practice guidelines, and clinical strategies for addressing polypharmacy in a variety of health care settings were found throughout the literature. Several screening instruments for use in primary care to assess potentially inappropriate prescription of medications in the elderly, such as the Beers Criteria and the STOPP screening tool, were identified. However, these screening instruments were not included in a standardized protocol to manage polypharmacy in primary care. Polypharmacy in the elderly is a critical problem that may result in adverse drug events such as falls, hospitalizations, and increased expenditures for both the patient and the health care system. No standardized protocols to address polypharmacy specific to the primary care setting were identified in this review of the literature. Given the growing population of elderly in this country and the high number of medications they consume, it is critical to focus on the utilization of a standardized protocol to address the potential harm of polypharmacy in the primary care setting and evaluate its effects on patient outcomes. Copyright © 2015 Elsevier Inc. All rights reserved.

Maternal dental history and child’s birth outcome and early cognitive development

PubMed Central

Daniels, JL; Rowland, AS; Longnecker, MP; Crawford, P; Golding, J

2013-01-01

Summary Prenatal exposure to high levels of mercury, radiation, and inflammation have been associated with adverse reproductive outcomes such as increases in preterm delivery, low birthweight, and delayed neurodevelopment. Few data are available to evaluate the potential effects of prenatal low-level exposure to these factors as might occur during dental care. We evaluated maternal dental history prior to and during pregnancy in relation to birth outcomes and early communicative development among offspring in a large cohort (n=7375) of British children born in 1991–1992. Dental history was assessed by questionnaire. The child’s communicative development was assessed using the MacArthur Communicative Development Inventory at 15 months of age. Total mercury was measured in umbilical cord tissue for a subset of the children. Overall, dental care, including amalgam fillings, was not associated with birth outcomes or language development. Having x-rays taken during pregnancy was not associated with birthweight measured continuously (β=14.7, p=0.4), but was associated with slightly increased odds of having a term, low birthweight baby (OR 1.9, 95%CI 1.0–3.4). More detailed evaluation of the potential adverse effects of elective dental treatment during pregnancy, particularly dental x-rays, may be warranted. PMID:17697075

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

PubMed

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

2009-12-01

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

Screening and Evaluation of Medications for Treating Cannabis Use Disorder

PubMed Central

Panlilio, Leigh V.; Justinova, Zuzana; Trigo, Jose M.; Le Foll, Bernard

2016-01-01

Cannabis use has been increasingly accepted legally and in public opinion. However, cannabis has the potential to produce adverse physical and mental health effects and can result in cannabis use disorder (CUD) in a substantial percentage of both occasional and daily cannabis users. Many people have difficulty discontinuing use. Therefore, it would be beneficial to develop safe and effective medications for treating CUD. To achieve this, methods have been developed for screening and evaluating potential medications using animal models and controlled experimental protocols in human volunteers. In this chapter we describe: 1) animal models available for assessing the effect of potential medications on specific aspects of CUD; 2) the main findings obtained so far with these animal models; 3) the approaches used to assess potential medications in humans in laboratory experiments and clinical trials; and 4) the effectiveness of several potential pharmacotherapies on the particular aspects of CUD modeled in these human studies. PMID:27055612

Early childhood adversity potentiates the adverse association between prenatal organophosphate pesticide exposure and child IQ: The CHAMACOS cohort.

PubMed

Stein, Lauren J; Gunier, Robert B; Harley, Kim; Kogut, Katherine; Bradman, Asa; Eskenazi, Brenda

2016-09-01

Previous studies have observed an adverse association between prenatal exposure to organophosphate pesticide (OPs) and child cognition, but few studies consider the potential role of social stressors in modifying this relationship. We seek to explore the potential role of early social adversities in modifying the relationship between OPs and child IQ in an agricultural Mexican American population. Participants from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study, a prospective longitudinal pre-birth cohort study, include 329 singleton infants and their mothers followed from pregnancy through age 7. Dialkyl phosphate metabolite concentrations (DAPs), a biomarker of organophosphate pesticide exposure, were measured in maternal urine collected twice during pregnancy and averaged. Child cognitive ability was assessed at 7 years using the Wechsler Intelligence Scale for Children - Fourth Edition. Demographic characteristics and adversity information were collected during interviews and home visits at numerous time points from pregnancy until age 7. Among low-income Latina mothers and their children in the Salinas Valley, total adversity and specific domains of adversity including poor learning environment and adverse parent-child relationships were negatively associated with child cognition. Adverse associations between DAP concentrations and IQ were stronger in children experiencing greater adversity; these associations varied by child sex. For example, the association between prenatal OP exposure and Full-Scale IQ is potentiated among boys who experienced high adversity in the learning environment (β=-13.3; p-value <0.01). Greater total and domain-specific adversity modifies negative relationships between prenatal OP exposure and child IQ differently among male and female children. These findings emphasize the need to consider plausible interactive pathways between social adversities and environmental exposures. Copyright © 2016 Elsevier B.V. All rights reserved.

Long-term fate of depleted uranium at Aberdeen and Yuma Proving Grounds: Human health and ecological risk assessments

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

Ebinger, M.H.; Beckman, R.J.; Myers, O.B.

1996-09-01

The purpose of this study was to evaluate the immediate and long-term consequences of depleted uranium (DU) in the environment at Aberdeen Proving Ground (APG) and Yuma Proving Ground (YPG) for the Test and Evaluation Command (TECOM) of the US Army. Specifically, we examined the potential for adverse radiological and toxicological effects to humans and ecosystems caused by exposure to DU at both installations. We developed contaminant transport models of aquatic and terrestrial ecosystems at APG and terrestrial ecosystems at YPG to assess potential adverse effects from DU exposure. Sensitivity and uncertainty analyses of the initial models showed the portionsmore » of the models that most influenced predicted DU concentrations, and the results of the sensitivity analyses were fundamental tools in designing field sampling campaigns at both installations. Results of uranium (U) isotope analyses of field samples provided data to evaluate the source of U in the environment and the toxicological and radiological doses to different ecosystem components and to humans. Probabilistic doses were estimated from the field data, and DU was identified in several components of the food chain at APG and YPG. Dose estimates from APG data indicated that U or DU uptake was insufficient to cause adverse toxicological or radiological effects. Dose estimates from YPG data indicated that U or DU uptake is insufficient to cause radiological effects in ecosystem components or in humans, but toxicological effects in small mammals (e.g., kangaroo rats and pocket mice) may occur from U or DU ingestion. The results of this study were used to modify environmental radiation monitoring plans at APG and YPG to ensure collection of adequate data for ongoing ecological and human health risk assessments.« less

Early vulnerabilities for psychiatric disorders in elementary schoolchildren from four Brazilian regions.

PubMed

Paula, Cristiane S; Mari, Jair J; Bordin, Isabel Altenfelder Santos; Miguel, Euripedes C; Fortes, Isabela; Barroso, Natalia; Rohde, Luis Augusto; Coutinho, Evandro Silva Freire

2018-05-01

The purpose of the study is to identify early vulnerabilities for psychiatric disorders among Brazilian elementary school children, controlling for familial and community adversities. This is a cross-sectional study examining the association between child psychiatric disorders and potential early vulnerabilities (disability, low intellectual quotient, and negative dimensions of the temperament trait self-directedness (low resourcefulness, low purposefulness, low enlightened second nature), controlling for the potential confounders: familial and community adversities. Four probabilistic samples of second-to-sixth grade students from public schools in four towns from different Brazilian regions (N = 1620). The following instruments were applied: the K-SADS-PL (to assess child/adolescent psychiatric disorders); the Ten-Question Screen (to measure child disability); three structured questions used as proxy of self-directedness; and the reduced version of the WISC-III to measure IQ. To evaluate familial/community adversities: Self-Report Questionnaire-SRQ-20 (to assess maternal/primary caretaker anxiety/depression); questions derived from structured questionnaires (to measure child abuse, marital physical violence, neighborhood violence); Brazilian Association of Research Companies questionnaire (to evaluate poverty/socioeconomic status). Trained psychologists interviewed mothers/primary caretakers and evaluated children/adolescents individually. A final logistic regression model showed that children/adolescents with low resourcefulness, low purposefulness, low enlightened second nature, lower IQ and disability were more likely to present any child psychiatric disorders. Early vulnerabilities such as low IQ, presence of disability, and dimensions of temperament were associated with psychiatric disorders among Brazilian elementary school children, after controlling for familial and ecological confounders. These early vulnerabilities should be considered in mental health prevention/intervention programs in low-middle-income countries like Brazil.

Drug use among men with unfulfilled wish to father children: a retrospective analysis and discussion of specific drug classes.

PubMed

Pompe, Sina V; Strobach, Dorothea; Stief, Christian G; Becker, Armin J; Trottmann, Matthias

2016-06-01

Male infertility is a multifactorial state. Among other risk factors, drugs can adversely affect male fertility and male sexual function. In a retrospective study we aimed to analyse how many involuntarily childless men seeking fertility evaluation consume drugs, which drugs and if these are potentially affecting male reproductive function. We retrospectively identified involuntarily childless men presenting for fertility evaluation at an andrologic outpatient department from 2011 to 2014. Medical records were searched for current drug use, age, diseases affecting male fertility, and number and kind of drugs. Drugs were classified according to their Anatomical Therapeutic Chemical code. Adverse drug reactions on male sexual function and fertility were searched in two independent literature sources. Drug use was documented for 244 of 522 patients (46.7%). The patients' mean age was 37.7 ± 8.7; the total number of drug intakes was 554 (mean 2.3 ± 1.9), corresponding to 201 different drugs. The most often involved Anatomical Therapeutic Chemical groups were nervous system (N), alimentary tract/metabolism (A), cardiovascular (C), and respiratory system (R) (n = 277; 50.0%). Fertility impairment was reported for 15.9%, and adverse drug reactions on male sexual function were found for 51.2% of all identified drugs. Underreporting of consumed drugs was likely, especially for non-prescription drugs. A high percentage of involuntarily childless men is taking drugs that can potentially influence male reproductive function. As drug intake represents a modifiable risk factor, fertility evaluation requires a comprehensive medication review including prescription and non-prescription drugs. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

The Efficacy of Asthma Case Management in an Urban School District in Reducing School Absences and Hospitalizations for Asthma

ERIC Educational Resources Information Center

Levy, Marian; Heffner, Brenda; Stewart, Tara; Beeman, Gail

2006-01-01

Pediatric asthma rates are reaching epidemic proportions, adversely affecting children's quality of life, educational potential, and health care costs, especially those in the inner city. This study evaluated the effectiveness of a school-based asthma case management (CM) approach with medically undeserved inner-city children attending Memphis…

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

PubMed

Kellihan, M J

1993-01-01

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

Use of contrast media in diagnostic imaging: medico-legal considerations.

PubMed

Pomara, C; Pascale, N; Maglietta, F; Neri, M; Riezzo, I; Turillazzi, E

2015-09-01

Contrast media (CM) are used in imaging techniques to enhance the differences between body tissues on images. The ideal contrast medium should achieve very high concentration in the tissues without producing any adverse effects. Unfortunately, this has not been possible so far and all CM have adverse effects. The increasing use of CM is likely to give rise to a wide range of pitfalls, including compliance with and appropriateness of indications for the use of CM themselves, the choice of the 'best' contrast agent, off-label use, evaluation of special populations of patients, and competence to tackle emergency scenarios following the administration of CM. Even more prominent, and potentially more important, is the issue of informed consent which brings with it a duty to inform patients awaiting the administration of CM with regard to the nature of the procedure, the existence of alternative procedures, the extent of the risks relating to the use of CM and, finally, the risks relating to refusal of the procedure. All these issues may give rise to concerns about liability for failure to offer adequate information to patients or to carefully evaluate and balance the potential risks and benefits of the procedure or, finally, for being unprepared in the event of adverse reactions to CM, especially when these are severe and life-threatening. Educational and training programmes for radiologists are likely to shape change in the medical liability environment in the coming years.

Expansion of flight simulator capability for study and solution of aircraft directional control problems on runways

NASA Technical Reports Server (NTRS)

Kibbee, G. W.

1978-01-01

The development, evaluation, and evaluation results of a DC-9-10 runway directional control simulator are described. An existing wide bodied flight simulator was modified to this aircraft configuration. The simulator was structured to use either two of antiskid simulations; (1) an analog mechanization that used aircraft hardware; or (2) a digital software simulation. After the simulation was developed it was evaluated by 14 pilots who made 818 simulated flights. These evaluations involved landings, rejected takeoffs, and various ground maneuvers. Qualitatively most pilots evaluated the simulator as realistic with good potential especially for pilot training for adverse runway conditions.

Design and in vivo evaluation of solid lipid nanoparticulate systems of Olanzapine for acute phase schizophrenia treatment: Investigations on antipsychotic potential and adverse effects.

PubMed

Joseph, Emil; Reddi, Satish; Rinwa, Vibhu; Balwani, Garima; Saha, Ranendra

2017-06-15

The present paper discusses the design, characterization and in vivo evaluation of glyceryl monostearate nanoparticles of Olanzapine, an atypical antipsychotic drug for acute schizophrenia treatment, during which hospitalization is mandatory and adverse effects are at its peak. The solid lipid nanoparticulate system was obtained by emulsification-ultra sonication technique wherein three factors such as solid lipid content, concentration of surfactant and drug: solid lipid ratio were selected at three different levels in order to study their influence on significant characteristic responses such as particle size, encapsulation efficiency and drug content. A Box Behnken design with 17 runs involving whole factors at three levels was employed for the study. The optimized formulation was further coated with Polysorbate 80 in order to enhance its brain targeting potential through endocytosis transport process via blood brain barrier. The designed formulations were pre-clinically tested successfully in Wistar rat model for in vivo antipsychotic efficacy (apomorphine induced psychosis) and adverse effects (weight gain study for 28days). The results obtained indicated that solid lipid nanoparticles had very narrow size distribution (151.29±3.36nm) with very high encapsulation efficiency (74.51±1.75%). Morphological studies by SEM have shown that solid lipid nanoparticles were spherical in shape with smooth surface. Olanzapine-loaded nanoparticles prepared from solid lipid, extended the release of drug for 48h, as found by the in vitro release studies. The formulations also exhibited high redispersibility after freeze-drying and stability study results demonstrated good stability, with no significant change for a period of 6months. In vivo evaluation and adverse effects studies of Olanzapine-loaded nanoparticulate systems in animal model have demonstrated an improved therapeutic efficacy than pure Olanzapine. The antipsychotic effect of drug loaded nanoparticulate systems was maintained for 48h as compared to 8h antipsychotic action of pure Olanzapine solution. The weight gain studies for 28days demonstrated a significant inhibition in weight gain for Olanzapine-loaded nanoparticulate systems as compared to the pure Olanzapine. The present research findings indicate that OLN-loaded nanoparticulate systems may be highly promising for effective delivery of Olanzapine with better efficacy and minimum adverse effects. Copyright © 2017 Elsevier B.V. All rights reserved.

Aflatoxin Exposure During Pregnancy, Maternal Anemia, and Adverse Birth Outcomes

PubMed Central

Smith, Laura E.; Prendergast, Andrew J.; Turner, Paul C.; Humphrey, Jean H.; Stoltzfus, Rebecca J.

2017-01-01

Pregnant women and their developing fetuses are vulnerable to multiple environmental insults, including exposure to aflatoxin, a mycotoxin that may contaminate as much as 25% of the world food supply. We reviewed and integrated findings from studies of aflatoxin exposure during pregnancy and evaluated potential links to adverse pregnancy outcomes. We identified 27 studies (10 human cross-sectional studies and 17 animal studies) assessing the relationship between aflatoxin exposure and adverse birth outcomes or anemia. Findings suggest that aflatoxin exposure during pregnancy may impair fetal growth. Only one human study investigated aflatoxin exposure and prematurity, and no studies investigated its relationship with pregnancy loss, but animal studies suggest aflatoxin exposure may increase risk for prematurity and pregnancy loss. The fetus could be affected by maternal aflatoxin exposure through direct toxicity as well as indirect toxicity, via maternal systemic inflammation, impaired placental growth, or elevation of placental cytokines. The cytotoxic and systemic effects of aflatoxin could plausibly mediate maternal anemia, intrauterine growth restriction, fetal loss, and preterm birth. Given the widespread exposure to this toxin in developing countries, longitudinal studies in pregnant women are needed to provide stronger evidence for the role of aflatoxin in adverse pregnancy outcomes, and to explore biological mechanisms. Potential pathways for intervention to reduce aflatoxin exposure are urgently needed, and this might reduce the global burden of stillbirth, preterm birth, and low birthweight. PMID:28500823

Aflatoxin Exposure During Pregnancy, Maternal Anemia, and Adverse Birth Outcomes.

PubMed

Smith, Laura E; Prendergast, Andrew J; Turner, Paul C; Humphrey, Jean H; Stoltzfus, Rebecca J

2017-04-01

AbstractPregnant women and their developing fetuses are vulnerable to multiple environmental insults, including exposure to aflatoxin, a mycotoxin that may contaminate as much as 25% of the world food supply. We reviewed and integrated findings from studies of aflatoxin exposure during pregnancy and evaluated potential links to adverse pregnancy outcomes. We identified 27 studies (10 human cross-sectional studies and 17 animal studies) assessing the relationship between aflatoxin exposure and adverse birth outcomes or anemia. Findings suggest that aflatoxin exposure during pregnancy may impair fetal growth. Only one human study investigated aflatoxin exposure and prematurity, and no studies investigated its relationship with pregnancy loss, but animal studies suggest aflatoxin exposure may increase risk for prematurity and pregnancy loss. The fetus could be affected by maternal aflatoxin exposure through direct toxicity as well as indirect toxicity, via maternal systemic inflammation, impaired placental growth, or elevation of placental cytokines. The cytotoxic and systemic effects of aflatoxin could plausibly mediate maternal anemia, intrauterine growth restriction, fetal loss, and preterm birth. Given the widespread exposure to this toxin in developing countries, longitudinal studies in pregnant women are needed to provide stronger evidence for the role of aflatoxin in adverse pregnancy outcomes, and to explore biological mechanisms. Potential pathways for intervention to reduce aflatoxin exposure are urgently needed, and this might reduce the global burden of stillbirth, preterm birth, and low birthweight.

The risks associated with consumer magazines giving advice on complementary therapies.

PubMed

Mantle, Fiona

The increased popularity of complementary and alternative medicine (CAM) has led to increased demand for information on it, giving rise to the concept of "new experts". However, there is concern about the quality and accuracy of this information, much of which is published in popular magazines and written by contributors with no medical qualifications. To examine the extent of CAM product advice in women's and health magazines, and the potential for adverse drug/herbal interaction. Fifteen women's magazines were examined over one month. A total of 150 articles were identified, of which 131 were written by non-medically qualified contributors, mainly journalists. Out of the 150, 95 discussed ingested herbs which had the potential for adverse interactions and are contraindicated for certain groups. The findings have legal and ethical implications. The re-evaluation of the journalists' code of conduct to reflect this development in journalism should be considered.

Evaluating the risk of patient re-identification from adverse drug event reports

PubMed Central

2013-01-01

Background Our objective was to develop a model for measuring re-identification risk that more closely mimics the behaviour of an adversary by accounting for repeated attempts at matching and verification of matches, and apply it to evaluate the risk of re-identification for Canada’s post-marketing adverse drug event database (ADE).Re-identification is only demonstrably plausible for deaths in ADE. A matching experiment between ADE records and virtual obituaries constructed from Statistics Canada vital statistics was simulated. A new re-identification risk is considered, it assumes that after gathering all the potential matches for a patient record (all records in the obituaries that are potential matches for an ADE record), an adversary tries to verify these potential matches. Two adversary scenarios were considered: (a) a mildly motivated adversary who will stop after one verification attempt, and (b) a highly motivated adversary who will attempt to verify all the potential matches and is only limited by practical or financial considerations. Methods The mean percentage of records in ADE that had a high probability of being re-identified was computed. Results Under scenario (a), the risk of re-identification from disclosing the province, age at death, gender, and exact date of the report is quite high, but the removal of province brings down the risk significantly. By only generalizing the date of reporting to month and year and including all other variables, the risk is always low. All ADE records have a high risk of re-identification under scenario (b), but the plausibility of that scenario is limited because of the financial and practical deterrent even for highly motivated adversaries. Conclusions It is possible to disclose Canada’s adverse drug event database while ensuring that plausible re-identification risks are acceptably low. Our new re-identification risk model is suitable for such risk assessments. PMID:24094134

Adverse fetal outcome in road accidents: Injury mechanism study and injury criteria development in a pregnant woman finite element model.

PubMed

Auriault, F; Thollon, L; Pérès, J; Behr, M

2016-12-01

This study documents the development of adverse fetal outcome predictors dedicated to the analysis of road accidents involving pregnant women. To do so, a pre-existing whole body finite element model representative of a 50th percentile 26 weeks pregnant woman was used. A total of 8 accident scenarios were simulated with the model positioned on a sled. Each of these scenarios was associated to a risk of adverse fetal outcome based on results from real car crash investigations involving pregnant women from the literature. The use of airbags and accidents involving unbelted occupants were not considered in this study. Several adverse fetal outcome potential predictors were then evaluated with regard to their correlation to this risk of fetal injuries. Three predictors appeared strongly correlated to the risk of adverse fetal outcome: (1) the intra uterine pressure at the placenta fetal side area (r=0.92), (2) the fetal head acceleration (HIC) (r=0.99) and (3) area of utero-placental interface over a strain threshold (r=0.90). Finally, sensitivity analysis against slight variations of the simulation parameters was performed and assess robustness of these criteria. Copyright © 2016 Elsevier Ltd. All rights reserved.

An evaluation of selected herbal reference texts and comparison to published reports of adverse herbal events.

PubMed

Haller, Christine A; Anderson, Ilene B; Kim, Susan Y; Blanc, Paul D

2002-01-01

There has been a recent proliferation of medical reference texts intended to guide practitioners whose patients use herbal therapies. We systematically assessed six herbal reference texts to evaluate the information they contain on herbal toxicity. We selected six major herbal references published from 1996 to 2000 to evaluate the adequacy of their toxicological information in light of published adverse events. To identify herbs most relevant to toxicology, we reviewed herbal-related calls to our regional California Poison Control System, San Francisco division (CPCS-SF) in 1998 and identified the 12 herbs (defined as botanical dietary supplements) most frequently involved in these CPCS-SF referrals. We searched Medline (1966 to 2000) to identify published reports of adverse effects potentially related to these same 12 herbs. We scored each herbal reference text on the basis of information inclusiveness for the target 12 herbs, with a maximal overall score of 3. The herbs, identified on the basis of CPCS-SF call frequency were: St John's wort, ma huang, echinacea, guarana, ginkgo, ginseng, valerian, tea tree oil, goldenseal, arnica, yohimbe and kava kava. The overall herbal reference scores ranged from 2.2 to 0.4 (median 1.1). The Natural Medicines Comprehensive Database received the highest overall score and was the most complete and useful reference source. All of the references, however, lacked sufficient information on management of herbal medicine overdose, and several had incorrect overdose management guidelines that could negatively impact patient care. Current herbal reference texts do not contain sufficient information for the assessment and management of adverse health effects of botanical therapies.

Preoperative Evaluation and Patient Selection for Office-Based Oral Surgery Anesthesia.

PubMed

Lieblich, Stuart

2018-05-01

Provision of an outpatient anesthetic requires careful review of the patient's medical history along with salient aspects of the physical examination. The oral and maxillofacial surgeon may need to consult with the patient's medical providers to gain an understanding of the patient's potential risks for an adverse event. This article reviews key aspects of the patient evaluation so that an informed determination of suitability for an office anesthetic can be made. Copyright © 2018 Elsevier Inc. All rights reserved.

Environmental adversities and psychotic symptoms: The impact of timing of trauma, abuse, and neglect.

PubMed

Schalinski, Inga; Breinlinger, Susanne; Hirt, Vanessa; Teicher, Martin H; Odenwald, Michael; Rockstroh, Brigitte

2017-11-13

Trauma and adverse childhood experiences (ACE) occur more often in mental illness, including psychosis, than in the general population. Individuals with psychosis (cases) report a higher number and severity (dose) of adversities than healthy controls. While a dose-dependent increase of adversities has been related to more severe psychopathology, the role of type and timing is still insufficiently understood on the exacerbation of positive and negative psychotic symptoms. Moreover, dissociative symptoms were examined as potential mediator between adversities and severity of psychotic symptoms. Exposure to adversities were assessed by interviews in n=180 cases and n=70 controls. In cases, symptom severities were obtained for psychotic symptoms and dissociation. Conditioned random forest regression determined the importance of type and timing of ACE for positive and negative symptom severity, and mediator analyses evaluated the role of dissociative symptoms in the relationship between adversities and psychotic symptoms. Cases experienced substantially more abuse and neglect than controls. Adversities were related in a dose-dependent manner to psychotic disorder. An array of adversities was associated with more severe positive symptoms, while the conditioned random forest regression depicted neglect at age 10 as the most important predictor. Dissociative symptoms mediated the small relation of trauma load in childhood and positive symptoms. The role of trauma and ACE on psychotic symptoms can be specified by neglect during frontocortical development in the exacerbation of positive symptoms. The mediating role of dissociation is restricted to the relation of childhood trauma and positive symptoms. Copyright © 2017 Elsevier B.V. All rights reserved.

Use of contrast media in computed tomography and magnetic resonance imaging in horses: Techniques, adverse events and opportunities.

PubMed

Nelson, B B; Goodrich, L R; Barrett, M F; Grinstaff, M W; Kawcak, C E

2017-07-01

The use of contrast media in computed tomography (CT) and magnetic resonance imaging (MRI) is increasing in horses. These contrast-enhanced imaging techniques provide improved tissue delineation and evaluation, thereby expanding diagnostic capabilities. While generally considered safe, not all contrast media exhibit the same safety profiles. The safety of contrast media use and descriptions of adverse events occurring in horses are sparsely reported. This review summarises the reported evidence of contrast media use and adverse events that occur in horses, with added contribution from other veterinary species and studies in man for comparison. This comprehensive data set empowers equine clinicians to develop use and monitoring strategies when working with contrast media. Finally, it summarises the current state-of-the-art and highlights the potential applications of contrast-enhanced CT and MRI for assessment of diseased or injured equine tissues, as well as (patho)physiological processes. © 2017 EVJ Ltd.

Use of systemic antifungals in daily clinical practice in the haematology and oncology setting: results of a prospective observational analysis.

PubMed

Metzke, Barbara; Neubauer, Werner Christian; Hieke, Stefanie; Jung, Manfred; Wäsch, Ralph; Engelhardt, Monika

2012-09-01

To assess the role of systemic antifungal drugs as well as the frequency of potential drug interactions and adverse drug events of commonly used antifungals in an unselected haematology/oncology patient cohort. A prospective analysis was performed in our haematology/oncology department between October 2006 and September 2009. Data were obtained from 250 consecutive patients who received treatment and/or prophylaxis with fluconazole (n = 191), liposomal amphotericin B (n = 105), voriconazole (n = 62), caspofungin (n = 27) and/or posaconazole (n = 22). We performed detailed reviews of patient charts and laboratory values in close cooperation with treating physicians and nursing staff and participated regularly in ward and chart rounds. Potential drug interactions were assessed using the electronic database Micromedex® 1.0 (Healthcare Series). In terms of adverse drug events, caspofungin (56%) and voriconazole (58%) revealed a slightly more favourable safety profile than liposomal amphotericin B (66%) and posaconazole (64%). We confirmed frequent nephrotoxic effects with the use of liposomal amphotericin B (20%). Regarding potential drug interactions, 97 (66%) of 147 evaluated patients were exposed to at least 1 of 22 different potentially interacting drug combinations involving systemic antifungal agents. Cyclosporine was the most prevalent potentially interacting drug in our cohort. Systemic antifungal drugs are widely used in the haematology/oncology setting and exhibit numerous potential drug interactions and adverse events in cancer patients. Our results highlight the challenges related to antifungal drugs and should valuably contribute to a safe and efficient application of this increasingly important class of drugs. Copyright © 2012 John Wiley & Sons, Ltd.

Efficacy and Safety of Remifentanil as an Alternative Labor Analgesic

PubMed Central

Devabhakthuni, Sandeep

2013-01-01

The objective of this review was to evaluate the clinical efficacy and safety of remifentanil in the management of labor pain. Although neuraxial analgesia is the best option during labor, alternative analgesic options are needed for patients with contraindications. Using a systematic literature search, clinical outcomes of remifentanil for labor pain have been summarized. Also, comparisons of remifentanil to other options including meperidine, epidural analgesia, fentanyl, and nitrous oxide are provided. Based on the literature review, remifentanil is associated with high overall maternal satisfaction and favorable side-effect profile. However, due to the low reporting of adverse events, large, randomized controlled trials are needed to evaluate maternal and neonatal safety adequately and determine the optimal dosing needed to provide effective analgesia. While remifentanil is a feasible alternative for patients who cannot or do not want to receive epidural analgesia, administration should be monitored closely for potential adverse effects. PMID:24665213

Gestational bisphenol A exposure and testis development.

PubMed

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

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

A 90-day repeated-dose toxicity study of dietary alpha linolenic acid-enriched diacylglycerol oil in rats.

PubMed

Bushita, Hiroto; Ito, Yuichi; Saito, Tetsuji; Nukada, Yuko; Ikeda, Naohiro; Nakagiri, Hideaki; Saito, Kazutoshi; Morita, Osamu

2018-05-31

Diets supplemented with alpha-linolenic acid (ALA)-enriched diacylglycerol (DAG) oil-which mainly consists of oleic and linolenic, linoleic acids-have potential health benefits in terms of preventing or managing obesity. Although safety of DAG oil has been extensively investigated, toxicity of ALA-DAG oil has not been well understood. Hence, the present study was conducted to clarify the potential adverse effects, if any, of ALA-DAG oil in rats (10/sex/group) fed diets containing 1.375%, 2.75%, or 5.5% ALA-DAG oil for 90 days. Compared to control rats fed rapeseed oil or ALA-triacylglycerol oil (flaxseed oil), rats receiving ALA-DAG oil did not reveal any toxicologically significant treatment-related changes as evaluated by clinical signs, functional observational battery, body weight, food consumption, ophthalmology, urinalysis, hematology, clinical chemistry, organ weight, necropsy and histopathology. The no observed adverse effect levels for dietary exposure to ALA-DAG oil for male and female rats were 2916 and 3326 mg/kg body weight/day, respectively, the highest dose tested. The findings from this study suggest that consumption of ALA-DAG oil is unlikely to cause adverse effects. Copyright © 2018. Published by Elsevier Inc.

Screening the Emission Sources of Volatile Organic Compounds (VOCs) in China Based on Multi-effect Evaluation

NASA Astrophysics Data System (ADS)

Niu, H., Jr.

2015-12-01

Volatile organic compounds (VOCs) in the atmosphere have adverse impacts via three main pathways: photochemical ozone formation, secondary organic aerosol production, and direct toxicity to humans. Few studies have integrated these effects to prioritize control measures for VOCs sources. In this study, we developed a multi-effect evaluation methodology based on updated emission inventories and source profiles, which was combined with ozone formation potential (OFP), secondary organic aerosol potential (SOAP), and VOC toxicity data to identify important emission sources and key species. We derived species-specific emission inventories for 152 sources. The OFPs, SOAPs, and toxicity of each source were determined, and the contribution and share of each source to each of these adverse effects was calculated. Weightings were given to the three adverse effects by expert scoring, and the integrated impact was determined. Using 2012 as the base year, solvent usage and industrial process were found to be the most important anthropogenic sources, accounting for 24.2 and 23.1% of the integrated environmental effect, respectively. This was followed by biomass burning, transportation, and fossil fuel combustion, all of which had a similar contribution ranging from 16.7 to 18.6%. The top five industrial sources, including plastic products, rubber products, chemical fiber products, the chemical industry, and oil refining, accounted for nearly 70.0% of industrial emissions. In China, emissions reductions are required for styrene, toluene, ethylene, benzene, and m/p-xylene. The 10 most abundant chemical species contributed 76.5% of the integrated impact. Beijing, Chongqing, Shanghai, Jiangsu, and Guangdong were the five leading provinces when considering the integrated effects. Besides, the chemical mass balance model (CMB) was used to verify the VOCs inventories of 47 cities in China, so as to optimize our evaluation results. We suggest that multi-effect evaluation is necessary to identify the need for abatement at the source type and substance levels.

Treatment of Congenital Toxoplasmosis: Safety of the Sulfadoxine-Pyrimethamine Combination in Children Based on a Method of Causality Assessment.

PubMed

Teil, Julie; Dupont, Damien; Charpiat, Bruno; Corvaisier, Stéphane; Vial, Thierry; Leboucher, Gilles; Wallon, Martine; Peyron, François

2016-06-01

The treatment of newborns and infants with congenital toxoplasmosis is standard practice. Some observational studies have examined safety in newborns, but most of these failed to provide sufficient details for a provisional assessment of causality. The aim of this study was to evaluate the clinical and biological adverse effects of the combination of sulfadoxine-pyrimethamine. Sixty-five children treated for 1 year with a combination of sulfadoxine-pyrimethamine (1 dose every 10 days) for congenital toxoplasmosis were followed up to evaluate abnormal hematological values and potential adverse events using a standardized method of causality assessment. Nine patients (13.8%) presented at least 1 adverse clinical event that was nonspecific, such as diarrhea on the day of drug administration, vomiting and agitation. In 1 patient, erythema appeared at the end of the treatment and resolved within 10 days. None of these events was attributed to the treatment. Six patients (9.2%) developed an adverse hematological event (neutropenia, n = 3; eosinophilia, n = 2 and both anemia and eosinophilia, n = 1) that was considered to be possibly related to the sulfadoxine-pyrimethamine combination. Four treatments were temporarily interrupted, and toxicity was observed after readministration of treatment in 1 case only. However, none of these adverse events was life threatening. According to our results and previously published data, the combination of sulfadoxine-pyrimethamine seems to be well tolerated. However, the sample size of our study was too small to rule out the risk of less frequent, but nevertheless severe, reactions and, in particular, of hypersensitivity reactions.

Synthesis and biological evaluation of febrifugine analogues as potential antimalarial agents.

PubMed

Zhu, Shuren; Zhang, Quan; Gudise, Chandrashekar; Wei, Lai; Smith, Erika; Zeng, Yuling

2009-07-01

Febrifugine is an alkaloid isolated from Dichroa febrifuga Lour as the active component against Plasmodium falciparum. Adverse side effects have precluded febrifugine as a potential clinical drug. In this study novel febrifugine analogues were designed and synthesized. Lower toxicity was achieved by reducing or eliminating the tendency of forming chemically reactive and toxic intermediates and metabolites. Synthesized compounds were evaluated for acute toxicity and in vitro and in vivo antimalarial efficacy. Some compounds are much less toxic than the natural product febrifugine and existing antimalarial drug chloroquine and are expected to possess wide therapeutic windows. These compounds, as well as the underlying design rationale, may find usefulness in the discovery and development of new antimalarial drugs.

Meat Consumption During Pregnancy and Substance Misuse Among Adolescent Offspring: Stratification of TCN2 Genetic Variants.

PubMed

Hibbeln, Joseph R; SanGiovanni, John Paul; Golding, Jean; Emmett, Pauline M; Northstone, Kate; Davis, John M; Schuckit, Marc; Heron, Jon

2017-11-01

Reducing meat consumption is often advised; however, inadvertent nutritional deficiencies during pregnancy may result in residual neurodevelopmental harms to offspring. This study assessed possible effects of maternal diets in pregnancy on adverse substance use among adolescent offspring. Pregnant women and their 13-year-old offspring taking part in a prospective birth cohort study, the Avon Longitudinal Study of Parents and Children (ALSPAC), provided Food Frequency Questionnaire data from which dietary patterns were derived using principal components analysis. Multivariable logistic regression models including potential confounders evaluated adverse alcohol, cannabis, and tobacco use of the children at 15 years of age. Lower maternal meat consumption was associated with greater problematic substance use among 15-year-old offspring in dose-response patterns. Comparing never to daily meat consumption after adjustment, risks were greater for all categories of problem substance use: alcohol, odds ratio OR = 1.75, 95% CI = (1.23, 2.56), p < 0.001; tobacco use OR = 1.85, 95% CI = (1.28, 2.63), p < 0.001; and cannabis OR = 2.70, 95% CI = (1.89, 4.00), p < 0.001. Given the likelihood of residual confounding, potential causality was evaluated using stratification for maternal allelic variants that impact biological activity of cobalamin (vitamin B12) and iron. Lower meat consumption disproportionally increased the risks of offspring substance misuse among mothers with optimally functional (homozygous) variants (rs1801198) of the gene transcobalamin 2 gene (TCN2) which encodes the vitamin B12 transport protein transcobalamin 2 implicating a causal role for cobalamin deficits. Functional maternal variants in iron metabolism were unrelated to the adverse substance use. Risks potentially attributable to cobalamin deficits during pregnancy include adverse adolescent alcohol, cannabis, and tobacco use (14, 37, and 23, respectively). Lower prenatal meat consumption was associated with increased risks of adolescent substance misuse. Interactions between TCN2 variant status and meat intake implicate cobalamin deficiencies. Copyright © 2017 by the Research Society on Alcoholism.

Benefit-risk analysis : a brief review and proposed quantitative approaches.

PubMed

Holden, William L

2003-01-01

Given the current status of benefit-risk analysis as a largely qualitative method, two techniques for a quantitative synthesis of a drug's benefit and risk are proposed to allow a more objective approach. The recommended methods, relative-value adjusted number-needed-to-treat (RV-NNT) and its extension, minimum clinical efficacy (MCE) analysis, rely upon efficacy or effectiveness data, adverse event data and utility data from patients, describing their preferences for an outcome given potential risks. These methods, using hypothetical data for rheumatoid arthritis drugs, demonstrate that quantitative distinctions can be made between drugs which would better inform clinicians, drug regulators and patients about a drug's benefit-risk profile. If the number of patients needed to treat is less than the relative-value adjusted number-needed-to-harm in an RV-NNT analysis, patients are willing to undergo treatment with the experimental drug to derive a certain benefit knowing that they may be at risk for any of a series of potential adverse events. Similarly, the results of an MCE analysis allow for determining the worth of a new treatment relative to an older one, given not only the potential risks of adverse events and benefits that may be gained, but also by taking into account the risk of disease without any treatment. Quantitative methods of benefit-risk analysis have a place in the evaluative armamentarium of pharmacovigilance, especially those that incorporate patients' perspectives.

DTC advertising harms patients and should be tightly regulated.

PubMed

Lurie, Peter

2009-01-01

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

Machine Learning for Social Services: A Study of Prenatal Case Management in Illinois.

PubMed

Pan, Ian; Nolan, Laura B; Brown, Rashida R; Khan, Romana; van der Boor, Paul; Harris, Daniel G; Ghani, Rayid

2017-06-01

To evaluate the positive predictive value of machine learning algorithms for early assessment of adverse birth risk among pregnant women as a means of improving the allocation of social services. We used administrative data for 6457 women collected by the Illinois Department of Human Services from July 2014 to May 2015 to develop a machine learning model for adverse birth prediction and improve upon the existing paper-based risk assessment. We compared different models and determined the strongest predictors of adverse birth outcomes using positive predictive value as the metric for selection. Machine learning algorithms performed similarly, outperforming the current paper-based risk assessment by up to 36%; a refined paper-based assessment outperformed the current assessment by up to 22%. We estimate that these improvements will allow 100 to 170 additional high-risk pregnant women screened for program eligibility each year to receive services that would have otherwise been unobtainable. Our analysis exhibits the potential for machine learning to move government agencies toward a more data-informed approach to evaluating risk and providing social services. Overall, such efforts will improve the efficiency of allocating resource-intensive interventions.

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

PubMed

Zhang, Patrick M; Sarkar, Indra Neil

2018-01-01

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

Adverse Event extraction from Structured Product Labels using the Event-based Text-mining of Health Electronic Records (ETHER)system.

PubMed

Pandey, Abhishek; Kreimeyer, Kory; Foster, Matthew; Botsis, Taxiarchis; Dang, Oanh; Ly, Thomas; Wang, Wei; Forshee, Richard

2018-01-01

Structured Product Labels follow an XML-based document markup standard approved by the Health Level Seven organization and adopted by the US Food and Drug Administration as a mechanism for exchanging medical products information. Their current organization makes their secondary use rather challenging. We used the Side Effect Resource database and DailyMed to generate a comparison dataset of 1159 Structured Product Labels. We processed the Adverse Reaction section of these Structured Product Labels with the Event-based Text-mining of Health Electronic Records system and evaluated its ability to extract and encode Adverse Event terms to Medical Dictionary for Regulatory Activities Preferred Terms. A small sample of 100 labels was then selected for further analysis. Of the 100 labels, Event-based Text-mining of Health Electronic Records achieved a precision and recall of 81 percent and 92 percent, respectively. This study demonstrated Event-based Text-mining of Health Electronic Record's ability to extract and encode Adverse Event terms from Structured Product Labels which may potentially support multiple pharmacoepidemiological tasks.

Cancer screening in Portugal: sex differences in prevalence, awareness of organized programmes and perception of benefits and adverse effects.

PubMed

Costa, Ana Rute; Silva, Susana; Moura-Ferreira, Pedro; Villaverde-Cabral, Manuel; Santos, Osvaldo; Carmo, Isabel do; Barros, Henrique; Lunet, Nuno

2017-04-01

Cancer screening has contributed to downward trends in cancer mortality, but is also associated with adverse effects, which highlights the importance of promoting the participation based on informed decisions. We aimed to describe the use of cancer screening (either in organized programmes or as opportunistic screening), awareness of organized programmes and perception of its potential benefits and adverse effects, depicting possible sex differences. We evaluated 1624 Portuguese-speaking dwellers, aged between 16 and 79 years, through face-to-face interviews. To quantify sex differences, adjusted prevalence ratios and respective 95% confidence intervals were computed using Poisson regression. Among eligible age groups, the lifetime prevalence of screening for breast and cervical cancers was 89.8 and 71.9%, respectively. The prevalence was 23.7% for colorectal cancer and no significant sex differences were observed. Prostate cancer screening was reported by 63.8% of men. Over half of the participants referred that cancers such as prostate, skin, lung and stomach should be screened for, in addition to those for which organized programmes are recommended. Reassurance by negative results was identified as the main potential benefit of screening by nearly one-third of men and women. Anxiety while waiting for results was the most mentioned potential adverse effect (60.4%); men refer less often this and financial costs, although statistical significance of these results was borderline. This study provides a benchmark to plan and monitor the effects of awareness-raising interventions, as well as for international comparisons across countries with different cancer prevention and control structures. © 2016 The Authors. Health Expectations Published by John Wiley & Sons Ltd.

Adverse event rates and classifications in medial opening wedge high tibial osteotomy.

PubMed

Martin, Robin; Birmingham, Trevor B; Willits, Kevin; Litchfield, Robert; Lebel, Marie-Eve; Giffin, J Robert

2014-05-01

Previously reported complications in medial opening wedge (MOW) high tibial osteotomy (HTO) vary considerably in both rate and severity. (1) To determine the rates of adverse events in MOW HTO classified into different grades of severity based on the treatments required and (2) to compare patient-reported outcomes between the different adverse event classifications. Case series; Level of evidence, 4. All patients receiving MOW HTO at a single medical center from 2005 to 2009 were included. Internal fixation was used in all cases, with either a nonlocking (Puddu) or locking (Tomofix) plate. Patients were evaluated at 2, 6, and 12 weeks; 6 and 12 months; and annually thereafter. Types of potential surgical and postoperative adverse events, categorized into 3 classes of severity based on the subsequent treatments, were defined a priori. Medical records and radiographs were then reviewed by an independent observer. The Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores were compared in subgroups of patients based on the categories of adverse events observed. A total of 323 consecutive procedures (242 males) were evaluated (age, mean ± standard deviation, 46 ± 9 years; body mass index, mean ± standard deviation, 30 ± 5 kg/m(2)). Adverse events requiring no additional treatment (class 1) were undisplaced lateral cortical breaches (20%), displaced (>2 mm) lateral hinge fracture (6%), delayed wound healing (6%), undisplaced lateral tibial plateau fracture (3%), hematoma (3%), and increased tibial slope ≥10° (1%). Adverse events requiring additional or extended nonoperative management (class 2) were delayed union (12%), cellulitis (10%), limited hardware failure (1 broken screw; 4%), postoperative stiffness (1%), deep vein thrombosis (1%), and complex regional pain syndrome (CRPS) type 1 (1%). Adverse events requiring additional or revision surgery and/or long-term medical care (class 3) were aseptic nonunion (3%), deep infection (2%), CRPS type 2 (1%), and severe hardware failure with loss of correction (1%). Additional surgery rate was 3%. Class 1 and 2 adverse events did not affect patient-reported outcomes at 6, 12, or 24 months postoperatively. Patients with class 3 adverse events had significantly lower total WOMAC scores at 6 months but not at 12 or 24 months postoperatively. The most common adverse event in MOW HTO requiring extended nonoperative treatment (class 2) is delayed union (12%). The rate of severe adverse events requiring additional surgery and/or long-term medical care (class 3) is low (7%).

Evaluation of the systemic toxicity and mutagenicity of OLIGOPIN®, procyanidolic oligomers (OPC) extracted from French Maritime Pine Bark extract.

PubMed

Segal, L; Penman, M G; Piriou, Y

2018-01-01

The potential systemic toxicity of Oligopin®, a French Maritime Pine Bark extract (FMPBE) rich in procyanidolic oligomers, was evaluated in an acute oral limit test and a 90-day repeated dose oral toxicity study with Sprague Dawley rats. The potential mutagenicity was assessed in a bacterial reverse mutation assay and in vitro mammalian chromosome aberration assay with human lymphocytes. The results indicate that Oligopin® was nongenotoxic in both bacterial and human cell assays, was not acutely toxic via oral administration at up to 2000 mg/kg and was well tolerated following 90 days of oral administration to SD rats, with a no observed adverse effect level of 1000 mg/kg/day. The lack of significant adverse systemic effects in the 90 day study is concordant with findings from several human clinical trials. The acute toxicity and mutagenicity data are consistent with data reported by AFSSA in a summary of FMPBE safety, in which a NOAEL of 100 mg/kg/day was established. In contrast, the NOAEL derived from the 90-day study with Oligopin® was 1000 mg/kg/day, suggesting that it is less systemically toxic than other FMPBE previously evaluated in subchronic studies, and comparable to proanthocyanidins extracted from grape seeds, which are widely used as nutritional supplement ingredients.

Adverse reactions of trivalent influenza vaccine in HIV-infected individuals.

PubMed

Hajiabdolbaghi, Mahboube; Jam, Sara; SeyedAlinaghi, SeyedAhmad; Jafari, Sirous; Badie, Banafshe Moradmand; Sabzvari, Duman

2010-01-01

In this study, we assessed the adverse reactions to influenza vaccination in HIV-infected individuals. From November 2006 to January 2007, a total of 203 HIV-infected persons were recruited. Demographic data were collected. Subjects were evaluated 48 h and 15 days after vaccination for symptoms and significant health events as possible side effects. Participants were instructed to measure their temperature in the morning and evening for 2 days post-immunization and to assess injection site and systemic adverse reactions. 80.3% of the subjects were male. The mean age of the subjects was 36.9 +/- 7.9 years. Local and systemic reactions were reported by 61 (30%) and 62 (30.5%) persons, respectively. The most common adverse reactions to the influenza vaccine included skin redness (37 cases), induration (32 cases), and pain (55 cases) as local reactions, and fever (22 cases), myalgia (46 cases), headache (12 cases) and weakness (35 cases) as general reactions. 1.4 % of the subjects had fever over 38.5 degrees C. There were significant associations between myalgia and flushing with CD4 counts (P<0.05). We found no relationship between adverse reactions and sex, history of smoking, allergy, alcohol, and drug usage, stage of HIV infection, anti-retroviral therapies, anti-TB medication and previous vaccination. We concluded that inactivated influenza vaccine administered in HIV-infected adults did not result in potential adverse events in this study population.

The Association Between Learning Climate and Adverse Obstetrical Outcomes in 16 Nontertiary Obstetrics-Gynecology Departments in the Netherlands.

PubMed

Smirnova, Alina; Ravelli, Anita C J; Stalmeijer, Renée E; Arah, Onyebuchi A; Heineman, Maas Jan; van der Vleuten, Cees P M; van der Post, Joris A M; Lombarts, Kiki M J M H

2017-12-01

To investigate the association between learning climate and adverse perinatal and maternal outcomes in obstetrics-gynecology departments. The authors analyzed 23,629 births and 103 learning climate evaluations from 16 nontertiary obstetrics-gynecology departments in the Netherlands in 2013. Multilevel logistic regressions were used to calculate the odds of adverse perinatal and maternal outcomes, by learning climate score tertile, adjusting for maternal and department characteristics. Adverse perinatal outcomes included fetal or early neonatal mortality, five-minute Apgar score < 7, or neonatal intensive care unit admission for ≥ 24 hours. Adverse maternal outcomes included postpartum hemorrhage and/or transfusion, death, uterine rupture, or third- or fourth-degree perineal laceration. Bias analyses were conducted to quantify the sensitivity of the results to uncontrolled confounding and selection bias. Learning climate scores were significantly associated with increased odds of adverse perinatal outcomes (aOR 2.06, 95% CI 1.14-3.72). Compared with the lowest tertile, departments in the middle tertile had 46% greater odds of adverse perinatal outcomes (aOR 1.46, 95% CI 1.09-1.94); departments in the highest tertile had 69% greater odds (aOR 1.69, 95% CI 1.24-2.30). Learning climate was not associated with adverse maternal outcomes (middle vs. lowest tertile: OR 1.04, 95% CI 0.93-1.16; highest vs. lowest tertile: OR 0.98, 95% CI 0.88-1.10). Learning climate was associated with significantly increased odds of adverse perinatal, but not maternal, outcomes. Research in similar clinical contexts is needed to replicate these findings and explore potential mechanisms behind these associations.

NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Di-n-Butyl Phthalate (DBP).

PubMed

2003-04-01

TThe National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for di-n-butyl phthalate (DBP) to cause adverse effects on reproduction and development in humans. DBP is one of 7 phthalate chemicals evaluated by the NTP CERHR Phthalates Expert Panel. These phthalates were selected for evaluation because of high production volume, extent of human exposures, use in children's products, and/or published evidence of reproductive or developmental toxicity. Unlike many phthalates, DBP is not currently used as a plasticizer in polyvinyl chloride plastics. DBP is a component of latex adhesives and is used in cosmetics and other personal care products, as a plasticizer in cellulose plastics, and as a solvent for dyes. The results of this evaluation on DBP are published in a NTP-CERHR monograph which includes: 1) the NTP Brief, 2) the Expert Panel Report on the Reproductive and Developmental Toxicity of Di-n-Butyl Phthalate, and 3) public comments received on the Expert Panel Report. As stated in the NTP Brief, the NTP reached the following conclusions regarding the possible effects of exposure to DBP on human development and reproduction. First, although DBP could possibly affect human reproduction and development if exposures are sufficiently high, the NTP concludes that there is negligible concern for reproductive toxicity in exposed adults. Second, the NTP concludes that there is minimal concern for developmental effects when pregnant women are exposed to DBP levels estimated by the panel (2-10 mug/kg body weight/day). There is no direct evidence that exposure of people to DBP adversely affects reproduction or development, but studies reviewed by the expert panel show that oral exposure to high doses of DBP (>/=100 mg/kg body weight/day) may adversely affect the prenatal and early postnatal development in rodents. Finally, based on exposure estimates in women of reproductive age, the NTP concludes that there is some concern for DBP causing adverse effects to human development, particularly development of the male reproductive system. NTP-CERHR monographs are transmitted to federal and state agencies, interested parties, and the public and are available electronically in PDF format on the CERHR web site (http://cerhr.niehs.nih.gov) and in printed text or CD-ROM from the CERHR (National Institute of Environmental Health Sciences, P.O. Box 12233, MD EC-32, Research Triangle Park, NC; fax: 919-316-4511).

The AXL receptor tyrosine kinase is associated with adverse prognosis and distant metastasis in esophageal squamous cell carcinoma

PubMed Central

Wong, Li-Fan; Lee, Jang-Ming

2016-01-01

Esophageal squamous cell carcinoma (ESCC) is a frequently recurrent deadly cancer for which no efficient targeted drug exists. AXL is an adverse prognostic factor in some cancers. Strong clinical evidence to support the prognostic role of AXL in ESCC is lacking. A total of 116 patients diagnosed with operable primary ESCC were enrolled. Both AXL and HER2 expression were detected by immunohistochemistry (IHC) in esophageal tissue and were correlated with the clinical outcome of patients. The efficacy of the AXL targeted drug foretinib was also evaluated in ESCC cells. Expression of AXL was found in about 80 % of ESCC tissue, and was significantly correlated with progression of tumor (P<0.001), increased risk of death (Hazard ratio HR [95 % CI=2.09[1.09-4.04], P=0.028], and distant metastasis (odds ratio OR [95 %CI]=3.96 (1.16-13.60), P=0.029). The adverse clinical impact of AXL was more evident when cumulatively expressed with HER2. In cell model, ESCC cells were more sensitive to AXL inhibitor foretinib than to the HER2 inhibitor lapatinib. Meanwhile, the AXL inhibitor foretinib showed a synergistic effect with HER2 inhibitors and the potential to overcome drug resistance to lapatinib. We thus concluded that AXL is a strong adverse prognostic factor for ESCC. Therapeutic agents targeting AXL have great potential to improve prognosis of ESCC patients. PMID:27172793

Investigating methotrexate toxicity within a randomized double-blinded, placebo-controlled trial: Rationale and design of the Cardiovascular Inflammation Reduction Trial-Adverse Events (CIRT-AE) Study.

PubMed

Sparks, Jeffrey A; Barbhaiya, Medha; Karlson, Elizabeth W; Ritter, Susan Y; Raychaudhuri, Soumya; Corrigan, Cassandra C; Lu, Fengxin; Selhub, Jacob; Chasman, Daniel I; Paynter, Nina P; Ridker, Paul M; Solomon, Daniel H

2017-08-01

The role of low dose methotrexate (LDM) in potential serious toxicities remains unclear despite its common use. Prior observational studies investigating LDM toxicity compared LDM to other active drugs. Prior placebo-controlled clinical trials of LDM in inflammatory conditions were not large enough to investigate toxicity. The Cardiovascular Inflammation Reduction Trial (CIRT) is an ongoing NIH-funded, randomized, double-blind, placebo-controlled trial of LDM in the secondary prevention of cardiovascular disease. We describe here the rationale and design of the CIRT-Adverse Events (CIRT-AE) ancillary study which aims to investigate adverse events within CIRT. CIRT will randomize up to 7000 participants with cardiovascular disease and no systemic rheumatic disease to either LDM (target dose: 15-20mg/week) or placebo for an average follow-up period of 3-5 years; subjects in both treatment arms receive folic acid 1mg daily for 6 days each week. The primary endpoints of CIRT include recurrent cardio vascular events, incident diabetes, and all-cause mortality, and the ancillary CIRT-AE study has been designed to adjudicate other clinically important adverse events including hepatic, gastrointestinal, respiratory, hematologic, infectious, mucocutaneous, oncologic, renal, neurologic, and musculoskeletal outcomes. Methotrexate polyglutamate levels and genome-wide single nucleotide polymorphisms will be examined for association with adverse events. CIRT-AE will comprehensively evaluate potential LDM toxicities among subjects with cardiovascular disease within the context of a large, ongoing, double-blind, placebo-controlled trial. This information may lead to a personalized approach to monitoring LDM in clinical practice. Copyright © 2017 Elsevier Inc. All rights reserved.

