Sample records for background adverse drug

  1. 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

  2. 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

  3. Postmarket Drug Surveillance Without Trial Costs: Discovery of Adverse Drug Reactions Through Large-Scale Analysis of Web Search Queries

    PubMed Central

    Gabrilovich, Evgeniy

    2013-01-01

    Background Postmarket drug safety surveillance largely depends on spontaneous reports by patients and health care providers; hence, less common adverse drug reactions—especially those caused by long-term exposure, multidrug treatments, or those specific to special populations—often elude discovery. Objective Here we propose a low cost, fully automated method for continuous monitoring of adverse drug reactions in single drugs and in combinations thereof, and demonstrate the discovery of heretofore-unknown ones. Methods We used aggregated search data of large populations of Internet users to extract information related to drugs and adverse reactions to them, and correlated these data over time. We further extended our method to identify adverse reactions to combinations of drugs. Results We validated our method by showing high correlations of our findings with known adverse drug reactions (ADRs). However, although acute early-onset drug reactions are more likely to be reported to regulatory agencies, we show that less acute later-onset ones are better captured in Web search queries. Conclusions Our method is advantageous in identifying previously unknown adverse drug reactions. These ADRs should be considered as candidates for further scrutiny by medical regulatory authorities, for example, through phase 4 trials. PMID:23778053

  4. 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

  5. Adverse Reactions to Hallucinogenic Drugs.

    ERIC Educational Resources Information Center

    Meyer, Roger E. , Ed.

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

  6. Severe Cutaneous Adverse Drug Reactions: A Clinicoepidemiological Study

    PubMed Central

    Sasidharanpillai, Sarita; Riyaz, Najeeba; Khader, Anza; Rajan, Uma; Binitha, Manikoth P; Sureshan, Deepthi N

    2015-01-01

    Background: Drug eruptions range from transient erythema to the life threatening severe cutaneous adverse reactions (SCAR) that encompass Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms complex (DRESS). Aims and Objectives: To study the clinical and epidemiological aspects of cutaneous adverse drug reactions (CADR). Materials and Methods: Ethical clearance was obtained from the institutional ethics committee. All patients admitted in the Dermatology ward of our tertiary care hospital with CADR (those who fit in the category of probable or possible drug reaction as per WHO casuality assessment) from first September 2011 to 31st August 2012 were included in this cross sectional study after obtaining written informed consent. The drug reaction patterns observed in the study population were determined and the common offending drugs were identified. Results: In the study, population of males outnumbered females and the majority were between 46 and 60 years of age. The commonest reaction pattern observed was SJS- TEN spectrum of illness and aromatic anticonvulsants were the common offending drugs. Prompt withdrawal of the culprit drug and administration of systemic steroids with or without I/V Ig reverted the adverse reaction in all except one. Conclusion: Severe drug reactions predominated as the study population was comprised of inpatients of a tertiary referral centre. Though; previous authors had reported a mortality rate of up to 20% in DRESS, all our patients with this reaction pattern, responded well to treatment. The mortality rate among TEN cases was much lower than the previous reports. Early diagnosis, prompt withdrawal of the suspected drug, careful monitoring for development of complications and immediate intervention can improve the prognosis of CADR. PMID:25657416

  7. Automatically Recognizing Medication and Adverse Event Information From Food and Drug Administration’s Adverse Event Reporting System Narratives

    PubMed Central

    Polepalli Ramesh, Balaji; Belknap, Steven M; Li, Zuofeng; Frid, Nadya; West, Dennis P

    2014-01-01

    Background The Food and Drug Administration’s (FDA) Adverse Event Reporting System (FAERS) is a repository of spontaneously-reported adverse drug events (ADEs) for FDA-approved prescription drugs. FAERS reports include both structured reports and unstructured narratives. The narratives often include essential information for evaluation of the severity, causality, and description of ADEs that are not present in the structured data. The timely identification of unknown toxicities of prescription drugs is an important, unsolved problem. Objective The objective of this study was to develop an annotated corpus of FAERS narratives and biomedical named entity tagger to automatically identify ADE related information in the FAERS narratives. Methods We developed an annotation guideline and annotate medication information and adverse event related entities on 122 FAERS narratives comprising approximately 23,000 word tokens. A named entity tagger using supervised machine learning approaches was built for detecting medication information and adverse event entities using various categories of features. Results The annotated corpus had an agreement of over .9 Cohen’s kappa for medication and adverse event entities. The best performing tagger achieves an overall performance of 0.73 F1 score for detection of medication, adverse event and other named entities. Conclusions In this study, we developed an annotated corpus of FAERS narratives and machine learning based models for automatically extracting medication and adverse event information from the FAERS narratives. Our study is an important step towards enriching the FAERS data for postmarketing pharmacovigilance. PMID:25600332

  8. 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.

  9. Reporting of adverse drug reactions in randomised controlled trials – a systematic survey

    PubMed Central

    Loke, Yoon Kong; Derry, Sheena

    2001-01-01

    Background Decisions on treatment are guided, not only by the potential for benefit, but also by the nature and severity of adverse drug reactions. However, some researchers have found numerous deficiencies in trial reports of adverse effects. We sought to confirm these findings by evaluating trials of drug therapy published in seven eminent medical journals in 1997. Methods Literature review to determine whether the definition, recording and reporting of adverse drug reactions in clinical trials were in accordance with published recommendations on structured reporting. Results Of the 185 trials reviewed, 25 (14%) made no mention of adverse drug reactions. Data in a further 60 (32%) could not be fully evaluated, either because numbers were not given for each treatment arm (31 trials), or because a generic statement was made without full details (29 trials). When adverse drug reactions such as clinical events or patient symptoms were mentioned in the reports, details on how they had been recorded were given in only 14/95 (15%) and 18/104 (17%) trials respectively. Of the 86 trials that mentioned severity of adverse drug reactions, only 42 (49%) stated how severity had been defined. The median amount of space used for safety data in the Results and Discussion sections was 5.8%. Conclusions Trial reports often failed to provide details on how adverse drug reactions were defined or recorded. The absence of such methodological information makes comparative evaluation of adverse reaction rates potentially unreliable. Authors and journals should adopt recommendations on the structured reporting of adverse effects. PMID:11591227

  10. Adverse drug reactions in hospitalized Colombian children.

    PubMed

    de Las Salas, Roxana; Díaz-Agudelo, Daniela; Burgos-Flórez, Francisco Javier; Vaca, Claudia; Serrano-Meriño, Dolores Vanessa

    2016-09-30

    The occurrence of adverse drug reactions is an important issue due to the lack of drug safety data in children. To describe the Adverse Drug Reactions in inpatient children under 6 years of age in two general pediatrics wards located in Barranquilla, Colombia. A prospective cohort study based on intensive pharmacovigilance was conducted during six months in order to monitor the emergence of Adverse Drug Reactions in inpatients children under 6 years of age with at least one medication prescribed. The study was conducted in two pediatric wards of two hospitals located in Barranquilla, Colombia. Naranjo´s Algorithm was used to evaluate imputability, the modified Hartwig and Siegel assessment scale to establish severity and the Schumock and Thornton criteria to determine preventability. Of a total of 772 monitored patients, 156 Adverse Drug Reactions were detected on 147 children. The cumulative incidence of Adverse Drug Reactions was 19.0% (147/772); the incidence density was 37.6 Adverse Drug Reactions per 1,000 patients-days (147/3,913). The frequency was higher in children under 2 years of age (12.7%). Emergence of Adverse Drug Reactions was higher in male patients (RR= 1.66; 95% CI= 1.22-2.22, p = 0.001) and in those who used systemic antibiotics (RR= 1.82; 95% CI= 1.17-2.82, p = 0.005). Adverse Drug Reactions are common among hospitalized children and represent an additional burden of morbidity and risk, particularly in those who used several medicines, including antibiotics.

  11. Adverse Drug Reactions in Dental Practice

    PubMed Central

    Becker, Daniel E.

    2014-01-01

    Adverse reactions may occur with any of the medications prescribed or administered in dental practice. Most of these reactions are somewhat predictable based on the pharmacodynamic properties of the drug. Others, such as allergic and pseudoallergic reactions, are less common and unrelated to normal drug action. This article will review the most common adverse reactions that are unrelated to drug allergy. PMID:24697823

  12. Adverse drug reactions induced by valproic acid.

    PubMed

    Nanau, Radu M; Neuman, Manuela G

    2013-10-01

    Valproic acid is a widely-used first-generation antiepileptic drug, prescribed predominantly in epilepsy and psychiatric disorders. VPA has good efficacy and pharmacoeconomic profiles, as well as a relatively favorable safety profile. However, adverse drug reactions have been reported in relation with valproic acid use, either as monotherapy or polytherapy with other antiepileptic drugs or antipsychotic drugs. This systematic review discusses valproic acid adverse drug reactions, in terms of hepatotoxicity, mitochondrial toxicity, hyperammonemic encephalopathy, hypersensitivity syndrome reactions, neurological toxicity, metabolic and endocrine adverse events, and teratogenicity. Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  13. 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

  14. Adverse drug event monitoring at the Food and Drug Administration.

    PubMed

    Ahmad, Syed Rizwanuddin

    2003-01-01

    The Food and Drug Administration (FDA) is responsible not only for approving drugs but also for monitoring their safety after they reach the market. The complete adverse event profile of a drug is not known at the time of approval because of the small sample size, short duration, and limited generalizability of pre-approval clinical trials. This report describes the FDA's postmarketing surveillance system, to which many clinicians submit reports of adverse drug events encountered while treating their patients. Despite its limitations, the spontaneous reporting system is an extremely valuable mechanism by which hazards with drugs that were not observed or recognized at the time of approval are identified. Physicians are strongly encouraged to submit reports of adverse outcomes with suspect drugs to the FDA, and their reports make a difference. The FDA is strengthening its postmarketing surveillance with access to new data sources that have the potential to further improve the identification, quantification, and subsequent management of drug risk.

  15. Adverse Drug Event Monitoring at the Food and Drug Administration

    PubMed Central

    Ahmad, Syed Rizwanuddin

    2003-01-01

    The Food and Drug Administration (FDA) is responsible not only for approving drugs but also for monitoring their safety after they reach the market. The complete adverse event profile of a drug is not known at the time of approval because of the small sample size, short duration, and limited generalizability of pre-approval clinical trials. This report describes the FDA's postmarketing surveillance system, to which many clinicians submit reports of adverse drug events encountered while treating their patients. Despite its limitations, the spontaneous reporting system is an extremely valuable mechanism by which hazards with drugs that were not observed or recognized at the time of approval are identified. Physicians are strongly encouraged to submit reports of adverse outcomes with suspect drugs to the FDA, and their reports make a difference. The FDA is strengthening its postmarketing surveillance with access to new data sources that have the potential to further improve the identification, quantification, and subsequent management of drug risk. PMID:12534765

  16. [Management of adverse drug effects].

    PubMed

    Schlienger, R G

    2000-09-01

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

  17. Promoting adverse drug reaction reporting: comparison of different approaches

    PubMed Central

    Ribeiro-Vaz, Inês; Santos, Cristina Costa; Cruz-Correia, Ricardo

    2016-01-01

    ABSTRACT OBJECTIVE To describe different approaches to promote adverse drug reaction reporting among health care professionals, determining their cost-effectiveness. METHODS We analyzed and compared several approaches taken by the Northern Pharmacovigilance Centre (Portugal) to promote adverse drug reaction reporting. Approaches were compared regarding the number and relevance of adverse drug reaction reports obtained and costs involved. Costs by report were estimated by adding the initial costs and the running costs of each intervention. These costs were divided by the number of reports obtained with each intervention, to assess its cost-effectiveness. RESULTS All the approaches seem to have increased the number of adverse drug reaction reports. We noted the biggest increase with protocols (321 reports, costing 1.96 € each), followed by first educational approach (265 reports, 20.31 €/report) and by the hyperlink approach (136 reports, 15.59 €/report). Regarding the severity of adverse drug reactions, protocols were the most efficient approach, costing 2.29 €/report, followed by hyperlinks (30.28 €/report, having no running costs). Concerning unexpected adverse drug reactions, the best result was obtained with protocols (5.12 €/report), followed by first educational approach (38.79 €/report). CONCLUSIONS We recommend implementing protocols in other pharmacovigilance centers. They seem to be the most efficient intervention, allowing receiving adverse drug reactions reports at lower costs. The increase applied not only to the total number of reports, but also to the severity, unexpectedness and high degree of causality attributed to the adverse drug reactions. Still, hyperlinks have the advantage of not involving running costs, showing the second best performance in cost per adverse drug reactions report. PMID:27143614

  18. Promoting adverse drug reaction reporting: comparison of different approaches.

    PubMed

    Ribeiro-Vaz, Inês; Santos, Cristina Costa; Cruz-Correia, Ricardo

    2016-01-01

    To describe different approaches to promote adverse drug reaction reporting among health care professionals, determining their cost-effectiveness. We analyzed and compared several approaches taken by the Northern Pharmacovigilance Centre (Portugal) to promote adverse drug reaction reporting. Approaches were compared regarding the number and relevance of adverse drug reaction reports obtained and costs involved. Costs by report were estimated by adding the initial costs and the running costs of each intervention. These costs were divided by the number of reports obtained with each intervention, to assess its cost-effectiveness. All the approaches seem to have increased the number of adverse drug reaction reports. We noted the biggest increase with protocols (321 reports, costing 1.96 € each), followed by first educational approach (265 reports, 20.31 €/report) and by the hyperlink approach (136 reports, 15.59 €/report). Regarding the severity of adverse drug reactions, protocols were the most efficient approach, costing 2.29 €/report, followed by hyperlinks (30.28 €/report, having no running costs). Concerning unexpected adverse drug reactions, the best result was obtained with protocols (5.12 €/report), followed by first educational approach (38.79 €/report). We recommend implementing protocols in other pharmacovigilance centers. They seem to be the most efficient intervention, allowing receiving adverse drug reactions reports at lower costs. The increase applied not only to the total number of reports, but also to the severity, unexpectedness and high degree of causality attributed to the adverse drug reactions. Still, hyperlinks have the advantage of not involving running costs, showing the second best performance in cost per adverse drug reactions report.

  19. 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.

  20. 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.

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

    PubMed Central

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

    2001-01-01

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

  2. The impact of herbal drug use on adverse drug reaction profiles of patients on antiretroviral therapy in zimbabwe.

    PubMed

    Mudzviti, Tinashe; Maponga, Charles C; Khoza, Star; Ma, Qing; Morse, Gene D

    2012-01-01

    Background. The main objective was to determine the impact of herbal drug use on adverse drug reactions in patients on antiretroviral therapy (ART). Methodology. Patients receiving first-line ART from the national roll-out program participated in this cross-sectional study. Participants were interviewed and a data collection sheet was used to collect information from the corresponding medical record. Results. The majority (98.2%) of participants were using at least one herbal drug together with ART. The most common herbal remedies used were Allium Sativum (72.7%), Bidens pilosa (66.0%), Eucalyptus globulus (52.3%), Moringa oleifera (44.1%), Lippia javanica (36.3%), and Peltoforum africanum (34.3%). Two indigenous herbs, Musakavakadzi (OR = 0.25; 95% CI 0.076-0.828) and Peltoforum africanum (OR = 0.495; 95% CI 0.292-0.839) reduced the occurrence of adverse drug events. Conclusions. The use of herbal drugs is high in the HIV-infected population and there is need for pharmacovigilance programs to recognize the role they play in altering ADR profiles.

  3. The Impact of Herbal Drug Use on Adverse Drug Reaction Profiles of Patients on Antiretroviral Therapy in Zimbabwe

    PubMed Central

    Mudzviti, Tinashe; Maponga, Charles C.; Khoza, Star; Ma, Qing; Morse, Gene D.

    2012-01-01

    Background. The main objective was to determine the impact of herbal drug use on adverse drug reactions in patients on antiretroviral therapy (ART). Methodology. Patients receiving first-line ART from the national roll-out program participated in this cross-sectional study. Participants were interviewed and a data collection sheet was used to collect information from the corresponding medical record. Results. The majority (98.2%) of participants were using at least one herbal drug together with ART. The most common herbal remedies used were Allium Sativum (72.7%), Bidens pilosa (66.0%), Eucalyptus globulus (52.3%), Moringa oleifera (44.1%), Lippia javanica (36.3%), and Peltoforum africanum (34.3%). Two indigenous herbs, Musakavakadzi (OR = 0.25; 95% CI 0.076–0.828) and Peltoforum africanum (OR = 0.495; 95% CI 0.292–0.839) reduced the occurrence of adverse drug events. Conclusions. The use of herbal drugs is high in the HIV-infected population and there is need for pharmacovigilance programs to recognize the role they play in altering ADR profiles. PMID:22506106

  4. iADRs: towards online adverse drug reaction analysis.

    PubMed

    Lin, Wen-Yang; Li, He-Yi; Du, Jhih-Wei; Feng, Wen-Yu; Lo, Chiao-Feng; Soo, Von-Wun

    2012-12-01

    Adverse Drug Reaction (ADR) is one of the most important issues in the assessment of drug safety. In fact, many adverse drug reactions are not discovered during limited pre-marketing clinical trials; instead, they are only observed after long term post-marketing surveillance of drug usage. In light of this, the detection of adverse drug reactions, as early as possible, is an important topic of research for the pharmaceutical industry. Recently, large numbers of adverse events and the development of data mining technology have motivated the development of statistical and data mining methods for the detection of ADRs. These stand-alone methods, with no integration into knowledge discovery systems, are tedious and inconvenient for users and the processes for exploration are time-consuming. This paper proposes an interactive system platform for the detection of ADRs. By integrating an ADR data warehouse and innovative data mining techniques, the proposed system not only supports OLAP style multidimensional analysis of ADRs, but also allows the interactive discovery of associations between drugs and symptoms, called a drug-ADR association rule, which can be further developed using other factors of interest to the user, such as demographic information. The experiments indicate that interesting and valuable drug-ADR association rules can be efficiently mined.

  5. Data-driven prediction of adverse drug reactions induced by drug drug interactions

    DTIC Science & Technology

    2017-06-08

    currently on the market and for which drug-protein interaction information is available . These predictions are publicly accessible at http://avoid...associated with these ADRs via DDIs. We made the predictions publicly available via internet access. Keywords: Drug-drug interactions, Adverse drug reactions...ˆDeceased Department of Defense Biotechnology High Performance Computing Software Applications Institute, Telemedicine and Advanced Technology Research

  6. US Emergency Department Visits for Outpatient Adverse Drug Events, 2013-2014.

    PubMed

    Shehab, Nadine; Lovegrove, Maribeth C; Geller, Andrew I; Rose, Kathleen O; Weidle, Nina J; Budnitz, Daniel S

    2016-11-22

    The Patient Protection and Affordable Care Act of 2010 brought attention to adverse drug events in national patient safety efforts. Updated, detailed, nationally representative data describing adverse drug events can help focus these efforts. To describe the characteristics of emergency department (ED) visits for adverse drug events in the United States in 2013-2014 and describe changes in ED visits for adverse drug events since 2005-2006. Active, nationally representative, public health surveillance in 58 EDs located in the United States and participating in the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project. Drugs implicated in ED visits. National weighted estimates of ED visits and subsequent hospitalizations for adverse drug events. Based on data from 42 585 cases, an estimated 4.0 (95% CI, 3.1-5.0) ED visits for adverse drug events occurred per 1000 individuals annually in 2013 and 2014 and 27.3% (95% CI, 22.2%-32.4%) of ED visits for adverse drug events resulted in hospitalization. An estimated 34.5% (95% CI, 30.3%-38.8%) of ED visits for adverse drug events occurred among adults aged 65 years or older in 2013-2014 compared with an estimated 25.6% (95% CI, 21.1%-30.0%) in 2005-2006; older adults experienced the highest hospitalization rates (43.6%; 95% CI, 36.6%-50.5%). Anticoagulants, antibiotics, and diabetes agents were implicated in an estimated 46.9% (95% CI, 44.2%-49.7%) of ED visits for adverse drug events, which included clinically significant adverse events, such as hemorrhage (anticoagulants), moderate to severe allergic reactions (antibiotics), and hypoglycemia with moderate to severe neurological effects (diabetes agents). Since 2005-2006, the proportions of ED visits for adverse drug events from anticoagulants and diabetes agents have increased, whereas the proportion from antibiotics has decreased. Among children aged 5 years or younger, antibiotics were the most common drug class implicated

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

    PubMed Central

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

    2017-01-01

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

  8. An adverse drug event manager facilitates spontaneous reporting of adverse drug reactions.

    PubMed

    Vinther, Siri; Klarskov, Pia; Borgeskov, Hanne; Darsø, Perle; Christophersen, Anette Kvindebjerg; Borck, Bille; Christensen, Catrine; Hansen, Melissa Voigt; Halladin, Natalie Monica Løvland; Christensen, Mikkel Bring; Harboe, Kirstine Moll; Lund, Marie; Jimenez-Solem, Espen

    2017-01-01

    Spontaneous reporting of adverse drug reactions (ADRs) is used for continuous risk-benefit evaluation of marketed pharmaceutical products and for signal detection. The Adverse Drug Event Manager (ADEM) is a service offered to clinicians employed at hospitals in the Capital Region of Denmark. The ADEM assists healthcare professionals in reporting suspected ADRs to the Danish Health Authority. The aim of this retrospective observational study was to quantify and describe ADRs reported via the ADEM in 2014. All ADR reports handled by the ADEM in 2014 were recorded anonymously and analysed descriptively. A total of 484 ADRs were reported through the ADEM in 2014 (the median number of reports per month was 37; range: 17-78). The majority of the reports came from departments of internal medicine (61%), psychiatry (14%) and dermatology, ophthalmology or otorhinolaryngology (11%). The drugs most frequently reported were lisdexamphetamine (n = 40), rivaroxaban (n = 16) and warfarin (n = 15) (vaccines excluded). In 13 out of 484 reports, the ADR was associated with a fatal outcome. The findings of this study indicate that an ADEM promotes and facilitates spontaneous ADR reporting and helps raise awareness about ADRs, including how and why they should be reported. Hopefully, this will assist national and European spontaneous reporting systems in their work to increase patient safety nationally and abroad. none. not relevant. .

  9. Adverse Drug Reactions (ADR) and Emergencies.

    PubMed

    Schurig, A Marlen; Böhme, Miriam; Just, Katja S; Scholl, Catharina; Dormann, Harald; Plank-Kiegele, Bettina; Seufferlein, Thomas; Gräff, Ingo; Schwab, Matthias; Stingl, Julia C

    2018-04-13

    Adverse drug reactions (ADR) are a common reason for emergency room visits and for hospitalization. An ADR is said to have occurred when the patient's symptoms and signs are considered to be possibly, probably, or definitely related to the intake of a drug. In four large hospital emergency departments, one in each of four German cities ( Ulm, Fürth, Bonn, and Stuttgart), the percentage of suspected ADR cases among all patients presenting to the emergency room was determined during a 30-day period of observation. ADRs were ascertained by screening the digital records of all patients seen in the emergency room; causality was assessed as specified by the WHO-UMC (Uppsala Monitoring Center). ADR were sought in a total of 10 174 emergency department visits. 665 cases of suspected ADR were found, yielding a prevalence of 6.5%. The prevalence of ADR among patients with documented drug intake was 11.6%. Among the patients with documented suspected ADRs, 89% were hospitalized (in contrast to the 43.7% hospitalization rate in the entire group of 10 174 emergency department visits). A possible causal relationship between the patient's symptoms and signs and the intake of a drug was found in 74-84% of cases. Patients with ADR were found to be taking a median of 7 different drugs simultaneously. Adverse drug reactions are a relevant cause of emergency department visits, accounting for 6.5% of the total visits in this study, and often lead to hospital admission. The ADRED (Adverse Drug Reactions in Emergency Departments) study, which is now being conducted, is intended to shed further light on their causes, patient risk factors, and potential avoidability.

  10. Predictive modeling of structured electronic health records for adverse drug event detection

    PubMed Central

    2015-01-01

    Background The digitization of healthcare data, resulting from the increasingly widespread adoption of electronic health records, has greatly facilitated its analysis by computational methods and thereby enabled large-scale secondary use thereof. This can be exploited to support public health activities such as pharmacovigilance, wherein the safety of drugs is monitored to inform regulatory decisions about sustained use. To that end, electronic health records have emerged as a potentially valuable data source, providing access to longitudinal observations of patient treatment and drug use. A nascent line of research concerns predictive modeling of healthcare data for the automatic detection of adverse drug events, which presents its own set of challenges: it is not yet clear how to represent the heterogeneous data types in a manner conducive to learning high-performing machine learning models. Methods Datasets from an electronic health record database are used for learning predictive models with the purpose of detecting adverse drug events. The use and representation of two data types, as well as their combination, are studied: clinical codes, describing prescribed drugs and assigned diagnoses, and measurements. Feature selection is conducted on the various types of data to reduce dimensionality and sparsity, while allowing for an in-depth feature analysis of the usefulness of each data type and representation. Results Within each data type, combining multiple representations yields better predictive performance compared to using any single representation. The use of clinical codes for adverse drug event detection significantly outperforms the use of measurements; however, there is no significant difference over datasets between using only clinical codes and their combination with measurements. For certain adverse drug events, the combination does, however, outperform using only clinical codes. Feature selection leads to increased predictive performance for both

  11. Fatal adverse drug reactions of anticancer drugs detected by all-case post-marketing surveillance in Japan.

    PubMed

    Mori, Jinichi; Tanimoto, Tetsuya; Miura, Yuji; Kami, Masahiro

    2015-06-01

    All-case post-marketing surveillance of newly approved anticancer drugs is usually conducted on all patients in Japan. The present study investigates whether all-case post-marketing surveillance identifies fatal adverse drug reactions undetected before market entry. We examined fatal adverse drug reactions identified via all-case post-marketing surveillance by reviewing the disclosed post-marketing surveillance results, and determined the time points in which the fatal adverse drug reactions were initially reported by reviewing drug labels. We additionally scanned emergency alerts on the Japanese regulatory authority website to assess the relationship between all-case post-marketing surveillance and regulatory action. Twenty-five all-case post-marketing surveillances were performed between January 1999 and December 2009. Eight all-case post-marketing surveillances with final results included information on all fatal cases. Of these, the median number of patients was 1287 (range: 106-4998), the median number of fatal adverse drug reactions was 14.5 (range: 4-23). Of the 111 fatal adverse drug reactions detected in the eight post-marketing surveillances, only 28 (25.0%) and 22 (19.6%) were described on the initial global and the initial Japanese drug label, respectively, and 58 (52.3%) fatal adverse drug reactions were first described in the all-case post-marketing surveillance reports. Despite this, the regulatory authority issued only four warning letters, and two of these were prompted by case reports from the all-case post-marketing surveillance. All-case post-marketing surveillance of newly approved anticancer drugs in Japan was useful for the rigorous compilation of non-specific adverse drug reactions, but it rarely detected clinically significant fatal adverse drug reactions. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  12. Facilitating adverse drug event detection in pharmacovigilance databases using molecular structure similarity: application to rhabdomyolysis

    PubMed Central

    Vilar, Santiago; Harpaz, Rave; Chase, Herbert S; Costanzi, Stefano; Rabadan, Raul

    2011-01-01

    Background Adverse drug events (ADE) cause considerable harm to patients, and consequently their detection is critical for patient safety. The US Food and Drug Administration maintains an adverse event reporting system (AERS) to facilitate the detection of ADE in drugs. Various data mining approaches have been developed that use AERS to detect signals identifying associations between drugs and ADE. The signals must then be monitored further by domain experts, which is a time-consuming task. Objective To develop a new methodology that combines existing data mining algorithms with chemical information by analysis of molecular fingerprints to enhance initial ADE signals generated from AERS, and to provide a decision support mechanism to facilitate the identification of novel adverse events. Results The method achieved a significant improvement in precision in identifying known ADE, and a more than twofold signal enhancement when applied to the ADE rhabdomyolysis. The simplicity of the method assists in highlighting the etiology of the ADE by identifying structurally similar drugs. A set of drugs with strong evidence from both AERS and molecular fingerprint-based modeling is constructed for further analysis. Conclusion The results demonstrate that the proposed methodology could be used as a pharmacovigilance decision support tool to facilitate ADE detection. PMID:21946238

  13. ICD-10 codes used to identify adverse drug events in administrative data: a systematic review

    PubMed Central

    Hohl, Corinne M; Karpov, Andrei; Reddekopp, Lisa; Stausberg, Jürgen

    2014-01-01

    Background Adverse drug events, the unintended and harmful effects of medications, are important outcome measures in health services research. Yet no universally accepted set of International Classification of Diseases (ICD) revision 10 codes or coding algorithms exists to ensure their consistent identification in administrative data. Our objective was to synthesize a comprehensive set of ICD-10 codes used to identify adverse drug events. Methods We developed a systematic search strategy and applied it to five electronic reference databases. We searched relevant medical journals, conference proceedings, electronic grey literature and bibliographies of relevant studies, and contacted content experts for unpublished studies. One author reviewed the titles and abstracts for inclusion and exclusion criteria. Two authors reviewed eligible full-text articles and abstracted data in duplicate. Data were synthesized in a qualitative manner. Results Of 4241 titles identified, 41 were included. We found a total of 827 ICD-10 codes that have been used in the medical literature to identify adverse drug events. The median number of codes used to search for adverse drug events was 190 (IQR 156–289) with a large degree of variability between studies in the numbers and types of codes used. Authors commonly used external injury (Y40.0–59.9) and disease manifestation codes. Only two papers reported on the sensitivity of their code set. Conclusions Substantial variability exists in the methods used to identify adverse drug events in administrative data. Our work may serve as a point of reference for future research and consensus building in this area. PMID:24222671

  14. Enhancing Communication about Paediatric Medicines: Lessons from a Qualitative Study of Parents' Experiences of Their Child's Suspected Adverse Drug Reaction

    PubMed Central

    Arnott, Janine; Hesselgreaves, Hannah; Nunn, Anthony J.; Peak, Matthew; Pirmohamed, Munir; Smyth, Rosalind L.

    2012-01-01

    Background There is little research on parents' experiences of suspected adverse drug reactions in their children and hence little evidence to guide clinicians when communicating with families about problems associated with medicines. Objective To identify any unmet information and communication needs described by parents whose child had a suspected adverse drug reaction. Methods Semi-structured qualitative interviews with parents of 44 children who had a suspected adverse drug reaction identified on hospital admission, during in-patient treatment or reported by parents using the Yellow Card Scheme (the UK system for collecting spontaneous reports of adverse drug reactions). Interviews were conducted face-to-face or by telephone; most interviews were audiorecorded and transcribed. Analysis was informed by the principles of the constant comparative method. Results Many parents described being dissatisfied with how clinicians communicated about adverse drug reactions and unclear about the implications for their child's future use of medicines. A few parents felt that clinicians had abandoned their child and reported refusing the use of further medicines because they feared a repeated adverse drug reaction. The accounts of parents of children with cancer were different. They emphasised their confidence in clinicians' management of adverse drug reactions and described how clinicians prospectively explained the risks associated with medicines. Parents linked symptoms to medicines in ways that resembled the established reasoning that clinicians use to evaluate the possibility that a medicine has caused an adverse drug reaction. Conclusion Clinicians' communication about adverse drug reactions was poor from the perspective of parents, indicating that improvements are needed. The accounts of parents of children with cancer indicate that prospective explanation about adverse drug reactions at the time of prescription can be effective. Convergence between parents and

  15. Adverse reactions to antituberculosis drugs in Manguinhos, Rio de Janeiro, Brazil

    PubMed Central

    Damasceno, Glauciene Santana; Guaraldo, Lusiele; Engstrom, Elyne Montenegro; Filha, Mariza Miranda Theme; Santos, Reinaldo Souza-; Vasconcelos, Ana Gloria Godoi; Rozenfeld, Suely

    2013-01-01

    OBJECTIVES: This study aimed to characterize and estimate the frequency of adverse reactions to antituberculosis drugs in the population treated at the Centro de Saúde Escola Germano Sinval Faria, a primary health care clinic in Manguinhos, Rio de Janeiro City, and to explore the relationship between adverse drug reactions and some of the patients' demographic and health characteristics. METHODS: This descriptive study was conducted via patient record review of incident cases between 2004 and 2008. RESULTS: Of the 176 patients studied, 41.5% developed one or more adverse reactions to antituberculosis drugs, totaling 126 occurrences. The rate of adverse reactions to antituberculosis drugs was higher among women, patients aged 50 years or older, those with four or more comorbidities, and those who used five or more drugs. Of the total reactions, 71.4% were mild. The organ systems most affected were as follows: the gastrointestinal tract (29.4%), the skin and appendages (21.4%), and the central and peripheral nervous systems (14.3%). Of the patients who experienced adverse reactions to antituberculosis drugs, 65.8% received no drug treatment for their adverse reactions, and 4.1% had one of the antituberculosis drugs suspended because of adverse reactions. “Probable reactions” (75%) predominated over “possible reactions” (24%). In the study sample, 64.3% of the reactions occurred during the first two months of treatment, and most (92.6%) of the reactions were ascribed to the combination of rifampicin + isoniazid + pyrazinamide (Regimen I). A high dropout rate from tuberculosis treatment (24.4%) was also observed. CONCLUSION: This study suggests a high rate of adverse reactions to antituberculosis drugs. PMID:23644852

  16. Why Clinicians Don't Report Adverse Drug Events: Qualitative Study.

    PubMed

    Hohl, Corinne M; Small, Serena S; Peddie, David; Badke, Katherin; Bailey, Chantelle; Balka, Ellen

    2018-02-27

    Adverse drug events are unintended and harmful events related to medications. Adverse drug events are important for patient care, quality improvement, drug safety research, and postmarketing surveillance, but they are vastly underreported. Our objectives were to identify barriers to adverse drug event documentation and factors contributing to underreporting. This qualitative study was conducted in 1 ambulatory center, and the emergency departments and inpatient wards of 3 acute care hospitals in British Columbia between March 2014 and December 2016. We completed workplace observations and focus groups with general practitioners, hospitalists, emergency physicians, and hospital and community pharmacists. We analyzed field notes by coding and iteratively analyzing our data to identify emerging concepts, generate thematic and event summaries, and create workflow diagrams. Clinicians validated emerging concepts by applying them to cases from their clinical practice. We completed 238 hours of observations during which clinicians investigated 65 suspect adverse drug events. The observed events were often complex and diagnosed over time, requiring the input of multiple providers. Providers documented adverse drug events in charts to support continuity of care but never reported them to external agencies. Providers faced time constraints, and reporting would have required duplication of documentation. Existing reporting systems are not suited to capture the complex nature of adverse drug events or adapted to workflow and are simply not used by frontline clinicians. Systems that are integrated into electronic medical records, make use of existing data to avoid duplication of documentation, and generate alerts to improve safety may address the shortcomings of existing systems and generate robust adverse drug event data as a by-product of safer care. ©Corinne M Hohl, Serena S Small, David Peddie, Katherin Badke, Chantelle Bailey, Ellen Balka. Originally published in JMIR

  17. The pharmacist and adverse drug reaction reporting.

    PubMed

    Pearson, K

    1982-08-01

    During premarketing trials, the number of patients exposed to a drug and the length of exposure to a drug are both limited. After marketing, many thousands, frequently millions, of patients are exposed to the drug over considerably longer periods of time, and adverse drug reactions not previously recognized appear. Because of these factors, postmarketing surveillance is extremely important. Pharmacists can contribute to drug safety and improved patient care by understanding and actively participating in the Food and Drug Administration's Spontaneous Reporting Program.

  18. VNIR hyperspectral background characterization methods in adverse weather conditions

    NASA Astrophysics Data System (ADS)

    Romano, João M.; Rosario, Dalton; Roth, Luz

    2009-05-01

    Hyperspectral technology is currently being used by the military to detect regions of interest where potential targets may be located. Weather variability, however, may affect the ability for an algorithm to discriminate possible targets from background clutter. Nonetheless, different background characterization approaches may facilitate the ability for an algorithm to discriminate potential targets over a variety of weather conditions. In a previous paper, we introduced a new autonomous target size invariant background characterization process, the Autonomous Background Characterization (ABC) or also known as the Parallel Random Sampling (PRS) method, features a random sampling stage, a parallel process to mitigate the inclusion by chance of target samples into clutter background classes during random sampling; and a fusion of results at the end. In this paper, we will demonstrate how different background characterization approaches are able to improve performance of algorithms over a variety of challenging weather conditions. By using the Mahalanobis distance as the standard algorithm for this study, we compare the performance of different characterization methods such as: the global information, 2 stage global information, and our proposed method, ABC, using data that was collected under a variety of adverse weather conditions. For this study, we used ARDEC's Hyperspectral VNIR Adverse Weather data collection comprised of heavy, light, and transitional fog, light and heavy rain, and low light conditions.

  19. Adverse drug reactions and outcome of short course anti-tuberculosis drugs between single daily dose and split drug dose (BID) in pulmonary tuberculosis.

    PubMed

    Chuchottaworn, Charoen; Saipan, Benjawan; Kittisup, Chomnapa; Cheewakul, Krisana

    2012-08-01

    Standard six months short course regimen for treatment of pulmonary tuberculosis is very effective and is recommended as standard treatment. But this regimen composes of many drugs and causes high adverse drug reactions especially gastrointestinal irritation. Spitted administration of drugs to two times a day may reduce adverse drug reactions. To study adverse drug reactions and outcome of single daily versus split drug (two times a day) administration of standard six month short course regimen in newly diagnosed pulmonary tuberculosis. Newly diagnosed pulmonary tuberculosis patients of the Central Chest Institute of Thailand were randomized to receive standard six months regimen once daily or two times a day (split drug). Patients were followed-up every two weeks and a questionnaire was used to detect adverse drug reactions. Outcome of treatment was evaluated according to national tuberculosis treatment guideline. 122 pulmonary tuberculosis were eligible for the present study and 61 patients were enrolled to each group of once daily or split drug regimen. Pulmonary tuberculosis patients who received split drug regimen had a higher cure rate but not statistical significance because of lower transfer out rate. Adverse drug reactions were similar in both groups of patients who received once daily and split drug regimen. Although split drug group had lower gastrointestinal adverse drug reactions. Split drug regimen has the same cure rate of treatment as single daily regimen and same adverse drug reactions.

  20. Unusual and Interesting Adverse Cutaneous Drug Reactions.

    PubMed

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

    2018-01-01

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

  1. Unusual and Interesting Adverse Cutaneous Drug Reactions

    PubMed Central

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

    2018-01-01

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

  2. Adverse drug events in hospital: pilot study with trigger tool

    PubMed Central

    Rozenfeld, Suely; Giordani, Fabiola; Coelho, Sonia

    2013-01-01

    OBJECTIVE To estimate the frequency of and to characterize the adverse drug events at a terciary care hospital. METHODS A retrospective review was carried out of 128 medical records from a hospital in Rio de Janeiro in 2007, representing 2,092 patients. The instrument used was a list of triggers, such as antidotes, abnormal laboratory analysis results and sudden suspension of treatment, among others. A simple random sample of patients aged 15 and over was extracted. Oncologic and obstetric patients were excluded as were those hospitalized for less than 48 hours or in the emergency room. Social and demographic characteristics and those of the disease of patients who underwent adverse events were compared with those of patients who did not in order to test for differences between the groups. RESULTS Around 70.0% of the medical records assessed showed at least one trigger. Adverse drug events triggers had an overall positive predictive value of 14.4%. The incidence of adverse drug events was 26.6 per 100 patients and 15.6% patients suffered one or more event. The median length of stay for patients suffering an adverse drug event was 35.2 days as against 10.7 days for those who did not (p < 0.01). The pharmacological classes most commonly associated with an adverse drug event were related to the cardiovascular system, nervous system and alimentary tract and metabolism. The most common active substances associated with an adverse drug event were tramadol, dypirone, glibenclamide and furosemide. Over 80.0% of events provoked or contributed to temporary harm to the patient and required intervention and 6.0% may have contributed to the death of the patient. It was estimated that in the hospital, 131 events involving drowsiness or fainting 33 involving falls, and 33 episodes of hemorrhage related to adverse drug effects occur annually. CONCLUSIONS Almost one-sixth of in-patients (16,0%) suffered an adverse drug event. The instrument used may prove useful as a technique for

  3. Adverse drug reactions induced by cardiovascular drugs in outpatients.

    PubMed

    Gholami, Kheirollah; Ziaie, Shadi; Shalviri, Gloria

    2008-01-01

    Considering increased use of cardiovascular drugs and limitations in pre-marketing trials for drug safety evaluation, post marketing evaluation of adverse drug reactions (ADRs) induced by this class of medicinal products seems necessary. To determine the rate and seriousness of adverse reactions induced by cardiovascular drugs in outpatients. To compare sex and different age groups in developing ADRs with cardiovascular agents. To assess the relationship between frequencies of ADRs and the number of drugs used. This cross-sectional study was done in cardiovascular clinic at a teaching hospital. All patients during an eight months period were evaluated for cardiovascular drugs induced ADRs. Patient and reaction factors were analyzed in detected ADRs. Patients with or without ADRs were compared in sex and age by using chi-square test. Assessing the relationship between frequencies of ADRs and the number of drugs used was done by using Pearson analysis. The total number of 518 patients was visited at the clinic. ADRs were detected in 105 (20.3%) patients. The most frequent ADRs were occurred in the age group of 51-60. The highest rate of ADRs was recorded to be induced by Diltiazem (23.5%) and the lowest rate with Atenolol (3%). Headache was the most frequent detected ADR (23%). Assessing the severity and preventability of ADRs revealed that 1.1% of ADRs were detected as severe and 1.9% as preventable reactions. Women significantly developed more ADRs in this study (chi square = 3.978, P<0.05). ADRs more frequently occurred with increasing age in this study (chi square = 15.871, P<0.05). With increasing the number of drugs used, the frequency of ADRs increased (Pearson=0.259, P<0.05). Monitoring ADRs in patients using cardiovascular drugs is a matter of importance since this class of medicines is usually used by elderly patients with critical conditions and underlying diseases.

  4. 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.

  5. Study of Natural Health Product Adverse Reactions (SONAR): Active Surveillance of Adverse Events Following Concurrent Natural Health Product and Prescription Drug Use in Community Pharmacies

    PubMed Central

    Vohra, Sunita; Cvijovic, Kosta; Boon, Heather; Foster, Brian C.; Jaeger, Walter; LeGatt, Don; Cembrowski, George; Murty, Mano; Tsuyuki, Ross T.; Barnes, Joanne; Charrois, Theresa L.; Arnason, John T.; Necyk, Candace; Ware, Mark; Rosychuk, Rhonda J.

    2012-01-01

    Background Many consumers use natural health products (NHPs) concurrently with prescription medications. As NHP-related harms are under-reported through passive surveillance, the safety of concurrent NHP-drug use remains unknown. To conduct active surveillance in participating community pharmacies to identify adverse events related to concurrent NHP-prescription drug use. Methodology/Principal Findings Participating pharmacists asked individuals collecting prescription medications about (i) concurrent NHP/drug use in the previous three months and (ii) experiences of adverse events. If an adverse event was identified and if the patient provided written consent, a research pharmacist conducted a guided telephone interview to gather additional information after obtaining additional verbal consent and documenting so within the interview form. Over a total of 112 pharmacy weeks, 2615 patients were screened, of which 1037 (39.7%; 95% CI: 37.8% to 41.5%) reported concurrent NHP and prescription medication use. A total of 77 patients reported a possible AE (2.94%; 95% CI: 2.4% to 3.7%), which represents 7.4% of those using NHPs and prescription medications concurrently (95%CI: 6.0% to 9.2%). Of 15 patients available for an interview, 4 (26.7%: 95% CI: 4.3% to 49.0%) reported an AE that was determined to be “probably” due to NHP use. Conclusions/Significance Active surveillance markedly improves identification and reporting of adverse events associated with concurrent NHP-drug use. Although not without challenges, active surveillance is feasible and can generate adverse event data of sufficient quality to allow for meaningful adjudication to assess potential harms. PMID:23028841

  6. HLA Association with Drug-Induced Adverse Reactions

    PubMed Central

    Fan, Wen-Lang; Shiao, Meng-Shin; Hui, Rosaline Chung-Yee; Wang, Chuang-Wei; Chang, Ya-Ching

    2017-01-01

    Adverse drug reactions (ADRs) remain a common and major problem in healthcare. Severe cutaneous adverse drug reactions (SCARs), such as Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) with mortality rate ranges from 10% to more than 30%, can be life threatening. A number of recent studies demonstrated that ADRs possess strong genetic predisposition. ADRs induced by several drugs have been shown to have significant associations with specific alleles of human leukocyte antigen (HLA) genes. For example, hypersensitivity to abacavir, a drug used for treating of human immunodeficiency virus (HIV) infection, has been proposed to be associated with allele 57:01 of HLA-B gene (terms HLA-B∗57:01). The incidences of abacavir hypersensitivity are much higher in Caucasians compared to other populations due to various allele frequencies in different ethnic populations. The antithyroid drug- (ATDs- ) induced agranulocytosis are strongly associated with two alleles: HLA-B∗38:02 and HLA-DRB1∗08:03. In addition, HLA-B∗15:02 allele was reported to be related to carbamazepine-induced SJS/TEN, and HLA-B∗57:01 in abacavir hypersensitivity and flucloxacillin induced drug-induced liver injury (DILI). In this review, we summarized the alleles of HLA genes which have been proposed to have association with ADRs caused by different drugs. PMID:29333460

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

    PubMed

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

    2014-10-23

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

  8. [Cutaneous adverse drug reaction: prospective study of 118 cases].

    PubMed

    Chaabane, Hend; Masmoudi, Abderrahmen; Amouri, Meriem; Ghorbel, Sonda; Boudaya, Sonia; Hammami, Serriya; Zghal, Khaled; Turki, Hamida

    2013-01-01

    Few prospective studies are available on the incidence and analysis of the characteristics of adverse cutaneous drug reactions. To describe the adverse cutaneous reactions, their epidemiologic characteristics as well as the different causative drugs through a prospective hospital study. A 12-month prospective study was managed in our department of dermatology of the teaching hospital Hedi Chaker of Sfax. Requested information included patient characteristics (associated disorders), drug intake (list and chronology of the drug intake during the 3 weeks preceding the adverse reaction) and characteristics of the skin reaction (type, course). The diagnosis was based on a beam of clinical and anamnestic arguments. The drug imputability was evaluated according to the Begaud's French method. One hundred eighteen cases were collected. A prevalence of 1.08/100 among patients consulting in dermatology department was estimated. The macular and papular exanthema represented the most frequent clinical aspects (42 cases) followed by acute urticaria (23 cases), photosensitivity (19 cases) and fixed drug eruption (15 cases). Principal imputable drugs were antibiotics, mainly penicillins followed by analgesics and non-steroidal anti-inflammatory. Although it was monocentric, this study revealed a high frequency of drug-induced dermatitis with different clinical presentation. The high incidence of drug-induced dermatitis induced by antibiotics, analgesics and anti-inflammatory is due to their widespread use, often in self-medication.

  9. Adverse Drug Events caused by Serious Medication Administration Errors

    PubMed Central

    Sawarkar, Abhivyakti; Keohane, Carol A.; Maviglia, Saverio; Gandhi, Tejal K; Poon, Eric G

    2013-01-01

    OBJECTIVE To determine how often serious or life-threatening medication administration errors with the potential to cause patient harm (or potential adverse drug events) result in actual patient harm (or adverse drug events (ADEs)) in the hospital setting. DESIGN Retrospective chart review of clinical events that transpired following observed medication administration errors. BACKGROUND Medication errors are common at the medication administration stage for hospitalized patients. While many of these errors are considered capable of causing patient harm, it is not clear how often patients are actually harmed by these errors. METHODS In a previous study where 14,041 medication administrations in an acute-care hospital were directly observed, investigators discovered 1271 medication administration errors, of which 133 had the potential to cause serious or life-threatening harm to patients and were considered serious or life-threatening potential ADEs. In the current study, clinical reviewers conducted detailed chart reviews of cases where a serious or life-threatening potential ADE occurred to determine if an actual ADE developed following the potential ADE. Reviewers further assessed the severity of the ADE and attribution to the administration error. RESULTS Ten (7.5% [95% C.I. 6.98, 8.01]) actual adverse drug events or ADEs resulted from the 133 serious and life-threatening potential ADEs, of which 6 resulted in significant, three in serious, and one life threatening injury. Therefore 4 (3% [95% C.I. 2.12, 3.6]) serious and life threatening potential ADEs led to serious or life threatening ADEs. Half of the ten actual ADEs were caused by dosage or monitoring errors for anti-hypertensives. The life threatening ADE was caused by an error that was both a transcription and a timing error. CONCLUSION Potential ADEs at the medication administration stage can cause serious patient harm. Given previous estimates of serious or life-threatening potential ADE of 1.33 per 100

  10. [Application analysis of adverse drug reaction terminology WHOART and MedDRA].

    PubMed

    Liu, Jing; Xie, Yan-ming; Gai, Guo-zhong; Liao, Xing

    2015-12-01

    Drug safety has always been a global focus. Discovery and accurate information acquisition of adverse drug reaction have been the most crucial concern. Terminology of adverse drug reaction makes adverse reaction medical report meaningful, standardized and accurate. This paper discussed the domestic use of the terminology WHOART and MedDRA in terms of content, structure, and application situation. It also analysed the differences between the two terminologies and discusses the future trend of application in our country

  11. Adverse drug events and the Freedom of Information Act: an apple in Eden.

    PubMed

    Stang, P E; Fox, J L

    1992-02-01

    To review some of the abuses and proper uses of the Food and Drug Administration's (FDA's) spontaneous adverse-reaction reporting system, as a way of educating the reader to its strengths and limitations. Published literature and reports based on information obtained from the FDA's database of spontaneous adverse drug-event reports. The Freedom of Information Act has increased public access to the FDA's database of spontaneous adverse drug reaction reports. As these reports are voluntarily received and reported to the FDA, their use for comparisons of drug safety is severely limited. Despite these limitations and the FDA's caveats for use of these data, consumer advocacy groups, researchers, and various pharmaceutical marketing groups have used this source to project the incidence of adverse drug reactions. The FDA's spontaneous adverse-event reporting system is designed to generate signals of unexpected adverse drug events. Use of the data gathered by this system to make drug safety comparisons is beyond their credible scope because many factors influence the reporting of adverse events. Researchers and peer reviewers should place these data in the proper perspective and support sound research into questions of drug safety.

  12. A Pharmacovigilance Approach for Post-Marketing in Japan Using the Japanese Adverse Drug Event Report (JADER) Database and Association Analysis

    PubMed Central

    Fujiwara, Masakazu; Kawasaki, Yohei; Yamada, Hiroshi

    2016-01-01

    Background Rapid dissemination of information regarding adverse drug reactions is a key aspect for improving pharmacovigilance. There is a possibility that unknown adverse drug reactions will become apparent through post-marketing administration. Currently, although there have been studies evaluating the relationships between a drug and adverse drug reactions using the JADER database which collects reported spontaneous adverse drug reactions, an efficient approach to assess the association between adverse drug reactions of drugs with the same indications as well as the influence of demographics (e.g. gender) has not been proposed. Methods and Findings We utilized the REAC and DEMO tables from the May 2015 version of JADER for patients taking antidepressant drugs (SSRI, SNRI, and NaSSA). We evaluated the associations using association analyses with an apriori algorithm. Support, confidence, lift, and conviction were used as indicators for associations. The highest score in adverse drug reactions for SSRI was obtained for "aspartate aminotransferase increased", "alanine aminotransferase increased", with values of 0.0059, 0.93, 135.5, and 13.9 for support, confidence, lift and conviction, respectively. For SNRI, "international normalized ratio increased", "drug interaction" were observed with 0.0064, 1.00, 71.9, and NA. For NaSSA, "anxiety", "irritability" were observed with 0.0058, 0.80, 49.9, and 4.9. For female taking SSRI, the highest support scores were observed in "twenties", "suicide attempt", whereas "thirties", "neuroleptic malignant syndrome" were observed for male. Second, for SNRI, "eighties", "inappropriate antidiuretic hormone secretion" were observed for female, whereas "interstitial lung disease" and "hepatitis fulminant" were for male. Finally, for NaSSA, "suicidal ideation" was for female, and "rhabdomyolysis" was for male. Conclusions Different combinations of adverse drug reactions were noted between the antidepressants. In addition, the reported

  13. Adverse Drug Events and Medication Errors in African Hospitals: A Systematic Review.

    PubMed

    Mekonnen, Alemayehu B; Alhawassi, Tariq M; McLachlan, Andrew J; Brien, Jo-Anne E

    2018-03-01

    Medication errors and adverse drug events are universal problems contributing to patient harm but the magnitude of these problems in Africa remains unclear. The objective of this study was to systematically investigate the literature on the extent of medication errors and adverse drug events, and the factors contributing to medication errors in African hospitals. We searched PubMed, MEDLINE, EMBASE, Web of Science and Global Health databases from inception to 31 August, 2017 and hand searched the reference lists of included studies. Original research studies of any design published in English that investigated adverse drug events and/or medication errors in any patient population in the hospital setting in Africa were included. Descriptive statistics including median and interquartile range were presented. Fifty-one studies were included; of these, 33 focused on medication errors, 15 on adverse drug events, and three studies focused on medication errors and adverse drug events. These studies were conducted in nine (of the 54) African countries. In any patient population, the median (interquartile range) percentage of patients reported to have experienced any suspected adverse drug event at hospital admission was 8.4% (4.5-20.1%), while adverse drug events causing admission were reported in 2.8% (0.7-6.4%) of patients but it was reported that a median of 43.5% (20.0-47.0%) of the adverse drug events were deemed preventable. Similarly, the median mortality rate attributed to adverse drug events was reported to be 0.1% (interquartile range 0.0-0.3%). The most commonly reported types of medication errors were prescribing errors, occurring in a median of 57.4% (interquartile range 22.8-72.8%) of all prescriptions and a median of 15.5% (interquartile range 7.5-50.6%) of the prescriptions evaluated had dosing problems. Major contributing factors for medication errors reported in these studies were individual practitioner factors (e.g. fatigue and inadequate knowledge

  14. National differences in publishing papers on adverse drug reactions

    PubMed Central

    Ferner, R E; Aronson, J K

    2005-01-01

    Aims To examine how countries differ in attitudes to adverse drug reactions by examining published scientific papers. Methods We searched Ovid EMBASE for publications indexed by the category ′therapeutic agents′, and the subcategory ′adverse effects′, by country for 43 countries. Results We counted 1 810 202 papers world-wide regarding therapeutic agents during 14 years, of which 195 154 (10.8%) were included in the adverse effects subcategory. There were substantial differences between countries, not explained by population, economic variation, overall publication rate on therapeutic agents, or the presence of large indigenous pharmaceutical companies. Conclusions Many local cultural factors influence the ratio of papers on adverse reactions to all drug effects, so it may be difficult to improve their recognition and reporting by international efforts. PMID:15606448

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

    PubMed

    Vilar, Santiago; Hripcsak, George

    2016-01-01

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

  16. The role of drug profiles as similarity metrics: applications to repurposing, adverse effects detection and drug-drug interactions.

    PubMed

    Vilar, Santiago; Hripcsak, George

    2017-07-01

    Explosion of the availability of big data sources along with the development in computational methods provides a useful framework to study drugs' actions, such as interactions with pharmacological targets and off-targets. Databases related to protein interactions, adverse effects and genomic profiles are available to be used for the construction of computational models. In this article, we focus on the description of biological profiles for drugs that can be used as a system to compare similarity and create methods to predict and analyze drugs' actions. We highlight profiles constructed with different biological data, such as target-protein interactions, gene expression measurements, adverse effects and disease profiles. We focus on the discovery of new targets or pathways for drugs already in the pharmaceutical market, also called drug repurposing, in the interaction with off-targets responsible for adverse reactions and in drug-drug interaction analysis. The current and future applications, strengths and challenges facing all these methods are also discussed. Biological profiles or signatures are an important source of data generation to deeply analyze biological actions with important implications in drug-related studies. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Testing an explanatory model of nurses' intention to report adverse drug reactions in hospital settings.

    PubMed

    Angelis, Alessia De; Pancani, Luca; Steca, Patrizia; Colaceci, Sofia; Giusti, Angela; Tibaldi, Laura; Alvaro, Rosaria; Ausili, Davide; Vellone, Ercole

    2017-05-01

    To test an explanatory model of nurses' intention to report adverse drug reactions in hospital settings, based on the theory of planned behaviour. Under-reporting of adverse drug reactions is an important problem among nurses. A cross-sectional design was used. Data were collected with the adverse drug reporting nurses' questionnaire. Confirmatory factor analysis was performed to test the factor validity of the adverse drug reporting nurses' questionnaire, and structural equation modelling was used to test the explanatory model. The convenience sample comprised 500 Italian hospital nurses (mean age = 43.52). Confirmatory factor analysis supported the factor validity of the adverse drug reporting nurses' questionnaire. The structural equation modelling showed a good fit with the data. Nurses' intention to report adverse drug reactions was significantly predicted by attitudes, subjective norms and perceived behavioural control (R² = 0.16). The theory of planned behaviour effectively explained the mechanisms behind nurses' intention to report adverse drug reactions, showing how several factors come into play. In a scenario of organisational empowerment towards adverse drug reaction reporting, the major predictors of the intention to report are support for the decision to report adverse drug reactions from other health care practitioners, perceptions about the value of adverse drug reaction reporting and nurses' favourable self-assessment of their adverse drug reaction reporting skills. © 2017 John Wiley & Sons Ltd.

  18. Prediction of adverse drug reactions using decision tree modeling.

    PubMed

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

    2010-07-01

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

  19. 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.

  20. Epidemiology of adverse drug reactions to phenformin and metformin.

    PubMed Central

    Bergman, U; Boman, G; Wiholm, B E

    1978-01-01

    Adverse drug reactions (ADRs) to phenformin and metformin reported to the Swedish Adverse Drug Reaction Committee during 1965--77 were analysed in relation to sales and prescription data. The biguanides accounted for 0.6% of all reported adverse drug reactions but for 6% of the fatal cases (all phenformin). Sixty-four ADRs to phenformin and eight to metformin were classified as causal relation "probable" or "not excluded." Fifty-one of these reactions (71%) were lactic acidosis, all but one being reactions to phenformin. After 1973 phenformin was prescribed less in Sweden and metformin became predominant. A nationwide prescription survey during 1975--6 disclosed no differences in age and sex between patients receiving phenformin and metformin. The mean daily doses prescribed in 1976 were 74 mg of phenformin and 1.5 g of metformin. The numbers of ADRs to the two drugs reported during 1975--7 were related to use. The relative incidences of ADRs reported for phenformin and metformin did not differ. Significantly more cases of lactic acidosis and deaths were reported for phenformin. PMID:678924

  1. Ophthalmic adverse drug reactions to systemic drugs: a systematic review.

    PubMed

    Miguel, Ana; Henriques, Filipe; Azevedo, Luís Filipe; Pereira, Altamiro Costa

    2014-03-01

    To perform a comprehensive and systematic review regarding ophthalmic adverse drug reactions (ADRs) to systemic drugs to: (i) systematically summarize existing evidence, (ii) identify areas, ophthalmic ADRs or drugs that lacked systematization or assessment (namely drugs with original studies characterizing specific ophthalmic ADRs but without causality assessment nor without meta-analysis). Systematic review of several electronic databases (last search 1/7/2012): Medline, SCOPUS, ISI web of knowledge, ISI Conference Proceedings, International Pharmaceutical Abstracts and Google scholar. Search query included: eye, ocular, ophthalmic, ophthalmology, adverse and reaction. Inclusion criteria were: (i) Primary purpose was to assess an ophthalmic ADR to a systemic medication; (ii) Patient evaluation performed by an ophthalmologist; (iii) Studies that specified diagnostic criteria for an ocular ADR. Different types of studies were included and analyzed separately. Two independent reviewers assessed eligibility criteria, extracted data and evaluated risk of bias. From 562 studies found, 32 were included (1 systematic review to sildenafil, 11 narrative reviews, 1 trial, 1 prospective study, 6 transversal studies, 6 spontaneous reports and 6 case series). Drugs frequently involved included amiodarone, sildenafil, hydroxychloroquine and biphosphonates. Frequent ophthalmic ADRs included: keratopathy, dry eye and retinopathy. To increase evidence about ophthalmic ADRs, there is a need for performing specific systematic reviews, applying strictly the World Health Organization's (WHO) definition of ADR and WHO causality assessment of ADRs. Some ophthalmic ADRs may be frequent, but require ophthalmological examination; therefore, ophthalmologists' education and protocols of collaboration between other specialties whenever they prescribe high-risk drugs are suggestions for the future. Copyright © 2014 John Wiley & Sons, Ltd.

  2. Evaluation of adverse drug event information in US manufacturer labels.

    PubMed

    Harrington, Catherine A; Garcia, Angela S; Sircar-Ramsewak, Feroza

    2011-02-01

    Pharmaceutical manufacturer labels are an important source of adverse drug event (ADE) information. The study objective was to determine the sufficiency of ADE reporting in US drug labels. A sample of 50 labels was evaluated from the top 200 drugs dispensed in the US. Electronic copies of labels were obtained and reviewed by 2 pharmacists for ADE incidence and discontinuation data. ADE incidence data were provided in 86% of labels. However, discontinuation rates due to ADEs and ADE incidence by dose were only reported in 60%. ADE incidence reporting by age (46%) or gender (18%) was also low. ADEs that occurred in less than 2% of the population were rarely reported. Incidence rates were based on small populations (median of 794) and short term studies (median of 84 days for chronic conditions). Labels for 19 drugs used chronically had no long term study data. Methods for collecting ADE data were stated in only 12% of labels. Adverse drug event and drug discontinuation data is under-reported in US labels. More information on adverse events causing discontinuation (especially serious events) and those related to dose, age, and gender is needed in labels to ensure safe prescribing and dispensing of drugs.

  3. 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.

  4. Pharmacovigilance and drug safety 2011 in Calabria (Italy): Adverse events analysis

    PubMed Central

    Scicchitano, Francesca; Giofrè, Chiara; Palleria, Caterina; Mazzitello, Carmela; Ciriaco, Miriam; Gallelli, Luca; Paletta, Laura; Marrazzo, Giuseppina; De Fazio, Salvatore; Menniti, Michele; Curia, Rubens; Arena, Concetta; Chimirri, Serafina; Patanè, Marinella; Esposito, Stefania; Cilurzo, Felisa; Staltari, Orietta; Russo, Emilio; De Sarro, Giovambattista

    2012-01-01

    Background: Pharmacovigilance assesses the safety profile of drugs. Its main aim is the increase of spontaneous reporting of adverse drug reactions (ADRs). The Italian Drug Agency (AIFA; Agenzia Italiana del Farmaco) is financing several projects to the aim of increasing reporting, and in Calabria a Pharmacovigilance Information Centre has been created. Materials and Methods: We analyzed the AIFA database relatively to Calabria in the year 2011 and we have analyzed ADRs using descriptive statistics. We have also collected a questionnaire-based interview in order to describe the background knowledge in the field. Results: Regarding the number of AIFA reported ADRs from Calabria, a 38% increase (138 vs. 100) in comparison to 2010 was evidenced. Hospital Doctors represent the main source of signaling (71.7 %). Ketoprofene and the combination amoxicillin/clavulanic acid represent the most frequently reported drugs causing ADRs. Our questionnaires indicated that despite the health professionals have met at least once an ADR only a small percentage of them was reported to the authorities (37%). There is a very good knowledge of the ADR concept and reporting system (90% of interviewed distinguish an ADR and knows how to report it), and there is a strong interest in participating to training courses in the field (95% are interested). Conclusions: Despite Calabria has had a positive increase in the number of reported ADRs, the total number is very low and the pharmacovigilance culture is far from being achieved in this region. PMID:23826016

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

    PubMed

    Bjånes, Tormod Karlsen

    2011-03-04

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

  6. Identifying genomic and developmental causes of adverse drug reactions in children

    PubMed Central

    Becker, Mara L; Leeder, J Steven

    2011-01-01

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

  7. 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.

  8. 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

  9. Knowledge discovery of drug data on the example of adverse reaction prediction

    PubMed Central

    2014-01-01

    Background Antibiotics are the widely prescribed drugs for children and most likely to be related with adverse reactions. Record on adverse reactions and allergies from antibiotics considerably affect the prescription choices. We consider this a biomedical decision-making problem and explore hidden knowledge in survey results on data extracted from a big data pool of health records of children, from the Health Center of Osijek, Eastern Croatia. Results We applied and evaluated a k-means algorithm to the dataset to generate some clusters which have similar features. Our results highlight that some type of antibiotics form different clusters, which insight is most helpful for the clinician to support better decision-making. Conclusions Medical professionals can investigate the clusters which our study revealed, thus gaining useful knowledge and insight into this data for their clinical studies. PMID:25079450

  10. [Pharmacotherapy of hyperthyreosis--adverse drug reactions].

    PubMed

    Perger, Ludwig; Bürgi, Ulrich; Fattinger, Karin

    2011-06-01

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

  11. OpenVigil FDA - Inspection of U.S. American Adverse Drug Events Pharmacovigilance Data and Novel Clinical Applications.

    PubMed

    Böhm, Ruwen; von Hehn, Leocadie; Herdegen, Thomas; Klein, Hans-Joachim; Bruhn, Oliver; Petri, Holger; Höcker, Jan

    2016-01-01

    Pharmacovigilance contributes to health care. However, direct access to the underlying data for academic institutions and individual physicians or pharmacists is intricate, and easily employable analysis modes for everyday clinical situations are missing. This underlines the need for a tool to bring pharmacovigilance to the clinics. To address these issues, we have developed OpenVigil FDA, a novel web-based pharmacovigilance analysis tool which uses the openFDA online interface of the Food and Drug Administration (FDA) to access U.S. American and international pharmacovigilance data from the Adverse Event Reporting System (AERS). OpenVigil FDA provides disproportionality analyses to (i) identify the drug most likely evoking a new adverse event, (ii) compare two drugs concerning their safety profile, (iii) check arbitrary combinations of two drugs for unknown drug-drug interactions and (iv) enhance the relevance of results by identifying confounding factors and eliminating them using background correction. We present examples for these applications and discuss the promises and limits of pharmacovigilance, openFDA and OpenVigil FDA. OpenVigil FDA is the first public available tool to apply pharmacovigilance findings directly to real-life clinical problems. OpenVigil FDA does not require special licenses or statistical programs.

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

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

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

    2007-11-05

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

  13. Data-mining for detecting signals of adverse drug reactions of fluoxetine using the Korea Adverse Event Reporting System (KAERS) database.

    PubMed

    Kim, Seonji; Park, Kyounghoon; Kim, Mi-Sook; Yang, Bo Ram; Choi, Hyun Jin; Park, Byung-Joo

    2017-10-01

    Selective serotonin reuptake inhibitors (SSRIs) have become one of the most broadly used medications in psychiatry. Fluoxetine is the first representative antidepressant SSRI drug approved by the Food and Drug Administration (FDA) in 1987. Safety information on fluoxetine use alone was less reported than its combined use with other drugs. There were no published papers on adverse drug reactions (ADRs) of fluoxetine analyzing spontaneous adverse events reports. We detected signals of the adverse drug reactions of fluoxetine by data mining using the Korea Adverse Events Reporting System (KAERS) database. We defined signals in this study by the reporting odds ratios (ROR), proportional reporting ratios (PRR), and information components (IC) indices. The KAERS database included 860,224 AE reports, among which 866 reports contained fluoxetine. We compared the labels of fluoxetine among the United States, UK, Germany, France, China, and Korea. Some of the signals, including emotional lability, myositis, spinal stenosis, paradoxical drug reaction, drug dependence, extrapyramidal disorder, adrenal insufficiency, and intracranial hemorrhage, were not labeled in the six countries. In conclusion, we identified new signals that were not known at the time of market approval. However, certain factors should be required for signal evaluation, such as clinical significance, preventability, and causality of the detected signals. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. The knowledge, attitude and behaviours of nurses about pharmacovigilance, adverse drug reaction and adverse event reporting in a state hospital

    PubMed Central

    Vural, Fisun; Ciftci, Seval; Vural, Birol

    2015-01-01

    OBJECTIVE: With the use of any drug comes the possibility of unintended consequences which when harmful are referred to as adverse drug reactions (ADRs). The development of national pharmacovigilance systems is the responsibility of all health workers. The aim of this study was to investigate the knowledge of nurses about pharmacovigilance and attitudes about ADR and adverse event reporting. METHODS: This descriptive-cross sectional study was performed in 112 nurses working in a public hospital. The questionnaire was applied about pharmacovigilance and adverse drug reactions. The knowledge, attitudes and practices about adverse drug reactions were asked. RESULTS: The 74.1% of the nurses definition of “severe adverse effect” of drug therapy. The ratio of participants who knew that ADRs are reported to contact person responsible from pharmacovigilance was 34.9%. Although 70.5% of nurses knew the necessity of ADR reporting, the 8% of the nurses knew Turkish Pharmacovigilance Center (TÜFAM). Only 8% of nurses reported ADRs in their professionality. CONCLUSION: Although most of the participants knew the importance of ADR event reporting, event reporting was low. Thiese results showed that there is a lack of knowledge about pharmacovigilance. Futher studies with different settings and healthcare staff are needed to improve awareness about pharmacovigilance. PMID:28058321

  15. Causality Patterns for Detecting Adverse Drug Reactions From Social Media: Text Mining Approach.

    PubMed

    Bollegala, Danushka; Maskell, Simon; Sloane, Richard; Hajne, Joanna; Pirmohamed, Munir

    2018-05-09

    Detecting adverse drug reactions (ADRs) is an important task that has direct implications for the use of that drug. If we can detect previously unknown ADRs as quickly as possible, then this information can be provided to the regulators, pharmaceutical companies, and health care organizations, thereby potentially reducing drug-related morbidity and saving lives of many patients. A promising approach for detecting ADRs is to use social media platforms such as Twitter and Facebook. A high level of correlation between a drug name and an event may be an indication of a potential adverse reaction associated with that drug. Although numerous association measures have been proposed by the signal detection community for identifying ADRs, these measures are limited in that they detect correlations but often ignore causality. This study aimed to propose a causality measure that can detect an adverse reaction that is caused by a drug rather than merely being a correlated signal. To the best of our knowledge, this was the first causality-sensitive approach for detecting ADRs from social media. Specifically, the relationship between a drug and an event was represented using a set of automatically extracted lexical patterns. We then learned the weights for the extracted lexical patterns that indicate their reliability for expressing an adverse reaction of a given drug. Our proposed method obtains an ADR detection accuracy of 74% on a large-scale manually annotated dataset of tweets, covering a standard set of drugs and adverse reactions. By using lexical patterns, we can accurately detect the causality between drugs and adverse reaction-related events. ©Danushka Bollegala, Simon Maskell, Richard Sloane, Joanna Hajne, Munir Pirmohamed. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 09.05.2018.

  16. Adverse drug reactions in patients with phaeochromocytoma: incidence, prevention and management.

    PubMed

    Eisenhofer, Graeme; Rivers, Graham; Rosas, Alejandro L; Quezado, Zena; Manger, William M; Pacak, Karel

    2007-01-01

    The dangers of phaeochromocytomas are mainly due to the capability of these neuroendocrine tumours to secrete large quantities of vasoactive catecholamines, thereby increasing blood pressure and causing other related adverse events or complications. Phaeochromocytomas are often missed, sometimes only becoming apparent during therapeutic interventions that provoke release or interfere with the disposition of catecholamines produced by the tumours. Because phaeochromocytomas are rare, evidence contraindicating use of specific drugs is largely anecdotal or based on case reports. The heterogeneous nature of the tumours also makes adverse reactions highly variable among patients. Some drugs, such as dopamine D(2) receptor antagonists (e.g. metoclopramide, veralipride) and beta-adrenergic receptor antagonists (beta-blockers) clearly carry high potential for adverse reactions, while others such as tricyclic antidepressants seem more inconsistent in producing complications. Other drugs capable of causing adverse reactions include monoamine oxidase inhibitors, sympathomimetics (e.g. ephedrine) and certain peptide and corticosteroid hormones (e.g. corticotropin, glucagon and glucocorticoids). Risks associated with contraindicated medications are easily minimised by adoption of appropriate safeguards (e.g. adrenoceptor blockade). Without such precautions, the state of cardiovascular vulnerability makes some drugs and manipulations employed during surgical anaesthesia particularly dangerous. Problems arise most often when drugs or therapeutic procedures are employed in patients in whom the tumour is not suspected. In such cases, it is extremely important for the clinician to recognise the possibility of an underlying catecholamine-producing tumour and to take the most appropriate steps to manage and treat adverse events and clinical complications.

  17. Illicit drug use and adverse birth outcomes: is it drugs or context?

    PubMed

    Schempf, Ashley H; Strobino, Donna M

    2008-11-01

    Prenatal drug use is commonly associated with adverse birth outcomes, yet no studies have controlled for a comprehensive set of associated social, psychosocial, behavioral, and biomedical risk factors. We examined the degree to which adverse birth outcomes associated with drug use are due to the drugs versus surrounding factors. Data are from a clinical sample of low-income women who delivered at Johns Hopkins Hospital between 1995 and 1996 (n = 808). Use of marijuana, cocaine, and opiates was determined by self-report, medical record, and urine toxicology screens at delivery. Information on various social, psychosocial, behavioral, and biomedical risk factors was gathered from a postpartum interview or the medical record. Multivariable regression models of birth outcomes (continuous birth weight and low birth weight ([LBW] < 2,500 g)) were used to assess the effect of drug use independent of associated factors. In unadjusted results, all types of drug use were related to birth weight decrements and increased odds of LBW. However, only the effect of cocaine on continuous birth weight remained significant after adjusting for all associated factors (-142 g, p = 0.05). No drug was significantly related to LBW in fully adjusted models. About 70% of the unadjusted effect of cocaine use on continuous birth weight was explained by surrounding psychosocial and behavioral factors, particularly smoking and stress. Most of the unadjusted effects of opiate use were explained by smoking and lack of early prenatal care. Thus, prevention efforts that aim to improve newborn health must also address the surrounding context in which drug use frequently occurs.

  18. 21 CFR 314.80 - Postmarketing reporting of adverse drug experiences.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications... resubmit to FDA adverse drug experience reports forwarded to the applicant by FDA; however, applicants must submit all followup information on such reports to FDA. Any person subject to the reporting requirements...

  19. 21 CFR 314.80 - Postmarketing reporting of adverse drug experiences.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications... resubmit to FDA adverse drug experience reports forwarded to the applicant by FDA; however, applicants must submit all followup information on such reports to FDA. Any person subject to the reporting requirements...

  20. 21 CFR 314.80 - Postmarketing reporting of adverse drug experiences.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications... resubmit to FDA adverse drug experience reports forwarded to the applicant by FDA; however, applicants must submit all followup information on such reports to FDA. Any person subject to the reporting requirements...

  1. Patterns in spontaneous adverse event reporting among branded and generic antiepileptic drugs.

    PubMed

    Bohn, J; Kortepeter, C; Muñoz, M; Simms, K; Montenegro, S; Dal Pan, G

    2015-05-01

    Spontaneous adverse event reports constitute an important source of information on previously unknown adverse reactions to marketed medicines. However, the dynamics of such reporting following generic introduction are poorly understood. Using adverse event reports on five antiepileptic drugs from the US Food and Drug Administration's Adverse Event Reporting System, we describe temporal trends in adverse event reporting before and after generic introduction, and survey the quality of product-identifying information contained therein. The majority of reports were sent by innovator drug manufacturers while few were sent by generic manufacturers, even when generics accounted for >90% of dispensed prescriptions. We manually reviewed narratives from 2,500 reports and found that the suspect product type (brand or generic) could not be determined in 84% of reports, while generic products (16%) were identified more often than brand-name products (<1%). These results suggest that pharmacovigilance stakeholders should act to promote more detailed reporting practices. © 2015 American Society for Clinical Pharmacology and Therapeutics.

  2. 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

  3. [Characterization of adverse drug reactions in adults over 44 years of age in Bogota, January-December, 2012].

    PubMed

    Chaves, Marlén

    2015-01-01

    In Colombia, aging of the population is a reality and elders consume more drugs than the young do. Consequently, they are more exposed to adverse drug reactions. To characterize suspected adverse drug reactions in adults over 44 years of age in Bogota in 2012. We conducted a pharmacological surveillance study that included 470 reports of adverse drug events and associated problems with the use of drugs in adults over 44 years old included in the database of Bogotá´s pharmacosurveillance program. We evaluated 470 reports of adverse drug events and associated problems with the use of drugs in adults over 44 years of age. From these, 432 reports (91.9%) were classified as suspected adverse drug reactions and 28 (6%), as associated problems with the use of drugs. The incidence rate for adverse drug events reported in Bogotá was 22.5 for every 100,000 elders, which increased in direct proportion to patients´ age. The most frequently reported drug was antibacterials with 94 notifications (20%). The organ system with the highest number of alterations was the skin and annexes with 21.2% of cases. Regarding severity assessment, 69.5% of adverse drug reactions were moderate, and as for causality, most adverse drug reactions were classified as possible, with 45.8% of the reports. The characterization of adverse drug reactions in older adults in Bogotá is similar to that reported in the literature for this population age group.

  4. 21 CFR 314.80 - Postmarketing reporting of adverse drug experiences.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... identification number and adverse reaction term(s)); and (c) a history of actions taken since the last report...; an adverse event occurring from drug withdrawal; and any failure of expected pharmacological action... circumstance, the nonapplicant shall maintain a record of this action which shall include: (A) A copy of each...

  5. Evaluation of naranjo adverse drug reactions probability scale in causality assessment of drug-induced liver injury.

    PubMed

    García-Cortés, M; Lucena, M I; Pachkoria, K; Borraz, Y; Hidalgo, R; Andrade, R J

    2008-05-01

    Causality assessment in hepatotoxicity is challenging. The current standard liver-specific Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale is complex and difficult to implement in daily practice. The Naranjo Adverse Drug Reactions Probability Scale is a simple and widely used nonspecific scale, which has not been specifically evaluated in drug-induced liver injury. To compare the Naranjo method with the standard liver-specific Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale in evaluating the accuracy and reproducibility of Naranjo Adverse Drug Reactions Probability Scale in the diagnosis of hepatotoxicity. Two hundred and twenty-five cases of suspected hepatotoxicity submitted to a national registry were evaluated by two independent observers and assessed for between-observer and between-scale differences using percentages of agreement and the weighted kappa (kappa(w)) test. A total of 249 ratings were generated. Between-observer agreement was 45% with a kappa(w) value of 0.17 for the Naranjo Adverse Drug Reactions Probability Scale, while there was a higher agreement when using the Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method scale (72%, kappa(w): 0.71). Concordance between the two scales was 24% (kappa(w): 0.15). The Naranjo Adverse Drug Reactions Probability Scale had low sensitivity (54%) and poor negative predictive value (29%) and showed a limited capability to distinguish between adjacent categories of probability. The Naranjo scale lacks validity and reproducibility in the attribution of causality in hepatotoxicity.

  6. Adverse drug events in the oral cavity.

    PubMed

    Yuan, Anna; Woo, Sook-Bin

    2015-01-01

    Adverse reactions to medications are common and may have a variety of clinical presentations in the oral cavity. Targeted therapies and the new biologic agents have revolutionized the treatment of cancers, autoimmune diseases, and inflammatory and rheumatologic diseases but have also been associated with adverse events in the oral cavity. Some examples include osteonecrosis, seen with not only bisphosphonates but also antiangiogenic agents, and the distinctive ulcers caused by mammalian target of rapamycin inhibitors. As newer therapeutic agents are approved, it is likely that more adverse drug events will be encountered. This review describes the most common clinical presentations of oral mucosal reactions to medications, namely, xerostomia, lichenoid reactions, ulcers, bullous disorders, pigmentation, fibrovascular hyperplasia, white lesions, dysesthesia, osteonecrosis, infection, angioedema, and malignancy. Oral health care providers should be familiar with such events, as they will encounter them in their practice. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Personalized Medicine and Adverse Drug Reactions: The Experience of An Italian Teaching Hospital.

    PubMed

    La Russa, Raffaele; Finesch, Vittorio; Di Sanzo, Mariantonia; Gatto, Vittorio; Santurro, Alessandro; Martini, Gabriella; Scopetti, Matteo; Frati, Paola

    2017-01-01

    The personalized medicine is a model of medicine based on inherent difference given by the genetic heritage that characterizes us, diversity that can affect also our response to administered therapy. Nowadays, the term "adverse drug reaction" is identified with any harmful effect involuntary resulting from the use of a medicinal product; pharmacogenomics, in this field, has the aim to improve the drug response and to reduce the adverse reaction. We analyzed all reports of adverse reaction collected in the Pharmacovigilance Centre database of an Italian University Hospital, at the Sant'Andrea Hospital Sapienza University of Rome, in a period of two years. Comparing the data result from our analysis with several studies found in literature, it is evident that adverse drug reactions represent an important problem in the management of a health care system. However, the development of pharmacogenetics and pharmacogenomics, allowing a personalized treatment, can improve clinical practice. This study highlights the great potential of pharmacogenomics in reducing adverse reactions and suggests the need for further pharmacogenomic clinical trials to better personalize drug treatment and to refine the current pharmacovigilance strategies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Adverse drug reactions: classification, susceptibility and reporting.

    PubMed

    Kaufman, Gerri

    2016-08-10

    Adverse drug reactions (ADRs) are increasingly common and are a significant cause of morbidity and mortality. Historically, ADRs have been classified as type A or type B. Type A reactions are predictable from the known pharmacology of a drug and are associated with high morbidity and low mortality. Type B reactions are idiosyncratic, bizarre or novel responses that cannot be predicted from the known pharmacology of a drug and are associated with low morbidity and high mortality. Not all ADRs fit into type A and type B categories; therefore, additional categories have been developed. These include type C (continuing), type D (delayed use), and type E (end of use) reactions. Susceptibility to ADRs is influenced by age, gender, disease states, pregnancy, ethnicity and polypharmacy. Drug safety is reliant on nurses and other healthcare professionals being alert to the possibility of ADRs, working with patients to optimise medicine use and exercising vigilance in the reporting of ADRs through the Yellow Card Scheme.