Therapeutic potential of n-3 polyunsaturated fatty acids in disease.

PubMed

Fetterman, James W; Zdanowicz, Martin M

2009-07-01

The potential therapeutic benefits of supplementation with n-3 polyunsaturated fatty acids (PUFAs) in various diseases are reviewed, and the antiinflammatory actions, activity, and potential drug interactions and adverse effects of n-3 PUFAs are discussed. Fish oils are an excellent source of long-chain n-3 PUFAs, such as eicosapentaenoic acid and docosahexaenoic acid. After consumption, n-3 PUFAs can be incorporated into cell membranes and reduce the amount of arachidonic acid available for the synthesis of proinflammatory eicosanoids (e.g., prostaglandins, leukotrienes). Likewise, n-3 PUFAs can also reduce the production of inflammatory cytokines, such as tumor necrosis factor alpha, interleukin-1, and interleukin-6. Considerable research has been conducted to evaluate the potential therapeutic effects of fish oils in numerous conditions, including arthritis, coronary artery disease, inflammatory bowel disease, asthma, and sepsis, all of which have inflammation as a key component of their pathology. Additional investigations into the use of supplementation with fish oils in patients with neural injury, cancer, ocular diseases, and critical illness have recently been conducted. The most commonly reported adverse effects of fish oil supplements are a fishy aftertaste and gastrointestinal upset. When recommending an n-3 PUFA, clinicians should be aware of any possible adverse effect or drug interaction that, although not necessarily clinically significant, may occur, especially for patients who may be susceptible to increased bleeding (e.g., patients taking warfarin). The n-3 PUFAs have been shown to be efficacious in treating and preventing various diseases. The wide variation in dosages and formulations used in studies makes it difficult to recommend dosages for specific treatment goals.

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

PubMed

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

2014-06-12

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

Evaluation of submarine atmospheres: effects of carbon monoxide, carbon dioxide and oxygen on general toxicology, neurobehavioral performance, reproduction and development in rats. I. Subacute exposures.

PubMed

Hardt, Daniel J; James, R Arden; Gut, Chester P; McInturf, Shawn M; Sweeney, Lisa M; Erickson, Richard P; Gargas, Michael L

2015-02-01

The inhalation toxicity of submarine contaminants is of concern to ensure the health of men and women aboard submarines during operational deployments. Due to a lack of adequate prior studies, potential general, neurobehavioral, reproductive and developmental toxicity was evaluated in male and female rats exposed to mixtures of three critical submarine atmospheric components: carbon monoxide (CO) and carbon dioxide (CO2; levels elevated above ambient), and oxygen (O2; levels decreased below ambient). In a 14-day, 23 h/day, whole-body inhalation study of exposure to clean air (0.4 ppm CO, 0.1% CO2 and 20.6% O2), low-dose, mid-dose and high-dose gas mixtures (high dose of 88.4 ppm CO, 2.5% CO2 and 15.0% O2), no adverse effects on survival, body weight or histopathology were observed. Reproductive, developmental and neurobehavioral performance were evaluated after a 28-day exposure in similar atmospheres. No adverse effects on estrus phase, mating, gestation or parturition were observed. No developmental or functional deficits were observed in either exposed parents or offspring related to motor activity, exploratory behavior or higher-level cognitive functions (learning and memory). Only minimal effects were discovered in parent-offspring emotionality tests. While statistically significant increases in hematological parameters were observed in the offspring of exposed parents compared to controls, these parameters remained within normal clinical ranges for blood cells and components and were not considered adverse. In summary, subacute exposures to elevated concentrations of the submarine atmosphere gases did not affect the ability of rats to reproduce and did not appear to have any significant adverse health effects.

Plaque imaging with CT—a comprehensive review on coronary CT angiography based risk assessment

PubMed Central

Kolossváry, Márton; Szilveszter, Bálint; Merkely, Béla

2017-01-01

CT based technologies have evolved considerably in recent years. Coronary CT angiography (CTA) provides robust assessment of coronary artery disease (CAD). Early coronary CTA imaging—as a gate-keeper of invasive angiography—has focused on the presence of obstructive stenosis. Coronary CTA is currently the only non-invasive imaging modality for the evaluation of non-obstructive CAD, which has been shown to contribute to adverse cardiac events. Importantly, improved spatial resolution of CT scanners and novel image reconstruction algorithms enable the quantification and characterization of atherosclerotic plaques. State-of-the-art CT imaging can therefore reliably assess the extent of CAD and differentiate between various plaque features. Recent studies have demonstrated the incremental prognostic value of adverse plaque features over luminal stenosis. Comprehensive coronary plaque assessment holds potential to significantly improve individual risk assessment incorporating adverse plaque characteristics, the extent and severity of atherosclerotic plaque burden. As a result, several coronary CTA based composite risk scores have been proposed recently to determine patients at high risk for adverse events. Coronary CTA became a promising modality for the evaluation of functional significance of coronary lesions using CT derived fractional flow reserve (FFR-CT) and/or rest/dynamic myocardial CT perfusion. This could lead to substantial reduction in unnecessary invasive catheterization procedures and provide information on ischemic burden of CAD. Discordance between the degree of stenosis and ischemia has been recognized in clinical landmark trials using invasive FFR. Both lesion stenosis and composition are possibly related to myocardial ischemia. The evaluation of lesion-specific ischemia using combined functional and morphological plaque information could ultimately improve the diagnostic performance of CTA and thus patient care. In this review we aimed to summarize current evidence on comprehensive coronary artery plaque assessment using coronary CTA. PMID:29255692

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.

Electroretinography and Visual Evoked Potentials in Childhood Brain Tumor Survivors.

PubMed

Pietilä, Sari; Lenko, Hanna L; Oja, Sakari; Koivisto, Anna-Maija; Pietilä, Timo; Mäkipernaa, Anne

2016-07-01

This population-based cross-sectional study evaluates the clinical value of electroretinography and visual evoked potentials in childhood brain tumor survivors. A flash electroretinography and a checkerboard reversal pattern visual evoked potential (or alternatively a flash visual evoked potential) were done for 51 survivors (age 3.8-28.7 years) after a mean follow-up time of 7.6 (1.5-15.1) years. Abnormal electroretinography was obtained in 1 case, bilaterally delayed abnormal visual evoked potentials in 22/51 (43%) cases. Nine of 25 patients with infratentorial tumor location, and altogether 12 out of 31 (39%) patients who did not have tumors involving the visual pathways, had abnormal visual evoked potentials. Abnormal electroretinographies are rarely observed, but abnormal visual evoked potentials are common even without evident anatomic lesions in the visual pathway. Bilateral changes suggest a general and possibly multifactorial toxic/adverse effect on the visual pathway. Electroretinography and visual evoked potential may have clinical and scientific value while evaluating long-term effects of childhood brain tumors and tumor treatment. © The Author(s) 2016.

Careless and Random Responding on Clinical and Research Measures in the Addictions: A Concerning Problem and Investigation of Their Detection

ERIC Educational Resources Information Center

Meyer, Joseph F.; Faust, Kyle A.; Faust, David; Baker, Aaron M.; Cook, Nathan E.

2013-01-01

Even when relatively infrequent, careless and random responding (C/RR) can have robust effects on individual and group data and thereby distort clinical evaluations and research outcomes. Given such potential adverse impacts and the broad use of self-report measures when appraising addictions and addictive behavior, the detection of C/RR can…

A progressive 5-week exercise therapy program leads to significant improvement in knee function early after anterior cruciate ligament injury.

PubMed

Eitzen, Ingrid; Moksnes, Håvard; Snyder-Mackler, Lynn; Risberg, May Arna

2010-11-01

Prospective cohort study without a control group. Firstly, to present our 5-week progressive exercise therapy program in the early stage after anterior cruciate ligament (ACL) injury. Secondly, to evaluate changes in knee function after completion of the program for patients with ACL injury in general and also when classified as potential copers or noncopers, and, finally, to examine potential adverse events. Few studies concerning early-stage ACL rehabilitation protocols exist. Consequently, little is known about the tolerance for, and outcomes from, short-term exercise therapy programs in the early stage after injury. One-hundred patients were included in a 5-week progressive exercise therapy program, within 3 months after injury. Knee function before and after completion of the program was evaluated from isokinetic quadriceps and hamstrings muscle strength tests, 4 single-leg hop tests, 2 different self-assessment questionnaires, and a global rating of knee function. A 2-way mixed-model analysis of variance was conducted to evaluate changes from pretest to posttest for the limb symmetry index for muscle strength and single-leg hop tests, and the change in scores for the patient-reported questionnaires. In addition, absolute values and the standardized response mean for muscle strength and single-leg hop tests were calculated at pretest and posttest for the injured and uninjured limb. Adverse events during the 5-week period were recorded. The progressive 5-week exercise therapy program led to significant improvements (P<.05) in knee function from pretest to posttest both for patients classified as potential copers and noncopers. Standardized response mean values for changes in muscle strength and single-leg hop performance from pretest to posttest for the injured limb were moderate to strong (0.49-0.84), indicating the observed improvements to be clinically relevant. Adverse events occurred in 3.9% of the patients. Short-term progressive exercise therapy programs are well tolerated and should be incorporated in early-stage ACL rehabilitation, either to improve knee function before ACL reconstruction or as a first step in further nonoperative management. Therapy, level 2b.

A proposed framework for the systematic review and integrated assessment (SYRINA) of endocrine disrupting chemicals.

PubMed

Vandenberg, Laura N; Ågerstrand, Marlene; Beronius, Anna; Beausoleil, Claire; Bergman, Åke; Bero, Lisa A; Bornehag, Carl-Gustaf; Boyer, C Scott; Cooper, Glinda S; Cotgreave, Ian; Gee, David; Grandjean, Philippe; Guyton, Kathryn Z; Hass, Ulla; Heindel, Jerrold J; Jobling, Susan; Kidd, Karen A; Kortenkamp, Andreas; Macleod, Malcolm R; Martin, Olwenn V; Norinder, Ulf; Scheringer, Martin; Thayer, Kristina A; Toppari, Jorma; Whaley, Paul; Woodruff, Tracey J; Rudén, Christina

2016-07-14

The issue of endocrine disrupting chemicals (EDCs) is receiving wide attention from both the scientific and regulatory communities. Recent analyses of the EDC literature have been criticized for failing to use transparent and objective approaches to draw conclusions about the strength of evidence linking EDC exposures to adverse health or environmental outcomes. Systematic review methodologies are ideal for addressing this issue as they provide transparent and consistent approaches to study selection and evaluation. Objective methods are needed for integrating the multiple streams of evidence (epidemiology, wildlife, laboratory animal, in vitro, and in silico data) that are relevant in assessing EDCs. We have developed a framework for the systematic review and integrated assessment (SYRINA) of EDC studies. The framework was designed for use with the International Program on Chemical Safety (IPCS) and World Health Organization (WHO) definition of an EDC, which requires appraisal of evidence regarding 1) association between exposure and an adverse effect, 2) association between exposure and endocrine disrupting activity, and 3) a plausible link between the adverse effect and the endocrine disrupting activity. Building from existing methodologies for evaluating and synthesizing evidence, the SYRINA framework includes seven steps: 1) Formulate the problem; 2) Develop the review protocol; 3) Identify relevant evidence; 4) Evaluate evidence from individual studies; 5) Summarize and evaluate each stream of evidence; 6) Integrate evidence across all streams; 7) Draw conclusions, make recommendations, and evaluate uncertainties. The proposed method is tailored to the IPCS/WHO definition of an EDC but offers flexibility for use in the context of other definitions of EDCs. When using the SYRINA framework, the overall objective is to provide the evidence base needed to support decision making, including any action to avoid/minimise potential adverse effects of exposures. This framework allows for the evaluation and synthesis of evidence from multiple evidence streams. Finally, a decision regarding regulatory action is not only dependent on the strength of evidence, but also the consequences of action/inaction, e.g. limited or weak evidence may be sufficient to justify action if consequences are serious or irreversible.

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.

IRIS Toxicological Review of Ammonia (External Review Draft ...

EPA Pesticide Factsheets

EPA is conducting a peer review of the scientific basis supporting the human health hazard and dose-response assessment of ammonia that will appear in the Integrated Risk Information System (IRIS) database. EPA is undertaking an Integrated Risk Information System (IRIS) health assessment for ammonia. IRIS is an EPA database containing Agency scientific positions on potential adverse human health effects that may result from chronic (or lifetime) exposure to chemicals in the environment. IRIS contains chemical-specific summaries of qualitative and quantitative health information in support of two steps of the risk assessment paradigm, i.e., hazard identification and dose-response evaluation. IRIS assessments are used in combination with specific situational exposure assessment information to evaluate potential public health risk associated with environmental contaminants.

IRIS Toxicological Review of n-Butanol (External Review Draft ...

EPA Pesticide Factsheets

EPA is conducting a peer review of the scientific basis supporting the human health hazard and dose-response assessment of n-butanol that will appear in the Integrated Risk Information System (IRIS) database. EPA is undertaking an Integrated Risk Information System (IRIS) health assessment for n-butanol. IRIS is an EPA database containing Agency scientific positions on potential adverse human health effects that may result from chronic (or lifetime) exposure to chemicals in the environment. IRIS contains chemical-specific summaries of qualitative and quantitative health information in support of two steps of the risk assessment paradigm, i.e., hazard identification and dose-response evaluation. IRIS assessments are used in combination with specific situational exposure assessment information to evaluate potential public health risk associated with environmental contaminants.

Halogenated flame retardants: do the fire safety benefits justify the risks?

PubMed

Shaw, Susan D; Blum, Arlene; Weber, Roland; Kannan, Kurunthachalam; Rich, David; Lucas, Donald; Koshland, Catherine P; Dobraca, Dina; Hanson, Sarah; Birnbaum, Linda S

2010-01-01

Since the 1970s, an increasing number of regulations have expanded the use of brominated and chlorinated flame retardants. Many of these chemicals are now recognized as global contaminants and are associated with adverse health effects in animals and humans, including endocrine and thyroid disruption, immunotoxicity, reproductive toxicity, cancer, and adverse effects on fetal and child development and neurologic function. Some flame retardants such as polybrominated diphenyl ethers (PBDEs) have been banned or voluntarily phased out by manufacturers because of their environmental persistence and toxicity, only to be replaced by other organohalogens of unknown toxicity. Despite restrictions on further production in some countries, consumer products previously treated with banned retardants are still in use and continue to release toxic chemicals into the environment, and the worldwide use of organohalogen retardants continues to increase. This paper examines major uses and known toxic effects of commonly-used organohalogen flame retardants, replacements for those that have been phased out, their combustion by-products, and their effectiveness at reducing fire hazard. Policy and other solutions to maintain fire safety while reducing toxicity are suggested. The major conclusions are: (1) Flammability regulations can cause greater adverse environmental and health impacts than fire safety benefits. (2) The current options for end-of-life disposal of products treated with organohalogens retardants are problematic. (3) Life-cycle analyses evaluating benefits and risks should consider the health and environmental effects of the chemicals, as well as their fire safety impacts. (4) Most fire deaths and most fire injuries result from inhaling carbon monoxide, irritant gases, and soot. The incorporation of organohalogens can increase the yield of these toxic by-products during combustion. (5) Fire-safe cigarettes, fire-safe candles, child-resistant lighters, sprinklers, and smoke detectors can prevent fires without the potential adverse effects of flame retardant chemicals. (6) Alternatives to organohalogen flame retardant chemicals include using less flammable materials, design changes, and safer chemicals. To date, before evaluating their health and environmental impacts, many flame retardant chemicals have been produced and used, resulting in high levels of human exposure. As a growing literature continues to find adverse impacts from such chemicals, a more systematic approach to their regulation is needed. Before implementing new flammability standards, decision-makers should evaluate the potential fire safety benefit versus the health and environmental impacts of the chemicals, materials, or technologies likely to be used to meet the standard. Reducing the use of toxic or untested flame retardant chemicals in consumer products can protect human and animal health and the global environment without compromising fire safety.

Psychiatric stigma in the military.

PubMed

Porter, T L; Johnson, W B

1994-09-01

There is potential for the stigma of mental health care to directly affect an active duty member's career. The authors are aware of cases in which fear of adverse career consequences has led service members to avoid needed mental health care. In order to investigate the legitimacy of this fear, the authors surveyed 252 USN and USMC commanding and executive officers concerning their attitudes about service members who had received mental health and other services; 138 responded. Overall the responses were neutral and there were relatively few negative evaluations of service members who had received services. Military health care providers should take an active role in diminishing the stigma of mental illness, and in allaying fears of adverse career consequences for seeking care.

A Systematic Review of Economic Evaluations of Pharmacogenetic Testing for Prevention of Adverse Drug Reactions.

PubMed

Plumpton, Catrin O; Roberts, Daniel; Pirmohamed, Munir; Hughes, Dyfrig A

2016-08-01

Pharmacogenetics offers the potential to improve health outcomes by identifying individuals who are at greater risk of harm from certain medicines. Routine adoption of pharmacogenetic tests requires evidence of their cost effectiveness. The present review aims to systematically review published economic evaluations of pharmacogenetic tests that aim to prevent or reduce the incidence of ADRs. We conducted a systematic literature review of economic evaluations of pharmacogenetic tests aimed to reduce the incidence of adverse drug reactions. Literature was searched using Embase, MEDLINE and the NHS Economic Evaluation Database with search terms relating to pharmacogenetic testing, adverse drug reactions, economic evaluations and pharmaceuticals. Titles were screened independently by two reviewers. Articles deemed to meet the inclusion criteria were screened independently on abstract, and full texts reviewed. We identified 852 articles, of which 47 met the inclusion criteria. There was evidence supporting the cost effectiveness of testing for HLA-B*57:01 (prior to abacavir), HLA-B*15:02 and HLA-A*31:01 (prior to carbamazepine), HLA-B*58:01 (prior to allopurinol) and CYP2C19 (prior to clopidogrel treatment). Economic evidence was inconclusive with respect to TPMT (prior to 6-mercaptoputine, azathioprine and cisplatin therapy), CYP2C9 and VKORC1 (to inform genotype-guided dosing of coumarin derivatives), MTHFR (prior to methotrexate treatment) and factor V Leiden testing (prior to oral contraception). Testing for A1555G is not cost effective before prescribing aminoglycosides. Our systematic review identified robust evidence of the cost effectiveness of genotyping prior to treatment with a number of common drugs. However, further analyses and (or) availability of robust clinical evidence is necessary to make recommendations for others.

Allostatic load: A theoretical model for understanding the relationship between maternal posttraumatic stress disorder and adverse birth outcomes.

PubMed

Li, Yang; Rosemberg, Marie-Anne Sanon; Seng, Julia S

2018-07-01

Adverse birth outcomes such as preterm birth and low birth weight are significant public health concerns and contribute to neonatal morbidity and mortality. Studies have increasingly been exploring the predictive effects of maternal posttraumatic stress disorder (PTSD) on adverse birth outcomes. However, the biological mechanisms by which maternal PTSD affects birth outcomes are not well understood. Allostatic load refers to the cumulative dysregulations of the multiple physiological systems as a response to multiple social-ecological levels of chronic stress. Allostatic load has been well documented in relation to both chronic stress and adverse health outcomes in non-pregnant populations. However, the mediating role of allostatic load is less understood when it comes to maternal PTSD and adverse birth outcomes. To propose a theoretical model that depicts how allostatic load could mediate the impact of maternal PTSD on birth outcomes. We followed the procedures for theory synthesis approach described by Walker and Avant (2011), including specifying focal concepts, identifying related factors and relationships, and constructing an integrated representation. We first present a theoretical overview of the allostatic load theory and the other 4 relevant theoretical models. Then we provide a brief narrative review of literature that empirically supports the propositions of the integrated model. Finally, we describe our theoretical model. The theoretical model synthesized has the potential to advance perinatal research by delineating multiple biomarkers to be used in future. After it is well validated, it could be utilized as the theoretical basis for health care professionals to identify high-risk women by evaluating their experiences of psychosocial and traumatic stress and to develop and evaluate service delivery and clinical interventions that might modify maternal perceptions or experiences of stress and eliminate their impacts on adverse birth outcomes. Copyright © 2018. Published by Elsevier Ltd.

The Structured Trauma-Related Experiences and Symptoms Screener (STRESS): Development and Preliminary Psychometrics.

PubMed

Grasso, Damion J; Felton, Julia W; Reid-Quiñones, Kathryn

2015-08-01

The Structured Trauma-Related Experiences and Symptoms Screener (STRESS) is a self-report instrument for youth of age 7-18 that inventories 25 adverse childhood experiences and potentially traumatic events and assesses symptoms of post-traumatic stress disorder using the revised criteria published in the Diagnostic and Statistical Manual for Mental Disorders, fifth edition (DSM-5). The STRESS can be administered by computer such that questions are read aloud and automatic scoring and feedback are provided. Data were collected on a sample of 229 children and adolescents of age 7-17 undergoing a forensic child abuse and neglect evaluation. The purpose of the current study was to examine preliminary psychometric characteristics of the computer-administered STRESS as well as its underlying factor structure in relation to the four-factor DSM-5 model. Results provide initial support for the use of the STRESS in assessing adverse and potentially traumatic experiences and traumatic stress in children and adolescents. © The Author(s) 2015.

[Evaluation of reporting quality of RCT on nephrotoxicity of Tripterygium wilfordii preparations according to CONSORT HARMs statement].

PubMed

Feng, Xue; Fang, Sai-Nan; Gao, Yu-Xin; Liu, Jian-Ping; Chen, Wei

2018-02-01

To evaluate the quality of randomized controlled trials(RCT) on nephrotoxicity of Tripterygium wilfordii preparations according to the CONSORT HARMs statement. The report quality of each included study was evaluated according to the CONSORT HARMs statement， and the number of entries that comply with CONSORT HARMs statement was calculated in each study to evaluate the report quality on nephrotoxicity-related adverse reactions of T. wilfordii preparations and summarize the problems in domestic studies on nephrotoxicity-related adverse reactions. A total of 16 RCTs were included， with an average of 7 entries complying with CONSORT HARMs statement per study. The report of the nephrotoxic-associated RCT of T. wilfordii preparations was of poor quality and the most non-repeating entries included the following ones： using validated tools to report adverse effects， standards for coding of the adverse reactions， describing how and when to collect data on adverse reactions in Method， describing how adverse reactions are attributed to T. wilfordii， clearly stating who has reported the adverse reactions， describing the analysis method of adverse reactions， describing the method of collecting recurrent adverse reaction data， describing any subgroup analysis and exploratory analysis associated with the hazard. We suggest that the studies on adverse reactions of traditional Chinese medicine should strictly report the entries according to the CONSORT HARMs statement， and take the characteristics of traditional Chinese medicine into account to report the details of the Chinese medicine like compositions， dose， taking time， combined medication and the dialectical typology of research objects. Copyright© by the Chinese Pharmaceutical Association.

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

PubMed

Vinken, Mathieu

2013-10-04

Adverse outcome pathways (AOPs) are novel tools in toxicology and human risk assessment with broad potential. AOPs are designed to provide a clear-cut mechanistic representation of critical toxicological effects that span over different layers of biological organization. AOPs share a common structure consisting of a molecular initiating event, a series of intermediate steps and key events, and an adverse outcome. Development of AOPs ideally complies with OECD guidelines. This also holds true for AOP evaluation, which includes consideration of the Bradford Hill criteria for weight-of-evidence assessment and meeting a set of key questions defined by the OECD. Elaborate AOP frameworks have yet been proposed for chemical-induced skin sensitization, cholestasis, liver fibrosis and liver steatosis. These newly postulated AOPs can serve a number of ubiquitous purposes, including the establishment of (quantitative) structure-activity relationships, the development of novel in vitro toxicity screening tests and the elaboration of prioritization strategies. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Face and neck dermatitis from a stainless steel orthodontic appliance.

PubMed

Ehrnrooth, Minna; Kerosuo, Heidi

2009-11-01

Although nickel is the most common cause of contact allergy, nickel-containing orthodontic appliances seldom cause adverse reactions that result in discontinuation of treatment. We report on an eruption of dermatitis in the face and neck of an adult female patient after placement of a rapid maxillary expansion appliance (RME). Because the patient suspected nickel allergy, her tolerance to the appliance material was tested intraorally before treatment by cementing bands on four teeth for a week. No visible adverse reactions were seen during the test. One week after cementation of the RME appliance, the patient reported strong itching of the face and a red rash. Clinical examination showed itchy papular erythema on the face and neck. No intraoral reactions or symptoms were present. The RME appliance was removed, and symptoms disappeared in 4 to 5 days. The patient was referred for a nickel patch test, which gave a strong positive result. Adverse patient reactions of potential allergic origin should be diagnosed carefully, and their possible impact on further treatment should be evaluated accordingly.

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

PubMed

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

2017-01-01

Childhood adversity is associated with a range of mental disorders, functional impairment and higher health care costs in adulthood. In this study we evaluated if childhood adversity was predictive of adverse clinical and functional outcomes and health care costs in a sample of patients at ultra-high risk (UHR) for developing a psychosis. Structural Equation Modeling was used to examine the effect of childhood adversity on depression, anxiety, transition to psychosis and overall functioning at 4-year follow-up. In addition, we evaluated economic costs of childhood adversity in terms of health care use and productivity loss. Data pertain to 105 UHR participants of the Dutch Early Detection and Intervention Evaluation (EDIE-NL). Physical abuse was associated with higher depression rates (b=0.381, p=0.012) and lower social functional outcome (b=-0.219, p=0.017) at 4-year follow-up. In addition, emotional neglect was negatively associated with social functioning (b=-0.313, p=0.018). We did not find evidence that childhood adversity was associated with transition to psychosis, but the experience of childhood adversity was associated with excess health care costs at follow-up. The data indicate long-term negative effects of childhood adversity on depression, social functioning and health care costs at follow-up in a sample of UHR patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Safety of intravenous lacosamide in critically ill children.

PubMed

Welsh, Sarah S; Lin, Nan; Topjian, Alexis A; Abend, Nicholas S

2017-11-01

Acute seizures are common in critically ill children. These patients would benefit from intravenous anti-seizure medications with few adverse effects. We reviewed the usage and effects of intravenous lacosamide in critically ill children with seizures or status epilepticus. This retrospective series included consecutive patients who received at least one dose of intravenous lacosamide from April 2011 to February 2016 in the pediatric intensive care unit of a quaternary care children's hospital, including patients with new lacosamide initiation and continuation of outpatient oral lacosamide. Dosing and prescribing practices were reviewed. Adverse effects were defined by predefined criteria, and most were evaluated during the full admission. We identified 51 intensive care unit admissions (47 unique patients) with intravenous lacosamide administration. Lacosamide was utilized as a third or fourth-line anti-seizure medication for acute seizures or status epilepticus in the lacosamide-naïve cohort. One patient experienced bradycardia and one patient experienced a rash that were considered potentially related to lacosamide. No other adverse effects were identified, including no evidence of PR interval prolongation. Lacosamide was well tolerated in critically ill children. Further study is warranted to evaluate the effectiveness of earlier lacosamide use for pediatric status epilepticus and acute seizures. Copyright © 2017 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

New digital cholangiopancreatoscopy for diagnosis and therapy of pancreaticobiliary diseases (with videos).

PubMed

Tanaka, Reina; Itoi, Takao; Honjo, Mitsusyoshi; Tsuchiya, Takayoshi; Kurihara, Toshio; Tsuji, Shujiro; Tonozuka, Ryosuke; Kamada, Kentato; Sofuni, Atsushi; Mukai, Shuntaro

2016-04-01

Recently, a new digital cholangiopancreatoscopy (DCPS) has been developed. The aim of this study is to retrospectively evaluate the utility of new DCPS in patients with pancreaticobiliary diseases. Digital cholangiopancreatoscopy was used in 26 patients (16 men) with pancreaticobiliary diseases that could not be diagnosed and treated by standard endoscopic retrograde cholangiopancreatography (ERCP). The procedures included DCPS-guided tissue sampling and interventions. Technical success and adverse events were evaluated. Among the 26 patients, 19 patients were classified for diagnostic purposes and seven for therapeutic purposes. The detailed breakdown of the particular conditions and numbers of patients was as follows: indeterminate bile duct (BD) lesion, indeterminate pancreatic duct (PD) lesion, lithotripsy by yttrium aluminum garnet-laser or electrohydraulic lithotripsy, removal of migrated BD stent and PD stent, and guidewire passing across the biliary stricture. The overall technical success rates of visualizing the target lesions and therapeutic interventions were 100% and 85.7%, respectively. The incidence of procedure-related adverse events among the patients was 7.7% (2/26). Cholangitis developed in one of the patients and post-endoscopic sphincterotomy bleeding in one patient. All adverse events were successfully treated by conservative therapy. Digital cholangiopancreatoscopy has a high potential for providing an accurate diagnosis and facilitating therapy in patients with pancreaticobiliary diseases. © 2016 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

Filling quality of the reports of adverse drug reactions received at the Pharmacovigilance Centre of São Paulo (Brazil): missing information hinders the analysis of suspected associations.

PubMed

Ribeiro, Adalton; Lima, Silvana; Zampieri, Maria-Elisa; Peinado, Mirtes; Figueras, Albert

2017-12-01

The completeness and accuracy of the reports of suspected adverse drug reactions is important in pharmacovigilance. The aim of the present study was to analyze the quality of the information included in the reports sent to the Pharmacovigilance Centre of São Paulo (Brazil). A sample of 999 reports received from January 2013 to December 2014 was selected. The quality of the filled information was evaluated according to a 'sufficiency' criterion to apply the Karch-Lasagna causality algorithm. There were 820 reports from manufacturers and 179 from health centres. Only 4.4% (44) were fully filled, thus allowing the adequate analysis of the causal relationship between the suspected medication and the adverse event. In 30% of the reports from manufacturers, the information about the critical variables was lacking or incomplete, preventing the adequate evaluation of the report. It was also noted that the reports' poor filling quality was not related with less severity or with old and well-known medicines. The poor quality of the information included in the reports received by this centre, especially those sent by pharmaceutical manufacturers, hampers the identification of potential safety signals. Measures to improve the quality of the reports must be urgently adopted.

The clinical content of preconception care: reproductive history.

PubMed

Stubblefield, Phillip G; Coonrod, Dean V; Reddy, Uma M; Sayegh, Raja; Nicholson, Wanda; Rychlik, Daniel F; Jack, Brian W

2008-12-01

A history of previous birth of a low birthweight infant, previous cesarean sections, multiple previous spontaneous abortions, prior stillbirth, or uterine anomaly identifies women at increased risk for recurrent abortion, preterm birth, or stillbirth. We review the evidence for the potential benefit of reproductive history in identifying strategies for evaluation and treatment to prevent recurrent adverse pregnancy outcome. We offer evidence-based recommendations for management of women with these histories.

Predicting nutrient and sediment loadings to streams from landscape metrics: A multiple watershed study from the United States Mid-Atlantic Region

Treesearch

K. Bruce Jones; Anne C. Neale; Malisha S. Nash; Rick D. van Remortel; James D. Wickham; Kurt H. Riitters; Robert V. O' Neill

2001-01-01

There has been an increasing interest in evaluating the relative condition or health of water resources at regional and national scales. Of particular interest is an ability to identify those areas where surface and ground waters have the greatest potential for high levels of nutrient and sediment loadings. High levels of nutrient and sediment loadings can have adverse...

Launch Vehicle Manual Steering with Adaptive Augmenting Control:In-Flight Evaluations of Adverse Interactions Using a Piloted Aircraft

NASA Technical Reports Server (NTRS)

Hanson, Curt; Miller, Chris; Wall, John H.; VanZwieten, Tannen S.; Gilligan, Eric T.; Orr, Jeb S.

2015-01-01

An Adaptive Augmenting Control (AAC) algorithm for the Space Launch System (SLS) has been developed at the Marshall Space Flight Center (MSFC) as part of the launch vehicle's baseline flight control system. A prototype version of the SLS flight control software was hosted on a piloted aircraft at the Armstrong Flight Research Center to demonstrate the adaptive controller on a full-scale realistic application in a relevant flight environment. Concerns regarding adverse interactions between the adaptive controller and a potential manual steering mode were also investigated by giving the pilot trajectory deviation cues and pitch rate command authority, which is the subject of this paper. Two NASA research pilots flew a total of 25 constant pitch rate trajectories using a prototype manual steering mode with and without adaptive control, evaluating six different nominal and off-nominal test case scenarios. Pilot comments and PIO ratings were given following each trajectory and correlated with aircraft state data and internal controller signals post-flight.

Biological Effects of Space Radiation and Development of Effective Countermeasures

PubMed Central

Kennedy, Ann R.

2014-01-01

As part of a program to assess the adverse biological effects expected from astronaut exposure to space radiation, numerous different biological effects relating to astronaut health have been evaluated. There has been major focus recently on the assessment of risks related to exposure to solar particle event (SPE) radiation. The effects related to various types of space radiation exposure that have been evaluated are: gene expression changes (primarily associated with programmed cell death and extracellular matrix (ECM) remodeling), oxidative stress, gastrointestinal tract bacterial translocation and immune system activation, peripheral hematopoietic cell counts, emesis, blood coagulation, skin, behavior/fatigue (including social exploration, submaximal exercise treadmill and spontaneous locomotor activity), heart functions, alterations in biological endpoints related to astronaut vision problems (lumbar puncture/intracranial pressure, ocular ultrasound and histopathology studies), and survival, as well as long-term effects such as cancer and cataract development. A number of different countermeasures have been identified that can potentially mitigate or prevent the adverse biological effects resulting from exposure to space radiation. PMID:25258703

Biological effects of space radiation and development of effective countermeasures

NASA Astrophysics Data System (ADS)

Kennedy, Ann R.

2014-04-01

As part of a program to assess the adverse biological effects expected from astronauts' exposure to space radiation, numerous different biological effects relating to astronauts' health have been evaluated. There has been major focus recently on the assessment of risks related to exposure to solar particle event (SPE) radiation. The effects related to various types of space radiation exposure that have been evaluated are: gene expression changes (primarily associated with programmed cell death and extracellular matrix (ECM) remodeling), oxidative stress, gastrointestinal tract bacterial translocation and immune system activation, peripheral hematopoietic cell counts, emesis, blood coagulation, skin, behavior/fatigue (including social exploration, submaximal exercise treadmill and spontaneous locomotor activity), heart functions, alterations in biological endpoints related to astronauts' vision problems (lumbar puncture/intracranial pressure, ocular ultrasound and histopathology studies), and survival, as well as long-term effects such as cancer and cataract development. A number of different countermeasures have been identified that can potentially mitigate or prevent the adverse biological effects resulting from exposure to space radiation.

Novel unconventional therapeutic approaches to atopic eczema.

PubMed

Worm, M; Henz, B M

2000-01-01

Atopic eczema is a chronic, recurrent, multifactorial skin disease, and, accordingly, there are numerous therapeutic options for its symptomatic treatment. Conventional medications are however often unsatisfactory for many patients because of adverse effects on long-term use. For this reason, patients often readily welcome unconventional therapeutic approaches. We present here a selected number of such treatment modalities, namely gamma-linolenic acid, Chinese herbal tea, diets eliminating allergens, pseudoallergens, metal salts and sodium, and bioresonance. When stringent scientific criteria are applied in the evaluation of such study results, none of the reviewed alternative treatments provides unequivocal, convincing evidence of its efficacy, even when double-blind, placebo-controlled studies are available. With Chinese herbal tea, potentially serious adverse effects should be considered as well. Any new type of unconventional therapy should thus be thoroughly evaluated and shown to be equal or superior to conventional treatments with regard to both efficacy and tolerability before it is recommended for use in clinical practice. Copyright 2000 S. Karger AG, Basel.

Evaluation of the in vitro cytogenotoxicity profile of antipsychotic drug haloperidol using human peripheral blood lymphocytes.

PubMed

Gajski, Goran; Gerić, Marko; Garaj-Vrhovac, Vera

2014-07-01

Haloperidol (HLP) is a potent antipsychotic drug that is commonly used for the treatments of schizophrenia and bipolar disorders but has a tendency to cause adverse effects. In the present study, the cyto/genotoxic potential of clinically relevant concentrations of HLP was evaluated in human peripheral blood lymphocytes (HPBLs) as sensitive biomarkers of exposure. HLP was administered as HLP hydrochloride in the final concentrations of 5, 10 and 20 ng/ml for 4 and 24 h period. Cytotoxicity was determined using differential staining of HPBLs with acridine orange and ethidium bromide while chromosomal aberrations, micronucleus and comet assays were applied to estimate the chromosomal and DNA damage after the treatment. The results of the present study indicate that HLP is capable of inducing cyto/genotoxicity in tested cells. Present study has also confirmed the need for further cytogenetic research and regular patient monitoring to minimize the risk of any possible adverse events. Copyright © 2014 Elsevier B.V. All rights reserved.

Association of PCBs and allergies in children.

PubMed

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

2015-05-01

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

IRIS Toxicological Review of Ammonia Noncancer Inhalation ...

EPA Pesticide Factsheets

EPA has finalized the Integrated Risk Information System (IRIS) Assessment of Ammonia (Noncancer Inhalation). This assessment addresses the potential noncancer human health effects from long-term inhalation exposure to ammonia. Now final, this assessment will update the current toxicological information on ammonia posted in 1991. EPA’s program and regional offices may use this assessment to inform decisions to protect human health. EPA completed the Integrated Risk Information System (IRIS) health assessment for ammonia. IRIS is an EPA database containing Agency scientific positions on potential adverse human health effects that may result from chronic (or lifetime) exposure to chemicals in the environment. IRIS contains chemical-specific summaries of qualitative and quantitative health information in support of two steps of the risk assessment paradigm, i.e., hazard identification and dose-response evaluation. IRIS assessments are used in combination with specific situational exposure assessment information to evaluate potential public health risk associated with environmental contaminants.

[Feasibility and relevance of an operating room safety checklist for developing countries: Study in a French hospital in Djibouti].

PubMed

Becret, A; Clapson, P; Andro, C; Chapelier, X; Gauthier, J; Kaiser, E

2013-01-01

The use of the World Health Organization surgical safety checklist, mandatory in operating rooms (OR) in France, significantly reduces morbidity and mortality. Our objective was to evaluate the use of this checklist in the OR of a French military hospital in Djibouti (Horn of Africa). The study was performed in three stages: a retrospective evaluation of the checklist use over the previous two months, to assess the utilization and completeness rates; provision of information to the OR staff; and thereafter, prospective evaluation for a one-month period of checklist use, the reasons for non-compliance, and the cases in which the checklist identified errors and thus prevented serious adverse events. The initial utilization rate was 49%, with only 24% complete. After staff training and during the study these rates reached 100% and 99%. The staff encountered language difficulties in 53% of cases, and an interpreter was available for 81% of them. The capacity of the surgical safety checklist to detect serious adverse events was highlighted. The utilization and completeness rates were initially worse than those observed in metropolitan French ORs, but a simple staff information program was rapidly effective. Language difficulties are frequent but an interpreter is often available, unlike in developed countries where language problems are uncommon and the availability of interpreters difficult. Moreover, this study illustrates the ability of the checklist to detect and therefore prevent potentially serious adverse events.

Analysis of adverse events of renal impairment related to platinum-based compounds using the Japanese Adverse Drug Event Report database.

PubMed

Naganuma, Misa; Motooka, Yumi; Sasaoka, Sayaka; Hatahira, Haruna; Hasegawa, Shiori; Fukuda, Akiho; Nakao, Satoshi; Shimada, Kazuyo; Hirade, Koseki; Mori, Takayuki; Yoshimura, Tomoaki; Kato, Takeshi; Nakamura, Mitsuhiro

2018-01-01

Platinum compounds cause several adverse events, such as nephrotoxicity, gastrointestinal toxicity, myelosuppression, ototoxicity, and neurotoxicity. We evaluated the incidence of renal impairment as adverse events are related to the administration of platinum compounds using the Japanese Adverse Drug Event Report database. We analyzed adverse events associated with the use of platinum compounds reported from April 2004 to November 2016. The reporting odds ratio at 95% confidence interval was used to detect the signal for each renal impairment incidence. We evaluated the time-to-onset profile of renal impairment and assessed the hazard type using Weibull shape parameter and used the applied association rule mining technique to discover undetected relationships such as possible risk factor. In total, 430,587 reports in the Japanese Adverse Drug Event Report database were analyzed. The reporting odds ratios (95% confidence interval) for renal impairment resulting from the use of cisplatin, oxaliplatin, carboplatin, and nedaplatin were 2.7 (2.5-3.0), 0.6 (0.5-0.7), 0.8 (0.7-1.0), and 1.3 (0.8-2.1), respectively. The lower limit of the reporting odds ratio (95% confidence interval) for cisplatin was >1. The median (lower-upper quartile) onset time of renal impairment following the use of platinum-based compounds was 6.0-8.0 days. The Weibull shape parameter β and 95% confidence interval upper limit of oxaliplatin were <1. In the association rule mining, the score of lift for patients who were treated with cisplatin and co-administered furosemide, loxoprofen, or pemetrexed was high. Similarly, the scores for patients with hypertension or diabetes mellitus were high. Our findings suggest a potential risk of renal impairment during cisplatin use in real-world setting. The present findings demonstrate that the incidence of renal impairment following cisplatin use should be closely monitored when patients are hypertensive or diabetic, or when they are co-administered furosemide, loxoprofen, or pemetrexed. In addition, healthcare professionals should closely assess a patient's background prior to treatment.

Putative adverse outcome pathways relevant to neurotoxicity

PubMed Central

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

2016-01-01

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

Adversity and Resilience: A Synthesis of International Research

ERIC Educational Resources Information Center

Noltemeyer, Amity L.; Bush, Kevin R.

2013-01-01

Children and adolescents worldwide experience a variety of adversities that have the potential to disrupt typical development. However, some of these individuals exhibit resilience, evidencing normal development in the face of adversity. Here we review research on these constructs of risk, adversity, and resilience; synthesize international…

Waste incineration and adverse birth and neonatal outcomes: a systematic review.

PubMed

Ashworth, Danielle C; Elliott, Paul; Toledano, Mireille B

2014-08-01

Public concern about potential health risks associated with incineration has prompted studies to investigate the relationship between incineration and risk of cancer, and more recently, birth outcomes. We conducted a systematic review of epidemiologic studies evaluating the relationship between waste incineration and the risk of adverse birth and neonatal outcomes. Literature searches were performed within the MEDLINE database, through PubMed and Ovid interfaces, for the search terms; incineration, birth, reproduction, neonatal, congenital anomalies and all related terms. Here we discuss and critically evaluate the findings of these studies. A comprehensive literature search yielded fourteen studies, encompassing a range of outcomes (including congenital anomalies, birth weight, twinning, stillbirths, sex ratio and infant death), exposure assessment methods and study designs. For congenital anomalies most studies reported no association with proximity to or emissions from waste incinerators and "all anomalies", but weak associations for neural tube and heart defects and stronger associations with facial clefts and urinary tract defects. There is limited evidence for an association between incineration and twinning and no evidence of an association with birth weight, stillbirths or sex ratio, but this may reflect the sparsity of studies exploring these outcomes. The current evidence-base is inconclusive and often limited by problems of exposure assessment, possible residual confounding, lack of statistical power with variability in study design and outcomes. However, we identified a number of higher quality studies reporting significant positive relationships with broad groups of congenital anomalies, warranting further investigation. Future studies should address the identified limitations in order to help improve our understanding of any potential adverse birth outcomes associated with incineration, particularly focussing on broad groups of anomalies, to inform risk assessment and waste policy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Simulating adverse event spontaneous reporting systems as preferential attachment networks: application to the Vaccine Adverse Event Reporting System.

PubMed

Scott, J; Botsis, T; Ball, R

2014-01-01

Spontaneous Reporting Systems [SRS] are critical tools in the post-licensure evaluation of medical product safety. Regulatory authorities use a variety of data mining techniques to detect potential safety signals in SRS databases. Assessing the performance of such signal detection procedures requires simulated SRS databases, but simulation strategies proposed to date each have limitations. We sought to develop a novel SRS simulation strategy based on plausible mechanisms for the growth of databases over time. We developed a simulation strategy based on the network principle of preferential attachment. We demonstrated how this strategy can be used to create simulations based on specific databases of interest, and provided an example of using such simulations to compare signal detection thresholds for a popular data mining algorithm. The preferential attachment simulations were generally structurally similar to our targeted SRS database, although they had fewer nodes of very high degree. The approach was able to generate signal-free SRS simulations, as well as mimicking specific known true signals. Explorations of different reporting thresholds for the FDA Vaccine Adverse Event Reporting System suggested that using proportional reporting ratio [PRR] > 3.0 may yield better signal detection operating characteristics than the more commonly used PRR > 2.0 threshold. The network analytic approach to SRS simulation based on the principle of preferential attachment provides an attractive framework for exploring the performance of safety signal detection algorithms. This approach is potentially more principled and versatile than existing simulation approaches. The utility of network-based SRS simulations needs to be further explored by evaluating other types of simulated signals with a broader range of data mining approaches, and comparing network-based simulations with other simulation strategies where applicable.

JCL roundtable: Risk evaluation and mitigation strategy.

PubMed

Brown, W Virgil; Bramlet, Dean A; Ross, Joyce L; Underberg, James A

Many factors enter into the decision by the Food and Drug Administration (FDA) to approve a new drug for use by physicians and other health care providers in treating diseases. Initially, the FDA authority was restricted to issues of safety and only later did the documentation of efficacy become part of the review process required for approval. However, all drugs have the potential for causing harm at some dose level to all and at lower doses in certain patients with vulnerability to the particular pharmacology of the agent. As new drugs have been designed to manage disorders that are uncommon, but of significant consequence, they may have adverse effects that are acceptable only because they are so uniquely beneficial to these specific conditions. The risk of these adverse effects may be acceptable since the benefit can outweigh the harm in most patients and the adversity can be predicted and managed. The approval of this category of drugs has grown rapidly since definition of a mechanism of action to manage and modify the risk has been provided by a process known as known as Risk Evaluation and Mitigation Strategy or "REMS." In 2007, the Food and Drug Administration Amendments Act (FDAAA) allowed the FDA to require postmarketing studies and the authority to mandate the implementation of a REMS for drugs with efficacy but documented potential for harm. Two relatively new drugs useful in the management of severe elevations of low-density lipoprotein cholesterol have been approved under a requirement for a REMS. These are lomitapide, an inhibitor of microsomal triglyceride transfer protein and mipomersen, an antisense oligonucleotide which reduces the synthesis of apolipoprotein B. Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Objective evaluation of acute adverse events and image quality of gadolinium-based contrast agents (gadobutrol and gadobenate dimeglumine) by blinded evaluation. Pilot study.

PubMed

Semelka, Richard C; Hernandes, Mateus de A; Stallings, Clifton G; Castillo, Mauricio

2013-01-01

The purpose was to objectively evaluate a recently FDA-approved gadolinium-based contrast agent (GBCA) in comparison to our standard GBCA for acute adverse events and image quality by blinded evaluation. Evaluation was made of a recently FDA-approved GBCA, gadobutrol (Gadavist; Bayer), in comparison to our standard GBCA, gadobenate dimeglumine (MultiHance; Bracco), in an IRB- and HIPAA-compliant study. Both the imaging technologist and patient were not aware of the brand of the GBCA used. A total of 59 magnetic resonance studies were evaluated (59 patients, 31 men, 28 women, age range of 5-85 years, mean age of 52 years). Twenty-nine studies were performed with gadobutrol (22 abdominal and 7 brain studies), and 30 studies were performed with gadobenate dimeglumine (22 abdominal and 8 brain studies). Assessment was made of acute adverse events focusing on objective observations of vomiting, hives, and moderate and severe reactions. Adequacy of enhancement was rated as poor, fair and good by one of two experienced radiologists who were blinded to the type of agent evaluated. No patient experienced acute adverse events with either agent. The target minor adverse events of vomiting or hives, and moderate and severe reactions were not observed in any patient. Adequacy of enhancement was rated as good for both agents in all patients. Objective, blinded evaluation is feasible and readily performable for the evaluation of GBCAs. This proof-of-concept study showed that both GBCAs evaluated exhibited consistent good image quality and no noteworthy adverse events. Copyright © 2013 Elsevier Inc. All rights reserved.

Adverse Events After Routine Immunization of Extremely Low Birth Weight Infants

PubMed Central

DeMeo, Stephen D.; Raman, Sudha R.; Hornik, Christoph P.; Wilson, Catherine C.; Clark, Reese; Smith, P. Brian

2015-01-01

Importance Immunization of extremely low birth weight (ELBW) infants in the neonatal intensive care unit (NICU) is associated with adverse events including fever and apnea/bradycardia in the immediate post-immunization period. This presents a diagnostic dilemma for clinicians, leading to the potential for immunization delay and sepsis evaluations. Objective To compare the incidence of sepsis evaluations, need for increased respiratory support, intubation, seizures, and death among immunized ELBW infants in the 3 days pre- and post-immunization. Design Multicenter retrospective cohort study. Setting 348 NICUs managed by the Pediatrix Medical Group. Participants 13,926 ELBW infants ≤28 weeks gestation who were discharged between 2007 and 2012. Exposure At least one immunization between day of life 53 and 110. Main Outcomes and Measures Incidence of sepsis evaluations, need for increased respiratory support, intubation, seizures, and death. Results Most (91%) of the infants received 3 or more immunizations. The incidence of sepsis evaluations increased from 5.4/1000 patient days in the pre-immunization period to 19.3/1000 patient days post-immunization (adjusted rate ratio [ARR], 3.7; 95% CI, 3.2–4.4). The need for increased respiratory support increased from 6.6/1000 patient days in the pre-immunization period to 14.0/1000 patient days post-immunization (ARR, 2.1; 95% CI, 1.9–2.5), and intubation increased from 2.0/1000 patient days to 3.6/1000 patient days (ARR, 1.7; 95% CI, 1.3–2.2). The post-immunization incidence of adverse events was similar across immunization types, including combination vaccines when compared to single-dose vaccines. Infants who were 23–24 weeks gestation had a higher risk of sepsis evaluation and intubation post-immunization. A prior history of sepsis was associated with higher risk of sepsis evaluation post-immunization. Conclusion ELBW infants in the NICU had an increased incidence of sepsis evaluations as well as increased respiratory support and intubation after routine immunization. Our findings provide no evidence to suggest that clinicians should not use combination vaccines in ELBW infants. Further studies are needed to determine whether timing or spacing of immunization administrations confers risk for the developing adverse events and whether a prior history of sepsis confers risk for an altered immune response in ELBW infants. PMID:26030302

Cumulative adversity and depressive symptoms among older adults in Israel: the differential roles of self-oriented versus other-oriented events of potential trauma

PubMed Central

Shmotkin, Dov; Litwin, Howard

2013-01-01

Background The study examined the association between cumulative adversity and current depressive symptoms in a national sample of Israelis aged 50+. Referring to cumulative adversity as exposure to potentially traumatic events along life, the study distinguished between events primarily inflicted upon the self (self-oriented adversity) versus upon another person (other-oriented adversity). Method Data were drawn from the Israeli component of the Survey of Health, Aging and Retirement in Europe (SHARE). During 2005–2006, 1710 Jews and Arabs completed an inventory of potentially traumatic events and two measures of depressive symptoms: the European Depression scale (Euro-D) and the Adapted Center for Epidemiological Studies—Depression scale (ACES-D). The Euro-D is more detailed in querying cognitions and motivations while the ACES-D is more detailed in querying feelings and social alienation. Results In line with the hypothesis, self-oriented adversity had a positive association with depressive symptoms whereas other-oriented adversity had either no association or an inverse association with depressive symptoms. Sociodemographic characteristics and perceived health were controlled in the multivariate regressions. Conclusions The differential association of self- versus other-oriented adversity with depressive symptoms may be explained in terms of social commitments that are inherent in other-oriented adversity and incompatible with depressive symptoms. The study points to the variations in the symptom compositions represented by the Euro-D and ACES-D, with the latter better capturing the difference between self- and other-oriented adversities. PMID:19288036

IRIS Toxicological Review of Tetrahydrofuran (THF) (External ...

EPA Pesticide Factsheets

EPA is conducting a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of tetrahydrofuran (THF) that when finalized will appear on the Integrated Risk Information System (IRIS) database. EPA is undertaking an Integrated Risk Information System (IRIS) health assessment for tetrahydrofuran. IRIS is an EPA database containing Agency scientific positions on potential adverse human health effects that may result from chronic (or lifetime) exposure to chemicals in the environment. IRIS contains chemical-specific summaries of qualitative and quantitative health information in support of two steps of the risk assessment paradigm, i.e., hazard identification and dose-response evaluation. IRIS assessments are used in combination with specific situational exposure assessment information to evaluate potential public health risk associated with environmental contaminants.

What is the role of steroids in pneumonia therapy?

PubMed

Póvoa, Pedro; Salluh, Jorge I F

2012-04-01

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

Evaluation of the Expression Profile of Extrapyramidal Symptoms Due to Antipsychotics by Data Mining of Japanese Adverse Drug Event Report (JADER) Database.

PubMed

Kose, Eiji; Uno, Kana; Hayashi, Hiroyuki

2017-01-01

 Typical antipsychotics are easily expressed as adverse events such as extrapyramidal symptom (EPS). On the other hand, incidence of adverse events due to atypical antipsychotics is low. Therefore, currently, atypical antipsychotics are widely used to treat schizophrenia. However, it has been reported that there is no difference in the frequency of EPS in atypical and typical antipsychotics. This study aimed to evaluate the expression profile of EPS in atypical and typical antipsychotics treatment using the Japanese Adverse Drug Event Report (JADER) database. We analyzed reports of EPS in the JADER database and calculated the reporting odds ratio (ROR) of antipsychotics potentially associated with EPS. We applied the Weibull shape parameter to time-to-event data in the JADER database. Consequently, there was little information to distinguish between the ROR of atypical and typical antipsychotics. A significant difference related to the time of onset of EPS in both antipsychotics was not recognized. However, when comparing each drug, Paliperidone, Perospirone, Blonanserin, and Aripiprazole were relatively developed as EPS in the early stage. On the other hand, Risperidone, Clozapine, Olanzapine, and Quetiapine were developed as EPS not only at an early stage but also after long-term use. In addition, this finding was suggested from the result of the cumulative incidence of EPS in each drug and of the time-to-onset analysis using Weibull distribution. These findings may contribute to future clinical practice because we revealed the expression profile of EPS in treatment with atypical and typical antipsychotics.

The Seamless Transfer-of-Care Protocol: a randomized controlled trial assessing the efficacy of an electronic transfer-of-care communication tool.

PubMed

Okoniewska, Barbara M; Santana, Maria J; Holroyd-Leduc, Jayna; Flemons, Ward; O'Beirne, Maeve; White, Deborah; Clement, Fiona; Forster, Alan; Ghali, William A

2012-11-21

The transition between acute care and community care represents a vulnerable period in health care delivery. The vulnerability of this period has been attributed to changes to patients' medication regimens during hospitalization, failure to reconcile discrepancies between admission and discharge and the burdening of patients/families to take over care responsibilities at discharge and to relay important information to the primary care physician. Electronic communication platforms can provide an immediate link between acute care and community care physicians (and other community providers), designed to ensure consistent information transfer. This study examines whether a transfer-of-care (TOC) communication tool is efficacious and cost-effective for reducing hospital readmission, adverse events and adverse drug events as well as reducing death. A randomized controlled trial conducted on the Medical Teaching Unit of a Canadian tertiary care centre will evaluate the efficacy and cost-effectiveness of a TOC communication tool. Medical in-patients admitted to the unit will be considered for this study. Data will be collected upon admission, and a total of 1400 patients will be randomized. The control group's acute care stay will be summarized using a traditional dictated summary, while the intervention group will have a summary generated using the TOC communication tool. The primary outcome will be a composite, at 3 months, of death or readmission to any Alberta acute-care hospital. Secondary outcomes will be the occurrence of post-discharge adverse events and adverse drug events at 1 month post discharge. Patients with adverse outcomes will have their cases reviewed by two Royal College certified internists or College-certified family physicians, blinded to patients' group assignments, to determine the type, severity, preventability and ameliorability of all detected adverse outcomes. An accompanying economic evaluation will assess the cost per life saved, cost per readmission avoided and cost per QALY gained with the TOC communication tool compared to traditional dictation summaries. This paper outlines the study protocol for a randomized controlled trial evaluating an electronic transfer-of-care communication tool, with sufficient statistical power to assess the impact of the tool on the significant outcomes of post-discharge death or readmission. The study findings will inform health systems around the world on the potential benefits of such tools, and the value for money associated with their widespread implementation. ClinicalTrials.gov NCT01402609.

Children of Misfortune: Early Adversity and Cumulative Inequality in Perceived Life Trajectories1

PubMed Central

Schafer, Markus H.; Ferraro, Kenneth F.; Mustillo, Sarah A.

2011-01-01

Adversity early in life may alter pathways of aging, but what interpretive processes can soften the blow of early insults? Drawing from cumulative inequality theory, the authors analyze trajectories of life evaluations and then consider whether early adversity offsets favorable expectations for the future. Results reveal that early adversity contributes to more negative views of the past but rising expectations for the future. Early adversity also has enduring effects on life evaluations, offsetting the influence of buoyant expectations. The findings draw attention to the limits of human agency under the constraints of early adversity—a process described as biographical structuration. PMID:21648247

Adjunctive Role of Glucagon-Like Peptide-1 Receptor Agonists in the Management of Type 1 Diabetes Mellitus.

PubMed

Harris, Kira B; Boland, Cassie L

2016-09-01

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are commonly used in combination with insulin to manage type 2 diabetes mellitus, and four agents are currently approved for this indication: exenatide, liraglutide, dulaglutide, and albiglutide. The distinctive properties of GLP-1 RAs-potential hemoglobin A1c (A1C) reduction, weight loss, potential to reduce insulin doses, and lower hypoglycemia risk-have made these agents potential treatment options for patients with type 1 diabetes mellitus (T1DM) as well. These positive effects are due to glucose-dependent insulin secretion, reduced glucagon secretion, increased satiety, and delayed gastric emptying. Patients with T1DM are unable to suppress glucagon during meals, which contributes to postprandial hyperglycemia and may be improved with GLP-1 therapy. In this review, we evaluated the available literature on the clinical efficacy and safety of GLP-1 RAs in patients with T1DM. We conducted a search of the PubMed (1966-May 2016) and Ovid (1946-May 2016) databases. Abstracts presented at the scientific and clinical sessions of the American Diabetes Association and the American Association of Clinical Endocrinologists were also searched. The references of the published articles were also reviewed to identify additional studies appropriate for inclusion. All identified articles published in English were evaluated. Studies were included if they evaluated the clinical use or safety of GLP-1 RAs in patients with T1DM. Twelve studies were included, with four evaluating exenatide, one evaluating exenatide extended release, and seven evaluating liraglutide. Both exenatide and liraglutide showed significant reductions in hemoglobin A1C, plasma glucose concentration, body weight, and insulin doses when administered to patients with T1DM already receiving insulin therapy, without increasing the occurrence of hypoglycemia. Adverse effects were mostly gastrointestinal in nature but were mild and transient. Patients who may benefit most are those experiencing adverse effects from insulin, those not at their A1C goal but hypoglycemia prevents insulin titration, and those who may benefit from weight loss. © 2016 Pharmacotherapy Publications, Inc.

40 CFR 264.93 - Hazardous constituents.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Administrator will consider the following: (1) Potential adverse effects on ground-water quality, considering... (2) Potential adverse effects on hydraulically-connected surface water quality, considering: (i) The... specify in the facility permit the hazardous constituents to which the ground-water protection standard of...

40 CFR 264.94 - Concentration limits.

Code of Federal Regulations, 2013 CFR

2013-07-01

... consider the following factors: (1) Potential adverse effects on ground-water quality, considering: (i) The...) Potential adverse effects on hydraulically-connected surface-water quality, considering: (i) The volume and... specify in the facility permit concentration limits in the ground water for hazardous constituents...

40 CFR 264.94 - Concentration limits.

Code of Federal Regulations, 2012 CFR

2012-07-01

... consider the following factors: (1) Potential adverse effects on ground-water quality, considering: (i) The...) Potential adverse effects on hydraulically-connected surface-water quality, considering: (i) The volume and... specify in the facility permit concentration limits in the ground water for hazardous constituents...

40 CFR 264.94 - Concentration limits.

Code of Federal Regulations, 2014 CFR

2014-07-01

... consider the following factors: (1) Potential adverse effects on ground-water quality, considering: (i) The...) Potential adverse effects on hydraulically-connected surface-water quality, considering: (i) The volume and... specify in the facility permit concentration limits in the ground water for hazardous constituents...

40 CFR 264.93 - Hazardous constituents.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Administrator will consider the following: (1) Potential adverse effects on ground-water quality, considering... (2) Potential adverse effects on hydraulically-connected surface water quality, considering: (i) The... specify in the facility permit the hazardous constituents to which the ground-water protection standard of...

Decision support environment for medical product safety surveillance.

PubMed

Botsis, Taxiarchis; Jankosky, Christopher; Arya, Deepa; Kreimeyer, Kory; Foster, Matthew; Pandey, Abhishek; Wang, Wei; Zhang, Guangfan; Forshee, Richard; Goud, Ravi; Menschik, David; Walderhaug, Mark; Woo, Emily Jane; Scott, John

2016-12-01

We have developed a Decision Support Environment (DSE) for medical experts at the US Food and Drug Administration (FDA). The DSE contains two integrated systems: The Event-based Text-mining of Health Electronic Records (ETHER) and the Pattern-based and Advanced Network Analyzer for Clinical Evaluation and Assessment (PANACEA). These systems assist medical experts in reviewing reports submitted to the Vaccine Adverse Event Reporting System (VAERS) and the FDA Adverse Event Reporting System (FAERS). In this manuscript, we describe the DSE architecture and key functionalities, and examine its potential contributions to the signal management process by focusing on four use cases: the identification of missing cases from a case series, the identification of duplicate case reports, retrieving cases for a case series analysis, and community detection for signal identification and characterization. Published by Elsevier Inc.

Adverse weather conditions and fatal motor vehicle crashes in the United States, 1994-2012.

PubMed

Saha, Shubhayu; Schramm, Paul; Nolan, Amanda; Hess, Jeremy

2016-11-08

Motor vehicle crashes are a leading cause of injury mortality. Adverse weather and road conditions have the potential to affect the likelihood of motor vehicle fatalities through several pathways. However, there remains a dearth of assessments associating adverse weather conditions to fatal crashes in the United States. We assessed trends in motor vehicle fatalities associated with adverse weather and present spatial variation in fatality rates by state. We analyzed the Fatality Analysis Reporting System (FARS) datasets from 1994 to 2012 produced by the National Highway Traffic Safety Administration (NHTSA) that contains reported weather information for each fatal crash. For each year, we estimated the fatal crashes that were associated with adverse weather conditions. We stratified these fatalities by months to examine seasonal patterns. We calculated state-specific rates using annual vehicle miles traveled data for all fatalities and for those related to adverse weather to examine spatial variations in fatality rates. To investigate the role of adverse weather as an independent risk factor for fatal crashes, we calculated odds ratios for known risk factors (e.g., alcohol and drug use, no restraint use, poor driving records, poor light conditions, highway driving) to be reported along with adverse weather. Total and adverse weather-related fatalities decreased over 1994-2012. Adverse weather-related fatalities constituted about 16 % of total fatalities on average over the study period. On average, 65 % of adverse weather-related fatalities happened between November and April, with rain/wet conditions more frequently reported than snow/icy conditions. The spatial distribution of fatalities associated with adverse weather by state was different than the distribution of total fatalities. Involvement of alcohol or drugs, no restraint use, and speeding were less likely to co-occur with fatalities during adverse weather conditions. While adverse weather is reported for a large number of motor vehicle fatalities for the US, the type of adverse weather and the rate of associated fatality vary geographically. These fatalities may be addressed and potentially prevented by modifying speed limits during inclement weather, improving road surfacing, ice and snow removal, and providing transit alternatives, but the impact of potential interventions requires further research.

Application of the Beers Criteria to Alternate Level of Care Patients in Hospital Inpatient Units

PubMed Central

Slaney, Heather; MacAulay, Stacey; Irvine-Meek, Janice; Murray, Joshua

2015-01-01

Background: The Beers criteria were developed to help in identifying potentially inappropriate medications (PIMs) for elderly patients. These medications are often associated with adverse events and limited effectiveness in older adults. Patients awaiting an alternate level of care (ALC patients) are those who no longer require acute care hospital services and are waiting for placement elsewhere. They are often elderly, have complex medication regimens, and are at high risk of adverse events. At the time of this study no studies had applied the Beers criteria to ALC patients in Canadian hospitals. Objectives: To determine the proportion of ALC patients receiving PIMs and the proportion experiencing selected PIM-related adverse events. Methods: A retrospective chart review of ALC patients 65 years of age or older was performed to identify PIMs and the occurrence of selected adverse events (specifically central nervous system [CNS] events, falls, bradycardia, hypoglycemia, seizures, insomnia, gastrointestinal bleeding, and urinary tract infections). A logistic regression model with a random intercept for each patient was constructed to estimate odds ratios and probabilities of adverse events. Results: Fifty-two ALC patients were included in the study. Of these, 48 (92%) were taking a PIM. Of the 922 adverse events evaluated, 407 (44.1%) were associated with a regularly scheduled PIM. Among patients who were taking regularly scheduled PIMs, there was a significantly increased probability of an adverse CNS event and of a fall (p < 0.001 for both). The most common PIM medication classes were first-generation antihistamines (24 [46%] of the 52 patients), antipsychotics (21 patients [40%]), short-acting benzodiazepines (15 patients [29%]), and nonbenzodiazepine hypnotics (14 patients [27%]). Conclusions: A high proportion of ALC patients were taking PIMs and experienced an adverse event that may have been related to these drugs. These findings suggest that the ALC population might benefit from regular medication review and monitoring to prevent or detect adverse events. PMID:26157183

Intermittent blood pressure control: potential consequences for outcome.

PubMed

Leenen, F H

1999-05-01

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

Creating an Oversight Infrastructure for Electronic Health Record-Related Patient Safety Hazards

PubMed Central

Singh, Hardeep; Classen, David C.; Sittig, Dean F.

2013-01-01

Electronic health records (EHRs) have potential quality and safety benefits. However, reports of EHR-related safety hazards are now emerging. The Office of the National Coordinator (ONC) for Health Information Technology (HIT) recently sponsored an Institute of Medicine committee to evaluate how HIT use affects patient safety. In this paper, we propose the creation of a national EHR oversight program to provide dedicated surveillance of EHR-related safety hazards and to promote learning from identified errors, close calls, and adverse events. The program calls for data gathering, investigation/analysis and regulatory components. The first two functions will depend on institution-level EHR safety committees that will investigate all known EHR-related adverse events and near-misses and report them nationally using standardized methods. These committees should also perform routine safety self-assessments to proactively identify new risks. Nationally, we propose the long-term creation of a centralized, non-partisan board with an appropriate legal and regulatory infrastructure to ensure the safety of EHRs. We discuss the rationale of the proposed oversight program and its potential organizational components and functions. These include mechanisms for robust data collection and analyses of all safety concerns using multiple methods that extend beyond reporting; multidisciplinary investigation of selected high-risk safety events; and enhanced coordination with other national agencies in order to facilitate broad dissemination of hazards information. Implementation of this proposed infrastructure can facilitate identification of EHR-related adverse events and errors and potentially create a safer and more effective EHR-based health care delivery system. PMID:22080284

Interactions Between Depression and Lower Urinary Tract Symptoms: The Role of Adverse Life Events and Inflammatory Mechanisms. Results From the European Male Ageing Study.

PubMed

Castellini, Giovanni; Wu, Frederick C W; Finn, Joseph D; OʼNeill, Terrence W; Lean, Michael E J; Pendleton, Neil; Rastrelli, Giulia; Rutter, Martin K; Gacci, Mauro; Ricca, Valdo; Maggi, Mario

2016-01-01

Depression and lower urinary tract symptoms (LUTSs) have been found to co-occur among aging men. The present study attempted to clarify the nature of this relationship, considering adverse life events as potential moderators and the inflammation as an underlying biological mechanism. The relationship between depression and LUTS was evaluated using data from the European Male Ageing Study, the largest multicenter population-based study of aging in European men. The sample included 3369 men who were assessed by means of several self-reported questionnaires, including the Beck Depression Inventory-II, the International Prostate Symptom Score, and the Adverse Life Events Scale. Participants were asked to provide information regarding general health and life-style, and medical comorbidities. Biological measures including prostate-specific antigen, testosterone, and C-reactive protein were measured. LUTS and depressive symptoms were correlated (R = 0.32, β = .10, p < .001), even after adjusting for life-style, psychological, and medical variables. A history of adverse life events was associated with both higher LUTS and Beck Depression Inventory scores. Furthermore, adverse life events moderated the LUTS-depression association (F = 22.62, b = 0.061, p < .001), which increased as a function of the number of life events. C-reactive protein was found to mediate the LUTS-depression association. This mediation effect was moderated by number of adverse life events. Participants with a history of adverse life events represent a vulnerable population in whom the association between somatic and depressive symptoms is stronger. One of the biological mechanisms underlying this association could be an activation of the central inflammatory signaling pathways.

Wind turbines and health: An examination of a proposed case definition.

PubMed

McCunney, Robert J; Morfeld, Peter; Colby, W David; Mundt, Kenneth A

2015-01-01

Renewable energy demands have increased the need for new wind farms. In turn, concerns have been raised about potential adverse health effects on nearby residents. A case definition has been proposed to diagnose "Adverse Health Effects in the Environs of Industrial Wind Turbines" (AHE/IWT); initially in 2011 and then with an update in 2014. The authors invited commentary and in turn, we assessed its scientific merits by quantitatively evaluating its proposed application. We used binomial coefficients to quantitatively assess the potential of obtaining a diagnosis of AHE/IWT. We also reviewed the methodology and process of the development of the case definition by contrasting it with guidelines on case definition criteria of the USA Institute of Medicine. The case definition allows at least 3,264 and up to 400,000 possibilities for meeting second- and third-order criteria, once the limited first-order criteria are met. IOM guidelines for clinical case definitions were not followed. The case definition has virtually no specificity and lacks scientific support from peer-reviewed literature. If applied as proposed, its application will lead to substantial potential for false-positive assessments and missed diagnoses. Virtually any new illness that develops or any prevalent illness that worsens after the installation of wind turbines within 10 km of a residence could be considered AHE/IWT if the patient feels better away from home. The use of this case definition in the absence of a thorough medical evaluation with appropriate diagnostic studies poses risks to patients in that treatable disorders would be overlooked. The case definition has significant potential to mislead patients and its use cannot be recommended for application in any health-care or decision-making setting.

Wind turbines and health: An examination of a proposed case definition

PubMed Central

McCunney, Robert J.; Morfeld, Peter; Colby, W. David; Mundt, Kenneth A.

2015-01-01

Renewable energy demands have increased the need for new wind farms. In turn, concerns have been raised about potential adverse health effects on nearby residents. A case definition has been proposed to diagnose “Adverse Health Effects in the Environs of Industrial Wind Turbines” (AHE/IWT); initially in 2011 and then with an update in 2014. The authors invited commentary and in turn, we assessed its scientific merits by quantitatively evaluating its proposed application. We used binomial coefficients to quantitatively assess the potential of obtaining a diagnosis of AHE/IWT. We also reviewed the methodology and process of the development of the case definition by contrasting it with guidelines on case definition criteria of the USA Institute of Medicine. The case definition allows at least 3,264 and up to 400,000 possibilities for meeting second- and third-order criteria, once the limited first-order criteria are met. IOM guidelines for clinical case definitions were not followed. The case definition has virtually no specificity and lacks scientific support from peer-reviewed literature. If applied as proposed, its application will lead to substantial potential for false-positive assessments and missed diagnoses. Virtually any new illness that develops or any prevalent illness that worsens after the installation of wind turbines within 10 km of a residence could be considered AHE/IWT if the patient feels better away from home. The use of this case definition in the absence of a thorough medical evaluation with appropriate diagnostic studies poses risks to patients in that treatable disorders would be overlooked. The case definition has significant potential to mislead patients and its use cannot be recommended for application in any health-care or decision-making setting. PMID:26168947

Association rule mining in the US Vaccine Adverse Event Reporting System (VAERS).

PubMed

Wei, Lai; Scott, John

2015-09-01

Spontaneous adverse event reporting systems are critical tools for monitoring the safety of licensed medical products. Commonly used signal detection algorithms identify disproportionate product-adverse event pairs and may not be sensitive to more complex potential signals. We sought to develop a computationally tractable multivariate data-mining approach to identify product-multiple adverse event associations. We describe an application of stepwise association rule mining (Step-ARM) to detect potential vaccine-symptom group associations in the US Vaccine Adverse Event Reporting System. Step-ARM identifies strong associations between one vaccine and one or more adverse events. To reduce the number of redundant association rules found by Step-ARM, we also propose a clustering method for the post-processing of association rules. In sample applications to a trivalent intradermal inactivated influenza virus vaccine and to measles, mumps, rubella, and varicella (MMRV) vaccine and in simulation studies, we find that Step-ARM can detect a variety of medically coherent potential vaccine-symptom group signals efficiently. In the MMRV example, Step-ARM appears to outperform univariate methods in detecting a known safety signal. Our approach is sensitive to potentially complex signals, which may be particularly important when monitoring novel medical countermeasure products such as pandemic influenza vaccines. The post-processing clustering algorithm improves the applicability of the approach as a screening method to identify patterns that may merit further investigation. Copyright © 2015 John Wiley & Sons, Ltd.

Baduanjin Exercise Prevents post-Myocardial Infarction Left Ventricular Remodeling (BE-PREMIER trial): Design and Rationale of a Pragmatic Randomized Controlled Trial.

PubMed

Mao, Shuai; Zhang, Xiaoxuan; Shao, Biying; Hu, Xiyan; Hu, Yanan; Li, Winny; Guo, Liheng; Zhang, Minzhou

2016-06-01

Left ventricular (LV) remodeling following myocardial infarction (MI) is an established prognostic factor for adverse cardiovascular events and the leading cause of heart failure. Empirical observations have suggested that Baduanjin exercise, an important component of traditional Chinese Qigong, may exert potential benefits on cardiopulmonary function. However, the impact of a Baduanjin exercise-based cardiac rehabilitation program for patients recovering from a recent MI has yet to be assessed. The aim of this trial is to evaluate the potential role of Baduanjin exercise in preventing the maladaptive progression to adverse LV remodeling in patients post-MI. A total of 110 clinically stable patients following an MI after undergoing successful infarct-related artery reperfusion will be randomly assigned to the Baduanjin exercise group or usual exercise control group. In addition to usual physical activity, participants in the Baduanjin exercise group will participate in a 45 min Baduanjin exercise training session twice a week, for a total of 12 weeks. The primary endpoint will be the percentage change in LV end-diastolic volume index (LVEDVi) assessed using echocardiography from baseline to 6 months. The results of this study may provide novel evidence on the efficacy of Baduanjin exercise therapy in post-MI patients in reversing adverse LV remodeling and improving clinical outcome. Clinical Trials.gov: NCT02693795.

Safety of stable isotope use.

PubMed

Koletzko, B; Sauerwald, T; Demmelmair, H

1997-08-01

The increased employment of stable isotope tracers for diagnostic and research purposes frequently raises questions on potential risks associated with their use, which is of particular importance in the paediatric age group. Biological effects and the potential of adverse events has been evaluated in a large number of animal and, in part, also human studies. Possible differences in physical, chemical and biochemical behaviour resulting in kinetic and thermodynamic isotope effects between stable isotopes of the same element are related to the relative differences in atomic weight. Deuterium (2H), which differs markedly in mass from the predominant hydrogen isotope 1H, may induce serious side-effects at high concentrations in body fluids. The threshold dose for the occurrence of side-effects lies well above the usual tracer dosages for clinical use. In contrast to deuterium, heavier stable isotopes such as 13C, 15N or 18O that differ relatively little in mass from the predominant isotopes such as 12C, does not show any adverse biological effects even at highest enrichments. The doses of stable isotope tracer substances that are used for clinical diagnostic and research purposes appear safe and without any adverse effects. Stable isotope tracers should only be used in children if the trace is safe at the doses applied, and tracer is chemically pure and stable. In the case of intravenous application, the tracer preparation must also be sterile and pyrogen free.

Correlates of adverse childhood events among adults with schizophrenia spectrum disorders.

PubMed

Rosenberg, Stanley D; Lu, Weili; Mueser, Kim T; Jankowski, Mary Kay; Cournos, Francine

2007-02-01

Multiple studies have found that childhood adversity is related to a range of poor mental health, substance abuse, poor physical health, and poor social functioning outcomes in the general population of adults. However, despite the high rates of childhood adversity in schizophrenia, the clinical correlates of these events have not been systematically evaluated. This study evaluated the relationship between adverse experiences in childhood and functional, clinical, and health outcomes among adults with schizophrenia. The authors surveyed 569 adults with schizophrenia regarding adverse childhood events (including physical abuse, sexual abuse, parental mental illnesses, loss of a parent, parental separation or divorce, witnessing domestic violence, and foster or kinship care). The relationships between cumulative exposure to these events and psychiatric, physical, and functional outcomes were evaluated. Increased exposure to adverse childhood events was strongly related to psychiatric problems (suicidal thinking, hospitalizations, distress, and posttraumatic stress disorder), substance abuse, physical health problems (HIV infection), medical service utilization (physician visits), and poor social functioning (homelessness or criminal justice involvement). The findings extend the results of research in the general population by suggesting that childhood adversity contributes to worse mental health, substance abuse, worse physical health, and poor functional outcomes in schizophrenia.

Computational Approaches for Identifying Adverse Outcome Pathways

EPA Science Inventory

Adverse Outcome Pathways (AOPs) provide a framework for organizing toxicity information to improve predictions of the potential adverse impact of environment stressors on humans or wildlife populations, but these benefits are currently limited by the small number of AOPs currentl...

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...

Understanding the nature of errors in nursing: using a model to analyse critical incident reports of errors which had resulted in an adverse or potentially adverse event.

PubMed

Meurier, C E

2000-07-01

Human errors are common in clinical practice, but they are under-reported. As a result, very little is known of the types, antecedents and consequences of errors in nursing practice. This limits the potential to learn from errors and to make improvement in the quality and safety of nursing care. The aim of this study was to use an Organizational Accident Model to analyse critical incidents of errors in nursing. Twenty registered nurses were invited to produce a critical incident report of an error (which had led to an adverse event or potentially could have led to an adverse event) they had made in their professional practice and to write down their responses to the error using a structured format. Using Reason's Organizational Accident Model, supplemental information was then collected from five of the participants by means of an individual in-depth interview to explore further issues relating to the incidents they had reported. The detailed analysis of one of the incidents is discussed in this paper, demonstrating the effectiveness of this approach in providing insight into the chain of events which may lead to an adverse event. The case study approach using critical incidents of clinical errors was shown to provide relevant information regarding the interaction of organizational factors, local circumstances and active failures (errors) in producing an adverse or potentially adverse event. It is suggested that more use should be made of this approach to understand how errors are made in practice and to take appropriate preventative measures.

Guide wire entrapment by inferior vena cava filters: an experimental study.

PubMed

Rosen, Michael J; Burns, Justin M; Cobb, William S; Jacobs, David G; Heniford, B Todd; Sing, Ronald F

2005-09-01

In situ vena cava filters are at risk for complications with the use of J-tipped guide wires. The purpose of this study was to evaluate the impact of two commonly used J-tipped guide wires on the stability of the four most recently released vena cava filters in an in vitro flow model. Four filters (OptEase [F1], Günther Tulip [F2], Vena Tech LP [F3], and Recovery [F4]) were inserted into an in vitro flow model. Two J-tipped guide wires (0.032-inch [GW-1], 0.035-inch [GW-2]) were passed through each filter (n = 50 passes per wire) for a distance of 10 cm. The inserter was blind as to the effects of the wire. The filters were monitored by an independent observer for adverse events occurring between the filters and the guide wires. These were defined as: migrations (>1 cm), change of position (tilt>10 degrees), and entrapment of the wire (unable to remove wire). Descriptive statistics, chi-square, and Fisher's exact test were used (p < 0.05 considered significant). GW-1 resulted in a lower incidence of entrapment, migration, and tilt for all filters compared with GW-2 (F1, p = 0.003; F2, p < 0.0001; F3, p < 0.0001; F4, p = 0.0004). GW-1 resulted in entrapment in 0%, migration in 7.5%, and tilt in 10.5% of insertions. GW-2 resulted in entrapment in 1%, migration in 26.5%, and tilt in 5.5% of insertions. The incidence of adverse events for GW-1 was significantly different compared with all filters (F1, 0%; F2, 46%; F3, 4%; and F4, 22%; p < 0.0001). Similarly, the incidence of adverse events for GW-2 was significantly different when evaluating all filters (F1, 12%; F2, 48%; F3, 22%; F4 60%; p < 0.0001). The smaller-diameter guide wire resulted in a decreased incidence of adverse events for all filters, but there is still risk for complications. Knowledge of potential complications associated with vena cava filters and the postinsertion use of guide wires are essential to avoid potential mishaps.

A Gynecologic Oncology Group phase II trial of the protein kinase C-beta inhibitor, enzastaurin and evaluation of markers with potential predictive and prognostic value in persistent or recurrent epithelial ovarian and primary peritoneal malignancies

PubMed Central

Usha, Lydia; Sill, Michael W.; Darcy, Kathleen M.; Benbrook, Doris M.; Hurteau, Jean A; Michelin, David P.; Mannel, Robert S.; Hanjani, Parviz; De Geest, Koen; Godwin, Andrew K.

2011-01-01

Purpose Protein kinase C (PKC) activation contributes to proliferation and angiogenesis in epithelial ovarian or primary peritoneal carcinoma (EOC/PPC). A multi-institutional phase II trial was conducted to evaluate the efficacy and safety of PKCβ inhibitor enzastaurin in persistent or recurrent EOC/PPC and to explore potential prognostic and predictive biomarkers. Methods Eligible women with measurable platinum-sensitive and resistant EOC/PPC were treated with continuous administration of oral enzastaurin until disease progression or unacceptable toxicity. A two-stage sequential design was used to evaluate progression-free survival (PFS) ≥ 6-months, tumor response, and toxicity. Translational studies included sequencing of the TP53, PTEN, PIK3CA and PKCβII genes for somatic mutations, quantitative PCR assays for AKT2 and PTEN copy number alterations, and measurement of circulating VEGF-A plasma levels. Results Among 27 eligible and evaluable patients, 3 women with PFS ≥ 6-months (11%) and 2 women with partial responses (7%) were observed. One of them achieved a durable response and remains on the study. No grade 4 adverse events were observed. Most common grade 3 adverse events were constitutional (4) and gastrointestinal (3). Mutations in the TP53 gene and abnormal copy number in the PTEN gene were common (56% and 48% of cases, respectively). Conclusions Enzastaurin was tolerable but had insufficient activity to proceed with the second stage of accrual. However, 1 patient has been progression-free for 44 months. No association between a biomarker and response to enzastaurin has been found. Exploratory analysis suggested an association between survival and PTEN copy number losses. PMID:21414654

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).

Risk Associated with Bee Venom Therapy: A Systematic Review and Meta-Analysis

PubMed Central

Park, Jeong Hwan; Yim, Bo Kyung; Lee, Jun-Hwan; Lee, Sanghun; Kim, Tae-Hun

2015-01-01

Objective The safety of bee venom as a therapeutic compound has been extensively studied, resulting in the identification of potential adverse events, which range from trivial skin reactions that usually resolve over several days to life-threating severe immunological responses such as anaphylaxis. In this systematic review, we provide a summary of the types and prevalence of adverse events associated with bee venom therapy. Methods We searched the literature using 12 databases from their inception to June 2014, without language restrictions. We included all types of clinical studies in which bee venom was used as a key intervention and adverse events that may have been causally related to bee venom therapy were reported. Results A total of 145 studies, including 20 randomized controlled trials, 79 audits and cohort studies, 33 single-case studies, and 13 case series, were evaluated in this review. The median frequency of patients who experienced adverse events related to venom immunotherapy was 28.87% (interquartile range, 14.57–39.74) in the audit studies. Compared with normal saline injection, bee venom acupuncture showed a 261% increased relative risk for the occurrence of adverse events (relative risk, 3.61; 95% confidence interval, 2.10 to 6.20) in the randomized controlled trials, which might be overestimated or underestimated owing to the poor reporting quality of the included studies. Conclusions Adverse events related to bee venom therapy are frequent; therefore, practitioners of bee venom therapy should be cautious when applying it in daily clinical practice, and the practitioner’s education and qualifications regarding the use of bee venom therapy should be ensured. PMID:25996493

Validating new summary indices for the Childhood Trauma Interview: associations with first onsets of major depressive disorder and anxiety disorders.

PubMed

Vrshek-Schallhorn, Suzanne; Wolitzky-Taylor, Kate; Doane, Leah D; Epstein, Alyssa; Sumner, Jennifer A; Mineka, Susan; Zinbarg, Richard E; Craske, Michelle G; Isaia, Ashley; Hammen, Constance; Adam, Emma K

2014-09-01

Childhood and adolescent adversity is of great interest in relation to risk for psychopathology, and interview measures of adversity are thought to be more reliable and valid than their questionnaire counterparts. One interview measure, the Childhood Trauma Interview (CTI; Fink et al., 1995), has been positively evaluated relative to similar measures, but there are some psychometric limitations to an existing scoring approach that limit the full potential of this measure. We propose several new summary indices for the CTI that permit examination of different types of adversity and different developmental periods. Our approach creates several summary indices: one sums the severity scores of adversities endorsed; another utilizes the number of minor and major (moderate to severe) adversities. The new indices were examined in association with first onsets of major depressive disorder (MDD) and anxiety disorders across a 5-year period using annual clinical diagnostic interviews (Structured Clinical Interview for DSM-IV-TR). Summary scores derived with the previously used approach were also examined for comparison. Data on 332 participants came from the Youth Emotion Project, a longitudinal study of risk for emotional disorders. Results support the predictive validity of the proposed summary scoring methods and indicate that several forms of major (but typically not minor) adversity are significantly associated with first onsets of MDD and anxiety disorders. Finally, multivariate regression models show that, in many instances, the new indices contributed significant unique variance predicting disorder onsets over and above the previously used summary indices. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Prenatal Tdap immunization and risk of maternal and newborn adverse events.

PubMed

Layton, J Bradley; Butler, Anne M; Li, Dongmei; Boggess, Kim A; Weber, David J; McGrath, Leah J; Becker-Dreps, Sylvia

2017-07-24

Many countries recommend combined tetanus toxoid, reduced diphtheria toxoid and acellular pertussis immunization (Tdap) during pregnancy to stimulate transplacental transmission of pertussis antibodies to newborns. The immune system can be altered during pregnancy, potentially resulting in differing immunization risks in pregnant women. The safety of widespread Tdap immunization during pregnancy needs to be established. Our objective was to assess whether prenatal Tdap immunization was associated with adverse birth outcomes, and to evaluate the effect of timing of Tdap administration on these outcomes. We identified pregnancies at delivery in a large insurance claims database (2010-2014). Tdap immunization was categorized as optimal prenatal (27+weeks), early prenatal (<27weeks), postpartum (≤7days post-delivery), or none. Medical claims were searched to identify maternal adverse immunization reactions (e.g. anaphylaxis, fever, Guillian-Barre syndrome [GBS]), adverse birth outcomes (e.g. preeclampsia/eclampsia, premature rupture or membranes, chorioamnionitis) and newborn outcomes (e.g. respiratory distress, pulmonary hypertension, neonatal jaundice). Women with optimal or early prenatal Tdap were compared to those not immunized in pregnancy, using propensity score-weighted log-binomial regression and Cox proportional hazards models to estimate risk ratios (RR) and hazard ratios (HR). We identified 1,079,034 deliveries and 677,075 linked newborns; 11.5% were immunized optimally and 2.3% immunized early. There were 1 case of post-immunization anaphylaxis, and 12 cases of maternal encephalopathy (all post- delivery); there were no cases of GBS. Optimally-timed immunization was associated with small increased relative risks of: chorioamnionitis [RR=1.11, (95% CI: 1.07-1.15), overall risk=2.8%], and postpartum hemorrhage [RR=1.23 (95% DI: 1.18-1.28), overall risk=2.4%]; however, these relative increases corresponded to low absolute risk increases. Tdap was not associated with increased risk of any adverse newborn outcome. Overall, prenatal Tdap immunization was not associated with newborn adverse events, but potential associations with chorioamnionitis consistent with one previous study and postpartum hemorrhage require further investigation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cost effectiveness of high-sensitivity troponin compared to conventional troponin among patients presenting with undifferentiated chest pain: A trial based analysis.

PubMed

Kaambwa, Billingsley; Ratcliffe, Julie; Horsfall, Matthew; Astley, Carolyn; Karnon, Jonathan; Coates, Penelope; Arstall, Margaret; Zeitz, Christopher; Worthley, Matthew; Beltrame, John; Chew, Derek P

2017-07-01

Patients with low and intermediate risk chest pain features comprise the greatest proportion presenting to emergency services for evaluation of suspected acute coronary syndromes (ACS). The efficient and timely identification of patients with these features remains a major challenge within clinical practice. Troponin assays are increasingly being used for the determination of risk among patients presenting with chest pain potentially facilitating more appropriate care. To date, no economic evaluation comparing high-sensitivity troponin T (hs-TnT) reporting to standard troponin T (c-TnT) reporting in the routine management of suspected ACS and based on longer-term clinical outcomes has been conducted. An economic evaluation was conducted with 1937 participants randomized to either hs-TnT (n=973) or c-TnT (n=964) with 12month follow-up. The primary outcome measure was the number of cumulative combined outcomes of all-cause mortality and new or recurrent ACS avoided. Mean per participant Australian Medicare costs were higher in the hs-TnT arm compared to the c-TnT arm (by $1285/patient). Mean total adverse clinical outcomes avoided were higher in the hs-TnT arm (by 0.0120/patient) resulting in an incremental cost-effectiveness ratio (ICER) of $108,552/adverse clinical outcome avoided. An ICER of $49,030/adverse clinical outcome avoided was obtained when the analysis was restricted to patients below the threshold of normal Troponin testing (actual c-TnT levels <30ng/L). hs-TnT reporting leads to fewer adverse clinical events but at a high ICER. For the routine implementation of hs-TnT to be more cost-effective, substantial changes in clinical practice will be required. Australian New Zealand Clinical Trials Registry (ACTRN12614000189628). https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=365726. Copyright © 2017 Elsevier B.V. All rights reserved.

Implant Evaluation of an Insertable Cardiac Monitor Outside the Electrophysiology Lab Setting

PubMed Central

Pachulski, Roman; Cockrell, James; Solomon, Hemant; Yang, Fang; Rogers, John

2013-01-01

Background To date, insertable cardiac monitors (ICM) have been implanted in the hospital without critical evaluation of other potential settings. Providing alternatives to in-hospital insertion may increase access to ICM, decrease waiting times for patients awaiting diagnosis, and reduce hospital resources. Methods This was a prospective, non-randomized, clinical trial involving nine clinical sites throughout the United States designed to assess the feasibility of ICM implants in a non-hospital setting. Other than the Reveal® ICM, implant supplies and techniques were left to physician discretion in patients who met indications. Patients were followed up to 90 days post-implant. The primary objective was to characterize the number of procedure-related adverse events that required surgical intervention within 90 days. Results Sixty-five patients were implanted at nine out-of-hospital sites. The insertion procedure was well tolerated by all patients. There were no deaths, systemic infections or endocarditis. There were two (3%) procedure-related adverse events requiring device explant and four (6%) adverse events not requiring explant. ICM use led to 16 diagnoses (24.6%) with 9 patients proceeding to alternate cardiac device implants during the course of the 90-day follow up. Conclusion Out-of-hospital ICM insertion can be accomplished with comparable procedural safety and represents a reasonable alternative to the in-hospital setting. Clinicaltrials.gov registration number: NCT01168427 PMID:23977071

Evaluation of a Broad-Spectrum Partially Automated Adverse Event Surveillance System: A Potential Tool for Patient Safety Improvement in Hospitals With Limited Resources.

PubMed

Saikali, Melody; Tanios, Alain; Saab, Antoine

2017-11-21

The aim of the study was to evaluate the sensitivity and resource efficiency of a partially automated adverse event (AE) surveillance system for routine patient safety efforts in hospitals with limited resources. Twenty-eight automated triggers from the hospital information system's clinical and administrative databases identified cases that were then filtered by exclusion criteria per trigger and then reviewed by an interdisciplinary team. The system, developed and implemented using in-house resources, was applied for 45 days of surveillance, for all hospital inpatient admissions (N = 1107). Each trigger was evaluated for its positive predictive value (PPV). Furthermore, the sensitivity of the surveillance system (overall and by AE category) was estimated relative to incidence ranges in the literature. The surveillance system identified a total of 123 AEs among 283 reviewed medical records, yielding an overall PPV of 52%. The tool showed variable levels of sensitivity across and within AE categories when compared with the literature, with a relatively low overall sensitivity estimated between 21% and 44%. Adverse events were detected in 23 of the 36 AE categories defined by an established harm classification system. Furthermore, none of the detected AEs were voluntarily reported. The surveillance system showed variable sensitivity levels across a broad range of AE categories with an acceptable PPV, overcoming certain limitations associated with other harm detection methods. The number of cases captured was substantial, and none had been previously detected or voluntarily reported. For hospitals with limited resources, this methodology provides valuable safety information from which interventions for quality improvement can be formulated.

In vitro approaches to screening and prioritization of chemicals for potential developmental neurotoxicity

EPA Science Inventory

Characterization of the potential adverse effects is lacking for tens of thousands of chemicals that are present in the environment, and characterization of developmental neurotoxicity (DNT) hazard lags behind that of other adverse outcomes (e.g. hepatotoxicity). This is due in p...

In vitro approaches to screening and prioritizing chemicals for potential developmental neurotoxicity

EPA Science Inventory

Characterization of the potential adverse effects is lacking for tens of thousands of chemicals that are present in the environment, and characterization of developmental neurotoxicity (DNT) hazard lags behind that of other adverse outcomes (e.g. hepatotoxicity). This is due in p...

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.

Selective TNF-α inhibitor-induced injection site reactions.

PubMed

Murdaca, Giuseppe; Spanò, Francesca; Puppo, Francesco

2013-03-01

During the last decade, many new biological immune modulators entered the market as new therapeutic principles. TNF-α is a pro-inflammatory cytokine known to a have a key role in the pathogenic mechanisms of various immune-mediated or inflammatory diseases. TNF-α blockers have demonstrated efficacy in large, randomized controlled clinical trials either as monotherapy or in combination with other anti-inflammatory or disease-modifying anti-rheumatic drugs. Although generally well tolerated and safe, potential adverse events may be associated with TNF-α inhibitor treatment. The authors will briefly review the potential adverse drug reactions and the immunological mechanisms of injection site reactions (ISRs) in patients treated with etanercept and adalimumab. Patients treated with TNF-α inhibitors can develop ISR around the sites of injections. 'Type IV delayed type reaction' or 'recall ISRs'. Eosinophilic cellulitis or 'Wells syndrome', 'type III' and 'type I' reactions are reported. Long-term studies are necessary to determine the durability of response and the real risk of ISRs with golimumab and certolizumab pegol. Further studies are also necessary to evaluate the immunogenicity of these drugs.

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

PubMed

Singare, Pravin U

2015-11-15

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

Quality of life in children with adverse drug reactions: a narrative and systematic review.

PubMed

Del Pozzo-Magaña, Blanca R; Rieder, Michael J; Lazo-Langner, Alejandro

2015-10-01

Adverse drug reactions are a common problem affecting adults and children. The economic impact of the adverse drug reactions has been widely evaluated; however, studies of the impact on the quality of life of children with adverse drug reactions are scarce. The aim was to evaluate studies assessing the health-related quality of life of children with adverse drug reactions. We conducted a systematic review that included the following electronic databases: MEDLINE, EMBASE and the Cochrane Library (including the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, the Cochrane Controlled Trials Register and the Health Technology Assessment Databases). Nine studies were included. Four of the studies were conducted in children with epilepsy; the rest of them involved children with chronic viral hepatitis, Crohn's disease, paediatric cancer and multiple adverse drug reactions compared with healthy children. Based on their findings, authors of all studies concluded that adverse drug reactions had a negative impact on the quality of life of children. No meta-analysis was conducted given the heterogeneous nature of the studies. To date, there is no specific instrument that measures quality of life of children with adverse drug reactions, and the information available is poor and variable. In general, adverse drug reactions have a negative impact on the quality of life of affected children. For those interested in this area, more work needs to be done to improve tools that help to evaluate efficiently the health-related quality of life of children with adverse drug reactions and chronic diseases. © 2014 The British Pharmacological Society.

Quality of life in children with adverse drug reactions: a narrative and systematic review

PubMed Central

Del Pozzo-Magaña, Blanca R; Rieder, Michael J; Lazo-Langner, Alejandro

2015-01-01

Aims Adverse drug reactions are a common problem affecting adults and children. The economic impact of the adverse drug reactions has been widely evaluated; however, studies of the impact on the quality of life of children with adverse drug reactions are scarce. The aim was to evaluate studies assessing the health-related quality of life of children with adverse drug reactions. Methods We conducted a systematic review that included the following electronic databases: MEDLINE, EMBASE and the Cochrane Library (including the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, the Cochrane Controlled Trials Register and the Health Technology Assessment Databases). Results Nine studies were included. Four of the studies were conducted in children with epilepsy; the rest of them involved children with chronic viral hepatitis, Crohn’s disease, paediatric cancer and multiple adverse drug reactions compared with healthy children. Based on their findings, authors of all studies concluded that adverse drug reactions had a negative impact on the quality of life of children. No meta-analysis was conducted given the heterogeneous nature of the studies. Conclusions To date, there is no specific instrument that measures quality of life of children with adverse drug reactions, and the information available is poor and variable. In general, adverse drug reactions have a negative impact on the quality of life of affected children. For those interested in this area, more work needs to be done to improve tools that help to evaluate efficiently the health-related quality of life of children with adverse drug reactions and chronic diseases. PMID:24833305

Evaluation of Neurophysiologic and Systematic Changes during Aeromedical Evacuation and en Route Care of Combat Casualties in a Swine Polytrauma

DTIC Science & Technology

2017-02-01

ambient conditions such as cabin pressure and temperature could potentially have detrimental effects on the already vulnerable brain. There is evidence...long-range aero-medical evacuation has adverse effects on brain blood flow and tissue oxygenation , as well as lung function in swine models of...differences in partial pressure of arterial oxygen or oxygen delivery, extraction and consumption data. This suggests that in this particular model

Pharmacological evaluation of aqueous extract of Althaea officinalis flower grown in Lebanon.

PubMed

Hage-Sleiman, Rouba; Mroueh, Mohamad; Daher, Costantine F

2011-03-01

Althaea officinalis Linn. (Malvaideae) flower is commonly used in folk medicine in Lebanon and neighboring countries. Although most of the studies have been conducted on the mucilage-rich roots, little is known about the flower. This study investigates the potential role of aqueous extract of Althaea officinalis flower in lipemia, gastric ulcer, inflammation, and platelet aggregation using the rat model. Blood lipid profile and liver function were assessed after 1 month of extract intake via drinking water. Anti-inflammatory activity was tested against acute and chronic inflammation induced by carrageenan and formalin, respectively. Antiulcer activity was evaluated using ethanol-induced gastric ulcer. Antiplatelet activity was investigated in vitro using the adenosine 5'-diphosphate (ADP)-induced platelet aggregation bioassay. The 50 mg/kg body weight dose resulted in significant increase in serum HDL cholesterol level with no effects on stool cholesterol and triacylglycerol. Increasing the dose to 500 mg/kg body weight caused a significant decrease in stool water content. No adverse effect on liver enzymes was observed. Significant anti-inflammatory (acute and chronic inflammation) and antiulcerogenic activities were observed at all used doses (50, 100, and 250 mg/kg body). Time-dependent inhibition of platelet aggregation was demonstrated at 500 µg/ml concentration. The aqueous extract of Althaea officinalis flower demonstrated potential benefits in lipemia, inflammation, gastric ulcer, and platelet aggregation with no visible adverse effect.

Nanotoxicity: a growing need for study in the endocrine system.

PubMed

Lu, Xuefei; Liu, Ying; Kong, Xiangjun; Lobie, Peter E; Chen, Chunying; Zhu, Tao

2013-05-27

Nanomaterials (NMs) are engineered for commercial purposes such as semiconductors, building materials, cosmetics, and drug carriers, while natural nanoparticles (NPs) already exist in the environment. Due to their unique physicochemical properties, they may interact actively with biological systems. Some of these interactions might be detrimental to human health, and therefore studies on the potential 'nanotoxicity' of these materials in different organ systems are warranted. The purpose of developing the concept of nanotoxicity is to recognize and evaluate the hazards and risks of NMs and evaluate safety. This review will summarize and discuss recent reports derived from cell lines or animal models concerning the effects of NMs on, and their application in, the endocrine system of mammalian and other species. It will present an update on current studies of the effects of some typical NMs-such as metal-based NMs, carbon-based NMs, and dendrimers-on endocrine functions, in which some effects are adverse or unwanted and others are favorable or intended. Disruption of endocrine function is associated with adverse health outcomes including reproductive failure, metabolic syndrome, and some types of cancer. Further investigations are therefore required to obtain a thorough understanding of any potential risk of pathological endocrine disruption from products containing NMs. This review aims to provide impetus for further studies on the interactions of NMs with endocrine functions. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

IRIS Toxicological Review of Tetrahydrofuran (THF) ...

EPA Pesticide Factsheets

EPA is releasing the draft report, Toxicological Review of Tetrahydrofuran, that was distributed to Federal agencies and White House Offices for comment during the Science Discussion step of the IRIS Assessment Development Process. Comments received from other Federal agencies and White House Offices are provided below with external peer review panel comments. EPA is undertaking an Integrated Risk Information System (IRIS) health assessment for tetrahydrofuran. IRIS is an EPA database containing Agency scientific positions on potential adverse human health effects that may result from chronic (or lifetime) exposure to chemicals in the environment. IRIS contains chemical-specific summaries of qualitative and quantitative health information in support of two steps of the risk assessment paradigm, i.e., hazard identification and dose-response evaluation. IRIS assessments are used in combination with specific situational exposure assessment information to evaluate potential public health risk associated with environmental contaminants.

Energy Drink Consumption in Europe: A Review of the Risks, Adverse Health Effects, and Policy Options to Respond

PubMed Central

Breda, João Joaquim; Whiting, Stephen Hugh; Encarnação, Ricardo; Norberg, Stina; Jones, Rebecca; Reinap, Marge; Jewell, Jo

2014-01-01

With the worldwide consumption of energy drinks increasing in recent years, concerns have been raised both in the scientific community and among the general public about the health effects of these products. Recent studies provide data on consumption patterns in Europe; however, more research is needed to determine the potential for adverse health effects related to the increasing consumption of energy drinks, particularly among young people. A review of the literature was conducted to identify published articles that examined the health risks, consequences, and policies related to energy drink consumption. The health risks associated with energy drink consumption are primarily related to their caffeine content, but more research is needed that evaluates the long-term effects of consuming common energy drink ingredients. The evidence indicating adverse health effects due to the consumption of energy drinks with alcohol is growing. The risks of heavy consumption of energy drinks among young people have largely gone unaddressed and are poised to become a significant public health problem in the future. PMID:25360435

Recent Updates on the Systemic and Local Safety of Intranasal Steroids.

PubMed

Jang, Tae Young; Kim, Young Hyo

2016-01-01

Allergic rhinitis is a global health problem, and its prevalence rate and socioeconomic burden continue to increase. Intranasal steroid (INS) is the first treatment choice in the majority of patients, because of its ability to effectively control allergic symptoms. However, patients and clinicians are concerned about the potential adverse effects of prolonged INS use. We performed to review for evaluating systemic and local safety of INS use, by searching MEDLINE, EMBASE, and Cochrane Library database for identification of relevant articles. In the present study, the systemic bioavailabilities of several commercially available INSs were researched, and then systemic safeties were reviewed with focus on suppression of the hypothalamus-pituitary-adrenal axis and their effects on pediatric growth. In addition, local adverse effects, such as, epistaxis and nasal septal perforation, were investigated. Finally, the authors proposed some techniques in order to avoid these complications. INSs offer a safe, effective means of treating allergic rhinitis in the short- and long-term with no or minimal adverse systemic and local effects. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Energy drink consumption in europe: a review of the risks, adverse health effects, and policy options to respond.

PubMed

Breda, João Joaquim; Whiting, Stephen Hugh; Encarnação, Ricardo; Norberg, Stina; Jones, Rebecca; Reinap, Marge; Jewell, Jo

2014-01-01

With the worldwide consumption of energy drinks increasing in recent years, concerns have been raised both in the scientific community and among the general public about the health effects of these products. Recent studies provide data on consumption patterns in Europe; however, more research is needed to determine the potential for adverse health effects related to the increasing consumption of energy drinks, particularly among young people. A review of the literature was conducted to identify published articles that examined the health risks, consequences, and policies related to energy drink consumption. The health risks associated with energy drink consumption are primarily related to their caffeine content, but more research is needed that evaluates the long-term effects of consuming common energy drink ingredients. The evidence indicating adverse health effects due to the consumption of energy drinks with alcohol is growing. The risks of heavy consumption of energy drinks among young people have largely gone unaddressed and are poised to become a significant public health problem in the future.

[BACE1 inhibitors for the treatment of Alzheimer disease].

PubMed

Tomita, Taisuke

2016-03-01

β-Site amyloid precursor protein cleaving enzyme 1 (BACEl) is the enzyme required for the production of the amyloid-β peptide(Aβ), which is associated with Alzheimer disease (AD). BACEl has emerged as a prime molecular target for reducing the brain Aβ levels. Recently, several BACEl inhibitors have been developed in clinical trials to test the efficacy in AD patients and individuals with prodromal AD. However, identification of BACE1 substrates and phenotypes of Bace1 knockout mice have raised concerns regarding potential mechanism-based adverse effects. This review summarizes the current status of the development of BACE1 inhibitors and the evaluation of their therapeutic potential against AD.

Evidence Does Not Support Clinical Screening of Literacy

PubMed Central

Wolf, Michael S.

2007-01-01

Limited health literacy is a significant risk factor for adverse health outcomes. Despite controversy, many health care professionals have called for routine clinical screening of patients’ literacy skills. Whereas brief literacy screening tools exist that with further evaluation could potentially be used to detect limited literacy in clinical settings, no screening program for limited literacy has been shown to be effective. Yet there is a noted potential for harm, in the form of shame and alienation, which might be induced through clinical screening. There is fair evidence to suggest that possible harm outweighs any current benefits; therefore, clinical screening for literacy should not be recommended at this time. PMID:17992564

Dietary supplements: physician knowledge and adverse event reporting.

PubMed

Cellini, Matthew; Attipoe, Selasi; Seales, Paul; Gray, Robert; Ward, Andrew; Stephens, Mark; Deuster, Patricia A

2013-01-01

Dietary supplement (DS) use among US military personnel is widespread. Many consume several different DS with multiple ingredients one or more times each week, representing a potential public health concern. The overall purpose of the study was to assess the knowledge and behaviors of health professionals and physicians regarding patterns of DS use and possible adverse events (AE) associated with DS use. We also determined how providers address the issue of DS with patients and evaluated provider knowledge regarding reporting systems. Two prospective, cross-sectional, web-based questionnaires were administered. First, health care providers who accessed the Natural Medicines Comprehensive Database to gather evidenced-based information on DS and herbal products were queried. Second, physicians who had graduated from the Uniformed Services University were sent a web-based questionnaire regarding DS knowledge, AE knowledge and reporting, and communication with patients about DS. The frequencies of responses were evaluated. Although 60% of the military physicians who responded to the questionnaires believed they had observed AE in association with a DS, only 18% actually reported them. Three of four physician respondents (approximately 73%) did not know how or where to report AE associated with DS. The majority of physicians (66%) routinely asked most of their patients about DS use, and 65% did not have a reliable source of information for herbal and DS products. Information gaps in DS information and AE reporting were identified. A centralized AE reporting system could serve to identify potentially harmful DS for further evaluation. Health professionals need to remain vigilant for AE associated with DS use and better informed on how to report these events.

Nursing Workload as a Risk Factor for Healthcare Associated Infections in ICU: A Prospective Study

PubMed Central

Daud-Gallotti, Renata M.; Costa, Silvia F.; Guimarães, Thais; Padilha, Katia Grillo; Inoue, Evelize Naomi; Vasconcelos, Tiago Nery; da Silva Cunha Rodrigues, Fernanda; Barbosa, Edizângela Vasconcelos; Figueiredo, Walquíria Barcelos; Levin, Anna S.

2012-01-01

Introduction Nurse understaffing is frequently hypothesized as a potential risk factor for healthcare-associated infections (HAI). This study aimed to evaluate the role of nursing workload in the occurrence of HAI, using Nursing Activities Score (NAS). Methods This prospective cohort study enrolled all patients admitted to 3 Medical ICUs and one step-down unit during 3 months (2009). Patients were followed-up until HAI, discharge or death. Information was obtained from direct daily observation of medical and nursing rounds, chart review and monitoring of laboratory system. Nursing workload was determined using NAS. Non-compliance to the nurses’ patient care plans (NPC) was identified. Demographic data, clinical severity, invasive procedures, hospital interventions, and the occurrence of other adverse events were also recorded. Patients who developed HAI were compared with those who did not. Results 195 patients were included and 43 (22%) developed HAI: 16 pneumonia, 12 urinary-tract, 8 bloodstream, 2 surgical site, 2 other respiratory infections and 3 other. Average NAS and average proportion of non compliance with NPC were significantly higher in HAI patients. They were also more likely to suffer other adverse events. Only excessive nursing workload (OR: 11.41; p: 0.019) and severity of patient’s clinical condition (OR: 1.13; p: 0.015) remained as risk factors to HAI. Conclusions Excessive nursing workload was the main risk factor for HAI, when evaluated together with other invasive devices except mechanical ventilation. To our knowledge, this study is the first to evaluate prospectively the nursing workload as a potential risk factor for HAI, using NAS. PMID:23300645

NTP-CERHR monograph on the potential human reproductive and developmental effects of hydroxyurea.