  9. Detecting drug-drug interactions using a database for spontaneous adverse drug reactions: an example with diuretics and non-steroidal anti-inflammatory drugs.

    PubMed

    van Puijenbroek, E P; Egberts, A C; Heerdink, E R; Leufkens, H G

    2000-12-01

    Drug-drug interactions are relatively rarely reported to spontaneous reporting systems (SRSs) for adverse drug reactions. For this reason, the traditional approach for analysing SRS has major limitations for the detection of drug-drug interactions. We developed a method that may enable signalling of these possible interactions, which are often not explicitly reported, utilising reports of adverse drug reactions in data sets of SRS. As an example, the influence of concomitant use of diuretics and non-steroidal anti-inflammatory drugs (NSAIDs) on symptoms indicating a decreased efficacy of diuretics was examined using reports received by the Netherlands Pharmacovigilance Foundation Lareb. Reports received between 1 January 1990 and 1 January 1999 of patients older than 50 years were included in the study. Cases were defined as reports with symptoms indicating a decreased efficacy of diuretics, non-cases as all other reports. Exposure categories were the use of NSAIDs or diuretics versus the use of neither of these drugs. The influence of the combined use of both drugs was examined using logistic regression analysis. The odds ratio of the statistical interaction term of the combined use of both drugs was increased [adjusted odds ratio 2.0, 95% confidence interval (CI) 1.1-3.7], which may indicate an enhanced effect of concomitant drug use. The findings illustrate that spontaneous reporting systems have a potential for signal detection and the analysis of possible drug-drug interactions. The method described may enable a more active approach in the detection of drug-drug interactions after marketing.

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

    PubMed

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

    2016-06-01

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

  11. 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.

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

    PubMed

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

    2016-07-01

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

  13. Idiosyncratic Adverse Drug Reactions: Current Concepts

    PubMed Central

    Naisbitt, Dean J.

    2013-01-01

    Idiosyncratic drug reactions are a significant cause of morbidity and mortality for patients; they also markedly increase the uncertainty of drug development. The major targets are skin, liver, and bone marrow. Clinical characteristics suggest that IDRs are immune mediated, and there is substantive evidence that most, but not all, IDRs are caused by chemically reactive species. However, rigorous mechanistic studies are very difficult to perform, especially in the absence of valid animal models. Models to explain how drugs or reactive metabolites interact with the MHC/T-cell receptor complex include the hapten and P-I models, and most recently it was found that abacavir can interact reversibly with MHC to alter the endogenous peptides that are presented to T cells. The discovery of HLA molecules as important risk factors for some IDRs has also significantly contributed to our understanding of these adverse reactions, but it is not yet clear what fraction of IDRs have a strong HLA dependence. In addition, with the exception of abacavir, most patients who have the HLA that confers a higher IDR risk with a specific drug will not have an IDR when treated with that drug. Interindividual differences in T-cell receptors and other factors also presumably play a role in determining which patients will have an IDR. The immune response represents a delicate balance, and immune tolerance may be the dominant response to a drug that can cause IDRs. PMID:23476052

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

    PubMed

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

    2017-06-01

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

  15. Adverse Drug Reactions Related to Drug Administration in Hospitalized Patients.

    PubMed

    Gallelli, Luca; Siniscalchi, Antonio; Palleria, Caterina; Mumoli, Laura; Staltari, Orietta; Squillace, Aida; Maida, Francesca; Russo, Emilio; Gratteri, Santo; De Sarro, Giovambattista

    2017-01-01

    Drug treatment may be related to the development of adverse drug reactions (ADRs). In this paper, we evaluated the ADRs in patients admitted to Catanzaro Hospital. After we obtained the approval by local Ethical Committee, we performed a retrospective study on clinical records from March 01, 2013 to April 30, 2015. The association between drug and ADR or between drug and drug-drug-interactions (DDIs) was evaluated using the Naranjo's probability scale and Drug Interaction Probability Scale (DIPS), respectively. During the study period, we analyzed 2870 clinical records containing a total of 11,138 prescriptions, and we documented the development of 770 ADRs. The time of hospitalization was significantly higher (P<0.05) in women with ADRs (12.6 ± 1.2 days) with respect to men (11.8± 0.83 days). Using the Naranjo score, we documented a probable association in 78% of these reactions, while DIPS revealed that about 22% of ADRs were related to DDIs. Patients with ADRs received 3052 prescriptions on 11,138 (27.4%) having a mean of 6.1±0.29 drugs that was significantly higher (P<0.01) with respect to patients not experiencing ADRs (mean of 3.4±0.13 drugs). About 19% of ADRs were not diagnosed and were treated as new diseases. Our results indicate that drug administration induces the development of ADRs also during the hospitalization, particularly in elderly women. Moreover, we also documented that ADRs in some patients are under-diagnosed, therefore, it is important to motivate healthcare to report the ADRs in order to optimize the patients' safety. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Use of a trigger tool to detect adverse drug reactions in an emergency department.

    PubMed

    de Almeida, Silvana Maria; Romualdo, Aruana; de Abreu Ferraresi, Andressa; Zelezoglo, Giovana Roberta; Marra, Alexandre R; Edmond, Michael B

    2017-11-15

    Although there are systems for reporting adverse drug reactions (ADR), these safety events remain under reported. The low-cost, low-tech trigger tool method is based on the detection of events through clues, and it seems to increase the detection of adverse events compared to traditional methodologies. This study seeks to estimate the prevalence of adverse reactions to drugs in patients seeking care in the emergency department. Retrospective study from January to December, 2014, applying the Institute for Healthcare Improvement (IHI) trigger tool methodology for patients treated at the emergency room of a tertiary care hospital. The estimated prevalence of adverse reactions in patients presenting to the emergency department was 2.3% [CI 95 1.3% to 3.3%]; 28.6% of cases required hospitalization at an average cost of US$ 5698.44. The most common triggers were hydrocortisone (57% of the cases), diphenhydramine (14%) and fexofenadine (14%). Anti-infectives (19%), cardiovascular agents (14%), and musculoskeletal drugs (14%) were the most common causes of adverse reactions. According to the Naranjo Scale, 71% were classified as possible and 29% as probable. There was no association between adverse reactions and age and sex in the present study. The use of the trigger tool to identify adverse reactions in the emergency department was possible to identify a prevalence of 2.3%. It showed to be a viable method that can provide a better understanding of adverse drug reactions in this patient population.

  17. Predictive modeling of structured electronic health records for adverse drug event detection.

    PubMed

    Zhao, Jing; Henriksson, Aron; Asker, Lars; Boström, Henrik

    2015-01-01

    The digitization of healthcare data, resulting from the increasingly widespread adoption of electronic health records, has greatly facilitated its analysis by computational methods and thereby enabled large-scale secondary use thereof. This can be exploited to support public health activities such as pharmacovigilance, wherein the safety of drugs is monitored to inform regulatory decisions about sustained use. To that end, electronic health records have emerged as a potentially valuable data source, providing access to longitudinal observations of patient treatment and drug use. A nascent line of research concerns predictive modeling of healthcare data for the automatic detection of adverse drug events, which presents its own set of challenges: it is not yet clear how to represent the heterogeneous data types in a manner conducive to learning high-performing machine learning models. Datasets from an electronic health record database are used for learning predictive models with the purpose of detecting adverse drug events. The use and representation of two data types, as well as their combination, are studied: clinical codes, describing prescribed drugs and assigned diagnoses, and measurements. Feature selection is conducted on the various types of data to reduce dimensionality and sparsity, while allowing for an in-depth feature analysis of the usefulness of each data type and representation. Within each data type, combining multiple representations yields better predictive performance compared to using any single representation. The use of clinical codes for adverse drug event detection significantly outperforms the use of measurements; however, there is no significant difference over datasets between using only clinical codes and their combination with measurements. For certain adverse drug events, the combination does, however, outperform using only clinical codes. Feature selection leads to increased predictive performance for both data types, in isolation and

  18. Sharing adverse drug event data using business intelligence technology.

    PubMed

    Horvath, Monica M; Cozart, Heidi; Ahmad, Asif; Langman, Matthew K; Ferranti, Jeffrey

    2009-03-01

    Duke University Health System uses computerized adverse drug event surveillance as an integral part of medication safety at 2 community hospitals and an academic medical center. This information must be swiftly communicated to organizational patient safety stakeholders to find opportunities to improve patient care; however, this process is encumbered by highly manual methods of preparing the data. Following the examples of other industries, we deployed a business intelligence tool to provide dynamic safety reports on adverse drug events. Once data were migrated into the health system data warehouse, we developed census-adjusted reports with user-driven prompts. Drill down functionality enables navigation from aggregate trends to event details by clicking report graphics. Reports can be accessed by patient safety leadership either through an existing safety reporting portal or the health system performance improvement Web site. Elaborate prompt screens allow many varieties of reports to be created quickly by patient safety personnel without consultation with the research analyst. The reduction in research analyst workload because of business intelligence implementation made this individual available to additional patient safety projects thereby leveraging their talents more effectively. Dedicated liaisons are essential to ensure clear communication between clinical and technical staff throughout the development life cycle. Design and development of the business intelligence model for adverse drug event data must reflect the eccentricities of the operational system, especially as new areas of emphasis evolve. Future usability studies examining the data presentation and access model are needed.

  19. Pharmacovigilance and drug safety 2011 in Calabria (Italy): Adverse events analysis.

    PubMed

    Scicchitano, Francesca; Giofrè, Chiara; Palleria, Caterina; Mazzitello, Carmela; Ciriaco, Miriam; Gallelli, Luca; Paletta, Laura; Marrazzo, Giuseppina; De Fazio, Salvatore; Menniti, Michele; Curia, Rubens; Arena, Concetta; Chimirri, Serafina; Patanè, Marinella; Esposito, Stefania; Cilurzo, Felisa; Staltari, Orietta; Russo, Emilio; De Sarro, Giovambattista

    2012-09-01

    Pharmacovigilance assesses the safety profile of drugs. Its main aim is the increase of spontaneous reporting of adverse drug reactions (ADRs). The Italian Drug Agency (AIFA; Agenzia Italiana del Farmaco) is financing several projects to the aim of increasing reporting, and in Calabria a Pharmacovigilance Information Centre has been created. We analyzed the AIFA database relatively to Calabria in the year 2011 and we have analyzed ADRs using descriptive statistics. We have also collected a questionnaire-based interview in order to describe the background knowledge in the field. Regarding the number of AIFA reported ADRs from Calabria, a 38% increase (138 vs. 100) in comparison to 2010 was evidenced. Hospital Doctors represent the main source of signaling (71.7 %). Ketoprofene and the combination amoxicillin/clavulanic acid represent the most frequently reported drugs causing ADRs. Our questionnaires indicated that despite the health professionals have met at least once an ADR only a small percentage of them was reported to the authorities (37%). There is a very good knowledge of the ADR concept and reporting system (90% of interviewed distinguish an ADR and knows how to report it), and there is a strong interest in participating to training courses in the field (95% are interested). Despite Calabria has had a positive increase in the number of reported ADRs, the total number is very low and the pharmacovigilance culture is far from being achieved in this region.

  20. Adverse drug reactions in Colombian patients, 2007-2013: Analysis of population databases.

    PubMed

    Machado-Alba, Jorge Enrique; Londoño-Builes, Manuel José; Echeverri-Cataño, Luis Felipe; Ochoa-Orozco, Sergio Andrés

    2016-03-03

    Recognizing adverse drug reactions (ADRs) is becoming more important in clinical practice.  To determine the frequency of adverse drug reactions and ADR suspicions among the population affiliated to the Colombian health system and to describe the drugs, reactions and associated variables.  We revised ADRs and ADRs suspicion databases from drugs dispensed by Audifarma, S.A., both for inpatient and outpatient care from 2007 to 2013. Variables included ADR report date, city, drug, drug's Anatomical Therapeutic Classification (ATC), ADR severity, ADR type, ADR classification and ADR probability according to the World Health Organization's definitions.  We obtained 5,342 reports for 468 different drugs. The ATC groups with the most reports were anti-infectives for systemic use (25.5%), nervous system agents (17.1%) and cardiovascular system drugs (15.0%). The drugs with the highest number of reports were metamizole (4.2%), enalapril (3.8%), clarithromycin (2.8%), warfarin (2.5%) and ciprofloxacin (2.4%). The most common ADR, classified following the World Health Organization adverse reaction terminology, were: skin and appendages disorders (35.3%), general disorders (14.2%) and gastrointestinal system disorders (11.8%). Overall, 49.4% of the ADRs were classified as "moderate" and 45.1% as "mild".  An increasing number of ADR reports were found coinciding with a worldwide tendency. Differences between inpatient and outpatient ADR reports were found when compared to scientific publications. The information on ADR reports, mainly gathered by the Instituto Nacional de Vigilancia de Medicamentos y Alimentos - Invima, should be made public for academic and institutional use.

  1. Ontology-based literature mining and class effect analysis of adverse drug reactions associated with neuropathy-inducing drugs.

    PubMed

    Hur, Junguk; Özgür, Arzucan; He, Yongqun

    2018-06-07

    Adverse drug reactions (ADRs), also called as drug adverse events (AEs), are reported in the FDA drug labels; however, it is a big challenge to properly retrieve and analyze the ADRs and their potential relationships from textual data. Previously, we identified and ontologically modeled over 240 drugs that can induce peripheral neuropathy through mining public drug-related databases and drug labels. However, the ADR mechanisms of these drugs are still unclear. In this study, we aimed to develop an ontology-based literature mining system to identify ADRs from drug labels and to elucidate potential mechanisms of the neuropathy-inducing drugs (NIDs). We developed and applied an ontology-based SciMiner literature mining strategy to mine ADRs from the drug labels provided in the Text Analysis Conference (TAC) 2017, which included drug labels for 53 neuropathy-inducing drugs (NIDs). We identified an average of 243 ADRs per NID and constructed an ADR-ADR network, which consists of 29 ADR nodes and 149 edges, including only those ADR-ADR pairs found in at least 50% of NIDs. Comparison to the ADR-ADR network of non-NIDs revealed that the ADRs such as pruritus, pyrexia, thrombocytopenia, nervousness, asthenia, acute lymphocytic leukaemia were highly enriched in the NID network. Our ChEBI-based ontology analysis identified three benzimidazole NIDs (i.e., lansoprazole, omeprazole, and pantoprazole), which were associated with 43 ADRs. Based on ontology-based drug class effect definition, the benzimidazole drug group has a drug class effect on all of these 43 ADRs. Many of these 43 ADRs also exist in the enriched NID ADR network. Our Ontology of Adverse Events (OAE) classification further found that these 43 benzimidazole-related ADRs were distributed in many systems, primarily in behavioral and neurological, digestive, skin, and immune systems. Our study demonstrates that ontology-based literature mining and network analysis can efficiently identify and study specific group of

  2. Commonality of drug-associated adverse events detected by 4 commonly used data mining algorithms.

    PubMed

    Sakaeda, Toshiyuki; Kadoyama, Kaori; Minami, Keiko; Okuno, Yasushi

    2014-01-01

    Data mining algorithms have been developed for the quantitative detection of drug-associated adverse events (signals) from a large database on spontaneously reported adverse events. In the present study, the commonality of signals detected by 4 commonly used data mining algorithms was examined. A total of 2,231,029 reports were retrieved from the public release of the US Food and Drug Administration Adverse Event Reporting System database between 2004 and 2009. The deletion of duplicated submissions and revision of arbitrary drug names resulted in a reduction in the number of reports to 1,644,220. Associations with adverse events were analyzed for 16 unrelated drugs, using the proportional reporting ratio (PRR), reporting odds ratio (ROR), information component (IC), and empirical Bayes geometric mean (EBGM). All EBGM-based signals were included in the PRR-based signals as well as IC- or ROR-based ones, and PRR- and IC-based signals were included in ROR-based ones. The PRR scores of PRR-based signals were significantly larger for 15 of 16 drugs when adverse events were also detected as signals by the EBGM method, as were the IC scores of IC-based signals for all drugs; however, no such effect was observed in the ROR scores of ROR-based signals. The EBGM method was the most conservative among the 4 methods examined, which suggested its better suitability for pharmacoepidemiological studies. Further examinations should be performed on the reproducibility of clinical observations, especially for EBGM-based signals.

  3. Causality or Relatedness Assessment in Adverse Drug Reaction and Its Relevance in Dermatology.

    PubMed

    Pande, Sushil

    2018-01-01

    Causality assessment essentially means finding a causal association or relationship between a drug and drug reaction. Identifying the culprit drug or drugs can be lifesaving or helpful in preventing the further damage caused by the drug to our body systems. In dermatology practice, when it comes to cutaneous adverse drug reaction, this is much more important and relevant because many aetiologies can produce a similar cutaneous manifestation. There are multiple criteria or algorithms available as of now for establishing a causal relationship in cases of adverse drug reaction (ADR), indicating that none of them is specific or complete. Most of these causality assessment tools (CATs) use four cardinal principles of diagnosis of ADR such as temporal relationship of drug with the drug reaction, biological plausibility of the drug causing a reaction, dechallenge, and rechallenge. The present study reviews some of the established or commonly used CATs and its implications or relevance to dermatology in clinical practice.

  4. Factors that condition the spontaneous reporting of adverse drug reactions among nurses: an integrative review.

    PubMed

    De Angelis, Alessia; Colaceci, Sofia; Giusti, Angela; Vellone, Ercole; Alvaro, Rosaria

    2016-03-01

    To describe and synthesise previous research on factors conditioning the spontaneous reporting of adverse drug reactions among nurses. Spontaneous reports of adverse drug reactions by health-care providers, are a main instrument for the continuous evaluation of the risk-benefit ratio of every drug. Under-reporting of adverse drug reactions by all health-care providers, in particular by nurses, is a major limitation to this system. An integrated review of the literature was conducted using MEDLINE, CINAHL, Embase, Scopus databases and Google Scholar. After evaluation for appropriateness related to inclusion/exclusion criteria, 16 studies were included in the final analysis and synthesis. Two factors emerged from the study: (1) intrinsic factors related to nurses' knowledge and attitudes; (2) extrinsic factors related to nurses' interaction with health-care organisations and to the relationship between nurses and physicians. Nurses' attitudes that hinder reporting include ignorance, insecurity, fear and lethargy. Nurses are not fully aware of their role in adverse drug reaction reporting. Nurses must acquire greater knowledge to implement specific skills into their daily clinical practice. To improve nurses' reporting of adverse drug reactions, it is necessary to develop management approaches that modify both intrinsic and extrinsic factors. © 2015 John Wiley & Sons Ltd.

  5. Pattern Mining for Extraction of mentions of Adverse Drug Reactions from User Comments

    PubMed Central

    Nikfarjam, Azadeh; Gonzalez, Graciela H.

    2011-01-01

    Rapid growth of online health social networks has enabled patients to communicate more easily with each other. This way of exchange of opinions and experiences has provided a rich source of information about drugs and their effectiveness and more importantly, their possible adverse reactions. We developed a system to automatically extract mentions of Adverse Drug Reactions (ADRs) from user reviews about drugs in social network websites by mining a set of language patterns. The system applied association rule mining on a set of annotated comments to extract the underlying patterns of colloquial expressions about adverse effects. The patterns were tested on a set of unseen comments to evaluate their performance. We reached to precision of 70.01% and recall of 66.32% and F-measure of 67.96%. PMID:22195162

  6. Biometrical issues in the analysis of adverse events within the benefit assessment of drugs.

    PubMed

    Bender, Ralf; Beckmann, Lars; Lange, Stefan

    2016-07-01

    The analysis of adverse events plays an important role in the benefit assessment of drugs. Consequently, results on adverse events are an integral part of reimbursement dossiers submitted by pharmaceutical companies to health policy decision-makers. Methods applied in the analysis of adverse events commonly include simple standard methods for contingency tables. However, the results produced may be misleading if observations are censored at the time of discontinuation due to treatment switching or noncompliance, resulting in unequal follow-up periods. In this paper, we present examples to show that the application of inadequate methods for the analysis of adverse events in the reimbursement dossier can lead to a downgrading of the evidence on a drug's benefit in the subsequent assessment, as greater harm from the drug cannot be excluded with sufficient certainty. Legal regulations on the benefit assessment of drugs in Germany are presented, in particular, with regard to the analysis of adverse events. Differences in safety considerations between the drug approval process and the benefit assessment are discussed. We show that the naive application of simple proportions in reimbursement dossiers frequently leads to uninterpretable results if observations are censored and the average follow-up periods differ between treatment groups. Likewise, the application of incidence rates may be misleading in the case of recurrent events and unequal follow-up periods. To allow for an appropriate benefit assessment of drugs, adequate survival time methods accounting for time dependencies and duration of follow-up are required, not only for time-to-event efficacy endpoints but also for adverse events. © 2016 The Authors. Pharmaceutical Statistics published by John Wiley & Sons Ltd. © 2016 The Authors. Pharmaceutical Statistics published by John Wiley & Sons Ltd.

  7. Automatic detection of adverse events to predict drug label changes using text and data mining techniques.

    PubMed

    Gurulingappa, Harsha; Toldo, Luca; Rajput, Abdul Mateen; Kors, Jan A; Taweel, Adel; Tayrouz, Yorki

    2013-11-01

    The aim of this study was to assess the impact of automatically detected adverse event signals from text and open-source data on the prediction of drug label changes. Open-source adverse effect data were collected from FAERS, Yellow Cards and SIDER databases. A shallow linguistic relation extraction system (JSRE) was applied for extraction of adverse effects from MEDLINE case reports. Statistical approach was applied on the extracted datasets for signal detection and subsequent prediction of label changes issued for 29 drugs by the UK Regulatory Authority in 2009. 76% of drug label changes were automatically predicted. Out of these, 6% of drug label changes were detected only by text mining. JSRE enabled precise identification of four adverse drug events from MEDLINE that were undetectable otherwise. Changes in drug labels can be predicted automatically using data and text mining techniques. Text mining technology is mature and well-placed to support the pharmacovigilance tasks. Copyright © 2013 John Wiley & Sons, Ltd.

  8. Adverse childhood experiences among women prisoners: relationships to suicide attempts and drug abuse.

    PubMed

    Friestad, Christine; Åse-Bente, Rustad; Kjelsberg, Ellen

    2014-02-01

    Women prisoners are known to suffer from an accumulation of factors known to increase the risk for several major health problems. This study examines the prevalence of adverse childhood experiences (ACE) and the relationship between such experiences and suicide attempts and drug use among incarcerated women in Norway. A total of 141 women inmates (75% of all eligible) were interviewed using a structured interview guide covering information on demographics and a range of ACE related to abuse and neglect, and household dysfunction. The main outcome variables were attempted suicide and adult drug abuse. Emotional, physical and sexual abuse during childhood was experienced by 39%, 36% and 19%, respectively, and emotional and physical neglect by 31% and 33%, respectively. Looking at the full range of ACE, 17% reported having experienced none, while 34% reported having experienced more than five ACEs. After controlling for age, immigrant background and marital status, the number of ACEs significantly increased the risk of attempted suicide and current drug abuse. The associations observed between early life trauma and later health risk behaviour indicate the need for early prevention. The findings also emphasize the important role of prison health services in secondary prevention among women inmates.

  9. Patterns of adverse drug reaction signals in NAFDAC Pharmacovigilance activities from September to November, 2014.

    PubMed

    Awodele, Olufunsho; Ibrahim, Ali; Orhii, Paul

    2016-03-16

    Adverse drug reaction signals are reported information on possible causal relationships between an adverse event and a drug. The National Pharmacovigilance Centre (NPC) in Nigeria has over 3,000 reported adverse drug reaction cases which have been adequately entered into the ADR data bank. Data mining of ADR reports from September to November, 2014 were carried out in this present study with the intention to describe the pattern of ADRs and generate possible signals. A total of about 100 reported cases with arrays of adverse drug reactions were reported between September and November, 2014 and the data were analyzed using SPSS version 17. Efavirenz/Tenofovir/Lamivudine combination was the highest reported drugs (24.2%) while efavirenz alone was reported in 8 times (8.8%) and HIV (63.3%) was the highest reported indication of drug use. Efavirenz caused central nervous system adverse reactions as revealed in the ADRs analyses. Zidovudine/Lamivudine/Nevirapine combination in concomitant use with Cotrimoxazole were reported 8 times with generalized maculopapular rashes on the trunk with some area of hyper pigmentation with intense itching documented twice and big/swollen rashes all over the faces. Zidovudine was also reported four times to cause severe anaemia. More surveillance is advocated so as to ascertain the consistency of the observed ADRs and thereafter establish appropriate signals.

  10. Association between Selective Beta-adrenergic Drugs and Blood Pressure Elevation: Data Mining of the Japanese Adverse Drug Event Report (JADER) Database.

    PubMed

    Ohyama, Katsuhiro; Inoue, Michiko

    2016-01-01

    Selective beta-adrenergic drugs are used clinically to treat various diseases. Because of imperfect receptor selectivity, beta-adrenergic drugs cause some adverse drug events by stimulating other adrenergic receptors. To examine the association between selective beta-adrenergic drugs and blood pressure elevation, we reviewed the Japanese Adverse Drug Event Reports (JADERs) submitted to the Japan Pharmaceuticals and Medical Devices Agency. We used the Medical Dictionary for Regulatory Activities (MedDRA) Preferred Terms extracted from Standardized MedDRA queries for hypertension to identify events related to blood pressure elevation. Spontaneous adverse event reports from April 2004 through May 2015 in JADERs, a data mining algorithm, and the reporting odds ratio (ROR) were used for quantitative signal detection, and assessed by the case/non-case method. Safety signals are considered significant if the ROR estimates and lower bound of the 95% confidence interval (CI) exceed 1. A total of 2021 reports were included in this study. Among the nine drugs examined, significant signals were found, based on the 95%CI for salbutamol (ROR: 9.94, 95%CI: 3.09-31.93) and mirabegron (ROR: 7.52, 95%CI: 4.89-11.55). The results of this study indicate that some selective beta-adrenergic drugs are associated with blood pressure elevation. Considering the frequency of their indications, attention should be paid to their use in elderly patients to avoid adverse events.

  11. Worldwide withdrawal of medicinal products because of adverse drug reactions: a systematic review and analysis.

    PubMed

    Onakpoya, Igho J; Heneghan, Carl J; Aronson, Jeffrey K

    2016-07-01

    We have systematically identified medicinal products withdrawn worldwide because of adverse drug reactions, assessed the level of evidence used for making the withdrawal decisions, and explored the patterns of withdrawals over time. We searched PubMed, the WHO database of withdrawn products, and selected texts. We included products that were withdrawn after launch from 1950 onwards, excluding non-human and over-the-counter medicines. We assessed the levels of evidence on which withdrawals were based using the Oxford Center for Evidence Based Medicine Levels of Evidence. Of 353 medicinal products withdrawn from any country, only 40 were withdrawn worldwide. Anecdotal reports were cited as evidence for withdrawal in 30 (75%) and deaths occurred in 27 (68%). Hepatic, cardiac, and nervous system toxicity accounted for over 60% of withdrawals. In 28 cases, the first withdrawal was initiated by the manufacturer. The median interval between the first report of an adverse drug reaction that led to withdrawal and the first withdrawal was 1 year (range 0-43 years). Worldwide withdrawals occurred within 1 year after the first withdrawal in any country. In conclusion, the time it takes for drugs to be withdrawn worldwide after reports of adverse drug reactions has shortened over time. However, there are inconsistencies in current withdrawal procedures when adverse drug reactions are suspected. A uniform method for establishing worldwide withdrawal of approved medicinal products when adverse drug reactions are suspected should be developed, to facilitate global withdrawals. Rapid synthesis of the evidence on harms should be a priority when serious adverse reactions are suspected.

  12. Adverse reactions and interactions with beta-adrenoceptor blocking drugs.

    PubMed

    Lewis, R V; McDevitt, D G

    1986-01-01

    beta-Blocking drugs are widely used throughout the world and serious adverse reactions are relatively uncommon. Most of those which do occur are pharmacologically predictable and may be avoided by ensuring that patients who are to be given beta-blockers do not have a predisposition to the development of bronchospasm, cardiac failure or peripheral ischaemia. In some situations, the use of a beta 1-selective blocking drug may reduce the risk of a severe adverse reaction, but there is little evidence that other ancillary properties such as partial agonist activity are of relevance in this context. Long term experience with many of the beta-blockers in current use suggests that unpredictable major adverse reactions such as the practolol oculomucocutaneous syndrome are unlikely to be repeated, although some of these drugs may be associated with immunological disturbances and some have been implicated in the development of retroperitoneal fibrosis. beta-Blocking drugs appear to be associated with a number of subjective side effects including muscle fatigue, peripheral coldness and some neurological symptoms. These side effects are highly subjective and are therefore difficult to quantify and it is not known whether they are of major importance in terms of their effect upon patients' overall well-being. It cannot be assumed that simply because such side effects can be elicited that they do, in fact, matter. However, because beta-blockers are often prescribed for patients who have no symptoms and for whom the benefits of therapy are generally small, such side effects would be of considerable importance if they had an overall effect upon quality of life. There are theoretical reasons to suppose that the incidence and severity of such side effects may be related to the ancillary properties of the individual drugs, but there is little evidence that parameters such as beta 1-selectivity, or partial agonist activity are clinically important determinants of the severity of these

  13. Refining adverse drug reaction signals by incorporating interaction variables identified using emergent pattern mining.

    PubMed

    Reps, Jenna M; Aickelin, Uwe; Hubbard, Richard B

    2016-02-01

    To develop a framework for identifying and incorporating candidate confounding interaction terms into a regularised cox regression analysis to refine adverse drug reaction signals obtained via longitudinal observational data. We considered six drug families that are commonly associated with myocardial infarction in observational healthcare data, but where the causal relationship ground truth is known (adverse drug reaction or not). We applied emergent pattern mining to find itemsets of drugs and medical events that are associated with the development of myocardial infarction. These are the candidate confounding interaction terms. We then implemented a cohort study design using regularised cox regression that incorporated and accounted for the candidate confounding interaction terms. The methodology was able to account for signals generated due to confounding and a cox regression with elastic net regularisation correctly ranking the drug families known to be true adverse drug reactions above those that are not. This was not the case without the inclusion of the candidate confounding interaction terms, where confounding leads to a non-adverse drug reaction being ranked highest. The methodology is efficient, can identify high-order confounding interactions and does not require expert input to specify outcome specific confounders, so it can be applied for any outcome of interest to quickly refine its signals. The proposed method shows excellent potential to overcome some forms of confounding and therefore reduce the false positive rate for signal analysis using longitudinal data. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Reporting adverse drug reactions: contribution, knowledge and perception of German pharmacy professionals.

    PubMed

    Laven, Anna; Schmitz, Katharina; Franzen, Wilhelm-Hubertus

    2018-06-16

    Background The detection, assessment and prevention of adverse drug reactions along the product's life cycle is known as pharmacovigilance. German pharmacists are obliged by law to conduct pharmacovigilance measures, a specific training is not required. Objectives To assess the knowledge, contribution and perception of German pharmacy professionals regarding pharmacovigilance activities, in order to identify their needs to report better on the issue. Setting A semi-quantitative survey among German pharmacy professionals was conducted in November 2017. Method A questionnaire with 20 questions was developed and distributed to pharmacy professionals in four different German regions. Main outcome measures To assess the knowledge the number of right answered questions were examined; for perception a six-point-Likert was used and for contribution, yes or no questions. Results The participation ratio was 64.5% (n = 127). Nearly half of the participants (47.2%, n = 60) stated that they had already reported adverse drug reactions. Regarding the knowledge questions, there was neither a statistically significant difference between the correct answers of pharmacists and pharmacy technical assistents (p = 0.7209), nor between the different regions (p > 0.5054). For better reporting, the participants recommended better training, shorter forms to fill in and/or a contact person to call. Conclusion For the successful integration of pharmacovigilance reporting in daily practice, we suggest the following: (1) A structured, mandatory training of the pharmacy team. (2) The preparation of a standard operating procedure for the pharmacy or its integration into the pharmacy software.

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

    PubMed Central

    Shamliyan, Tatyana

    2010-01-01

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

  16. Can Drosophila melanogaster represent a model system for the detection of reproductive adverse drug reactions?

    PubMed

    Avanesian, Agnesa; Semnani, Sahar; Jafari, Mahtab

    2009-08-01

    Once a molecule is identified as a potential drug, the detection of adverse drug reactions is one of the key components of its development and the FDA approval process. We propose using Drosophila melanogaster to screen for reproductive adverse drug reactions in the early stages of drug development. Compared with other non-mammalian models, D. melanogaster has many similarities to the mammalian reproductive system, including putative sex hormones and conserved proteins involved in genitourinary development. Furthermore, the D. melanogaster model would present significant advantages in time efficiency and cost-effectiveness compared with mammalian models. We present data on methotrexate (MTX) reproductive adverse events in multiple animal models, including fruit flies, as proof-of-concept for the use of the D. melanogaster model.

  17. 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.

  18. Nephrotic syndrome under treatment with dasatinib: be aware of a possible adverse drug reaction.

    PubMed

    Muller-Hansma, A H G; van der Lugt, J; Zwaan, C M

    2017-12-01

    The protein kinase inhibitor dasatinib, targeting BCR-ABL and Src family kinases, is used in chronic myeloid leukaemia and Philadelphia-chromosome positive acute lymphoblastic leukaemia. The Netherlands Pharmacovigilance Centre Lareb has received one report of nephrotic syndrome associated with the use of dasatinib. With some other protein kinase inhibitors, targeting vascular endothelial growth factor, nephrotic syndrome is a well-known adverse drug reaction. The Dutch and European pharmacovigilance databases and scientific literature contain several cases indicating a causal relationship between dasatinib and nephrotic syndrome. Nephrotic syndrome was recently added to the list of adverse drug reactions in the Dutch summary of product characteristics for dasatinib. It is important to recognise the possibility of this adverse drug reaction when a patient develops nephrotic syndrome under treatment with dasatinib.

  19. A Systematic Investigation of Computation Models for Predicting Adverse Drug Reactions (ADRs)

    PubMed Central

    Kuang, Qifan; Wang, MinQi; Li, Rong; Dong, YongCheng; Li, Yizhou; Li, Menglong

    2014-01-01

    Background Early and accurate identification of adverse drug reactions (ADRs) is critically important for drug development and clinical safety. Computer-aided prediction of ADRs has attracted increasing attention in recent years, and many computational models have been proposed. However, because of the lack of systematic analysis and comparison of the different computational models, there remain limitations in designing more effective algorithms and selecting more useful features. There is therefore an urgent need to review and analyze previous computation models to obtain general conclusions that can provide useful guidance to construct more effective computational models to predict ADRs. Principal Findings In the current study, the main work is to compare and analyze the performance of existing computational methods to predict ADRs, by implementing and evaluating additional algorithms that have been earlier used for predicting drug targets. Our results indicated that topological and intrinsic features were complementary to an extent and the Jaccard coefficient had an important and general effect on the prediction of drug-ADR associations. By comparing the structure of each algorithm, final formulas of these algorithms were all converted to linear model in form, based on this finding we propose a new algorithm called the general weighted profile method and it yielded the best overall performance among the algorithms investigated in this paper. Conclusion Several meaningful conclusions and useful findings regarding the prediction of ADRs are provided for selecting optimal features and algorithms. PMID:25180585

  20. 21 CFR 310.305 - Records and reports concerning adverse drug experiences on marketed prescription drugs for human...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... one copy of each report to the Central Document Room, Center for Drug Evaluation and Research, Food...” for an adverse drug experience obtained from a postmarketing study (whether or not conducted under an... addresses of individual patients; instead, the manufacturer, packer, and distributor should assign a unique...

  1. 21 CFR 310.305 - Records and reports concerning adverse drug experiences on marketed prescription drugs for human...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... one copy of each report to the Central Document Room, Center for Drug Evaluation and Research, Food...” for an adverse drug experience obtained from a postmarketing study (whether or not conducted under an... addresses of individual patients; instead, the manufacturer, packer, and distributor should assign a unique...

  2. 21 CFR 310.305 - Records and reports concerning adverse drug experiences on marketed prescription drugs for human...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... one copy of each report to the Central Document Room, Center for Drug Evaluation and Research, Food...” for an adverse drug experience obtained from a postmarketing study (whether or not conducted under an... addresses of individual patients; instead, the manufacturer, packer, and distributor should assign a unique...

  3. 21 CFR 310.305 - Records and reports concerning adverse drug experiences on marketed prescription drugs for human...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... one copy of each report to the Central Document Room, Center for Drug Evaluation and Research, Food...” for an adverse drug experience obtained from a postmarketing study (whether or not conducted under an... addresses of individual patients; instead, the manufacturer, packer, and distributor should assign a unique...

  4. Pharmacovigilance and drug safety in Calabria (Italy): 2012 adverse events analysis

    PubMed Central

    Giofrè, Chiara; Scicchitano, Francesca; Palleria, Caterina; Mazzitello, Carmela; Ciriaco, Miriam; Gallelli, Luca; Paletta, Laura; Marrazzo, Giuseppina; Leporini, Christian; Ventrice, Pasquale; Carbone, Claudia; Saullo, Francesca; Rende, Pierandrea; Menniti, Michele; Mumoli, Laura; Chimirri, Serafina; Patanè, Marinella; Esposito, Stefania; Cilurzo, Felisa; Staltari, Orietta; Russo, Emilio; De Sarro, Giovambattista

    2013-01-01

    Introduction: Pharmacovigilance (PV) is designed to monitor drugs continuously after their commercialization, assessing and improving their safety profile. The main objective is to increase the spontaneous reporting of adverse drug reactions (ADRs), in order to have a wide variety of information. The Italian Drug Agency (Agenzia Italiana del Farmaco [AIFA]) is financing several projects to increase reporting. In Calabria, a PV information center has been created in 2010. Materials and Methods: We obtained data using the database of the National Health Information System AIFA relatively to Italy and Calabria in the year 2012. Descriptive statistics were performed to analyze the ADRs. Results: A total number of 461 ADRs have been reported in the year 2012 with an increase of 234% compared with 2011 (138 reports). Hospital doctors are the main source of this reporting (51.62%). Sorafenib (Nexavar®), the combination of amoxicillin/clavulanic acid and ketoprofen represent the drugs most frequently reported causing adverse reactions. Adverse events in female patients (61.83%) were more frequently reported, whereas the age groups “41-65” (39.07%) and “over 65” (27.9%) were the most affected. Conclusions: Calabria has had a positive increase in the number of ADRs reported, although it has not yet reached the gold standard set by World Health Organization (about 600 reports), the data have shown that PV culture is making inroads in this region and that PV projects stimulating and increasing PV knowledge are needed. PMID:24347984

  5. Pharmacovigilance and drug safety in Calabria (Italy): 2012 adverse events analysis.

    PubMed

    Giofrè, Chiara; Scicchitano, Francesca; Palleria, Caterina; Mazzitello, Carmela; Ciriaco, Miriam; Gallelli, Luca; Paletta, Laura; Marrazzo, Giuseppina; Leporini, Christian; Ventrice, Pasquale; Carbone, Claudia; Saullo, Francesca; Rende, Pierandrea; Menniti, Michele; Mumoli, Laura; Chimirri, Serafina; Patanè, Marinella; Esposito, Stefania; Cilurzo, Felisa; Staltari, Orietta; Russo, Emilio; De Sarro, Giovambattista

    2013-12-01

    Pharmacovigilance (PV) is designed to monitor drugs continuously after their commercialization, assessing and improving their safety profile. The main objective is to increase the spontaneous reporting of adverse drug reactions (ADRs), in order to have a wide variety of information. The Italian Drug Agency (Agenzia Italiana del Farmaco [AIFA]) is financing several projects to increase reporting. In Calabria, a PV information center has been created in 2010. We obtained data using the database of the National Health Information System AIFA relatively to Italy and Calabria in the year 2012. Descriptive statistics were performed to analyze the ADRs. A total number of 461 ADRs have been reported in the year 2012 with an increase of 234% compared with 2011 (138 reports). Hospital doctors are the main source of this reporting (51.62%). Sorafenib (Nexavar(®)), the combination of amoxicillin/clavulanic acid and ketoprofen represent the drugs most frequently reported causing adverse reactions. Adverse events in female patients (61.83%) were more frequently reported, whereas the age groups "41-65" (39.07%) and "over 65" (27.9%) were the most affected. Calabria has had a positive increase in the number of ADRs reported, although it has not yet reached the gold standard set by World Health Organization (about 600 reports), the data have shown that PV culture is making inroads in this region and that PV projects stimulating and increasing PV knowledge are needed.