PubMed

2008-10-01

The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for hydroxyurea to cause adverse effects on reproduction and development in humans. Hydroxyurea is a drug used to treat cancer, sickle cell disease, and thalassemia. It is the only treatment for sickle cell disease in children, aside from blood transfusion and, in severe cases, hematopoietic stem cell transplantation. Hydroxyurea is FDA-approved for use in adults with sickle cell anemia to reduce the frequency of painful crises and the need for blood transfusions. Hydroxyurea may be given to children and adults with sickle cell disease for an extended period of time or for repeated cycles of therapy. Treatment with hydroxyurea is associated with known side effects such as cytotoxicity and myelosuppression, and hydroxyurea is genotoxic (can damage DNA). CERHR selected hydroxyurea for evaluation because of: its increasing use for treatment of sickle cell disease in children and adults, knowledge that it inhibits DNA synthesis and is cytotoxic, and published evidence of reproductive and developmental toxicity in rodents. The results of this evaluation are published in the NTP-CERHR Monograph on Hydroxyurea, which includes the NTP Brief and Expert Panel Report on the Reproductive and Developmental Toxicity of Hydroxyurea. Additional information related to the evaluation process, including public comments received on the draft NTP Brief and the final expert panel report, are available on the CERHR website (http:// cerhr.niehs.nih.gov/). See hydroxyurea under "CERHR Chemicals" on the homepage or go directly to http://cerhr.niehs.nih.gov/chemicals/hydroxyurea/hydroxyurea-eval.html). The NTP reached the following conclusions on the possible effects of exposure to hydroxyurea on human reproduction or development. The possible levels of concern, from lowest to highest, are negligible concern, minimal concern, some concern, concern, and serious concern. The NTP expresses serious concern that exposure of men to therapeutic doses of hydroxyurea may adversely affect sperm production. This level of concern is for all males who have reached puberty. The NTP concurs with the Expert Panel that there is concern that exposure of pregnant women to hydroxyurea may result in birth defects, abnormalities of fetal growth, or abnormal postnatal development in offspring. The NTP concurs with the Expert Panel that there is minimal concern that exposure of children to therapeutic doses of hydroxyurea at 5 -15 years of age will adversely affect growth. NTP will transmit the NTP-CERHR Monograph on the Potential Human Reproductive and Developmental Effects of Hydroxyurea to federal and state agencies, interested parties, and the public and make it available in electronic PDF format on the CERHR web site (http://cerhr niehs nih gov) and in printed text or CD from CERHR.

Evaluation of normalization of cerebro-placental ratio as a potential predictor for adverse outcome in SGA fetuses.

PubMed

Monteith, Cathy; Flood, Karen; Mullers, Sieglinde; Unterscheider, Julia; Breathnach, Fionnuala; Daly, Sean; Geary, Michael P; Kennelly, Mairead M; McAuliffe, Fionnuala M; O'Donoghue, Keelin; Hunter, Alison; Morrison, John J; Burke, Gerald; Dicker, Patrick; Tully, Elizabeth C; Malone, Fergal D

2017-03-01

Intrauterine growth restriction accounts for a significant proportion of perinatal morbidity and mortality currently encountered in obstetric practice. The primary goal of antenatal care is the early recognition of such conditions to allow treatment and optimization of both maternal and fetal outcomes. Management of pregnancies complicated by intrauterine growth restriction remains one of the greatest challenges in obstetrics. Frequently, however, clinical evidence of underlying uteroplacental dysfunction may only emerge at a late stage in the disease process. With advanced disease the only therapeutic intervention is delivery of the fetus and placenta. The cerebroplacental ratio is gaining much interest as a useful tool in differentiating the at-risk fetus in both intrauterine growth restriction and the appropriate-for-gestational-age setting. The cerebroplacental ratio quantifies the redistribution of the cardiac output resulting in a brain-sparing effect. The Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction group previously demonstrated that the presence of a brain-sparing effect is significantly associated with an adverse perinatal outcome in the intrauterine growth restriction cohort. The aim of the Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction study was to evaluate the optimal management of fetuses with an estimated fetal weight <10th centile. The objective of this secondary analysis was to evaluate if normalizing cerebroplacental ratio predicts adverse perinatal outcome. In all, 1116 consecutive singleton pregnancies with intrauterine growth restriction completed the study protocol over 2 years at 7 centers, undergoing serial sonographic evaluation and multivessel Doppler measurement. Cerebroplacental ratio was calculated using the pulsatility and resistance indices of the middle cerebral and umbilical artery. Abnormal cerebroplacental ratio was defined as <1.0. Adverse perinatal outcome was defined as a composite of intraventricular hemorrhage, periventricular leukomalacia, hypoxic ischemic encephalopathy, necrotizing enterocolitis, bronchopulmonary dysplasia, sepsis, and death. Data for cerebroplacental ratio calculation were available in 881 cases, with a mean gestational age of 33 (interquartile range, 28.7-35.9) weeks. Of the 87 cases of abnormal serial cerebroplacental ratio with an initial value <1.0, 52% (n = 45) of cases remained abnormal and 22% of these (n = 10) had an adverse perinatal outcome. The remaining 48% (n = 42) demonstrated normalizing cerebroplacental ratio on serial sonography, and 5% of these (n = 2) had an adverse perinatal outcome. Mean gestation at delivery was 33.4 weeks (n = 45) in the continuing abnormal cerebroplacental ratio group and 36.5 weeks (n = 42) in the normalizing cerebroplacental ratio group (P value <.001). The Prospective Observational Trial to Optimize Pediatric Health in Intrauterine Growth Restriction group previously demonstrated that the presence of a brain-sparing effect was significantly associated with an adverse perinatal outcome in our intrauterine growth restriction cohort. It was hypothesized that a normalizing cerebroplacental ratio would be a further predictor of an adverse outcome due to the loss of this compensatory mechanism. However, in this subanalysis we did not demonstrate an additional poor prognostic effect when the cerebroplacental ratio value returned to a value >1.0. Overall, this secondary analysis demonstrated the importance of a serial abnormal cerebroplacental ratio value of <1 within the <34 weeks' gestation population. Contrary to our proposed hypothesis, we recognize that reversion of an abnormal cerebroplacental ratio to a normal ratio is not associated with a heightened degree of adverse perinatal outcome. Copyright © 2016 Elsevier Inc. All rights reserved.

NTP-CERHR monograph on the potential human reproductive and developmental effects of di (2-ethylhexyl) phthalate (DEHP).

PubMed

Shelby, Michael D

2006-11-01

The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an updated evaluation of the potential for DEHP to cause adverse effects on reproduction and development in humans. The first CERHR expert panel evaluation of DEHP was completed in 2000 by the Phthalates Expert Panel. CERHR selected DEHP for an updated evaluation because of: (1) widespread human exposure, (2) public and government interest in adverse health effects, (3) recently available human exposure studies, and (4) the large number of relevant toxicity papers published since the earlier evaluation. DEHP (CAS RN: 117-81-7) is a high production volume chemical used as a plasticizer of polyvinyl chloride in the manufacture of a wide variety of consumer goods, such as building products, car products, clothing, food packaging, children's products (but not in toys intended for mouthing), and in medical devices made of polyvinyl chloride. The public can be exposed to DEHP by ingesting food, drink or dust that has been in contact with DEHP-containing materials, by inhaling contaminated air or dust, or by undergoing a medical procedure that uses polyvinyl chloride medical tubing or storage bags. It is estimated that the general population of the United States is exposed to DEHP levels ranging from 1 to 30 microg/kg bw/day (micrograms per kilogram body weight per day). The results of this DEHP update evaluation are published in an NTP-CERHR monograph that includes: (1) the NTP Brief, (2) the Expert Panel Update on the Reproductive and Developmental Toxicity of DEHP, and (3) public comments on the expert panel report. The NTP reached the following conclusions on the possible effects of exposure to DEHP on human development and reproduction. Note that the possible levels of concern, from lowest to highest, are negligible concern, minimal concern, some concern, concern, and serious concern. There is serious concern that certain intensive medical treatments of male infants may result in DEHP exposure levels that adversely affect development of the male reproductive tract. DEHP exposure from medical procedures in infants was estimated to be as high as 6000 microg/kg bw/day. There is concern for adverse effects on development of the reproductive tract in male offspring of pregnant and breast feeding women undergoing certain medical procedures that may result in exposure to high levels of DEHP. There is concern for effects of DEHP exposure on development of the male reproductive tract for infants less than one year old. Diet, mouthing of DEHP-containing objects, and certain medical treatments may lead to DEHP exposures that are higher than those experienced by the general population. There is some concern for effects of DEHP exposure on development of the reproductive tract of male children older than one year. As in infants, exposures of children to DEHP may be higher than in the general population. There is some concern for adverse effects of DEHP exposure on development of the male reproductive tract in male offspring of pregnant women not medically exposed to DEHP. Although DEHP exposures are assumed to be the same as for the general population, the developing male reproductive tract is sensitive to the adverse effects of DEHP. There is minimal concern for reproductive toxicity in adults exposed to DEHP at 1 - 30 microg/kg bw/day. This level of concern is not altered for adults medically exposed to DEHP. NTP will transmit the NTP-CERHR Monograph on DEHP to federal and state agencies, interested parties, and the public and it will be available in electronic PDF format on the CERHR web site http://cerhr.niehs.nih.gov and in printed text or CD-ROM from the CERHR.

[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.

Clinical review: insulin pump-associated adverse events in adults and children.

PubMed

Ross, P L; Milburn, J; Reith, D M; Wiltshire, E; Wheeler, B J

2015-12-01

Insulin pumps are a vital and rapidly developing tool in the treatment of type 1 diabetes mellitus in both adults and children. Many studies have highlighted outcomes and assessed their potential advantages, but much of the data on adverse outcomes are limited and often based on outdated technology. We aimed to review and summarize the available literature on insulin pump-associated adverse events in adults and children. A literature search was undertaken using PubMed, EMBASE, and the Cochrane library. Articles were then screened by title, followed by abstract, and full text as needed. A by-hand search of reference lists in identified papers was also utilised. All searches were limited to English language material, but no time limits were used. Current and past literature regarding insulin pump-associated adverse events is discussed, including potential metabolic and non-metabolic adverse events, in particular: pump malfunction; infusion set/site issues; and cutaneous problems. We show that even with modern technology, adverse events are common, occurring in over 40 % of users per year, with a minority, particularly in children, requiring hospital management. Hyperglycaemia and ketosis are now the most common consequences of adverse events and are usually associated with infusion set failure. This differs from older technology where infected infusion sites predominated. This timely review covers all potential insulin pump-associated adverse events, including their incidence, features, impacts, and contributory factors such as the pump user. The importance of ongoing anticipatory education and support for patients and families using this intensive insulin technology is highlighted, which if done well should improve the overall experience of pump therapy for users, and hopefully reduce the incidence and impact of severe adverse events.

Automatic Extraction of Drug Adverse Effects from Product Characteristics (SPCs): A Text Versus Table Comparison.

PubMed

Lamy, Jean-Baptiste; Ugon, Adrien; Berthelot, Hélène

2016-01-01

Potential adverse effects (AEs) of drugs are described in their summary of product characteristics (SPCs), a textual document. Automatic extraction of AEs from SPCs is useful for detecting AEs and for building drug databases. However, this task is difficult because each AE is associated with a frequency that must be extracted and the presentation of AEs in SPCs is heterogeneous, consisting of plain text and tables in many different formats. We propose a taxonomy for the presentation of AEs in SPCs. We set up natural language processing (NLP) and table parsing methods for extracting AEs from texts and tables of any format, and evaluate them on 10 SPCs. Automatic extraction performed better on tables than on texts. Tables should be recommended for the presentation of the AEs section of the SPCs.

New developments in the management of periocular capillary hemangioma in children.

PubMed

Ni, Nina; Wagner, Rudolph S; Langer, Paul; Guo, Suqin

2011-01-01

The authors describe the theories of pathogenesis for capillary hemangioma and discuss the benefits and side effects of current treatment options, such as systemic and intralesional corticosteroids, laser therapy, and surgical excision. They also evaluate the recent systemic and topical applications of beta-blockers to treat infantile hemangioma. Although no major adverse events from beta-blocker treatment have been reported, the incidence of potential side effects such as bronchospasm, hypoglycemia, heart block, bradycardia, and congestive heart failure is unknown due to the novelty of the treatment. It has been postulated that topical application for localized superficial tumor may reduce systemic effects. Further research is necessary to compare the effectiveness of different treatments and to find the optimal dosing and delivery methods to minimize adverse effects in the treatment of this disorder. Copyright 2011, SLACK Incorporated.

Efficacy and Biological Correlates of Response in a Phase 2 Study of Venetoclax Monotherapy in Patients with Acute Myelogenous Leukemia

PubMed Central

Konopleva, Marina; Pollyea, Daniel A.; Potluri, Jalaja; Chyla, Brenda; Hogdal, Leah; Busman, Todd; McKeegan, Evelyn; Salem, Ahmed Hamed; Zhu, Ming; Ricker, Justin L.; Blum, William; DiNardo, Courtney D.; Kadia, Tapan; Dunbar, Martin; Kirby, Rachel; Falotico, Nancy; Leverson, Joel; Humerickhouse, Rod; Mabry, Mack; Stone, Richard; Kantarjian, Hagop; Letai, Anthony

2017-01-01

We present a phase 2, single-arm study evaluating 800 mg daily venetoclax, a highly selective, oral small-molecule B-cell leukemia/lymphoma-2 (BCL-2) inhibitor in patients with high-risk relapsed/refractory acute myelogenous leukemia (AML) or unfit for intensive chemotherapy. Responses were evaluated following revised International Working Group (IWG) criteria. The overall response rate was 19%; an additional 19% of patients demonstrated anti-leukemic activity not meeting IWG criteria (partial bone marrow response and incomplete hematologic recovery). Twelve (38%) patients had isocitrate dehydrogenase 1/2 mutations, of whom 4 (33%) achieved complete response/complete response with incomplete blood count recovery. Six (19%) patients had BCL-2–sensitive protein index at screening, which correlated with time on study. BH3 profiling was consistent with on-target BCL-2 inhibition and identified potential resistance mechanisms. Common adverse events included nausea, diarrhea and vomiting (all grades), and febrile neutropenia and hypokalemia (grade 3/4). Venetoclax demonstrated activity and acceptable tolerability in patients with AML and adverse features. PMID:27520294

Oral contraceptives in polycystic ovary syndrome: risk-benefit assessment.

PubMed

Yildiz, Bulent O

2008-01-01

Combined oral contraceptive pills (OCPs) have been a key component of the chronic treatment of polycystic ovary syndrome (PCOS) by improving androgen excess and regulating menstrual cycles. Earlier epidemiologic studies with second- and third-generation OCPs in the general population have raised important questions regarding long-term cardiometabolic effects of these agents. In PCOS, there are only a few short-term studies with contradictory results evaluating potential adverse effects of OCPs on cardiovascular risk factors and glucose homeostasis. These studies included a small number of participants and did not take into account several confounding factors that might influence the outcome. Nevertheless, limited available data support the benefits of long-term OCP use in PCOS. By contrast, solid evidence for cardiometabolic adverse outcome with the use of these agents, especially with newer OCPs containing antiandrogenic progestins, is lacking. More studies are needed to resolve controversies regarding the safety of long-term OCP use in PCOS. Meanwhile, assessment of each PCOS patient's personal cardiometabolic risk profile should be an essential component of the evaluation before prescribing OCPs and also during follow-up.

A Comparative Analysis of Drug-Induced Hepatotoxicity in Clinically Relevant Situations

PubMed Central

Thiel, Christoph; Cordes, Henrik; Fabbri, Lorenzo; Aschmann, Hélène Eloise; Baier, Vanessa; Atkinson, Francis; Blank, Lars Mathias; Kuepfer, Lars

2017-01-01

Drug-induced toxicity is a significant problem in clinical care. A key problem here is a general understanding of the molecular mechanisms accompanying the transition from desired drug effects to adverse events following administration of either therapeutic or toxic doses, in particular within a patient context. Here, a comparative toxicity analysis was performed for fifteen hepatotoxic drugs by evaluating toxic changes reflecting the transition from therapeutic drug responses to toxic reactions at the cellular level. By use of physiologically-based pharmacokinetic modeling, in vitro toxicity data were first contextualized to quantitatively describe time-resolved drug responses within a patient context. Comparatively studying toxic changes across the considered hepatotoxicants allowed the identification of subsets of drugs sharing similar perturbations on key cellular processes, functional classes of genes, and individual genes. The identified subsets of drugs were next analyzed with regard to drug-related characteristics and their physicochemical properties. Toxic changes were finally evaluated to predict both molecular biomarkers and potential drug-drug interactions. The results may facilitate the early diagnosis of adverse drug events in clinical application. PMID:28151932

Short- and long-term evaluation of cognitive functions after electroconvulsive therapy in a Japanese population.

PubMed

Takagi, Shunsuke; Takeuchi, Takashi; Yamamoto, Naoki; Fujita, Munehisa; Furuta, Ko; Ishikawa, Hiroyo; Motohashi, Nobutaka; Nishikawa, Toru

2018-02-01

While electroconvulsive therapy (ECT) is a well-established, safe, and effective treatment for mental illnesses, the potential for adverse effects on cognitive functions remains controversial. We aimed to evaluate multiple cognitive functions in different time periods before and after ECT in a Japanese population. A battery of five neurocognitive tests was administered to patients who underwent a course of ECT treatment at three time points: before, immediately after, and 4 weeks after ECT. A transient but significant decline in letter fluency function was observed immediately after ECT, but had recovered well by 4 weeks. We also observed a significant improvement in the trail-making task at 4 weeks after ECT. In a Japanese population, adverse effects of ECT on verbal fluency function-related and other cognitive impairments were transient. Over the longer term, we detected significant improvements in the performance of tasks that presumably reflected information processing speed and executive functions. © 2017 The Authors. Psychiatry and Clinical Neurosciences © 2017 Japanese Society of Psychiatry and Neurology.

Cross-reactivity and masqueraders in seafood reactions.

PubMed

Banks, Taylor A; Gada, Satyen M

2013-01-01

Confounding variables play a significant role in many adverse seafood reactions and a clear understanding of these factors is important in properly characterizing reactions associated with potential masqueraders and mimics. Although the medical literature is replete with reviews of seafood hypersensitivity and reports of cross-reactive and newly characterized allergens, there has not been a recent effort to provide an updated overview of the several processes that may lead clinicians to draw incorrect conclusions in evaluating reported reactions to seafood. Ranging from seafood intoxications to other nonallergic or complex seafood reactions, these events can easily be misconstrued as representing a seafood IgE-mediated allergy. Among these are the more familiar topics of cross-reactivity and scombroid intoxication, and those with a still evolving understanding such as ciguatera fish poisoning and Anisakis reactions. This article seeks to provide an accessible but comprehensive summary of the relevant information surrounding these confounders in assessing adverse reactions to seafood. Such knowledge may be instrumental in unraveling complex or otherwise unclear presentations and aid clinicians in accurately evaluating and managing patients with reported seafood reactions.

Challenges in Coding Adverse Events in Clinical Trials: A Systematic Review

PubMed Central

Schroll, Jeppe Bennekou; Maund, Emma; Gøtzsche, Peter C.

2012-01-01

Background Misclassification of adverse events in clinical trials can sometimes have serious consequences. Therefore, each of the many steps involved, from a patient's adverse experience to presentation in tables in publications, should be as standardised as possible, minimising the scope for interpretation. Adverse events are categorised by a predefined dictionary, e.g. MedDRA, which is updated biannually with many new categories. The objective of this paper is to study interobserver variation and other challenges of coding. Methods Systematic review using PRISMA. We searched PubMed, EMBASE and The Cochrane Library. All studies were screened for eligibility by two authors. Results Our search returned 520 unique studies of which 12 were included. Only one study investigated interobserver variation. It reported that 12% of the codes were evaluated differently by two coders. Independent physicians found that 8% of all the codes deviated from the original description. Other studies found that product summaries could be greatly affected by the choice of dictionary. With the introduction of MedDRA, it seems to have become harder to identify adverse events statistically because each code is divided in subgroups. To account for this, lumping techniques have been developed but are rarely used, and guidance on when to use them is vague. An additional challenge is that adverse events are censored if they already occurred in the run-in period of a trial. As there are more than 26 ways of determining whether an event has already occurred, this can lead to bias, particularly because data analysis is rarely performed blindly. Conclusion There is a lack of evidence that coding of adverse events is a reliable, unbiased and reproducible process. The increase in categories has made detecting adverse events harder, potentially compromising safety. It is crucial that readers of medical publications are aware of these challenges. Comprehensive interobserver studies are needed. PMID:22911755

Biofeedback: Making the Science Real

PubMed Central

Baker, Robert A.; Newland, Richard F.; Bennetts, Jayme

2009-01-01

Abstract: Neurological deficits such as stroke and subtle psychological, cognitive, and behavioral changes are known risks associated with cardiac surgery. These altered neurologic outcomes have a significant impact on patients and their quality of life postoperatively. Perioperative events, such as cerebral embolism and decrease in cerebral oxygenation and hypoperfusion have been identified as factors causal in producing adverse neurologic outcomes. More importantly, a number of mechanisms related to operative techniques have been found to cause these adverse events. Identifying practices associated with adverse outcomes and implementing practice changes may benefit clinical outcomes for cardiac surgery patients. Standardizing techniques among clinicians will also achieve continuous quality improvement in the process of care. Optimal intra-operative management systems contribute significantly to ensuring good patient outcomes (i.e., avoiding neurological injury in patients which is an important cause of post-operative morbidity and mortality). Groom and colleagues (2004) have developed a system to obtain a thorough understanding and redesign of the process of care associated with cardiac surgery. They have developed a system that simultaneously measures some embolic activity, cerebral oxygen saturation, and physiologic parameters, as well as uses a video recording device during cardiac surgery. To date, the evaluation of this methodology in a rigorous, prospective manner has not been reported. Our aim is to conduct a randomised clinical trial to evaluate the influence of continuous quality improvement in cardiac surgery using biofeedback (i.e., real time information on physiologic functioning from an integrated monitoring system) to reduce the incidence of potentially adverse events during surgery. By achieving the outcomes of this project, we plan to be able to not only introduce change in our own practice, but provide a framework for other units to introduce change. PMID:20092086

Reproductive and Developmental Toxicity of Formaldehyde: A Systematic Review

PubMed Central

Duong, Anh; Steinmaus, Craig; McHale, Cliona M.; Vaughan, Charles P.; Zhang, Luoping

2011-01-01

Formaldehyde, the recently classified carcinogen and ubiquitous environmental contaminant, has long been suspected of causing adverse reproductive and developmental effects, but previous reviews were inconclusive, due in part, to limitations in the design of many of the human population studies. In the current review, we systematically evaluated evidence of an association between formaldehyde exposure and adverse reproductive and developmental effects, in human populations and in vivo animal studies, in the peer-reviewed literature. The mostly retrospective human studies provided evidence of an association of maternal exposure with adverse reproductive and developmental effects. Further assessment of this association by meta-analysis revealed an increased risk of spontaneous abortion (1.76, 95% CI 1.20–2.59, p=0.002) and of all adverse pregnancy outcomes combined (1.54, 95% CI 1.27–1.88, p<0.001), in formaldehyde-exposed women, although differential recall, selection bias, or confounding cannot be ruled out. Evaluation of the animal studies including all routes of exposure, doses and dosing regimens studied, suggested positive associations between formaldehyde exposure and reproductive toxicity, mostly in males. Potential mechanisms underlying formaldehyde-induced reproductive and developmental toxicities, including chromosome and DNA damage (genotoxicity), oxidative stress, altered level and/or function of enzymes, hormones and proteins, apoptosis, toxicogenomic and epigenomic effects (such as DNA methylation), were identified. To clarify these associations, well-designed molecular epidemiologic studies, that include quantitative exposure assessment and diminish confounding factors, should examine both reproductive and developmental outcomes associated with exposure in males and females. Together with mechanistic and animal studies, this will allow us to better understand the systemic effect of formaldehyde exposure. PMID:21787879

Choline supplementation in children with fetal alcohol spectrum disorders has high feasibility and tolerability.

PubMed

Wozniak, Jeffrey R; Fuglestad, Anita J; Eckerle, Judith K; Kroupina, Maria G; Miller, Neely C; Boys, Christopher J; Brearley, Ann M; Fink, Birgit A; Hoecker, Heather L; Zeisel, Steven H; Georgieff, Michael K

2013-11-01

There are no biological treatments for fetal alcohol spectrum disorders (FASDs), lifelong conditions associated with physical anomalies, brain damage, and neurocognitive abnormalities. In preclinical studies, choline partially ameliorates memory and learning deficits from prenatal alcohol exposure. This phase I pilot study evaluated the feasibility, tolerability, and potential adverse effects of choline supplementation in children with FASD. We hypothesized that choline would be well tolerated with minimal adverse events. The study design was a double-blind, randomized, placebo-controlled trial. Participants included 20 children aged 2.5 to 4.9 years with prenatal alcohol exposure and FASD diagnoses. Participants were randomly assigned to 500 mg choline or placebo daily for 9 months (10 active, 10 placebo). Primary outcome measures included feasibility, tolerability, adverse effects, and serum choline levels. Seventeen participants completed the study. Compliance was 82% to 87%, as evidenced by parent-completed log sheets and dose counts. Periodic 24-hour dietary recalls showed no evidence of dietary confounding. Adverse events were minimal and were equivalent in the active and placebo arms with the exception of fishy body odor, which occurred only in the active group. There were no serious adverse events to research participants. This phase I pilot study demonstrates that choline supplementation at 500 mg/d for 9 months in children aged 2 to 5 years is feasible and has high tolerability. Further examination of the efficacy of choline supplementation in FASD is currently underway. © 2013.

Choline supplementation in children with Fetal Alcohol Spectrum Disorders (FASD) has high feasibility and tolerability

PubMed Central

Wozniak, Jeffrey R.; Fuglestad, Anita J.; Eckerle, Judith K.; Kroupina, Maria G.; Miller, Neely C.; Boys, Christopher J.; Brearley, Ann M.; Fink, Birgit A.; Hoecker, Heather L.; Zeisel, Steven H.; Georgieff, Michael K.

2013-01-01

There are no biological treatments for fetal alcohol spectrum disorders (FASD), lifelong conditions associated with physical anomalies, brain damage, and neurocognitive abnormalities. In pre-clinical studies, choline partially ameliorates memory and learning deficits from prenatal alcohol exposure. This Phase I pilot study evaluated the feasibility, tolerability, and potential adverse effects of choline supplementation in children with FASD. We hypothesized that choline would be well-tolerated with minimal adverse events. The study design was a double-blind, randomized, placebo-controlled trial. Participants included 20 children, ages 2.5–4.9y, with prenatal alcohol exposure and FASD diagnoses. Participants were randomly assigned to 500 mg. choline or placebo daily for nine months (10 active; 10 placebo). Primary outcome measures included feasibility, tolerability, adverse effects, and serum choline levels. Seventeen participants completed the study. Compliance was 82–87% as evidenced by parent-completed logsheets and dose counts. Periodic 24-hour dietary recalls showed no evidence of dietary confounding. Adverse events were minimal and were equivalent in the active and placebo arms with the exception of fishy body odor, which occurred only in the active group. There were no serious adverse events to research participants. This Phase I pilot study demonstrates that choline supplementation at 500 mg per day for nine months in children ages 2–5 is feasible and has high tolerability. Further examination of the efficacy of choline supplementation in FASD is currently underway. PMID:24176229

Technology assessment of solar energy systems: Residential use of fuelwood in the Pacific Northwest

NASA Astrophysics Data System (ADS)

Petty, P. N.; Hopp, W. J.

1981-08-01

The evidence of impacts associated with the use of fuelwood for residential space heating in the region including the states of Washington, Oregon, and Idaho is identified and evaluated. The use of fuelwood for space heating was projected into the future, and then the potential size of the impacts that had been identified and estimated was evaluated. These projections are provided in five year increments beginning in 1980 and proceeding to the year 2000. Policy options are suggested which may mitigate the adverse impacts identified, while preserving the positive effect of reducing residential demand for energy derived from nonrenewable sources.

Adler's psychology (of use) today: personal history of traumatic life events as a self-handicapping strategy.

PubMed

DeGree, C E; Snyder, C R

1985-06-01

We investigated the hypothesis that the reporting of a history of traumatic life events may serve as a strategy to control attributions about performance in an evaluative setting (i.e., self-handicapping). Following from Alfred Adler's early theorization in the psychology of use, as well as more recent theory and research on self-handicapping, we predicted that individuals would emphasize the adversity of events and experiences in their background when an uncertain evaluation was expected and when a traumatic background would serve as a suitable excuse for potential failure. Results generally supported the hypothesized self-protective reporting of traumatic life events.

Nutrient- and non-nutrient-based natural health product (NHP) use in adults with mood disorders: prevalence, characteristics and potential for exposure to adverse events

PubMed Central

2013-01-01

Background To address knowledge gaps regarding natural health product (NHP) usage in mental health populations, we examined their use in adults with mood disorders, and explored the potential for adverse events. Methods Food and NHP intake was obtained from 97 adults with mood disorders. NHP data was used to compare prevalence with population norms (British Columbia Nutrition Survey; BCNS). Bivariate and regression analyses examined factors associated with NHP use. Assessment of potential adverse effects of NHP use was based on comparing nutrient intakes from food plus supplements with the Dietary Reference Intakes and by reviewing databases for reported adverse health effects. Results Two-thirds (66%; 95% CI 56 to 75) were taking at least one NHP; 58% (95% CI 47 to 68) were taking NHPs in combination with psychiatric medications. The proportion of each type of NHP used was generally higher than the BCNS (range of p’s < 0.05 to 0.0001). When intakes from food and NHP sources were combined, a small proportion exceeded any Lowest-Observed-Adverse-Effect-Levels: only for niacin (n = 17) and magnesium (n = 6), two nutrients for which the potential for adverse effects is minimal. Conversely, about 38% (95% CI 28 to 49) of the sample were taking a non-nutrient based NHP for which previous adverse events had been documented. Conclusions The prevalent use of NHPs in this population suggests that health care providers need to be knowledgeable about their characteristics. The efficacy and safety of NHPs in relation to mental health warrants further investigation. PMID:23570306

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

PubMed

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

2015-12-01

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

Moving Upstream: Evaluating Adverse Upstream Endpoints for Improved Risk Assessment and Decision-Making

EPA Science Inventory

Background: Assessing adverse effects from environmental chemical exposure is integral to public health policies. Toxicology assays identifying early biological changes from chemical exposure are increasing our ability to evaluate links between early biological disturbances and ...

Novel alginate biphasic scaffold for osteochondral regeneration: an in vivo evaluation in rabbit and sheep models.

PubMed

Filardo, Giuseppe; Perdisa, Francesco; Gelinsky, Michael; Despang, Florian; Fini, Milena; Marcacci, Maurilio; Parrilli, Anna Paola; Roffi, Alice; Salamanna, Francesca; Sartori, Maria; Schütz, Kathleen; Kon, Elizaveta

2018-05-26

Current therapeutic strategies for osteochondral restoration showed a limited regenerative potential. In fact, to promote the growth of articular cartilage and subchondral bone is a real challenge, due to the different functional and anatomical properties. To this purpose, alginate is a promising biomaterial for a scaffold-based approach, claiming optimal biocompatibility and good chondrogenic potential. A previously developed mineralized alginate scaffold was investigated in terms of the ability to support osteochondral regeneration both in a large and medium size animal model. The results were evaluated macroscopically and by microtomography, histology, histomorphometry, and immunohistochemical analysis. No evidence of adverse or inflammatory reactions was observed in both models, but limited subchondral bone formation was present, together with a slow scaffold resorption time.The implantation of this biphasic alginate scaffold provided partial osteochondral regeneration in the animal model. Further studies are needed to evaluate possible improvement in terms of osteochondral tissue regeneration for this biomaterial.

Environmental and workplace contamination in the semiconductor industry: implications for future health of the workforce and community.

PubMed Central

Edelman, P

1990-01-01

The semiconductor industry has been an enormous worldwide growth industry. At the heart of computer and other electronic technological advances, the environment in and around these manufacturing facilities has not been scrutinized to fully detail the health effects to the workers and the community from such exposures. Hazard identification in this industry leads to the conclusion that there are many sources of potential exposure to chemicals including arsenic, solvents, photoactive polymers and other materials. As the size of the semiconductor work force expands, the potential for adverse health effects, ranging from transient irritant symptoms to reproductive effects and cancer, must be determined and control measures instituted. Risk assessments need to be effected for areas where these facilities conduct manufacturing. The predominance of women in the manufacturing areas requires evaluating the exposures to reproductive hazards and outcomes. Arsenic exposures must also be evaluated and minimized, especially for maintenance workers; evaluation for lung and skin cancers is also appropriate. PMID:2401268

Leveraging existing data for prioritization of the ecological risks of human and veterinary pharmaceuticals to aquatic organisms

PubMed Central

LaLone, Carlie A.; Berninger, Jason P.; Villeneuve, Daniel L.; Ankley, Gerald T.

2014-01-01

Medicinal innovation has led to the discovery and use of thousands of human and veterinary drugs. With this comes the potential for unintended effects on non-target organisms exposed to pharmaceuticals inevitably entering the environment. The impracticality of generating whole-organism chronic toxicity data representative of all species in the environment has necessitated prioritization of drugs for focused empirical testing as well as field monitoring. Current prioritization strategies typically emphasize likelihood for exposure (i.e. predicted/measured environmental concentrations), while incorporating only rather limited consideration of potential effects of the drug to non-target organisms. However, substantial mammalian pharmacokinetic and mechanism/mode of action (MOA) data are produced during drug development to understand drug target specificity and efficacy for intended consumers. An integrated prioritization strategy for assessing risks of human and veterinary drugs would leverage available pharmacokinetic and toxicokinetic data for evaluation of the potential for adverse effects to non-target organisms. In this reiview, we demonstrate the utility of read-across approaches to leverage mammalian absorption, distribution, metabolism and elimination data; analyse cross-species molecular target conservation and translate therapeutic MOA to an adverse outcome pathway(s) relevant to aquatic organisms as a means to inform prioritization of drugs for focused toxicity testing and environmental monitoring. PMID:25405975

Multicentric randomised study of Helicobacter pylori eradication and pepsinogen testing for prevention of gastric cancer mortality: the GISTAR study.

PubMed

Leja, Marcis; Park, Jin Young; Murillo, Raul; Liepniece-Karele, Inta; Isajevs, Sergejs; Kikuste, Ilze; Rudzite, Dace; Krike, Petra; Parshutin, Sergei; Polaka, Inese; Kirsners, Arnis; Santare, Daiga; Folkmanis, Valdis; Daugule, Ilva; Plummer, Martyn; Herrero, Rolando

2017-08-11

Population-based eradication of Helicobacter pylori has been suggested to be cost-effective and is recommended by international guidelines. However, the potential adverse effects of widespread antibiotic use that this would entail have not been sufficiently studied. An alternative way to decrease gastric cancer mortality is by non-invasive search for precancerous lesions, in particular gastric atrophy; pepsinogen tests are the best currently available alternative. The primary objective of GISTAR is to determine whether H pylori eradication combined with pepsinogen testing reduces mortality from gastric cancer among 40-64-year-old individuals. The secondary objectives include evaluation of H pylori eradication effectiveness in gastric cancer prevention in patients with precancerous lesions and evaluation of the potential adverse events, including effects on microbiome. Individuals are recruited from general population (50% men) in areas with high gastric cancer risk in Europe and undergo detailed lifestyle and medical history questionnaire before being randomly allocated to intervention or control groups. The intervention group undergoes H pylori testing and is offered eradication therapy if positive; in addition, pepsinogen levels are detected in plasma and those with decreased levels are referred for upper endoscopy. All participants are offered faecal occult blood testing as an incentive for study participation. Effectiveness of eradication and the spectrum of adverse events are evaluated in study subpopulations. A 35% difference in gastric cancer mortality between the groups is expected to be detectable at 90% power after 15 years if 30 000 individuals are recruited. Biological materials are biobanked for the main and ancillary studies. The study procedure and assumptions will be tested during the pilot phase. The study was approved by the respective ethics committees. An independent Data Safety and Monitoring Board has been established. The findings will be published in peer-reviewed journals and presented at scientific meetings. NCT02047994. © 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.

Modifying welding process parameters can reduce the neurotoxic potential of manganese-containing welding fumes.

PubMed

Sriram, Krishnan; Lin, Gary X; Jefferson, Amy M; Stone, Samuel; Afshari, Aliakbar; Keane, Michael J; McKinney, Walter; Jackson, Mark; Chen, Bean T; Schwegler-Berry, Diane; Cumpston, Amy; Cumpston, Jared L; Roberts, Jenny R; Frazer, David G; Antonini, James M

2015-02-03

Welding fumes (WF) are a complex mixture of toxic metals and gases, inhalation of which can lead to adverse health effects among welders. The presence of manganese (Mn) in welding electrodes is cause for concern about the potential development of Parkinson's disease (PD)-like neurological disorder. Consequently, from an occupational safety perspective, there is a critical need to prevent adverse exposures to WF. As the fume generation rate and physicochemical characteristics of welding aerosols are influenced by welding process parameters like voltage, current or shielding gas, we sought to determine if changing such parameters can alter the fume profile and consequently its neurotoxic potential. Specifically, we evaluated the influence of voltage on fume composition and neurotoxic outcome. Rats were exposed by whole-body inhalation (40 mg/m(3); 3h/day × 5 d/week × 2 weeks) to fumes generated by gas-metal arc welding using stainless steel electrodes (GMA-SS) at standard/regular voltage (25 V; RVSS) or high voltage (30 V; HVSS). Fumes generated under these conditions exhibited similar particulate morphology, appearing as chain-like aggregates; however, HVSS fumes comprised of a larger fraction of ultrafine particulates that are generally considered to be more toxic than their fine counterparts. Paradoxically, exposure to HVSS fumes did not elicit dopaminergic neurotoxicity, as monitored by the expression of dopaminergic and PD-related markers. We show that the lack of neurotoxicity is due to reduced solubility of Mn in HVSS fumes. Our findings show promise for process control procedures in developing prevention strategies for Mn-related neurotoxicity during welding; however, it warrants additional investigations to determine if such modifications can be suitably adapted at the workplace to avert or reduce adverse neurological risks. Published by Elsevier Ireland Ltd.

Modifying welding process parameters can reduce the neurotoxic potential of manganese-containing welding fumes

PubMed Central

Sriram, Krishnan; Lin, Gary X.; Jefferson, Amy M.; Stone, Samuel; Afshari, Aliakbar; Keane, Michael J.; McKinney, Walter; Jackson, Mark; Chen, Bean T.; Schwegler-Berry, Diane; Cumpston, Amy; Cumpston, Jared L.; Roberts, Jenny R.; Frazer, David G.; Antonini, James M.

2015-01-01

Welding fumes (WF) are a complex mixture of toxic metals and gases, inhalation of which can lead to adverse health effects among welders. The presence of manganese (Mn) in welding electrodes is cause for concern about the potential development of Parkinson’s disease (PD)-like neurological disorder. Consequently, from an occupational safety perspective, there is a critical need to prevent adverse exposures to WF. As the fume generation rate and physicochemical characteristics of welding aerosols are influenced by welding process parameters like voltage, current or shielding gas, we sought to determine if changing such parameters can alter the fume profile and consequently its neurotoxic potential. Specifically, we evaluated the influence of voltage on fume composition and neurotoxic outcome. Rats were exposed by whole-body inhalation (40 mg/m3; 3 h/day × 5 d/week × 2 weeks) to fumes generated by gas–metal arc welding using stainless steel electrodes (GMA-SS) at standard/regular voltage (25 V; RVSS) or high voltage (30 V; HVSS). Fumes generated under these conditions exhibited similar particulate morphology, appearing as chain-like aggregates; however, HVSS fumes comprised of a larger fraction of ultrafine particulates that are generally considered to be more toxic than their ne counterparts. Paradoxically, exposure to HVSS fumes did not elicit dopaminergic neurotoxicity, as monitored by the expression of dopaminergic and PD-related markers. We show that the lack of neurotoxicity is due to reduced solubility of Mn in HVSS fumes. Our findings show promise for process control procedures in developing prevention strategies for Mn-related neurotoxicity during welding; however, it warrants additional investigations to determine if such modifications can be suitably adapted at the workplace to avert or reduce adverse neurological risks. PMID:25549921

Balancing the benefits and risks of disease-modifying therapy in patients with multiple sclerosis.

PubMed

Sørensen, Per Soelberg

2011-12-01

Balancing efficacy versus burden of therapy is essential for the choice of disease-modifying therapy in every MS patient. The first-line therapies, interferon-? and glatiramer acetate, have well-established efficacy and present no major safety concerns. Certain second-line therapies, such as natalizumab, offer potentially greater efficacy, but are associated with an increased level of risk. Over the last year, the first two oral treatments of relapsing-remitting multiple sclerosis, cladribine and fingolimod, have been marketed in certain countries, although cladribine was subsequently withdrawn. In the Phase III clinical development programme, both drugs appeared effective and reasonably safe. However, there were cases of serious adverse events (malignancies and fatal infections) whose relationship with treatment was unclear. Specific postmarketing studies will be necessary to assess the risks of these new oral therapies. Indeed, both natalizumab and mitoxantrone are known today to be associated with rare adverse drug reactions (progressive multifocal leukoencephalopathy for natalizumab and treatment-related leukaemia for mitoxantrone), which were not identified before the treatments were approved. The use of therapies carrying potential serious risks is justified in patients who cannot be treated effectively with safe first-line therapies, but probably not in the average relapsing-remitting multiple sclerosis or clinical isolated syndrome patient. Pivotal Phase III clinical trials, on which basis drug approval is generally granted, are designed to demonstrate clinical efficacy and reveal frequently occurring adverse effects of a new drug. However, post-approval trials with extensive patient exposure are needed to generate knowledge of more patient-specific clinical effectiveness and long-term safety, in particular with respect to rare adverse reactions. Other post-approval measures, such as risk management programmes, pharmacovigilance studies, or phased launch of the drug, may be useful to ensure that risks associated with new treatments are identified and minimised. The final evaluation of the benefits to risks balance of a drug should be made in every patient by weighing benefits in disease activity and progression, quality of life and health economy against both commonly occurring mild side-effects and rare potentially life-threatening adverse drug effects. This decision should be shared between the physician and patient, who may not share the same perceptions of acceptable risk. Copyright © 2011 Elsevier B.V. All rights reserved.

Clinical Use of Aromatase Inhibitors in Adult Males.

PubMed

Tan, Ronny B W; Guay, Andre T; Hellstrom, Wayne J G

2014-04-01

There is a growing interest in the treatment of late-onset hypogonadism, another name for the study of testosterone deficiency in an older age group. Initial attempts at testosterone replacement have also brought attention to the possible adverse effects on the patients' cardiovascular risk factors and their prostate health. The "female" hormone estradiol is no longer considered as the feminizing hormone, as it has been identified to have an effect on the sexual and general well-being of adult males. Urologists and endocrinologists alike have started to pay attention to the serum T/E 2 (testosterone : estradiol) ratio that appears to be more important than the respective individual hormonal levels. Therein lies the possible role of aromatase inhibitors (AIs) in restoring the normal balance of serum testosterone and estradiol levels for the adequate treatment of late-onset hypogonadism, while limiting the potential adverse effects. Currently, other established clinical indications of AIs include the treatment of breast cancer in female patients and developmental growth problems in pediatric patients. This review evaluates the role of AIs as a treatment option for late-onset hypogonadism and the evidence for its other clinical uses in men, including its possible adverse effects. A literature review was performed with regards to the use of aromatase inhibitors in adult males, the role of estrogens in adult males, as well as adverse effect of AIs on bone health in adult males. To evaluate the evidence for the use of AIs in adult males to treat late-onset hypogonadism, obesity-related hypogonadotropic hypogonadism, gynecomastia, and male subfertility. To evaluate the evidence for the possible adverse effects on the bone health of adult males with the use of AIs. Currently there is no literature to recommend the use of AIs in adult males to treat late-onset hypogonadism, obesity-related hypogonadotropic hypogonadism, gynecomastia, or male subfertility, although some positive effects have been reported. The adverse effects on bone health seen in females treated with AIs are not seen in males. With the better understanding of the T/E 2 ratio in adult males, the lack of scientific data to show that bone health is adversely affected by AI usage in adult males, the positive effects of AIs on the treatment of conditions like late-onset hypogonadism and male subfertility encourages conducting large-scale, multicenter, randomized controlled trials for the clinical use of AIs in adult males. Tan RBW, Guay AT, and Hellstrom WJG. Clinical use of aromatase inhibitors in adult males. Sex Med Rev 2014;2:79-90. Copyright © 2014 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Estimating the risks for adverse effects of total phosphorus in receiving streams with the Stochastic Empirical Loading and Dilution Model (SELDM)

USGS Publications Warehouse

Granato, Gregory E.; Jones, Susan C.

2015-01-01

Results of this study indicate the potential benefits of the multi-decade simulations that SELDM provides because these simulations quantify risks and uncertainties that affect decisions made with available data and statistics. Results of the SELDM simulations indicate that the WQABI criteria concentrations may be too stringent for evaluating the stormwater quality in receiving streams, highway runoff, and BMP discharges; especially with the substantial uncertainties inherent in selecting representative data.

Evaluation of Neurophysiologic and Systematic Changes during Aeromedical Evacuation and en Route Care of Combat Casualties in a Swine Polytrauma

DTIC Science & Technology

2016-02-01

changes in ambient conditions such as cabin pressure and temperature could potentially have detrimental effects on the already vulnerable brain. There...during simulated long-range aero-medical evacuation has adverse effects on brain blood flow and tissue oxygenation , as well as lung function in swine...is a dearth of knowledge about the effects of long range aero-medical evacuation on injured organs, as well as an emerging published database

Examination of the Pharmacology of Oxytocin and Clinical Guidelines for Use in Labor.

PubMed

Page, Katie; McCool, William F; Guidera, Mamie

2017-07-01

The use of exogenous oxytocin to induce or augment labor has increased in recent years. This literature-informed review examines the action of this medication and the potential associated complications, with an evaluation of current professional practice guidelines. A brief history of the use of exogenous oxytocin for labor induction or augmentation is presented. In addition, risk management strategies for the prevention of oxytocin-related adverse outcomes and subsequent litigation are identified. © 2017 by the American College of Nurse-Midwives.

[Find your way in the jungle of mAbs].

PubMed

Watier, H

2017-09-01

The rapidly increasing number of approved monoclonal antibodies (mAbs) and the huge number of mAbs in clinical development are a matter of concern for who wants to easily identify targets, indications, mechanisms of action and possible adverse effects. The current nomenclature being of limited interest, simple rationales will be presented for helping practitioners in rapidly classify mAbs depending on their structure-pharmacology relationship and in evaluating their potential effects, particularly in transfusion medicine. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Impact of active controls technology on structural integrity

NASA Technical Reports Server (NTRS)

Noll, Thomas; Austin, Edward; Donley, Shawn; Graham, George; Harris, Terry

1991-01-01

This paper summarizes the findings of The Technical Cooperation Program to assess the impact of active controls technology on the structural integrity of aeronautical vehicles and to evaluate the present state-of-the-art for predicting the loads caused by a flight-control system modification and the resulting change in the fatigue life of the flight vehicle. The potential for active controls to adversely affect structural integrity is described, and load predictions obtained using two state-of-the-art analytical methods are given.

Adverse events and the relation with quality of life in adults with intellectual disability and challenging behaviour using psychotropic drugs.

PubMed

Scheifes, Arlette; Walraven, Sanne; Stolker, Joost Jan; Nijman, Henk L I; Egberts, Toine C G; Heerdink, Eibert R

2016-01-01

Psychotropic drugs are prescribed to approximately 30-40% of adults with intellectual disability (ID) and challenging behaviour, despite the limited evidence of effectiveness and the potential of adverse events. To assess the prevalence of adverse events in association with psychotropic drug use in adults with ID and challenging behaviour and to examine the relation of these adverse events with the person's quality of life. The presence of adverse events was measured with a questionnaire that had to be filled in by the physicians of the participants. Movement disorders were measured separately with a standardised protocol. The strength of the association between adverse events and Intellectual Disability Quality of Life-16 (IDQOL-16), and daily functioning was investigated using linear regression analyses, taking into account the severity of disease (CGI-S) as potential confounder. Virtually all of 103 adults with ID and challenging behaviour had at least one adverse event (84.4%) and almost half had ≥3 adverse events (45.6%) across different subclasses. Using psychotropic drugs increased the prevalence of adverse events significantly. Respectively 13% of the patients without psychotropic drugs and 61% of the patients with ≥2 psychotropic drugs had ≥3 adverse events. Having adverse events had a significantly negative influence on the quality of life. A large majority of all patients had at least one adverse event associated with psychotropic drug use. More attention is needed for these adverse events and their negative influence on the quality of life of these patients, taking into account the lack of evidence of effectiveness of psychotropic drugs for challenging behaviour. Copyright © 2015. Published by Elsevier Ltd.

Recommendations for safety planning, data collection, evaluation and reporting during drug, biologic and vaccine development: a report of the safety planning, evaluation, and reporting team.

PubMed

Crowe, Brenda J; Xia, H Amy; Berlin, Jesse A; Watson, Douglas J; Shi, Hongliang; Lin, Stephen L; Kuebler, Juergen; Schriver, Robert C; Santanello, Nancy C; Rochester, George; Porter, Jane B; Oster, Manfred; Mehrotra, Devan V; Li, Zhengqing; King, Eileen C; Harpur, Ernest S; Hall, David B

2009-10-01

The Safety Planning, Evaluation and Reporting Team (SPERT) was formed in 2006 by the Pharmaceutical Research and Manufacturers of America. SPERT's goal was to propose a pharmaceutical industry standard for safety planning, data collection, evaluation, and reporting, beginning with planning first-in-human studies and continuing through the planning of the post-product-approval period. SPERT's recommendations are based on our review of relevant literature and on consensus reached in our discussions. An important recommendation is that sponsors create a Program Safety Analysis Plan early in development. We also give recommendations for the planning of repeated, cumulative meta-analyses of the safety data obtained from the studies conducted within the development program. These include clear definitions of adverse events of special interest and standardization of many aspects of data collection and study design. We describe a 3-tier system for signal detection and analysis of adverse events and highlight proposals for reducing "false positive" safety findings. We recommend that sponsors review the aggregated safety data on a regular and ongoing basis throughout the development program, rather than waiting until the time of submission. We recognize that there may be other valid approaches. The proactive approach we advocate has the potential to benefit patients and health care providers by providing more comprehensive safety information at the time of new product marketing and beyond.

Important exposure controls for protection against antineoplastic agents: Highlights for oncology health care workers.

PubMed

Alehashem, Maryam; Baniasadi, Shadi

2018-01-01

A great number of antineoplastic drugs (ANPDs) are used globally in cancer treatment. Due to their adverse health effects, occupational exposure to ANPDs is considered a potential health risk to health care workers. The current study aimed to evaluate safe-handling practices of ANPDs, exposure controls, and adverse health implications for health care providers exposed to ANDPs. Prevention measures, including engineering, administrative, and work practice controls, as well as personal protective equipment (PPE), were recorded daily through a questionnaire for six weeks. Acute adverse health effects experienced by health care workers were also documented. The implemented exposure controls for preparation, administration, cleaning, and waste disposal were not in accordance with the safe handling guidelines. Central nervous system disorders (26.33%) were the most frequent acute adverse effects reported by health care workers. A significant correlation was found between the number of experienced adverse effects and handling characteristics, including the number of preparations (r = 0.38, p < 0.05), dose, and the number of prepared drugs (r = 0.46, p < 0.01 and 0.39, p < 0.05), and working hours in different locations of oncology setting for six weeks (preparation room: r = 0.38, P < 0.05, treatment room: r = 0.46, P < 0.01, patient room: r = 0.63, P < 0.01, and station: r = 0.68, P < 0.01). Due to inadequate control measures, oncology health care workers were in danger of exposure to ANPDs and experienced acute adverse health effects. Implementation of appropriate exposure controls is required to prevent occupational exposure to ANPDs.

Feasibility trial of a scalable psychological intervention for women affected by urban adversity and gender-based violence in Nairobi.

PubMed

Dawson, Katie S; Schafer, Alison; Anjuri, Dorothy; Ndogoni, Lincoln; Musyoki, Caroline; Sijbrandij, Marit; van Ommeren, Mark; Bryant, Richard A

2016-11-18

Living in conditions of chronic adversity renders many women more vulnerable to experiencing gender-based violence (GBV). In addition to GBV's physical and social consequences, the psychological effects can be pervasive. Access to evidence-based psychological interventions that seek to support the mental health of women affected by such adversity is rare in low- and middle-income countries. The current study evaluates a brief evidence-informed psychological intervention developed by the World Health Organization for adults impacted by adversity (Problem Management Plus; PM+). A feasibility randomised control trial (RCT) was conducted to inform a fully powered trial. Community health workers delivered the intervention to 70 women residing in three peri-urban settings in Nairobi, Kenya. Women, among whom 80% were survivors of GBV (N = 56), were randomised to receive five sessions of either PM+ (n = 35) by community health workers or enhanced treatment as usual (ETAU; n = 35). PM+ was not associated with any adverse events. Although the study was not powered to identify effects and accordingly did not identify effects on the primary outcome measure of general psychological distress, women survivors of adversity, including GBV, who received PM+ displayed greater reductions in posttraumatic stress disorder symptoms following treatment than those receiving ETAU. This feasibility study suggests that PM+ delivered by lay health workers is an acceptable and safe intervention to reach women experiencing common mental disorders and be inclusive for those affected by GBV and can be studied in a RCT in this setting. The study sets the stage for a fully powered, definitive controlled trial to assess this potentially effective intervention. ACTRN12614001291673 , 10/12/2014, retrospectively registered during the recruitment phase.

Can Erythrocytes Transmit Oxidative Stress Beyond the Lungs? An Adverse Outcome Pathway for the Cardiovascular Effects of Air Pollution.

EPA Science Inventory

Adverse outcome pathways (AOPs) are systems biology roadmaps with potential utility in xenobiotic exposure risk assessment. AOPs connect molecular initiating events (MIEs) to population-level adverse outcomes (AOs) via cellular, organ, and organism key events (KE) and KE relatio...

Low-intensity red and infrared laser effects at high fluences on Escherichia coli cultures

PubMed Central

Barboza, L.L.; Campos, V.M.A.; Magalhães, L.A.G.; Paoli, F.; Fonseca, A.S.

2015-01-01

Semiconductor laser devices are readily available and practical radiation sources providing wavelength tenability and high monochromaticity. Low-intensity red and near-infrared lasers are considered safe for use in clinical applications. However, adverse effects can occur via free radical generation, and the biological effects of these lasers from unusually high fluences or high doses have not yet been evaluated. Here, we evaluated the survival, filamentation induction and morphology of Escherichia coli cells deficient in repair of oxidative DNA lesions when exposed to low-intensity red and infrared lasers at unusually high fluences. Cultures of wild-type (AB1157), endonuclease III-deficient (JW1625-1), and endonuclease IV-deficient (JW2146-1) E. coli, in exponential and stationary growth phases, were exposed to red and infrared lasers (0, 250, 500, and 1000 J/cm2) to evaluate their survival rates, filamentation phenotype induction and cell morphologies. The results showed that low-intensity red and infrared lasers at high fluences are lethal, induce a filamentation phenotype, and alter the morphology of the E. coli cells. Low-intensity red and infrared lasers have potential to induce adverse effects on cells, whether used at unusually high fluences, or at high doses. Hence, there is a need to reinforce the importance of accurate dosimetry in therapeutic protocols. PMID:26445339

Evaluating Suspension Formulations of Theophylline Cocrystals With Artificial Sweeteners.