  6. Pharmacogenetics of adverse reactions to antiepileptic drugs.

    PubMed

    Fricke-Galindo, I; Jung-Cook, H; LLerena, A; López-López, M

    2018-04-01

    Adverse drug reactions (ADRs) are a major public health concern and a leading cause of morbidity and mortality in the world. In the case of antiepileptic drugs (AEDs), ADRs constitute a barrier to successful treatment since they decrease treatment adherence and impact patients' quality of life of patients. Pharmacogenetics aims to identify genetic polymorphisms associated with drug safety. This article presents a review of genes coding for drug metabolising enzymes and drug transporters, and HLA system genes that have been linked to AED-induced ADRs. To date, several genetic variations associated with drug safety have been reported: CYP2C9*2 and *3 alleles, which code for enzymes with decreased activity, have been linked to phenytoin (PHT)-induced neurotoxicity; GSTM1 null alleles with hepatotoxicity induced by carbamazepine (CBZ) and valproic acid (VPA); EPHX1 polymorphisms with teratogenesis; ABCC2 genetic variations with CBZ- and VPA-induced neurological ADRs; and HLA alleles (e.g. HLA-B*15:02, -A*31:01, -B*15:11, -C*08:01) with cutaneous ADRs. Published findings show that there are ADRs with a pharmacogenetic basis and a high interethnic variability, which indicates a need for future studies in different populations to gather more useful results for larger number of patients. The search for biomarkers that would allow predicting ADRs to AEDs could improve pharmacotherapy for epilepsy. Copyright © 2014 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. Evaluation of a procedure to assess the adverse effects of illicit drugs.

    PubMed

    van Amsterdam, J G C; Best, W; Opperhuizen, A; de Wolff, F A

    2004-02-01

    The assessment procedure of new synthetic illicit drugs that are not documented in the UN treaty on psychotropic drugs was evaluated using a modified Electre model. Drugs were evaluated by an expert panel via the open Delphi approach, where the written score was discussed on 16 items, covering medical, health, legal, and criminalistic issues of the drugs. After this face-to-face discussion the drugs were scored again. Taking the assessment of ketamine as an example, it appeared that each expert used its own scale to score, and that policymakers do not score deviant from experts trained in the medical-biological field. Of the five drugs evaluated by the panel, p-methoxy-metamphetamine (PMMA), gamma-hydroxybutyric acid (GHB), and 4-methylthio-amphetamine (MTA) were assessed as more adverse than ketamine and psilocine and psilocybine-containing mushrooms. Whereas some experts slightly adjusted during the assessment procedure their opinion on ketamine and PMMA, the opinion on mushrooms was not affected by the discussion held between the two scoring rounds. All experts rank the five drugs in a similar way on the adverse effect scale i.e., concordance scale of the Electre model, indicating unanimity in the expert panel with respect to the risk classification of these abused drugs.

  8. [Trends in drug-induced liver injury based on reports of adverse reactions to PMDA in Japan].

    PubMed

    Sudo, Chie; Maekawa, Keiko; Segawa, Katsunori; Hanatani, Tadaaki; Sai, Kimie; Saito, Yoshiro

    2012-01-01

    Reports on drug-related adverse reactions from manufacturing/distributing pharmaceutical companies or medical institutions/pharmacies are regulated under the Pharmaceutical Affairs Law of Japan, and this system is important for post-marketing safety measures. Although association between the medicine and the adverse event has not been clearly evaluated, and an incidence may be redundantly reported, this information would be useful to roughly grasp the current status of drug-related adverse reactions. In the present study, we analyzed the incidence of drug-induced liver injury by screening the open-source data publicized by the homepage of Pharmaceutical and Medical Devices Agency from 2005 to 2011 fiscal years. Major drug-classes suspected to cause general drug-induced liver injury were antineoplastics, anti-inflammatory agents/common cold drugs, chemotherapeutics including antituberculous drugs, antidiabetics, antiulcers and antiepileptics. In addition, reported cases for fulminant hepatitis were also summarized. We found that antituberculous isoniazid and antineoplastic tegafur-uracil were the top two suspected drugs. These results might deepen understanding of current situations for the drug-induced liver injury in Japan.

  9. Development of a database and processing method for detecting hematotoxicity adverse drug events.

    PubMed

    Shimai, Yoshie; Takeda, Toshihiro; Manabe, Shirou; Teramoto, Kei; Mihara, Naoki; Matsumura, Yasushi

    2015-01-01

    Adverse events are detected by monitoring the patient's status, including blood test results. However, it is difficult to identify all adverse events based on recognition by individual doctors. We developed a system that can be used to detect hematotoxicity adverse events according to blood test results recorded in an electronic medical record system. The blood test results were graded based on Common Terminology Criteria for Adverse Events (CTCAE) and changes in the blood test results (Up, Down, Flat) were assessed according to the variation in the grade. The changes in the blood test and injection data were stored in a database. By comparing the date of injection and start and end dates of the change in the blood test results, adverse events related to a designated drug were detected. Using this method, we searched for the occurrence of serious adverse events (CTCAE Grades 3 or 4) concerning WBC, ALT and creatinine related to paclitaxel at Osaka University Hospital. The rate of occurrence of a decreased WBC count, increased ALT level and increased creatinine level was 36.0%, 0.6% and 0.4%, respectively. This method is useful for detecting and estimating the rate of occurrence of hematotoxicity adverse drug events.

  10. Physician access to drug profiles to reduce adverse reactions

    NASA Astrophysics Data System (ADS)

    Yasnoff, William A.; Tomkins, Edward L.; Dunn, Louise M.

    1995-10-01

    Adverse drug reactions (ADRs) are a major source of preventable morbidity and mortality, especially among the elderly, who use more drugs and are more sensitive to them. The insurance industry has recently addressed this problem through the implementation of drug interaction alerts to pharmacists in conjunction with immediate online claims adjudication for almost 60% of prescriptions (expected to reach 90% within 5 years). These alerts are based on stored patient drug profiles maintained by pharmacy benefit managers (PBMs) which are updated whenever prescriptions are filled. While these alerts are very helpful, the pharmacist does not prescribe, resulting in time-consuming and costly delays to contact the physician and remedy potential interactions. We have developed and demonstrated the feasibility of the PINPOINT (Pharmaceutical Information Network for prevention of interactions) system for making the drug profile and interaction information easily available to the physician before the prescription is written. We plan to test the cost-effectiveness of the system in a prospective controlled clinical trial.

  11. Impact of medication reconciliation and review and counselling, on adverse drug events and healthcare resource use.

    PubMed

    Al-Hashar, Amna; Al-Zakwani, Ibrahim; Eriksson, Tommy; Sarakbi, Alaa; Al-Zadjali, Badriya; Al Mubaihsi, Saif; Al Zaabi, Mohammed

    2018-05-12

    Background Adverse drug events from preventable medication errors can result in patient morbidity and mortality, and in cost to the healthcare system. Medication reconciliation can improve communication and reduce medication errors at transitions in care. Objective Evaluate the impact of medication reconciliation and counselling intervention delivered by a pharmacist for medical patients on clinical outcomes 30 days after discharge. Setting Sultan Qaboos University Hospital, Muscat, Oman. Methods A randomized controlled study comparing standard care with an intervention delivered by a pharmacist and comprising medication reconciliation on admission and discharge, a medication review, a bedside medication counselling, and a take-home medication list. Medication discrepancies during hospitalization were identified and reconciled. Clinical outcomes were evaluated by reviewing electronic health records and telephone interviews. Main outcome measures Rates of preventable adverse drug events as primary outcome and healthcare resource utilization as secondary outcome at 30 days post discharge. Results A total of 587 patients were recruited (56 ± 17 years, 57% female); 286 randomized to intervention; 301 in the standard care group. In intervention arm, 74 (26%) patients had at least one discrepancy on admission and 100 (35%) on discharge. Rates of preventable adverse drug events were significantly lower in intervention arm compared to standard care arm (9.1 vs. 16%, p = 0.009). No significant difference was found in healthcare resource use. Conclusion The implementation of an intervention comprising medication reconciliation and counselling by a pharmacist has significantly reduced the rate of preventable ADEs 30 days post discharge, compared to the standard care. The effect of the intervention on healthcare resource use was insignificant. Pharmacists should be included in decentralized, patient-centred roles. The findings should be interpreted in the context

  12. Imputation of adverse drug reactions: Causality assessment in hospitals

    PubMed Central

    Mastroianni, Patricia de Carvalho

    2017-01-01

    Background & objectives Different algorithms have been developed to standardize the causality assessment of adverse drug reactions (ADR). Although most share common characteristics, the results of the causality assessment are variable depending on the algorithm used. Therefore, using 10 different algorithms, the study aimed to compare inter-rater and multi-rater agreement for ADR causality assessment and identify the most consistent to hospitals. Methods Using ten causality algorithms, four judges independently assessed the first 44 cases of ADRs reported during the first year of implementation of a risk management service in a medium complexity hospital in the state of Sao Paulo (Brazil). Owing to variations in the terminology used for causality, the equivalent imputation terms were grouped into four categories: definite, probable, possible and unlikely. Inter-rater and multi-rater agreement analysis was performed by calculating the Cohen´s and Light´s kappa coefficients, respectively. Results None of the algorithms showed 100% reproducibility in the causal imputation. Fair inter-rater and multi-rater agreement was found. Emanuele (1984) and WHO-UMC (2010) algorithms showed a fair rate of agreement between the judges (k = 0.36). Interpretation & conclusions Although the ADR causality assessment algorithms were poorly reproducible, our data suggest that WHO-UMC algorithm is the most consistent for imputation in hospitals, since it allows evaluating the quality of the report. However, to improve the ability of assessing the causality using algorithms, it is necessary to include criteria for the evaluation of drug-related problems, which may be related to confounding variables that underestimate the causal association. PMID:28166274

  13. Drug Adverse Event Detection in Health Plan Data Using the Gamma Poisson Shrinker and Comparison to the Tree-based Scan Statistic

    PubMed Central

    Brown, Jeffrey S.; Petronis, Kenneth R.; Bate, Andrew; Zhang, Fang; Dashevsky, Inna; Kulldorff, Martin; Avery, Taliser R.; Davis, Robert L.; Chan, K. Arnold; Andrade, Susan E.; Boudreau, Denise; Gunter, Margaret J.; Herrinton, Lisa; Pawloski, Pamala A.; Raebel, Marsha A.; Roblin, Douglas; Smith, David; Reynolds, Robert

    2013-01-01

    Background: Drug adverse event (AE) signal detection using the Gamma Poisson Shrinker (GPS) is commonly applied in spontaneous reporting. AE signal detection using large observational health plan databases can expand medication safety surveillance. Methods: Using data from nine health plans, we conducted a pilot study to evaluate the implementation and findings of the GPS approach for two antifungal drugs, terbinafine and itraconazole, and two diabetes drugs, pioglitazone and rosiglitazone. We evaluated 1676 diagnosis codes grouped into 183 different clinical concepts and four levels of granularity. Several signaling thresholds were assessed. GPS results were compared to findings from a companion study using the identical analytic dataset but an alternative statistical method—the tree-based scan statistic (TreeScan). Results: We identified 71 statistical signals across two signaling thresholds and two methods, including closely-related signals of overlapping diagnosis definitions. Initial review found that most signals represented known adverse drug reactions or confounding. About 31% of signals met the highest signaling threshold. Conclusions: The GPS method was successfully applied to observational health plan data in a distributed data environment as a drug safety data mining method. There was substantial concordance between the GPS and TreeScan approaches. Key method implementation decisions relate to defining exposures and outcomes and informed choice of signaling thresholds. PMID:24300404

  14. Patient knowledge on reporting adverse drug reactions in Poland

    PubMed Central

    Staniszewska, Anna; Dąbrowska-Bender, Marta; Olejniczak, Dominik; Duda-Zalewska, Aneta; Bujalska-Zadrożny, Magdalena

    2017-01-01

    Aim The aim of the study was to assess patient knowledge on reporting of adverse drug reactions. Materials and methods A prospective study was conducted among 200 patients. The study was based on an original survey composed of 15 single- and multiple-choice questions. The study involved individuals who have experienced adverse reactions as well as individuals who have never experienced any adverse reactions; people over the age of 18; literate; residing in Mazowieckie Voivodeship, who have not been diagnosed with any disease that could compromise their logical thinking skills. Results The respondents who lived in the city had a greater knowledge compared to the respondents who lived in the countryside (Pearson’s χ2=47.70, P=0.0013). The respondents who lived in the city were also more statistically likely to provide a correct answer to the question about the type of adverse reactions to be reported (Pearson’s χ2=50.66, P=0.012). Statistically significant associations were found between the place of residence of the respondents and the correct answer to the question about the data that must be included in the report on adverse reactions (Pearson’s χ2=11.7, P<0.0001). PMID:28096661

  15. Enhancing communication about paediatric medicines: lessons from a qualitative study of parents' experiences of their child's suspected adverse drug reaction.

    PubMed

    Arnott, Janine; Hesselgreaves, Hannah; Nunn, Anthony J; Peak, Matthew; Pirmohamed, Munir; Smyth, Rosalind L; Turner, Mark A; Young, Bridget

    2012-01-01

    There is little research on parents' experiences of suspected adverse drug reactions in their children and hence little evidence to guide clinicians when communicating with families about problems associated with medicines. To identify any unmet information and communication needs described by parents whose child had a suspected adverse drug reaction. Semi-structured qualitative interviews with parents of 44 children who had a suspected adverse drug reaction identified on hospital admission, during in-patient treatment or reported by parents using the Yellow Card Scheme (the UK system for collecting spontaneous reports of adverse drug reactions). Interviews were conducted face-to-face or by telephone; most interviews were audiorecorded and transcribed. Analysis was informed by the principles of the constant comparative method. Many parents described being dissatisfied with how clinicians communicated about adverse drug reactions and unclear about the implications for their child's future use of medicines. A few parents felt that clinicians had abandoned their child and reported refusing the use of further medicines because they feared a repeated adverse drug reaction. The accounts of parents of children with cancer were different. They emphasised their confidence in clinicians' management of adverse drug reactions and described how clinicians prospectively explained the risks associated with medicines. Parents linked symptoms to medicines in ways that resembled the established reasoning that clinicians use to evaluate the possibility that a medicine has caused an adverse drug reaction. Clinicians' communication about adverse drug reactions was poor from the perspective of parents, indicating that improvements are needed. The accounts of parents of children with cancer indicate that prospective explanation about adverse drug reactions at the time of prescription can be effective. Convergence between parents and clinicians in their reasoning for linking children

  16. Adverse drug reaction reports for cardiometabolic drugs from sub-Saharan Africa: a study in VigiBase.

    PubMed

    Berhe, Derbew Fikadu; Juhlin, Kristina; Star, Kristina; Beyene, Kidanemariam G M; Dheda, Mukesh; Haaijer-Ruskamp, Flora M; Taxis, Katja; Mol, Peter G M

    2015-06-01

    Identifying key features in individual case safety reports (ICSR) of suspected adverse drug reactions (ADRs) with cardiometabolic drugs from sub-Saharan Africa (SSA) compared with reports from the rest of the world (RoW). Reports on suspected ADRs of cardiometabolic drugs (ATC: A10[antidiabetic], B01[antithrombotics] and C[cardiovascular]) were extracted from WHO Global database, VigiBase(®) (1992-2013). We used vigiPoint, a logarithmic odds ratios (log2 OR)-based method to study disproportional reporting between SSA and RoW. Case-defining features were considered relevant if the lower limit of the 99% CI > 0.5. In SSA, 3773 (9%) of reported ADRs were for cardiometabolic drugs, in RoW for 18%. Of these, 79% originated from South Africa and 81% were received after 2007. Most reports were for drugs acting on the renin-angiotensin system (36% SSA & 14% RoW). Compared with RoW, reports were more often sent for patients 18-44 years old (log2 OR 0.95 [99 CI 0.80; 1.09]) or with non-fatal outcome (log2 OR 1.16 [99 CI 1.10; 1.22]). Eight ADRs (cough, angioedema, lip swelling, face oedema, swollen tongue, throat irritation, drug ineffective and blood glucose abnormal) and seven drugs (enalapril, rosuvastatin, perindopril, vildagliptin, insulin glulisine, nifedipine and insulin lispro) were disproportionally more reported in SSA than in the RoW. 'In recent years, the number of adverse drug reactions (ADRs) reported in Sub-Saharan Africa (SSA) has sharply increased. The data showed the well-known population-based differential ADR profile of ACE inhibitors in the SSA population.' © 2015 John Wiley & Sons Ltd.

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

    PubMed

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

    2009-01-01

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

  18. Drugp-Induced Rhabdomyolysis Atlas (DIRA) for idiosyncratic adverse drug reaction management.

    PubMed

    Wen, Zhining; Liang, Yu; Hao, Yingyi; Delavan, Brian; Huang, Ruili; Mikailov, Mike; Tong, Weida; Li, Menglong; Liu, Zhichao

    2018-06-11

    Drug-induced rhabdomyolysis (DIR) is an idiosyncratic and fatal adverse drug reaction (ADR) characterized in severe muscle injuries accompanied by multiple-organ failure. Limited knowledge regarding the pathophysiology of rhabdomyolysis is the main obstacle to developing early biomarkers and prevention strategies. Given the lack of a centralized data resource to curate, organize, and standardize widespread DIR information, here we present a Drug-Induced Rhabdomyolysis Atlas (DIRA) that provides DIR-related information, including: a classification scheme for DIR based on drug labeling information; postmarketing surveillance data of DIR; and DIR drug property information. To elucidate the utility of DIRA, we used precision dosing, concomitant use of DIR drugs, and predictive modeling development to exemplify strategies for idiosyncratic ADR (IADR) management. Published by Elsevier Ltd.

  19. [Analysis of rational clinical uses of traditional Chinese medicine injections and factors influencing adverse drug reactions].

    PubMed

    Sun, Shi-Guang; Li, Zi-Feng; Xie, Yan-Ming; Liu, Jian; Lu, Yan; Song, Yi-Fei; Han, Ying-Hua; Liu, Li-Da; Peng, Ting-Ting

    2013-09-01

    To rationalize the clinical use and safety are some of the key issues in the surveillance of traditional Chinese medicine injections (TCMIs). In this 2011 study, 240 medical records of patients who had been discharged following treatment with TCMIs between 1 and 12 month previously were randomly selected from hospital records. Consistency between clinical use and the description of TCMIs was evaluated. Research on drug use and adverse drug reactions/events using logistic regression analysis was carried out. There was poor consistency between clinical use and best practice advised in manuals on TCMIs. Over-dosage and overly concentrated administration of TCMIs occurred, with the outcome of modifying properties of the blood. Logistic regression analysis showed that, drug concentration was a valid predictor for both adverse drug reactions/events and benefits associated with TCMIs. Surveillance of rational clinical use and safety of TCMIs finds that clinical use should be consistent with technical drug manual specifications, and drug use should draw on multi-layered logistic regression analysis research to help avoid adverse drug reactions/events.

  20. [Designing a tool to describe drug interactions and adverse events for learning and clinical routine].

    PubMed

    Auzéric, M; Bellemère, J; Conort, O; Roubille, R; Allenet, B; Bedouch, P; Rose, F-X; Juste, M; Charpiat, B

    2009-11-01

    Pharmacists play an important role in prescription analysis. They are involved in therapeutic drug monitoring, particularly for drugs with a narrow therapeutic index, prevention and management of drug interactions, and may be called in to identify side effects and adverse events related to drug therapy. For the polymedicated patient, the medical file, the list of prescribed drugs and the history of their administration may be insufficient to adequately assign the responsibility of a given adverse effect to one or more drugs. Graphical representations can sometimes be useful to describe and clarify a sequence of events. In addition, as part of their academic course, students have many occasions to hear about "side effects" and "drug interactions". However, in the academic setting, there are few opportunities to observe the evolution and the consequences of these events. In the course of their hospital training, these students are required to perform patient follow-up for pharmacotherapeutic or educational purposes and to comment case reports to physicians. The aim of this paper is to present a tool facilitating the graphic display of drug interaction consequences and side effects. This tool can be a useful aid for causality assessment. It structures the students' training course and helps them better understand the commentaries pharmacists provide for physicians. Further development of this tool should contribute to the prevention of adverse drug events.

  1. 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.

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

    PubMed

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

    2007-06-01

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

  3. A prospective study of adverse drug reactions in hospitalized children

    PubMed Central

    Martínez-Mir, Inocencia; García-López, Mercedes; Palop, Vicente; Ferrer, José M; Rubio, Elena; Morales-Olivas, Francisco J

    1999-01-01

    Aims There are few publications of adverse drug reactions (ADRs) among paediatric patients, though ADR incidence is usually stated to be higher during the first year of life and in male patients. We have carried out a prospective study to assess the extent, pattern and profile risk for ADRs in hospitalized patients between 1 and 24 months of age. Methods An intensive events monitoring scheme was used. A total of 512 successive admissions to two medical paediatric wards (47 beds) were analysed. The hospital records were screened daily during two periods (summer, 105 days and winter, 99 days), and adverse clinical events observed were recorded. Results A total of 282 events were detected; of these, 112 were considered to be manifestations of ADRs. The cumulative incidence was 16.6%, no differences being observed between periods. Although there were no differences between patients under and over 12 months of age, risk was found to be significantly higher among girls compared with boys (RR = 1.66, 95% CI 1.03–2.52). The gastro-intestinal system was most frequently affected. The therapeutic group most commonly implicated was anti-infective drugs and vaccines (41.5%). The ADRs were mild or moderate in over 90% of cases. A consistent relationship was noted between the number of drugs administered and the incidence of ADRs. Conclusions Hospitalized patients exhibited an ADR risk profile that included female sex and the number of drugs administered. No particular age predisposition was observed. The most commonly prescribed drugs are those most often implicated in ADRs in paediatric patients. PMID:10383547

  4. ICD-10 codes used to identify adverse drug events in administrative data: a systematic review.

    PubMed

    Hohl, Corinne M; Karpov, Andrei; Reddekopp, Lisa; Doyle-Waters, Mimi; Stausberg, Jürgen

    2014-01-01

    Adverse drug events, the unintended and harmful effects of medications, are important outcome measures in health services research. Yet no universally accepted set of International Classification of Diseases (ICD) revision 10 codes or coding algorithms exists to ensure their consistent identification in administrative data. Our objective was to synthesize a comprehensive set of ICD-10 codes used to identify adverse drug events. We developed a systematic search strategy and applied it to five electronic reference databases. We searched relevant medical journals, conference proceedings, electronic grey literature and bibliographies of relevant studies, and contacted content experts for unpublished studies. One author reviewed the titles and abstracts for inclusion and exclusion criteria. Two authors reviewed eligible full-text articles and abstracted data in duplicate. Data were synthesized in a qualitative manner. Of 4241 titles identified, 41 were included. We found a total of 827 ICD-10 codes that have been used in the medical literature to identify adverse drug events. The median number of codes used to search for adverse drug events was 190 (IQR 156-289) with a large degree of variability between studies in the numbers and types of codes used. Authors commonly used external injury (Y40.0-59.9) and disease manifestation codes. Only two papers reported on the sensitivity of their code set. Substantial variability exists in the methods used to identify adverse drug events in administrative data. Our work may serve as a point of reference for future research and consensus building in this area.

  5. A Pharmacovigilance Approach for Post-Marketing in Japan Using the Japanese Adverse Drug Event Report (JADER) Database and Association Analysis.

    PubMed

    Fujiwara, Masakazu; Kawasaki, Yohei; Yamada, Hiroshi

    2016-01-01

    Rapid dissemination of information regarding adverse drug reactions is a key aspect for improving pharmacovigilance. There is a possibility that unknown adverse drug reactions will become apparent through post-marketing administration. Currently, although there have been studies evaluating the relationships between a drug and adverse drug reactions using the JADER database which collects reported spontaneous adverse drug reactions, an efficient approach to assess the association between adverse drug reactions of drugs with the same indications as well as the influence of demographics (e.g. gender) has not been proposed. We utilized the REAC and DEMO tables from the May 2015 version of JADER for patients taking antidepressant drugs (SSRI, SNRI, and NaSSA). We evaluated the associations using association analyses with an apriori algorithm. Support, confidence, lift, and conviction were used as indicators for associations. The highest score in adverse drug reactions for SSRI was obtained for "aspartate aminotransferase increased", "alanine aminotransferase increased", with values of 0.0059, 0.93, 135.5, and 13.9 for support, confidence, lift and conviction, respectively. For SNRI, "international normalized ratio increased", "drug interaction" were observed with 0.0064, 1.00, 71.9, and NA. For NaSSA, "anxiety", "irritability" were observed with 0.0058, 0.80, 49.9, and 4.9. For female taking SSRI, the highest support scores were observed in "twenties", "suicide attempt", whereas "thirties", "neuroleptic malignant syndrome" were observed for male. Second, for SNRI, "eighties", "inappropriate antidiuretic hormone secretion" were observed for female, whereas "interstitial lung disease" and "hepatitis fulminant" were for male. Finally, for NaSSA, "suicidal ideation" was for female, and "rhabdomyolysis" was for male. Different combinations of adverse drug reactions were noted between the antidepressants. In addition, the reported adverse drug reactions differed by gender

  6. Vertigo/dizziness as a Drugs' adverse reaction.

    PubMed

    Chimirri, Serafina; Aiello, Rossana; Mazzitello, Carmela; Mumoli, Laura; Palleria, Caterina; Altomonte, Mariolina; Citraro, Rita; De Sarro, Giovambattista

    2013-12-01

    Vertigo, dizziness, and nausea encompass a spectrum of balance-related symptoms caused by a variety of etiologies. Balance is affected by many systems: Proprioceptive pathways and visual, cerebellar, vestibulocochlear, and vascular / vasovagal systems. Vertigo is a subtype of dizziness, in which a subject, as a result to a dysfunction of the vestibular system, improperly experiments the perception of motion. The most useful clinical subdivision is to categorize vertigo into true vertigo and pseudovertigo, whereas from a pathophysiological point of view, vertigo can be classified into central, peripheral, and psychogenic. It is not easy to identify the cause of vertigo since the patients often are not able to precisely describe their symptoms. An impressive list of drugs may cause vertigo or dizziness. The aim of the present study was to analyze the data extracted from the reporting cards of the ADRs (adverse drug reactions), received at our Pharmacovigilance Regional Center (Calabria, Italy) in 2012. In particular, the data concerning the occurrence of vertigo and dizziness, after taking certain classes of drugs, have been considered. Our results show that, among the side-effects of different classes of drugs such as anti-convulsants, anti-hypertensives, antibiotics, anti-depressants, anti-psychotics, and anti-inflammatory, also vertigo or dizziness are included. Spontaneous reports of vertigo or dizziness, as side-effect of certain drugs, received at our Pharmacovigilance Center, represented the 5% of all reports in 2012. Considering the high incidence of such an ADR for several drugs' classes, it can be speculated that under-reporting also affect vertigo and dizziness. Despite the fact that these ADRs might not represent a direct threaten for life, indirectly they can cause secondary damage to patients such as falls, fractures etc. Balance should be accurately monitored during drug use and particularly in fragile patients.

  7. [Nursing role in reporting adverse drug reactions].

    PubMed

    Zurita-Garaicoechea, Ana; Reis-Carvalho, Joana; Ripa-Aisa, Irantzu; Jiménez-Mendoza, Ana; Díaz-Balén, Almudena; Oroviogoicoechea, Cristina

    2015-01-01

    The spontaneous report system, in which suspected adverse drug reaction (ADR) are reported by healthcare workers, is currently one of the primary methods to prevent and discover new and serious ADR to marketed medicinal products. The collaboration of nursing professionals with this task makes it possible to improve patient safety and to reduce ADR costs. Although a total of 781 cases of ADR cases were reported in Navarra in 2011, only 7.33% were reported by nurses. The objectives werw to determine the factors that influence nurses in reporting of ADR, and second, to devise strategies which help to increase reporting. A bibliographic search for articles that included the words: reacciones adversas medicamentosas (adverse drug reactions), notificación (reporting) and enfermería (nursing) was conducted using the PubMed and Cinhal databases. A total of 107 articles were retrieved, of which 27 were selected according to inclusion and exclusion criteria. The conclusion learned by reading and analyzing the selected articles was that the factors that affect the notification depend on the attitude of the notifier, as well as personal and professional factors. The main strategies to encourage notification are education and training, motivation, and the availability of facilitating tools. The main factors that have an influence on under-notification are the lack of knowledge and motivation among professionals. To solve the problem of under-notification, the main actions and strategies to undertake are education, motivation and persistence. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

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

    PubMed

    Legehar, Ashenafi; Xhaard, Henri; Ghemtio, Leo

    2016-01-01

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

  9. Cutaneous Adverse Drug Reactions in Dogs Treated with Antiepileptic Drugs

    PubMed Central

    Koch, Tina; Mueller, Ralf S.; Dobenecker, Britta; Fischer, Andrea

    2016-01-01

    Epilepsy is one of the most common neurologic disorders in dogs and life-long treatment with antiepileptic drugs (AED) is frequently required. Adverse events of AED targeting the skin are only rarely reported in veterinary medicine and the true incidence and spectrum of cutaneous reactions in epileptic dogs remains unknown. In this study, we hypothesized that cutaneous reactions commonly occur in epileptic dogs and are related to AED treatment. A retrospective case review of 185 dogs treated for epilepsy identified 20.0% with simultaneous appearance of dermatologic signs. In a subsequent prospective case investigation (n = 137), we identified newly appearing or distinct worsening of skin lesions following initiation of AED therapy in 10.9% of dogs treated for epilepsy (95% CI 6.8–17.7%). Cutaneous lesions were classified as probably drug-induced in 40.0% of these cases. Patch testing and intradermal testing were further investigated as potential diagnostic methods to confirm AED hypersensitivity. They were of high specificity but sensitivity and positive predictive value appeared inappropriate to recommend their routine use in clinical practice. PMID:27148543

  10. Trends of adverse drug reactions related-hospitalizations in Spain (2001-2006)

    PubMed Central

    2010-01-01

    Background Adverse drug reactions (ADR) are a substantial cause of hospital admissions. We conducted a nationwide study to estimate the burden of hospital admissions for ADRs in Spain during a six-year period (2001-2006) along with the associated total health cost. Methods Data were obtained from the national surveillance system for hospital data (Minimum Basic Data Set) maintained by the Ministry of Health and Consumer Affairs, and covering more than 95% of Spanish hospitals. From these admissions we selected all hospitalization that were code as drug-related (ICD-9-CM codes E), but intended forms of overdoses, errors in administration and therapeutics failure were excluded. The average number of hospitalizations per year, annual incidence of hospital admissions, average length of stay in the hospital, and case-fatality rate, were calculated. Results During the 2001-2006 periods, the total number of hospitalized patients with ADR diagnosis was 350,835 subjects, 1.69% of all acute hospital admissions in Spain. The estimated incidence of admissions due to ADR decreased during the period 2001-2006 (p < 0.05). More than five percent of patients (n = 19,734) died during an ADR-related hospitalization. The drugs most commonly associated with ADR-related hospitalization were antineoplastic and immunosuppressive drugs (n = 75,760), adrenal cortical steroids (n = 47,539), anticoagulants (n = 26,546) and antibiotics (n = 22,144). The costs generated by patients in our study increased by 19.05% between 2001 and 2006. Conclusions Approximately 1.69% of all acute hospital admissions were associated with ADRs. The rates were much higher for elderly patients. The total cost of ADR-related hospitalization to the Spanish health system is high and has increased between 2001 and 2006. ADRs are an important cause of admission, resulting in considerable use of national health system beds and a significant number of deaths. PMID:20942906

  11. 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

  12. [Current movements of four serious adverse events induced by medicinal drugs based on spontaneous reports in Japan].

    PubMed

    Sudo, Chie; Azuma, Yu-ichiro; Maekawa, Keiko; Kaniwa, Nahoko; Sai, Kimie; Saito, Yoshiro

    2011-01-01

    Spontaneous reports on suspected serious adverse events caused by medicines from manufacturing/distributing pharmaceutical companies or medical institutions/pharmacies are regulated by the Pharmaceutical Affairs Law of Japan, and this system is important for post-marketing safety features. Although causal relationship between the medicine and the adverse event is not evaluated, and one incidence may be redundantly reported, this information would be useful to roughly grasp the current movements of drug-related serious adverse events, We searched open-source data of the spontaneous reports publicized by Pharmaceutical and Medical Devices Agency for 4 serious adverse events (interstitial lung disease, rhabdomyolysis, anaphylaxis, and Stevens-Johnson syndrome/toxic epidermal necrolysis) from 2004 to 2010 fiscal year (for 2010, from April 1 st to January 31th). Major drug-classes suspected to the adverse events were antineoplastics for interstitial lung disease, hyperlipidemia agents and psychotropics for rhabdomyolysis, antibiotics/chemotherapeutics, antineoplastics and intracorporeal diagnostic agents for anaphylaxis (anaphylactic shock, anaphylactic reactions, anaphylactoid shock and anaphylactoid reactions), and antibiotics/chemotherapeutics, antipyretics and analgesics, anti-inflammatory agents/common cold drugs, and antiepileptics for Stevens-Johnson syndrome/toxic epidermal necrolysis. These results would help understanding of current situations of the 4 drug-related serious adverse events in Japan.

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

    PubMed

    Meirinho, Sara; Relvas, Ricardo; Alves, Gilberto

    2018-02-12

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

  14. Comparison of brand versus generic antiepileptic drug adverse event reporting rates in the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).

    PubMed

    Rahman, Md Motiur; Alatawi, Yasser; Cheng, Ning; Qian, Jingjing; Plotkina, Annya V; Peissig, Peggy L; Berg, Richard L; Page, David; Hansen, Richard A

    2017-09-01

    Despite the cost saving role of generic anti-epileptic drugs (AEDs), debate exists as to whether generic substitution of branded AEDs may lead to therapeutic failure and increased toxicity. This study compared adverse event (AE) reporting rates for brand vs. authorized generic (AG) vs. generic AEDs. Since AGs are pharmaceutically identical to brand but perceived as generics, the generic vs. AG comparison minimized potential bias against generics. Events reported to the U.S. Food and Drug Administration Adverse Event Reporting System between January 2004 to March 2015 with lamotrigine, carbamazepine, and oxcarbazepine listed as primary or secondary suspect were classified as brand, generic, or AG based on the manufacturer. Disproportionality analyses using the reporting odds ratio (ROR) assessed the relative rate of reporting of labeled AEs compared to reporting these events with all other drugs. The Breslow-Day statistic compared RORs across brand, AG, and other generics using a Bonferroni-corrected P<0.01. A total of 27,150 events with lamotrigine, 13,950 events with carbamazepine, and 5077 events with oxcarbazepine were reported, with generics accounting for 27%, 41%, and 32% of reports, respectively. Although RORs for the majority of known AEs were different between brand and generics for all three drugs of interest (Breslow-Day P<0.001), RORs generally were similar for AG and generic comparisons. Generic lamotrigine and carbamazepine were more commonly involved in reports of suicide or suicidal ideation compared with the respective AGs based on a multiple comparison-adjusted P<0.01. Similar AED reporting rates were observed for the AG and generic comparisons for most outcomes and drugs, suggesting that brands and generics have similar reporting rates after accounting for generic perception biases. Disproportional suicide reporting was observed for generics compared with AGs and brand, although this finding needs further study. Copyright © 2017 Elsevier B

  15. Effect of database profile variation on drug safety assessment: an analysis of spontaneous adverse event reports of Japanese cases

    PubMed Central

    Nomura, Kaori; Takahashi, Kunihiko; Hinomura, Yasushi; Kawaguchi, Genta; Matsushita, Yasuyuki; Marui, Hiroko; Anzai, Tatsuhiko; Hashiguchi, Masayuki; Mochizuki, Mayumi

    2015-01-01

    Background The use of a statistical approach to analyze cumulative adverse event (AE) reports has been encouraged by regulatory authorities. However, data variations affect statistical analyses (eg, signal detection). Further, differences in regulations, social issues, and health care systems can cause variations in AE data. The present study examined similarities and differences between two publicly available databases, ie, the Japanese Adverse Drug Event Report (JADER) database and the US Food and Drug Administration Adverse Event Reporting System (FAERS), and how they affect signal detection. Methods Two AE data sources from 2010 were examined, ie, JADER cases (JP) and Japanese cases extracted from the FAERS (FAERS-JP). Three methods for signals of disproportionate reporting, ie, the reporting odds ratio, Bayesian confidence propagation neural network, and Gamma Poisson Shrinker (GPS), were used on drug-event combinations for three substances frequently recorded in both systems. Results The two databases showed similar elements of AE reports, but no option was provided for a shareable case identifier. The average number of AEs per case was 1.6±1.3 (maximum 37) in the JP and 3.3±3.5 (maximum 62) in the FAERS-JP. Between 5% and 57% of all AEs were signaled by three quantitative methods for etanercept, infliximab, and paroxetine. Signals identified by GPS for the JP and FAERS-JP, as referenced by Japanese labeling, showed higher positive sensitivity than was expected. Conclusion The FAERS-JP was different from the JADER. Signals derived from both datasets identified different results, but shared certain signals. Discrepancies in type of AEs, drugs reported, and average number of AEs per case were potential contributing factors. This study will help those concerned with pharmacovigilance better understand the use and pitfalls of using spontaneous AE data. PMID:26109846

  16. Anaphylaxis following intravenous ranitidine: a rare adverse reaction of a common drug.

    PubMed

    Chopra, Deepti; Arora, Pooja; Khan, Shamimullah; Dwivedi, Shridhar

    2014-01-01

    Ranitidine hydrochloride is a widely used drug that is generally well-tolerated. Anaphylaxis is rarely observed with ranitidine. We report a case who developed severe anaphylaxis following single dose of intravenous ranitidine. The article highlights the importance of recognition of this serious adverse event and re-emphasizes the need for cautious use of drugs, especially in those with known history of allergy.

  17. 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.

  18. Predicting and detecting adverse drug reactions in old age: challenges and opportunities.

    PubMed

    Mangoni, Arduino A

    2012-05-01

    Increased, often inappropriate, drug exposure, pharmacokinetic and pharmacodynamic changes, reduced homeostatic reserve and frailty increase the risk of adverse drug reactions (ADRs) in the older population, thereby imposing a significant public health burden. Predicting and diagnosing ADRs in old age presents significant challenges for the clinician, even when specific risk scoring systems are available. The picture is further compounded by the potential adverse impact of several drugs on more 'global' health indicators, for example, physical function and independence, and the fragmentation of care (e.g., increased number of treating doctors and care transitions) experienced by older patients during their clinical journey. The current knowledge of drug safety in old age is also curtailed by the lack of efficacy and safety data from pre-marketing studies. Moreover, little consideration is given to individual patients' experiences and reporting of specific ADRs, particularly in the presence of cognitive impairment. Pending additional data on these issues, the close review and monitoring of individual patients' drug prescribing, clinical status and biochemical parameters remain essential to predict and detect ADRs in old age. Recently developed strategies, for example, medication reconciliation and trigger tool methodology, have the potential for ADRs risk mitigation in this population. However, more information is required on their efficacy and applicability in different healthcare settings.

  19. [Drug surveillance and adverse reactions to drugs. The literature and importance of historical data].

    PubMed

    Mariani, L; Minora, T; Ventresca, G P

    1996-12-01

    The authors highlight the essential role of pharmacovigilance and the need for a simple, efficient and low-cost system of adverse reaction (AR) reporting which could cover the whole population and all marketed drugs, and suggest that the only one presently viable is based on spontaneous reporting. To support their proposal the authors provide a definition of AR and of the different monitoring system, and list as many drugs as possible to find in the literature that have been associated with a specific AR, together with the active molecule, the therapeutic indication, the features of the AR and the regulatory actions (withdrawal from the market, restriction of use). Moreover, by describing the "history" behind some of these drugs the authors highlight the contribution that pharmacovigilance and spontaneous reporting have had to the development of regulations for approval and marketing of new drugs. It is also highlighted how some of these unexpected events (thalidomide, DES) have had a significant and important contribution to pharmacological and toxicological knowledge.

  20. [Adverse reactions and other drug-related problems in an emergency service department].

    PubMed

    Güemes Artiles, M; Sanz Alvarez, E; Garcia Sánchez-Colomer, M

    1999-01-01

    Adverse Drug Reactions (ADR) and Drug-Related Problems (DRP's) are a frequency cause of hospital emergency room visits and require better assessment. An analysis was made of 1097 consecutive admission to the emergency room at the Nuestra Senora de los Volcanes, Hospital (currently the General Hospital of Lanzarote) in Arrecife de Lanzarote (Canary Islands) over a three-month period in order to detect any possible DAR or any other drug-related problems. Nineteen (19) of the 1097 admissions were due to Adverse Drug Reactions (ADR) (1.73%; 95% IC:0.96%-2.5%). Some of the most outstanding of the other "Drug-Related Problems" (DRP's) were medication overdose, which was diagnosed in 5 (0.45%) of the patients; the worsening of the symptoms due to ceasing to take the medication was involved in 8 (0.72%), and incorrect treatments which involved medical care at the emergency room totaled 11 (1.0%). The number of drug-related problems (DRP's) in the sample totaled 43 (3.9%). The drug-related problems (DRP's) led to hospitalization in 1.9% of the cases seen in the emergency room and led to hospitalization in 9.6% of all of hospital admission through the emergency room for the period of time under study. The ADR led to 4.1% of the hospital admissions. Drug-related problems are a frequent, major problem which has not been well-analyzed in the emergency rooms. Additionally, emergency rooms can function as the first point of detection of a ADR among an outpatient population.

  1. [Drug safety warnings in psychiatry: adverse drug reactions' signaling from 2002 to 2014].