PubMed

Aitipamula, Srinivasulu; Wong, Annie B H; Kanaujia, Parijat

2018-02-01

Pharmaceutical cocrystals have garnered significant interest as potential solids to address issues associated with formulation development of drug substances. However, studies concerning the understanding of formulation behavior of cocrystals are still at the nascent stage. We present results of our attempts to evaluate suspension formulations of cocrystals of an antiasthmatic drug, theophylline, with 2 artificial sweeteners. Stability, solubility, drug release, and taste of the suspension formulations were evaluated. Suspension that contained cocrystal with acesulfame showed higher drug release rate, while a cocrystal with saccharin showed a significant reduction in drug release rate. The cocrystal with saccharin was found stable in suspension for over 9 weeks at accelerated test condition; in contrast, the cocrystal with acesulfame was found unstable. Taste analysis using an electronic taste-sensing system revealed improved sweetness of the suspension formulations with cocrystals. Theophylline has a narrow therapeutic index with a short half-life which necessitates frequent dosing. This adversely impacts patient compliance and enhances risk of gastrointestinal and cardiovascular adverse effects. The greater thermodynamic stability, sweetness, and sustained drug release of the suspension formulation of theophylline-saccharin could offer an alternative solution to the short half-life of theophylline and make it a promising formulation for treating asthmatic pediatric and geriatric patients. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Safety of Pseudomonas chlororaphis as a gene source for genetically modified crops.

PubMed

Anderson, Jennifer A; Staley, Jamie; Challender, Mary; Heuton, Jamie

2018-02-01

Genetically modified crops undergo extensive evaluation to characterize their food, feed and environmental safety prior to commercial introduction, using a well-established, science-based assessment framework. One component of the safety assessment includes an evaluation of each introduced trait, including its source organism, for potential adverse pathogenic, toxic and allergenic effects. Several Pseudomonas species have a history of safe use in agriculture and certain species represent a source of genes with insecticidal properties. The ipd072Aa gene from P. chlororaphis encodes the IPD072Aa protein, which confers protection against certain coleopteran pests when expressed in maize plants. P. chlororaphis is ubiquitous in the environment, lacks known toxic or allergenic properties, and has a history of safe use in agriculture and in food and feed crops. This information supports, in part, the safety assessment of potential traits, such as IPD072Aa, that are derived from this source organism.

Stakeholders' Perspectives on Preclinical Testing for Alzheimer's Disease.

PubMed

Arias, Jalayne J; Cummings, Jeffrey; Grant, Alexander Rae; Ford, Paul J

2015-01-01

Progress towards validating amyloid beta as an early indicator of Alzheimer's disease (AD) heightens the need for evaluation of stakeholders' perspectives of the benefits and harms of preclinical testing in asymptomatic individuals. Investigators conducted and analyzed 14 semi-structured interviews with family members of patients diagnosed with AD. Participants reported benefits, including the potential to seek treatment, make lifestyle changes, and prepare for cognitive impairment. Participants identified harms, including social harms, adverse life decisions, and psychological harms. Nine participants reported either a "positive global perspective" or a "positive global perspective (qualified)." Results from this study characterized stakeholders' perspectives on the potential benefits and harms of clinical use of preclinical testing for AD. Investigators used data from this study to develop a framework that contributes to ongoing discussions that will evaluate widespread adoption of preclinical testing and will inform future research. Copyright 2015 The Journal of Clinical Ethics. All rights reserved.

The role of vegetation in mitigating air quality impacts from ...

EPA Pesticide Factsheets

On Apri1 27-28, 2019, a multi-disciplinary group of researchers and po1icymakers met to discuss the state-of-the-science regarding the potential of roadside vegetation to mitigate near-road air quality impacts. Concerns over population exposures to traffic-generated pollutants near roads have grown with an increasing number of health studies reporting links between proximity to roads and adverse health effects. A recent EM article described how roadway design, including the presence of roadside vegetation, may be a means of mitigating air pollutant concentrations near roads. As a first step in evaluating this concept, representatives from government agencies, academia, state and local agencies, and non-governmental environmental organizations with expertise in air quality, urban forestry, ecosystem services, and environmental policy reviewed the current science and identified future activities in evaluating the potential role of vegetation in mitigating near-road air pollutant concentrations. journal article

Transcriptional responses of human aortic endothelial cells to nanoconstructs used in biomedical applications

PubMed Central

Moos, Philip J.; Honeggar, Matthew; Malugin, Alexander; Herd, Heather; Thiagarajan, Giridhar; Ghandehari, Hamidreza

2013-01-01

Understanding the potential toxicities of manufactured nanoconstructs used for drug delivery and biomedical applications may help improve their safety. We sought to determine if surface modified silica nanoparticles and poly(amido amine) dendrimers elicit genotoxic responses on vascular endothelial cells. The nanoconstructs utilized in this study had distinct geometry (spheres vs. worms) and surface charge, which were used to evaluate the contributions of these parameters to any potential adverse effects of these materials. Time-dependent cytotoxicity was found for surfaced-functionalized but geometrically distinct silica materials while amine-terminated dendrimers displayed time-independent cytotoxicity and carboxylated dendrimers were nontoxic in our assays. Transcriptomic evaluation of HAEC responses indicated time-dependent gene induction following silica exposure, consisting of cell cycle gene repression and pro-inflammatory gene induction. However, the dendrimers did not induce genomic toxicity, despite displaying general cytotoxicity. PMID:23806026

Transcriptional responses of human aortic endothelial cells to nanoconstructs used in biomedical applications.

PubMed

Moos, Philip J; Honeggar, Matthew; Malugin, Alexander; Herd, Heather; Thiagarajan, Giridhar; Ghandehari, Hamidreza

2013-08-05

Understanding the potential toxicities of manufactured nanoconstructs used for drug delivery and biomedical applications may help improve their safety. We sought to determine if surface-modified silica nanoparticles and poly(amido amine) dendrimers elicit genotoxic responses on vascular endothelial cells. The nanoconstructs utilized in this study had a distinct geometry (spheres vs worms) and surface charge, which were used to evaluate the contributions of these parameters to any potential adverse effects of these materials. Time-dependent cytotoxicity was found for surfaced-functionalized but geometrically distinct silica materials, while amine-terminated dendrimers displayed time-independent cytotoxicity and carboxylated dendrimers were nontoxic in our assays. Transcriptomic evaluation of human aortic endothelial cell (HAEC) responses indicated time-dependent gene induction following silica exposure, consisting of cell cycle gene repression and pro-inflammatory gene induction. However, the dendrimers did not induce genomic toxicity, despite displaying general cytotoxicity.

Blood gene expression profiling of an early acetaminophen response.

PubMed

Bushel, P R; Fannin, R D; Gerrish, K; Watkins, P B; Paules, R S

2017-06-01

Acetaminophen can adversely affect the liver especially when overdosed. We used whole blood as a surrogate to identify genes as potential early indicators of an acetaminophen-induced response. In a clinical study, healthy human subjects were dosed daily with 4 g of either acetaminophen or placebo pills for 7 days and evaluated over the course of 14 days. Alanine aminotransferase (ALT) levels for responders to acetaminophen increased between days 4 and 9 after dosing, and 12 genes were detected with expression profiles significantly altered within 24 h. The early responsive genes separated the subjects by class and dose period. In addition, the genes clustered patients who overdosed on acetaminophen apart from controls and also predicted the exposure classifications with 100% accuracy. The responsive genes serve as early indicators of an acetaminophen exposure, and their gene expression profiles can potentially be evaluated as molecular indicators for further consideration.

Blood Gene Expression Profiling of an Early Acetaminophen Response

PubMed Central

Bushel, Pierre R.; Fannin, Rick D.; Gerrish, Kevin; Watkins, Paul B.; Paules, Richard S.

2018-01-01

Acetaminophen can adversely affect the liver especially when overdosed. We used whole blood as a surrogate to identify genes as potential early indicators of an acetaminophen-induced response. In a clinical study, healthy human subjects were dosed daily with 4g of either acetaminophen or placebo pills for 7 days and evaluated over the course of 14 days. Alanine aminotransferase (ALT) levels for responders to acetaminophen increased between days 4 and 9 after dosing and 12 genes were detected with expression profiles significantly altered within 24 hrs. The early responsive genes separated the subjects by class and dose period. In addition, the genes clustered patients who overdosed on acetaminophen apart from controls and also predicted the exposure classifications with 100% accuracy. The responsive genes serve as early indicators of an acetaminophen exposure and their gene expression profiles can potentially be evaluated as molecular indicators for further consideration. PMID:26927286

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.

Development of the Vaccine Analytic Unit's research agenda for investigating potential adverse events associated with anthrax vaccine adsorbed.

PubMed

Payne, Daniel C; Franzke, Laura H; Stehr-Green, Paul A; Schwartz, Benjamin; McNeil, Michael M

2007-01-01

In 2002, the Centers for Disease Control and Prevention established the Vaccine Analytic Unit (VAU) in collaboration with the Department of Defense (DoD). The focus of this report is to describe the process by which the VAU's anthrax vaccine safety research plan was developed following a comprehensive review of these topics. Public health literature, surveillance data, and clinical sources were reviewed to create a list of adverse events hypothesized to be potentially related to anthrax vaccine adsorbed (AVA). From this list, a consensus process was used to select 11 important research topics. Adverse event background papers were written for each of these topics, addressing predetermined criteria. These were independently reviewed and ranked by a National Vaccine Advisory Committee (NVAC) workgroup. The adverse events included in the final priority list will be the subject of observational or other post marketing surveillance studies using the Defense Medical Surveillance System (DMSS) database. A review of various information sources identified over 100 potential adverse events. The review process recommended 11 topics as potentially warranting further study. The NVAC workgroup identified the following adverse event topics for study: arthritis, optic neuritis, and Stevens-Johnson syndrome/Toxic epidermal necrolysis. Two additional topics (systemic lupus erythematosus (SLE) and multiple, near-concurrent military vaccinations) were added in response to emerging public health and military concerns. The experience described, while specific for establishing the VAU's research agenda for the safety of the current anthrax vaccine, may be useful and adapted for research planning in other areas of public health research. Copyright (c) 2006 John Wiley & Sons, Ltd.

Relationship between medication event rates and the Leapfrog computerized physician order entry evaluation tool.

PubMed

Leung, Alexander A; Keohane, Carol; Lipsitz, Stuart; Zimlichman, Eyal; Amato, Mary; Simon, Steven R; Coffey, Michael; Kaufman, Nathan; Cadet, Bismarck; Schiff, Gordon; Seger, Diane L; Bates, David W

2013-06-01

The Leapfrog CPOE evaluation tool has been promoted as a means of monitoring computerized physician order entry (CPOE). We sought to determine the relationship between Leapfrog scores and the rates of preventable adverse drug events (ADE) and potential ADE. A cross-sectional study of 1000 adult admissions in five community hospitals from October 1, 2008 to September 30, 2010 was performed. Observed rates of preventable ADE and potential ADE were compared with scores reported by the Leapfrog CPOE evaluation tool. The primary outcome was the rate of preventable ADE and the secondary outcome was the composite rate of preventable ADE and potential ADE. Leapfrog performance scores were highly related to the primary outcome. A 43% relative reduction in the rate of preventable ADE was predicted for every 5% increase in Leapfrog scores (rate ratio 0.57; 95% CI 0.37 to 0.88). In absolute terms, four fewer preventable ADE per 100 admissions were predicted for every 5% increase in overall Leapfrog scores (rate difference -4.2; 95% CI -7.4 to -1.1). A statistically significant relationship between Leapfrog scores and the secondary outcome, however, was not detected. Our findings support the use of the Leapfrog tool as a means of evaluating and monitoring CPOE performance after implementation, as addressed by current certification standards. Scores from the Leapfrog CPOE evaluation tool closely relate to actual rates of preventable ADE. Leapfrog testing may alert providers to potential vulnerabilities and highlight areas for further improvement.

Missing data treatments matter: an analysis of multiple imputation for anterior cervical discectomy and fusion procedures.

PubMed

Ondeck, Nathaniel T; Fu, Michael C; Skrip, Laura A; McLynn, Ryan P; Cui, Jonathan J; Basques, Bryce A; Albert, Todd J; Grauer, Jonathan N

2018-04-09

The presence of missing data is a limitation of large datasets, including the National Surgical Quality Improvement Program (NSQIP). In addressing this issue, most studies use complete case analysis, which excludes cases with missing data, thus potentially introducing selection bias. Multiple imputation, a statistically rigorous approach that approximates missing data and preserves sample size, may be an improvement over complete case analysis. The present study aims to evaluate the impact of using multiple imputation in comparison with complete case analysis for assessing the associations between preoperative laboratory values and adverse outcomes following anterior cervical discectomy and fusion (ACDF) procedures. This is a retrospective review of prospectively collected data. Patients undergoing one-level ACDF were identified in NSQIP 2012-2015. Perioperative adverse outcome variables assessed included the occurrence of any adverse event, severe adverse events, and hospital readmission. Missing preoperative albumin and hematocrit values were handled using complete case analysis and multiple imputation. These preoperative laboratory levels were then tested for associations with 30-day postoperative outcomes using logistic regression. A total of 11,999 patients were included. Of this cohort, 63.5% of patients had missing preoperative albumin and 9.9% had missing preoperative hematocrit. When using complete case analysis, only 4,311 patients were studied. The removed patients were significantly younger, healthier, of a common body mass index, and male. Logistic regression analysis failed to identify either preoperative hypoalbuminemia or preoperative anemia as significantly associated with adverse outcomes. When employing multiple imputation, all 11,999 patients were included. Preoperative hypoalbuminemia was significantly associated with the occurrence of any adverse event and severe adverse events. Preoperative anemia was significantly associated with the occurrence of any adverse event, severe adverse events, and hospital readmission. Multiple imputation is a rigorous statistical procedure that is being increasingly used to address missing values in large datasets. Using this technique for ACDF avoided the loss of cases that may have affected the representativeness and power of the study and led to different results than complete case analysis. Multiple imputation should be considered for future spine studies. Copyright © 2018 Elsevier Inc. All rights reserved.

Adverse childhood experiences and disability in U.S. adults.

PubMed

Schüssler-Fiorenza Rose, Sophia Miryam; Xie, Dawei; Stineman, Margaret

2014-08-01

To assess relationships between adverse childhood experiences and self-reported disabilities in adult life. Cross-sectional, random-digit-dialed, state-population-based survey (Behavioral Risk Factor Surveillance System). Fourteen states and the District of Columbia. Noninstitutionalized adults ages ≥18 years surveyed in 2009 and/or in 2010 (n = 81,184). The Behavioral Risk Factor Surveillance System Adverse Childhood Experience (ACE) Module asks about abuse (physical, sexual, emotional), family dysfunction (exposures to domestic violence, living with mentally ill, substance abusing, or incarcerated family member(s), and/or parental separation and/or divorce) that occurred before age 18 years. The ACE score sums affirmed ACE categories (range, 0-8). We controlled for demographic characteristics (age, race, education, income, and marital status) and self-reported physical health conditions (stroke, myocardial infarction, diabetes, coronary heart disease, asthma). Five states asked participants about mental health conditions (anxiety, depression). A subset analysis of participants in these states evaluated the effect of adjusting for these conditions. The primary outcome was disability (self-reported activity limitation and/or assistive device use). More than half of participants (57%) reported at least 1 adverse childhood experience category, and 23.2% reported disability. The odds ratio (95% confidence interval) of disability increased in a graded fashion from odds ratio 1.3 (95% confidence interval, 1.2-1.4) among those who experienced 1 adverse experience to odds ratio 5.8 (95% confidence interval, 4.6-7.5) among those with 7-8 adverse experiences compared with those with no such experiences when adjusting for demographic factors. The relationship between adverse experiences and disability remained strong after adjusting for physical and mental health conditions. There is a strong graded relationship between childhood exposure to abuse and household dysfunction and self-reported disability in adulthood, even after adjusting for potentially mediating health conditions. Greater clinician, researcher, and policymaker awareness of the impact of childhood adversity on disability is crucial to help those affected by childhood adversity lead more functional lives. Copyright © 2014 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Community Level Stressors and Their Impacts on Food ...

EPA Pesticide Factsheets

Research is needed to understand a community’s food resources, utilization of those resources, and how the built and natural environment impact access to resources and potential chemical exposures. This research will identify stressors, relationships between those stressors, and explore potential interactions between food resources and chemical and non-chemical stressors. By evaluating various chemical and non-chemical stressors, an understanding of a community’s food resources and utilization with potential exposures can be obtained. With this understanding about the community’s potential dietary exposures and contributing factors, it will be possible to evaluate ways to mitigate and alleviate issues that could impact public health. The objectives of this research are 1) to obtain information on a community’s environmental exposures (chemical and non-chemical stressors) from various available databases and data and 2) to evaluate impacts on dietary exposure which may lead to adverse public health outcomes. This research will enhance public tools, in particular, the Community-Focused Exposure and Risk Screening Tool (CFERST), which can be utilized by community leaders in decision making by bridging all pertinent information to inform policy. Community level health analyses can support protective actions, be used by communities to identify and prioritize their risks based on scientific data and ensure that resources are directed where they will provi

Toward multimodal signal detection of adverse drug reactions.

PubMed

Harpaz, Rave; DuMouchel, William; Schuemie, Martijn; Bodenreider, Olivier; Friedman, Carol; Horvitz, Eric; Ripple, Anna; Sorbello, Alfred; White, Ryen W; Winnenburg, Rainer; Shah, Nigam H

2017-12-01

Improving mechanisms to detect adverse drug reactions (ADRs) is key to strengthening post-marketing drug safety surveillance. Signal detection is presently unimodal, relying on a single information source. Multimodal signal detection is based on jointly analyzing multiple information sources. Building on, and expanding the work done in prior studies, the aim of the article is to further research on multimodal signal detection, explore its potential benefits, and propose methods for its construction and evaluation. Four data sources are investigated; FDA's adverse event reporting system, insurance claims, the MEDLINE citation database, and the logs of major Web search engines. Published methods are used to generate and combine signals from each data source. Two distinct reference benchmarks corresponding to well-established and recently labeled ADRs respectively are used to evaluate the performance of multimodal signal detection in terms of area under the ROC curve (AUC) and lead-time-to-detection, with the latter relative to labeling revision dates. Limited to our reference benchmarks, multimodal signal detection provides AUC improvements ranging from 0.04 to 0.09 based on a widely used evaluation benchmark, and a comparative added lead-time of 7-22 months relative to labeling revision dates from a time-indexed benchmark. The results support the notion that utilizing and jointly analyzing multiple data sources may lead to improved signal detection. Given certain data and benchmark limitations, the early stage of development, and the complexity of ADRs, it is currently not possible to make definitive statements about the ultimate utility of the concept. Continued development of multimodal signal detection requires a deeper understanding the data sources used, additional benchmarks, and further research on methods to generate and synthesize signals. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison between herbal medicine and fluoxetine for depression: a systematic review of randomized controlled trials.

PubMed

Ren, Yi; Zhu, Chenjun; Wu, Jianjun; Zheng, Ruwen; Cao, Huijaun

2015-10-01

To evaluate the effectiveness and safety of Chinese herbal medicine (CHM) versus fluoxetine on depression. A systematic review of randomized controlled trials (RCTs). RCT with two parallel groups that compared CHM and fluoxetine on treatment of depression with reported decreased Hamilton Depression Scale (HAMD) and adverse events during treatment were included after searching through six electric-databases. The methodological quality of RCTs was assessed according to the Cochrane risk of bias tool. Meta-analysis was conducted using RevMan 5.3 software with pooled mean difference (MD) or risk ratio (RR) and their 95% confidence interval (CI) if no significant heterogeneity was detected. A SOF table was generated using GRADEPro software to evaluate the overall quality of the evidence. Twenty-six trials with 3294 participants were included in the review. Most of them had high risk of bias during conducting and reporting. The results achieved weak evidence which showed CHM had similar effect to fluoxetine (20mg/day) on relieving depression according to HAMD assessment (for primary depression: MD=-0.08, 95%CI -0.98-0.82; for secondary depression: MD=-0.36, 95%CI -1.55-0.83), but fewer incidences of adverse events than the drug (for primary depression: RR=0.31, 95%CI 0.17-0.59; for post-stroke depression: RR=0.04, 95%CI 0.00-0.25). No serious adverse event was found in neither CHM nor fluoxetine group. Due to the poor quality of included trials and the potential publication bias of this review, no confirmed conclusion could be draw to evaluate the effectiveness and safety of CHM for depression compared with fluoxetine. Copyright © 2015 Elsevier Ltd. All rights reserved.

Practice-based learning and improvement: a two-year experience with the reporting of morbidity and mortality cases by general surgery residents.

PubMed

Falcone, John L; Lee, Kenneth K W; Billiar, Timothy R; Hamad, Giselle G

2012-01-01

The Accreditation Council for Graduate Medical Education (ACGME) core competency of practice-based learning and improvement can be assessed with surgical Morbidity and Mortality Conference (MMC). We aim to describe the MMC reporting patterns of general surgery residents, describe the adverse event rate for patients and compare that with existing published rates, and describe the nature of our institutional adverse events. We hypothesize that reporting patterns and incidence rates will remain constant over time. In this retrospective cohort study, archived MMC case lists were evaluated from January 1, 2009 to December 31, 2010. The reporting patterns of the residents, the adverse event ratios, and the specific categories of adverse events were described over the academic years. χ(2) and Fisher's exact tests were used to compare across academic years, using an α = 0.05. There were 85 surgical MMC case lists evaluated. Services achieved a reporting rate above 80% (p < 0.001). The most consistent reporting was done by postgraduate year (PGY) 5 level chief residents for all services (p > 0.05). Out of 11,368 patients evaluated from complete MMC submissions, 289 patients had an adverse event reported (2.5%). This was lower than published reporting rates for patient adverse event rates (p < 0.001). Adverse event rates were consistent for residents at the postgraduate year 2, 4, and 5 levels for all services (p > 0.05). Over 2 years, 522 adverse events were reported for 461 patients. A majority of adverse events were from death (24.1%), hematologic and/or vascular events (16.7%), and gastrointestinal system events (16.1%). Surgery resident MMC reporting patterns and adverse event rates are generally stable over time. This study shows which adverse event cases are important for chief residents to report. Copyright © 2012 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

Within-Hospital Variation in 30-Day Adverse Events: Implications for Measuring Quality.

PubMed

Burke, Robert E; Glorioso, Thomas; Barón, Anna K; Kaboli, Peter J; Ho, P Michael

Novel measures of hospital quality are needed. Because quality improvement efforts seek to reduce variability in processes and outcomes, hospitals with higher variability in adverse events may be delivering poorer quality care. We sought to evaluate whether within-hospital variability in adverse events after a procedure might function as a quality metric that is correlated with facility-level mortality rates. We analyzed all percutaneous coronary interventions (PCIs) performed in the Veterans Health Administration (VHA) system from 2007 to 2013 to evaluate the correlation between within-hospital variability in 30-day postdischarge adverse events (readmission, emergency department visit, and repeat revascularization), and facility-level mortality rates, after adjustment for patient demographics, comorbidities, PCI indication, and PCI urgency. The study cohort included 47,567 patients at 48 VHA hospitals. The overall 30-day adverse event rate was 22.0% and 1-year mortality rate was 4.9%. The most variable sites had relative changes of 20% in 30-day rates of adverse events period-to-period. However, within-hospital variability in 30-day events was not correlated with 1-year mortality rates (correlation coefficient = .06; p = .66). Thus, measuring within-hospital variability in postdischarge adverse events may not improve identification of low-performing hospitals. Evaluation in other conditions, populations, and in relationship with other quality metrics may reveal stronger correlations with care quality.

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.

Evaluation of malnutrition as a predictor of adverse outcomes in febrile neutropenia associated with paediatric haematological malignancies.

PubMed

Chaudhuri, Jasodhara; Biswas, Tamoghna; Datta, Jyotishka; Sabui, Tapas Kumar; Chatterjee, Sukanta; Ray, Somosri; Raychaudhuri, Dibyendu; Mandal, Kalyanbrata; Chatterjee, Kaushani; Chakraborty, Swapna

2016-07-01

Malnutrition has been reported in the literature to be adversely associated with outcomes in paediatric malignancies. Our objective in this paper was to evaluate malnutrition as a potential predictor for adverse outcomes in febrile neutropenia associated with haematological malignancies. A prospective observational study was performed in a tertiary care teaching hospital of Kolkata, India. Forty-eight participants, suffering from haematological malignancy, were included. Participants were included if they experienced at least one episode of febrile neutropenia. For children aged <5 years, weight for height, height for age and weight for age were used as criteria for defining malnutrition, while body mass index for age was used in children ≥5 years. A total of 162 episodes of febrile neutropenia were studied. Thirty patients (30/48, 62.5%) included in the study had malnutrition. In bivariate analyses at patient level, there is a strong association between malnutrition and death (odds ratio (OR) 7.286, 95% confidence interval (CI) 0.838-63.345, one-tailed P = 0.044), and life-threatening complications show a moderate trend towards significance (OR 3.333, 95% CI 0.791-14.052, one-tailed P = 0.084). Survival functions were significantly different between malnourished and non-malnourished children (log rank test χ(2)  = 4.609, degree of freedom = 1, P = 0.032). Wasting was associated with life-threatening complications in children aged <5 years (OR 14, 95% CI 1.135-172.642, one-tailed P = 0.036). Logistic regression analyses at episode level revealed that phase of treatment and respiratory system involvement were significant predictors of death, while malnutrition was not. Malnutrition may be a potential predictor of mortality in febrile neutropenia. © 2016 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).

CYP3A-Mediated Generation of Aldehyde and Hydrazine in Atazanavir MetabolismS⃞

PubMed Central

Li, Feng; Lu, Jie; Wang, Laiyou

2011-01-01

Atazanavir (ATV) is an antiretroviral drug of the protease inhibitor class. Multiple adverse effects of ATV have been reported in clinical practice, such as jaundice, nausea, abdominal pain, and headache. The exact mechanisms of ATV-related adverse effects are unknown. It is generally accepted that a predominant pathway of drug-induced toxicity is through the generation of reactive metabolites. Our current study was designed to explore reactive metabolites of ATV. We used a metabolomic approach to profile ATV metabolism in mice and human liver microsomes. We identified 5 known and 13 novel ATV metabolites. Three potential reactive metabolites were detected and characterized for the first time: one aromatic aldehyde, one α-hydroxyaldehyde, and one hydrazine. These potential reactive metabolites were primarily generated by CYP3A. Our results provide a clue for studies on ATV-related adverse effects from the aspect of metabolic activation. Further studies are suggested to illustrate the impact of these potential reactive metabolites on ATV-related adverse effects. PMID:21148252

Field evaluation of smart sensor vehicle detectors at intersections - volume 2 : performance under adverse weather conditions.

DOT National Transportation Integrated Search

2013-04-01

Two microwave-based systems for vehicle detection (by Wavetronix and MS SEDCO) were evaluated at stop bar and : advance zones of a signalized intersection under three adverse weather conditions: (1) wind, (2) snow-covered roadway, : and (3) rain. Wea...

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...

21 CFR 600.80 - Postmarketing reporting of adverse experiences.

Code of Federal Regulations, 2011 CFR

2011-04-01

... epidemiological/surveillance studies, reports in the scientific literature, and unpublished scientific papers... products to the Center for Biologics Evaluation and Research (HFM-210), or to the Center for Drug Evaluation and Research (see mailing addresses in § 600.2). Submit all vaccine adverse experience reports to...

21 CFR 600.80 - Postmarketing reporting of adverse experiences.

Code of Federal Regulations, 2012 CFR

2012-04-01

... epidemiological/surveillance studies, reports in the scientific literature, and unpublished scientific papers... products to the Center for Biologics Evaluation and Research (HFM-210), or to the Center for Drug Evaluation and Research (see mailing addresses in § 600.2). Submit all vaccine adverse experience reports to...

21 CFR 600.80 - Postmarketing reporting of adverse experiences.

Code of Federal Regulations, 2014 CFR

2014-04-01

... epidemiological/surveillance studies, reports in the scientific literature, and unpublished scientific papers... products to the Center for Biologics Evaluation and Research (HFM-210), or to the Center for Drug Evaluation and Research (see mailing addresses in § 600.2). Submit all vaccine adverse experience reports to...

21 CFR 600.80 - Postmarketing reporting of adverse experiences.

Code of Federal Regulations, 2013 CFR

2013-04-01

... epidemiological/surveillance studies, reports in the scientific literature, and unpublished scientific papers... products to the Center for Biologics Evaluation and Research (HFM-210), or to the Center for Drug Evaluation and Research (see mailing addresses in § 600.2). Submit all vaccine adverse experience reports to...

21 CFR 812.46 - Monitoring investigations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED...) Unanticipated adverse device effects. (1) A sponsor shall immediately conduct an evaluation of any unanticipated adverse device effect. (2) A sponsor who determines that an unanticipated adverse device effect presents...

A survey of the use of herbs among patients attending secondary-level health care facilities in southwestern Nigeria.

PubMed

Fakeye, Titilayo Oyelola; Tijani, Abu; Adebisi, O

2007-01-01

This study was carried out to evaluate the herb usage among patients attending secondary health facilities in Southwestern Nigeria. Data including allergies to drug and herbs, use of social drugs, and herbs and their perceived efficacy to herbs was collected from 265 patients (inpatients n = 65; outpatients n = 200) using structured questionnaire and patients' drug charts. A total of 15.4% of inpatients were found to be using herbs that may be potentially harmful due to drug-drug/drug-herb interactions. Nine percent experienced adverse effects with the use of herbs, whereas 2% experienced adverse reactions on coadministration with prescribed drugs. A high percent of outpatients, 38%, were using alcoholic beverages for extracting the plant materials themselves. The study showed that the use of herbs with drugs is widely practiced among patients attending secondary health care facilities in Nigeria, usually without the doctor or pharmacist's knowledge.

Dietary iron intake, iron status, and gestational diabetes.

PubMed

Zhang, Cuilin; Rawal, Shristi

2017-12-01

Pregnant women are particularly vulnerable to iron deficiency and related adverse pregnancy outcomes and, as such, are routinely recommended for iron supplementation. Emerging evidence from both animal and population-based studies, however, has raised potential concerns because significant associations have been observed between greater iron stores and disturbances in glucose metabolism, including increased risk of type 2 diabetes among nonpregnant individuals. Yet, the evidence is uncertain regarding the role of iron in the development of gestational diabetes mellitus (GDM), a common pregnancy complication which has short-term and long-term adverse health ramifications for both women and their children. In this review, we critically and systematically evaluate available data examining the risk of GDM associated with dietary iron, iron supplementation, and iron status as measured by blood concentrations of several indicators. We also discuss major methodologic concerns regarding the available epidemiologic studies on iron and GDM. © 2017 American Society for Nutrition.

Safety pharmacology--current and emerging concepts.

PubMed

Hamdam, Junnat; Sethu, Swaminathan; Smith, Trevor; Alfirevic, Ana; Alhaidari, Mohammad; Atkinson, Jeffrey; Ayala, Mimieveshiofuo; Box, Helen; Cross, Michael; Delaunois, Annie; Dermody, Ailsa; Govindappa, Karthik; Guillon, Jean-Michel; Jenkins, Rosalind; Kenna, Gerry; Lemmer, Björn; Meecham, Ken; Olayanju, Adedamola; Pestel, Sabine; Rothfuss, Andreas; Sidaway, James; Sison-Young, Rowena; Smith, Emma; Stebbings, Richard; Tingle, Yulia; Valentin, Jean-Pierre; Williams, Awel; Williams, Dominic; Park, Kevin; Goldring, Christopher

2013-12-01

Safety pharmacology (SP) is an essential part of the drug development process that aims to identify and predict adverse effects prior to clinical trials. SP studies are described in the International Conference on Harmonisation (ICH) S7A and S7B guidelines. The core battery and supplemental SP studies evaluate effects of a new chemical entity (NCE) at both anticipated therapeutic and supra-therapeutic exposures on major organ systems, including cardiovascular, central nervous, respiratory, renal and gastrointestinal. This review outlines the current practices and emerging concepts in SP studies including frontloading, parallel assessment of core battery studies, use of non-standard species, biomarkers, and combining toxicology and SP assessments. Integration of the newer approaches to routine SP studies may significantly enhance the scope of SP by refining and providing mechanistic insight to potential adverse effects associated with test compounds. Copyright © 2013 Elsevier Inc. All rights reserved.

A Lousy Reason for Surgery Cancellations.

PubMed

Walker, Christian; Sebastian, Roby; Krishna, Senthil; Tobias, Joseph D

2016-07-01

Cancellation of surgery has significant adverse impact on patients, health care providers, and their associated facilities. Although head lice infestation has not been shown to be associated with adverse surgical outcomes, it often prompts case cancellation by surgical and anesthesia personnel. The purpose of our study was to evaluate the extent and impact of surgery cancellations due to head lice infestation. In our study, a total of 9 patients were cancelled over a 3-year period. Although there is no direct evidence to show that head lice infestation poses a risk to surgical outcomes, the possibility of underlying secondary bacterial infection at the skin excoriation site is often the concern in these patients. This study offers the first investigation into the impact of head lice infections on operating room cancellations, which may prove to be a potential source of intervention to prevent cancellations. © The Author(s) 2015.

Food allergies are rarely a concern when considering vaccines for adolescents.

PubMed

Buyantseva, Larisa V; Horwitz, Alexandra

2014-03-01

Routine immunization provides protection from numerous infectious diseases and substantially reduces morbidity mortality from these diseases. In the United States, vaccination programs focused on infants and children have successfully decreased the incidence of many childhood vaccine-preventable diseases. However, vaccination coverage among adolescents has remained stagnant. Contributing to this lack of coverage is that patients with food allergies might be advised unnecessarily to avoid certain vaccinations, thus potentially causing adverse personal and community health. Studies have shown that food allergies are rarely contraindications to vaccine administration. Most adolescents who avoid vaccination because of food allergy concerns are actually able to receive their appropriate vaccinations. However, there are situations when evaluation by an allergist is recommended. In the present article, the authors provide guidance for physicians when administering vaccines to patients with food allergies to prevent adverse events and improve disease protection.

Immune-mediated Adverse Effects of Anti-CTLA-4 Antibody Therapy in Metastatic Melanoma

PubMed Central

Quirk, Shannon K.; Shure, Anna K.; Agrawal, Devendra K.

2015-01-01

Ipilimumab, an antibody that blocks cytotoxic T lymphocyte-associated antigen-4 (CTLA-4; CD152), was approved by the Food and Drug Administration (FDA) in 2011 for the treatment of unresectable stage III or IV malignant melanoma. Although the addition of this particular immunotherapy has broadened treatment options, immune-related adverse events (irAEs) are associated with ipilimumab therapy, including dermatologic effects, colitis and diarrhea, endocrine effects, hepatotoxicity, ocular effects, renal effects, neurologic effects, and others. In this article, a critical evaluation of the underlying mechanisms of irAEs associated with anti-CTLA-4 therapy is presented. Additionally, potentially beneficial effects of combinational therapies to alleviate ipilimumab-induced irAEs in malignant melanoma are discussed. Future research is warranted to elucidate the efficacy of such combination therapies as well as specific biomarkers that would help to predict a clinical response to ipilimumab in patients with malignant melanoma. PMID:26118951

Maternal vaccination for the prevention of influenza: current status and hopes for the future

PubMed Central

Phadke, Varun K.; Omer, Saad B.

2016-01-01

Influenza is an important cause of morbidity and mortality among pregnant women and young infants, and influenza infection during pregnancy has also been associated with adverse obstetric and birth outcomes. There is substantial evidence – from randomized trials and observational studies – that maternal influenza immunization can protect pregnant women and their infants from influenza disease. In addition, there is compelling observational evidence that prevention of influenza in pregnant women can also protect against certain adverse pregnancy outcomes, including stillbirth and preterm birth. In this article we will review and evaluate the literature on both the burden of influenza disease in pregnant women and infants, as well as the multiple potential benefits of maternal influenza immunization for mother, fetus, and infant. We will also review key clinical aspects of maternal influenza immunization, as well as identify remaining knowledge gaps, and discuss avenues for future investigation. PMID:27070268

Does the evidence about health risks associated with nitrate ingestion warrant an increase of the nitrate standard for drinking water?

PubMed Central

van Grinsven, Hans JM; Ward, Mary H; Benjamin, Nigel; de Kok, Theo M

2006-01-01

Several authors have suggested that it is safe to raise the health standard for nitrate in drinking water, and save money on measures associated with nitrate pollution of drinking water resources. The major argument has been that the epidemiologic evidence for acute and chronic health effects related to drinking water nitrate at concentrations near the health standard is inconclusive. With respect to the chronic effects, the argument was motivated by the absence of evidence for adverse health effects related to ingestion of nitrate from dietary sources. An interdisciplinary discussion of these arguments led to three important observations. First, there have been only a few well-designed epidemiologic studies that evaluated ingestion of nitrate in drinking water and risk of specific cancers or adverse reproductive outcomes among potentially susceptible subgroups likely to have elevated endogenous nitrosation. Positive associations have been observed for some but not all health outcomes evaluated. Second, the epidemiologic studies of cancer do not support an association between ingestion of dietary nitrate (vegetables) and an increased risk of cancer, because intake of dietary nitrate is associated with intake of antioxidants and other beneficial phytochemicals. Third, 2–3 % of the population in Western Europe and the US could be exposed to nitrate levels in drinking water exceeding the WHO standard of 50 mg/l nitrate, particularly those living in rural areas. The health losses due to this exposure cannot be estimated. Therefore, we conclude that it is not possible to weigh the costs and benefits from changing the nitrate standard for drinking water and groundwater resources by considering the potential consequences for human health and by considering the potential savings due to reduced costs for nitrate removal and prevention of nitrate pollution. PMID:16989661

Conceptual model for assessing criteria air pollutants in a multipollutant context: A modified adverse outcome pathway approach.

PubMed

Buckley, Barbara; Farraj, Aimen

2015-09-01

Air pollution consists of a complex mixture of particulate and gaseous components. Individual criteria and other hazardous air pollutants have been linked to adverse respiratory and cardiovascular health outcomes. However, assessing risk of air pollutant mixtures is difficult since components are present in different combinations and concentrations in ambient air. Recent mechanistic studies have limited utility because of the inability to link measured changes to adverse outcomes that are relevant to risk assessment. New approaches are needed to address this challenge. The purpose of this manuscript is to describe a conceptual model, based on the adverse outcome pathway approach, which connects initiating events at the cellular and molecular level to population-wide impacts. This may facilitate hazard assessment of air pollution mixtures. In the case reports presented here, airway hyperresponsiveness and endothelial dysfunction are measurable endpoints that serve to integrate the effects of individual criteria air pollutants found in inhaled mixtures. This approach incorporates information from experimental and observational studies into a sequential series of higher order effects. The proposed model has the potential to facilitate multipollutant risk assessment by providing a framework that can be used to converge the effects of air pollutants in light of common underlying mechanisms. This approach may provide a ready-to-use tool to facilitate evaluation of health effects resulting from exposure to air pollution mixtures. Published by Elsevier Ireland Ltd.

Towards Large-scale Twitter Mining for Drug-related Adverse Events.

PubMed

Bian, Jiang; Topaloglu, Umit; Yu, Fan

2012-10-29

Drug-related adverse events pose substantial risks to patients who consume post-market or Drug-related adverse events pose substantial risks to patients who consume post-market or investigational drugs. Early detection of adverse events benefits not only the drug regulators, but also the manufacturers for pharmacovigilance. Existing methods rely on patients' "spontaneous" self-reports that attest problems. The increasing popularity of social media platforms like the Twitter presents us a new information source for finding potential adverse events. Given the high frequency of user updates, mining Twitter messages can lead us to real-time pharmacovigilance. In this paper, we describe an approach to find drug users and potential adverse events by analyzing the content of twitter messages utilizing Natural Language Processing (NLP) and to build Support Vector Machine (SVM) classifiers. Due to the size nature of the dataset (i.e., 2 billion Tweets), the experiments were conducted on a High Performance Computing (HPC) platform using MapReduce, which exhibits the trend of big data analytics. The results suggest that daily-life social networking data could help early detection of important patient safety issues.

Can the frequency and risks of fatal adverse drug events be determined?

PubMed

Kelly, W N

2001-05-01

Death is the ultimate adverse drug event. Despite its importance, the frequency of fatal adverse drug events is unknown. Estimates in the United States are as high as 140,000/year, although this number is heavily disputed. Potential reasons and risks for fatal adverse drug events, as well as epidemiologic designs for studying this important public health issue, are discussed and issues are raised to promote further thought.

Orthopaedic Snafus: When Adverse Events Happen in Orthopaedics.

PubMed

Smith, Mary Atkinson; Walsh, Colleen; Levin, Barbara; Eaten, Kathyrn; Yager, Melissa

The potential for adverse events exists when treating and managing orthopaedic patients in the intraoperative or postoperative environments, especially when it comes to falls, surgical site infections, venous thromboembolism, and injuries to nerves and blood vessels. Orthopaedic nurses play a vital role in the promotion and use of evidence-based interventions to decrease the incidence of these adverse events, improve quality of care, and minimize the financial burden related to these adverse events.

Differences between Drug-Induced and Contrast Media-Induced Adverse Reactions Based on Spontaneously Reported Adverse Drug Reactions.

PubMed

Ryu, JiHyeon; Lee, HeeYoung; Suh, JinUk; Yang, MyungSuk; Kang, WonKu; Kim, EunYoung

2015-01-01

We analyzed differences between spontaneously reported drug-induced (not including contrast media) and contrast media-induced adverse reactions. Adverse drug reactions reported by an in-hospital pharmacovigilance center (St. Mary's teaching hospital, Daejeon, Korea) from 2010-2012 were classified as drug-induced or contrast media-induced. Clinical patterns, frequency, causality, severity, Schumock and Thornton's preventability, and type A/B reactions were recorded. The trends among causality tools measuring drug and contrast-induced adverse reactions were analyzed. Of 1,335 reports, 636 drug-induced and contrast media-induced adverse reactions were identified. The prevalence of spontaneously reported adverse drug reaction-related admissions revealed a suspected adverse drug reaction-reporting rate of 20.9/100,000 (inpatient, 0.021%) and 3.9/100,000 (outpatients, 0.004%). The most common adverse drug reaction-associated drug classes included nervous system agents and anti-infectives. Dermatological and gastrointestinal adverse drug reactions were most frequently and similarly reported between drug and contrast media-induced adverse reactions. Compared to contrast media-induced adverse reactions, drug-induced adverse reactions were milder, more likely to be preventable (9.8% vs. 1.1%, p < 0.001), and more likely to be type A reactions (73.5% vs. 18.8%, p < 0.001). Females were over-represented among drug-induced adverse reactions (68.1%, p < 0.001) but not among contrast media-induced adverse reactions (56.6%, p = 0.066). Causality patterns differed between the two adverse reaction classes. The World Health Organization-Uppsala Monitoring Centre causality evaluation and Naranjo algorithm results significantly differed from those of the Korean algorithm version II (p < 0.001). We found differences in sex, preventability, severity, and type A/B reactions between spontaneously reported drug and contrast media-induced adverse reactions. The World Health Organization-Uppsala Monitoring Centre and Naranjo algorithm causality evaluation afforded similar results.

Differences between Drug-Induced and Contrast Media-Induced Adverse Reactions Based on Spontaneously Reported Adverse Drug Reactions

PubMed Central

Suh, JinUk; Yang, MyungSuk; Kang, WonKu; Kim, EunYoung

2015-01-01

Objective We analyzed differences between spontaneously reported drug-induced (not including contrast media) and contrast media-induced adverse reactions. Methods Adverse drug reactions reported by an in-hospital pharmacovigilance center (St. Mary’s teaching hospital, Daejeon, Korea) from 2010–2012 were classified as drug-induced or contrast media-induced. Clinical patterns, frequency, causality, severity, Schumock and Thornton’s preventability, and type A/B reactions were recorded. The trends among causality tools measuring drug and contrast-induced adverse reactions were analyzed. Results Of 1,335 reports, 636 drug-induced and contrast media-induced adverse reactions were identified. The prevalence of spontaneously reported adverse drug reaction-related admissions revealed a suspected adverse drug reaction-reporting rate of 20.9/100,000 (inpatient, 0.021%) and 3.9/100,000 (outpatients, 0.004%). The most common adverse drug reaction-associated drug classes included nervous system agents and anti-infectives. Dermatological and gastrointestinal adverse drug reactions were most frequently and similarly reported between drug and contrast media-induced adverse reactions. Compared to contrast media-induced adverse reactions, drug-induced adverse reactions were milder, more likely to be preventable (9.8% vs. 1.1%, p < 0.001), and more likely to be type A reactions (73.5% vs. 18.8%, p < 0.001). Females were over-represented among drug-induced adverse reactions (68.1%, p < 0.001) but not among contrast media-induced adverse reactions (56.6%, p = 0.066). Causality patterns differed between the two adverse reaction classes. The World Health Organization–Uppsala Monitoring Centre causality evaluation and Naranjo algorithm results significantly differed from those of the Korean algorithm version II (p < 0.001). Conclusions We found differences in sex, preventability, severity, and type A/B reactions between spontaneously reported drug and contrast media-induced adverse reactions. The World Health Organization–Uppsala Monitoring Centre and Naranjo algorithm causality evaluation afforded similar results. PMID:26544039

Standard Information Models for Representing Adverse Sensitivity Information in Clinical Documents.

PubMed

Topaz, M; Seger, D L; Goss, F; Lai, K; Slight, S P; Lau, J J; Nandigam, H; Zhou, L

2016-01-01

Adverse sensitivity (e.g., allergy and intolerance) information is a critical component of any electronic health record system. While several standards exist for structured entry of adverse sensitivity information, many clinicians record this data as free text. This study aimed to 1) identify and compare the existing common adverse sensitivity information models, and 2) to evaluate the coverage of the adverse sensitivity information models for representing allergy information on a subset of inpatient and outpatient adverse sensitivity clinical notes. We compared four common adverse sensitivity information models: Health Level 7 Allergy and Intolerance Domain Analysis Model, HL7-DAM; the Fast Healthcare Interoperability Resources, FHIR; the Consolidated Continuity of Care Document, C-CDA; and OpenEHR, and evaluated their coverage on a corpus of inpatient and outpatient notes (n = 120). We found that allergy specialists' notes had the highest frequency of adverse sensitivity attributes per note, whereas emergency department notes had the fewest attributes. Overall, the models had many similarities in the central attributes which covered between 75% and 95% of adverse sensitivity information contained within the notes. However, representations of some attributes (especially the value-sets) were not well aligned between the models, which is likely to present an obstacle for achieving data interoperability. Also, adverse sensitivity exceptions were not well represented among the information models. Although we found that common adverse sensitivity models cover a significant portion of relevant information in the clinical notes, our results highlight areas needed to be reconciled between the standards for data interoperability.

[Analysis of Kudiezi injection's security literature].

PubMed

Chang, Yan-Peng; Xie, Yan-Ming

2012-09-01

By retrieving the relevant database, aim was to achieve the security reported of Kudiezi injection (Yueanxin). To analysis the gender, age, underlying disease, medication dosage, solvent, adverse event/adverse reaction time of occurrence, clinical presentation of patients, It was found the adverse event/adverse reaction usually occur in older people, involving the organs and systems include skin and its appendages, digestive system, nervous system, circulatory system, respiratory system, systemic reaction, part of the adverse event/adverse reaction's cause were not according to the instructions. It was found on the adverse event/adverse reaction of the judgment on the lack of objective evidence, to produce certain effect for objective evaluation of security of Kudiezi injection (Yueanxin).

Generic versus brand-name drugs used in cardiovascular diseases.

PubMed

Manzoli, Lamberto; Flacco, Maria Elena; Boccia, Stefania; D'Andrea, Elvira; Panic, Nikola; Marzuillo, Carolina; Siliquini, Roberta; Ricciardi, Walter; Villari, Paolo; Ioannidis, John P A

2016-04-01

This meta-analysis aimed to compare the efficacy and adverse events, either serious or mild/moderate, of all generic versus brand-name cardiovascular medicines. We searched randomized trials in MEDLINE, Scopus, EMBASE, Cochrane Controlled Clinical Trial Register, and ClinicalTrials.gov (last update December 1, 2014). Attempts were made to contact the investigators of all potentially eligible trials. Two investigators independently extracted and analyzed soft (including systolic blood pressure, LDL cholesterol, and others) and hard efficacy outcomes (including major cardiovascular adverse events and death), minor/moderate and serious adverse events. We included 74 randomized trials; 53 reported ≥1 efficacy outcome (overall sample 3051), 32 measured mild/moderate adverse events (n = 2407), and 51 evaluated serious adverse events (n = 2892). We included trials assessing ACE inhibitors (n = 12), anticoagulants (n = 5), antiplatelet agents (n = 17), beta-blockers (n = 11), calcium channel blockers (n = 7); diuretics (n = 13); statins (n = 6); and others (n = 3). For both soft and hard efficacy outcomes, 100 % of the trials showed non-significant differences between generic and brand-name drugs. The aggregate effect size was 0.01 (95 % CI -0.05; 0.08) for soft outcomes; -0.06 (-0.71; 0.59) for hard outcomes. All but two trials showed non-significant differences in mild/moderate adverse events, and aggregate effect size was 0.07 (-0.06; 0.20). Comparable results were observed for each drug class and in each stratified meta-analysis. Overall, 8 serious possibly drug-related adverse events were reported: 5/2074 subjects on generics; 3/2076 subjects on brand-name drugs (OR 1.69; 95 % CI 0.40-7.20). This meta-analysis strengthens the evidence for clinical equivalence between brand-name and generic cardiovascular drugs. Physicians could be reassured about prescribing generic cardiovascular drugs, and health care organization about endorsing their wider use.

Safety and Efficacy of Ziagen (Abacavir Sulfate) in HIV-Infected Korean Patients.

PubMed

Ann, Heawon; Kim, Ki Hyon; Choi, Hyun Young; Chang, Hyun Ha; Han, Sang Hoon; Kim, Kye Hyung; Lee, Jin Soo; Kim, Yeon Sook; Park, Kyung Hwa; Kim, Young Keun; Sohn, Jang Wook; Yun, Na Ra; Lee, Chang Seop; Choi, Young Wha; Lee, Yil Seob; Kim, Shin Woo

2017-09-01

Abacavir is a widely-used nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) infection. Mandatory postmarketing surveillance was conducted in Korea to monitor the safety and evaluate the effectiveness of Ziagen® (abacavir sulfate 300 mg; ViiV Healthcare, Middlesex, UK). An open-label, multi-center, non-interventional postmarketing surveillance study was conducted from June 2010 to June 2016 to monitor the safety and effectiveness of Ziagen across 12 hospitals in Korea. Subjects older than 18 years taking Ziagen according to prescribing information were enrolled. The primary outcome was defined as the occurrence of any adverse events after Ziagen administration. Secondary outcomes included the occurrence of adverse drug reactions, occurrence of serious adverse events, and effectiveness of Ziagen administration. A total of 669 patients were enrolled in this study, with a total observation period of 1047.8 person-years. Of these, 90.7% of patients were male. The mean age of patients was 45.8±11.9 years. One-hundred ninety-six (29.3%) patients reported 315 adverse events, and four patients reported seven serious adverse events, without any fatal events. There was one potential case of an abacavir hypersensitivity reaction. Among the 97 adverse drug reactions that were reported from 75 patients, the most frequent adverse drug reactions included diarrhea (12 events), dyspepsia (10 events), and rash (9 events). No ischemic heart disease was observed. In the effectiveness analysis, 91% of patients achieved HIV-1 RNA under 50 copies/mL after 24 months of observation with abacavir administration. Our data showed the safety and effectiveness of Ziagen in a real-world setting. During the study period, Ziagen was well-tolerated, with one incident of a clinically suspected abacavir hypersensitivity reaction. The postmarketing surveillance of Ziagen did not highlight any new safety information. These data may be helpful in understanding abacavir and the HIV treatment practices in Korea. Copyright © 2017 by The Korean Society of Infectious Diseases and Korean Society for Chemotherapy

Descriptions of Adverse Drug Reactions Are Less Informative in Forums Than in the French Pharmacovigilance Database but Provide More Unexpected Reactions

PubMed Central

Karapetiantz, Pierre; Bellet, Florelle; Audeh, Bissan; Lardon, Jérémy; Leprovost, Damien; Aboukhamis, Rim; Morlane-Hondère, François; Grouin, Cyril; Burgun, Anita; Katsahian, Sandrine; Jaulent, Marie-Christine; Beyens, Marie-Noëlle; Lillo-Le Louët, Agnès; Bousquet, Cédric

2018-01-01

Background: Social media have drawn attention for their potential use in Pharmacovigilance. Recent work showed that it is possible to extract information concerning adverse drug reactions (ADRs) from posts in social media. The main objective of the Vigi4MED project was to evaluate the relevance and quality of the information shared by patients on web forums about drug safety and its potential utility for pharmacovigilance. Methods: After selecting websites of interest, we manually evaluated the relevance of the content of posts for pharmacovigilance related to six drugs (agomelatine, baclofen, duloxetine, exenatide, strontium ranelate, and tetrazepam). We compared forums to the French Pharmacovigilance Database (FPVD) to (1) evaluate whether they contained relevant information to characterize a pharmacovigilance case report (patient’s age and sex; treatment indication, dose and duration; time-to-onset (TTO) and outcome of the ADR, and drug dechallenge and rechallenge) and (2) perform impact analysis (nature, seriousness, unexpectedness, and outcome of the ADR). Results: The cases in the FPVD were significantly more informative than posts in forums for patient description (age, sex), treatment description (dose, duration, TTO), and outcome of the ADR, but the indication for the treatment was more often found in forums. Cases were more often serious in the FPVD than in forums (46% vs. 4%), but forums more often contained an unexpected ADR than the FPVD (24% vs. 17%). Moreover, 197 unexpected ADRs identified in forums were absent from the FPVD and the distribution of the MedDRA System Organ Classes (SOCs) was different between the two data sources. Discussion: This study is the first to evaluate if patients’ posts may qualify as potential and informative case reports that should be stored in a pharmacovigilance database in the same way as case reports submitted by health professionals. The posts were less informative (except for the indication) and focused on less serious ADRs than the FPVD cases, but more unexpected ADRs were presented in forums than in the FPVD and their SOCs were different. Thus, web forums should be considered as a secondary, but complementary source for pharmacovigilance. PMID:29765326

Rethinking risk assessment for emerging technology first-in-human trials.

PubMed

Genske, Anna; Engel-Glatter, Sabrina

2016-03-01

Recent progress in synthetic biology (SynBio) has enabled the development of novel therapeutic opportunities for the treatment of human disease. In the near future, first-in-human trials (FIH) will be indicated. FIH trials mark a key milestone in the translation of medical SynBio applications into clinical practice. Fostered by uncertainty of possible adverse events for trial participants, a variety of ethical concerns emerge with regards to SynBio FIH trials, including 'risk' minimization. These concerns are associated with any FIH trial, however, due to the novelty of the approach, they become more pronounced for medical applications of emerging technologies (emTech) like SynBio. To minimize potential harm for trial participants, scholars, guidelines, regulations and policy makers alike suggest using 'risk assessment' as evaluation tool for such trials. Conversely, in the context of emTech FIH trials, we believe it to be at least questionable to contextualize uncertainty of potential adverse events as 'risk' and apply traditional risk assessment methods. Hence, this issue needs to be discussed to enable alterations of the evaluation process before the translational phase of SynBio applications begins. In this paper, we will take the opportunity to start the debate and highlight how a misunderstanding of the concept of risk, and the possibilities and limitations of risk assessment, respectively, might impair decision-making by the relevant regulatory authorities and research ethics committees, and discuss possible solutions to tackle the issue.

Development, evaluation, and application of sediment quality targets for assessing and managing contaminated sediments in Tampa Bay, Florida

USGS Publications Warehouse

MacDonald, D.D.; Carr, R.S.; Eckenrod, D.; Greening, H.; Grabe, S.; Ingersoll, C.G.; Janicki, S.; Janicki, T.; Lindskoog, R.A.; Long, E.R.; Pribble, R.; Sloane, G.; Smorong, D.E.