    PubMed

    Prisco, Vincenzo; Iannaccone, Teresa; Tusciano, Adriano; Boccardi, Mariangela; Perris, Francesco; Capuano, Annalisa; Catapano, Francesco; Fabrazzo, Michele

    2016-01-01

    Monitoring drug-related side effects in psychiatric patients is highly recommended. In fact, frequent exposure to long-term polipharmacotherapy, poor compliance to pharmachological treatment and comorbidity with organic illnesses requiring the prescription of other drugs are causes of pharmacokinetic/pharmacodynamic interactions. These vulnerability factors result in a certain increase in adverse drug reactions (ADRs). This study performes an analysis of Italian Medicine Agency data, in the section "signal analysis", to attempt an assessment of the safety warnings among the different psychotropic drug classes, belonging to the ATC class: N03 (antiepileptics), N05 (antipsychotics), N06 (psycho-analectic drugs). Then we analysed, in a descriptive way, the different association between the drug and the related ADR, evaluating the different safety profiles, in relation to experimental studies, supporting the importance of the signal. In the last years, among the new 25 ADRs, 10 were related to antidepressant drugs (8 SSRI, 1 mirtazapine, 1 agomelatine). In relation to antipsychotic drugs, 6 new correlations were found between drug and ADR onset, mainly among atypical antispychotics. Other correlations (6 above all) were found among antiepileptic drugs. Among benzodiazepines, a signal linked to rabdomylysis onset was found. It is also recommended an evaluation of safety profile in relation to zolpidem prescription. The results of our systematic review are a motivational input, considering the continuous increase of safety warnings, to attentively monitor drug's prescription. Spontaneous ADRs' signaling is a classical system to provide the required attention in relation to a potential risk. The clinician in charge must report this because he is the key figure in the drugs' safety process. In psychiatry, in which a long-term pharmachological therapy is frequent, clinicians are requested to find and signal ADRs to the competent authority.

  2. Adverse drug reactions amongst adult patients admitted in Lagos State University Teaching Hospital Lagos, Nigeria.

    PubMed

    Aderemi-Williams, R I; Awodele, O; Boyle, C A

    2015-01-01

    Adverse drug reaction (ADR) is a global drug therapy problem. It has been rated as one of the top leading causes of morbidity and mortality. In Nigeria, not much is known about ADRs especially with the existing weak post marketing surveillance for monitoring drug use, and its effect on the population. The study is aimed at determining the incidence of ADRs, presentations of ADRs, classes of drugs that frequently cause ADRs and predictors of ADRs in adult medical in-patients in LASUTH. A retrospective study of six hundred and twenty four (624) case notes of all patients admitted to the medical wards in LASUTH between January 1, 2009 and December 31, 2009 was carried out. Information obtained included age, gender, and adverse drug reaction and drug details. The results obtained were analyzed using SPSS version 16 statistical software. Level of significance was set at p ≤ 0.05. A total of 624 case notes consisting of 358 males and 266 females were assessed. The number of patients who experienced adverse drug reactions was 67 (n = 624, 10.7%). The incidence rate of ADRs in LASUTH from the study was 10.7 per 100 patients' population. Most of the ADRs observed were type A reactions (97.8%). Mostly implicated classes of drugs were antidiabetics (26.7%) and NSAIDs (29.3%). The incidence rate of ADRs was 10.7%. ADRs which are predictable and preventable occur in hospitalized patients, such may be prevented or minimized by implementing measures to target specific drugs that are commonly suspected.

  3. Signal Detection of Imipenem Compared to Other Drugs from Korea Adverse Event Reporting System Database

    PubMed Central

    Park, Kyounghoon; Soukavong, Mick; Kim, Jungmee; Kwon, Kyoung-eun; Jin, Xue-mei; Lee, Joongyub; Yang, Bo Ram

    2017-01-01

    Purpose To detect signals of adverse drug events after imipenem treatment using the Korea Institute of Drug Safety & Risk Management-Korea adverse event reporting system database (KIDS-KD). Materials and Methods We performed data mining using KIDS-KD, which was constructed using spontaneously reported adverse event (AE) reports between December 1988 and June 2014. We detected signals calculated the proportional reporting ratio, reporting odds ratio, and information component of imipenem. We defined a signal as any AE that satisfied all three indices. The signals were compared with drug labels of nine countries. Results There were 807582 spontaneous AEs reports in the KIDS-KD. Among those, the number of antibiotics related AEs was 192510; 3382 reports were associated with imipenem. The most common imipenem-associated AE was the drug eruption; 353 times. We calculated the signal by comparing with all other antibiotics and drugs; 58 and 53 signals satisfied the three methods. We compared the drug labelling information of nine countries, including the USA, the UK, Japan, Italy, Switzerland, Germany, France, Canada, and South Korea, and discovered that the following signals were currently not included in drug labels: hypokalemia, cardiac arrest, cardiac failure, Parkinson's syndrome, myocardial infarction, and prostate enlargement. Hypokalemia was an additional signal compared with all other antibiotics, and the other signals were not different compared with all other antibiotics and all other drugs. Conclusion We detected new signals that were not listed on the drug labels of nine countries. However, further pharmacoepidemiologic research is needed to evaluate the causality of these signals. PMID:28332362

  4. Signal Detection of Imipenem Compared to Other Drugs from Korea Adverse Event Reporting System Database.

    PubMed

    Park, Kyounghoon; Soukavong, Mick; Kim, Jungmee; Kwon, Kyoung Eun; Jin, Xue Mei; Lee, Joongyub; Yang, Bo Ram; Park, Byung Joo

    2017-05-01

    To detect signals of adverse drug events after imipenem treatment using the Korea Institute of Drug Safety & Risk Management-Korea adverse event reporting system database (KIDS-KD). We performed data mining using KIDS-KD, which was constructed using spontaneously reported adverse event (AE) reports between December 1988 and June 2014. We detected signals calculated the proportional reporting ratio, reporting odds ratio, and information component of imipenem. We defined a signal as any AE that satisfied all three indices. The signals were compared with drug labels of nine countries. There were 807582 spontaneous AEs reports in the KIDS-KD. Among those, the number of antibiotics related AEs was 192510; 3382 reports were associated with imipenem. The most common imipenem-associated AE was the drug eruption; 353 times. We calculated the signal by comparing with all other antibiotics and drugs; 58 and 53 signals satisfied the three methods. We compared the drug labelling information of nine countries, including the USA, the UK, Japan, Italy, Switzerland, Germany, France, Canada, and South Korea, and discovered that the following signals were currently not included in drug labels: hypokalemia, cardiac arrest, cardiac failure, Parkinson's syndrome, myocardial infarction, and prostate enlargement. Hypokalemia was an additional signal compared with all other antibiotics, and the other signals were not different compared with all other antibiotics and all other drugs. We detected new signals that were not listed on the drug labels of nine countries. However, further pharmacoepidemiologic research is needed to evaluate the causality of these signals. © Copyright: Yonsei University College of Medicine 2017

  5. Differences in reproductive toxicology between alopecia drugs: an analysis on adverse events among female and male cases

    PubMed Central

    Li, Qingfeng

    2016-01-01

    Alopecia is a dermatological condition with limited therapeutic options. Only two drugs, finasteride and minoxidil, are approved by FDA for alopecia treatment. However, little is known about the differences in adverse effects between these two drugs. We examined the clinical reports submitted to the FDA Adverse Event Reporting System (FAERS) from 2004 to 2014. For both female and males, finasteride was found to be more associated with reproductive toxicity as compared to minoxidil. Among male alopecia cases, finasteride was significantly more concurrent with several forms of sexual dysfunction. Among female alopecia cases, finasteride was significantly more concurrent with harm to fetus and disorder of uterus. In addition, drug-gene network analysis indicated that finasteride could profoundly disturb pathways related to sex hormone signaling and oocyte maturation. These findings could provide clues for subsequent toxicological research. Taken together, this analysis suggested that finasteride could be more liable to various reproductive adverse effects. Some of these adverse effects have yet to be warned in FDA-approved drug label. This information can help improve the treatment regimen of alopecia and post-marketing regulation of drug products. PMID:27738338

  6. 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.

  7. Association Between the Occurrence of Adverse Drug Events and Modification of First-Line Highly Active Antiretroviral Therapy in Ghanaian HIV Patients.

    PubMed

    Tetteh, Raymond A; Nartey, Edmund T; Lartey, Margaret; Mantel-Teeuwisse, Aukje K; Leufkens, Hubert G M; Yankey, Barbara A; Dodoo, Alexander N O

    2016-11-01

    Patients initiated on highly active antiretroviral therapy (HAART) generally remain on medication indefinitely. A modification in the HAART regimen may become necessary because of possible acute or chronic toxicities, concomitant clinical conditions, development of virological failure or the advent of adverse drug events. The study documents adverse drug events of HIV-positive Ghanaian patients with HAART modifications. It also investigates the association between documented adverse drug events and HAART modification using an unmatched case-control study design. The study was conducted in the Fevers Unit of the Korle Bu Teaching Hospital and involved patients who attended the HIV Care Clinic between January 2004 and December 2009. Data from 298 modified therapy patients (cases) were compared with 298 continuing therapy patients (controls) who had been on treatment for at least 1 month before the end of study. Controls were sampled from the same database of a cohort of HIV-positive patients on HAART, at the time a case occurred, in terms of treatment initiation ±1 month. Data were obtained from patients' clinical folders and the HIV clinic database linked to the pharmacy database. The nature of the documented adverse drug events of the cases was described and the association between the documented adverse drug events and HAART modification was determined by logistic regression with reported odds ratios (ORs) and their 95 % confidence interval (CI). Among the 298 modified therapy patients sampled in this study, 52.7 % of them had at least one documented adverse drug event. The most documented adverse drug event was anaemia, recorded in 18.5 % of modified therapy patients, all of whom were on a zidovudine-based regimen. The presence of documented adverse drug events was significantly associated with HAART modification [adjusted OR = 2.71 (95 % CI 2.11-3.48), p < 0.001]. Among HIV patients on HAART, adverse drug events play a major role in treatment

  8. Anaphylaxis following intravenous ranitidine: A rare adverse reaction of a common drug

    PubMed Central

    Chopra, Deepti; Arora, Pooja; Khan, Shamimullah; Dwivedi, Shridhar

    2014-01-01

    Ranitidine hydrochloride is a widely used drug that is generally well-tolerated. Anaphylaxis is rarely observed with ranitidine. We report a case who developed severe anaphylaxis following single dose of intravenous ranitidine. The article highlights the importance of recognition of this serious adverse event and re-emphasizes the need for cautious use of drugs, especially in those with known history of allergy. PMID:24741203

  9. 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

  10. Drug-drug interactions and adverse drug reactions in polypharmacy among older adults: an integrative review 1

    PubMed Central

    Rodrigues, Maria Cristina Soares; de Oliveira, Cesar

    2016-01-01

    ABSTRACT Objective: to identify and summarize studies examining both drug-drug interactions (DDI) and adverse drug reactions (ADR) in older adults polymedicated. Methods: an integrative review of studies published from January 2008 to December 2013, according to inclusion and exclusion criteria, in MEDLINE and EMBASE electronic databases were performed. Results: forty-seven full-text studies including 14,624,492 older adults (≥ 60 years) were analyzed: 24 (51.1%) concerning ADR, 14 (29.8%) DDI, and 9 studies (19.1%) investigating both DDI and ADR. We found a variety of methodological designs. The reviewed studies reinforced that polypharmacy is a multifactorial process, and predictors and inappropriate prescribing are associated with negative health outcomes, as increasing the frequency and types of ADRs and DDIs involving different drug classes, moreover, some studies show the most successful interventions to optimize prescribing. Conclusions: DDI and ADR among older adults continue to be a significant issue in the worldwide. The findings from the studies included in this integrative review, added to the previous reviews, can contribute to the improvement of advanced practices in geriatric nursing, to promote the safety of older patients in polypharmacy. However, more research is needed to elucidate gaps. PMID:27598380

  11. Post-marketing withdrawal of analgesic medications because of adverse drug reactions: a systematic review.

    PubMed

    Onakpoya, Igho J; Heneghan, Carl J; Aronson, Jeffrey K

    2018-01-01

    Many analgesics have been withdrawn from the market because of adverse drug reactions. Controversy still surrounds the use of some approved analgesics for pain management. However, the trends and reasons for withdrawal of analgesics when harms are attributed to their use have not been systematically assessed. Areas covered: We conducted searches in PubMed; Embase; Google Scholar; clinicaltrials.gov; WHO databases of withdrawn products; websites of the European Medicines Agency, the US Food and Drug Administration, the UK Medicines and Healthcare products Regulatory Agency; Meyler's Side Effects of Drugs; Stephens' Detection of New Adverse Drug Reactions; the Pharmaceutical Manufacturing Encyclopedia; and the Merck Index. We included licensed analgesics that were withdrawn after marketing because of adverse reactions between 1950 and March 2017. We excluded herbal products, non-human medicines, and non-prescription medicines. We used the Oxford Centre for Evidence Based Medicine criteria to document the levels of evidence, and chi-squared tests to compare withdrawal patterns across geographical regions. Expert opinion: Pharmacovigilance systems in low-resource settings should be strengthened. Greater co-ordination across regulatory authorities in assessing and interpreting the benefit-harm balance of new analgesics should be encouraged. Future reporting of harms in clinical trials of analgesics should follow standardized guidelines.

  12. Adverse Drug Reactions to Antiretroviral Therapy: Prospective Study in Children in Sikasso (Mali)

    PubMed Central

    Oumar, Aboubacar A.; Diallo, Korotoumou; Dembélé, Jean P.; Samaké, Lassana; Sidibé, Issa; Togo, Boubacar; Sylla, Mariam; Tounkara, Anatole; Dao, Sounkalo; Tulkens, Paul M.

    2012-01-01

    OBJECTIVES Adverse events during antiretroviral treatment are frequent and various. Their diagnosis incurs some various difficulties according to the geographic context. Our aim was to describe the frequency, nature, and preventability of adverse drug reactions (ADRs) due to antiretroviral treatment in Malian outpatient children. METHODS The study was a 6-month (June 1 to November 30, 2010) prospective, observational study of 92 children admitted to a pediatric hospital in Sikasso, Mali. The patients were treated with a generic drug and/or drug combinations. Prior to treatment initiation, demographic characteristics, clinical history, and biologic parameters, including CD4 cell counts, were collected for each patient. The World Health Organization's adverse drug reactions classification was used to characterize the side effects. Adverse effects and toxicities were graded 1, 2, and 3. Analysis of data was performed using SPSS Version 17.0 software. RESULTS Ninety-two human immunodeficiency virus–infected children met the criteria of inclusion. After 24 weeks of treatment, we observed that 14.1% of children had at least one side effect during our study. Side effects were many and varied, with the most frequent being cutaneous rash, nausea, vomiting, and diarrhea (38.5%, 23.1%, 15.4%, and 15.4%, respectively). Side effects were grade 1 in most cases. One case of grade 2 and one case of grade 3 were observed with rash. We observed one case of grade 3 side effects during our study. The treatment regimen was changed in 15.2% of cases, including one case because of side effects. CONCLUSION ADRs are not rare in Mali, particularly in children. These ADRs have an impact on quality of life for patients. We recommend a pharmacovigilance system for sustainable management of side effects in patients infected with human immunodeficiency virus in Mali. PMID:23411444

  13. Did intense adverse media publicity impact on prescribing of paroxetine and the notification of suspected adverse drug reactions? Analysis of routine databases, 2001-2004.

    PubMed

    Martin, Richard M; May, Margaret; Gunnell, David

    2006-02-01

    To document the impact on clinical practice in England of media attention around possible adverse effects of paroxetine. Analysis of national selective serotonin reuptake inhibitor (SSRI) prescribing trends and yellow-card adverse drug reaction reports, 2001-2004. From a steady state in 2001, paroxetine prescribing declined sharply from April 2002, coinciding with a USA regulatory action; the subsequent decline in paroxetine prescribing was 1.87% per month (95% confidence interval - 2.06, -1.68). Other SSRI prescribing increased by 1% per month until a major UK review of SSRIs in children in December 2003, after which prescribing plateaued. Media publicity was associated with short-term peaks in yellow-card reports related to paroxetine. Falls in paroxetine and other SSRI prescribing in the UK coincided, respectively, with regulatory communications from the USA and the UK, but associations may have noncausal or other explanations. Reports of adverse reactions to paroxetine appeared to increase after adverse media publicity about the drug.

  14. Identifying adverse drug event information in clinical notes with distributional semantic representations of context.

    PubMed

    Henriksson, Aron; Kvist, Maria; Dalianis, Hercules; Duneld, Martin

    2015-10-01

    For the purpose of post-marketing drug safety surveillance, which has traditionally relied on the voluntary reporting of individual cases of adverse drug events (ADEs), other sources of information are now being explored, including electronic health records (EHRs), which give us access to enormous amounts of longitudinal observations of the treatment of patients and their drug use. Adverse drug events, which can be encoded in EHRs with certain diagnosis codes, are, however, heavily underreported. It is therefore important to develop capabilities to process, by means of computational methods, the more unstructured EHR data in the form of clinical notes, where clinicians may describe and reason around suspected ADEs. In this study, we report on the creation of an annotated corpus of Swedish health records for the purpose of learning to identify information pertaining to ADEs present in clinical notes. To this end, three key tasks are tackled: recognizing relevant named entities (disorders, symptoms, drugs), labeling attributes of the recognized entities (negation, speculation, temporality), and relationships between them (indication, adverse drug event). For each of the three tasks, leveraging models of distributional semantics - i.e., unsupervised methods that exploit co-occurrence information to model, typically in vector space, the meaning of words - and, in particular, combinations of such models, is shown to improve the predictive performance. The ability to make use of such unsupervised methods is critical when faced with large amounts of sparse and high-dimensional data, especially in domains where annotated resources are scarce. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  15. ADEpedia 2.0: Integration of Normalized Adverse Drug Events (ADEs) Knowledge from the UMLS.

    PubMed

    Jiang, Guoqian; Liu, Hongfang; Solbrig, Harold R; Chute, Christopher G

    2013-01-01

    A standardized Adverse Drug Events (ADEs) knowledge base that encodes known ADE knowledge can be very useful in improving ADE detection for drug safety surveillance. In our previous study, we developed the ADEpedia that is a standardized knowledge base of ADEs based on drug product labels. The objectives of the present study are 1) to integrate normalized ADE knowledge from the Unified Medical Language System (UMLS) into the ADEpedia; and 2) to enrich the knowledge base with the drug-disorder co-occurrence data from a 51-million-document electronic medical records (EMRs) system. We extracted 266,832 drug-disorder concept pairs from the UMLS, covering 14,256 (1.69%) distinct drug concepts and 19,006 (3.53%) distinct disorder concepts. Of them, 71,626 (26.8%) concept pairs from UMLS co-occurred in the EMRs. We performed a preliminary evaluation on the utility of the UMLS ADE data. In conclusion, we have built an ADEpedia 2.0 framework that intends to integrate known ADE knowledge from disparate sources. The UMLS is a useful source for providing standardized ADE knowledge relevant to indications, contraindications and adverse effects, and complementary to the ADE data from drug product labels. The statistics from EMRs would enable the meaningful use of ADE data for drug safety surveillance.

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

    PubMed

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

    2012-05-01

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

  17. Study on the Increased Probability of Detecting Adverse Drug Reactions Based on Bayes' Theorem: Evaluation of the Usefulness of Information on the Onset Timing of Adverse Drug Reactions.

    PubMed

    Oshima, Shinji; Enjuji, Takako; Negishi, Akio; Akimoto, Hayato; Ohara, Kousuke; Okita, Mitsuyoshi; Numajiri, Sachihiko; Inoue, Naoko; Ohshima, Shigeru; Terao, Akira; Kobayashi, Daisuke

    2017-09-01

    In order to avoid adverse drug reactions (ADRs), pharmacists are reconstructing ADR-related information based on various types of data gathered from patients, and then providing this information to patients. Among the data provided to patients is the time-to-onset of ADRs after starting the medication (i.e., ADR onset timing information). However, a quantitative evaluation of the effect of onset timing information offered by pharmacists on the probability of ADRs occurring in patients receiving this information has not been reported to date. In this study, we extracted 40 ADR-drug combinations from the data in the Japanese Adverse Drug Event Report database. By applying Bayes' theorem to these combinations, we quantitatively evaluated the usefulness of onset timing information as an ADR detection predictor. As a result, when information on days after taking medication was added, 54 ADR-drug combinations showed a likelihood ratio (LR) in excess of 2. In particular, when considering the ADR-drug combination of anaphylactic shock with levofloxacin or loxoprofen, the number of days elapsed between start of medication and the onset of the ADR was 0, which corresponded to increased likelihood ratios (LRs) of 138.7301 or 58.4516, respectively. When information from 1-7 d after starting medication was added to the combination of liver disorder and acetaminophen, the LR was 11.1775. The results of this study indicate the clinical usefulness of offering information on ADR onset timing.

  18. Immunohistopathological Findings of Severe Cutaneous Adverse Drug Reactions

    PubMed Central

    2017-01-01

    Diagnosis of severe cutaneous adverse drug reactions should involve immunohistopathological examination, which gives insight into the pathomechanisms of these disorders. The characteristic histological findings of erythema multiforme (EM), Stevens–Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN) provide conclusive evidence demonstrating that SJS/TEN can be distinguished from EM. Established SJS/TEN shows full-thickness, extensive keratinocyte necrosis that develops into subepidermal bullae. Drug-induced hypersensitivity syndrome (DIHS) and exanthema in drug reaction with eosinophilia and systemic symptoms (DRESS) each display a variety of histopathological findings, which may partly correlate with the clinical manifestations. Although the histopathology of DRESS is nonspecific, the association of two or more of the four patterns—eczematous changes, interface dermatitis, acute generalized exanthematous pustulosis- (AGEP-) like patterns, and EM-like patterns—might appear in a single biopsy specimen, suggesting the diagnosis and severe cutaneous manifestations of DRESS. Cutaneous dendritic cells may be involved in the clinical course. AGEP typically shows spongiform superficial epidermal pustules accompanied with edema of the papillary dermis and abundant mixed perivascular infiltrates. Mutations in IL36RN may have a definite effect on pathological similarities between AGEP and generalized pustular psoriasis. PMID:29226159

  19. Systematic drug repositioning through mining adverse event data in ClinicalTrials.gov.

    PubMed

    Su, Eric Wen; Sanger, Todd M

    2017-01-01

    Drug repositioning (i.e., drug repurposing) is the process of discovering new uses for marketed drugs. Historically, such discoveries were serendipitous. However, the rapid growth in electronic clinical data and text mining tools makes it feasible to systematically identify drugs with the potential to be repurposed. Described here is a novel method of drug repositioning by mining ClinicalTrials.gov. The text mining tools I2E (Linguamatics) and PolyAnalyst (Megaputer) were utilized. An I2E query extracts "Serious Adverse Events" (SAE) data from randomized trials in ClinicalTrials.gov. Through a statistical algorithm, a PolyAnalyst workflow ranks the drugs where the treatment arm has fewer predefined SAEs than the control arm, indicating that potentially the drug is reducing the level of SAE. Hypotheses could then be generated for the new use of these drugs based on the predefined SAE that is indicative of disease (for example, cancer).

  20. Drug-Associated Adverse Events and Their Relationship with Outcomes in Patients Receiving Treatment for Extensively Drug-Resistant Tuberculosis in South Africa

    PubMed Central

    Shean, Karen; Streicher, Elizabeth; Pieterson, Elize; Symons, Greg; van Zyl Smit, Richard; Theron, Grant; Lehloenya, Rannakoe; Padanilam, Xavier; Wilcox, Paul; Victor, Tommie C.; van Helden, Paul; Groubusch, Martin; Warren, Robin; Badri, Motasim; Dheda, Keertan

    2013-01-01

    Background Treatment-related outcomes in patients with extensively drug-resistant tuberculosis (XDR-TB) are poor. However, data about the type, frequency and severity of presumed drug-associated adverse events (AEs) and their association with treatment-related outcomes in patients with XDR-TB are scarce. Methods Case records of 115 South-African XDR-TB patients were retrospectively reviewed by a trained researcher. AEs were estimated and graded according to severity [grade 0 = none; grade 1–2 = mild to moderate; and grade 3–5 = severe (drug stopped, life-threatening or death)]. Findings 161 AEs were experienced by 67/115(58%) patients: 23/67(34%) required modification of treatment, the offending drug was discontinued in 19/67(28%), reactions were life-threatening in 2/67(3.0%), and 6/67(9.0%) died. ∼50% of the patients were still on treatment at the time of data capture. Sputum culture-conversion was less likely in those with severe (grade 3–5) vs. grade 0–2 AEs [2/27(7%) vs. 24/88(27%); p = 0.02]. The type, frequency and severity of AEs was similar in HIV-infected and uninfected patients. Capreomycin, which was empirically administered in most cases, was withdrawn in 14/104(14%) patients, implicated in (14/34) 41% of the total drug withdrawals, and was associated with all 6 deaths in the severe AE group (renal failure in five patients and hypokalemia in one patient). Conclusion Drug-associated AEs occur commonly with XDR-TB treatment, are often severe, frequently interrupt therapy, and negatively impact on culture conversion outcomes. These preliminary data inform on the need for standardised strategies (including pre-treatment counselling, early detection, monitoring, and follow-up) and less toxic drugs to optimally manage patients with XDR-TB. PMID:23667572

  1. Adverse event management in mass drug administration for neglected tropical diseases.

    PubMed

    Caplan, Arthur; Zink, Amanda

    2014-03-01

    The ethical challenges of reporting and managing adverse events (AEs) and serious AEs (SAEs) in the context of mass drug administration (MDA) for the treatment of neglected tropical diseases (NTDs) require reassessment of domestic and international policies on a global scale. Although the World Health Organization has set forth AE/SAE guidelines specifically for NTD MDA that incorporate suspected causality, and recommends that only SAEs get reported in this setting, most regulatory agencies continue to require the reporting of all SAEs exhibiting even a merely temporal relationship to activities associated with an MDA program. This greatly increases the potential for excess "noise" and undue risk aversion and is not only impractical but arguably unethical where huge proportions of populations are being treated for devastating diseases, and no good baseline exists against which to compare possible AE/SAE reports. Other population-specific variables that might change the way drug safety ought to be assessed include differing efficacy rates of a drug, background morbidity/mortality rates of the target disease in question, the growth rate of the incidence of disease, the availability of rescue or salvage therapies, and the willingness of local populations to take risks that other populations might not. The fact that NTDs are controllable and potentially eradicable with well-tolerated, effective, existing drugs might further alter our assessment of MDA safety and AE/SAE tolerability. At the same time, diffuseness of population, communication barriers, lack of resources, and other difficult surveillance challenges may present in NTD-affected settings. These limitations could impair the ability to monitor an MDA program's success, as well as hinder efforts to obtain informed consent or provide rescue therapy. Denying beneficial research interventions and MDA programs intended to benefit millions requires sound ethical justification based on more than the identification of

  2. Improving drug safety: From adverse drug reaction knowledge discovery to clinical implementation.

    PubMed

    Tan, Yuxiang; Hu, Yong; Liu, Xiaoxiao; Yin, Zhinan; Chen, Xue-Wen; Liu, Mei

    2016-11-01

    Adverse drug reactions (ADRs) are a major public health concern, causing over 100,000 fatalities in the United States every year with an annual cost of $136 billion. Early detection and accurate prediction of ADRs is thus vital for drug development and patient safety. Multiple scientific disciplines, namely pharmacology, pharmacovigilance, and pharmacoinformatics, have been addressing the ADR problem from different perspectives. With the same goal of improving drug safety, this article summarizes and links the research efforts in the multiple disciplines into a single framework from comprehensive understanding of the interactions between drugs and biological system and the identification of genetic and phenotypic predispositions of patients susceptible to higher ADR risks and finally to the current state of implementation of medication-related decision support systems. We start by describing available computational resources for building drug-target interaction networks with biological annotations, which provides a fundamental knowledge for ADR prediction. Databases are classified by functions to help users in selection. Post-marketing surveillance is then introduced where data-driven approach can not only enhance the prediction accuracy of ADRs but also enables the discovery of genetic and phenotypic risk factors of ADRs. Understanding genetic risk factors for ADR requires well organized patient genetics information and analysis by pharmacogenomic approaches. Finally, current state of clinical decision support systems is presented and described how clinicians can be assisted with the integrated knowledgebase to minimize the risk of ADR. This review ends with a discussion of existing challenges in each of disciplines with potential solutions and future directions. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Pirfenidone and nintedanib for pulmonary fibrosis in clinical practice: Tolerability and adverse drug reactions.

    PubMed

    Galli, Jonathan A; Pandya, Aloknath; Vega-Olivo, Michelle; Dass, Chandra; Zhao, Huaqing; Criner, Gerard J

    2017-08-01

    The real-world tolerability of pirfenidone and nintedanib in non-clinical trial patients is unknown. Many patients with pulmonary fibrosis have significant medical co-morbidities or baseline characteristics that exclude them from clinical trial participation. We conducted a retrospective chart review study on subjects prescribed nintedanib or pirfenidone for pulmonary fibrosis treatment (any aetiology) from September 2014 to February 2016. A total of 186 subjects were included: 129 received pirfenidone and 57 were prescribed nintedanib and followed up for mean observation periods of 52 ± 17 weeks for pirfenidone and 41 ± 15 weeks for nintedanib. The primary outcome was drug discontinuation as a result of an adverse event. Subjects had significant respiratory impairment at baseline, 63% required home oxygen therapy and mean diffusion capacity of carbon monoxide (DLCO) was 36 ± 14% predicted. Drug discontinuation as a result of an adverse event occurred in 20.9% of subjects on pirfenidone and 26.3% on nintedanib. Drug discontinuation rates for both pirfenidone and nintedanib did not significantly differ from corresponding large clinical trials (ASCEND/CAPACITY and INPULSIS 1 and 2, respectively). Adverse events that occurred with highest frequency on pirfenidone were nausea (26.4%), rash/photosensitivity (14.7%) and dyspepsia/gastroesophageal reflux disease (GERD) (12.4%). Diarrhoea (52.6%) and nausea (29.8%) were reported most often with nintedanib therapy. Patients with pulmonary fibrosis treated with nintedanib or pirfenidone in routine clinical practice had drug tolerability and adverse event profiles comparable with subjects enrolled in clinical trials despite having a greater degree of respiratory impairment and a high prevalence of co-morbid medical conditions. © 2017 Asian Pacific Society of Respirology.

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

    PubMed

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

    2018-04-01

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

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

    PubMed

    Teixeira, Marcus Zulian

    2013-01-01

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

  6. Adverse drug event reporting systems: a systematic review

    PubMed Central

    Peddie, David; Wickham, Maeve E.; Badke, Katherin; Small, Serena S.; Doyle‐Waters, Mary M.; Balka, Ellen; Hohl, Corinne M.

    2016-01-01

    Aim Adverse drug events (ADEs) are harmful and unintended consequences of medications. Their reporting is essential for drug safety monitoring and research, but it has not been standardized internationally. Our aim was to synthesize information about the type and variety of data collected within ADE reporting systems. Methods We developed a systematic search strategy, applied it to four electronic databases, and completed an electronic grey literature search. Two authors reviewed titles and abstracts, and all eligible full‐texts. We extracted data using a standardized form, and discussed disagreements until reaching consensus. We synthesized data by collapsing data elements, eliminating duplicate fields and identifying relationships between reporting concepts and data fields using visual analysis software. Results We identified 108 ADE reporting systems containing 1782 unique data fields. We mapped them to 33 reporting concepts describing patient information, the ADE, concomitant and suspect drugs, and the reporter. While reporting concepts were fairly consistent, we found variability in data fields and corresponding response options. Few systems clarified the terminology used, and many used multiple drug and disease dictionaries such as the Medical Dictionary for Regulatory Activities (MedDRA). Conclusion We found substantial variability in the data fields used to report ADEs, limiting the comparability of ADE data collected using different reporting systems, and undermining efforts to aggregate data across cohorts. The development of a common standardized data set that can be evaluated with regard to data quality, comparability and reporting rates is likely to optimize ADE data and drug safety surveillance. PMID:27016266

  7. Adverse drug event reporting systems: a systematic review.

    PubMed

    Bailey, Chantelle; Peddie, David; Wickham, Maeve E; Badke, Katherin; Small, Serena S; Doyle-Waters, Mary M; Balka, Ellen; Hohl, Corinne M

    2016-07-01

    Adverse drug events (ADEs) are harmful and unintended consequences of medications. Their reporting is essential for drug safety monitoring and research, but it has not been standardized internationally. Our aim was to synthesize information about the type and variety of data collected within ADE reporting systems. We developed a systematic search strategy, applied it to four electronic databases, and completed an electronic grey literature search. Two authors reviewed titles and abstracts, and all eligible full-texts. We extracted data using a standardized form, and discussed disagreements until reaching consensus. We synthesized data by collapsing data elements, eliminating duplicate fields and identifying relationships between reporting concepts and data fields using visual analysis software. We identified 108 ADE reporting systems containing 1782 unique data fields. We mapped them to 33 reporting concepts describing patient information, the ADE, concomitant and suspect drugs, and the reporter. While reporting concepts were fairly consistent, we found variability in data fields and corresponding response options. Few systems clarified the terminology used, and many used multiple drug and disease dictionaries such as the Medical Dictionary for Regulatory Activities (MedDRA). We found substantial variability in the data fields used to report ADEs, limiting the comparability of ADE data collected using different reporting systems, and undermining efforts to aggregate data across cohorts. The development of a common standardized data set that can be evaluated with regard to data quality, comparability and reporting rates is likely to optimize ADE data and drug safety surveillance. © 2016 The British Pharmacological Society.

  8. Pharmacogenetics of drugs withdrawn from the market.

    PubMed

    Zhang, Wei; Roederer, Mary W; Chen, Wang-Qing; Fan, Lan; Zhou, Hong-Hao

    2012-01-01

    The safety and efficacy of candidate compounds are critical factors during the development of drugs, and most drugs have been withdrawn from the market owing to severe adverse reactions. Individuals/populations with different genetic backgrounds may show significant differences in drug metabolism and efficacy, which can sometimes manifest as severe adverse drug reactions. With an emphasis on the mechanisms underlying abnormal drug effects caused by genetic mutations, pharmacogenetic studies may enhance the safety and effectiveness of drug use, provide more comprehensive delineations of the scope of usage, and change the fates of drugs withdrawn from the market.

  9. Opportunities for Web-based Drug Repositioning: Searching for Potential Antihypertensive Agents with Hypotension Adverse Events.

    PubMed

    Wang, Kejian; Wan, Mei; Wang, Rui-Sheng; Weng, Zuquan

    2016-04-01

    Drug repositioning refers to the process of developing new indications for existing drugs. As a phenotypic indicator of drug response in humans, clinical side effects may provide straightforward signals and unique opportunities for drug repositioning. We aimed to identify drugs frequently associated with hypotension adverse reactions (ie, the opposite condition of hypertension), which could be potential candidates as antihypertensive agents. We systematically searched the electronic records of the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) through the openFDA platform to assess the association between hypotension incidence and antihypertensive therapeutic effect regarding a list of 683 drugs. Statistical analysis of FAERS data demonstrated that those drugs frequently co-occurring with hypotension events were more likely to have antihypertensive activity. Ranked by the statistical significance of frequent hypotension reporting, the well-known antihypertensive drugs were effectively distinguished from others (with an area under the receiver operating characteristic curve > 0.80 and a normalized discounted cumulative gain of 0.77). In addition, we found a series of antihypertensive agents (particularly drugs originally developed for treating nervous system diseases) among the drugs with top significant reporting, suggesting the good potential of Web-based and data-driven drug repositioning. We found several candidate agents among the hypotension-related drugs on our list that may be redirected for lowering blood pressure. More important, we showed that a pharmacovigilance system could alternatively be used to identify antihypertensive agents and sustainably create opportunities for drug repositioning.

  10. Adverse drug reactions and drug–drug interactions with over-the-counter NSAIDs

    PubMed Central

    Moore, Nicholas; Pollack, Charles; Butkerait, Paul

    2015-01-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen have a long history of safe and effective use as both prescription and over-the-counter (OTC) analgesics/antipyretics. The mechanism of action of all NSAIDs is through reversible inhibition of cyclooxygenase enzymes. Adverse drug reactions (ADRs) including gastrointestinal bleeding as well as cardiovascular and renal effects have been reported with NSAID use. In many cases, ADRs may occur because of drug–drug interactions (DDIs) between the NSAID and a concomitant medication. For example, DDIs have been reported when NSAIDs are coadministered with aspirin, alcohol, some antihypertensives, antidepressants, and other commonly used medications. Because of the pharmacologic nature of these interactions, there is a continuum of risk in that the potential for an ADR is dependent on total drug exposure. Therefore, consideration of dose and duration of NSAID use, as well as the type or class of comedication administered, is important when assessing potential risk for ADRs. Safety findings from clinical studies evaluating prescription-strength NSAIDs may not be directly applicable to OTC dosing. Health care providers can be instrumental in educating patients that using OTC NSAIDs at the lowest effective dose for the shortest required duration is vital to balancing efficacy and safety. This review discusses some of the most clinically relevant DDIs reported with NSAIDs based on major sites of ADRs and classes of medication, with a focus on OTC ibuprofen, for which the most data are available. PMID:26203254

  11. Using constrained information entropy to detect rare adverse drug reactions from medical forums.

    PubMed

    Yi Zheng; Chaowang Lan; Hui Peng; Jinyan Li

    2016-08-01

    Adverse drug reactions (ADRs) detection is critical to avoid malpractices yet challenging due to its uncertainty in pre-marketing review and the underreporting in post-marketing surveillance. To conquer this predicament, social media based ADRs detection methods have been proposed recently. However, existing researches are mostly co-occurrence based methods and face several issues, in particularly, leaving out the rare ADRs and unable to distinguish irrelevant ADRs. In this work, we introduce a constrained information entropy (CIE) method to solve these problems. CIE first recognizes the drug-related adverse reactions using a predefined keyword dictionary and then captures high- and low-frequency (rare) ADRs by information entropy. Extensive experiments on medical forums dataset demonstrate that CIE outperforms the state-of-the-art co-occurrence based methods, especially in rare ADRs detection.

  12. Adverse drug events with hyperkalaemia during inpatient stays: evaluation of an automated method for retrospective detection in hospital databases

    PubMed Central

    2014-01-01

    Background Adverse drug reactions and adverse drug events (ADEs) are major public health issues. Many different prospective tools for the automated detection of ADEs in hospital databases have been developed and evaluated. The objective of the present study was to evaluate an automated method for the retrospective detection of ADEs with hyperkalaemia during inpatient stays. Methods We used a set of complex detection rules to take account of the patient’s clinical and biological context and the chronological relationship between the causes and the expected outcome. The dataset consisted of 3,444 inpatient stays in a French general hospital. An automated review was performed for all data and the results were compared with those of an expert chart review. The complex detection rules’ analytical quality was evaluated for ADEs. Results In terms of recall, 89.5% of ADEs with hyperkalaemia “with or without an abnormal symptom” were automatically identified (including all three serious ADEs). In terms of precision, 63.7% of the automatically identified ADEs with hyperkalaemia were true ADEs. Conclusions The use of context-sensitive rules appears to improve the automated detection of ADEs with hyperkalaemia. This type of tool may have an important role in pharmacoepidemiology via the routine analysis of large inter-hospital databases. PMID:25212108

  13. Overdose and adverse drug event experiences among adult patients in the emergency department.

    PubMed

    Bohnert, Amy S B; Walton, Maureen A; Cunningham, Rebecca M; Ilgen, Mark A; Barry, Kristen; Chermack, Stephen T; Blow, Frederic C

    2017-11-16

    Overdose is a leading cause of injury and death in the United States. Emergency Department (ED) patients have an elevated prevalence of substance use. This study describes overdose/adverse drug event experiences among adult ED patients to inform strategies to address overdose risk. Patients seeking care at a large ED in the city of Flint, Michigan participated in a computerized self-assessment during 2011-2013 (n=4571). Overdose was assessed with a broad definition and included occurrences that could be considered adverse drug events. Among those with this type of experience, additional items assessed symptoms, outcomes, and intent. 12% reported an overdose history. Of participants' most serious overdoses, 74% were without clear intent for self-harm, although this was true of only 61% of overdoses involving opiates or sedatives, and 52% had symptoms present that indicated that it was life-threatening. Binge drinking on a monthly basis (ORs=1.4) was associated with a medically serious overdose compared to never having an overdose. Compared to no drug use in the last year, use of one drug was associated with an OR of 1.8, two drugs was associated with an OR of 5.8, three drugs was associated with an OR of 8.4, and four or more drugs was associated with an OR of 25.1 of having had a medically serious overdose (all p<0.05). Most overdose experiences among ED patients were without clear intent of self-harm. The ED may be an appropriate setting for efforts to reduce overdose risk, especially among polysubstance users. Published by Elsevier Ltd.