2004-01-01

Tampa Bay is a large, urban estuary that is located in west central Florida. Although water quality conditions represent an important concern in this estuary, information from numerous sources indicates that sediment contamination also has the potential to adversely affect aquatic organisms, aquatic-dependent wildlife, and human health. As such, protecting relatively uncontaminated areas of the bay from contamination and reducing the amount of toxic chemicals in contaminated sediments have been identified as high-priority sediment management objectives for Tampa Bay. To address concerns related to sediment contamination in the bay, an ecosystem-based framework for assessing and managing sediment quality conditions was developed that included identification of sediment quality issues and concerns, development of ecosystem goals and objectives, selection of ecosystem health indicators, establishment of metrics and targets for key indicators, and incorporation of key indicators, metrics, and targets into watershed management plans and decision-making processes. This paper describes the process that was used to select and evaluate numerical sediment quality targets (SQTs) for assessing and managing contaminated sediments. These SQTs included measures of sediment chemistry, whole-sediment and pore-water toxicity, and benthic invertebrate community structure. In addition, the paper describes how the SQTs were used to develop site-specific concentration-response models that describe how the frequency of adverse biological effects changes with increasing concentrations of chemicals of potential concern. Finally, a key application of the SQTs for defining sediment management areas is discussed.

A Procedure For Evaluation Of Non-Ionizing Photocopier Emissions

NASA Astrophysics Data System (ADS)

Lehman, Richard; Edmunds, H. D.

1980-10-01

Recent consumer awareness of previously unquestioned devices, tne misuse of products and developments in optical technology have created a demand for a better understanding of the potentially adverse effects from intense optical sources. The commercial application of lasers and the various standards for laser product performance have also accelerated this demand for an understanding of the effects of broad band optical sources. The potential for adverse eye changes while viewing the sun during solar eclipse has been recorded since early timer and the reddening of skin and sunburn have been experienced by most people. The Biomedical studies to quantify the effects of spectral emission and dose relationship from manmade sources has recently been undertaken. It is only within the last several decades that the need for understanding the biological effects of optical radiation upon man has become of interest. Much of the early work in understanding these effects resulted from interest in therapeutic application. It is only within the last decade that research has considered the non-therapeutic effects. To our knowledge only a few organizations have thus far established exposure criteria from broad band optical sources to prevent the harmful effects of overexposure. This paper will detail the techniques used by the Xerox Corporation to evaluate broad band optical sources for use in office machines. While the specific examples will be for fluorescent lamp sources, the limits and procedures are equally valid for other broad band optical sources such as arc, flash and lamp arrays found in most industrial, commercial and military applications.

Perioperative analgesia for patients undergoing endoscopic sinus surgery: an evidence-based review.

PubMed

Svider, Peter F; Nguyen, Brandon; Yuhan, Brian; Zuliani, Giancarlo; Eloy, Jean Anderson; Folbe, Adam J

2018-04-12

Misuse and diversion of prescription opioids have been critical in facilitating the opioid epidemic. Our objective was to perform a systematic evidence-based review delineating perioperative regimens (including opioid alternatives) evaluated for endoscopic sinus surgery. PubMed/MEDLINE, Cochrane Library, and EmBase databases were evaluated for studies detailing analgesics employed after endoscopic sinus surgery. Studies were assessed for level of evidence. Bias risk was evaluated using the Cochrane Bias tool and GRADE criteria. Medication, administration, adverse effects, pain scores, and rescue analgesic consumption were evaluated. A summary of evidence detailing benefits, harm, and cost was prepared. Thirty-two studies encompassing 1812 patients were included. The GRADE criteria determined the overall evidence to be of moderate quality. Perioperative acetaminophen had few adverse events and reduced immediate need for opioid rescue after sinus surgery; studies evaluating acetaminophen demonstrate a preponderance of benefit over harm. Nonsteroidal anti-inflammatory drugs (NSAIDs) also reduce postoperative opioid consumption, although a small portion of patients undergoing sinus surgery harbor the potential for NSAID intolerance. The aggregate level of evidence for studies evaluating NSAIDs was grade A, whereas the aggregate grade of evidence for several other agents was grade B. There is evidence supporting the use of NSAIDs and gabapentin for the control of pain after endoscopic sinus surgery. Acetaminophen, α-agonists, and local anesthetics are also viable options for postoperative analgesia. Familiarity with these data is essential to facilitate the use of opioid alternatives. Further large-scale, multi-institutional, randomized trials are needed to provide conclusive recommendations for these perioperative analgesics. © 2018 ARS-AAOA, LLC.

Isolation, characterization and antimicrobial evaluation of a novel compound N-octacosan 7β ol, from Fumaria parviflora Lam.

PubMed

Jameel, Mohammad; Islamuddin, Mohammad; Ali, Abuzer; Afrin, Farhat; Ali, Mohammed

2014-03-12

Fumaria parviflora Lam. (Fumaraceae) is widely used in traditional as well as folkloric system of medicine from ancient. It is commonly known as 'Pitpapra' or 'Shahtrah' in Indian traditional system of medicine and used for treating numerous ailments like diarrhea, fever, influenza, blood purifier and other complications. The object of the present study was to evaluate the Antileishmanial, antibacterial, antifungal and cytotoxic potential of isolated compound. Methanolic extract of whole plant of Fumaria parviflora was dried under reduced pressure to obtain a dark brown residue which was adsorbed on silica gel column grade (60-120 mesh) to obtain a slurry and chromatographed over silica gel loaded column in petroleum ether-chloroform (3:1, 1:1 and 1:3 v/v). The in vitro antileishmanial evaluation of isolated compound against Leishmania donovani promastigotes was investigated by growth kinetics assay, reversibility assay, analysis of cellular morphology, adverse toxicity and determination of 50% growth inhibitory concentration (GI50). Disc diffusion and broth micro dilution methods were used to study the antibacterial (Gram + Staphylococcus epidermidis and Bacillus subtilis; Gram - Escherichia coli and Salmonella typhimurium) and antifungal (Candida albicans and Aspergillus niger) potential in vitro. Structure elucidation by spectral data analysis revealed a novel compound, n-octacosan-7β-ol (OC), yield (0.471%), having significant antimicrobial activity against Leishmania donovani promastigotes, Staphylococcus epidermidis, Escherichia coli, Candida albicans and Aspergillus niger in vitro with GI50 = 5.35, MIC 250, MIC 250 and MFC 500 and MIC 250 μg ml(-1) respectively. The isolated compound did not show adverse effect against mammalian macrophages. The available evidence of compound suggested that it may be used as antimicrobial agent in future and may provide new platform for drug discovery programmes for leishmaniasis.

The food and environmental safety of Bt crops.

PubMed

Koch, Michael S; Ward, Jason M; Levine, Steven L; Baum, James A; Vicini, John L; Hammond, Bruce G

2015-01-01

Bacillus thuringiensis (Bt) microbial pesticides have a 50-year history of safety in agriculture. Cry proteins are among the active insecticidal ingredients in these pesticides, and genes coding for Cry proteins have been introduced into agricultural crops using modern biotechnology. The Cry gene sequences are often modified to enable effective expression in planta and several Cry proteins have been modified to increase biological activity against the target pest(s). Additionally, the domains of different but structurally conserved Cry proteins can be combined to produce chimeric proteins with enhanced insecticidal properties. Environmental studies are performed and include invertebrates, mammals, and avian species. Mammalian studies used to support the food and feed safety assessment are also used to support the wild mammal assessment. In addition to the NTO assessment, the environmental assessment includes a comparative assessment between the Bt crop and the appropriate conventional control that is genetically similar but lacks the introduced trait to address unintended effects. Specific phenotypic, agronomic, and ecological characteristics are measured in the Bt crop and the conventional control to evaluate whether the introduction of the insect resistance has resulted in any changes that might cause ecological harm in terms of altered weed characteristics, susceptibility to pests, or adverse environmental impact. Additionally, environmental interaction data are collected in field experiments for Bt crop to evaluate potential adverse effects. Further to the agronomic and phenotypic evaluation, potential movement of transgenes from a genetically modified crop plants into wild relatives is assessed for a new pest resistance gene in a new crop. This review summarizes the evidence for safety of crops containing Cry proteins for humans, livestock, and other non-target organisms.

The food and environmental safety of Bt crops

PubMed Central

Koch, Michael S.; Ward, Jason M.; Levine, Steven L.; Baum, James A.; Vicini, John L.; Hammond, Bruce G.

2015-01-01

Bacillus thuringiensis (Bt) microbial pesticides have a 50-year history of safety in agriculture. Cry proteins are among the active insecticidal ingredients in these pesticides, and genes coding for Cry proteins have been introduced into agricultural crops using modern biotechnology. The Cry gene sequences are often modified to enable effective expression in planta and several Cry proteins have been modified to increase biological activity against the target pest(s). Additionally, the domains of different but structurally conserved Cry proteins can be combined to produce chimeric proteins with enhanced insecticidal properties. Environmental studies are performed and include invertebrates, mammals, and avian species. Mammalian studies used to support the food and feed safety assessment are also used to support the wild mammal assessment. In addition to the NTO assessment, the environmental assessment includes a comparative assessment between the Bt crop and the appropriate conventional control that is genetically similar but lacks the introduced trait to address unintended effects. Specific phenotypic, agronomic, and ecological characteristics are measured in the Bt crop and the conventional control to evaluate whether the introduction of the insect resistance has resulted in any changes that might cause ecological harm in terms of altered weed characteristics, susceptibility to pests, or adverse environmental impact. Additionally, environmental interaction data are collected in field experiments for Bt crop to evaluate potential adverse effects. Further to the agronomic and phenotypic evaluation, potential movement of transgenes from a genetically modified crop plants into wild relatives is assessed for a new pest resistance gene in a new crop. This review summarizes the evidence for safety of crops containing Cry proteins for humans, livestock, and other non-target organisms. PMID:25972882

Application of Adverse Outcome Pathways to U.S. EPA’s Endocrine Disruptor Screening Program

PubMed Central

Noyes, Pamela D.; Casey, Warren M.; Dix, David J.

2017-01-01

Background: The U.S. EPA’s Endocrine Disruptor Screening Program (EDSP) screens and tests environmental chemicals for potential effects in estrogen, androgen, and thyroid hormone pathways, and it is one of the only regulatory programs designed around chemical mode of action. Objectives: This review describes the EDSP’s use of adverse outcome pathway (AOP) and toxicity pathway frameworks to organize and integrate diverse biological data for evaluating the endocrine activity of chemicals. Using these frameworks helps to establish biologically plausible links between endocrine mechanisms and apical responses when those end points are not measured in the same assay. Results: Pathway frameworks can facilitate a weight of evidence determination of a chemical’s potential endocrine activity, identify data gaps, aid study design, direct assay development, and guide testing strategies. Pathway frameworks also can be used to evaluate the performance of computational approaches as alternatives for low-throughput and animal-based assays and predict downstream key events. In cases where computational methods can be validated based on performance, they may be considered as alternatives to specific assays or end points. Conclusions: A variety of biological systems affect apical end points used in regulatory risk assessments, and without mechanistic data, an endocrine mode of action cannot be determined. Because the EDSP was designed to consider mode of action, toxicity pathway and AOP concepts are a natural fit. Pathway frameworks have diverse applications to endocrine screening and testing. An estrogen pathway example is presented, and similar approaches are being used to evaluate alternative methods and develop predictive models for androgen and thyroid pathways. https://doi.org/10.1289/EHP1304 PMID:28934726

Integrative Approaches to Evaluating Neurotoxicity Data for Risk Assessment.

EPA Science Inventory

Risk assessment classically has been based on single adverse outcomes identified as the Lowest Observable Adverse Effect Level (LOAEL) or the highest dose level in a credible study producing a No Observable Adverse Effect Level (NOAEL). While this approach has been useful overal...

Field evaluation of smart sensor vehicle detectors at railroad grade crossings - volume 4 : performance in adverse weather conditions.

DOT National Transportation Integrated Search

2015-01-01

The performance of a microwave radar system for vehicle detection at a railroad grade crossing with quadrant gates was evaluated in : adverse weather conditions: rain (light and torrential), snow (light and heavy), dense fog, and wind. The first part...

Evaluation of video detection systems, volume 4 : effects of adverse weather conditions in the performance of video detection systems.

DOT National Transportation Integrated Search

2009-03-01

The performance of three video detection systems (VDS): Iteris, Autoscope, and Peek, was evaluated : using a side-by-side installation at a signalized intersection under various adverse weather conditions including : rain and snow in both day and nig...

Use of the Biopharmaceutics Drug Disposition Classification System (BDDCS) to Help Predict the Occurrence of Idiosyncratic Cutaneous Adverse Drug Reactions Associated with Antiepileptic Drug Usage.

PubMed

Chan, Rosa; Wei, Chun-Yu; Chen, Yuan-Tsong; Benet, Leslie Z

2016-05-01

Cutaneous adverse reactions (CARs) from antiepileptic drugs (AEDs) are common, ranging from mild to life-threatening, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The identification of subjects carrying the HLA-B*15:02, an inherited allelic variant of the HLA-B gene, and the avoidance of carbamazepine (CBZ) therapy in these subjects are strongly associated with a decrease in the incidence of carbamazepine-induced SJS/TEN. In spite of the strong genetic associations, the initiation of hypersensitivity for AEDs is still not very well characterized. Predicting the potential for other AEDs to cause adverse reactions will be undoubtedly beneficial to avoid CARs, which is the focus of this report. Here, we explore the use of the Biopharmaceutics Drug Disposition Classification System (BDDCS) to distinguish AEDs associated with and without CARs by examining the binding relationship of AEDs to HLA-B*15:02 and data from extensive reviews of medical records. We also evaluate the lack of benefit from a Hong Kong population policy on the effects of screening for HLA-B*15:02 and previous incorrect structure-activity hypotheses. Our analysis concludes that BDDCS class 2 AEDs are more prone to cause adverse cutaneous reactions than certain BDDCS class 1 AEDs and that BDDCS Class 3 drugs have the lowest levels of cutaneous adverse reactions. We propose that BDDCS Class 3 AEDs should be preferentially used for patients with Asian backgrounds (i.e., Han Chinese, Thai, and Malaysian populations) if possible and in patients predisposed to skin rashes.

Nurse Practitioners’ Experience With Herbal Therapy

DTIC Science & Technology

2000-05-01

supplements has also grown. Patient use, benefits, and potential adverse effects of herbal therapy have been well documented in the literature, but...established and a core variable emerged. Results identified nine theme categories related to knowledge, safety, validity and effectiveness , responsibility...decade. Advertisement and access to these supplements has also grown. Patient use, benefits, and potential adverse effects of herbal therapy have been

Will peripherally restricted kappa-opioid receptor agonists (pKORAs) relieve pain with less opioid adverse effects and abuse potential?

PubMed

Albert-Vartanian, A; Boyd, M R; Hall, A L; Morgado, S J; Nguyen, E; Nguyen, V P H; Patel, S P; Russo, L J; Shao, A J; Raffa, R B

2016-08-01

Optimal utilization of opioid analgesics is significantly limited by the central nervous system adverse effects and misuse/abuse potential of currently available drugs. It has been postulated that opioid-associated adverse effects and abuse potential would be greatly reduced if opioids could be excluded from reaching the brain. We review the basic science and clinical evidence of one such approach - peripherally restricted kappa-opioid receptor (KOR) agonists (pKORAs). Published and unpublished literature, websites and other sources were searched for basic science and clinical information related to the potential benefits and development of peripherally restricted kappa-opioid receptor agonists. Each source was summarized, reviewed and assessed. The historical development of pKORAs can be traced from the design of increasingly KOR-selective agonists, elucidation of the pharmacologic attributes of such compounds and strategies to restrict passage across the blood-brain barrier. Novel compounds are under development and have progressed to clinical trials. The results from recent clinical trials suggest that peripherally restricted opioids can be successfully designed and that they can retain analgesic efficacy with a more favourable adverse effect profile. © 2016 John Wiley & Sons Ltd.

Detection of Adverse Drug Reactions using Medical Named Entities on Twitter.

PubMed

MacKinlay, Andrew; Aamer, Hafsah; Yepes, Antonio Jimeno

2017-01-01

Adverse Drug Reactions (ADRs) are unintentional reactions caused by a drug or combination of drugs taken by a patient. The current ADR reporting systems inevitably have delays in reporting such events. The broad scope of social media conversations on sites such as Twitter means that inevitably health-related topics will be covered. This means that these sites could then be used to detect potentially novel ADRs with less latency for subsequent further investigation. In this work, we investigate ADR surveillance using a large corpus of Twitter data, containing around 50 billion tweets spanning 3 years (2012-2014), and evaluate against over 3000 drugs reported in the FAERS database. This is both a larger corpus and broader selection of drugs than previous work in the domain. We compare the ADRs identified using our method to the FDA Adverse Event Reporting System (FAERS) database of ADRs reported using more traditional techniques, and find that Twitter is a useful resource for ADR detection up to 72% micro-averaged precision. Micro-averaged recall of 6% is achievable using only 10% of Twitter, indicating that with a higher-volume or targeted feed it would be possible to detect a large percentage of ADRs.

Anti-prothrombin antibodies are associated with adverse pregnancy outcome.

PubMed

Marozio, Luca; Curti, Antonella; Botta, Giovanni; Canuto, Emilie M; Salton, Loredana; Tavella, Anna Maria; Benedetto, Chiara

2011-11-01

Women with antiphospholipid antibodies (aPL) such as lupus anticoagulant, anticardiolipin antibodies, and anti-β(2) glycoprotein-1 antibodies are at high risk of late pregnancy complications, such as severe pre-eclampsia, placental insufficiency, and fetal loss. It has been observed that aPL consists of a heterogeneous group of antibodies targeting several phospholipid-binding plasma proteins, including also anti-prothrombin (anti-PT), anti-protein S (anti-PS), and anti-protein C (anti-PC) antibodies. Their potential role in late pregnancy complications is not known. The aim of this work was to investigate the association between those autoantibodies and histories for adverse pregnancy outcome. Anti-PT, anti-PS, and anti-PC antibodies were evaluated in 163 patients with previous severe pre-eclampsia, fetal death, and/or placental abruption and in as many women with previous uneventful pregnancies, negative for aPL. The prevalence of anti-PT antibodies was higher in cases than in controls (OR, 95% CI: 10.92, 4.52-26.38). The highest prevalence was observed in subjects with fetal death. Anti-PT antibodies appear to be associated with adverse pregnancy outcome, irrespectively of aPL. © 2011 John Wiley & Sons A/S.

Indian Herbal Medicines: Possible Potent Therapeutic Agents for Rheumatoid Arthritis

PubMed Central

Rathore, Brijesh; Ali Mahdi, Abbas; Nath Paul, Bhola; Narayan Saxena, Prabhu; Kumar Das, Siddharth

2007-01-01

Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology and is mainly characterized by the progressive erosion of cartilage leading to chronic polyarthritis and joint distortion. Although the exact pathogenesis of the disease has yet not been elucidated, however, studies suggest that cellular proliferation of synoviocytes result in pannus formation which damages the cartilage and bone. Recent reports also support the role of free radicals in its pathogenesis. Apart from the conventional treatment strategies using nonsteroidal anti-inflammatory drugs, disease modifying antirheumatic drugs and glucocorticoids, newer and safer drugs are continuously being searched, as long term usage of these drugs have resulted in adverse effects. Alternative medicine provides another approach for treatment of RA and currently a number of medicinal plants are under scientific evaluation to develop a novel drug. There is a dire need to investigate the complete therapeutic potential and adverse effects, if any, of these herbals for providing newer and safer treatment options with minimum side effects. In this review we have tried to explore various Indian ancient Ayurvedic, Unani and Tibbi, as also some Chinese and Korean, herbals for their potential to treat RA. PMID:18392103

Hepatotoxicity and subchronic toxicity tests of Morinda citrifolia (noni) fruit.

PubMed

West, Brett J; Su, Chen X; Jensen, C Jarakae

2009-10-01

Morinda citrifolia (noni) fruit juice has been approved as a safe food in many nations. A few cases of hepatitis in people who had been drinking noni juice have been reported, even though no causal link could be established between the liver injury and ingestion of the juice. To more fully evaluate the hepatotoxic potential of noni fruit juice, in vitro hepatotoxicity tests were conducted in human liver cells, HepG2 cell line. A subchronic oral toxicity test of noni fruit was also performed in Sprague-Dawley (SD) rats to provide benchmark data for understanding the safety of noni juice, without the potential confounding variables associated with many commercial noni juice products. Freeze-dried filtered noni fruit puree did not decrease HepG2 cell viability or induce neutral lipid accumulation and phospholipidosis. There were no histopathological changes or evidence of dose-responses in hematological and clinical chemistry measurements, including liver function tests. The no-observed-adverse-effect level (NOAEL) for freeze-dried noni fruit puree is greater than 6.86 g/kg body weight, equivalent to approximately 90 ml of noni fruit juice/kg. These findings corroborate previous conclusions that consumption of noni fruit juice is unlikely to induce adverse liver effects.

Cardiovascular Safety Pharmacology of Sibutramine.

PubMed

Yun, Jaesuk; Chung, Eunyong; Choi, Ki Hwan; Cho, Dae Hyun; Song, Yun Jeong; Han, Kyoung Moon; Cha, Hey Jin; Shin, Ji Soon; Seong, Won-Keun; Kim, Young-Hoon; Kim, Hyung Soo

2015-07-01

Sibutramine is an anorectic that has been banned since 2010 due to cardiovascular safety issues. However, counterfeit drugs or slimming products that include sibutramine are still available in the market. It has been reported that illegal sibutramine-contained pharmaceutical products induce cardiovascular crisis. However, the mechanism underlying sibutramine-induced cardiovascular adverse effect has not been fully evaluated yet. In this study, we performed cardiovascular safety pharmacology studies of sibutramine systemically using by hERG channel inhibition, action potential duration, and telemetry assays. Sibutramine inhibited hERG channel current of HEK293 cells with an IC50 of 3.92 μM in patch clamp assay and increased the heart rate and blood pressure (76 Δbpm in heart rate and 51 ΔmmHg in blood pressure) in beagle dogs at a dose of 30 mg/kg (per oral), while it shortened action potential duration (at 10 μM and 30 μM, resulted in 15% and 29% decreases in APD50, and 9% and 17% decreases in APD90, respectively) in the Purkinje fibers of rabbits and had no effects on the QTc interval in beagle dogs. These results suggest that sibutramine has a considerable adverse effect on the cardiovascular system and may contribute to accurate drug safety regulation.

Drug safety in pregnancy--monitoring congenital anomalies.

PubMed

Morgan, Margery; De Jong-van den Berg, Lolkje T W; Jordan, Sue

2011-04-01

This paper outlines research into the causes of congenital anomalies, and introduces a pan-European study. The potential roles of nurses and midwives in this area are illustrated by a case report. Since the thalidomide disaster, use of drugs in pregnancy has been carefully monitored to prevent anything similar happening again. However, monitoring is incomplete and questions remain unanswered. Many medicines are essential for the health of pregnant women. However, drug use in pregnancy requires surveillance. Methods include spontaneous reporting of adverse events, cohort studies and case control studies. It is hoped that a Europe-wide study, combining data from several congenital anomaly registers, will provide a sufficiently large population to assess the impact of selected drugs on congenital anomalies. However, this work depends on the consistency of reporting by nurses and midwives. Drug safety in pregnancy remains undetermined. Collaboration across Europe has the potential to provide a framework for safety evaluation. Prescribers should consider the possibility of pregnancy in women of child-bearing age. Careful review of maternal drug use in early pregnancy is essential. Midwives and nurses should be aware of adverse event drug reporting systems, including congenital anomaly registers. © 2011 The Authors. Journal compilation © 2011 Blackwell Publishing Ltd.

Drug safety evaluation of naltrexone/bupropion for the treatment of obesity.

PubMed

Verpeut, Jessica L; Bello, Nicholas T

2014-06-01

Obesity is a known health risk for the development of several preventable diseases. Obesity-related metabolic alterations negatively impact different physiological mechanisms, which supports the rationale for the use of combined drug therapy. Naltrexone is an opioid antagonist for the treatment of opioid and alcohol dependency, whereas bupropion is a norepinephrine/dopamine reuptake inhibitor used to treat depression and smoking cessation. Although not effective as individual monotherapies for obesity, naltrexone and bupropion in combination produce weight loss and a metabolic profile beneficial for the potential treatment of obesity. This review examines the safety and antiobesity effects of naltrexone and bupropion alone and in combination. It reviews the results of four Phase III clinical trials of a novel fixed dose of sustained-released naltrexone/bupropion. Naltrexone/bupropion has a greater weight loss efficacy than two FDA-approved medications, orlistat and lorcaserin. Although the weight loss produced by phentermine/topiramate is superior to naltrexone/bupropion, the safety profile of naltrexone/bupropion has less severe adverse effects. In addition, naltrexone/bupropion is well tolerated, with nausea being the most reported adverse event. Unlike other centrally acting medications, lorcaserin and phentermine/topiramate, naltrexone/bupropion has no abuse potential.

Myopathy induced by statin-ezetimibe combination: Evaluation of potential risk factors.

PubMed

Brahmachari, Ballari; Chatterjee, Suparna

2015-01-01

Although both atorvastatin and ezetimibe may cause myopathy, statin-induced myopathy is less likely at low doses, and ezetimibe is only rarely reported to induce myopathy. Also, ezetimibe is not usually known to potentiate statin-induced myopathy. We report a case of myalgia with elevated serum creatinine phosphokinase in a patient after 2 months of therapy with fixed dose combination of atorvastatin and ezetimibe (10 mg each). At the time of the event, patient was undertaking moderate physical exertion in the form of brisk walking for 30-40 min a day and was detected to have low serum Vitamin D levels. The adverse event resolved after stopping atorvastatin-ezetimibe combination therapy. Potential risk factors, such as physical exertion and Vitamin D deficiency, co-existent in dyslipidemic patients, may exacerbate myopathy potential of these drugs, and precipitate muscular symptoms even at a low-dose.

Ultrasonographic evaluation of vincristine-induced gastric hypomotility and the prokinetic effect of mosapride in dogs.

PubMed

Tsukamoto, A; Ohno, K; Tsukagoshi, T; Maeda, S; Nakashima, K; Fukushima, K; Fujino, Y; Takeuchi, A; Tsujimoto, H

2011-01-01

Vincristine induces gastrointestinal motility disorders in humans. Adverse gastrointestinal events are commonly observed in dogs receiving vincristine. To evaluate gastric motility after vincristine administration in dogs and the prophylactic effect of a prokinetic agent, mosapride. Five healthy Beagle dogs. Five dogs received vincristine i.v. at a dosage of 0.75 mg/m(2). The motility index (MI) of the antral contraction was ultrasonographically evaluated 30 minutes postfeeding before administration of vincristine and for 6 days after vincristine treatment. After a 6-week washout period, the dogs received vincristine with mosapride (2 mg/kg p.o., q24h for 6 days), and the MI was re-evaluated. Adverse gastrointestinal events were evaluated according to the Veterinary Co-operative Group Common Terminology Criteria for Adverse Events (VCOG-CTCAE). After vincristine administration, a significant decrease (P < .05) in MI was observed on days 3 (6.64 ± 0.30) and 4 (8.02 ± 0.94), compared with pretreatment levels (10.00 ± 0.62). Gastrointestinal adverse events were observed in 4 dogs (grade 2 decreased appetite: 3 dogs; grade 1 vomiting: 2 dogs; and grade 1 diarrhea and grade 2 hematochezia: 1 dog). When mosapride citrate was administered with vincristine and for the next 5 days, no decrease in MI was observed. Furthermore, adverse gastrointestinal events occurred less frequently (grade 1 vomiting and grade 2 hematochezia in 1 dog each). Vincristine (0.75 mg/m(2)) induces gastric hypomotility in dogs. Preventive administration of mosapride citrate (2.0 mg/kg p.o., q24h) improves hypomotility and may decrease the adverse gastrointestinal effects of vincristine. Copyright © 2011 by the American College of Veterinary Internal Medicine.

Ventral striatal activity links adversity and reward processing in children.

PubMed

Kamkar, Niki H; Lewis, Daniel J; van den Bos, Wouter; Morton, J Bruce

2017-08-01

Adversity impacts many aspects of psychological and physical development including reward-based learning and decision-making. Mechanisms relating adversity and reward processing in children, however, remain unclear. Here, we show that adversity is associated with potentiated learning from positive outcomes and impulsive decision-making, but unrelated to learning from negative outcomes. We then show via functional magnetic resonance imaging that the link between adversity and reward processing is partially mediated by differences in ventral striatal response to rewards. The findings suggest that early-life adversity is associated with alterations in the brain's sensitivity to rewards accounting, in part, for the link between adversity and altered reward processing in children. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Additive Contributions of Childhood Adversity and Recent Stressors to Inflammation at Midlife: Findings from the MIDUS Study

ERIC Educational Resources Information Center

Hostinar, Camelia E.; Lachman, Margie E.; Mroczek, Daniel K.; Seeman, Teresa E.; Miller, Gregory E.

2015-01-01

We examined the joint contributions of self-reported adverse childhood experiences (ACEs) and recent life events (RLEs) to inflammation at midlife, by testing 3 competing theoretical models: stress generation, stress accumulation, and early life stress sensitization. We aimed to identify potential mediators between adversity and inflammation.…

Adverse drug reactions and off-label drug use in paediatric outpatients

PubMed Central

Horen, Benjamin; Montastruc, Jean-Louis; Lapeyre-mestre, Maryse

2002-01-01

Aims To investigate the potential relationship between off-label drug use and increased risk of adverse drug reactions in paediatric outpatients. Methods A prospective pharmacovigilance survey of drug prescribing in office based paediatricians was carried out in Haute-Garonne County (south west of France). Results The study involved a sample of 1419 children under 16 years old. Forty-two percent of patients were exposed to at least one off-label prescription. The incidence of adverse drug reactions was 1.41% (95% CI 0.79, 2.11). Off-label drug use was significantly associated with adverse drug reactions (relative risk 3.44; 95% CI 1.26, 9.38), particularly when it was due to an indication different than that defined in the Summary Product Characteristics (relative risk 4.42; 95% CI 1.60, 12.25). Conclusions Our data suggest an increasing risk of adverse drug reactions related to off-label drug use. This risk would be acceptable if further studies prove the potential benefit of such a drug use. PMID:12492616

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.

A cross-country comparison of rivaroxaban spontaneous adverse event reports and concomitant medicine use with the potential to increase the risk of harm.

PubMed

McDonald, Cameron J; Kalisch Ellett, Lisa M; Barratt, John D; Caughey, Gillian E

2014-12-01

Concerns with the safety profiles of the newer anticoagulants have been raised because of differences in treatment populations between pre-marketing studies (randomized controlled trials) and clinical practice. Little is known about the potential safety issues and the reporting in spontaneous adverse event databases associated with rivaroxaban. To analyse spontaneous adverse event reports associated with the oral anticoagulant rivaroxaban from Australia, Canada and the USA; and to examine concomitant medicine use that may increase the risk of adverse events. Spontaneous adverse event report databases from Australia, Canada and the USA were examined for all reports of adverse events associated with rivaroxaban and concomitant medicines from 1 August 2005 to 31 March 2013. Disproportionality analysis (the proportional reporting ratio [PRR] and reporting odds ratio [ROR]) was conducted for quantitative detection of signals, using the US database. There were 244 spontaneous adverse event reports associated with rivaroxaban from Australia, 536 from Canada and 1,638 from the USA. Reporting of haemorrhage (any type) was common, ranging from 30.7% for Australia to 37.5% for Canada. Gastrointestinal haemorrhage was the most commonly reported haemorrhage, accounting for 13.9% of Australian, 16.4% of Canadian and 11.1% of US adverse event reports. Positive signals were confirmed in the US data (haemorrhage [any type] PRR 11.93, χ (2) 4,414.78 and ROR 13.41, 95% confidence interval [CI] 12.13-14.81; gastrointestinal haemorrhage PRR 12.52, χ (2) 2,018.48 and ROR 13.15, 95% CI 11.36-15.21). Reporting of concomitant use of medicines with the potential to increase bleeding risk ranged from 63.7% in Australia to 89.2% in Canada. A large proportion of adverse event reports for rivaroxaban were associated with use of concomitant medicines, which may have increased the risk of adverse events-in particular, haemorrhage. Increased awareness of a patient's comorbidity and associated medicine use is needed when rivaroxaban is used in clinical practice.

A human tissue-based functional assay platform to evaluate the immune function impact of small molecule inhibitors that target the immune system.

PubMed

St Pierre, Cristina; Guo, Jane; Shin, John D; Engstrom, Laura W; Lee, Hyun-Hee; Herbert, Alan; Surdi, Laura; Baker, James; Salmon, Michael; Shah, Sanjiv; Ellis, J Michael; Houshyar, Hani; Crackower, Michael A; Kleinschek, Melanie A; Jones, Dallas C; Hicks, Alexandra; Zaller, Dennis M; Alves, Stephen E; Ramadas, Ravisankar A

2017-01-01

While the immune system is essential for the maintenance of the homeostasis, health and survival of humans, aberrant immune responses can lead to chronic inflammatory and autoimmune disorders. Pharmacological modulation of drug targets in the immune system to ameliorate disease also carry a risk of immunosuppression that could lead to adverse outcomes. Therefore, it is important to understand the 'immune fingerprint' of novel therapeutics as they relate to current and, clinically used immunological therapies to better understand their potential therapeutic benefit as well as immunosuppressive ability that might lead to adverse events such as infection risks and cancer. Since the mechanistic investigation of pharmacological modulators in a drug discovery setting is largely compound- and mechanism-centric but not comprehensive in terms of immune system impact, we developed a human tissue based functional assay platform to evaluate the impact of pharmacological modulators on a range of innate and adaptive immune functions. Here, we demonstrate that it is possible to generate a qualitative and quantitative immune system impact of pharmacological modulators, which might help better understand and predict the benefit-risk profiles of these compounds in the treatment of immune disorders.

Duodenal Electric Stimulation: Results of a First-in-Man Study.

PubMed

Aberle, Jens; Busch, Philipp; Veigel, Jochen; Duprée, Anna; Roesch, Thomas; zu Eulenburg, Christine; Paschen, Björn; Scholz, Bernd M; Wolter, Stefan; Sauer, Nina; Ludwig, Kaja; Izbicki, Jakob; Mann, Oliver

2016-02-01

The aim of this study was to demonstrate feasibility and safety of a new electric duodenal stimulation system (EDS, BALANCE) in humans. Secondary objectives were to evaluate the effect on glycemic control and weight loss in patients with obesity and type 2 diabetes mellitus (T2DM). In an open-labeled, prospective, single-arm, non-randomized multicenter study, 12 obese T2DM patients with a mean HbA1c of 8.0% received laparoscopic implantation of the BALANCE duodenal stimulating device. Adverse events, changes in glycemic control, cardiovascular parameters, and weight were collected. The follow-up period after implantation was 12 months. Device related severe adverse events did not occur. Mean HbA1c decreased by 0.8% (p = 0.02) and mean fasting blood glucose level (FBG) was reduced by 19% (p = 0.038) after the 12 months. Mean HDL level increased from 44 to 48 mg/dl (p = 0.033). EDS is a feasible and safe procedure. Positive effects on T2DM and some cardiovascular parameters (HDL, weight) were seen. However, further prospective randomized blinded studies are needed in order to evaluate the potential of this new minimally invasive method.

Photodynamic therapy for actinic cheilitis: a systematic review.

PubMed

Yazdani Abyaneh, Mohammad-Ali; Falto-Aizpurua, Leyre; Griffith, Robert D; Nouri, Keyvan

2015-02-01

Actinic cheilitis (AC) is a premalignant lesion of the lips that can progress to squamous cell carcinoma and metastasize. Actinic cheilitis is difficult to treat because surgical treatments have significant adverse effects whereas less invasive procedures have uncertain efficacy. Photodynamic therapy (PDT) may offer a noninvasive yet effective treatment option for AC. To systematically review the safety and efficacy of PDT for AC. The terms "photodynamic," "actinic," "solar," "cheilitis," and "cheilosis" were used in combinations to search the PubMed database. Studies were considered for inclusion based on eligibility criteria, and specific data were extracted from all studies. The authors identified 15 eligible case series encompassing a total of 242 treated subjects. Among studies that evaluated subjects for complete clinical response, 139 of 223 subjects (62%) showed complete response at final follow-ups ranging from 3 to 30 months. Among studies that evaluated subjects for histological outcome, 57 of 121 subjects (47%) demonstrated histological cure at final follow-ups ranging from 1.5 to 18 months. Cosmetic outcomes were good to excellent in the majority of subjects, and adverse events were well tolerated. Photodynamic therapy is safe and has the potential to clinically and histologically treat AC, with a need for future randomized controlled trials.

Evaluation of internet websites marketing herbal weight-loss supplements to consumers.

PubMed

Jordan, Melanie A; Haywood, Tasha

2007-11-01

The aim of this study was to evaluate the quality and quantity of drug information available to consumers on Internet websites marketing herbal weight-loss dietary supplements in the United States. We conducted an Internet search using the search engines Yahoo and Google and the keywords "herbal weight loss." Website content was evaluated for the presence of active/inactive ingredient names and strengths and other Food and Drug Administration (FDA) labeling requirements. Information related to drug safety for the most common herbal ingredients in the products evaluated was compared against standard herbal drug information references. Thirty-two (32) websites were evaluated for labeling requirements and safety information. All sites listed an FDA disclaimer statement and most sites (84.4%) listed active ingredients, although few listed strengths or inactive ingredients. Based on the drug information for the most common ingredients found in the weight-loss dietary supplements evaluated, potential contraindications for cardiovascular conditions, pregnancy/nursing, and high blood pressure were listed most frequently (73%, 65.5%, and 37%, respectively), whereas few websites listed potential drug interactions or adverse reactions. Potential hazards posed by dietary supplements may not be accurately, if at all, represented on Internet websites selling these products. Since consumers may not approach their physicians or pharmacists for information regarding use of dietary supplements in weight loss, it becomes necessary for health care providers to actively engage their patients in open discussion regarding the use, benefits, and hazards of dietary supplements.

Evaluation of hypothesized adverse outcome pathway linking thyroid peroxidase inhibition to fish early life stage toxicity

EPA Science Inventory

There is an interest in developing alternatives to the fish early-life stage (FELS) test (OECD test guideline 210), for predicting adverse outcomes (e.g., impacts on growth and survival) using less resource-intensive methods. Development and characterization of adverse outcome pa...

Practical approaches to adverse outcome pathway development and weight‐of‐evidence evaluation as illustrated by ecotoxicological case studies

EPA Science Inventory

Adverse Outcome Pathways (AOPs) describe toxicant effects as a sequential chain of causally linked events beginning with a molecular perturbation and culminating in an adverse outcome at an individual or population level. Strategies for developing AOPs are still evolving and dep...

Australian pharmacies prevent potential adverse reactions in patients taking warfarin requesting over-the-counter analgesia.

PubMed

MacFarlane, Brett V; Bergin, Jenny K; Reeves, Peter; Matthews, Andrew

2015-06-01

The objective of this article was to assess if Australian pharmacy staff prevent potential adverse reactions in warfarin patients requesting over-the-counter (OTC) analgesia. Mystery shoppers entered 170 pharmacies across Australia to request OTC analgesia for a hypothetical patient with a wrist injury who currently takes warfarin following a heart valve replacement. The request was made to the first pharmacist or non-pharmacist staff member to approach the mystery shopper. The interaction was audio-taped and assessed by a pharmacist. The OTC analgesic recommended was assessed for the potential to cause an adverse bleeding event. The quality of advice given with the OTC analgesic was assessed against determined criteria. Results were compared with scenarios of similar request type where the hypothetical patient was not taking warfarin. Mystery shoppers enquiring about taking OTC analgesics concomitantly with warfarin had access to the pharmacist in 97.0% of cases. All 170 pharmacies recommended OTC analgesics that were less likely to cause adverse events when taken with warfarin. The advice given and the communication between pharmacy staff and mystery shoppers were of high quality. Australian pharmacies support the quality use of medicines by patients taking warfarin by providing expeditious access to the pharmacist, appropriate recommendations of OTC analgesics, high standards of quality of advice and they communicate in a way to ensure ease of understanding by the consumer. The protocols used by pharmacy staff help prevent potentially serious adverse drug events. © 2014 Royal Pharmaceutical Society.

Gastrointestinal and hematologic adverse events after administration of vincristine, cyclophosphamide, and doxorubicin in dogs with lymphoma that underwent a combination multidrug chemotherapy protocol.

PubMed

Tomiyasu, Hirotaka; Takahashi, Masashi; Fujino, Yasuhito; Ohno, Koichi; Tsujimoto, Hajime

2010-11-01

The present study aimed to objectively evaluate the adverse events after the administration of chemotherapeutic agents used in the University of Wisconsin (UW)-Madison chemotherapy protocol (UW-25) for canine lymphoma, using the Veterinary Co-operative Oncology Group common terminology criteria for adverse events (VCOG-CTCAE). The medical records of 40 dogs with multicentric high-grade lymphoma that underwent UW-25 were reviewed. Gastrointestinal adverse events of grade 2 and above and blood/bone marrow adverse events of all grades were evaluated. Gastrointestinal adverse events occurring at least once during the entire period of UW-25 were observed in 50% (20/40), 17.9% (7/39), and 8.1% (3/37) of the dogs after the administration of vincristine (VCR), cyclophosphamide (CPA), and doxorubicin (DXR), respectively. Blood/bone marrow adverse events occurring at least once during UW-25 were observed in 57.5% (23/40), 41% (16/39), and 8.1% (3/37) of the dogs after the administration of VCR, CPA, and DXR, respectively. The rate of patients that experienced gastrointestinal adverse events was higher after the first administration of VCR than after the first administration of DXR. Findings obtained in this study will be helpful in predicting the adverse events that could occur when dogs with lymphoma are treated with UW-25.

Sodium oxybate for cataplexy.

PubMed

Lemon, Michael D; Strain, Joe D; Farver, Debra K

2006-03-01

To review the pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, precautions, dosing recommendations, and patient counseling of sodium oxybate for the treatment of cataplexy in patients with narcolepsy. OVID and PubMed databases were searched (1966-January 2006) using the key words sodium oxybate, gamma-hydroxybutyrate, narcolepsy, and cataplexy. Only English-language articles were selected. All information on sodium oxybate related to narcolepsy and cataplexy was considered. Study selection included human trials evaluating safety and efficacy of sodium oxybate for the treatment of cataplexy. Sodium oxybate is approved by the Food and Drug Administration for the treatment of excessive daytime sleepiness and cataplexy in patients with narcolepsy. In placebo-controlled trials, sodium oxybate demonstrated efficacy in reducing the number of cataplexy attacks. The dosing regimen includes a split dose given at bedtime and 2.5-4 hours later due to its short elimination half-life. The drug is generally well tolerated, with headache, nausea, dizziness, pain, and somnolence being the most common adverse events. Sodium oxybate is safe and effective for the treatment of cataplexy. Potential disadvantages include a multiple dosing regimen, abuse potential, cost, and a closed distribution system. Potential advantages demonstrated in clinical trials include significant decreases in the number of weekly cataplexy attacks, improvement in daytime sleepiness, and improvement in the Clinical Global Impression of Change score and nighttime awakenings. Overall, sodium oxybate provides a new option for the treatment of cataplexy.

Recommendations for the proper use of nonprescription cough suppressants and expectorants in solid-organ transplant recipients.

PubMed

Gabardi, Steven; Carter, Danielle; Martin, Spencer; Roberts, Keri

2011-03-01

To describe the pharmacology and safety of oral over-the-counter cough suppressants and expectorants and to present recommendations for the use of these agents in solid-organ transplant recipients based on the potential for adverse drug reactions or drug-disease interactions. Data from journal articles and other sources describing the pharmacology and safety of over-the-counter cough suppressants and expectorants, drug-drug interactions with immunosuppressive agents, and drug-disease state interactions are reviewed. Potential and documented drug-drug interactions between immunosuppressive agents and over-the-counter cough medications guaifenesin, dextromethorphan, diphenhydramine, and codeine were evaluated on the basis of pharmacokinetic and pharmacodynamic principles. Interactions between these cough medications and the physiological changes in the body following transplantation also were examined. Diphenhydramine requires additional monitoring when used to treat cough in transplant recipients owing to its anticholinergic properties and the potential for interactions with cyclosporine. Dextromethorphan can be used in most transplant recipients, although greater caution should be exercised if the patient has undergone liver transplant or has liver impairment. Guaifenesin can be used in transplant recipients but should be used with caution in patients receiving kidney or lung transplants and in patients with renal impairment. Codeine combined with guaifenesin is another option for cough and can be used in most transplant patients although those with reduced renal function should be monitored carefully for adverse events.

Safety assessment of non-animal chondroitin sulfate sodium: Subchronic study in rats, genotoxicity tests and human bioavailability.

PubMed

Miraglia, Niccolò; Bianchi, Davide; Trentin, Antonella; Volpi, Nicola; Soni, Madhu G

2016-07-01

Chondroitin sulfate, an amino sugar polymer made of glucuronic acid and N-acetyl-galactosamine, is used in dietary supplements to promote joint health. Commonly used chondroitin sulfate is of animal origin and can pose potential safety problems including bovine spongiform encephalopathy (BSE). The objective of the present study was to investigate potential adverse effects, if any, of microbial derived chondroitin sulfate sodium (CSS) in subchronic toxicity, genotoxicity and bioavailability studies. In the toxicity study, Sprague Dawley rats (10/sex/group) were gavaged with CSS at dose levels of 0, 250, 500 and 1000 mg/kg body weight (bw)/day for 90-days. No mortality or significant changes in clinical signs, body weights, body weight gain or feed consumption were noted. Similarly, no toxicologically relevant treatment-related changes in hematological, clinical chemistry, urinalysis and organ weights were noted. Macroscopic and microscopic examinations did not reveal treatment-related abnormalities. In vitro mutagenic and clastogenic potentials as evaluated by Ames assay, chromosomal aberration test and micronucleus assay did not reveal genotoxicity of CSS. In pharmacokinetic study in human, CSS showed higher absorption as compared to chondroitin sulfate of animal origin. The results of subchronic toxicity study supports the no-observed-adverse-effect level (NOAEL) for CSS as 1000 mg/kg bw/day, the highest dose tested. Copyright © 2016 Elsevier Ltd. All rights reserved.

Feasibility and potential effectiveness of a non-pharmacological multidisciplinary care programme for persons with generalised osteoarthritis: a randomised, multiple-baseline single-case study

PubMed Central

Kwakkenbos, Linda; Rietveld, Leonie; den Broeder, Alfons A; de Bie, Rob A; van den Ende, Cornelia H M

2012-01-01

Objectives To evaluate the feasibility and potential effectiveness of a 12-week, non-pharmacological multidisciplinary intervention in patients with generalised osteoarthritis (GOA). Design A randomised, concurrent, multiple-baseline single-case design. During the baseline period, the intervention period and the postintervention period, all participants completed several health outcomes twice a week on Visual Analogue Scales. Setting Rheumatology outpatient department of a specialised hospital in the Netherlands. Participants 1 man and four women (aged 51–76 years) diagnosed with GOA. Primary outcome measures To assess feasibility, the authors assessed the number of dropouts and adverse events, adherence rates and patients' satisfaction. Secondary outcome measures To assess the potential effectiveness, the authors assessed pain and self-efficacy using visual data inspection and randomisation tests. Results The intervention was feasible in terms of adverse events (none) and adherence rate but not in terms of participants' satisfaction with the intervention. Visual inspection of the data and randomisation testing demonstrated no effects on pain (p=0.93) or self-efficacy (p=0.85). Conclusions The results of the present study indicate that the proposed intervention for patients with GOA was insufficiently feasible and effective. The data obtained through this multiple-baseline study have highlighted several areas in which the therapy programme can be optimised. PMID:22815466

PFIESTERIA PISCICIDA IMPACTS

EPA Science Inventory

Recent evidence suggests that the estuarine dinofageflate, Pfiesteria piscicida, may release a toxin(s) which kills fish and adversely affects human health in laboratory and environmental settings. The potential for Pfresferia-like organisms to adversely impact estuarine ecosys...

Final Environmental Assessment for Constructing a Magnet School at Laughlin Air Force Base, Texas

DTIC Science & Technology

2016-10-01

agencies on the human health and environmental conditions in minority and low-income populations. Environmental justice analyses are performed to identify...potential disproportionately high and adverse human health or environmental effects from proposed federal actions on minority or low-income populations...considered to assess the potential for disproportionately high and adverse human health or environmental effects from proposed action on these

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 and represent a significant burden to patients, healthcare providers, and the pharmaceutical industry. • This review details the current state of the art in biomarkers of ADRs (both genetic and circulating). There is still significant variability in patient response which cannot be explained by current knowledge of genetic risk factors for ADRs; however, we discussed how specific advances in genomics have the potential to yield better and more predictive models. • Many current clinically utilized circulating biomarkers of tissue injury are valid biomarkers for a number of ADRs. However, they often give little insight into the specific cell or tissue subtype which may be affected. Emerging circulating biomarkers with potential to provide greater information on the etiology/pathophysiology of ADRs are described.

Yellow fever vaccine used in a psoriatic arthritis patient treated with methotrexate: a case report.

PubMed

Stuhec, Matej

2014-01-01

The yellow fever vaccines on the market are contraindicated for immunocompromised and elderly patients. A case of yellow fever vaccine used in a 27-year-old Slovenian male with psoriatic arthritis during treatment with methotrexate is described. We demonstrate a positive case, since there were no adverse effects in concurrent administration of yellow fever vaccine and methotrexate. This patient did not show severe adverse reactions and did not contract yellow fever despite potential exposure. More research is needed on possible adverse effects of concurrent administration of yellow fever vaccine and methotrexate to determine the potential of this method for more frequent use.

Patient safety culture in obstetrics and gynecology and neonatology units: the nurses' and the midwives' opinion.

PubMed

Ribeliene, Janina; Blazeviciene, Aurelija; Nadisauskiene, Ruta Jolanta; Tameliene, Rasa; Kudreviciene, Ausrele; Nedzelskiene, Irena; Macijauskiene, Jurate

2018-04-22

Patients treated in health care facilities that provide services in the fields of obstetrics, gynecology, and neonatology are especially vulnerable. Large multidisciplinary teams of physicians, multiple invasive and noninvasive diagnostic and therapeutic procedures, and the use of advanced technologies increase the probability of adverse events. The evaluation of knowledge about patient safety culture among nurses and midwives working in such units and the identification of critical areas at a health care institution would reduce the number of adverse events and improve patient safety. The aim of the study was to evaluate the opinion of nurses and midwives working in clinical departments that provide services in the fields of obstetrics, gynecology, and neonatology about patient safety culture and to explore potential predictors for the overall perception of safety. We used the Hospital Survey on Patient Safety Culture (HSOPSC) to evaluate nurses' and midwives' opinion about patient safety issues. The overall response rate in the survey was 100% (n = 233). The analysis of the dimensions of safety on the unit level showed that the respondents' most positive evaluations were in the Organizational Learning - Continuous Improvement (73.2%) and Feedback and Communication about Error (66.8%) dimensions, and the most negative evaluations in the Non-punitive Response to Error (33.5%) and Staffing (44.6%) dimensions. On the hospital level, the evaluation of the safety dimensions ranged between 41.4 and 56.8%. The percentage of positive responses in the outcome dimensions Frequency of Events Reported was 82.4%. We found a significant association between the outcome dimension Frequency of Events Reported and the Hospital Management Support for Patient Safety and Feedback and Communication about Error Dimensions. On the hospital level, the critical domains in health care facilities that provide services in the fields of obstetrics, gynecology, and neonatology were Teamwork Across Hospital Units, and on the unit level - Communication Openness, Teamwork Within Units, Non-punitive Response to Error, and Staffing. The remaining domains were seen as having a potential for improvement.

Using aversive images to enhance healthy food choices and implicit attitudes: An experimental test of evaluative conditioning.

PubMed

Hollands, Gareth J; Prestwich, Andrew; Marteau, Theresa M

2011-03-01

To examine the effect of communicating images of energy-dense snack foods paired with aversive images of the potential health consequences of unhealthy eating, on implicit and explicit attitudes and food choice behavior. Participants were randomly allocated to either an evaluative conditioning (EC) procedure that paired images of snack foods with images of potential adverse health consequences or a control condition that featured images of snack foods alone. Implicit attitudes were assessed pre- and post-intervention. Explicit attitudes and food choice behavior were assessed post-intervention. The conditioning intervention made implicit attitudes toward energy-dense snacks more negative, with this effect greatest in those with relatively more favorable implicit attitudes toward these snacks at baseline. Participants in the conditioning intervention were more likely to choose fruit rather than snacks in a behavioral choice task, a relationship mediated by changes in implicit attitudes. Presenting aversive images of potential health consequences with those of specific foodstuffs can change implicit attitudes, which impacts on subsequent food choice behavior. (c) 2011 APA, all rights reserved

Nanoparticle toxicity by the gastrointestinal route: evidence and knowledge gaps

PubMed Central

Bergin, Ingrid L.; Witzmann, Frank A.

2013-01-01

The increasing interest in nanoparticles for advanced technologies, consumer products, and biomedical applications has led to great excitement about potential benefits but also concern over the potential for adverse human health effects. The gastrointestinal tract represents a likely route of entry for many nanomaterials, both directly through intentional ingestion or indirectly via nanoparticle dissolution from food containers or by secondary ingestion of inhaled particles. Additionally, increased utilisation of nanoparticles may lead to increased environmental contamination and unintentional ingestion via water, food animals, or fish. The gastrointestinal tract is a site of complex, symbiotic interactions between host cells and the resident microbiome. Accordingly, evaluation of nanoparticles must take into consideration not only absorption and extraintestinal organ accumulation but also the potential for altered gut microbes and the effects of this perturbation on the host. The existing literature was evaluated for evidence of toxicity based on these considerations. Focus was placed on three categories of nanomaterials: nanometals and metal oxides, carbon-based nanoparticles, and polymer/dendrimers with emphasis on those particles of greatest relevance to gastrointestinal exposures. PMID:24228068

The effect of gestational diabetes on proliferation capacity and viability of human umbilical cord-derived stromal cells.

PubMed

Wajid, Nadia; Naseem, Rashida; Anwar, Sanam Saiqa; Awan, Sana Javaid; Ali, Muhammad; Javed, Sara; Ali, Fatima

2015-09-01

Stomal cells derived from Wharton's jelly of human umbilical cord (WJMSCs) are considered as the potential therapeutic agents for regeneration and are getting famous for stem cell banking. Our study aims to evaluate the effects of gestational diabetes on proliferation capacity and viability of WJMSCs. Mesenchymal stromal cells were isolated from Wharton's jelly of human umbilical cords from normal and gestational diabetic (DWJMSCs) mothers. Growth patterns of both types of cells were analyzed through MTT assay and population doubling time. Cell survival, cell death and glucose utilization were estimated through trypan blue exclusion assay, LDH assay and glucose detection assay respectively. Angiogenic ability was evaluated by immunocytochemistry and ELISA for VEGF A. Anti-cancerous potential was analyzed on HeLa cells. DWJMSCs exhibited low proliferative rate, increased population doubling time, reduced cell viability and increased cell death. Interestingly, DWJMSCs were found to have a reduced glucose utilization and anti-cancerous ability while enhanced angiogenic ability. Gestational diabetes induces adverse effects on growth, angiogenic and anti-cancerous potential of WJMSCs.