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

    PubMed

    Kim, Jong-Hoon; Kim, Min-Jung

    2009-01-01

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

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

    PubMed

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

    2017-01-01

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

  16. Big Data Mining and Adverse Event Pattern Analysis in Clinical Drug Trials

    PubMed Central

    Federer, Callie; Yoo, Minjae

    2016-01-01

    Abstract Drug adverse events (AEs) are a major health threat to patients seeking medical treatment and a significant barrier in drug discovery and development. AEs are now required to be submitted during clinical trials and can be extracted from ClinicalTrials.gov (https://clinicaltrials.gov/), a database of clinical studies around the world. By extracting drug and AE information from ClinicalTrials.gov and structuring it into a database, drug-AEs could be established for future drug development and repositioning. To our knowledge, current AE databases contain mainly U.S. Food and Drug Administration (FDA)-approved drugs. However, our database contains both FDA-approved and experimental compounds extracted from ClinicalTrials.gov. Our database contains 8,161 clinical trials of 3,102,675 patients and 713,103 reported AEs. We extracted the information from ClinicalTrials.gov using a set of python scripts, and then used regular expressions and a drug dictionary to process and structure relevant information into a relational database. We performed data mining and pattern analysis of drug-AEs in our database. Our database can serve as a tool to assist researchers to discover drug-AE relationships for developing, repositioning, and repurposing drugs. PMID:27631620

  17. Big Data Mining and Adverse Event Pattern Analysis in Clinical Drug Trials.

    PubMed

    Federer, Callie; Yoo, Minjae; Tan, Aik Choon

    2016-12-01

    Drug adverse events (AEs) are a major health threat to patients seeking medical treatment and a significant barrier in drug discovery and development. AEs are now required to be submitted during clinical trials and can be extracted from ClinicalTrials.gov ( https://clinicaltrials.gov/ ), a database of clinical studies around the world. By extracting drug and AE information from ClinicalTrials.gov and structuring it into a database, drug-AEs could be established for future drug development and repositioning. To our knowledge, current AE databases contain mainly U.S. Food and Drug Administration (FDA)-approved drugs. However, our database contains both FDA-approved and experimental compounds extracted from ClinicalTrials.gov . Our database contains 8,161 clinical trials of 3,102,675 patients and 713,103 reported AEs. We extracted the information from ClinicalTrials.gov using a set of python scripts, and then used regular expressions and a drug dictionary to process and structure relevant information into a relational database. We performed data mining and pattern analysis of drug-AEs in our database. Our database can serve as a tool to assist researchers to discover drug-AE relationships for developing, repositioning, and repurposing drugs.

  18. Immune-related adverse events for anti-PD-1 and anti-PD-L1 drugs: systematic review and meta-analysis

    PubMed Central

    Baxi, Shrujal; Yang, Annie; Gennarelli, Renee L; Khan, Niloufer; Wang, Ziwei; Boyce, Lindsay

    2018-01-01

    Abstract Objective To evaluate rates of serious organ specific immune-related adverse events, general adverse events related to immune activation, and adverse events consistent with musculoskeletal problems for anti-programmed cell death 1 (PD-1) drugs overall and compared with control treatments. Design Systematic review and meta-analysis. Data sources Medline, Embase, Cochrane Library, Web of Science, and Scopus searched to 16 March 2017 and combined with data from ClinicalTrials.gov. Study selection Eligible studies included primary clinical trial data on patients with cancer with recurrent or metastatic disease. Data extraction Three independent investigators extracted data on adverse events from ClinicalTrials.gov and the published studies. Risk of bias was assessed using the Cochrane tool by three independent investigators. Results 13 relevant studies were included; adverse event data were available on ClinicalTrials.gov for eight. Studies compared nivolumab (n=6), pembrolizumab (5), or atezolizumab (2) with chemotherapy (11), targeted drugs (1), or both (1). Serious organ specific immune-related adverse events were rare, but compared with standard treatment, rates of hypothyroidism (odds ratio 7.56, 95% confidence interval 4.53 to 12.61), pneumonitis (5.37, 2.73 to 10.56), colitis (2.88, 1.30 to 6.37), and hypophysitis (3.38, 1.02 to 11.08) were increased with anti-PD-1 drugs. Of the general adverse events related to immune activation, only the rate of rash (2.34, 2.73 to 10.56) increased. Incidence of fatigue (32%) and diarrhea (19%) were high but similar to control. Reporting of adverse events consistent with musculoskeletal problems was inconsistent; rates varied but were over 20% in some studies for arthraligia and back pain. Conclusions Organ specific immune-related adverse events are uncommon with anti-PD-1 drugs but the risk is increased compared with control treatments. General adverse events related to immune activation are largely similar. Adverse

  19. Immune-related adverse events for anti-PD-1 and anti-PD-L1 drugs: systematic review and meta-analysis.

    PubMed

    Baxi, Shrujal; Yang, Annie; Gennarelli, Renee L; Khan, Niloufer; Wang, Ziwei; Boyce, Lindsay; Korenstein, Deborah

    2018-03-14

    To evaluate rates of serious organ specific immune-related adverse events, general adverse events related to immune activation, and adverse events consistent with musculoskeletal problems for anti-programmed cell death 1 (PD-1) drugs overall and compared with control treatments. Systematic review and meta-analysis. Medline, Embase, Cochrane Library, Web of Science, and Scopus searched to 16 March 2017 and combined with data from ClinicalTrials.gov. Eligible studies included primary clinical trial data on patients with cancer with recurrent or metastatic disease. Three independent investigators extracted data on adverse events from ClinicalTrials.gov and the published studies. Risk of bias was assessed using the Cochrane tool by three independent investigators. 13 relevant studies were included; adverse event data were available on ClinicalTrials.gov for eight. Studies compared nivolumab (n=6), pembrolizumab (5), or atezolizumab (2) with chemotherapy (11), targeted drugs (1), or both (1). Serious organ specific immune-related adverse events were rare, but compared with standard treatment, rates of hypothyroidism (odds ratio 7.56, 95% confidence interval 4.53 to 12.61), pneumonitis (5.37, 2.73 to 10.56), colitis (2.88, 1.30 to 6.37), and hypophysitis (3.38, 1.02 to 11.08) were increased with anti-PD-1 drugs. Of the general adverse events related to immune activation, only the rate of rash (2.34, 2.73 to 10.56) increased. Incidence of fatigue (32%) and diarrhea (19%) were high but similar to control. Reporting of adverse events consistent with musculoskeletal problems was inconsistent; rates varied but were over 20% in some studies for arthraligia and back pain. Organ specific immune-related adverse events are uncommon with anti-PD-1 drugs but the risk is increased compared with control treatments. General adverse events related to immune activation are largely similar. Adverse events consistent with musculoskeletal problems are inconsistently reported but adverse

  20. Ontology-based knowledge management for personalized adverse drug events detection.

    PubMed

    Cao, Feng; Sun, Xingzhi; Wang, Xiaoyuan; Li, Bo; Li, Jing; Pan, Yue

    2011-01-01

    Since Adverse Drug Event (ADE) has become a leading cause of death around the world, there arises high demand for helping clinicians or patients to identify possible hazards from drug effects. Motivated by this, we present a personalized ADE detection system, with the focus on applying ontology-based knowledge management techniques to enhance ADE detection services. The development of electronic health records makes it possible to automate the personalized ADE detection, i.e., to take patient clinical conditions into account during ADE detection. Specifically, we define the ADE ontology to uniformly manage the ADE knowledge from multiple sources. We take advantage of the rich semantics from the terminology SNOMED-CT and apply it to ADE detection via the semantic query and reasoning.

  1. Markov Logic Networks for Adverse Drug Event Extraction from Text.

    PubMed

    Natarajan, Sriraam; Bangera, Vishal; Khot, Tushar; Picado, Jose; Wazalwar, Anurag; Costa, Vitor Santos; Page, David; Caldwell, Michael

    2017-05-01

    Adverse drug events (ADEs) are a major concern and point of emphasis for the medical profession, government, and society. A diverse set of techniques from epidemiology, statistics, and computer science are being proposed and studied for ADE discovery from observational health data (e.g., EHR and claims data), social network data (e.g., Google and Twitter posts), and other information sources. Methodologies are needed for evaluating, quantitatively measuring, and comparing the ability of these various approaches to accurately discover ADEs. This work is motivated by the observation that text sources such as the Medline/Medinfo library provide a wealth of information on human health. Unfortunately, ADEs often result from unexpected interactions, and the connection between conditions and drugs is not explicit in these sources. Thus, in this work we address the question of whether we can quantitatively estimate relationships between drugs and conditions from the medical literature. This paper proposes and studies a state-of-the-art NLP-based extraction of ADEs from text.

  2. 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

  3. Adverse Drug Reactions in Children: The Double-Edged Sword of Therapeutics.

    PubMed

    Elzagallaai, A A; Greff, Mje; Rieder, M J

    2017-06-01

    Adverse drug reactions (ADRs) represent a major health problem worldwide, with high morbidity and mortality rates. ADRs are classified into Type A (augmented) and Type B (bizarre) ADRs, with the former group being more common and the latter less common but often severe and clinically more problematic due to their unpredictable nature and occurrence at any dose. Pediatric populations are especially vulnerable to ADRs due to the lack of data for this age group from the drug development process and because of the wide use of off-label and unlicensed use of drugs. Children are more prone to specific types of ADRs because of the level of maturity of body systems involved in absorption, metabolism, transportation, and elimination of drugs. This state-of-the-art review provides an overview of definitions, classifications, epidemiology, and pathophysiology of ADRs and discusses the available evidence for related risk factors and causes of ADRs in the pediatric population. © 2017 American Society for Clinical Pharmacology and Therapeutics.

  4. Reported Adverse Drug Reactions in Infants: A Nationwide Analysis in Malaysia.

    PubMed

    Rosli, Rosliana; Dali, Ahmad Fauzi; Aziz, Noorizan Abd; Ming, Long Chiau; Manan, Mohamed Mansor

    2017-01-01

    Spontaneous adverse drug reactions (ADRs) reporting is a useful source of drug safety information in infants as only adult patients are routinely tested in clinical trials. This study was aimed to evaluate the spontaneously reported ADRs using WHO Adverse Reaction Terminology and to identify the common drugs associated with ADRs in children under 2 years of age. A retrospective analysis of ADR data for children below 2 years old from 2000 to 2013 was conducted using the data extracted from Malaysia's national pharmacovigilance database, QUEST2 System. From 2000 to 2013, Malaysia's National Pharmaceutical Control Bureau received a total of 11,932 reports for children from various healthcare facilities in Malaysia. 14.0% ( n = 1667) of the ADRs reported for those children were related to children under 2 years old. The data retrieved was analyzed in terms of age, gender, source of reporting, type of reporters, suspected medicines and characteristics of ADRs (category, onset, severity, and outcomes). A total of 1312 ADRs reported in 907 ADR reports were analyzed. The most common ADRs reported were skin appendage disorders (60.1%), and the most frequently reported symptoms were rash ( n = 215), maculopapular rash ( n = 206), urticaria ( n = 169), erythematous rash ( n = 76), and pruritus ( n = 58). In general, drugs from antibacterials for systemic use (58.8%) appeared to be the most common contributors to ADRs in children below 2 years old. Penicillins and other β-Lactam Antibacterials accounted for more than 40% of all drugs implicated in ADRs. The majority of ADRs were subacute reactions that occurred within 24 h of exposure to the drug. A high proportion of ADRs was classified as mild, and most victims had no sequela. Only one fatality was seen. There were 10 cases for each symptom, namely erythema multiforme and Stevens-Johnson Syndrome, observed in this study. A large proportion of ADRs in children under 2 years old were mainly caused by drugs from antibacterial

  5. Reported Adverse Drug Reactions in Infants: A Nationwide Analysis in Malaysia

    PubMed Central

    Rosli, Rosliana; Dali, Ahmad Fauzi; Aziz, Noorizan Abd.; Ming, Long Chiau; Manan, Mohamed Mansor

    2017-01-01

    Spontaneous adverse drug reactions (ADRs) reporting is a useful source of drug safety information in infants as only adult patients are routinely tested in clinical trials. This study was aimed to evaluate the spontaneously reported ADRs using WHO Adverse Reaction Terminology and to identify the common drugs associated with ADRs in children under 2 years of age. A retrospective analysis of ADR data for children below 2 years old from 2000 to 2013 was conducted using the data extracted from Malaysia’s national pharmacovigilance database, QUEST2 System. From 2000 to 2013, Malaysia’s National Pharmaceutical Control Bureau received a total of 11,932 reports for children from various healthcare facilities in Malaysia. 14.0% (n = 1667) of the ADRs reported for those children were related to children under 2 years old. The data retrieved was analyzed in terms of age, gender, source of reporting, type of reporters, suspected medicines and characteristics of ADRs (category, onset, severity, and outcomes). A total of 1312 ADRs reported in 907 ADR reports were analyzed. The most common ADRs reported were skin appendage disorders (60.1%), and the most frequently reported symptoms were rash (n = 215), maculopapular rash (n = 206), urticaria (n = 169), erythematous rash (n = 76), and pruritus (n = 58). In general, drugs from antibacterials for systemic use (58.8%) appeared to be the most common contributors to ADRs in children below 2 years old. Penicillins and other β-Lactam Antibacterials accounted for more than 40% of all drugs implicated in ADRs. The majority of ADRs were subacute reactions that occurred within 24 h of exposure to the drug. A high proportion of ADRs was classified as mild, and most victims had no sequela. Only one fatality was seen. There were 10 cases for each symptom, namely erythema multiforme and Stevens–Johnson Syndrome, observed in this study. A large proportion of ADRs in children under 2 years old were mainly caused by drugs from antibacterial

  6. Limitations and obstacles of the spontaneous adverse drugs reactions reporting: Two "challenging" case reports.

    PubMed

    Palleria, Caterina; Leporini, Christian; Chimirri, Serafina; Marrazzo, Giuseppina; Sacchetta, Sabrina; Bruno, Lucrezia; Lista, Rosaria M; Staltari, Orietta; Scuteri, Antonio; Scicchitano, Francesca; Russo, Emilio

    2013-12-01

    Nowadays, based on several epidemiological data, iatrogenic disease is an emerging public health problem, especially in industrialized countries. Adverse drugs reactions (ADRs) are extremely common and, therefore, clinically, socially, and economically worthy of attention. Spontaneous reporting system for suspected ADRs represents the cornerstone of the pharmacovigilance, because it allows rapid detection of potential alarm signals related to drugs use. However, spontaneous reporting system shows several limitations, which are mainly related to under-reporting. In this paper, we describe two particular case reports, which emphasize some reasons of under-reporting and other common criticisms of spontaneous reporting systems. We performed a computer-aided search of Medline, PubMed, Embase, Cochrane library databases, national and international databases of suspected ADRs reports in order to identify previous published case reports and spontaneous reports about the ADRs reviewed in this paper, and to examine the role of suspected drugs in the pathogenesis of the described adverse reactions. First, we reported a case of tizanidine-induced hemorrhagic cystitis. In the second case report, we presented an episode of asthma exacerbation after taking bimatoprost. Through the review of these two cases, we highlighted some common criticisms of spontaneous reporting systems: under-reporting and false causality attribution. Healthcare workers sometimes do not report ADRs because it is challenging to establish with certainty the causal relationship between drug and adverse reaction; however, according to a key principle of pharmacovigilance, it is always better to report even a suspicion to generate an alarm in the interest of protecting public health.

  7. 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.

  8. Adverse-drug-event data provided by pharmaceutical companies.

    PubMed

    Cudny, Magdalena E; Graham, Angie S

    2008-06-01

    Pharmaceutical company drug information center (PCDIC) responses to queries about adverse drug events (ADEs) were studied to determine whether PCDICs search sources other than the prescribing information on the package insert (PI) and whether the PCDICs' approach differs according to whether an ADE is listed in the PI (labeled) or not (unlabeled). Companies were selected from a list of PCDICs in the Physicians' Desk Reference. One oral or injectable prescription drug from each company was selected. For each drug, a labeled ADE and an unlabeled ADE about which to query the PCDICs were randomly selected from the index of an annual publication on ADEs. The investigators telephoned the PCDICs with an open-ended inquiry about the incidence, timing, and management of the ADE as reported in the literature and the company's internal data; they clarified that the request did not concern a specific patient. Whether or not information was provided, the source searched was recorded (PI, literature, internal database), and the percentages of PCDICs that used each source for labeled and for unlabeled ADEs were analyzed. Results were obtained from 100 companies to questions about 100 drugs (200 ADEs). For ADEs overall, 80% used the PI, 50% the medical literature, and 38% internal data. For labeled versus unlabeled ADEs, respectively, the PI was used by 84% and 76%; literature, both 50%; and internal data, 35% and 41%. The PCDIC specialists referencing the PI did not always provide accurate or up-to-date information. Some specialists, when asked to query internal databases, said that was not an option. For both labeled and unlabeled ADEs, the PI was the primary source used by PCDICs to answer safety questions about their products, and internal data were the least-used source. Most resources used by PCDICs are readily available to practicing pharmacists.

  9. Large-scale prediction of adverse drug reactions using chemical, biological, and phenotypic properties of drugs.

    PubMed

    Liu, Mei; Wu, Yonghui; Chen, Yukun; Sun, Jingchun; Zhao, Zhongming; Chen, Xue-wen; Matheny, Michael Edwin; Xu, Hua

    2012-06-01

    Adverse drug reaction (ADR) is one of the major causes of failure in drug development. Severe ADRs that go undetected until the post-marketing phase of a drug often lead to patient morbidity. Accurate prediction of potential ADRs is required in the entire life cycle of a drug, including early stages of drug design, different phases of clinical trials, and post-marketing surveillance. Many studies have utilized either chemical structures or molecular pathways of the drugs to predict ADRs. Here, the authors propose a machine-learning-based approach for ADR prediction by integrating the phenotypic characteristics of a drug, including indications and other known ADRs, with the drug's chemical structures and biological properties, including protein targets and pathway information. A large-scale study was conducted to predict 1385 known ADRs of 832 approved drugs, and five machine-learning algorithms for this task were compared. This evaluation, based on a fivefold cross-validation, showed that the support vector machine algorithm outperformed the others. Of the three types of information, phenotypic data were the most informative for ADR prediction. When biological and phenotypic features were added to the baseline chemical information, the ADR prediction model achieved significant improvements in area under the curve (from 0.9054 to 0.9524), precision (from 43.37% to 66.17%), and recall (from 49.25% to 63.06%). Most importantly, the proposed model successfully predicted the ADRs associated with withdrawal of rofecoxib and cerivastatin. The results suggest that phenotypic information on drugs is valuable for ADR prediction. Moreover, they demonstrate that different models that combine chemical, biological, or phenotypic information can be built from approved drugs, and they have the potential to detect clinically important ADRs in both preclinical and post-marketing phases.

  10. Influence of Japanese Regulatory Action on Denosumab-Related Hypocalcemia Using Japanese Adverse Drug Event Report Database.

    PubMed

    Takeyama, Mayu; Sai, Kimie; Imatoh, Takuya; Segawa, Katsunori; Hirasawa, Noriyasu; Saito, Yoshiro

    2017-01-01

    The anti-receptor activator of nuclear factor kappa-B ligand (RANKL) antibody, Denosumab (DEN), was approved in April 2012 in Japan, but a Dear Healthcare Professional Letter of Rapid Safety Communication was released in September, 2012 by the regulatory authority because of the severe hypocalcemia risks. Currently, the effectiveness of this regulatory action has not been evaluated and, therefore, this study aimed to assess its impact on DEN-induced hypocalcemia using the Japanese Adverse Drug Event Report database (JADER). The case reports from April 2012 to September 2014 were collected from the JADER, which included 151642 adverse events for the primary suspected drugs. The reporting odds ratio (ROR) of hypocalcemia as a signal of the target adverse event was analyzed for DEN and zoledronic acid (ZOL, a reference drug). Changes in RORs were compared between the pre- (Pre, April 2012 to September 2012) and post- (Post 1, October 2012 to September 2013 and Post 2, October 2013 to September 2014) periods of the regulatory action. A decrease in the hypocalcemia ROR was observed for DEN in the post-periods, especially Post 2. Multivariate logistic regression analysis showed a significant decrease in hypocalcemia signal in Post 1 (p=0.0306 vs. Pre) and Post 2 (p=0.0054 vs. Pre). ZOL caused no significant changes in ROR of hypocalcemia, and none of the drugs caused ROR changes in jaw osteonecrosis (a reference adverse event). This study suggests that the regulatory action against hypocalcemia in DEN effectively decreased hypocalcemia signal. Further studies using medical information databases are needed to confirm this result.

  11. Drug-Associated Acute Kidney Injury Identified in the United States Food and Drug Administration Adverse Event Reporting System Database.

    PubMed

    Welch, Hanna K; Kellum, John A; Kane-Gill, Sandra L

    2018-06-08

    Acute kidney injury (AKI) is a common condition associated with both short-term and long-term consequences including dialysis, chronic kidney disease, and mortality. Although the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database is a powerful tool to examine drug-associated events, to our knowledge, no study has analyzed this database to identify the most common drugs reported with AKI. The objective of this study was to analyze AKI reports and associated medications in the FAERS database. Retrospective pharmacovigilance disproportionality analysis. FAERS database. We queried the FAERS database for reports of AKI from 2004 quarter 1 through 2015 quarter 3. Extracted drugs were assessed using published references and categorized as known, possible, or new potential nephrotoxins. The reporting odds ratio (ROR), a measure of reporting disproportionality, was calculated for the 20 most frequently reported drugs in each category. We retrieved 7,241,385 adverse event reports, of which 193,996 (2.7%) included a report of AKI. Of the AKI reports, 16.5% were known nephrotoxins, 18.6% were possible nephrotoxins, and 64.8% were new potential nephrotoxins. Among the most commonly reported drugs, those with the highest AKI ROR were aprotinin (7,614 reports; ROR 115.70, 95% confidence interval [CI] 110.63-121.01), sodium phosphate (1,687 reports; ROR 55.81, 95% CI 51.78-60.17), furosemide (1,743 reports; ROR 12.61, 95% CI 11.94-13.32), vancomycin (1,270 reports, ROR 12.19, 95% CI 11.45-12.99), and metformin (4,701 reports; ROR 10.65, 95% CI 10.31-11.00). The combined RORs for the 20 most frequently reported drugs with each nephrotoxin classification were 3.71 (95% CI 3.66-3.76) for known nephrotoxins, 2.09 (95% CI 2.06-2.12) for possible nephrotoxins, and 1.55 (95% CI 1.53-1.57) for new potential nephrotoxins. AKI was a common reason for adverse event reporting in the FAERS. Most AKI reports were generated for medications not recognized

  12. [Patterns of drug consumption and the occurrence of adverse drug reactions among students of public health].

    PubMed

    Plichta, Danuta; Doryńska, Agnieszka; Spiewak, Radosław

    2012-04-01

    The research of drug consumption is focused mainly upon the elderly, while the knowledge of drug consumption patterns among young people remains insufficient. Public health students (PHS) seem of particular interest as future opinion leaders and drug policy makers. The aim of the study was to analyze opinions and patterns of drug consumption, and adverse drug reactions (ADR) in this group. 130 PHS took part in the anonymous questionnaire survey. All students admitted to using some drug at least once in their lives. While purchasing over-the-counter (OTC) drugs, 51.6% students trusted their own knowledge and experience. Women more often relied on a pharmacist's recommendation (47.2% vs 21.7% men; p = 0.045), while men were more influenced by advertising (34.8% vs 12.3% women, p = 0.008). Strict adherence to recommended dosage of OTC and prescription drugs (Rx) was declared by 41.1% and 71.9% students, respectively. Every fourth student (24.8%) admitted to having purchased a Rx drug at least once without having the prescription. Past episodes of ADR to OTC were reported by 7.8% students and to Rx by 38.4% (p < 0.001). Respectively 27.2% and 34.4% students were never, or hardly ever asked about past ADR by prescribing physicians. According to 89.2% students, drug advertising should be subject to regulation and policing, and 66.1% considered it inaccurate and unreliable. Forty-five percent of students had an OTC drug on them while responding the questionnaire, 20.0% had a prescription drug. Students of public health seem to be notorious consumers of drugs and their attitude seems not fully rational.

  13. Adverse drug reactions to antiretroviral therapy (ARVs): incidence, type and risk factors in Nigeria

    PubMed Central

    2012-01-01

    Background Data on adverse drug reactions (ADRs) related to antiretroviral (ARV) use in public health practice are few indicating the need for ART safety surveillance in clinical care. Objectives To evaluate the incidence, type and risk factors associated with adverse drug reactions (ADRs) among patients on antiretroviral drugs (ARV). Methods Patients initiated on ARVs between May 2006 and May 2009 were evaluated in a retrospective cohort analysis in three health facilities in Nigeria. Regimens prescribed include nucleoside backbone of zidovudine (AZT)/lamivudine (3TC), stavudine (d4T)/3TC, or tenofovir (TDF)/3TC in combination with either nevirapine (NVP) or efavirenz (EFV). Generalized Estimating Equation (GEE) model was used to identify risk factors associated with occurrence of ADR. Results 2650 patients were followed-up for 2456 person-years and reported 114 ADRs (incidence rate = 4.6/100 person-years).There were more females 1706(64%) and 73(64%) of the ADRs were reported by women. Overall, 61(54%) of ADRs were reported by patients on AZT with 54(47%) of these occurring in patients on AZT/NVP. The commonest ADRs reported were pain 25(30%) and skinrash 10(18%). Most ADRs were grade 1(39%) with only 1% being life threatening (grade 4). Adjusted GEE analysis showed that ADR was less likely to occur in patients on longer duration of ART compared to the first six months on treatment; 6-12 months AOR 0.38(95% CI:0.16-0.91) and 12-24 months AOR 0.34(95% CI:0.16-0.73) respectively. Compared to patients on TDF, ADR was less likely to occur in patients on d4T and AZT AOR 0.18(95% CI 0.05-0.64) and AOR 0.24(95% CI:0.7-0.9) respectively. Age, gender and CD4 count were not significantly associated with ADRs. Conclusion ADRs are more likely to occur within the first six months on treatment. Close monitoring within this period is required to prevent occurrence of severe ADR and improve ART adherence. Further research on the tolerability of tenofovir in this environment is

  14. Building a knowledge base of severe adverse drug events based on AERS reporting data using semantic web technologies.

    PubMed

    Jiang, Guoqian; Wang, Liwei; Liu, Hongfang; Solbrig, Harold R; Chute, Christopher G

    2013-01-01

    A semantically coded knowledge base of adverse drug events (ADEs) with severity information is critical for clinical decision support systems and translational research applications. However it remains challenging to measure and identify the severity information of ADEs. The objective of the study is to develop and evaluate a semantic web based approach for building a knowledge base of severe ADEs based on the FDA Adverse Event Reporting System (AERS) reporting data. We utilized a normalized AERS reporting dataset and extracted putative drug-ADE pairs and their associated outcome codes in the domain of cardiac disorders. We validated the drug-ADE associations using ADE datasets from SIDe Effect Resource (SIDER) and the UMLS. We leveraged the Common Terminology Criteria for Adverse Event (CTCAE) grading system and classified the ADEs into the CTCAE in the Web Ontology Language (OWL). We identified and validated 2,444 unique Drug-ADE pairs in the domain of cardiac disorders, of which 760 pairs are in Grade 5, 775 pairs in Grade 4 and 2,196 pairs in Grade 3.

  15. Molecular Docking for Prediction and Interpretation of Adverse Drug Reactions.

    PubMed

    Luo, Heng; Fokoue-Nkoutche, Achille; Singh, Nalini; Yang, Lun; Hu, Jianying; Zhang, Ping

    2018-05-23

    Adverse drug reactions (ADRs) present a major burden for patients and the healthcare industry. Various computational methods have been developed to predict ADRs for drug molecules. However, many of these methods require experimental or surveillance data and cannot be used when only structural information is available. We collected 1,231 small molecule drugs and 600 human proteins and utilized molecular docking to generate binding features among them. We developed machine learning models that use these docking features to make predictions for 1,533 ADRs. These models obtain an overall area under the receiver operating characteristic curve (AUROC) of 0.843 and an overall area under the precision-recall curve (AUPR) of 0.395, outperforming seven structural fingerprint-based prediction models. Using the method, we predicted skin striae for fluticasone propionate, dermatitis acneiform for mometasone, and decreased libido for irinotecan, as demonstrations. Furthermore, we analyzed the top binding proteins associated with some of the ADRs, which can help to understand and/or generate hypotheses for underlying mechanisms of ADRs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. [Adverse drug reaction reporting in emergency medicine].

    PubMed

    Milojevic, Kolia; Chassagnol, Isabelle; Brion, Nathalie; Cléro, Joël; Degrèze, Nathalie; Lambert, Yves

    2004-01-01

    A regional survey was performed between June and September 2002, to evaluate knowledge and attitudes of emergency physicians regarding adverse drug reaction (ADR) reporting in a French district. 100 questionnaires completed by physicians working in emergency departments and/or mobile intensive care units were analysed. The frequency of ADRs encountered by emergency practitioners was estimated at > or = 0.73 per year and per physician. The ADR notification rate in emergency medicine was estimated at < or = 6%. A minority of physicians were responsible for the majority of ADR reporting. Sixty-four percent of emergency physicians underestimated the conditions required for ADR notification: 28% thought that certain causality was an absolute necessary condition for notification, while 37% considered that notification was required only for ADRs that were both severe and unexpected. Interventions focused on advertising ADR reporting procedures could help to improve the notification rate in emergency medicine.

  17. HLA-B*1502 allele is associated with a cross-reactivity pattern of cutaneous adverse reactions to antiepileptic drugs.

    PubMed

    Wang, J; Zhang, J; Wu, X; Yu, P; Hong, Z

    2012-01-01

    The US Food and Drug Administration has recommended genetic screening for the human leucocyte antigen-B (HLA-B)*1502 allele in patients of Asian ethnicity before starting carbamazepine therapy, to avoid the fatal adverse treatment-related events associated with this drug. The association between cross-reactivity to antiepileptic drugs (AEDs) and the HLA-B*1502 allele has been only rarely reported. Here, two cases of cross-reactivity to AEDs, where cutaneous adverse drug reactions (cADRs) developed in female Han Chinese patients with epilepsy who tested positive for the HLA-B*1502 allele, are described. If the genetic association could be confirmed in larger studies, the HLA-B*1502 allele should be tested for in any patient experiencing cADRs, to avoid crossreactivity to AEDs.

  18. Adverse Reactions Associated With Cannabis Consumption as Evident From Search Engine Queries

    PubMed Central

    Lev-Ran, Shaul

    2017-01-01

    Background Cannabis is one of the most widely used psychoactive substances worldwide, but adverse drug reactions (ADRs) associated with its use are difficult to study because of its prohibited status in many countries. Objective Internet search engine queries have been used to investigate ADRs in pharmaceutical drugs. In this proof-of-concept study, we tested whether these queries can be used to detect the adverse reactions of cannabis use. Methods We analyzed anonymized queries from US-based users of Bing, a widely used search engine, made over a period of 6 months and compared the results with the prevalence of cannabis use as reported in the US National Survey on Drug Use in the Household (NSDUH) and with ADRs reported in the Food and Drug Administration’s Adverse Drug Reporting System. Predicted prevalence of cannabis use was estimated from the fraction of people making queries about cannabis, marijuana, and 121 additional synonyms. Predicted ADRs were estimated from queries containing layperson descriptions to 195 ICD-10 symptoms list. Results Our results indicated that the predicted prevalence of cannabis use at the US census regional level reaches an R2 of .71 NSDUH data. Queries for ADRs made by people who also searched for cannabis reveal many of the known adverse effects of cannabis (eg, cough and psychotic symptoms), as well as plausible unknown reactions (eg, pyrexia). Conclusions These results indicate that search engine queries can serve as an important tool for the study of adverse reactions of illicit drugs, which are difficult to study in other settings. PMID:29074469

  19. Adverse Health Consequences of Performance-Enhancing Drugs: An Endocrine Society Scientific Statement

    PubMed Central

    Pope, Harrison G.; Wood, Ruth I.; Rogol, Alan; Nyberg, Fred; Bowers, Larry

    2014-01-01

    Despite the high prevalence of performance-enhancing drug (PED) use, media attention has focused almost entirely on PED use by elite athletes to illicitly gain a competitive advantage in sports, and not on the health risks of PEDs. There is a widespread misperception that PED use is safe or that adverse effects are manageable. In reality, the vast majority of PED users are not athletes but rather nonathlete weightlifters, and the adverse health effects of PED use are greatly underappreciated. This scientific statement synthesizes available information on the medical consequences of PED use, identifies gaps in knowledge, and aims to focus the attention of the medical community and policymakers on PED use as an important public health problem. PED users frequently consume highly supraphysiologic doses of PEDs, combine them with other PEDs and/or other classical drugs of abuse, and display additional associated risk factors. PED use has been linked to an increased risk of death and a wide variety of cardiovascular, psychiatric, metabolic, endocrine, neurologic, infectious, hepatic, renal, and musculoskeletal disorders. Because randomized trials cannot ethically duplicate the large doses of PEDs and the many factors associated with PED use, we need observational studies to collect valid outcome data on the health risks associated with PEDs. In addition, we need studies regarding the prevalence of PED use, the mechanisms by which PEDs exert their adverse health effects, and the interactive effects of PEDs with sports injuries and other high-risk behaviors. We also need randomized trials to assess therapeutic interventions for treating the adverse effects of PEDs, such as the anabolic-androgen steroid withdrawal syndrome. Finally, we need to raise public awareness of the serious health consequences of PEDs. PMID:24423981

  20. Gingival bleeding, a possible "serious" adverse drug reaction: An observational study in the French PharmacoVigilance Database.

    PubMed

    Bondon-Guitton, Emmanuelle; Mourgues, Thibaut; Rousseau, Vanessa; Cousty, Sarah; Cottin, Judith; Drablier, Guillaume; Micallef, Joëlle; Montastruc, Jean-Louis

    2017-09-01

    Antithrombotic drugs are known to increase the risk of gingival bleeding because they affect coagulation. However, other drugs could also be involved in gingival bleeding. We performed a pharmacoepidemiological study to identify the drugs most frequently "suspected" in the occurrence of gingival bleeding. We selected reports of "gingival bleeding" from 1 January 1985 to 30 September 2014 in the French PharmacoVigilance Database. Among 523,808 reports of adverse drug reactions, we identified 454 reports of gingival bleeding (0.09%). Most of them were "serious" (58.4%) and occurred in females (54.6%). The frequency of gingival bleeding increased with age. The most frequently "suspected" drugs were antithrombotics (67.8%), particularly fluindione. Other drugs frequently involved were furosemide followed by paracetamol, amiodarone, amoxicillin, paroxetine, ketoprofen, zolpidem, enalapril and ramipril. Thirty-nine reports involved a drug-drug interaction with antithrombotics, mainly with anti-infectives. Gingival bleeding can be an adverse drug reaction, often "serious" and rarely fatal. Patients older than 50 years and women are particularly at risk. Among drugs known to increase the risk of gingival bleeding, the most frequently involved were fluindione, furosemide, paracetamol, amiodarone, amoxicillin, paroxetine or ketoprofen. We also identified signal for drugs not usually known to be involved in bleeding, like zolpidem, enalapril or ramipril. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Limitations and obstacles of the spontaneous adverse drugs reactions reporting: Two “challenging” case reports

    PubMed Central

    Palleria, Caterina; Leporini, Christian; Chimirri, Serafina; Marrazzo, Giuseppina; Sacchetta, Sabrina; Bruno, Lucrezia; Lista, Rosaria M.; Staltari, Orietta; Scuteri, Antonio; Scicchitano, Francesca; Russo, Emilio

    2013-01-01

    Introduction: Nowadays, based on several epidemiological data, iatrogenic disease is an emerging public health problem, especially in industrialized countries. Adverse drugs reactions (ADRs) are extremely common and, therefore, clinically, socially, and economically worthy of attention. Spontaneous reporting system for suspected ADRs represents the cornerstone of the pharmacovigilance, because it allows rapid detection of potential alarm signals related to drugs use. However, spontaneous reporting system shows several limitations, which are mainly related to under-reporting. In this paper, we describe two particular case reports, which emphasize some reasons of under-reporting and other common criticisms of spontaneous reporting systems. Materials and Methods: We performed a computer-aided search of Medline, PubMed, Embase, Cochrane library databases, national and international databases of suspected ADRs reports in order to identify previous published case reports and spontaneous reports about the ADRs reviewed in this paper, and to examine the role of suspected drugs in the pathogenesis of the described adverse reactions. Results: First, we reported a case of tizanidine-induced hemorrhagic cystitis. In the second case report, we presented an episode of asthma exacerbation after taking bimatoprost. Through the review of these two cases, we highlighted some common criticisms of spontaneous reporting systems: under-reporting and false causality attribution. Discussion and Conclusion: Healthcare workers sometimes do not report ADRs because it is challenging to establish with certainty the causal relationship between drug and adverse reaction; however, according to a key principle of pharmacovigilance, it is always better to report even a suspicion to generate an alarm in the interest of protecting public health. PMID:24347986

  2. Gender differences in the effects of childhood adversity on alcohol, drug, and polysubstance-related disorders.

    PubMed

    Evans, Elizabeth A; Grella, Christine E; Upchurch, Dawn M

    2017-07-01

    To examine gender differences in the associations between childhood adversity and different types of substance use disorders and whether gender moderates these relationships. We analyzed data from 19,209 women and 13,898 men as provided by Wave 2 (2004-2005) of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) to examine whether gender moderates the associations between childhood adversity and DSM-IV defined lifetime occurrence of alcohol, drug, and polysubstance-related disorders. We used multinomial logistic regression, weighted to be representative of the US adult civilian, noninstitutionalized population, and we calculated predicted probabilities by gender, controlling for covariates. To test which specific moderation contrasts were statistically significant, we conducted pair-wise comparisons corrected for multiple comparisons using Bonferroni's method. For each type of substance use disorder, risk was increased by more exposure to childhood adversity, and women had a lower risk than men. However, moderation effects revealed that with more experiences of childhood adversity, the gender gap in predicted probability for a disorder narrowed in relation to alcohol, it converged in relation to drugs such that risk among women surpassed that among men, and it widened in relation to polysubstances. Knowledge regarding substance-specific gender differences associated with childhood adversity exposure can inform evidence-based treatments. It may also be useful for shaping other types of gender-sensitive public health initiatives to ameliorate or prevent different types of substance use disorders.

  3. Predicting Adverse Drug Effects from Literature- and Database-Mined Assertions.

    PubMed

    La, Mary K; Sedykh, Alexander; Fourches, Denis; Muratov, Eugene; Tropsha, Alexander

    2018-06-06

    Given that adverse drug effects (ADEs) have led to post-market patient harm and subsequent drug withdrawal, failure of candidate agents in the drug development process, and other negative outcomes, it is essential to attempt to forecast ADEs and other relevant drug-target-effect relationships as early as possible. Current pharmacologic data sources, providing multiple complementary perspectives on the drug-target-effect paradigm, can be integrated to facilitate the inference of relationships between these entities. This study aims to identify both existing and unknown relationships between chemicals (C), protein targets (T), and ADEs (E) based on evidence in the literature. Cheminformatics and data mining approaches were employed to integrate and analyze publicly available clinical pharmacology data and literature assertions interrelating drugs, targets, and ADEs. Based on these assertions, a C-T-E relationship knowledge base was developed. Known pairwise relationships between chemicals, targets, and ADEs were collected from several pharmacological and biomedical data sources. These relationships were curated and integrated according to Swanson's paradigm to form C-T-E triangles. Missing C-E edges were then inferred as C-E relationships. Unreported associations between drugs, targets, and ADEs were inferred, and inferences were prioritized as testable hypotheses. Several C-E inferences, including testosterone → myocardial infarction, were identified using inferences based on the literature sources published prior to confirmatory case reports. Timestamping approaches confirmed the predictive ability of this inference strategy on a larger scale. The presented workflow, based on free-access databases and an association-based inference scheme, provided novel C-E relationships that have been validated post hoc in case reports. With refinement of prioritization schemes for the generated C-E inferences, this workflow may provide an effective computational method for

  4. Adverse drug events related to mood and emotion in paediatric patients treated for ADHD: A meta-analysis.

    PubMed

    Pozzi, Marco; Carnovale, Carla; Peeters, Gabriëlla G A M; Gentili, Marta; Antoniazzi, Stefania; Radice, Sonia; Clementi, Emilio; Nobile, Maria

    2018-05-22

    ADHD is frequently comorbid with anxiety and mood disorders, which may increase the severity of inattention and hyperactivity symptoms. Emotional symptoms (anxiety, irritability, mood lability) also affect patients without comorbidity or emerge as adverse drug events. The influence of ADHD drugs on emotional symptoms demands investigation to improve therapies. Systematic review of trials reporting adverse events in patients pharmacologically treated for ADHD. Meta-analysis of the occurrence of irritability, anxiety, apathy, reduced talk, sadness, crying, emotional lability, biting nails, staring, perseveration, euphoria. Meta-regression analysis. Forty-five trials were meta-analysed. The most frequently reported outcomes were irritability, anxiety, sadness, and apathy. Methylphenidates, especially immediate-release formulations, were most studied; amphetamines were half as studied and were predominantly mixed amphetamine salts. Reports on atomoxetine were scant. Meta-analysis showed that methylphenidates reduced the risk of irritability, anxiety, euphoria, whereas they worsened the risk of apathy and reduced talk; amphetamines worsened the risk of emotional lability. Factors influencing risks were study year and design, patients' sex and age, drug dose and release formulation. Possible discrepancy between adverse events as indicated in clinical trials and as summarised herein. Confounding due to the aggregation of drugs into groups; uninvestigated sources of bias; incomplete lists of adverse events; lack of observations on self-injury. Methylphenidates appeared safer than amphetamines, although younger patients and females may incur higher risks, especially with high-dose, immediate-release methylphenidates. Only atomoxetine holds a black-box warning, but amphetamines and methylphenidates also did not show a safe profile regarding mood and emotional symptoms. Copyright © 2018. Published by Elsevier B.V.

  5. Diagnostic patch testing following tuberculosis-associated cutaneous adverse drug reactions induces systemic reactions in HIV-infected persons.

    PubMed

    Lehloenya, R J; Todd, G; Wallace, J; Ngwanya, M R; Muloiwa, R; Dheda, K

    2016-07-01

    The incidence of cutaneous adverse drug reactions (CADRs) to first-line antituberculosis drugs (FLTDs) is higher in HIV-tuberculosis coinfection. However, the utility of patch testing to identify the offending drug in this patient subgroup has been poorly studied. To identify drugs causing adverse drug reactions in patients with HIV-tuberculosis coinfection. Fourteen consecutive patients underwent diagnostic work-up (patch testing followed by a skin prick test and an oral rechallenge) to pinpoint the offending drug after developing FLTD-associated CADR, which included drug rash with eosinophilia and systemic symptoms (n = 12), Stevens-Johnson syndrome (SJS, n = 1) and toxic epidermal necrolysis/SJS overlap (n = 1). A positive reaction to any of the three diagnostic modalities eliminated that drug from the regimen. Once patients were clinically stable postreaction, sequential and additive rechallenge with FLTDs was initiated. Eleven of the 14 participants with FLTD-associated CADR were HIV infected (median CD4 count 149 cells mm(-3) ). In this subgroup, patch testing resulted in generalized systemic reactions in 10 of 11 patients (91%). These included rash in 10 of 13 reactions (77%), eosinophilia in eight (62%), transaminitis in seven (54%) and fever in five (38%). Isoniazid caused six of 13 (46%) generalized systemic reactions, rifampicin four (31%), ethambutol two (15%) and pyrazinamide one reaction. Using the Common Terminology Criteria for Adverse Events, five of 13 reactions were mild, six were moderate and two were severe. There were no life-threatening or fatal reactions. In HIV-infected persons with tuberculosis-associated CADR, although patch-testing reactions to FLTD are common and tend to be associated with systemic features, they are not life threatening or fatal. These data inform clinical practice in HIV-endemic settings. © 2016 British Association of Dermatologists.

  6. High-Performance Signal Detection for Adverse Drug Events using MapReduce Paradigm.

    PubMed

    Fan, Kai; Sun, Xingzhi; Tao, Ying; Xu, Linhao; Wang, Chen; Mao, Xianling; Peng, Bo; Pan, Yue

    2010-11-13

    Post-marketing pharmacovigilance is important for public health, as many Adverse Drug Events (ADEs) are unknown when those drugs were approved for marketing. However, due to the large number of reported drugs and drug combinations, detecting ADE signals by mining these reports is becoming a challenging task in terms of computational complexity. Recently, a parallel programming model, MapReduce has been introduced by Google to support large-scale data intensive applications. In this study, we proposed a MapReduce-based algorithm, for common ADE detection approach, Proportional Reporting Ratio (PRR), and tested it in mining spontaneous ADE reports from FDA. The purpose is to investigate the possibility of using MapReduce principle to speed up biomedical data mining tasks using this pharmacovigilance case as one specific example. The results demonstrated that MapReduce programming model could improve the performance of common signal detection algorithm for pharmacovigilance in a distributed computation environment at approximately liner speedup rates.

  7. The importance of monitoring adverse drug reactions in pediatric patients: the results of a national surveillance program in Italy.

    PubMed

    Carnovale, Carla; Brusadelli, Tatiana; Zuccotti, GianVincenzo; Beretta, Silvia; Sullo, Maria Giuseppa; Capuano, Annalisa; Rossi, Francesco; Moschini, Martina; Mugelli, Alessandro; Vannacci, Alfredo; Laterza, Marcella; Clementi, Emilio; Radice, Sonia

    2014-09-01

    To gain information on safety of drugs used in pediatrics through a 4-year post-marketing active pharmacovigilance program. The program sampled the Italian population and was termed 'Monitoring of the Adverse Effects in Pediatric population' (MEAP). Adverse drug reactions (ADRs) were collected for individuals aged 0 - 17 years treated in hospitals and territorial health services in Lombardy, Tuscany, Apulia and Campania; located to gain an appropriate sampling of the population. ADRs were evaluated using the Adverse Drug Reaction Probability Scale (Naranjo) and analyzed with respect to time, age, sex, category of ADR, seriousness, suspected medicines, type of reporter and off-label use. We collected and analyzed reports from 3539 ADRs. Vaccines, antineoplastic and psychotropic drugs were the most frequently pharmacotherapeutic subgroups involved. Seventeen percent of reported ADRs were serious; of them fever, vomiting and angioedema were the most frequently reported. Eight percent of ADRs were associated with off-label use, and 10% were unknown ADRs. Analysis of these revealed possible strategies of therapy optimization. The MEAP project demonstrated that active post-marketing pharmacovigilance programs are a valid strategy to increase awareness on pediatric pharmacology, reduce underreporting and provide information on drug actions in pediatrics. This information enhances drug therapy optimization in the pediatric patients.

  8. Adverse Drug Reactions and Expected Effects to Therapy with Subcutaneous Mistletoe Extracts (Viscum album L.) in Cancer Patients

    PubMed Central

    Steele, Megan L.; Happe, Antje; Kröz, Matthias; Matthes, Harald; Schad, Friedemann

    2014-01-01

    Background. In Europe, mistletoe extracts are widely used as a complementary cancer therapy. We assessed the safety of subcutaneous mistletoe as a conjunctive therapy in cancer patients within an anthroposophic medicine setting in Germany. Methods. A multicentre, observational study was performed within the Network Oncology. Suspected mistletoe adverse drug reactions (ADRs) were described by frequency, causality, severity, and seriousness. Potential risk factors, dose relationships and drug-drug interactions were investigated. Results. Of 1923 cancer patients treated with subcutaneous mistletoe extracts, 283 patients (14.7%) reported 427 expected effects (local reactions <5 cm and increased body temperature <38°C). ADRs were documented in 162 (8.4%) patients who reported a total of 264 events. ADRs were mild (50.8%), moderate (45.1%), or severe (4.2%). All were nonserious. Logistic regression analysis revealed that expected effects were more common in females, while immunoreactivity decreased with increasing age and tumour stage. No risk factors were identified for ADRs. ADR frequency increased as mistletoe dose increased, while fewer ADRs occurred during mistletoe therapy received concurrent with conventional therapies. Conclusion. The results of this study indicate that mistletoe therapy is safe. ADRs were mostly mild to moderate in intensity and appear to be dose-related and explained by the immune-stimulating, pharmacological activity of mistletoe. PMID:24672577

  9. Attitudes and Usage of the Food and Drug Administration Adverse Event Reporting System Among Gastroenterology Nurse Practitioners and Physician Assistants.

    PubMed

    Salk, Allison; Ehrenpreis, Eli D

    2016-01-01

    The Food and Drug Administration Adverse Event Reporting System (FAERS) is used for postmarketing pharmacovigilance. Our study sought to assess attitudes and usage of the FAERS among gastroenterology nurse practitioners (NPs) and physician assistants (PAs). A survey was administered at the August 2012 Principles of Gastroenterology for the Nurse Practitioner and Physician Assistant course, held in Chicago, IL. Of the 128 respondents, 123 (96%) reported a specialty in gastroenterology or hepatology and were included in analysis. Eighty-nine participants were NPs and 32 PAs, whereas 2 did not report their profession. Although 119 (98%) agreed or strongly agreed with the statement that accurately reporting adverse drug reactions is an important process to optimize patient safety, the majority of participants (54% NPs and 81% PAs) were unfamiliar with the FAERS. In addition, only 20% of NPs and 9% of PAs reported learning about the FAERS in NP or PA schooling. Our study shows enthusiasm among gastroenterology NPs and PAs for the reporting of adverse drug reactions, coupled with a lack of familiarity with the FAERS. This presents an opportunity for enhanced education about reporting of adverse drug reactions for gastroenterology NPs and PAs.

  10. [Direct costs and clinical aspects of adverse drug reactions in patients admitted to a level 3 hospital internal medicine ward].

    PubMed

    Tribiño, Gabriel; Maldonado, Carlos; Segura, Omar; Díaz, Jorge

    2006-03-01

    Adverse drug reactions (ADRs) occur frequently in hospitals and increase costs of health care; however, few studies have quantified the clinical and economic impact of ADRs in Colombia. These impacts were evaluated by calculating costs associated with ADRs in patients hospitalized in the internal medicine ward of a Level 3 hospital located in Bogotá, Colombia. In addition, salient clinical features of ADRs were identified and characterized. Intensive follow-ups for a cohort of patients were conducted for a five month period in order to detect ADRs; different ways to classify them, according to literature, were considered as well. Information was collected using the INVIMA reporting format, and causal probability was evaluated with the Naranjo algorithm. Direct costs were calculated from the perspective of payer, based on the following costs: additional hospital stay, medications, paraclinical tests, additional procedures, patient displacement to intermediate or intensive care units, and other costs. Of 836 patients admitted to the service, 268 adverse drug reactions were detected in 208 patients (incidence proportion 25.1%, occurence rate 0.32). About the ADRs found, 74.3% were classified as probable, 92.5% were type A, and 81.3% were moderate. The body system most often affected was the circulatory system (33.9%). Drugs acting on the blood were most frequently those ones associated with adverse reactions (37.6%). The costs resulting from medical care of adverse drug reactions varied from COL dollar 93,633,422 (USD dollar 35,014.92) to COL dollar 122,155,406 (USD dollar 45,680.94), according to insurance type, during the study period. Adverse drug reactions have a significant negative health and financial impact on patient welfare. Because of the substantial resources required for their medical care and the significant proportion of preventable adverse reactions, active programs of institutional pharmacovigilance are highly recommended.

  11. Pharmacogenetics of risperidone therapy in autism: association analysis of eight candidate genes with drug efficacy and adverse drug reactions.

    PubMed

    Correia, C T; Almeida, J P; Santos, P E; Sequeira, A F; Marques, C E; Miguel, T S; Abreu, R L; Oliveira, G G; Vicente, A M

    2010-10-01

    Little has been reported on the factors, genetic or other, that underlie the variability in individual response, particularly for autism. In this study we simultaneously explored the effects of multiple candidate genes on clinical improvement and occurrence of adverse drug reactions, in 45 autistic patients who received monotherapy with risperidone up to 1 year. Candidate genes involved in the pharmacokinetics (CYP2D6 and ABCB1) and pharmacodynamics (HTR2A, HTR2C, DRD2, DRD3, HTR6) of the drug, and the brain-derived neurotrophic factor (BDNF) gene, were analysed. Using the generalized estimating equation method these genes were tested for association with drug efficacy, assessed with the Autism Treatment Evaluation Checklist, and with safety and tolerability measures, such as prolactin levels, body mass index (BMI), waist circumference and neurological adverse effects, including extrapyramidal movements. Our results confirm that risperidone therapy was very effective in reducing some autism symptoms and caused few serious adverse effects. After adjusting for confounding factors, the HTR2A c.-1438G>A, DRD3 Ser9Gly, HTR2C c.995G>A and ABCB1 1236C>T polymorphisms were predictors for clinical improvement with risperidone therapy. The HTR2A c.-1438G>A, HTR2C c.68G>C (p.C33S), HTR6 c.7154-2542C>T and BDNF c.196G>A (p.V66M) polymorphisms influenced prolactin elevation. HTR2C c.68G>C and CYP2D6 polymorphisms were associated with risperidone-induced increase in BMI or waist circumference. We thus identified for the first time several genes implicated in risperidone efficacy and safety in autism patients. Although association results require replication, given the small sample size, the study makes a preliminary contribution to the personalized therapy of risperidone in autism.

  12. Adverse Drug Reaction Identification and Extraction in Social Media: A Scoping Review

    PubMed Central

    Bellet, Florelle; Asfari, Hadyl; Souvignet, Julien; Texier, Nathalie; Jaulent, Marie-Christine; Beyens, Marie-Noëlle; Burgun, Anita; Bousquet, Cédric

    2015-01-01

    Background The underreporting of adverse drug reactions (ADRs) through traditional reporting channels is a limitation in the efficiency of the current pharmacovigilance system. Patients’ experiences with drugs that they report on social media represent a new source of data that may have some value in postmarketing safety surveillance. Objective A scoping review was undertaken to explore the breadth of evidence about the use of social media as a new source of knowledge for pharmacovigilance. Methods Daubt et al’s recommendations for scoping reviews were followed. The research questions were as follows: How can social media be used as a data source for postmarketing drug surveillance? What are the available methods for extracting data? What are the different ways to use these data? We queried PubMed, Embase, and Google Scholar to extract relevant articles that were published before June 2014 and with no lower date limit. Two pairs of reviewers independently screened the selected studies and proposed two themes of review: manual ADR identification (theme 1) and automated ADR extraction from social media (theme 2). Descriptive characteristics were collected from the publications to create a database for themes 1 and 2. Results Of the 1032 citations from PubMed and Embase, 11 were relevant to the research question. An additional 13 citations were added after further research on the Internet and in reference lists. Themes 1 and 2 explored 11 and 13 articles, respectively. Ways of approaching the use of social media as a pharmacovigilance data source were identified. Conclusions This scoping review noted multiple methods for identifying target data, extracting them, and evaluating the quality of medical information from social media. It also showed some remaining gaps in the field. Studies related to the identification theme usually failed to accurately assess the completeness, quality, and reliability of the data that were analyzed from social media. Regarding

  13. A case of adverse drug reaction induced by dispensing error.

    PubMed

    Gallelli, L; Staltari, O; Palleria, C; Di Mizio, G; De Sarro, G; Caroleo, B

    2012-11-01

    To report about a case of acute renal failure due to absence of communication between physician and patient. A 78 year old man with human immunodeficiency virus (HIV) accessed our hospital and was brought to our attention in August 2011 for severe renal failure. Clinical history revealed that he had been taking highly active antiretroviral therapy with lamivudine/abacavir and fosamprenavir since 2006. In April 2011 due to an augmentation in creatinine plasma levels, a reduction in lamivudine dosage to 100 mg/day and the prescription of abacavir 300 mg/day became necessary. Unfortunately, the patient took both lamivudine and abacavir therefore the association of the two medications (lamivudine/abacavir) lead to asthenia and acute renal failure within a few days. This case emphasizes the importance about how physicians must pay very careful attention during drug prescription, most particularly, as far as elderly patients are concerned. In fact, communication improvement between physicians and patients can prevent increase of adverse drug reactions related to drug dispensing, with consequential reduction of costs in the healthcare system. Copyright © 2012 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  14. On the creation of a clinical gold standard corpus in Spanish: Mining adverse drug reactions.

    PubMed

    Oronoz, Maite; Gojenola, Koldo; Pérez, Alicia; de Ilarraza, Arantza Díaz; Casillas, Arantza

    2015-08-01

    The advances achieved in Natural Language Processing make it possible to automatically mine information from electronically created documents. Many Natural Language Processing methods that extract information from texts make use of annotated corpora, but these are scarce in the clinical domain due to legal and ethical issues. In this paper we present the creation of the IxaMed-GS gold standard composed of real electronic health records written in Spanish and manually annotated by experts in pharmacology and pharmacovigilance. The experts mainly annotated entities related to diseases and drugs, but also relationships between entities indicating adverse drug reaction events. To help the experts in the annotation task, we adapted a general corpus linguistic analyzer to the medical domain. The quality of the annotation process in the IxaMed-GS corpus has been assessed by measuring the inter-annotator agreement, which was 90.53% for entities and 82.86% for events. In addition, the corpus has been used for the automatic extraction of adverse drug reaction events using machine learning. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    PubMed

    Hauben, Manfred; Aronson, Jeffrey K

    2007-01-01

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

  16. Spontaneous adverse drug reaction reporting in rural districts of Mozambique.

    PubMed

    Sevene, Esperança; Mariano, Alda; Mehta, Ushma; Machai, Maria; Dodoo, Alexander; Vilardell, David; Patel, Sam; Barnes, Karen; Carné, Xavier

    2008-01-01

    The roll out of various public health programmes involving mass administration of medicines calls for the deployment of responsive pharmacovigilance systems to permit identification of signals of rare or even common adverse reactions. In developing countries in Africa, these systems are mostly absent and their performance under any circumstance is difficult to predict given the known shortage of human, financial and technical resources. Nevertheless, the importance of such systems in all countries is not in doubt, and research to identify problems, with the aim of offering pragmatic solutions, is urgently needed. To examine the impact of training and monitoring of healthcare workers, making supervisory visits and the availability of telecommunication and transport facilities on the implementation of a pharmacovigilance system in Mozambique. This was a descriptive study enumerating the lessons learnt and challenges faced in implementing a spontaneous reporting system in two rural districts of Mozambique - Namaacha and Matutuíne - where remote location, poor telecommunication services and a low level of education of health professionals are ongoing challenges. A 'yellow card' system for spontaneous reporting of adverse drug reactions (ADRs) was instituted following training of health workers in the selected districts. Thirty-five health professionals (3 medical doctors, 2 technicians, 24 nurses, 4 basic healthcare agents and 2 pharmacy agents) in these districts were trained to diagnose, treat and report ADRs to all medicines using a standardized yellow card system. There were routine site visits to identify and clarify any problems in filling in and sending the forms. One focal person was identified in each district to facilitate communication between the health professionals and the National Pharmacovigilance Unit (NPU). The report form was assessed for quality and causality. The availability of telecommunications and transport was assessed. Fourteen months after

  17. Analysis of factors associated with hiccups based on the Japanese Adverse Drug Event Report database.

    PubMed

    Hosoya, Ryuichiro; Uesawa, Yoshihiro; Ishii-Nozawa, Reiko; Kagaya, Hajime

    2017-01-01

    Hiccups are occasionally experienced by most individuals. Although hiccups are not life-threatening, they may lead to a decline in quality of life. Previous studies showed that hiccups may occur as an adverse effect of certain medicines during chemotherapy. Furthermore, a male dominance in hiccups has been reported. However, due to the limited number of studies conducted on this phenomenon, debate still surrounds the few factors influencing hiccups. The present study aimed to investigate the influence of medicines and patient characteristics on hiccups using a large-sized adverse drug event report database and, specifically, the Japanese Adverse Drug Event Report (JADER) database. Cases of adverse effects associated with medications were extracted from JADER, and Fisher's exact test was performed to assess the presence or absence of hiccups for each medication. In a multivariate analysis, we conducted a multiple logistic regression analysis using medication and patient characteristic variables exhibiting significance. We also examined the role of dexamethasone in inducing hiccups during chemotherapy. Medicines associated with hiccups included dexamethasone, levofolinate, fluorouracil, oxaliplatin, carboplatin, and irinotecan. Patient characteristics associated with hiccups included a male gender and greater height. The combination of anti-cancer agent and dexamethasone use was noted in more than 95% of patients in the dexamethasone-use group. Hiccups also occurred in patients in the anti-cancer agent-use group who did not use dexamethasone. Most of the medications that induce hiccups are used in chemotherapy. The results of the present study suggest that it is possible to predict a high risk of hiccups using patient characteristics. We confirmed that dexamethasone was the drug that has the strongest influence on the induction of hiccups. However, the influence of anti-cancer agents on the induction of hiccups cannot be denied. We consider the results of the present

  18. Adverse Drug Events in Children: How Big is the Problem?

    PubMed

    Zed, Peter J

    2015-01-01

    Adverse drug events in children is an under appreciated but significant cause of health care contact resulting in ED visits and hospital admissions with associated resource utilization. In recent years we have started to better understand the impact of ADEs in children but there remains significant questions that must be addressed to further improve our understanding of the etiology of these ADEs and strategies for prevention and management. This paper will describe what is known regarding the frequency, severity, preventability and classification of ADEs in children. It will also describe some of the challenges and unanswered questions regarding patient, drug and system factors, which contribute to ADEs in children. Finally, areas of future research will be identified to further improve our understanding of ADEs in children to inform prevention strategies as well as early recognition and management approaches to minimize the significant ADEs can have on children, families and our health care system.

  19. Using the Personal Background Preparation Survey to Identify Health Science Professions Students at Risk for Adverse Academic Events

    ERIC Educational Resources Information Center

    Johnson, Craig W.; Johnson, Ronald; McKee, John C.; Kim, Mira

    2009-01-01

    In the first predictive validity study of a diagnostic and prescriptive instrument for averting adverse academic status events (AASE) among multiple populations of diverse health science professions students, entering matriculates' personal background and preparation survey (PBPS) scores consistently significantly predicted 1st- or 2nd-year AASE.…

  20. An update on adverse drug reactions related to β-lactam antibiotics.

    PubMed

    Vardakas, Konstantinos Z; Kalimeris, Georgios D; Triarides, Nikolaos A; Falagas, Matthew E

    2018-05-01

    β-lactams have been consistently associated with the majority of drug-related adverse events. Generally, these are mild under proper dosing and judicious selection. Areas covered: Immediate hypersensitivity reactions are the most feared adverse events encountered after β-lactam administration. Emerging evidence shows that immediate reactions are not as common as previously thought. Specialist consultation and testing seems prudent before a patient is officially declared allergic to β-lactams. The risk of cross-reactions between not only members of the β-lactam super-family but also between specific classes is also lower than previously thought. Newer studies have shown that cross-reactions are not universal and pertain to specific agents with similar side chains or metabolites of the β-lactam core. The frequency of severe kidney or liver toxicity, neurotoxicity, cytopenias and Clostiridium difficile infection following β-lactam administration seem to be agent-specific. Expert opinion: The currently available data denote that in addition to age, gender, co-morbidity, renal or liver function, and co-administered agents, the antibiotic levels rather than the dose itself seem to be associated with the emergence of adverse events. Most of them subside with time after withdrawal of the offending agent, but the number of cases resulting in chronic disabilities or even deaths in not negligible.

  1. Adverse drug reactions related to drugs used in orthostatic hypotension: a prospective and systematic pharmacovigilance study in France.

    PubMed

    Pathak, Atul; Raoul, Valérie; Montastruc, Jean-Louis; Senard, Jean-Michel

    2005-07-01

    The aim of the present study was to investigate and characterise adverse drug reactions (ADRs) to drugs used in France for orthostatic hypotension (OH). In this prospective and systematic study, 121 consecutive out-patients suffering from primary (Parkinson's disease, pure autonomic failure, multiple system atrophy, Lewy bodies disease) or secondary (diabetic and non-diabetic peripheral neuropathies) autonomic failure with symptomatic OH requiring pharmacological treatment with at least one drug marketed in France for OH were included together with six patients with refractory neurocardiogenic syncope. Of the patients, 85 received a monotherapy-mainly with midodrine (49.4%)-and 42 received various combinations, the association of midodrine and fludrocortisone being the most frequent (66.6%). Of all the 127 patients, 88 suffered from a total of 141 ADRs (1.60 per patient) with no statistical difference in ADR frequency between monotherapy and drug combinations (P>0.05). Among ADRs, 24 (17.0%) were considered as "serious" and 16 (11.3%) were considered as "unexpected", most of them observed with heptaminol. This study shows a high frequency of ADRs (especially serious and unexpected ADRs) with antihypotensive drugs. It strongly suggests the need for a better evaluation of the safety profile of antihypotensive drugs and improvement in summary of product characteristics.

  2. Adverse events reported to the Food and Drug Administration from 2004 to 2016 for cosmetics and personal care products marketed to newborns and infants.

    PubMed

    Cornell, Erika; Kwa, Michael; Paller, Amy S; Xu, Shuai

    2018-03-01

    Despite their ubiquitous use and several recent health controversies involving cosmetics and personal care products for children, the Food and Drug Administration has little oversight of these products and relies on consumer-submitted adverse event reports. We assessed the recently released Center for Food Safety and Applied Nutrition's Adverse Event Reporting System database for adverse event reports submitted to the Food and Drug Administration for baby personal care products and to determine whether useful insights can be derived. We extracted the Center for Food Safety and Applied Nutrition's Adverse Event Reporting System data file from 2004 to 2016 and examined the subset classified according to the Food and Drug Administration-designated product class as a baby product. Events were manually categorized into product type and symptom type to assess for trends. Only 166 total adverse events were reported to the Food and Drug Administration for baby products from 2004 to 2016. The majority of reports indicated rash or other skin reaction; 46% of reported events led to a health care visit. Pediatric dermatologists should consider submitting cosmetics and personal care product adverse event reports and encouraging consumers to do so likewise in situations in which a product adversely affects a child's health. © 2018 Wiley Periodicals, Inc.

  3. Design of a graphical and interactive interface for facilitating access to drug contraindications, cautions for use, interactions and adverse effects

    PubMed Central

    Lamy, Jean-Baptiste; Venot, Alain; Bar-Hen, Avner; Ouvrard, Patrick; Duclos, Catherine

    2008-01-01

    Background Drug iatrogeny is important but could be decreased if contraindications, cautions for use, drug interactions and adverse effects of drugs described in drug monographs were taken into account. However, the physician's time is limited during consultations, and this information is often not consulted. We describe here the design of "Mister VCM", a graphical interface based on the VCM graphical language, facilitating access to drug monographs. We also provide an assessment of the usability of this interface. Methods The "Mister VCM" interface was designed by dividing the screen into two parts: a graphical interactive one including VCM icons and synthetizing drug properties, a textual one presenting on demand drug monograph excerpts. The interface was evaluated over 11 volunteer general practitioners, trained in the use of "Mister VCM". They were asked to answer clinical questions related to fictitious randomly generated drug monographs, using a textual interface or "Mister VCM". When answering the questions, correctness of the responses and response time were recorded. Results "Mister VCM" is an interactive interface that displays VCM icons organized around an anatomical diagram of the human body with additional mental, etiological and physiological areas. Textual excerpts of the drug monograph can be displayed by clicking on the VCM icons. The interface can explicitly represent information implicit in the drug monograph, such as the absence of a given contraindication. Physicians made fewer errors with "Mister VCM" than with text (factor of 1.7; p = 0.034) and responded to questions 2.2 times faster (p < 0.001). The time gain with "Mister VCM" was greater for long monographs and questions with implicit replies. Conclusion "Mister VCM" seems to be a promising interface for accessing drug monographs. Similar interfaces could be developed for other medical domains, such as electronic patient records. PMID:18518945

  4. Childhood adversities predict strongly the use of psychotropic drugs in adulthood: a population-based cohort study of 24,284 Finns.

    PubMed

    Koskenvuo, Karoliina; Koskenvuo, Markku

    2015-04-01

    Exposure to adverse childhood experiences has been shown to be associated with negative health outcomes including mental health problems, but only a few studies with register-based data have used psychotropic drugs as an outcome variable. The purpose of this study is to examine whether adverse emotional childhood experiences, such as serious conflicts in the family and frequent fear of a family member, predict the use of psychotropic drugs in adulthood. In addition, the association of a child-parent relationship during childhood with the use of psychotropic drugs is studied. The participants of the population-based Health and Social Support Study (24,284 working aged Finns) were followed up for 9 years. The information on childhood experiences and child-parent relationships was obtained from the questionnaires in 1998 and 2003. The number of psychotropic purchases (antipsychotics, drugs for bipolar disorder, antidepressants, anxiolytics, hypnotics and sedatives) was obtained from the National-Drug-Prescription-Register. Logistic and multinomial regression models were used. A graded association between childhood adversities and the use of psychotropic drugs was found, even after adjustments for occupational training, work status, recent life events and health behaviour. Frequent fear of a family member showed the strongest association: the OR for multiple use of antidepressants was 3.08 (95% CI 2.72 to 3.49) and 2.69 (2.27 to 3.20) for multiple use of anxiolytics. Use of psychotropic drugs was clearly increased among those with poor child-parent relationship and multiple childhood adversities. The results highlight the effect of environmental factors during childhood on mental health and the need for early recognition of families at risk. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  5. [Similarity of Clinically Significant Neuropsychiatric Adverse Reactions Listed in Package Inserts between the Anti-influenza Drugs Oseltamivir and Amantadine (Possibility Attributable to Common Pharmacological Effects)].

    PubMed

    Ono, Hideki; Okamura, Maya; Fukushima, Akihiro

    2018-06-20

      The anti-influenza virus drug oseltamivir has been reported to have several pharmacological actions including blocking of nicotinic acetylcholine receptor channels and activation of the dopaminergic system. These pharmacological actions highly overlap those of amantadine, another anti-influenza virus drug authorized in Japan, and ester-type local anesthetics. Moreover, oseltamivir and amantadine can clinically induce similar adverse neuropsychiatric reactions. In the present study, from the database of the Pharmaceuticals and Medical Devices Agency (PMDA), we surveyed 2,576 drugs for which neuropsychiatric side effects similar to those of oseltamivir, amantadine and local anesthetics (abnormal behavior, confusion, consciousness disturbance, convulsion, delirium, delusion, hallucination, myoclonus, tremor) are listed as "clinically significant adverse reactions", and found 327 that had at least one of these adverse reactions. Other neuraminidase inhibitors (laninamivir, peramivir and zanamivir) did not elicit such adverse reactions. By discussing the pharmacological effects of drugs that elicit these adverse reactions, we propose that the similarity of adverse neuropsychiatric reactions between oseltamivir and amantadine is possibly attributable to their common pharmacological effects.

  6. [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.

  7. 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.

  8. Do Geriatric Conditions Increase Risk of Adverse Drug Reactions in Ambulatory Elders? Results From the VA GEM Drug Study

    PubMed Central

    Hanlon, Joseph T.; Sloane, Richard J.; Boscardin, W. John; Schmader, Kenneth E.

    2011-01-01

    Background. Many clinicians prescribe cautiously to older adults with common geriatric conditions for fear of causing adverse drug reactions (ADRs). However, little is known about the association between these conditions and risk of ADRs. Methods. Using data from the VA Geriatric Evaluation and Management Drug Study, we determined any, preventable, and serious ADRs in 808 elders for 12 months after hospital discharge using a validated process involving patient self-report and chart review adjudicated by two health care professionals. Eight common geriatric conditions (activities of daily living, dementia, incontinence, falls, difficulty ambulating, malnourishment, depression, and prolonged bed rest) were evaluated at study baseline through self-report and structured assessments. We used Poisson regression to model the relationship between these geriatric conditions and ADRs. Results. Participants had a mean of 2.9 ± 1.2 geriatric conditions. Over the 12-month follow-up period, 497 ADRs occurred in 269 participants, including 187 ADRs considered preventable and 127 considered severe. On multivariable analyses, participants with dependency in one or more activities of daily living were less likely to suffer ADRs than those who were fully independent (incidence rate ratio: 0.78, 95% confidence interval = 0.62–1.00). None of the other seven geriatric conditions assessed were associated with ADR risk. Results were similar for preventable and serious ADRs, although participants with a history of falls were more likely to develop serious ADRs (incidence rate ratio: 1.49, 95% confidence interval = 1.00–2.21). Conclusions. Many geriatric conditions were not associated with risk of ADRs. Although it is prudent to prescribe judiciously in patients with these conditions, excessive caution may not be warranted. PMID:21321003

  9. Programmable Infusion Pumps in ICUs: An Analysis of Corresponding Adverse Drug Events

    PubMed Central

    Bower, Anthony G.; Paddock, Susan M.; Hilborne, Lee H.; Wallace, Peggy; Rothschild, Jeffrey M.; Griffin, Anne; Fairbanks, Rollin J.; Carlson, Beverly; Panzer, Robert J.; Brook, Robert H.

    2007-01-01

    Background Patients in intensive care units (ICUs) frequently experience adverse drug events involving intravenous medications (IV-ADEs), which are often preventable. Objectives To determine how frequently preventable IV-ADEs in ICUs match the safety features of a programmable infusion pump with safety software (“smart pump”) and to suggest potential improvements in smart-pump design. Design Using retrospective medical-record review, we examined preventable IV-ADEs in ICUs before and after 2 hospitals replaced conventional pumps with smart pumps. The smart pumps alerted users when programmed to deliver duplicate infusions or continuous-infusion doses outside hospital-defined ranges. Participants 4,604 critically ill adults at 1 academic and 1 nonacademic hospital. Measurements Preventable IV-ADEs matching smart-pump features and errors involved in preventable IV-ADEs. Results Of 100 preventable IV-ADEs identified, 4 involved errors matching smart-pump features. Two occurred before and 2 after smart-pump implementation. Overall, 29% of preventable IV-ADEs involved overdoses; 37%, failures to monitor for potential problems; and 45%, failures to intervene when problems appeared. Error descriptions suggested that expanding smart pumps’ capabilities might enable them to prevent more IV-ADEs. Conclusion The smart pumps we evaluated are unlikely to reduce preventable IV-ADEs in ICUs because they address only 4% of them. Expanding smart-pump capabilities might prevent more IV-ADEs. PMID:18095043

  10. 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

  11. Adverse event detection using the FDA post-marketing drug safety surveillance system: Cardiotoxicity associated with loperamide abuse and misuse.

    PubMed

    Swank, Kimberley A; Wu, Eileen; Kortepeter, Cindy; McAninch, Jana; Levin, Robert L

    The purpose of this investigation was to identify and characterize post-marketing reports of cardiotoxicity, including torsades de pointes (TdP), associated with loperamide use. We searched the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database for post-marketing reports of serious cardiac adverse events associated with loperamide use from December 28, 1976 (U.S. drug approval date), through December 14, 2015. We also conducted a Pubmed and Google Scholar search to identify additional published reports of cardiotoxicity associated with loperamide in the medical literature through February 11, 2016. Forty-eight cases of serious cardiac adverse events associated with loperamide use composed the case series. The most frequently reported cardiac adverse events were syncope (n = 24), cardiac arrest (n = 13), QT-interval prolongation (n = 13), ventricular tachycardia (n = 10), and TdP (n = 7). There were 10 cases that resulted in death. Of the 48 cases, the most commonly reported reasons for use can be characterized as drug abuse (n = 22) and diarrhea treatment (n = 17). More than one-half of the 48 cases were reported after 2010. Of the 22 drug abuse cases, the median daily dose was 250 mg (range 70 mg to 1600 mg) and events occurred as early as 6 hours after a dose and as long as 18 months after initiation of loperamide. Thirteen of the 22 cases reported using loperamide for euphoric or analgesic effects, and 9 reported use to prevent opioid withdrawal symptoms. The FAERS case reports provide evidence to suggest that high doses of loperamide are associated with TdP and other serious cardiac adverse events. The majority of cases in this series occurred in the setting of drug abuse for the purpose of preventing opioid withdrawal or to produce euphoric effects. It is important for both clinicians and patients to be aware of this potential risk, because prompt therapy and discontinuation of the offending agent are often essential to

  12. USE OF CASE REPORTS IN ASSESSING ADVERSE OUTCOMES OF HUMAN PRENATAL DRUG EXPOSURES: AN APPROACH

    EPA Science Inventory

    The use of case reports for assessing the developmental consequences of prenatal drug exposure is limited by the inability to determine the incidence of adverse outcomes and by the high likelihood for bias. Yet, because it is impossible to conduct clinical trials for the assessme...

  13. [Adverse effects of oxcarbazepine].

    PubMed

    Fang, Shu; Gong, Zhi-Cheng

    2015-04-01

    Oxcarbazepine is a new antiepileptic drug. The results of clinical trials suggest that oxcarbazepine is well tolerated and has less drug interactions. It is being used more and more widely in clinical practice, but its adverse effects should not be ignored. The most common adverse effects of oxcarbazepine are usually related to the central nervous system and digestive system, including fatigue, drowsiness, diplopia, dizziness, nausea and vomit. The common skin adverse reaction is rash. Long-term use of oxcarbazepine may also cause hyponatremia. This article reviews the literature from China and overseas about the adverse effets of oxcarbazepine over the last 10 years in order to find information about rational clinical use of oxcarbazepine.

  14. [A study of incidence and clinical characteristics of adverse drug reactions in hospitalized patients.

    PubMed

    Esteban Jiménez, Óscar; Navarro Pemán, Cristina; González Rubio, Francisca; Lanuza Giménez, Francisco Javier; Montesa Lou, Cristina

    2017-12-22

    Adverse drug reactions (ADR) are one of the ten main causes of mortality in the world, as a cause of hospital admissions or prolongation hospitalizations days created an important health and economic impact. This study aimed to detect incidence and characterize ADRs that occurred during hospitalization and associated with admission in Internal Medicine service. Observational and prospective study of intensive RAM monitoring patients admitted in Internal Medicine services in a third level hospital over a twelve months period in 2014. The assessment consisted of a complete and protocol collecting information about the patients and related to suspected ADRs during hospitalization. Statistical analysis was performed using SPSS v.20.0. The study included 253 patients and in 54 (21,34%) ADR were detected, the risk of experiencing an ADR was associated with the age (p=0.012). ADR-related hospitalizations incidence were 7,11%, and fatal ADR incidence were 1,97%. With regard to severity 81,2% were severe. Gastrointestinal disorders represented the most common ADRs followed by metabolism and nutrition disorders and vascular disorders. The drugs most frequently associated with ADRs were cardiovascular agents, antiinfective drugs and central nervous system agents. 72.2% of the patients who suffered ADR had polypharmacy. In our study incidence of adverse drug reactions in hospitalized patients was 21,34%, this data and ADR´s related to admission to hospital or fatal ADR´s are mainly suffered by pluripathology and polymedicated elderly patients with worst renal function values. In these patients a more careful prescription should be made.

  15. Estimation of the prevalence of adverse drug reactions from social media.

    PubMed

    Nguyen, Thin; Larsen, Mark E; O'Dea, Bridianne; Phung, Dinh; Venkatesh, Svetha; Christensen, Helen

    2017-06-01

    This work aims to estimate the degree of adverse drug reactions (ADR) for psychiatric medications from social media, including Twitter, Reddit, and LiveJournal. Advances in lightning-fast cluster computing was employed to process large scale data, consisting of 6.4 terabytes of data containing 3.8 billion records from all the media. Rates of ADR were quantified using the SIDER database of drugs and side-effects, and an estimated ADR rate was based on the prevalence of discussion in the social media corpora. Agreement between these measures for a sample of ten popular psychiatric drugs was evaluated using the Pearson correlation coefficient, r, with values between 0.08 and 0.50. Word2vec, a novel neural learning framework, was utilized to improve the coverage of variants of ADR terms in the unstructured text by identifying syntactically or semantically similar terms. Improved correlation coefficients, between 0.29 and 0.59, demonstrates the capability of advanced techniques in machine learning to aid in the discovery of meaningful patterns from medical data, and social media data, at scale. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Adverse drug reaction, patent blue V dye and anaesthesia.

    PubMed

    Tripathy, Swagata; Nair, Priya V

    2012-11-01

    Patent blue vital (PBV) dye is used for varied perioperative indications, and has a potential for causing life-threatening allergic reactions. In this retrospective case series study, at a tertiary level neurosciences centre, we analysed the nature, management and outcome of adverse drug reaction to the preoperative use of PBV for marking vertebral level prior to back surgeries. Patients were identified from the theatre and radiology database. Data were collected from the patients' notes retrieved from the medical records division. Eleven of 1247 (0.88%) patients experienced adverse reactions: 6 (0.48%) patients had minor grade I reactions (urticaria, blue hives, pruritis or generalised rash), 4 (0.32%) had grade II reactions (transient hypotension/bronchospasm/laryngospasm) and grade III reaction (hypotension requiring prolonged vasopressor support) was noted in 1 (0.08%) patient. No mortality was seen. The time of onset (range 10-45 min) frequently coincided with induction of anaesthesia or prone positioning of patient. Seven (63.6%) cases were cancelled or postponed (range 2-63 days). Treatment varied independent of the grade of reaction. Allergy workup (often incomplete) was done for 6 (54%) patients. An awareness of the time of onset and infrequency of life-threatening reactions to patent blue dye may result in better management, less postponement, more complete workup and referral of these events.

  17. Exploratory study of factors associated with adverse clinical features in patients presenting with non-fatal drug overdose/self-poisoning to the ambulance service.

    PubMed

    Gwini, Stella May; Shaw, Deborah; Iqbal, Mohammad; Spaight, Anne; Siriwardena, Aloysius Niroshan

    2011-10-01

    To investigate the factors associated with adverse clinical features presented by drug overdose/self-poisoning patients and the treatments provided. Historical patient records collected over 3 months from ambulance crews attending non-fatal overdoses/self-poisoning incidents were reviewed. Logistic regression was used to investigate predictors of adverse clinical features (reduced consciousness, obstructed airway, hypotension or bradycardia, hypoglycaemia) and treatment. Of 22,728 calls attended to over 3 months, 585 (rate 26/1000 calls) were classified as overdose or self-poisoning. In the 585 patients identified, paracetamol-containing drugs were most commonly involved (31.5%). At least one adverse clinical feature occurred in 103 (17.7%) patients, with higher odds in men and opiate overdose or illegal drugs. Older patients and patients with reduced consciousness were more likely to receive oxygen. The latter also had a greater chance of receiving saline. Non-fatal overdose/self-poisoning accounted for 2.6% of patients attended by an ambulance. Gender, illegal drugs or opiates were important predictors of adverse clinical features. The treatments most often provided to patients were oxygen and saline.