Evaluation of nicotine and cotinine analogs as potential neuroprotective agents for Alzheimer's disease.

PubMed

Gao, Jie; Adam, Bao-Ling; Terry, Alvin V

2014-03-15

The currently available therapies for Alzheimer's disease (AD) and related forms of dementia are limited by modest efficacy, adverse side effects, and the fact that they do not prevent the relentless progression of the illness. The purpose of the studies described here was to investigate the neuroprotective effects of the nicotine metabolite cotinine as well as a small series of cotinine and nicotine analogs (including stereoisomers) and to compare their effects to the four clinically prescribed AD therapies. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Comparative study on four kinds of assessment methods of post-marketing safety of Danhong injection].

PubMed

Li, Xuelin; Tang, Jinfa; Meng, Fei; Li, Chunxiao; Xie, Yanming

2011-10-01

To study the adverse reaction of Danhong injection with four kinds of methods, central monitoring method, chart review method, literature study method and spontaneous reporting method, and to compare the differences between them, explore an appropriate method to carry out post-marketing safety evaluation of traditional Chinese medicine injection. Set down the adverse reactions' questionnaire of four kinds of methods, central monitoring method, chart review method, literature study method and collect the information on adverse reactions in a certain period. Danhong injection adverse reaction information from Henan Province spontaneous reporting system was collected with spontaneous reporting method. Carry on data summary and descriptive analysis. Study the adverse reaction of Danhong injection with four methods of central monitoring method, chart review method, literature study method and spontaneous reporting method, the rates of adverse events were 0.993%, 0.336%, 0.515%, 0.067%, respectively. Cyanosis, arrhythmia, hypotension, sweating, erythema, hemorrhage dermatitis, rash, irritability, bleeding gums, toothache, tinnitus, asthma, elevated aminotransferases, constipation, pain are new discovered adverse reactions. The central monitoring method is the appropriate method to carry out post-marketing safety evaluation of traditional Chinese medicine injection, which could objectively reflect the real world of clinical usage.

Adverse effects of salivary contamination for adhesives in restorative dentistry. A literature review.

PubMed

Nair, Pooja; Hickel, Reinhard; Ilie, Nicoleta

2017-06-01

To review and critically analyze the literature concerning the influence of salivary contamination on the bond quality of adhesives used in restorative materials by comparing and contrasting the different adhesive materials. A detailed search on PUBMED, Cochrane Library, Google Scholar and Web of Science was carried out to identify publications on salivary contamination and dental adhesive materials, from 1990-2017 (March) which resulted in a total of 6,202 web-identified publications. After screening titles/abstracts and de-duplicating, 54 publications were selected that matched the requirements for this review. The condition for selection was English literature concerning the effect of salivary contamination on the adhesives used in restorative dentistry. The obtained articles were systematically evaluated. Salivary contamination of adhesives during restorative procedures statistically (64.6%) showed an adverse effect on adhesives, occurring either at one or many stages of restoration. Methodological dissimilarities impeded the direct comparison of the selected studies. Nevertheless, the 2-step etch and rinse adhesives were relatively less vulnerable to salivary contamination than the others. 65% of the evaluated studies for decontamination achieved improved bonding when the contaminated surface was subjected to some kind of decontamination procedure. However, the duration and other specificities were not standard in all the evaluations and need further research to assess the course of action. It is necessary to do long term studies to evaluate the effectiveness of contaminated adhesive over time. Salivary contamination is a potential cause for poor bond quality of adhesive systems during restorative procedures and to provide a successful treatment, proper care must be taken to ensure the operating area is free from contamination. Understanding the properties of the materials and its constituents as well as considering measures to manage the potential vulnerabilities due to salivary contamination in the area of bonding might help a clinician to produce better results.

Platinum nanoparticle during electrochemical hydrogen evolution: Adsorbate distribution, active reaction species, and size effect

DOE PAGES

Tan, Teck L.; Wang, Lin -Lin; Zhang, Jia; ...

2015-03-02

For small Pt nanoparticles (NPs), catalytic activity is, as observed, adversely affected by size in the 1–3 nm range. We elucidate, via first-principles-based thermodynamics, the operation H* distribution and cyclic voltammetry (CV) during the hydrogen evolution reaction (HER) across the electrochemical potential, including the underpotential region (U ≤ 0) that is difficult to assess in experiment. We consider multiple adsorption sites on a 1 nm Pt NP model and show that the characteristic CV peaks from different H* species correspond well to experiment. We next quantify the activity contribution from each H* species to explain the adverse effect of size.more » From the resolved CV peaks at the standard hydrogen electrode potential (U = 0), we first deduce that the active species for the HER are the partially covered (100)-facet bridge sites and the (111)-facet hollow sites. Upon evaluation of the reaction barriers at operation H* distribution and microkinetic modeling of the exchange current, we find that the nearest-neighbor (100)-facet bridge site pairs have the lowest activation energy and contribute to ~75% of the NP activity. Edge bridge sites (fully covered by H*) per se are not active; however, they react with neighboring (100)-facet H* to account for ~18% of the activity, whereas (111)-facet hollow sites contribute little. As a result, extrapolating the relative contributions to larger NPs in which the ratio of facet-to-edge sites increases, we show that the adverse size effect of Pt NP HER activity kicks in for sizes below 2 nm.« less

Herbal medicine use among urban residents in Lagos, Nigeria

PubMed Central

2011-01-01

Background Over three-quarter of the world's population is using herbal medicines with an increasing trend globally. Herbal medicines may be beneficial but are not completely harmless. This study aimed to assess the extent of use and the general knowledge of the benefits and safety of herbal medicines among urban residents in Lagos, Nigeria. Methods The study involved 388 participants recruited by cluster and random sampling techniques. Participants were interviewed with a structured open- and close-ended questionnaire. The information obtained comprises the demography and types of herbal medicines used by the respondents; indications for their use; the sources, benefits and adverse effects of the herbal medicines they used. Results A total of 12 herbal medicines (crude or refined) were used by the respondents, either alone or in combination with other herbal medicines. Herbal medicines were reportedly used by 259 (66.8%) respondents. 'Agbo jedi-jedi' (35%) was the most frequently used herbal medicine preparation, followed by 'agbo-iba' (27.5%) and Oroki herbal mixture® (9%). Family and friends had a marked influence on 78.4% of the respondents who used herbal medicine preparations. Herbal medicines were considered safe by half of the respondents despite 20.8% of those who experienced mild to moderate adverse effects. Conclusions Herbal medicine is popular among the respondents but they appear to be ignorant of its potential toxicities. It may be necessary to evaluate the safety, efficacy and quality of herbal medicines and their products through randomised clinical trial studies. Public enlightenment programme about safe use of herbal medicines may be necessary as a means of minimizing the potential adverse effects. PMID:22117933

Psychosocial Distress and Knowledge Deficiencies in Parents of Children in Ireland Who Carry an Altered Cystic Fibrosis Gene.

PubMed

Quigley, S J; Linnane, B; Connellan, S; Ward, A; Ryan, P

2018-06-01

Significant gaps have been identified in parental understanding of CF newborn screening and the consequences of carrying an altered CF gene. Seven potential causes of psychosocial adversity arising from false positive newborn screening for CF have been identified. The current study aimed to increase parents understanding of CF, reduce their levels of stress, and investigate psychosocial adversity arising from false-positive screening. This national study was run over one year in the Republic of Ireland. Parents were recruited for the study following a diagnostic sweat test confirming their child carried a single altered CF gene. Parents were randomly assigned into a control and intervention group, with those in the intervention group receiving a carefully designed information pack. All parents took part in semi-structured interviews. Parents (n = 16) who received an information pack had significantly higher CF knowledge scores than parents (n = 16) in the control group. 66% of parents in the control group misunderstood the health implications of carrying an altered CF gene, no parents in the intervention group had the same misunderstanding. There was no significant difference in stress scores between the groups. Parents of infants who had more than one sweat test due to insufficient sweat quantity had higher overall stress percentiles (50%), than parents of infants who had one sweat test (30%), indicating greater parental stress. The combination of written and audio-visual information contained in the information pack successfully increased parents comprehension of CF. The study also evaluates the potential for psychosocial adversity following false positive newborn screening for CF.

A study of adverse birth outcomes and agricultural land use practices in Missouri.

PubMed

Almberg, Kirsten S; Turyk, Mary; Jones, Rachael M; Anderson, Robert; Graber, Judith; Banda, Elizabeth; Waller, Lance A; Gibson, Roger; Stayner, Leslie T

2014-10-01

Missouri is an agriculturally intensive state, primarily growing corn and soybeans with additional rice and cotton farming in some southeastern counties. Communities located in close proximity to pesticide-treated fields are known to have increased exposure to pesticides and may be at increased risk of adverse birth outcomes. The study aims were to assess the relationship between county-level measures of crop-specific agricultural production and adverse birth outcomes in Missouri and to evaluate the most appropriate statistical methodologies for doing so. Potential associations between county level data on the densities of particular crops and low birth weight and preterm births were examined in Missouri between 2004-2006. Covariates considered as potential confounders and effect modifiers included gender, maternal race/ethnicity, maternal age at delivery, maternal smoking, access to prenatal care, quarter of birth, county median household income, and population density. These data were analyzed using both standard Poisson regression models as well as models allowing for temporal and spatial correlation of the data. There was no evidence of an association between corn, soybean, or wheat densities with low birth weight or preterm births. Significant positive associations between both rice and cotton density were observed with both low birth weight and preterm births. Model results were consistent using Poisson and alternative models accounting for spatial and temporal variability. The associations of rice and cotton with low birth weight and preterm births warrant further investigation. Study limitations include the ecological study design and limited available covariate information. Copyright © 2014 Elsevier Inc. All rights reserved.

The validation of an invitro colonic motility assay as a biomarker for gastrointestinal adverse drug reactions

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

Keating, Christopher, E-mail: C.Keating@sheffield.ac.u; Martinez, Vicente; Ewart, Lorna

Motility-related gastrointestinal adverse drug reactions (GADRs), such as constipation and diarrhea, are some of the most frequently reported adverse events associated with the clinical development of new chemical entities, and for marketed drugs. However, biomarkers capable of detecting such GADRs are lacking. Here, we describe an in vitro assay developed to detect and quantify changes in intestinal motility as a surrogate biomarker for constipation/diarrhea-type GADRs. In vitro recordings of intraluminal pressure were used to monitor the presence of colonic peristaltic motor complexes (CPMCs) in mouse colonic segments. CPMC frequency, contractile and total mechanical activity were assessed. To validate the assay,more » two experimental protocols were conducted. Initially, five drugs with known gastrointestinal effects were tested to determine optimal parameters describing excitation and inhibition as markers for disturbances in colonic motility. This was followed by a 'blinded' evaluation of nine drugs associated with or without clinically identified constipation/diarrhea-type GADRs. Concentration-response relationships were determined for these drugs and the effects were compared with their maximal free therapeutic plasma concentration in humans. The assay detected stimulatory and inhibitory responses, likely correlating to the occurrence of diarrhea or constipation. Concentration-related effects were identified and potential mechanisms of action were inferred for several drugs. Based on the results from the fourteen drugs assessed, the sensitivity of the assay was calculated at 90%, with a specificity of 75% and predictive capacity of 86%. These results support the potential use of this assay in screening for motility-related GADRs during early discovery phase, safety pharmacology assessment.« less

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.

Workplace air measurements and likelihood of exposure to manufactured nano-objects, agglomerates, and aggregates

NASA Astrophysics Data System (ADS)

Brouwer, Derk H.; van Duuren-Stuurman, Birgit; Berges, Markus; Bard, Delphine; Jankowska, Elzbieta; Moehlmann, Carsten; Pelzer, Johannes; Mark, Dave

2013-11-01

Manufactured nano-objects, agglomerates, and aggregates (NOAA) may have adverse effect on human health, but little is known about occupational risks since actual estimates of exposure are lacking. In a large-scale workplace air-monitoring campaign, 19 enterprises were visited and 120 potential exposure scenarios were measured. A multi-metric exposure assessment approach was followed and a decision logic was developed to afford analysis of all results in concert. The overall evaluation was classified by categories of likelihood of exposure. At task level about 53 % showed increased particle number or surface area concentration compared to "background" level, whereas 72 % of the TEM samples revealed an indication that NOAA were present in the workplace. For 54 out of the 120 task-based exposure scenarios, an overall evaluation could be made based on all parameters of the decision logic. For only 1 exposure scenario (approximately 2 %), the highest level of potential likelihood was assigned, whereas in total in 56 % of the exposure scenarios the overall evaluation revealed the lowest level of likelihood. However, for the remaining 42 % exposure to NOAA could not be excluded.

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.

[Seed vigor evaluation based on adversity resistance index of wheat seed germination under stress conditions.

PubMed

Chen, Lei Tai; Sun, Ai Qing; Yang, Min; Chen, Lu Lu; Ma, Xue Li; Li, Mei Ling; Yin, Yan Ping

2016-09-01

A total of 16 wheat cultivars were selected to detect seed vigor of different genotypes using standard germination test, seed germination test under stress conditions and field emergence test. The adversity resistance indices of seed vigor indices and field emergence percentage under different germination conditions were used as the indices to evaluate adversity resistance. Principal component analysis and cluster analysis were used for the comprehensive evaluation of seed vigor. Results showed that drought stress, artificial aging and cold soaking treatments affected seed vigor to some extent. The adversity resistance indices of the artificial aging and cold soaking tests were significantly positively correlated with the field emergence percentage, while the adversity resistance index of drought stress test had no significant correlation with the field emergence percentage. 16 wheat cultivars were classified as three groups based on the principal component analysis and cluster analysis. Yunong 949, Yumai 49-198, Luyuan 502, Zhengyumai 9987, Shimai 21, Shannong 23, and Shixin 828 belonged to high vigor seeds. Xunong 5, Yunong 982, Tangmai 8, Jimai 20, Jimai 22, Jinan 17, and Shannong 20 belonged to medium vigor seeds. The other two cultivars, Chang 4738 and Lunxuan 061, belonged to low vigor seeds.

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.

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

Kastenberg, W.E.; Apostolakis, G.; Dhir, V.K.

Severe accident management can be defined as the use of existing and/or altemative resources, systems and actors to prevent or mitigate a core-melt accident. For each accident sequence and each combination of severe accident management strategies, there may be several options available to the operator, and each involves phenomenological and operational considerations regarding uncertainty. Operational uncertainties include operator, system and instrumentation behavior during an accident. A framework based on decision trees and influence diagrams has been developed which incorporates such criteria as feasibility, effectiveness, and adverse effects, for evaluating potential severe accident management strategies. The framework is also capable ofmore » propagating both data and model uncertainty. It is applied to several potential strategies including PWR cavity flooding, BWR drywell flooding, PWR depressurization and PWR feed and bleed.« less

Environmental Assessment for Construction of Small Arms Range at Tinker Air Force Base, Oklahoma

DTIC Science & Technology

2008-11-01

Air Force Material Command Tinker Air Force Base, Oklahoma Prepared by: CHEROKEE CRC, LLC 916 West 23rd Street Tulsa, OK 74107...activities to avoid potential for short-term soil erosion which could result in adverse effects to water quality. Hazardous Materials and Waste...erosion which could result in adverse effects to water quality. Hazardous Materials and Waste. Soil from the remediation activities could potentially

Preliminary results of M-VAC chemotherapy combined with mild hyperthermia, a new therapeutic strategy for advanced or metastatic transitional cell carcinoma of the urothelium.

PubMed

Yamada, Yoshiaki; Itoh, Youko; Aoki, Shigeyuki; Nakamura, Kogenta; Taki, Tomohiro; Naruse, Katsuya; Tobiume, Motoi; Zennami, Kenji; Katsuda, Remi; Kato, Yoshiharu; Watanabe, Masahito; Nishikawa, Genya; Minami, Miwako; Nakahira, Mariko; Ukai, Sayaka; Sawada, Masaki; Kitamura, Akiko; Honda, Nobuaki

2009-11-01

We evaluated the efficacy and safety of M-VAC chemotherapy combined with mild hyperthermia, a new therapeutic strategy for advanced metastatic transitional cell carcinoma of the urothelium. The subjects were 12 patients diagnosed with advanced metastatic transitional cell carcinoma of the urothelium. For mild hyperthermia, the patients' oral temperature was elevated to about 38 degrees C by heating for 20 min and retaining the heat for 20 min with a far-infrared heater. The antitumor effect was evaluated according to the RECIST, while adverse drug reactions were assessed based on the NCI-CTC. The antitumor effect was rated as partial remission (PR) in 10 of the 12 patients and stable disease in 2 patients, with an efficacy rate of 83% (10/12). All 10 patients who had achieved PR received three courses of treatment. Of the 12 patients, 5 died during the observation period, with survival for 9-23 months (mean: 15.6 months). Adverse drug reactions included myelosuppression in all patients (Grade 3 in 4 patients, Grade 4 in 8), and gastrointestinal toxicity, such as nausea or vomiting, which was mild (Grade 0 in 2 patients, Grade 1 in 8, Grade 2 in 1, Grade 3 in 1). The results of the present study suggest that M-VAC chemotherapy combined with mild hyperthermia, which potentiates the anticancer effect and reduces adverse drug reactions such as gastrointestinal symptoms, is a useful and safe method for the treatment of advanced transitional cell carcinoma of the urothelium.

The administration of probiotics and synbiotics in immune compromised adults: is it safe?

PubMed

Van den Nieuwboer, M; Brummer, R J; Guarner, F; Morelli, L; Cabana, M; Claasen, E

2015-03-01

This study aimed to systematically evaluate safety of probiotics and synbiotics in immune compromised adults (≥18 years). Safety was analysed using the Common Terminology Clinical Adverse Events (CTCAE version 4.0) classification, thereby providing an update on previous reports using the most recent available clinical data (2008-2013). Safety aspects are represented and related to number of participants per probiotic strain/culture, study duration, dosage, clinical condition and selected afflictions. Analysis of 57 clinical studies indicates that probiotic and/or synbiotic administration in immune compromised adults is safe with regard to the current evaluated probiotic strains, dosages and duration. Individuals were considered immune compromised if HIV-infected, critically ill, underwent surgery or had an organ- or an autoimmune disease. There were no major safety concerns in the study, as none of the serious adverse events (AE)s were related, or suspected to be related, to the probiotic or synbiotic product and the study products were well tolerated. Overall, AEs occurred less frequent in immune compromised subjects receiving probiotics and/or synbiotics compared to the control group. In addition, the results demonstrated a flaw in precise reporting and classification of AE in most studies. Furthermore, generalisability of conclusions are greatly limited by the inconsistent, imprecise and potentially incomplete reporting as well as the variation in probiotic strains, dosages, administration regimes, study populations and reported outcomes. We argue that standardised reporting on adverse events (CTCAE) in 'food' studies should be obligatory, thereby improving reliability of data and re-enforcing the safety profile of probiotics.

An observational study of the frequency, severity, and etiology of failures in postoperative care after major elective general surgery.

PubMed

Symons, Nicholas R A; Almoudaris, Alex M; Nagpal, Kamal; Vincent, Charles A; Moorthy, Krishna

2013-01-01

To investigate the nature of process failures in postoperative care, to assess their frequency and preventability, and to explore their relationship to adverse events. Adverse events are common and are frequently caused by failures in the process of care. These processes are often evaluated independently using clinical audit. There is little understanding of process failures in terms of their overall frequency, relative risk, and cumulative effect on the surgical patient. Patients were observed daily from the first postoperative day until discharge by an independent surgeon. Field notes on the circumstances surrounding any nonroutine or atypical event were recorded. Field notes were assessed by 2 surgeons to identify failures in the process of care. Preventability, the degree of harm caused to the patient, and the underlying etiology of process failures were evaluated by 2 independent surgeons. Fifty patients undergoing major elective general surgery were observed for a total of 659 days of postoperative care. A total of 256 process failures were identified, of which 85% were preventable and 51% directly led to patient harm. Process failures occurred in all aspects of care, the most frequent being medication prescribing and administration, management of lines, tubes, and drains, and pain control interventions. Process failures accounted for 57% of all preventable adverse events. Communication failures and delays were the main etiologies, leading to 54% of process failures. Process failures are common in postoperative care, are highly preventable, and frequently cause harm to patients. Interventions to prevent process failures will improve the reliability of surgical postoperative care and have the potential to reduce hospital stay.

Nasal mucosa and blood cell transcriptome profiles do not reflect respiratory symptoms associated with moisture-damage.

PubMed

Ndika, Joseph; Suojalehto, Hille; Täubel, Martin; Lehto, Maili; Karvala, Kirsi; Pallasaho, Paula; Sund, Jukka; Auvinen, Petri; Järvi, Kati; Pekkanen, Juha; Kinaret, Pia; Greco, Dario; Hyvärinen, Anne; Alenius, Harri

2018-05-04

Upper and lower respiratory symptoms and asthma are adverse health effects associated with moisture-damaged buildings. Quantitative measures to detect adverse health effects related to exposure to dampness and mold are needed. Here, we investigate differences in gene expression between occupants of moisture-damaged and reference buildings. Moisture-damaged (N=11) and control (N=5) buildings were evaluated for dampness and mold by trained inspectors. The transcriptomics cohort consisted of nasal brushings and peripheral blood mononuclear cells (PBMCs) from 86 teachers, with/without self-perceived respiratory symptoms. Subject categories comprised reference (R) and damaged (D) buildings with (S) or without (NS) symptoms; i.e. R-S, R-NS, DS and D-NS. Component analyses and k-means clustering of transcriptome profiles did not distinguish building status (R/D) or presence of respiratory symptoms (S/NS). Only one nasal mucosa gene (YBX3P1) exhibited a significant change in expression between D-S and D-NS. Nine other nasal mucosa genes were differentially expressed between R-S and D-S teachers. No differentially expressed genes were identified in PBMCs. We conclude that the observed mRNA differences provide very weak biological evidence for adverse health effects associated with subject occupancy of the specified moisture-damaged buildings. This emphasizes the need to evaluate all potential factors (including those not related to toxicity) influencing perceived/self-reported ill-health in moisture-damaged buildings. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Pharmacological management of obesity in pediatric patients.

PubMed

Boland, Cassie L; Harris, John Brock; Harris, Kira B

2015-02-01

To review current evidence of pharmacological options for managing pediatric obesity and provide potential areas for future research. A MEDLINE search (1966 to October 2014) was conducted using the following keywords: exenatide, liraglutide, lorcaserin, metformin, obesity, orlistat, pediatric, phentermine, pramlintide, topiramate, weight loss, and zonisamide. Identified articles were evaluated for inclusion, with priority given to randomized controlled trials with orlistat, metformin, glucagon-like peptide-1 agonists, topiramate, and zonisamide in human subjects and articles written in English. References were also reviewed for additional trials. Whereas lifestyle modification is considered first-line therapy for obese pediatric patients, severe obesity may benefit from pharmacotherapy. Orlistat is the only Food and Drug Administration (FDA)-approved medication for pediatric obesity and reduced body mass index (BMI) by 0.5 to 4 kg/m(2), but gastrointestinal (GI) adverse effects may limit use. Metformin has demonstrated BMI reductions of 0.17 to 1.8 kg/m(2), with mild GI adverse effects usually managed with dose titration. Exenatide reduced BMI by 1.1 to 1.7 kg/m(2) and was well-tolerated with mostly transient or mild GI adverse effects. Topiramate and zonisamide reduced weight when used in the treatment of epilepsy. Future studies should examine efficacy and safety of pharmacological agents in addition to lifestyle modifications for pediatric obesity. Lifestyle interventions remain the treatment of choice in pediatric obesity, but concomitant pharmacotherapy may be beneficial in some patients. Orlistat should be considered as second-line therapy for pediatric obesity. Evidence suggests that other diabetes and antiepileptic medications may also provide weight-loss benefits, but safety should be further evaluated. © The Author(s) 2014.

Structured vs. Unstructured: Factors Affecting Adverse Drug Reaction Documentation in an EMR Repository

PubMed Central

Skentzos, Stephen; Shubina, Maria; Plutzky, Jorge; Turchin, Alexander

2011-01-01

Adverse reactions to medications to which the patient was known to be intolerant are common. Electronic decision support can prevent them but only if history of adverse reactions to medications is recorded in structured format. We have conducted a retrospective study of 31,531 patients with adverse reactions to statins documented in the notes, as identified with natural language processing. The software identified statin adverse reactions with sensitivity of 86.5% and precision of 91.9%. Only 9020 of these patients had an adverse reaction to a statin recorded in structured format. In multivariable analysis the strongest predictor of structured documentation was utilization of EMR functionality that integrated the medication list with the structured medication adverse reaction repository (odds ratio 48.6, p < 0.0001). Integration of information flow between EMR modules can help improve documentation and potentially prevent adverse drug events. PMID:22195188

Impact of repeated ivermectin treatments against onchocerciasis on the transmission of loiasis: an entomologic evaluation in central Cameroon.

PubMed

Kouam, Marc K; Tchatchueng-Mbougua, Jules B; Demanou, Maurice; Boussinesq, Michel; Pion, Sébastien D S; Kamgno, Joseph

2013-09-27

Annual community-directed treatment with ivermectin (CDTI) have been carried out since 1999 in the Lekie division (central region of Cameroon where most cases of Loa-related post ivermectin severe adverse events were reported) as part of the joined activities of the African Programme for Onchocerciasis Control (APOC) and Mectizan® Donation Program (MDP). As large-scale administration of ivermetine was demonstrated to be an efficient means to control loiasis transmission, it was hypothesized that CDTI would have lowered or halted the transmission of Loa loa in the Lekie division after 13 years of annual drug administration, indicating a possible reduction in the occurrence of Loa-related post-ivermectin severe adverse events. A 4-month entomologic study was carried out from March to June 2012 in the Lekie division to evaluate the impact of 13 years of CDTI on the transmission of L. loa whose baseline data were recorded in 1999-2000. There was a significant reduction in the infection rate for Chrysops silacea and C. dimidiata from 6.8 and 9% in 1999-2000 to 3 and 3.6% in 2012, respectively. The differences in the infective rate (IR) (percentage of flies harboring head L3 larvae), potential infective rate (PIR) (percentage of flies bearing L3 larvae), mean head L3 larvae load (MHL3) (average L3 per infective fly) and mean fly L3 larvae load (MFL3) (average L3 per potentially infective fly) for both C. silacea and C. dimidiata were not significantly different between the two investigation periods. The biting density (BD) was almost three-fold higher in 2012 for C. silacea but not for C. dimidiata. The transmission potential (TP) which is a function of the BD, was higher in the present study than in the baseline investigation for each species. The infection rate remaining high, the high TP and the stability observed in the IR, PIR, MHL3 and MFL3 after 13 years of CDTI suggest that transmission of L. loa is still active. This is an indication that the risk of occurrence of severe adverse events such as fatal encephalopathies is still present, especially for heavily microfilaria-loaded people taken ivermectin for the first time.

Impact of repeated ivermectin treatments against onchocerciasis on the transmission of loiasis: an entomologic evaluation in central Cameroon

PubMed Central

2013-01-01

Background Annual community-directed treatment with ivermectin (CDTI) have been carried out since 1999 in the Lekie division (central region of Cameroon where most cases of Loa-related post ivermectin severe adverse events were reported) as part of the joined activities of the African Programme for Onchocerciasis Control (APOC) and Mectizan® Donation Program (MDP). As large-scale administration of ivermetine was demonstrated to be an efficient means to control loiasis transmission, it was hypothesized that CDTI would have lowered or halted the transmission of Loa loa in the Lekie division after 13 years of annual drug administration, indicating a possible reduction in the occurrence of Loa-related post-ivermectin severe adverse events. Methods A 4-month entomologic study was carried out from March to June 2012 in the Lekie division to evaluate the impact of 13 years of CDTI on the transmission of L. loa whose baseline data were recorded in 1999–2000. Results There was a significant reduction in the infection rate for Chrysops silacea and C. dimidiata from 6.8 and 9% in 1999–2000 to 3 and 3.6% in 2012, respectively. The differences in the infective rate (IR) (percentage of flies harboring head L3 larvae), potential infective rate (PIR) (percentage of flies bearing L3 larvae), mean head L3 larvae load (MHL3) (average L3 per infective fly) and mean fly L3 larvae load (MFL3) (average L3 per potentially infective fly) for both C. silacea and C. dimidiata were not significantly different between the two investigation periods. The biting density (BD) was almost three-fold higher in 2012 for C. silacea but not for C. dimidiata. The transmission potential (TP) which is a function of the BD, was higher in the present study than in the baseline investigation for each species. Conclusion The infection rate remaining high, the high TP and the stability observed in the IR, PIR, MHL3 and MFL3 after 13 years of CDTI suggest that transmission of L. loa is still active. This is an indication that the risk of occurrence of severe adverse events such as fatal encephalopathies is still present, especially for heavily microfilaria-loaded people taken ivermectin for the first time. PMID:24289520

Safety evaluation of Whole Algalin Protein (WAP) from Chlorella protothecoides.

PubMed

Szabo, Nancy J; Matulka, Ray A; Chan, Teresa

2013-09-01

Microalgae such as Chlorella spp., were once consumed as traditional human foods; now they are being developed as ingredients for modern diets. Whole Algalin Protein (WAP) from dried milled Chlorella protothecoides was evaluated for dietary safety in a 13-week feeding trial in rodents with genotoxic potential evaluated using in vitro and in vivo assays and the likelihood of food allergy potential evaluated via human repeat-insult patch test (HRIPT). In the subchronic study, rats consumed feed containing 0, 25,000, 50,000 or 100,000 ppm WAP for 92-93 days. No treatment-related mortalities or effects in general condition, body weight, food consumption, ophthalmology, urinalysis, hematology, clinical chemistry, gross pathology, organ weights, and histopathology occurred. Several endpoints exhibited statistically significant effects, but none was dose-related. The no-observed-adverse-effect level (NOAEL) was based on the highest WAP concentration consumed by the rats and was equivalent to 4805 mg/kg/day in males and 5518 mg/kg/day in females. No mutagenicity occurred in Salmonella typhimurium or Escherichia coli tester strains (≤5000 μg/plate WAP) with or without mutagenic activation. No clastogenic response occurred in bone marrow from mice administered a single oral dose (2000 mg/kg WAP). Skin sensitization was not induced by WAP via HRIPT, indicating little potential for food allergy. Copyright © 2013 Elsevier Ltd. All rights reserved.

Ameliorating the biological impacts of childhood adversity: A review of intervention programs.

PubMed

Purewal Boparai, Sukhdip K; Au, Vanessa; Koita, Kadiatou; Oh, Debora Lee; Briner, Susan; Burke Harris, Nadine; Bucci, Monica

2018-05-01

Childhood adversity negatively impacts the biological development of children and has been linked to poor health outcomes across the life course. The purpose of this literature review is to explore and evaluate the effectiveness of interventions that have addressed an array of biological markers and physical health outcomes in children and adolescents affected by adversity. PubMed, CINAHL, PsychInfo, Sociological Abstracts databases and additional sources (Cochrane, WHO, NIH trial registries) were searched for English language studies published between January 2007 and September 2017. Articles with a childhood adversity exposure, biological health outcome, and evaluation of intervention using a randomized controlled trial study design were selected. The resulting 40 intervention studies addressed cortisol outcomes (n = 20) and a range of neurological, epigenetic, immune, and other outcomes (n = 22). Across institutional, foster care, and community settings, intervention programs demonstrated success overall for improving or normalizing morning and diurnal cortisol levels, and ameliorating the impacts of adversity on brain development, epigenetic regulation, and additional outcomes in children. Factors such as earlier timing of intervention, high quality and nurturant parenting traits, and greater intervention engagement played a role in intervention success. This study underlines progress and promise in addressing the health impacts of adversity in children. Ongoing research efforts should collect baseline data, improve retention, replicate studies in additional samples and settings, and evaluate additional variables, resilience factors, mediators, and long-term implications of results. Clinicians should integrate lessons from the intervention sciences for preventing and treating the health effects of adversity in children and adolescents. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

In-hospital death according to dementia diagnosis in acutely ill elderly patients: the REPOSI study.

PubMed

Marengoni, A; Corrao, S; Nobili, A; Tettamanti, M; Pasina, L; Salerno, F; Iorio, A; Marcucci, M; Bonometti, F; Mannucci, P M

2011-09-01

The aim of the study was to explore the association of dementia with in-hospital death in acutely ill medical patients. Thirty-four internal medicine and 4 geriatric wards in Italy participated in the Registro Politerapie SIMI-REPOSI-study during 2008. One thousand three hundred and thirty two in-patients aged 65 years or older were enrolled. Logistic regression models were used to evaluate the association of dementia with in-hospital death. Socio-demographic characteristics, morbidity (single diseases and the Charlson Index), number of drugs, and adverse clinical events during hospitalization were considered as potential confounders. One hundred and seventeen participants were diagnosed as being affected by dementia. Patients with dementia were more likely to be women, older, to have cerebrovascular diseases, pneumonia, and a higher number of adverse clinical events during hospitalization. The percentage of patients affected by dementia who died during hospitalization was higher than that of patients without dementia (9.4 versus 4.9%). After multiadjustment, the diagnosis of dementia was associated with in-hospital death (OR = 2.1; 95% CI = 1.0-4.5). Having dementia and at least one adverse clinical event during hospitalization showed an additive effect on in-hospital mortality (OR = 20.7; 95% CI = 6.9-61.9). Acutely ill elderly patients affected by dementia are more likely to die shortly after hospital admission. Having dementia and adverse clinical events during hospital stay increases the risk of death. Copyright © 2010 John Wiley & Sons, Ltd.

Zidovudine for the prevention of vertical HIV transmission: a decision analytic approach.

PubMed

Rouse, D J; Owen, J; Goldenberg, R L; Vermund, S H

1995-08-01

The purpose of this study was to quantify the benefits of maternal-neonatal zidovudine (ZDV) administration for the prevention of vertical human immunodeficiency virus (HIV) transmission against the potential risks of drug-induced complications in uninfected children. A decision analysis model was created with use of a Markov cohort simulation, for evaluating both survival and quality of life for two hypothetical cohorts of HIV-exposed neonates: one with in utero and neonatal exposure to preventive ZDV therapy and the other not exposed. The model included the probability of congenital HIV infection with and without ZDV treatment (estimates derived from AIDS Clinical Trials Group study 076), the yearly probability of death with and without congenital HIV infection, a range of probabilities of adverse effects from ZDV use, and a range of ages in life when any adverse effect would manifest. In a series of scenarios, the impact of different estimates for the quality-of-life decrement from any adverse ZDV effect in HIV-uninfected children was assessed, and threshold values for this estimate were established, i.e., critical values below which withholding ZDV would be the preferred choice. Across a wide range of estimates for multiple contingencies, ZDV use was associated with a greater number of quality-adjusted life years than was non-use. Only in implausible, pessimistic scenarios (i.e., a high incidence of profound adverse effects beginning early in life) would withholding ZDV be the rational choice for an asymptomatic HIV-infected pregnant woman.(ABSTRACT TRUNCATED AT 250 WORDS)

Adverse conditions at the workplace are associated with increased suicide risk.

PubMed

Baumert, Jens; Schneider, Barbara; Lukaschek, Karoline; Emeny, Rebecca T; Meisinger, Christa; Erazo, Natalia; Dragano, Nico; Ladwig, Karl-Heinz

2014-10-01

The present study addressed potential harms of a negative working environment for employed subjects. The main aim was to evaluate if adverse working conditions and job strain are related to an increase in suicide mortality. The study population consisted of 6817 participants drawn from the MONICA/KORA Augsburg, Germany, surveys conducted in 1984-1995, being employed at baseline examination and followed up on average for 12.6 years. Adverse working conditions were assessed by an instrument of 16 items about chronobiological, physical and psychosocial conditions at the workplace, job strain was assessed as defined by Karasek. Suicide risks were estimated by Cox regression adjusted for suicide-related risk factors. A number of 28 suicide cases were observed within follow-up. High levels of adversity in chronobiological/physical working conditions significantly increased the risk for suicide mortality (HR 3.28, 95% CI 1.43-7.54) compared to low/intermediate levels in a model adjusted for age, sex and survey (p value 0.005). Additional adjustment for living alone, low educational level, smoking, high alcohol consumption, obesity and depressed mood attenuated this effect (HR 2.73) but significance remained (p value 0.022). Adverse psychosocial working conditions and job strain, in contrast, had no impact on subsequent suicide mortality risk (p values > 0.200). A negative working environment concerning chronobiological or physical conditions at the workplace had an unfavourable impact on suicide mortality risk, even after controlling for relevant suicide-related risk factors. Employer interventions aimed to improve workplace conditions might be considered as a suitable means to prevent suicides among employees. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

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.

Early life adversity and telomere length: a meta-analysis.

PubMed

Ridout, K K; Levandowski, M; Ridout, S J; Gantz, L; Goonan, K; Palermo, D; Price, L H; Tyrka, A R

2018-04-01

Early adversity, in the form of abuse, neglect, socioeconomic status and other adverse experiences, is associated with poor physical and mental health outcomes. To understand the biologic mechanisms underlying these associations, studies have evaluated the relationship between early adversity and telomere length, a marker of cellular senescence. Such results have varied in regard to the size and significance of this relationship. Using meta-analytic techniques, we aimed to clarify the relationship between early adversity and telomere length while exploring factors affecting the association, including adversity type, timing and study design. A comprehensive search in July 2016 of PubMed/MEDLINE, PsycINFO and Web of Science identified 2462 studies. Multiple reviewers appraised studies for inclusion or exclusion using a priori criteria; 3.9% met inclusion criteria. Data were extracted into a structured form; the Newcastle-Ottawa Scale assessed study quality, validity and bias. Forty-one studies (N=30 773) met inclusion criteria. Early adversity and telomere length were significantly associated (Cohen's d effect size=-0.35; 95% CI, -0.46 to -0.24; P<0.0001). Sensitivity analyses revealed no outlier effects. Adversity type and timing significantly impacted the association with telomere length (P<0.0001 and P=0.0025, respectively). Subgroup and meta-regression analyses revealed that medication use, medical or psychiatric conditions, case-control vs longitudinal study design, methodological factors, age and smoking significantly affected the relationship. Comprehensive evaluations of adversity demonstrated more extensive telomere length changes. These results suggest that early adversity may have long-lasting physiological consequences contributing to disease risk and biological aging.

Changes in risk of immediate adverse reactions to iodinated contrast media by repeated administrations in patients with hepatocellular carcinoma.

PubMed

Fujiwara, Naoto; Tateishi, Ryosuke; Akahane, Masaaki; Taguri, Masataka; Minami, Tatsuya; Mikami, Shintaro; Sato, Masaya; Uchino, Koji; Uchino, Kouji; Enooku, Kenichiro; Kondo, Yuji; Asaoka, Yoshinari; Yamashiki, Noriyo; Goto, Tadashi; Shiina, Shuichiro; Yoshida, Haruhiko; Ohtomo, Kuni; Koike, Kazuhiko

2013-01-01

To elucidate whether repeated exposures to iodinated contrast media increase the risk of adverse reaction. We retrospectively reviewed 1,861 patients with hepatocellular carcinoma who visited authors' institution, a tertiary referral center, between 2004 and 2008. We analyzed cumulative probability of adverse reactions and risk factors. We categorized all symptoms into hypersensitivity reactions, physiologic reactions, and other reactions, according to the American College of Radiology guidelines, and evaluated each category as an event. We estimated the association between hazard for adverse reactions and the number of cumulative exposures to contrast media. We also evaluated subsequent contrast media injections and adverse reactions. There were 23,684 contrast media injections in 1,729 patients. One hundred and thirty-two patients were excluded because they were given no contrast media during the study period. Adverse reactions occurred in 196 (0.83%) patients. The cumulative incidence at 10(th), 20(th), and 30(th) examination was 7.9%, 15.2%, and 24.1%, respectively. Presence of renal impairment was found to be one of risk factors for adverse reactions. The estimated hazard of overall adverse reaction gradually decreased until around 10(th) exposure and rose with subsequent exposures. The estimated hazard of hypersensitivity showed V-shaped change with cumulative number of exposures. The estimated hazard of physiologic reaction had a tendency toward decreasing and that of other reaction had a tendency toward increasing. Second adverse reaction was more severe than the initial in only one among 130 patients receiving subsequent injections. Repeated exposures to iodinated contrast media increase the risk of adverse reaction.

Fuzzy risk analysis of a modern γ-ray industrial irradiator.

PubMed

Castiglia, F; Giardina, M

2011-06-01

Fuzzy fault tree analyses were used to investigate accident scenarios that involve radiological exposure to operators working in industrial γ-ray irradiation facilities. The HEART method, a first generation human reliability analysis method, was used to evaluate the probability of adverse human error in these analyses. This technique was modified on the basis of fuzzy set theory to more directly take into account the uncertainties in the error-promoting factors on which the methodology is based. Moreover, with regard to some identified accident scenarios, fuzzy radiological exposure risk, expressed in terms of potential annual death, was evaluated. The calculated fuzzy risks for the examined plant were determined to be well below the reference risk suggested by International Commission on Radiological Protection.

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

PubMed

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

2015-01-01

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

A systematic evaluation of chemicals in hydraulic-fracturing fluids and wastewater for reproductive and developmental toxicity.

PubMed

Elliott, Elise G; Ettinger, Adrienne S; Leaderer, Brian P; Bracken, Michael B; Deziel, Nicole C

2017-01-01

Hydraulic-fracturing fluids and wastewater from unconventional oil and natural gas development contain hundreds of substances with the potential to contaminate drinking water. Challenges to conducting well-designed human exposure and health studies include limited information about likely etiologic agents. We systematically evaluated 1021 chemicals identified in hydraulic-fracturing fluids (n=925), wastewater (n=132), or both (n=36) for potential reproductive and developmental toxicity to triage those with potential for human health impact. We searched the REPROTOX database using Chemical Abstract Service registry numbers for chemicals with available data and evaluated the evidence for adverse reproductive and developmental effects. Next, we determined which chemicals linked to reproductive or developmental toxicity had water quality standards or guidelines. Toxicity information was lacking for 781 (76%) chemicals. Of the remaining 240 substances, evidence suggested reproductive toxicity for 103 (43%), developmental toxicity for 95 (40%), and both for 41 (17%). Of these 157 chemicals, 67 had or were proposed for a federal water quality standard or guideline. Our systematic screening approach identified a list of 67 hydraulic fracturing-related candidate analytes based on known or suspected toxicity. Incorporation of data on potency, physicochemical properties, and environmental concentrations could further prioritize these substances for future drinking water exposure assessments or reproductive and developmental health studies.

A Pathway to Psychological Difficulty: Perceived Chronic Social Adversity and Its Symptomatic Reactions.

PubMed

Ding, Cody; Zhang, Jingqiu; Yang, Dong

2018-01-01

In this paper, we attempt to predict and explain psychological maladjustment or difficulty. Specifically, we discuss the concept of perceived chronic social adversity, and we expect that such perceived chronic social adversity may potentially lead to chronic stress responses. Accordingly, we propose the symptomatic reactions of perceived chronic social adversity. We put forward a set of hypotheses regarding the relationships between perceived chronic social adversity and those chronic stress responses, and we further hypothesize a mediating role of individualized negative essentialism brought by perceived chronical social adversity. Resilience and individual differences in the ability to cope with perceived adversity are discussed. Future research and prevention need to pay more attention to effects of subjective personal experiences on psychological difficulty, focusing on the importance of exploring daily social experiences in improving cognitive construction processes and developing appropriate preventions.

Assessment of Regional Ecosystem Health—A Case Study of the Golden Triangle of Southern Fujian Province, China

PubMed Central

Wang, Ziyan; Qiu, Quanyi; Wu, Tong; Shao, Guofan

2018-01-01

Intensifying urbanization and rapid population growth in Fujian Province, China, has caused pollution of air and water resources; this has adversely impacted ecosystems and human health. China has recently begun pursuing a massive infrastructure and economic development strategy called the Belt and Road Initiative, which could potentially cause further environmental damage. Evaluations of ecosystem health are therefore a first step towards identifying the potential impacts from the development and planning sustainable development strategies in the Golden Triangle of Southern Fujian. To this end, our study analyzed landscape patterns and evaluated ecosystem health in this region. We used an index system method to develop a pressure–state–response (PSR) model for assessing the region’s ecosystem health. We found that: (1) the landscape type with the greatest area in the study region is cultivated land and there were no areas that were undisturbed by human activity; (2) the overall ecological health of the region is good, but there is distinct variation across the region. This study incorporates the landscape pattern into an evaluation of ecosystem health. Using counties as evaluation units, we provide a general evaluation index for this scale. The methods reported here can be used in complex ecological environments to inform sustainable management decisions. PMID:29671817

Changing Operating Room Culture: Implementation of a Postoperative Debrief and Improved Safety Culture.

PubMed

Magill, Stephen T; Wang, Doris D; Rutledge, W Caleb; Lau, Darryl; Berger, Mitchel S; Sankaran, Sujatha; Lau, Catherine Y; Imershein, Sarah G

2017-11-01

Patient safety is foundational to neurosurgical care. Postprocedural "debrief" checklists have been proposed to improve patient safety, but data about their use in neurosurgery are limited. Here, we implemented an initiative to routinely perform postoperative debriefs and evaluated the impact of debriefing on operating room (OR) safety culture. A 10-question safety attitude questionnaire (SAQ) was sent to neurosurgical OR staff at a major academic medical center before and 18 months after the implementation of a postoperative debriefing initiative. Rates of debrief compliance and changes in attitudes before and after the survey were evaluated. The survey used a Likert scale and analyzed with standard statistical methods. After the debrief initiative, the rate of debriefing increased from 51% to 86% of cases for the neurosurgery service. Baseline SAQ responses found that neurosurgeons had a more favorable perception of OR safety than did anesthesiologists and nurses. After implementation of the postoperative debriefing process, perceptions of OR safety significantly improved for neurosurgeons, anesthesiologists, and nurses. Furthermore, the disparity between nurses and surgeons was no longer significant. After debrief implementation, neurosurgical OR staff had improved perceptions of patient safety compared with surgical services that did not commonly perform debriefing. Debriefing identified OR efficiency concerns in 26.9% of cases, and prevention of potential adverse events/near misses was reported in 8% of cases. Postoperative debriefing can be effectively introduced into the OR and improves the safety culture after implementation. Debriefing is an effective tool to identify OR inefficiencies and potential adverse events. Copyright © 2017 Elsevier Inc. All rights reserved.

An Empirical Examination of Symptom Substitution Associated with Behavior Therapy for Tourette's Disorder

PubMed Central

Peterson, Alan L.; McGuire, Joseph F.; Wilhelm, Sabine; Piacentini, John; Woods, Douglas W.; Walkup, John T.; Hatch, John P.; Villarreal, Robert; Scahill, Lawrence

2018-01-01

Over the past 6 decades, behavior therapy has been a major contributor to the development of evidence-based psychotherapy treatments. However, a longstanding concern with behavior therapy among many nonbehavioral clinicians has been the potential risk for symptom substitution. Few studies have been conducted to evaluate symptom substitution in response to behavioral treatments, largely due to measurement and definitional challenges associated with treated psychiatric symptoms. Given the overt motor and vocal tics associated with Tourette’s disorder, it presents an excellent opportunity to empirically evaluate the potential risk for symptom substitution associated with behavior therapy. The present study examined the possible presence of symptom substitution using 4 methods: (1) the onset of new tic symptoms; (2) the occurrence of adverse events; (3) change in tic medications; and (4) worsening of co-occurring psychiatric symptoms. Two hundred twenty-eight participants with Tourette’s disorder or persistent motor or vocal tic disorders were randomly assigned to receive behavioral therapy or supportive therapy for tics. Both therapies consisted of 8 sessions over 10 weeks. Results indicated that participants treated with behavior therapy were not more likely to have an onset of new tic symptoms, experience adverse events, increase tic medications, or have an exacerbation in co-occurring psychiatric symptoms relative to participants treated with supportive therapy. Further analysis suggested that the emergence of new tics was attributed with the normal waxing and waning nature of Tourette’s disorder. Findings provide empirical support to counter the longstanding concern of symptom substitution in response to behavior therapy for individuals with Tourette's Disorder. PMID:26763495

Traditional Chinese medicine injection for angina pectoris: an overview of systematic reviews.

PubMed

Luo, Jing; Shang, Qinghua; Han, Mei; Chen, Keji; Xu, Hao

2014-01-01

Traditional Chinese medicine (TCM) injection is widely used to treat angina pectoris in China. This overview aims to systematically summarize the general characteristics of systematic reviews (SRs) on TCM injection in treating angina, and assess the methodological and reporting quality of these reviews. We searched PubMed, Embase, the Cochrane Library and four Chinese databases from inception until March 2013. Data were extracted according to a preset form. The AMSTAR and PRISMA checklists were used to explore the methodological quality and reporting characteristics of included reviews, respectively. All data analyses were descriptive. 46 SRs involving over 57,463 participants with angina reviewing 23 kinds of TCM injections were included. The main outcomes evaluated in the reviews were symptoms (43/46, 93.5%), surrogate outcomes (42/46, 91.3%) and adverse events (41/46, 87.0%). Few reviews evaluated endpoints (7/46, 15.2%) and quality of life (1/46, 2.2%). One third of the reviews (16/46, 34.8%) drew definitely positive conclusions while the others (30/46, 65.2%) suggested potential benefits mainly in symptoms, electrocardiogram and adverse events. With many serious flaws such as lack of a protocol and inappropriate data synthesis, the overall methodological and reporting quality of the reviews was limited. While many SRs of TCM injection on the treatment of angina suggested potential benefits or definitely positive effects, stakeholders should not accept the findings of these reviews uncritically due to the limited methodological and reporting quality. Future SRs should be appropriately conducted and reported according to international standards such as AMSTAR and PRISMA, rather than published in large numbers.

Evaluation of childhood trauma with respect to criminal behavior, dissociative experiences, adverse family experiences and psychiatric backgrounds among prison inmates.

PubMed

Altintas, Merih; Bilici, Mustafa

2018-04-01

To evaluate childhood trauma in relation to criminal behavior, dissociative experiences, adverse family experiences during childhood and psychiatric backgrounds among prison inmates. In total, 200 prison inmates were included in this questionnaire-based study. Data on demographic characteristics, adverse family experiences during childhood and psychiatric backgrounds were collected via face-to-face interviews, and a psychometric evaluation was conducted using the Childhood Trauma Questionnaire (CTQ-28) and Dissociative Experiences Scale (DES). Several historical items were more common in females than in males including family history of psychiatric disease (23.0% vs. 13.0%, p = 0.048), a personal history of psychiatric disease (51.0% vs. 29.0%, p < 0.001), and previous suicide attempts (49.0% vs. 25.0%, p < 0.001). In male inmates, in contrast, there were higher rates of substance abuse (48.0% vs. 29.0%, p < 0.001) and previous convictions (50.0% vs. 25.0%, p < 0.001). Males had a younger age at first crime (24.9 ± 8.9 years vs. 30.3 ± 9.2 years, p < 0.001), whereas females had higher rates of violent crimes (69.2% vs. 30.8% p < 0.001) and higher CTQ total scores (51.9 ± 20.9 vs. 46.2 ± 18.9, p = 0.04). A significant relationship of CTQ total score was noted with age at first offense (β = 0.772, p < 0.001) but not with sentence length (β = 0.075, p = 0.292). There were also possible mediating roles of psychiatric problems, adverse family experiences and DES in the relationship between CTQ and age at first offense. In conclusion, our findings revealed a high prevalence of and significant associations among childhood trauma, dissociative experiences, adverse family experiences and psychiatric problems in a cohort of incarcerated females and males. A psychiatric background, childhood trauma characterized by sexual abuse and violent crimes were found to be predominant in female prison inmates, whereas a criminal background with a younger age at first offense and frequent previous convictions, substance use and sexual crimes were more prevalent among male prison inmates. Our findings indicate a potential link between childhood traumatization and criminal behavior in terms of subsequent offending but not in terms of severity of the subsequent offense. Copyright © 2018. Published by Elsevier Inc.

Experiences of women in secure care who have been prescribed clozapine for borderline personality disorder.

PubMed

Dickens, Geoffrey L; Frogley, Catherine; Mason, Fiona; Anagnostakis, Katina; Picchioni, Marco M

2016-01-01

Clozapine is an atypical antipsychotic medicine which can cause significant side-effects. It is often prescribed off-license in severe cases of borderline personality disorder contrary to national treatment guidelines. Little is known about the experiences of those who take clozapine for borderline personality disorder. We explored the lived-experience of women in secure inpatient care who were prescribed clozapine for borderline personality disorder. Adult females ( N  = 20) participated in audio-taped semi-structured interviews. Transcripts were subject to thematic analysis. The central themes related to evaluation, wellbeing, understanding and self-management; for many, their subjective wellbeing on clozapine was preferred to prior levels of functioning and symptomatology, sometimes profoundly so. The negative and potentially adverse effects of clozapine were explained as regrettable but relatively unimportant. When psychological interventions are, at least initially, ineffective then clozapine treatment is likely to be evaluated positively by a group of women with borderline personality disorder in secure care despite the potential disadvantages.

Evaluation of potential relationships between benthic community structure and toxic metals in Laizhou Bay.

PubMed

Wu, Bin; Song, Jinming; Li, Xuegang

2014-10-15

The objective of the present study was to examine the relationships between benthic community structure and toxic metals using bivariate/multivariate techniques at 17 sediment locations in Laizhou Bay, North China. Sediment chemical data were evaluated against geochemical background values and sediment quality guidelines, which identified Cu and As as contaminants of concern with a moderate potential for adverse effects. Benthic community data were subjected to non-metric multidimensional scaling, which generated four groups of stations. Spearman rank correlation was then employed to explore the relationships between the major axes of heavy metals and benthic community structure. However, weak and insignificant correlations were found between these axes, indicating that contaminants of concern may not be the primary explanatory factors. Polychaeta were abundant in southern Laizhou Bay, serving as a warning regarding the health status of the ecosystem. Integrated sediment quality assessment showed sediments from northern central locations were impaired, displaying less diverse benthos and higher metal contamination. Copyright © 2014 Elsevier Ltd. All rights reserved.

Field evaluation of an avian risk assessment model

USGS Publications Warehouse

Vyas, N.B.; Spann, J.W.; Hulse, C.S.; Borges, S.L.; Bennett, R.S.; Torrez, M.; Williams, B.I.; Leffel, R.

2006-01-01

We conducted two laboratory subacute dietary toxicity tests and one outdoor subacute dietary toxicity test to determine the effectiveness of the U.S. Environmental Protection Agency's deterministic risk assessment model for evaluating the potential of adverse effects to birds in the field. We tested technical-grade diazinon and its D Z N- 50W (50% diazinon active ingredient wettable powder) formulation on Canada goose (Branta canadensis) goslings. Brain acetylcholinesterase activity was measured, and the feathers and skin, feet. and gastrointestinal contents were analyzed for diazinon residues. The dose-response curves showed that diazinon was significantly more toxic to goslings in the outdoor test than in the laboratory tests. The deterministic risk assessment method identified the potential for risk to birds in general, but the factors associated with extrapolating from the laboratory to the field, and from the laboratory test species to other species, resulted in the underestimation of risk to the goslings. The present study indicates that laboratory-based risk quotients should be interpreted with caution.

Adverse Effects of Electronic Cigarette Use: A Concept Mapping Approach

PubMed Central

Nasim, Aashir; Rosas, Scott

2016-01-01

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

Adverse effects of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine in 6- to 7-year-old children.

PubMed

Wei, Sung-Hsi; Chao, Yen-Nan; Huang, Song-En; Lee, Tsuey-Feng; Chang, Luan-Yin

2011-02-01

Although the safety profile of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines in adolescents and adults has been documented, few data have reported about their adverse events in children. Healthy 6- to 7-year-old children who were immunized with Tdap vaccine were evaluated for adverse events on Days 1, 2, 4, and 7 postimmunization. Information of sex, body mass index (BMI), and previous diphtheria-pertussis-tetanus (DPT) immunization history was obtained and evaluated for the association with the adverse events. A total of 243 6- to 7-year-old children were immunized with Tdap. Among the 243 children immunized, remarkable adverse events included redness more than or equal to 10 mm in 47 (19%) children, induration more than or equal to 10 mm in 57 (23%), tenderness in 130 (53%), and fever in 12 (5%). Redness and induration resolved in 7 days and fever resolved on Day 4. The adverse events were not associated with gender, BMI above the mean value, or the type of fourth DPT immunization. Adverse events after Tdap vaccination were mild and dissolved within 7 days in 6- to 7-year-old children. Copyright © 2011. Published by Elsevier B.V.

Recent life events and psychosis: The role of childhood adversities.

PubMed

Mansueto, Giovanni; Faravelli, Carlo

2017-10-01

Life events are commonly reported to be related to psychosis. However, less attention has been given to the role that recent events play on psychosis, in relation to exposure to childhood adversity. The current study aimed to evaluate the relationship between recent events and psychosis, taking into account the role of early adversities. 78 psychotic patients and 156 controls were enrolled. Childhood adversity was evaluated using a validated semi-structured interview and the Childhood Experience of Care and Abuse Questionnaire. Recent events were recorded using a semi-structured interview with a normative and contextual approach. The diagnosis of psychosis was made according to Jablenski's criteria. Chi-square, t-test, odds ratio, and binary logistic regression statistical analyses were performed. Psychotic patients reported an excess of recent events. The occurrence of more than one recent event increased the risk of psychosis; there was a cumulative effect between recent and childhood events on psychosis. Recent events were significantly related to psychosis, even in the absence of childhood adversity or when adjusted for it. Our findings suggested that the effect of recent events on psychosis may be amplified by previous exposure to early adversity. Recent events alone, could be also linked to psychosis independently of childhood adversity. Copyright © 2017 Elsevier B.V. All rights reserved.

Potential hazards due to food additives in oral hygiene products.

PubMed

Tuncer Budanur, Damla; Yas, Murat Cengizhan; Sepet, Elif

2016-01-01

Food additives used to preserve flavor or to enhance the taste and appearance of foods are also available in oral hygiene products. The aim of this review is to provide information concerning food additives in oral hygiene products and their adverse effects. A great many of food additives in oral hygiene products are potential allergens and they may lead to allergic reactions such as urticaria, contact dermatitis, rhinitis, and angioedema. Dental practitioners, as well as health care providers, must be aware of the possibility of allergic reactions due to food additives in oral hygiene products. Proper dosage levels, delivery vehicles, frequency, potential benefits, and adverse effects of oral health products should be explained completely to the patients. There is a necessity to raise the awareness among dental professionals on this subject and to develop a data gathering system for possible adverse reactions.

The prognostic value of CT coronary angiography in patients attending hospital with troponin-negative acute chest pain and inconclusive exercise treadmill tests.

PubMed

Mordi, Ify; Tzemos, Nikolaos

2016-05-01

Once acute coronary syndrome (ACS) is excluded in patients presenting to hospital with acute chest pain, usual practice is to stratify future risk of adverse cardiovascular events. Commonly this is performed by pre-discharge exercise treadmill testing (ETT). Often however, patients are unable to perform the test for various reasons, or the final result is inconclusive. This potentially could lead to uncertainty and to unnecessary invasive coronary angiography. We wished to evaluate the potential prognostic significance of CT coronary angiography (CTCA) in patients with prior inconclusive ETTs. Two hundred and thirty-two consecutive patients underwent CTCA and calcium scoring following hospital attendance with acute chest pain and following exclusion of ACS. All patients were followed up for a combined primary outcome of death, non-fatal myocardial infarction, and late revascularization. The mean follow-up period was 2.5 ± 0.9 years. The combined primary outcome occurred in 26 patients (11.2%). Calcium score (HR 1.16; 95% CI 1.02-1.31, P = 0.023 per 100 Agatston unit increase), the presence of coronary artery disease (CAD) on CTCA (non-obstructive CAD, HR 4.52; 95% CI 1.30-15.73, P = 0.018; obstructive CAD, HR 17.00; 95% CI 4.60-62.85, P < 0.001), and ≥3 segments with non-calcified plaque (HR 3.30; 95% CI 1.24-8.76, P = 0.017) were significant univariable predictors of the primary outcome. CTCA was the only significant multivariable predictor of adverse outcome. The presence of CAD assessed by CTCA is a strong predictor of adverse events in patients with troponin-negative acute chest pain and could potentially be used as an alternative, non-invasive risk stratifier in patients with inconclusive exercise tests. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

NTP-CERHR monograph on the potential human reproductive and developmental effects of amphetamines.

PubMed

2005-07-01

The National Toxicology Program (NTP) Center for the Evaluation of Risks to Human Reproduction (CERHR) conducted an evaluation of the potential for amphetamines to cause adverse effects on reproduction and development in humans. Amphetamines evaluated were D- and D,L-amphetamine and methamphetamine. Amphetamine is approved by the U.S. Food and Drug Administration for the treatment of attention deficit hyperactivity disorder (ADHD) in persons over 3 years of age and narcolepsy; methamphetamine is approved for the treatment of ADHD in persons 6 years of age and older and for short-term treatment of obesity. Amphetamines were selected for evaluation because of 1) widespread usage in children, 2) availability of developmental studies in children and experimental animals, and 3) public concern about the effect of this stimulant on child development. The results of this evaluation on amphetamines are published in an NTP-CERHR monograph which includes: 1) the NTP Brief, 2) the Expert Panel Report on the Reproductive and Developmental Toxicity of Methylphenidate, and 3) public comments received on the Expert Panel Report. As stated in the NTP Brief, the NTP reached the following conclusions regarding the possible effects of exposure to methylphenidate on human development and reproduction. First, there is some concern for developmental effects, specifically for potential neurobehavioral alterations, from prenatal amphetamine exposure in humans both in therapeutic and non-therapeutic settings. After prenatal exposure to therapeutic doses of amphetamine, rat pups demonstrated neurobehavioral alterations. Data from human and animal studies were judged insufficient for an evaluation of the effect of amphetamine exposure on growth and other related developmental effects. Second, there is concern for methamphetamine-induced adverse developmental effects, specifically on growth and neurobehavioral development, in therapeutic and non-therapeutic settings. This conclusion is based on evidence from studies in experimental animals that prenatal and postnatal exposures to methamphetamine produce neurobehavioral alterations, small litter size, and low birth weight. Results from studies in humans suggest that methamphetamine may cause low birth weight and shortened gestation, but study confounders such as possible multiple drug usage prevent a definite conclusion. NTP-CERHR monographs are transmitted to federal and state agencies, interested parties, and the public and are available in electronic PDF format on the CERHR web site (http://cerhr.niehs.nih.gov) and in printed text or CD-ROM from the CERHR (National Institute of Environmental Health Sciences, P.O. Box 12233, MD EC-32, Research Triangle Park, NC; fax: 919-316-4511).

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.

Quantitative Adverse Outcome Pathways and Their ...

EPA Pesticide Factsheets

A quantitative adverse outcome pathway (qAOP) consists of one or more biologically based, computational models describing key event relationships linking a molecular initiating event (MIE) to an adverse outcome. A qAOP provides quantitative, dose–response, and time-course predictions that can support regulatory decision-making. Herein we describe several facets of qAOPs, including (a) motivation for development, (b) technical considerations, (c) evaluation of confidence, and (d) potential applications. The qAOP used as an illustrative example for these points describes the linkage between inhibition of cytochrome P450 19A aromatase (the MIE) and population-level decreases in the fathead minnow (FHM; Pimephales promelas). The qAOP consists of three linked computational models for the following: (a) the hypothalamic-pitutitary-gonadal axis in female FHMs, where aromatase inhibition decreases the conversion of testosterone to 17β-estradiol (E2), thereby reducing E2-dependent vitellogenin (VTG; egg yolk protein precursor) synthesis, (b) VTG-dependent egg development and spawning (fecundity), and (c) fecundity-dependent population trajectory. While development of the example qAOP was based on experiments with FHMs exposed to the aromatase inhibitor fadrozole, we also show how a toxic equivalence (TEQ) calculation allows use of the qAOP to predict effects of another, untested aromatase inhibitor, iprodione. While qAOP development can be resource-intensive, the quan

A double-blind randomized placebo-controlled clinical trial of squalamine ointment for tinea capitis treatment.

PubMed

Coulibaly, Oumar; Thera, Mahamadou A; Koné, Abdoulaye K; Siaka, Goïta; Traoré, Pierre; Djimdé, Abdoulaye A; Brunel, Jean-Michel; Gaudart, Jean; Piarroux, Renaud; Doumbo, Ogobara K; Ranque, Stéphane

2015-04-01

Novel treatments against for tinea capitis are needed, and the natural aminosterol squalamine is a potential topical antidermatophyte drug candidate. This phase II randomized double-blind placebo-controlled clinical trial aimed at testing the efficacy and safety of a three-week squalamine ointment regimen for the treatment of tinea capitis. Males aged 6-15 years presenting with tinea capitis were treated with either topical squalamine ointment or placebo for 3 weeks. The primary endpoint was complete clinical cure. The secondary endpoints were the occurrence of local and/or systemic adverse events, mycological cure, and partial clinical response. Prospective follow-up of clinical adverse events was performed daily. Five patients were treated with 1% squalamine ointment and 15 with placebo. No complete cure was observed. No clinical or biological adverse event was recorded. A significantly (p = 0.03) better hair-growth score, indicating a partial clinical improvement of the tinea capitis lesion, was observed in the patients treated with squalamine compared to those treated with placebo. This three-week squalamine ointment regimen was well tolerated and showed an encouraging partial clinical activity for the treatment of tinea capitis. Further studies are needed to evaluate the efficacy of topical squalamine alone against tinea corporis or in combination with a systemic antidermatophyte drug against tinea capitis.

Applying Adverse Outcome Pathways (AOPs) to support Integrated Approaches to Testing and Assessment (IATA).

PubMed

Tollefsen, Knut Erik; Scholz, Stefan; Cronin, Mark T; Edwards, Stephen W; de Knecht, Joop; Crofton, Kevin; Garcia-Reyero, Natalia; Hartung, Thomas; Worth, Andrew; Patlewicz, Grace

2014-12-01

Chemical regulation is challenged by the large number of chemicals requiring assessment for potential human health and environmental impacts. Current approaches are too resource intensive in terms of time, money and animal use to evaluate all chemicals under development or already on the market. The need for timely and robust decision making demands that regulatory toxicity testing becomes more cost-effective and efficient. One way to realize this goal is by being more strategic in directing testing resources; focusing on chemicals of highest concern, limiting testing to the most probable hazards, or targeting the most vulnerable species. Hypothesis driven Integrated Approaches to Testing and Assessment (IATA) have been proposed as practical solutions to such strategic testing. In parallel, the development of the Adverse Outcome Pathway (AOP) framework, which provides information on the causal links between a molecular initiating event (MIE), intermediate key events (KEs) and an adverse outcome (AO) of regulatory concern, offers the biological context to facilitate development of IATA for regulatory decision making. This manuscript summarizes discussions at the Workshop entitled "Advancing AOPs for Integrated Toxicology and Regulatory Applications" with particular focus on the role AOPs play in informing the development of IATA for different regulatory purposes. Copyright © 2014 Elsevier Inc. All rights reserved.

SNP genetic polymorphisms of MDR-1, CYP1A2 and CYPB11 genes in four canine breeds upon toxicological evaluation

PubMed Central

Gagliardi, Rosa; Llambí, Silvia

2015-01-01

The fields of pharmacogenetics and pharmacogenomics have become increasingly promising regarding the clinical application of genetic data to aid in prevention of adverse reactions. Specific screening tests can predict which animals express modified proteins or genetic sequences responsible for adverse effects associated with a drug. Among the genetic variations that have been investigated in dogs, the multidrug resistance gene (MDR) is the best studied. However, other genes such as CYP1A2 and CYP2B11 control the protein syntheses involved in the metabolism of many drugs. In the present study, the MDR-1, CYP1A2 and CYP2B11 genes were examined to identify SNP polymorphisms associated with these genes in the following four canine breeds: Uruguayan Cimarron, Border Collie, Labrador Retriever and German Shepherd. The results revealed that several SNPs of the CYP1A2 and CYP2B11 genes are potential targets for drug sensitivity investigations. PMID:25797294

SNP genetic polymorphisms of MDR-1, CYP1A2 and CYPB11 genes in four canine breeds upon toxicological evaluation.

PubMed

Gagliardi, Rosa; Llambí, Silvia; Arruga, M Victoria

2015-01-01

The fields of pharmacogenetics and pharmacogenomics have become increasingly promising regarding the clinical application of genetic data to aid in prevention of adverse reactions. Specific screening tests can predict which animals express modified proteins or genetic sequences responsible for adverse effects associated with a drug. Among the genetic variations that have been investigated in dogs, the multidrug resistance gene (MDR) is the best studied. However, other genes such as CYP1A2 and CYP2B11 control the protein syntheses involved in the metabolism of many drugs. In the present study, the MDR-1, CYP1A2 and CYP2B11 genes were examined to identify SNP polymorphisms associated with these genes in the following four canine breeds: Uruguayan Cimarron, Border Collie, Labrador Retriever and German Shepherd. The results revealed that several SNPs of the CYP1A2 and CYP2B11 genes are potential targets for drug sensitivity investigations.

Quantifying the Risk of Analgesic-Related Adverse Events After Knee Arthroscopy.

PubMed

Gonzales, Jeff; Lovald, Scott T; Lau, Edmund C; Ong, Kevin L

Opioids are frequently used as part of multimodal pain management protocols for knee arthroscopy; however, their use may be associated with opioid-related adverse events. The purpose of this study was to evaluate the risk of potential analgesic-related complications after knee arthroscopy using a nationally representative database. Using 2010\\endash 2012 Medicare claims data, patients undergoing knee arthroscopy procedures (including ligament repair, meniscectomy, and chondroplasty) were identified. The risk of complications related to typical modalities of analgesia, including opioids, within 90 days following surgery was assessed using multivariate Cox regression. Based on follow-up of 16,567 cases, respiratory complications (bradypnea, pulmonary insufficiency, asphyxia, and hypoxemia) were the most frequently diagnosed complications ( n = 418; 2.52%), followed by postoperative nausea and vomiting ( n = 174; 1.05%) and urinary retention complications ( n = 166; 1.00%). Risk factors including older age, male gender, lower socioeconomic status, and a high number of comorbidities were associated with development of postsurgical complications.

Defense mechanisms against toxic phytochemicals in the diet of domestic animals.

PubMed

Fink-Gremmels, Johanna

2010-02-01

Plant secondary metabolites (PSMs) are non-nutritional components that occur in numerous feed materials and are able to exert toxic effects in animals. The current article aims to summarize innate defense strategies developed by different animal species to avoid excessive exposure to PSMs. These mechanisms include pre-systemic degradation of PSMs by rumen microbiota, the intestinal barrier including efflux transporters of monogastric species, as well as pre-hepatic and intra-hepatic biotransformation processes. These physiological barriers determine systemic exposure and ultimately the dose-dependent adverse effects in the target animal species. Considering the large number of potentially toxic PSMs, which makes an evaluation of all individual PSMs virtually impossible, such a mechanism-oriented approach could improve the predictability of adverse effects and support the interpretation of clinical field observations. Moreover, mechanistic data related to tissue disposition and excretion pathways of PSMs for example into milk, could substantially support the assessment of the risks for consumers of foods derived from PSM-exposed animals.

Cognitive functioning after subthalamic nucleotomy for refractory Parkinson's disease

PubMed Central

McCarter, R.; Walton, N.; Rowan, A.; Gill, S.; Palomo, M.

2000-01-01

OBJECTIVE—To evaluate whether subthalamic nucleotomy produces adverse cognitive effects in patients with Parkinson's disease.
METHOD—Twelve patients with Parkinson's disease underwent stereotactic surgery to the subthalamic nucleus. Presurgical and postsurgical neuropsychological assessment of attention, memory, executive function, language, and verbal intellect were undertaken with a battery of tests designed to minimise potential contamination of cognitive effects by motor symptoms.
RESULTS—There was no statistically significant difference in the cognitive tests results after operation for the group as a whole. Reliable change indexes were generated for the cognitive tests. Reliable change postoperatively was found on specific tests of verbal memory, attention, and planning. Left sided operations were associated with greater incidence of deterioration postsurgery.
CONCLUSIONS—Preliminary data on the first reported cognitive changes after subthalamic nucleotomy suggested few adverse cognitive effects of the surgery although discrete neuropsychological changes were seen in some patients. These effects were consistent with current theories on the cognitive functions of the basal ganglia.

 PMID:10864605

Toxicological relevance of pharmaceuticals in drinking water.

PubMed

Bruce, Gretchen M; Pleus, Richard C; Snyder, Shane A

2010-07-15

Interest in the public health significance of trace levels of pharmaceuticals in potable water is increasing, particularly with regard to the effects of long-term, low-dose exposures. To assess health risks and establish target concentrations for water treatment, human health risk-based screening levels for 15 pharmaceutically active ingredients and four metabolites were compared to concentrations detected at 19 drinking water treatment plants across the United States. Compounds were selected based on rate of use, likelihood of occurrence, and potential for toxicity. Screening levels were established based on animal toxicity data and adverse effects at therapeutic doses, focusing largely on reproductive and developmental toxicity and carcinogenicity. Calculated drinking water equivalent levels (DWELs) ranged from 0.49 microg/L (risperidone) to 20,000 microg/L (naproxen). None of the 10 detected compounds exceeded their DWEL. Ratios of DWELs to maximum detected concentrations ranged from 110 (phenytoin) to 6,000,000 (sulfamethoxazole). Based on this evaluation, adverse health effects from targeted pharmaceuticals occurring in U.S. drinking water are not expected.

Study of Nephrotoxic Potential of Acetaminophen in Birds

PubMed Central

Jayakumar, K.; Mohan, K.; Swamy, H. D. Narayana; Shridhar, N. B.; Bayer, M. D.

2010-01-01

The present study was designed to evaluate the effect of acetaminophen on kidneys of birds by comparison with diclofenac that is used as positive control. The birds of Group I served as negative control and received normal saline, whereas Group II birds received diclofenac injection (2.5 mg/kg IM) and Group III birds received acetaminophen injection (10 mg/kg IM) for a period of seven days daily. The birds treated with diclofenac showed severe clinical signs of toxicity accompanied with high mortality and significant increase (P<0.001) in serum creatinine and uric acid concentration. The creatinine and uric acid concentrations were consistent with gross and histopathological findings. The negative control and acetaminophen-treated groups showed no adverse clinical signs, serum creatinine and uric acid concentrations were normal, and no gross or histopathological changes in kidneys were observed. Thus, it was concluded that acetaminophen can be used for treatment in birds without any adverse effect on kidneys. PMID:21170252

Field Evaluation of Detection-Control System

DOT National Transportation Integrated Search

2014-10-01

High-speed signalized intersections present unique challenges to improving highway safety. Techniques for achieving safety often have an adverse effect on efficiency, and techniques for achieving efficiency sometimes have an adverse effect on safety....

Sharpening the focus on occupational safety and health in nanotechnology.

PubMed

Schulte, Paul; Geraci, Charles; Zumwalde, Ralph; Hoover, Mark; Castranova, Vincent; Kuempel, Eileen; Murashov, Vladimir; Vainio, Harri; Savolainen, Kai

2008-12-01

Increasing numbers of workers are involved with the production, use, distribution, and disposal of nanomaterials. At the same time, there is a growing number of reports of adverse biological effects of engineered nanoparticles in test systems. It is useful, at this juncture, to identify critical questions that will help address knowledge gaps concerning the potential occupational hazards of these materials. The questions address (i) hazard classification of engineered nanoparticles, (ii) exposure metrics, (iii) the actual exposures to the different engineered nanoparticles in the workplace, (iv) the limits of engineering controls and personal protective equipment with respect to engineered nanoparticles, (v) the kinds of surveillance programs that may be required at workplaces to protect potentially exposed workers, (vi) whether exposure registers should be established for workers potentially exposed to engineered nanoparticles, and, (vii) whether engineered nanoparticles should be treated as "new" substances and evaluated for safety and hazards?

Health effects in Army Gulf War veterans possibly exposed to chemical munitions destruction at Khamisiyah, Iraq: Part I. Morbidity associated with potential exposure.

PubMed

Mahan, Clare M; Page, William F; Bullman, Tim A; Kang, Han K

2005-11-01

In March 1991, U.S. troops detonated the Khamisiyah, Iraq, ammunition depot, possibly releasing two chemical warfare agents, sarin and cyclosarin. The long-term health effects associated with possible exposure to these chemical warfare agents are unknown. This study was undertaken to investigate whether possible exposure was associated with morbidity among Army Gulf War veterans using morbidity data for 5,555 Army veterans who were deployed to the Gulf region. Responses to 86 self-assessed health measures, as reported in the 1995 Department of Veterans Affairs National Health Survey of Gulf War Era Veterans, were evaluated. We found little association between potential exposure and health, after adjustment for demographic variables, and conclude that potential exposure to sarin or cyclosarin at Khamisiyah does not seem to have adversely affected self-perceived health status, as evidenced by a wide range of health measures.

Development, implementation and evaluation of a patient handoff tool to improve safety in orthopaedic surgery.

PubMed

Gagnier, Joel J; Derosier, Joseph M; Maratt, Joseph D; Hake, Mark E; Bagian, James P

2016-06-01

To develop, implement and test the effect of a handoff tool for orthopaedic trauma residents that reduces adverse events associated with the omission of critical information and the transfer of erroneous information. Components of this project included a literature review, resident surveys and observations, checklist development and refinement, implementation and evaluation of impact on adverse events through a chart review of a prospective cohort compared with a historical control group. Large teaching hospital. Findings of a literature review were presented to orthopaedic residents, epidemiologists, orthopaedic surgeons and patient safety experts in face-to-face meetings, during which we developed and refined the contents of a resident handoff tool. The tool was tested in an orthopaedic trauma service and its impact on adverse events was evaluated through a chart review. The handoff tool was developed and refined during the face-to-face meetings and a pilot implementation. Adverse event data were collected on 127 patients (n = 67 baseline period; n = 60 test period). A handoff tool for use by orthopaedic residents. Adverse events in patients handed off by orthopaedic trauma residents. After controlling for age, gender and comorbidities, testing resulted in fewer events per person (25-27% reduction; P < 0.10). Preliminary evidence suggests that our resident handoff tool may contribute to a decrease in adverse events in orthopaedic patients. © The Author 2016. Published by Oxford University Press in association with the International Society for Quality in Health Care; all rights reserved.

36 CFR 800.14 - Federal agency program alternatives.

Code of Federal Regulations, 2010 CFR

2010-07-01

... program or the resolution of adverse effects from certain complex project situations or multiple... by the agreement. (3) Developing programmatic agreements for complex or multiple undertakings. Consultation to develop a programmatic agreement for dealing with the potential adverse effects of complex...

Elevated blood pressure in offspring of rats exposed to diverse chemicals during pregnancy

EPA Science Inventory

Adverse intrauterine environments are associated with increased risk of later disease, including cardiovascular disease and hypertension. As a potential bioindicator of such an adverse environment, we measured blood pressure (BP), renal nephron endowment, renal glucocorticoid rec...

Pharmacokinetic Modeling of Perfluorooctanoic Acid During Gestation and Lactation in the Mouse

EPA Science Inventory

Perfluorooctanoic acid (PFOA) is a processing aid for the polymerization of commercially valuable fluoropolymers. Its widespread environmental distribution, presence in human blood, and adverse effects in animal toxicity studies have triggered attention to its potential adverse e...

Monitoring potential adverse event rate differences using data from blinded trials: the canary in the coal mine.

PubMed

Gould, A Lawrence; Wang, William B

2017-01-15

The development of drugs and biologicals whose mechanisms of action may extend beyond their target indications has led to a need to identify unexpected potential toxicities promptly even while blinded clinical trials are under way. One component of recently issued FDA rules regarding safety reporting requirements raises the possibility of breaking the blind for pre-identified serious adverse events that are not the clinical endpoints of a blinded study. Concern has been expressed that unblinding individual cases of frequently occurring adverse events could compromise the overall validity of the study. However, if external information is available about adverse event rates among patients not receiving the test product in populations similar to the study population, then it may be possible to address the potential for elevated risk without unblinding the trial. This article describes a Bayesian approach for determining the likelihood of elevated risk suitable binomial or Poisson likelihoods that applies regardless of the metric used to express the difference. The method appears to be particularly appropriate for routine monitoring of safety information for project development programs that include large blinded trials. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

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.

A tiered approach for integrating exposure and dosimetry with ...

EPA Pesticide Factsheets

High-throughput (HT) risk screening approaches apply in vitro dose-response data to estimate potential health risks that arise from exposure to chemicals. However, much uncertainty is inherent in relating bioactivities observed in an in vitro system to the perturbations of biological mechanisms that lead to apical adverse health outcomes in living organisms. The chemical-agnostic Adverse Outcome Pathway (AOP) framework addresses this uncertainty by acting as a scaffold onto which pathway-based data can be arranged to aid in the understanding of in vitro toxicity testing results. In addition, risk estimation also requires reconciling chemical concentrations sufficient to produce bioactivity in vitro with concentrations that trigger a molecular initiating event (MIE) at the relevant biological target in vivo. Such target site exposures (TSEs) can be estimated using computational models to integrate exposure information with a chemical’s absorption, distribution, metabolism, and elimination (ADME) processes. In this presentation, the utility of a tiered approach for integrating exposure, ADME, and hazard into risk-based decision making will be demonstrated using several case studies, along with the investigation of how uncertainties in exposure and ADME might impact risk estimates. These case studies involve 1) identifying and prioritizing chemicals capable of altering biological pathways based on their potential to reach an in vivo target; 2) evaluating the infl

The risks of self-made diets: the case of an amateur bodybuilder.

PubMed

Della Guardia, Lucio; Cavallaro, Maurizio; Cena, Hellas

2015-01-01

Following DIY (do it yourself) diets as well as consuming supplements exceeding by far the recommended daily intake levels, is common among athletes; these dietary habits often lead to an overconsumption of some macro and/or micronutrients, exposing athletes to potential health risks. The aim of this study is to document the development of possible adverse effects in a 33 year-old amateur bodybuilder who consumed for 16 years a DIY high protein diet associated to nutrient supplementation. Body composition, biochemical measures and anamnestic findings were evaluated. We present this case to put on alert about the possible risks of such behavior repeated over time, focusing on the adverse gastrointestinal effects. We discuss the energy and nutrient composition of his DIY diet as well as the use of supplements. This study provides preliminary data of the potential risks of a long-term DIY dietary supplementation and a high protein diet. In this case, permanent abdominal discomfort was evidenced in an amateur body builder with an intake exceeding tolerable upper limit for vitamin A, selenium and zinc, according to our national and updated recommendations. As many amateur athletes usually adopt self-made diets and supplementation, it would be advisable for them to be supervised in order to prevent health risks due to a long-term DIY diet and over-supplementation.

Radiotherapy before and after radical prostatectomy for high-risk and locally advanced prostate cancer.

PubMed

Perez, Bradford A; Koontz, Bridget F

2015-05-01

Men with localized high-risk prostate cancer carry significant risk of prostate cancer-specific mortality. The best treatment approach to minimize this risk is unclear. In this review, we evaluate the role of radiation before and after radical prostatectomy. A critical review of the literature was performed regarding the application of external radiation therapy (RT) in combination with prostatectomy for high-risk localized prostate cancer. Up to 70% of men with high-risk localized disease may require adjuvant therapy because of adverse pathologic features or biochemical recurrence in the absence of systemic disease. The utility of adjuvant RT among men with adverse pathologic features are well established at least regarding minimizing biochemical recurrence risk. The optimal timing of salvage radiation is the subject of ongoing studies. Neoadjuvant RT requires further study but is a potentially attractive method because of decreased radiation field sizes and potential radiobiologic benefits of delivering RT before surgery. Salvage prostatectomy is effective at treating local recurrence after radiation but is associated with significant surgical morbidity. Combining local therapies including radical prostatectomy and RT can be a reasonable approach. Care should be taken at the initial presentation of high-risk localized prostate cancer to consider and plan for the likelihood of multimodality care. Copyright © 2015 Elsevier Inc. All rights reserved.

Validation and Potential Mechanisms of Red Cell Distribution Width as a Prognostic Marker in Heart Failure

PubMed Central

ALLEN, LARRY A.; FELKER, G. MICHAEL; MEHRA, MANDEEP R.; CHIONG, JUN R.; DUNLAP, STEPHANIE H.; GHALI, JALAL K.; LENIHAN, DANIEL J.; OREN, RON M.; WAGONER, LYNNE E.; SCHWARTZ, TODD A.; ADAMS, KIRKWOOD F.

2014-01-01

Background: Adverse outcomes have recently been linked to elevated red cell distribution width (RDW) in heart failure. Our study sought to validate the prognostic value of RDW in heart failure and to explore the potential mechanisms underlying this association. Methods and Results: Data from the Study of Anemia in a Heart Failure Population (STAMINA-HFP) registry, a prospective, multicenter cohort of ambulatory patients with heart failure supported multivariable modeling to assess relationships between RDW and outcomes. The association between RDW and iron metabolism, inflammation, and neurohormonal activation was studied in a separate cohort of heart failure patients from the United Investigators to Evaluate Heart Failure (UNITE-HF) Biomarker registry. RDW was independently predictive of outcome (for each 1% increase in RDW, hazard ratio for mortality 1.06, 95% CI 1.01-1.12; hazard ratio for hospitalization or mortality 1.06; 95% CI 1.02-1.10) after adjustment for other covariates. Increasing RDW correlated with decreasing hemoglobin, increasing interleukin-6, and impaired iron mobilization. Conclusions: Our results confirm previous observations that RDW is a strong, independent predictor of adverse outcome in chronic heart failure and suggest elevated RDW may indicate inflammatory stress and impaired iron mobilization. These findings encourage further research into the relationship between heart failure and the hematologic system. PMID:20206898

Validation and potential mechanisms of red cell distribution width as a prognostic marker in heart failure.

PubMed

Allen, Larry A; Felker, G Michael; Mehra, Mandeep R; Chiong, Jun R; Dunlap, Stephanie H; Ghali, Jalal K; Lenihan, Daniel J; Oren, Ron M; Wagoner, Lynne E; Schwartz, Todd A; Adams, Kirkwood F

2010-03-01

Adverse outcomes have recently been linked to elevated red cell distribution width (RDW) in heart failure. Our study sought to validate the prognostic value of RDW in heart failure and to explore the potential mechanisms underlying this association. Data from the Study of Anemia in a Heart Failure Population (STAMINA-HFP) registry, a prospective, multicenter cohort of ambulatory patients with heart failure supported multivariable modeling to assess relationships between RDW and outcomes. The association between RDW and iron metabolism, inflammation, and neurohormonal activation was studied in a separate cohort of heart failure patients from the United Investigators to Evaluate Heart Failure (UNITE-HF) Biomarker registry. RDW was independently predictive of outcome (for each 1% increase in RDW, hazard ratio for mortality 1.06, 95% CI 1.01-1.12; hazard ratio for hospitalization or mortality 1.06; 95% CI 1.02-1.10) after adjustment for other covariates. Increasing RDW correlated with decreasing hemoglobin, increasing interleukin-6, and impaired iron mobilization. Our results confirm previous observations that RDW is a strong, independent predictor of adverse outcome in chronic heart failure and suggest elevated RDW may indicate inflammatory stress and impaired iron mobilization. These findings encourage further research into the relationship between heart failure and the hematologic system. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: Results of a randomized, placebo-controlled clinical trial.

PubMed

Campbell, Craig; McMillan, Hugh J; Mah, Jean K; Tarnopolsky, Mark; Selby, Kathryn; McClure, Ty; Wilson, Dawn M; Sherman, Matthew L; Escolar, Diana; Attie, Kenneth M

2017-04-01

ACE-031 is a fusion protein of activin receptor type IIB and IgG1-Fc, which binds myostatin and related ligands. It aims to disrupt the inhibitory effect on muscle development and provide potential therapy for myopathies like Duchenne muscular dystrophy (DMD). ACE-031 was administered subcutaneously every 2-4 weeks to DMD boys in a randomized, double-blind, placebo-controlled, ascending-dose trial. The primary objective was safety evaluation. Secondary objectives included characterization of pharmacokinetics and pharmacodynamics. ACE-031 was not associated with serious or severe adverse events. The study was stopped after the second dosing regimen due to potential safety concerns of epistaxis and telangiectasias. A trend for maintenance of the 6-minute walk test (6MWT) distance in the ACE-031 groups compared with a decline in the placebo group (not statistically significant) was noted, as was a trend for increased lean body mass and bone mineral density (BMD) and reduced fat mass. ACE-031 use demonstrated trends for pharmacodynamic effects on lean mass, fat mass, BMD, and 6MWT. Non-muscle-related adverse events contributed to the decision to discontinue the study. Myostatin inhibition is a promising therapeutic approach for DMD. Muscle Nerve 55: 458-464, 2017. © 2016 Wiley Periodicals, Inc.

Hospital staff should use more than one method to detect adverse events and potential adverse events: incident reporting, pharmacist surveillance and local real‐time record review may all have a place

PubMed Central

Olsen, Sisse; Neale, Graham; Schwab, Kat; Psaila, Beth; Patel, Tejal; Chapman, E Jane; Vincent, Charles

2007-01-01

Background Over the past five years, in most hospitals in England and Wales, incident reporting has become well established but it remains unclear how well reports match clinical adverse events. International epidemiological studies of adverse events are based on retrospective, multi‐hospital case record review. In this paper the authors describe the use of incident reporting, pharmacist surveillance and local real‐time record review for the recognition of clinical risks associated with hospital inpatient care. Methodology Data on adverse events were collected prospectively on 288 patients discharged from adult acute medical and surgical units in an NHS district general hospital using incident reports, active surveillance of prescription charts by pharmacists and record review at time of discharge. Results Record review detected 26 adverse events (AEs) and 40 potential adverse events (PAEs) occurring during the index admission. In contrast, in the same patient group, incident reporting detected 11 PAEs and no AEs. Pharmacy surveillance found 10 medication errors all of which were PAEs. There was little overlap in the nature of events detected by the three methods. Conclusion The findings suggest that incident reporting does not provide an adequate assessment of clinical adverse events and that this method needs to be supplemented with other more systematic forms of data collection. Structured record review, carried out by clinicians, provides an important component of an integrated approach to identifying risk in the context of developing a safety and quality improvement programme. PMID:17301203

Changes in Risk of Immediate Adverse Reactions to Iodinated Contrast Media by Repeated Administrations in Patients with Hepatocellular Carcinoma

PubMed Central

Fujiwara, Naoto; Tateishi, Ryosuke; Akahane, Masaaki; Taguri, Masataka; Minami, Tatsuya; Mikami, Shintaro; Sato, Masaya; Uchino, Kouji; Enooku, Kenichiro; Kondo, Yuji; Asaoka, Yoshinari; Yamashiki, Noriyo; Goto, Tadashi; Shiina, Shuichiro; Yoshida, Haruhiko; Ohtomo, Kuni; Koike, Kazuhiko

2013-01-01

Background To elucidate whether repeated exposures to iodinated contrast media increase the risk of adverse reaction. Materials and Methods We retrospectively reviewed 1,861 patients with hepatocellular carcinoma who visited authors’ institution, a tertiary referral center, between 2004 and 2008. We analyzed cumulative probability of adverse reactions and risk factors. We categorized all symptoms into hypersensitivity reactions, physiologic reactions, and other reactions, according to the American College of Radiology guidelines, and evaluated each category as an event. We estimated the association between hazard for adverse reactions and the number of cumulative exposures to contrast media. We also evaluated subsequent contrast media injections and adverse reactions. Results There were 23,684 contrast media injections in 1,729 patients. One hundred and thirty-two patients were excluded because they were given no contrast media during the study period. Adverse reactions occurred in 196 (0.83%) patients. The cumulative incidence at 10th, 20th, and 30th examination was 7.9%, 15.2%, and 24.1%, respectively. Presence of renal impairment was found to be one of risk factors for adverse reactions. The estimated hazard of overall adverse reaction gradually decreased until around 10th exposure and rose with subsequent exposures. The estimated hazard of hypersensitivity showed V-shaped change with cumulative number of exposures. The estimated hazard of physiologic reaction had a tendency toward decreasing and that of other reaction had a tendency toward increasing. Second adverse reaction was more severe than the initial in only one among 130 patients receiving subsequent injections. Conclusion Repeated exposures to iodinated contrast media increase the risk of adverse reaction. PMID:24098420

A case study to illustrate the utility of the Aggregate Exposure Pathway and Adverse Outcome Pathway frameworks for integrating human health and ecological data into cumulative risk assessment

EPA Science Inventory

Cumulative risk assessment (CRA) methods, which evaluate the risk of multiple adverse outcomes (AOs) from multiple chemicals, promote the use of a conceptual site model (CSM) to integrate risk from relevant stressors. The Adverse Outcome Pathway (AOP) framework can inform these r...

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.

A Pathway to Psychological Difficulty: Perceived Chronic Social Adversity and Its Symptomatic Reactions

PubMed Central

Ding, Cody; Zhang, Jingqiu; Yang, Dong

2018-01-01

In this paper, we attempt to predict and explain psychological maladjustment or difficulty. Specifically, we discuss the concept of perceived chronic social adversity, and we expect that such perceived chronic social adversity may potentially lead to chronic stress responses. Accordingly, we propose the symptomatic reactions of perceived chronic social adversity. We put forward a set of hypotheses regarding the relationships between perceived chronic social adversity and those chronic stress responses, and we further hypothesize a mediating role of individualized negative essentialism brought by perceived chronical social adversity. Resilience and individual differences in the ability to cope with perceived adversity are discussed. Future research and prevention need to pay more attention to effects of subjective personal experiences on psychological difficulty, focusing on the importance of exploring daily social experiences in improving cognitive construction processes and developing appropriate preventions. PMID:29755394

Elucidation of the molecular mechanisms underlying adverse reactions associated with a kinase inhibitor using systems toxicology

PubMed Central

Amemiya, Takahiro; Honma, Masashi; Kariya, Yoshiaki; Ghosh, Samik; Kitano, Hiroaki; Kurachi, Yoshihisa; Fujita, Ken-ichi; Sasaki, Yasutsuna; Homma, Yukio; Abernethy, Darrel R; Kume, Haruki; Suzuki, Hiroshi

2015-01-01

Background/Objectives: Targeted kinase inhibitors are an important class of agents in anticancer therapeutics, but their limited tolerability hampers their clinical performance. Identification of the molecular mechanisms underlying the development of adverse reactions will be helpful in establishing a rational method for the management of clinically adverse reactions. Here, we selected sunitinib as a model and demonstrated that the molecular mechanisms underlying the adverse reactions associated with kinase inhibitors can efficiently be identified using a systems toxicological approach. Methods: First, toxicological target candidates were short-listed by comparing the human kinase occupancy profiles of sunitinib and sorafenib, and the molecular mechanisms underlying adverse reactions were predicted by sequential simulations using publicly available mathematical models. Next, to evaluate the probability of these predictions, a clinical observation study was conducted in six patients treated with sunitinib. Finally, mouse experiments were performed for detailed confirmation of the hypothesized molecular mechanisms and to evaluate the efficacy of a proposed countermeasure against adverse reactions to sunitinib. Results: In silico simulations indicated the possibility that sunitinib-mediated off-target inhibition of phosphorylase kinase leads to the generation of oxidative stress in various tissues. Clinical observations of patients and mouse experiments confirmed the validity of this prediction. The simulation further suggested that concomitant use of an antioxidant may prevent sunitinib-mediated adverse reactions, which was confirmed in mouse experiments. Conclusions: A systems toxicological approach successfully predicted the molecular mechanisms underlying clinically adverse reactions associated with sunitinib and was used to plan a rational method for the management of these adverse reactions. PMID:28725458

Enhancing global vaccine pharmacovigilance: Proof-of-concept study on aseptic meningitis and immune thrombocytopenic purpura following measles-mumps containing vaccination

PubMed Central

Perez-Vilar, Silvia; Weibel, Daniel; Sturkenboom, Miriam; Black, Steven; Maure, Christine; Castro, Jose Luis; Bravo-Alcántara, Pamela; Dodd, Caitlin N.; Romio, Silvana A.; de Ridder, Maria; Nakato, Swabra; Molina-León, Helvert Felipe; Elango, Varalakshmi; Zuber, Patrick L.F.

2017-01-01

New vaccines designed to prevent diseases endemic in low and middle-income countries (LMICs) are now being introduced without prior record of utilization in countries with robust pharmacovigilance systems. To address this deficit, our objective was to demonstrate feasibility of an international hospital-based network for the assessment of potential epidemiological associations between serious and rare adverse events and vaccines in any setting. This was done through a proof-of-concept evaluation of the risk of immune thrombocytopenic purpura (ITP) and aseptic meningitis (AM) following administration of the first dose of measles-mumps-containing vaccines using the self-controlled risk interval method in the primary analysis. The World Health Organization (WHO) selected 26 sentinel sites (49 hospitals) distributed in 16 countries of the six WHO regions. Incidence rate ratios (IRR) of 5.0 (95% CI: 2.5-9.7) for ITP following first dose of measles-containing vaccinations, and of 10.9 (95% CI: 4.2-27.8) for AM following mumps-containing vaccinations were found. The strain-specific analyses showed significantly elevated ITP risk for measles vaccines containing Schwarz (IRR: 20.7; 95% CI: 2.7-157.6), Edmonston-Zagreb (IRR: 11.1; 95% CI: 1.4-90.3), and Enders´Edmonston (IRR: 8.5; 95% CI: 1.9-38.1) strains. A significantly elevated AM risk for vaccines containing the Leningrad-Zagreb mumps strain (IRR: 10.8; 95% CI: 1.3-87.4) was also found. This proof-of-concept study has shown, for the first time, that an international hospital-based network for the investigation of rare vaccine adverse events, using common standardized procedures and with high participation of LMICs, is feasible, can produce reliable results, and has the potential to characterize differences in risk between vaccine strains. The completion of this network by adding large reference hospitals, particularly from tropical countries, and the systematic WHO-led implementation of this approach, should permit the rapid post-marketing evaluation of safety signals for serious and rare adverse events for new and existing vaccines in all settings, including LMICs. PMID:28558983

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 concentrations below predicted toxicity thresholds. Consequently, there is a need to evaluate the environmental concerns related to pesticide exposures to fish populations based on current biological and toxicological techniques. This presentation reviews some of the agricultural chemicals that have emerged as contaminants of concern and potentially threaten fish populations in agricultural watersheds.

Enhancing global vaccine pharmacovigilance: Proof-of-concept study on aseptic meningitis and immune thrombocytopenic purpura following measles-mumps containing vaccination.

PubMed

Perez-Vilar, Silvia; Weibel, Daniel; Sturkenboom, Miriam; Black, Steven; Maure, Christine; Castro, Jose Luis; Bravo-Alcántara, Pamela; Dodd, Caitlin N; Romio, Silvana A; de Ridder, Maria; Nakato, Swabra; Molina-León, Helvert Felipe; Elango, Varalakshmi; Zuber, Patrick L F

2018-01-08

New vaccines designed to prevent diseases endemic in low and middle-income countries (LMICs) are now being introduced without prior record of utilization in countries with robust pharmacovigilance systems. To address this deficit, our objective was to demonstrate feasibility of an international hospital-based network for the assessment of potential epidemiological associations between serious and rare adverse events and vaccines in any setting. This was done through a proof-of-concept evaluation of the risk of immune thrombocytopenic purpura (ITP) and aseptic meningitis (AM) following administration of the first dose of measles-mumps-containing vaccines using the self-controlled risk interval method in the primary analysis. The World Health Organization (WHO) selected 26 sentinel sites (49 hospitals) distributed in 16 countries of the six WHO regions. Incidence rate ratios (IRR) of 5.0 (95% CI: 2.5-9.7) for ITP following first dose of measles-containing vaccinations, and of 10.9 (95% CI: 4.2-27.8) for AM following mumps-containing vaccinations were found. The strain-specific analyses showed significantly elevated ITP risk for measles vaccines containing Schwarz (IRR: 20.7; 95% CI: 2.7-157.6), Edmonston-Zagreb (IRR: 11.1; 95% CI: 1.4-90.3), and Enders'Edmonston (IRR: 8.5; 95% CI: 1.9-38.1) strains. A significantly elevated AM risk for vaccines containing the Leningrad-Zagreb mumps strain (IRR: 10.8; 95% CI: 1.3-87.4) was also found. This proof-of-concept study has shown, for the first time, that an international hospital-based network for the investigation of rare vaccine adverse events, using common standardized procedures and with high participation of LMICs, is feasible, can produce reliable results, and has the potential to characterize differences in risk between vaccine strains. The completion of this network by adding large reference hospitals, particularly from tropical countries, and the systematic WHO-led implementation of this approach, should permit the rapid post-marketing evaluation of safety signals for serious and rare adverse events for new and existing vaccines in all settings, including LMICs. Copyright © 2017 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

Trace element concentrations in surface estuarine and marine sediments along the Mississippi Gulf Coast following Hurricane Katrina.

PubMed

Warren, Crystal; Duzgoren-Aydin, Nurdan S; Weston, James; Willett, Kristine L

2012-01-01

Hurricanes are relatively frequent ecological disturbances that may cause potentially long-term impacts to the coastal environment. Hurricane Katrina hit the Mississippi Gulf Coast in August 2005, and caused a storm surge with the potential to change the trace element content of coastal surface sediments. In this study, surface estuarine and marine sediments were collected monthly following the storm from ten sites along the Mississippi Gulf Coast (Mobile Bay, Grand Bay Bayous Heron and Cumbest, Pascagoula, Ocean Springs, Biloxi Gulf, Back Biloxi Bay, Gulfport Gulf, Gulfport Courthouse Rd, and Gulfport Marina). Concentrations of V, Cr, Mn, Fe, Co, Ni, Zn, As, Cd, and Pb were measured by inductively coupled plasma-mass spectrometry to evaluate their temporal and spatial variations in the year following Hurricane Katrina. Sediments were characterized by pH, particle size distribution and total carbon and nitrogen content. Trace element contents of the sediments were determined in both <2 mm and <63 μm grain size fractions. Results revealed no significant temporal and spatial variability in trace element concentrations, in either size fraction. Potential ecological risk of the sediments was assessed by using NOAA SQuiRTs' guideline values; most concentrations remained below probable adverse effects guidelines to marine organisms suggesting that trace elements redistributed by Hurricane Katrina would not cause an adverse impact on resident organisms. Instead, the concentrations of trace elements were site-dependent, with specific contaminants relating to the use of the area prior to Hurricane Katrina.

Safe Handling of Oral Antineoplastic Medications: Focus on Targeted Therapeutics in the Home Setting

PubMed Central

Cass, Yaakov; Connor, Thomas H.; Tabachnik, Alexander

2017-01-01

Introduction With the growing number of oral targeted therapies being approved for use in cancer therapy, the potential for long-term administration of these drugs to cancer patients is expanding. The use of these drugs in the home setting has the potential to expose family members and caregivers to them either through direct contact with the drugs or indirectly by exposure to the parent compounds and/or their active metabolites in contaminated patient's waste. Methods A systematic literature review was performed and the known adverse health effect of 32 oral targeted therapeutics is summarized. In particular, the carcinogenicity, genotoxicity, and embryo-foetal toxicity, along with the route of excretion were evaluated. Results Carcinogenicity testing has not been performed on most of the oral targeted therapeutics and the genotoxicity data are mixed. However, the majority of these drugs exhibit adverse reproductive effects, some of which are severe. Currently available data does not permit the possibility of a health hazard from inappropriate handling of drugs and contaminated patients waste to be ignored, especially in a long-term home setting. Further research is needed to understand these issues. Conclusions With the expanding use of targeted therapies in the home setting, family members and caregivers, especially those of reproductive risk age, are, potentially at risk. Overall basic education and related precautions should be taken to protect family members and caregivers from indirect or direct exposure from these drugs. Further investigations and discussion on this subject is warranted. PMID:27009803

EMBRYONIC VASCULAR DISRUPTION ADVERSE OUTCOMES: LINKING HIGH THROUGHPUT SIGNALING SIGNATURES WITH FUNCTIONAL CONSEQUENCES

EPA Science Inventory

Embryonic vascular disruption is an important adverse outcome pathway (AOP) given the knowledge that chemical disruption of early cardiovascular system development leads to broad prenatal defects. High throughput screening (HTS) assays provide potential building blocks for AOP d...

40 CFR 35.1620-4 - Public participation.

Code of Federal Regulations, 2014 CFR

2014-07-01

... selecting alternatives; in assessing potential adverse environmental impacts; and in identifying measures to mitigate any adverse impacts that were identified. The recipient shall provide information relevant to..., or if the recipient or the Regional Administrator determines that a hearing would be beneficial. (c...

Adverse Outcome Pathways – Organizing Toxicological Information to Improve Decision Making

EPA Science Inventory

The number of chemicals for which environmental regulatory decisions are required far exceeds the current capacity for toxicity testing. High throughput screening (HTS) commonly used for drug discovery has the potential to increase this capacity. The adverse outcome pathway (AOP)...

An unintended consequence of electronic prescriptions: prevalence and impact of internal discrepancies

PubMed Central

Palchuk, Matvey B; Fang, Elizabeth A; Cygielnik, Janet M; Labreche, Matthew; Shubina, Maria; Ramelson, Harley Z; Hamann, Claus; Broverman, Carol; Einbinder, Jonathan S

2010-01-01

Many e-prescribing systems allow for both structured and free-text fields in prescriptions, making possible internal discrepancies. This study reviewed 2914 electronic prescriptions that contained free-text fields. Internal discrepancies were found in 16.1% of the prescriptions. Most (83.8%) of the discrepancies could potentially lead to adverse events and many (16.8%) to severe adverse events, involving a hospital admission or death. Discrepancies in doses, routes or complex regimens were most likely to have a potential for a severe event (p=0.0001). Discrepancies between structured and free-text fields in electronic prescriptions are common and can cause patient harm. Improvements in electronic medical record design are necessary to minimize the risk of discrepancies and resulting adverse events. PMID:20595316

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

PubMed

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

2007-06-01

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

Acute Cerebellar Ataxia Induced by Nivolumab

PubMed Central

Kawamura, Reina; Nagata, Eiichiro; Mukai, Masako; Ohnuki, Yoichi; Matsuzaki, Tomohiko; Ohiwa, Kana; Nakagawa, Tomoki; Kohno, Mitsutomo; Masuda, Ryota; Iwazaki, Masayuki; Takizawa, Shunya

2017-01-01

A 54-year-old woman with adenocarcinoma of the lung and lymph node metastasis experienced nystagmus and cerebellar ataxia 2 weeks after initiating nivolumab therapy. An evaluation for several autoimmune-related antibodies and paraneoplastic syndrome yielded negative results. We eventually diagnosed the patient with nivolumab-induced acute cerebellar ataxia, after excluding other potential conditions. Her ataxic gait and nystagmus resolved shortly after intravenous steroid pulse therapy followed by the administration of decreasing doses of oral steroids. Nivolumab, an immune checkpoint inhibitor, is known to induce various neurological adverse events. However, this is the first report of acute cerebellar ataxia associated with nivolumab treatment. PMID:29249765

Adverse Reactions to Vaccination: From Anaphylaxis to Autoimmunity.

PubMed

Gershwin, Laurel J

2018-03-01

Vaccines are important for providing protection from infectious diseases. Vaccination initiates a process that stimulates development of a robust and long-lived immune response to the disease agents in the vaccine. Side effects are sometimes associated with vaccination. These vary from development of acute hypersensitivity responses to vaccine components to local tissue reactions that are annoying but not significantly detrimental to the patient. The pathogenesis of these responses and the consequent clinical outcomes are discussed. Overstimulation of the immune response and the potential relationship to autoimmunity is evaluated in relation to genetic predisposition. Copyright © 2017 Elsevier Inc. All rights reserved.

When bad things happen: adverse event reporting and disclosure as patient safety and risk management tools in the neonatal intensive care unit.

PubMed

Donn, Steven M; McDonnell, William M

2012-01-01

The Institute of Medicine has recommended a change in culture from "name and blame" to patient safety. This will require system redesign to identify and address errors, establish performance standards, and set safety expectations. This approach, however, is at odds with the present medical malpractice (tort) system. The current system is outcomes-based, meaning that health care providers and institutions are often sued despite providing appropriate care. Nevertheless, the focus should remain to provide the safest patient care. Effective peer review may be hindered by the present tort system. Reporting of medical errors is a key piece of peer review and education, and both anonymous reporting and confidential reporting of errors have potential disadvantages. Diagnostic and treatment errors continue to be the leading sources of allegations of malpractice in pediatrics, and the neonatal intensive care unit is uniquely vulnerable. Most errors result from systems failures rather than human error. Risk management can be an effective process to identify, evaluate, and address problems that may injure patients, lead to malpractice claims, and result in financial losses. Risk management identifies risk or potential risk, calculates the probability of an adverse event arising from a risk, estimates the impact of the adverse event, and attempts to control the risk. Implementation of a successful risk management program requires a positive attitude, sufficient knowledge base, and a commitment to improvement. Transparency in the disclosure of medical errors and a strategy of prospective risk management in dealing with medical errors may result in a substantial reduction in medical malpractice lawsuits, lower litigation costs, and a more safety-conscious environment. Thieme Medical Publishers, Inc.

Evolution of pharmacological obesity treatments: focus on adverse side-effect profiles.

PubMed

Krentz, A J; Fujioka, K; Hompesch, M

2016-06-01

Pharmacotherapy directed toward reducing body weight may provide benefits for both curbing obesity and lowering the risk of obesity-associated comorbidities; however, many weight loss medications have been withdrawn from the market because of serious adverse effects. Examples include pulmonary hypertension (aminorex), cardiovascular toxicity, e.g. flenfluramine-induced valvopathy, stroke [phenylpropanolamine (PPA)], excess non-fatal cardiovascular events (sibutramine), and neuro-psychiatric issues (rimonabant; approved in Europe, but not in the USA). This negative experience has helped mould the current drug development and approval process for new anti-obesity drugs. Differences between the US Food and Drug Administration (FDA) and the European Medicines Agency, however, in perceptions of risk-benefit considerations for individual drugs have resulted in discrepancies in approval and/or withdrawal of weight-reducing medications. Thus, two drugs recently approved by the FDA, i.e. lorcaserin and phentermine + topiramate extended release, are not available in Europe. In contrast, naltrexone sustained release (SR)/bupropion SR received FDA approval, and liraglutide 3.0 mg was recently approved in both the USA and Europe. Regulatory strategies adopted by the FDA to manage the potential for uncommon but potentially serious post-marketing toxicity include: (i) risk evaluation and mitigation strategy programmes; (ii) stipulating post-marketing safety trials; (iii) considering responder rates and limiting cumulative exposure by discontinuation if weight loss is not attained within a reasonable timeframe; and (iv) requiring large cardiovascular outcome trials before or after approval. We chronicle the adverse effects of anti-obesity pharmacotherapy and consider how the history of high-profile toxicity issues has shaped the current regulatory landscape for new and future weight-reducing drugs. © 2016 John Wiley & Sons Ltd.