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

    PubMed

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

    2015-12-01

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

  19. 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

  20. [Data-mining characteristics of adverse drug reactions and pharmacovi-gilance of Chinese patent drugs including Aconitum herbs].

    PubMed

    Zhang, Xiao-Meng; Li, Fan; Zhang, Bing; Chen, Xiao-Fen; Piao, Jing-Zhu

    2018-01-01

    The common Aconitum herbs in clinical application mainly include Aconiti Radix(Chuanwu), Aconiti Kusnezoffii Radix(Caowu) and Aconiti Lateralis Radix Praeparaia(Fuzi), all of which have toxicity. Therefore, the safety of using Chinese patent drugs including Aconitum herbs has become an hot topic in clinical controversy. Based on the data-mining methods, this study explored the characteristics and causes of adverse drug reactions/events (ADR/ADE) of the Chinese patent drugs including Aconitum, in order to provide pharmacovigilance and rational drug use suggestions for clinical application. The detailed ADR/ADE reports about the Chinese patent drugs including Aconitum herbs were retrieved in the domestic literature databases since 1984 to now. The information extraction and data-mining were conducted based on the platforms of Microsoft office Excel 2016, Clementine 12.0 and Cytoscape 3.3.0. Finally, 78 detailed ADR/ADE reports involving a total of 30 varieties were included. 92.31% ADR/ADE were surely or likely led by the Chinese patent drugs including Aconitum, mostly involving multiple system/organ damages with good prognosis, and even 1 case of death. The incidence of included ADRs/ADEs was associated with various factors such as the patient idiosyncratic, drug toxicity, as well as clinical medication. The patient age was most closely related to ADR/ADEs, and those aged from 60 to 69 were more easily suffered from the ADRs/ADEs of Chinese patent drugs including Aconitum. The probability of ADR/ADEs for the drugs including Chuanwu or Caowu was greater than that of Fuzi, and the using beyond the instructions dose was the most important potential safety hazard in the clinical medication process. For the regular and characteristics of ADR/ADEs led by Chinese patent drugs including Aconitum, special attention shall be paid to the elder patients or with the patients with allergies; strictly control the dosage and course of treatment, strengthen the safety medication

  1. Severe Cutaneous Adverse Drug Reactions in Pediatric Patients: A Multicenter Study.

    PubMed

    Dibek Misirlioglu, Emine; Guvenir, Hakan; Bahceci, Semiha; Haktanir Abul, Mehtap; Can, Demet; Usta Guc, Belgin Emine; Erkocoğlu, Mustafa; Toyran, Muge; Nacaroglu, Hikmet Tekin; Civelek, Ersoy; Buyuktiryaki, Betul; Ginis, Tayfur; Orhan, Fazil; Kocabas, Can Naci

    The severe cutaneous adverse drug reactions (SCARs) are rare but could be life-threatening. These include drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis. The purpose of this study was the evaluation of the clinical characteristics of patients with the diagnosis of SCARs. Patients who were diagnosed with SCARs between January 2011 and May 2016 by pediatric allergy clinics in the provinces of Ankara, Trabzon, Izmir, Adana, and Bolu were included in this multicenter study. Clinical and laboratory findings, the time between suspected drug intake and development of clinical findings, treatments they have received, and length of recovery time were recorded. Fifty-eight patients with SCARs were included in this study. The median age of the patients was 8.2 years (interquartile range, 5.25-13 years) and 50% (n = 29) were males. Diagnosis was Stevens-Johnson syndrome/TEN in 60.4% (n = 35), DRESS in 27.6% (n = 16), and acute generalized exanthematous pustulosis in 12% (n = 7) of the patients. In 93.1% of the patients, drugs were the cause of the reactions. Antibiotics ranked first among the drugs (51.7%) and antiepileptic drugs were the second (31%) most common. A patient who was diagnosed with TEN developed lagophthalmos and a patient who was diagnosed with DRESS developed secondary diabetes mellitus. Only 1 patient with the diagnosis of TEN died. SCARs in children are not common but potentially serious. Early diagnosis and appropriate treatment of SCARs will reduce the incidence of morbidity and mortality. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  2. Suspected adverse drug reactions in elderly patients reported to the Committee on Safety of Medicines.

    PubMed

    Castleden, C M; Pickles, H

    1988-10-01

    1. Spontaneous reports of suspected adverse drug reactions (ADRs) reported to the Committee on Safety of Medicines (CSM) have been studied in relation to patient age. 2. The proportion of reports received for the elderly increased between 1965 and 1983. 3. There was a correlation between the use of drugs and the number of ADR reports. Thus age-related prescription figures for two non-steroidal anti-inflammatory drugs (NSAI) and co-trimoxazole matched ADR reports for each drug in each age group. 4. The reported ADR was more likely to be serious or fatal in the elderly. 5. The commonest ADRs reported for the elderly affected the gastrointestinal (GIT) and haemopoietic systems, where more reports were received than would be expected from prescription figures. 6. The drug suspected of causing a GIT reaction was a NSAI in 75% of the reports. 7. Ninety-one per cent of fatal reports of GIT bleeds and perforations associated with NSAI drugs were in patients over 60 years of age.

  3. Wheeze as an Adverse Event in Pediatric Vaccine and Drug Randomized Controlled Trials: A Systematic Review

    PubMed Central

    Marangu, Diana; Kovacs, Stephanie; Walson, Judd; Bonhoeffer, Jan; Ortiz, Justin R.; John-Stewart, Grace; Horne, David J.

    2016-01-01

    Introduction Wheeze is an important sign indicating a potentially severe adverse event in vaccine and drug trials, particularly in children. However, there are currently no consensus definitions of wheeze or associated respiratory compromise in randomized controlled trials (RCTs). Objective To identify definitions and severity grading scales of wheeze as an adverse event in vaccine and drug RCTs enrolling children <5 years and to determine their diagnostic performance based on sensitivity, specificity and inter-observer agreement. Methods We performed a systematic review of electronic databases and reference lists with restrictions for trial settings, English language and publication date ≥ 1970. Wheeze definitions and severity grading were abstracted and ranked by a diagnostic certainty score based on sensitivity, specificity and inter-observer agreement. Results Of 1,205 articles identified using our broad search terms, we identified 58 eligible trials conducted in 38 countries, mainly in high-income settings. Vaccines made up the majority (90%) of interventions, particularly influenza vaccines (65%). Only 15 trials provided explicit definitions of wheeze. Of 24 studies that described severity, 11 described wheeze severity in the context of an explicit wheeze definition. The remaining 13 studies described wheeze severity where wheeze was defined as part of a respiratory illness or a wheeze equivalent. Wheeze descriptions were elicited from caregiver reports (14%), physical examination by a health worker (45%) or a combination (41%). There were 21/58 studies in which wheeze definitions included combined caregiver report and healthcare worker assessment. The use of these two methods appeared to have the highest combined sensitivity and specificity. Conclusion Standardized wheeze definitions and severity grading scales for use in pediatric vaccine or drug trials are lacking. Standardized definitions of wheeze are needed for assessment of possible adverse events as

  4. A New Zealand platform to enable genetic investigation of adverse drug reactions.

    PubMed

    Maggo, Simran Ds; Chua, Eng Wee; Chin, Paul; Cree, Simone; Pearson, John; Doogue, Matthew; Kennedy, Martin A

    2017-12-01

    A multitude of factors can affect drug response in individuals. It is now well established that variations in genes, especially those coding for drug metabolising enzymes, can alter the pharmacokinetic and/or pharmacodynamic profile of a drug, impacting on efficacy and often resulting in drug-induced toxicity. The UDRUGS study is an initiative from the Carney Centre for Pharmacogenomics to biobank DNA and store associated clinical data from patients who have suffered rare and/or serious adverse drug reactions (ADRs). The aim is to provide a genetic explanation of drug-induced ADRs using methods ranging from Sanger sequencing to whole exome and whole genome sequencing. Participants for the UDRUGS study are recruited from various sources, mainly via referral through clinicians working in Canterbury District Health Board, but also from district health boards across New Zealand. Participants have also self-referred to us from word-of-mouth communication between participants. We have recruited various ADRs across most drug classes. Where possible, we have conducted genetic analyses in single or a cohort of cases to identify known and novel genetic association(s) to offer an explanation to why the ADR occurred. Any genetic results relevant to the ADR are communicated back to the referring clinician and/or participant. In conclusion, we have developed a programme for studying the genetic basis of severe, rare or unusual ADR cases resulting from pharmacological treatment. Genomic analyses could eventually identify most genetic variants that predispose to ADRs, enabling a priori detection of such variants with high throughput DNA tests.

  5. Effects of organizational safety practices and perceived safety climate on PPE usage, engineering controls, and adverse events involving liquid antineoplastic drugs among nurses.

    PubMed

    DeJoy, David M; Smith, Todd D; Woldu, Henok; Dyal, Mari-Amanda; Steege, Andrea L; Boiano, James M

    2017-07-01

    Antineoplastic drugs pose risks to the healthcare workers who handle them. This fact notwithstanding, adherence to safe handling guidelines remains inconsistent and often poor. This study examined the effects of pertinent organizational safety practices and perceived safety climate on the use of personal protective equipment, engineering controls, and adverse events (spill/leak or skin contact) involving liquid antineoplastic drugs. Data for this study came from the 2011 National Institute for Occupational Safety and Health (NIOSH) Health and Safety Practices Survey of Healthcare Workers which included a sample of approximately 1,800 nurses who had administered liquid antineoplastic drugs during the past seven days. Regression modeling was used to examine predictors of personal protective equipment use, engineering controls, and adverse events involving antineoplastic drugs. Approximately 14% of nurses reported experiencing an adverse event while administering antineoplastic drugs during the previous week. Usage of recommended engineering controls and personal protective equipment was quite variable. Usage of both was better in non-profit and government settings, when workers were more familiar with safe handling guidelines, and when perceived management commitment to safety was higher. Usage was poorer in the absence of specific safety handling procedures. The odds of adverse events increased with number of antineoplastic drugs treatments and when antineoplastic drugs were administered more days of the week. The odds of such events were significantly lower when the use of engineering controls and personal protective equipment was greater and when more precautionary measures were in place. Greater levels of management commitment to safety and perceived risk were also related to lower odds of adverse events. These results point to the value of implementing a comprehensive health and safety program that utilizes available hazard controls and effectively communicates

  6. Analysis of the adverse reactions induced by natural product-derived drugs

    PubMed Central

    Zeng, Zhi-Ping; Jiang, Jian-Guo

    2010-01-01

    Compared with the therapeutic effects of established medicinal drugs, it is often considered that natural product-derived drugs are of a more benign nature in side-effects, which has made natural medicines become a popular form of therapy. Traditional Chinese medicine (TCM) is generally considered as being natural and harmless. TCM has been paid much more attention than before and widely used for the treatment nowadays. However, with the increasing cases of adverse drug reactions (ADRs), the ADRs induced by TCM are becoming more widely recognized. Some ADRs are sometimes even life-threatening. This article reviews literatures on ADRs induced by TCM which was published in the past 10 years. A total of 3122 cases including complete data are selected for the present analysis. From the data of the 3122 cases, statistics is carried out to the distribution of administration routes and time of the occurrence of ADRs, the prognosis of ADRs, sex and age factors, types and clinical symptoms of ADRs, and drugs involved in ADRs. In addition, occurrence and influencing factors of TCM-induced diseases are also analysed, which includes spices confusion, processing drugs improperly, toxic components, long-term medication, improper concerted application, interaction of TCM and Western medicine. It is concluded that the efficacy and toxicity of TCM, often using the compound prescription involving various plants and animals, resulted from a variety of chemical constituents, which lead to a comprehensive response in the human body. The ‘toxicity’ of TCM should be correctly recognized and reasonably utilized. PMID:20233209

  7. Advancing Medication Safety: Establishing a National Action Plan for Adverse Drug Event Prevention.

    PubMed

    Harris, Yael; Hu, Dale J; Lee, Christine; Mistry, Mishale; York, Andrew; Johnson, Tisha K

    2015-08-01

    Adverse drug events (ADEs) are important contributors to preventable morbidity and mortality, comprising one third of all hospital adverse events. In response to growing evidence detailing the high prevalence of ADEs, particularly among vulnerable older adults, Congress requested that the Secretary of the Department of Health and Human Services (HHS) convene a Federal Interagency Steering Committee to establish a National Action Plan to focus on ADE prevention. In August 2014, the Office of Disease Prevention and Health Promotion released the final version of the National Action Plan for Adverse Drug Event Prevention. The Action Plan directly supports the goals of the HHS Strategic Plan and the Patient Protection and Affordable Care Act by providing guidance on tracking and preventing ADEs, as well as describing evidence-based tools and resources to enhance medication safety. ADE ACTION PLAN CONTENT: The Federal Interagency Steering Committee focused the Action Plan on ADEs that are clinically significant, account for the greatest number of measurable harms as identified by using existing surveillance tools, and are largely preventable. As such, the decision was made to target three medication classes: anticoagulants, diabetes agents (insulin and oral hypoglycemic agents), and opioids. The Action Plan is organized around four key areas: surveillance; evidence-based prevention; payment, policy incentives, and oversight; and research opportunities to advance medication safety. One measure of the ADE Action Plan's success will be the wider dissemination of information and educational resources to providers and patients (or consumers) regarding the risks associated with medications. Future Action Plan iterations are likely to consider other high-priority medication classes and update the recommendations.

  8. Modeling Liver-Related Adverse Effects of Drugs Using kNN QSAR Method

    PubMed Central

    Rodgers, Amie D.; Zhu, Hao; Fourches, Dennis; Rusyn, Ivan; Tropsha, Alexander

    2010-01-01

    Adverse effects of drugs (AEDs) continue to be a major cause of drug withdrawals both in development and post-marketing. While liver-related AEDs are a major concern for drug safety, there are few in silico models for predicting human liver toxicity for drug candidates. We have applied the Quantitative Structure Activity Relationship (QSAR) approach to model liver AEDs. In this study, we aimed to construct a QSAR model capable of binary classification (active vs. inactive) of drugs for liver AEDs based on chemical structure. To build QSAR models, we have employed an FDA spontaneous reporting database of human liver AEDs (elevations in activity of serum liver enzymes), which contains data on approximately 500 approved drugs. Approximately 200 compounds with wide clinical data coverage, structural similarity and balanced (40/60) active/inactive ratio were selected for modeling and divided into multiple training/test and external validation sets. QSAR models were developed using the k nearest neighbor method and validated using external datasets. Models with high sensitivity (>73%) and specificity (>94%) for prediction of liver AEDs in external validation sets were developed. To test applicability of the models, three chemical databases (World Drug Index, Prestwick Chemical Library, and Biowisdom Liver Intelligence Module) were screened in silico and the validity of predictions was determined, where possible, by comparing model-based classification with assertions in publicly available literature. Validated QSAR models of liver AEDs based on the data from the FDA spontaneous reporting system can be employed as sensitive and specific predictors of AEDs in pre-clinical screening of drug candidates for potential hepatotoxicity in humans. PMID:20192250

  9. Genetics or environment in drug transport: the case of organic anion transporting polypeptides and adverse drug reactions.

    PubMed

    Clarke, John D; Cherrington, Nathan J

    2012-03-01

    Organic anion transporting polypeptide (OATP) uptake transporters are important for the disposition of many drugs and perturbed OATP activity can contribute to adverse drug reactions (ADRs). It is well documented that both genetic and environmental factors can alter OATP expression and activity. Genetic factors include single nucleotide polymorphisms (SNPs) that change OATP activity and epigenetic regulation that modify OATP expression levels. SNPs in OATPs contribute to ADRs. Environmental factors include the pharmacological context of drug-drug interactions and the physiological context of liver diseases. Liver diseases such as non-alcoholic fatty liver disease, cholestasis and hepatocellular carcinoma change the expression of multiple OATP isoforms. The role of liver diseases in the occurrence of ADRs is unknown. This article covers the roles OATPs play in ADRs when considered in the context of genetic or environmental factors. The reader will gain a greater appreciation for the current evidence regarding the salience and importance of each factor in OATP-mediated ADRs. A SNP in a single OATP transporter can cause changes in drug pharmacokinetics and contribute to ADRs but, because of overlap in substrate specificities, there is potential for compensatory transport by other OATP isoforms. By contrast, the expression of multiple OATP isoforms is decreased in liver diseases, reducing compensatory transport and thereby increasing the probability of ADRs. To date, most research has focused on the genetic factors in OATP-mediated ADRs while the impact of environmental factors has largely been ignored.

  10. Concordance and predictive value of two adverse drug event data sets.

    PubMed

    Cami, Aurel; Reis, Ben Y

    2014-08-22

    Accurate prediction of adverse drug events (ADEs) is an important means of controlling and reducing drug-related morbidity and mortality. Since no single "gold standard" ADE data set exists, a range of different drug safety data sets are currently used for developing ADE prediction models. There is a critical need to assess the degree of concordance between these various ADE data sets and to validate ADE prediction models against multiple reference standards. We systematically evaluated the concordance of two widely used ADE data sets - Lexi-comp from 2010 and SIDER from 2012. The strength of the association between ADE (drug) counts in Lexi-comp and SIDER was assessed using Spearman rank correlation, while the differences between the two data sets were characterized in terms of drug categories, ADE categories and ADE frequencies. We also performed a comparative validation of the Predictive Pharmacosafety Networks (PPN) model using both ADE data sets. The predictive power of PPN using each of the two validation sets was assessed using the area under Receiver Operating Characteristic curve (AUROC). The correlations between the counts of ADEs and drugs in the two data sets were 0.84 (95% CI: 0.82-0.86) and 0.92 (95% CI: 0.91-0.93), respectively. Relative to an earlier snapshot of Lexi-comp from 2005, Lexi-comp 2010 and SIDER 2012 introduced a mean of 1,973 and 4,810 new drug-ADE associations per year, respectively. The difference between these two data sets was most pronounced for Nervous System and Anti-infective drugs, Gastrointestinal and Nervous System ADEs, and postmarketing ADEs. A minor difference of 1.1% was found in the AUROC of PPN when SIDER 2012 was used for validation instead of Lexi-comp 2010. In conclusion, the ADE and drug counts in Lexi-comp and SIDER data sets were highly correlated and the choice of validation set did not greatly affect the overall prediction performance of PPN. Our results also suggest that it is important to be aware of the

  11. Adverse drug reactions associated with the use of disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis.

    PubMed

    Machado-Alba, Jorge Enrique; Ruiz, Andrés Felipe; Machado-Duque, Manuel Enrique

    2014-12-01

    This study describes the adverse drug reactions (ADRs) and their incidence in patients with rheumatoid arthritis who were treated in the Colombian health system. A retrospective cohort study was conducted using information from all patients who were diagnosed with rheumatoid arthritis and attended specialized health care centers in the cities of Bogotá, Cali, Manizales, Medellin, and Pereira between 1 December 2009 and 30 August 2013. The ADRs were obtained from medical records and the pharmacovigilance system registry and sorted by frequency and affected tissue according to World Health Organization Adverse Reaction Terminology (WHO-ART). A total of 949 reports of ADRs were obtained from 419 patients (32.8 ADRs per 100 patient-years); these patients were from a cohort of 1,364 patients being treated for rheumatoid arthritis and followed up for an average of 23.8 months (± 12.9). The cohort was mostly female (366, 87.4%) and had a mean age of 52.7 years (± 13.1). The highest numbers of ADRs were reported following the use of tocilizumab, rituximab, and infliximab (28.8, 23.1, and 13.3 reports per 100 patient-years respectively). The most frequently reported ADRs were elevated transaminase levels and dyspepsia. Overall, 87.7% of ADRs were classified as type A, 36.6% as mild, 40.7% as moderate, and 22.7% as severe. As a result, 73.2% of patients who experienced an ADR stopped taking their drugs. The occurrence of ADRs in patients treated for rheumatoid arthritis is common, especially in those associated with the use of biotechnologically produced anti-rheumatic drugs. This outcome should be studied in future research and monitoring is needed to reduce the risks in these patients.

  12. Dictionary construction and identification of possible adverse drug events in Danish clinical narrative text.

    PubMed

    Eriksson, Robert; Jensen, Peter Bjødstrup; Frankild, Sune; Jensen, Lars Juhl; Brunak, Søren

    2013-01-01

    Drugs have tremendous potential to cure and relieve disease, but the risk of unintended effects is always present. Healthcare providers increasingly record data in electronic patient records (EPRs), in which we aim to identify possible adverse events (AEs) and, specifically, possible adverse drug events (ADEs). Based on the undesirable effects section from the summary of product characteristics (SPC) of 7446 drugs, we have built a Danish ADE dictionary. Starting from this dictionary we have developed a pipeline for identifying possible ADEs in unstructured clinical narrative text. We use a named entity recognition (NER) tagger to identify dictionary matches in the text and post-coordination rules to construct ADE compound terms. Finally, we apply post-processing rules and filters to handle, for example, negations and sentences about subjects other than the patient. Moreover, this method allows synonyms to be identified and anatomical location descriptions can be merged to allow appropriate grouping of effects in the same location. The method identified 1 970 731 (35 477 unique) possible ADEs in a large corpus of 6011 psychiatric hospital patient records. Validation was performed through manual inspection of possible ADEs, resulting in precision of 89% and recall of 75%. The presented dictionary-building method could be used to construct other ADE dictionaries. The complication of compound words in Germanic languages was addressed. Additionally, the synonym and anatomical location collapse improve the method. The developed dictionary and method can be used to identify possible ADEs in Danish clinical narratives.

  13. Reporting natural health product related adverse drug reactions: is it the pharmacist's responsibility?

    PubMed

    Walji, Rishma; Boon, Heather; Barnes, Joanne; Welsh, Sandy; Austin, Zubin; Baker, G Ross

    2011-12-01

    Herbal medicines and other natural health products (NHPs) are sold in Canadian pharmacies as over-the-counter products, yet there is limited information on their safety and adverse effect profile. Signals of safety concerns associated with medicines can arise through analysis of reports of suspected adverse drug reactions (ADRs) submitted to national pharmacovigilance centres by health professionals, including pharmacists and the public. However, typically such systems experience substantial under-reporting for NHPs. The objective of this paper is to explore pharmacists' experiences with and responses to receiving or identifying reports of suspected ADRs associated with NHPs from pharmacy customers. A qualitative study in which in-depth, semi-structured interviews were conducted with 12 community pharmacists in Toronto, Canada. Pharmacists generally did not submit reports of adverse events associated with NHPs to the national ADR reporting system and cited several barriers, including lack of time, complexity of the reporting process and lack of knowledge about NHPs. Pharmacists who accepted responsibility for adverse event reporting appeared to have different perceptions of their professional role: they saw themselves as 'knowledge generators', contributing to overall healthcare knowledge. Reporting behaviour for suspected ADRs associated with NHPs may be explained by a pharmacist's perception of his/her professional role and perceptions of the relative importance of generating knowledge to share in the wider system of health care. © 2011 The Authors. IJPP © 2011 Royal Pharmaceutical Society.

  14. Campania Preventability Assessment Committee (Italy): A Focus on the Preventability of Non-steroidal Anti-inflammatory Drugs' Adverse Drug Reactions.

    PubMed

    Sessa, Maurizio; Sportiello, Liberata; Mascolo, Annamaria; Scavone, Cristina; Gallipoli, Silvia; di Mauro, Gabriella; Cimmaruta, Daniela; Rafaniello, Concetta; Capuano, Annalisa

    2017-01-01

    Purpose: This study aims to investigate preventability criteria of adverse drug reactions (ADRs) involving non-steroidal anti-inflammatory drugs (NSAIDs) by analyzing individual case safety reports (ICSRs) sent through Campania region (Italy) spontaneous reporting system from July 2012 to October 2016. Methods: For all the ICSRs that reported NSAIDs as suspected drug, a trained multidisciplinary team of Campania Pharmacovigilance Regional Centre composed of clinical pharmacologists and pharmacists with pluriannual experience in Pharmacovigilance assessed preventability by using the P-method. Results: In all 19,039 ICSRs were sent to Campania Pharmacovigilance Regional Centre, of which 550 reported NSAIDs as suspected drug. In total, 94 cases (17.1%) out of 550 ICSRs were preventable. In the 94 preventable cases, 201 critical criteria were detected of which 182/201 (90.5%) related to healthcare professionals' practices, 0/201 (0.0%) to drug quality, and 19/201 (9.5%) to patient behavior. The most detected critical criteria were the necessary medication not given (52/182; 28.6%), labeled drug-drug interaction (36/182; 19.7%), incorrect drug administration duration (31/182; 16.9%), wrong indication (26/182; 14.2%), therapeutic duplication (18/182; 10.0%), and documented hypersensitivity to administered drug or drug class (10/182; 5.6%). In seventeen (18.1%) preventable cases, there were 19 critical criteria involving non-compliance (15/19 critical criteria; 78.9%) and self-medication with the non-over-the-counter drugs (4/19 critical criteria; 21.1%). In all, 17 out 94 (18.1%) preventable cases involved over-the-counter drugs. Conclusion: A call for action for Campania Pharmacovigilance Regional Centre is necessary in order to promote initiatives to increase the awareness of healthcare professionals and citizens on the risk associated with inappropriate use of NSAIDs.

  15. Semi-Supervised Recurrent Neural Network for Adverse Drug Reaction mention extraction.

    PubMed

    Gupta, Shashank; Pawar, Sachin; Ramrakhiyani, Nitin; Palshikar, Girish Keshav; Varma, Vasudeva

    2018-06-13

    Social media is a useful platform to share health-related information due to its vast reach. This makes it a good candidate for public-health monitoring tasks, specifically for pharmacovigilance. We study the problem of extraction of Adverse-Drug-Reaction (ADR) mentions from social media, particularly from Twitter. Medical information extraction from social media is challenging, mainly due to short and highly informal nature of text, as compared to more technical and formal medical reports. Current methods in ADR mention extraction rely on supervised learning methods, which suffer from labeled data scarcity problem. The state-of-the-art method uses deep neural networks, specifically a class of Recurrent Neural Network (RNN) which is Long-Short-Term-Memory network (LSTM). Deep neural networks, due to their large number of free parameters rely heavily on large annotated corpora for learning the end task. But in the real-world, it is hard to get large labeled data, mainly due to the heavy cost associated with the manual annotation. To this end, we propose a novel semi-supervised learning based RNN model, which can leverage unlabeled data also present in abundance on social media. Through experiments we demonstrate the effectiveness of our method, achieving state-of-the-art performance in ADR mention extraction. In this study, we tackle the problem of labeled data scarcity for Adverse Drug Reaction mention extraction from social media and propose a novel semi-supervised learning based method which can leverage large unlabeled corpus available in abundance on the web. Through empirical study, we demonstrate that our proposed method outperforms fully supervised learning based baseline which relies on large manually annotated corpus for a good performance.

  16. Knowledge, Practices and Attitudes Towards Adverse Drug Reaction Reporting by Private Practitioners from Klang Valley in Malaysia

    PubMed Central

    Agarwal, Renu; Daher, Aqil Mohammad; Mohd Ismail, Nafeeza

    2013-01-01

    Background: The study aimed to determine current status of knowledge, practices, and attitudes towards adverse drug reaction (ADR) reporting among private practitioners in Klang region of Malaysia. Methods: A total of 238 private practitioners in Klang valley were distributed a questionnaire consisting of seven questions, two knowledge-related, two practice-related and three attitude-related. Each favourable and unfavourable response was given a score of 1 and 0 respectively. Total score of 70% or more for each domain was considered “satisfactory” whereas less than 70% as “unsatisfactory”. Results: One hundred forty-five participants completed questionnaire. Knowledge assessment showed 83.4% responses stating that ADR reporting helps to identify safe drugs and 91.7% responded that it measures ADR incidence. Regarding practices, 76.6% respondents were willing to report only if confident that reaction is an ADR. Regarding attitudes, 81.9%, 66.9% and 23.5% participants showed complacency, ignorance, and indifference respectively. Unsatisfactory knowledge, practices, and attitudes were observed in 57.2%, 56.6%, and 73.1% respondents respectively. Satisfactory knowledge was significantly higher in respondent with higher qualification with odds ratio of 2.96 with 95% confidence interval of 1.48–5.93. Conclusion: The study showed unsatisfactory level of knowledge, practices, and attitudes towards ADR reporting among high proportion of private practitioners in Klang valley, Malaysia. PMID:23983578

  17. Background rates of adverse pregnancy outcomes for assessing the safety of maternal vaccine trials in sub-Saharan Africa.

    PubMed

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

    2012-01-01

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

  18. Campania Preventability Assessment Committee (Italy): A Focus on the Preventability of Non-steroidal Anti-inflammatory Drugs' Adverse Drug Reactions

    PubMed Central

    Sessa, Maurizio; Sportiello, Liberata; Mascolo, Annamaria; Scavone, Cristina; Gallipoli, Silvia; di Mauro, Gabriella; Cimmaruta, Daniela; Rafaniello, Concetta; Capuano, Annalisa

    2017-01-01

    Purpose: This study aims to investigate preventability criteria of adverse drug reactions (ADRs) involving non-steroidal anti-inflammatory drugs (NSAIDs) by analyzing individual case safety reports (ICSRs) sent through Campania region (Italy) spontaneous reporting system from July 2012 to October 2016. Methods: For all the ICSRs that reported NSAIDs as suspected drug, a trained multidisciplinary team of Campania Pharmacovigilance Regional Centre composed of clinical pharmacologists and pharmacists with pluriannual experience in Pharmacovigilance assessed preventability by using the P-method. Results: In all 19,039 ICSRs were sent to Campania Pharmacovigilance Regional Centre, of which 550 reported NSAIDs as suspected drug. In total, 94 cases (17.1%) out of 550 ICSRs were preventable. In the 94 preventable cases, 201 critical criteria were detected of which 182/201 (90.5%) related to healthcare professionals' practices, 0/201 (0.0%) to drug quality, and 19/201 (9.5%) to patient behavior. The most detected critical criteria were the necessary medication not given (52/182; 28.6%), labeled drug–drug interaction (36/182; 19.7%), incorrect drug administration duration (31/182; 16.9%), wrong indication (26/182; 14.2%), therapeutic duplication (18/182; 10.0%), and documented hypersensitivity to administered drug or drug class (10/182; 5.6%). In seventeen (18.1%) preventable cases, there were 19 critical criteria involving non-compliance (15/19 critical criteria; 78.9%) and self-medication with the non-over-the-counter drugs (4/19 critical criteria; 21.1%). In all, 17 out 94 (18.1%) preventable cases involved over-the-counter drugs. Conclusion: A call for action for Campania Pharmacovigilance Regional Centre is necessary in order to promote initiatives to increase the awareness of healthcare professionals and citizens on the risk associated with inappropriate use of NSAIDs. PMID:28603499

  19. Suspected adverse drug reactions in elderly patients reported to the Committee on Safety of Medicines.

    PubMed Central

    Castleden, C M; Pickles, H

    1988-01-01

    1. Spontaneous reports of suspected adverse drug reactions (ADRs) reported to the Committee on Safety of Medicines (CSM) have been studied in relation to patient age. 2. The proportion of reports received for the elderly increased between 1965 and 1983. 3. There was a correlation between the use of drugs and the number of ADR reports. Thus age-related prescription figures for two non-steroidal anti-inflammatory drugs (NSAI) and co-trimoxazole matched ADR reports for each drug in each age group. 4. The reported ADR was more likely to be serious or fatal in the elderly. 5. The commonest ADRs reported for the elderly affected the gastrointestinal (GIT) and haemopoietic systems, where more reports were received than would be expected from prescription figures. 6. The drug suspected of causing a GIT reaction was a NSAI in 75% of the reports. 7. Ninety-one per cent of fatal reports of GIT bleeds and perforations associated with NSAI drugs were in patients over 60 years of age. PMID:3263875

  20. 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

  1. A web-based quantitative signal detection system on adverse drug reaction in China.

    PubMed

    Li, Chanjuan; Xia, Jielai; Deng, Jianxiong; Chen, Wenge; Wang, Suzhen; Jiang, Jing; Chen, Guanquan

    2009-07-01

    To establish a web-based quantitative signal detection system for adverse drug reactions (ADRs) based on spontaneous reporting to the Guangdong province drug-monitoring database in China. Using Microsoft Visual Basic and Active Server Pages programming languages and SQL Server 2000, a web-based system with three software modules was programmed to perform data preparation and association detection, and to generate reports. Information component (IC), the internationally recognized measure of disproportionality for quantitative signal detection, was integrated into the system, and its capacity for signal detection was tested with ADR reports collected from 1 January 2002 to 30 June 2007 in Guangdong. A total of 2,496 associations including known signals were mined from the test database. Signals (e.g., cefradine-induced hematuria) were found early by using the IC analysis. In addition, 291 drug-ADR associations were alerted for the first time in the second quarter of 2007. The system can be used for the detection of significant associations from the Guangdong drug-monitoring database and could be an extremely useful adjunct to the expert assessment of very large numbers of spontaneously reported ADRs for the first time in China.

  2. Association of funding and conclusions in randomized drug trials: a reflection of treatment effect or adverse events?

    PubMed

    Als-Nielsen, Bodil; Chen, Wendong; Gluud, Christian; Kjaergard, Lise L

    2003-08-20

    Previous studies indicate that industry-sponsored trials tend to draw proindustry conclusions. To explore whether the association between funding and conclusions in randomized drug trials reflects treatment effects or adverse events. Observational study of 370 randomized drug trials included in meta-analyses from Cochrane reviews selected from the Cochrane Library, May 2001. From a random sample of 167 Cochrane reviews, 25 contained eligible meta-analyses (assessed a binary outcome; pooled at least 5 full-paper trials of which at least 1 reported adequate and 1 reported inadequate allocation concealment). The primary binary outcome from each meta-analysis was considered the primary outcome for all trials included in each meta-analysis. The association between funding and conclusions was analyzed by logistic regression with adjustment for treatment effect, adverse events, and additional confounding factors (methodological quality, control intervention, sample size, publication year, and place of publication). Conclusions in trials, classified into whether the experimental drug was recommended as the treatment of choice or not. The experimental drug was recommended as treatment of choice in 16% of trials funded by nonprofit organizations, 30% of trials not reporting funding, 35% of trials funded by both nonprofit and for-profit organizations, and 51% of trials funded by for-profit organizations (P<.001; chi2 test). Logistic regression analyses indicated that funding, treatment effect, and double blinding were the only significant predictors of conclusions. Adjusted analyses showed that trials funded by for-profit organizations were significantly more likely to recommend the experimental drug as treatment of choice (odds ratio, 5.3; 95% confidence interval, 2.0-14.4) compared with trials funded by nonprofit organizations. This association did not appear to reflect treatment effect or adverse events. Conclusions in trials funded by for-profit organizations may be more

  3. 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

  4. Mining Adverse Drug Reactions in Social Media with Named Entity Recognition and Semantic Methods.

    PubMed

    Chen, Xiaoyi; Deldossi, Myrtille; Aboukhamis, Rim; Faviez, Carole; Dahamna, Badisse; Karapetiantz, Pierre; Guenegou-Arnoux, Armelle; Girardeau, Yannick; Guillemin-Lanne, Sylvie; Lillo-Le-Louët, Agnès; Texier, Nathalie; Burgun, Anita; Katsahian, Sandrine

    2017-01-01

    Suspected adverse drug reactions (ADR) reported by patients through social media can be a complementary source to current pharmacovigilance systems. However, the performance of text mining tools applied to social media text data to discover ADRs needs to be evaluated. In this paper, we introduce the approach developed to mine ADR from French social media. A protocol of evaluation is highlighted, which includes a detailed sample size determination and evaluation corpus constitution. Our text mining approach provided very encouraging preliminary results with F-measures of 0.94 and 0.81 for recognition of drugs and symptoms respectively, and with F-measure of 0.70 for ADR detection. Therefore, this approach is promising for downstream pharmacovigilance analysis.

  5. A Comparison of Adverse Drug Reaction Profiles in Patients on Antiretroviral and Antitubercular Treatment in Zimbabwe.

    PubMed

    Masuka, Josiah T; Chipangura, Precious; Nyambayo, Priscilla P; Stergachis, Andy; Khoza, Star

    2018-01-01

    Few studies describe the adverse drug event profiles in patients simultaneously receiving antiretroviral and anti-tubercular medicines in resource-limited countries. To describe and compare the adverse drug reaction profiles in patients on highly active antiretroviral therapy only (HAART), HAART and isoniazid preventive therapy (HHART), and HAART and antitubercular treatment (ATTHAART). We analysed individual case safety reports (ICSRs) for patients on antiretroviral therapy and antitubercular treatment submitted to the national pharmacovigilance centre during the targeted spontaneous reporting (TSR) programme from 1 September 2012 through 31 August 2016. All reports considered certain, probable or possible were included in the analysis. A total of 1076 ICSRs were included in the analysis. Most of the reports were from the HAART only group (n = 882; 82.0%), followed by patients on HHART (n = 132; 12.3%), and ATTHAART (n = 62; 5.7%). The ATTHAART (35.5%) and HHAART (34.1%) had a higher frequency of hepatic disorders than the HAART group (5.0%) (p < 0.0001). A higher frequency of rash was reported in the HHAART (35.6%) and HAART groups (29.4%) than the ATTHAART group (14.5%) (p = 0.011). Peripheral neuropathy occurred more frequently in the ATTHAART group (19.3%) than other groups (p = 0.001) while Stevens-Johnson syndrome (14.7%; p < 0.001), gynaecomastia (18.2%; p < 0.001), and lipodystrophy (4.5%; p = 0.012) occurred more frequently in the HAART group. The HHAART group was associated with a higher frequency of psychosis (4.5%; p = 0.002). Antiretroviral therapy was associated with a higher frequency of Stevens-Johnson syndrome, gynaecomastia, and lipodystrophy. Co-administration of antiretroviral and antitubercular medicines was associated with a higher frequency of drug-induced liver injury and peripheral neuropathy. Similarly, co-administration of isoniazid preventive therapy and antiretroviral drugs was associated with a higher risk for

  6. A systematic investigation of computation models for predicting Adverse Drug Reactions (ADRs).

    PubMed

    Kuang, Qifan; Wang, MinQi; Li, Rong; Dong, YongCheng; Li, Yizhou; Li, Menglong

    2014-01-01

    Early and accurate identification of adverse drug reactions (ADRs) is critically important for drug development and clinical safety. Computer-aided prediction of ADRs has attracted increasing attention in recent years, and many computational models have been proposed. However, because of the lack of systematic analysis and comparison of the different computational models, there remain limitations in designing more effective algorithms and selecting more useful features. There is therefore an urgent need to review and analyze previous computation models to obtain general conclusions that can provide useful guidance to construct more effective computational models to predict ADRs. In the current study, the main work is to compare and analyze the performance of existing computational methods to predict ADRs, by implementing and evaluating additional algorithms that have been earlier used for predicting drug targets. Our results indicated that topological and intrinsic features were complementary to an extent and the Jaccard coefficient had an important and general effect on the prediction of drug-ADR associations. By comparing the structure of each algorithm, final formulas of these algorithms were all converted to linear model in form, based on this finding we propose a new algorithm called the general weighted profile method and it yielded the best overall performance among the algorithms investigated in this paper. Several meaningful conclusions and useful findings regarding the prediction of ADRs are provided for selecting optimal features and algorithms.

  7. Systematic drug safety evaluation based on public genomic expression (Connectivity Map) data: Myocardial and infectious adverse reactions as application cases

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

    Wang, Kejian, E-mail: kejian.wang.bio@gmail.com; Weng, Zuquan; Sun, Liya

    Adverse drug reaction (ADR) is of great importance to both regulatory agencies and the pharmaceutical industry. Various techniques, such as quantitative structure–activity relationship (QSAR) and animal toxicology, are widely used to identify potential risks during the preclinical stage of drug development. Despite these efforts, drugs with safety liabilities can still pass through safety checkpoints and enter the market. This situation raises the concern that conventional chemical structure analysis and phenotypic screening are not sufficient to avoid all clinical adverse events. Genomic expression data following in vitro drug treatments characterize drug actions and thus have become widely used in drug repositioning. Inmore » the present study, we explored prediction of ADRs based on the drug-induced gene-expression profiles from cultured human cells in the Connectivity Map (CMap) database. The results showed that drugs inducing comparable ADRs generally lead to similar CMap expression profiles. Based on such ADR-gene expression association, we established prediction models for various ADRs, including severe myocardial and infectious events. Drugs with FDA boxed warnings of safety liability were effectively identified. We therefore suggest that drug-induced gene expression change, in combination with effective computational methods, may provide a new dimension of information to facilitate systematic drug safety evaluation. - Highlights: • Drugs causing common toxicity lead to similar in vitro gene expression changes. • We built a model to predict drug toxicity with drug-specific expression profiles. • Drugs with FDA black box warnings were effectively identified by our model. • In vitro assay can detect severe toxicity in the early stage of drug development.« less

  8. Dictionary construction and identification of possible adverse drug events in Danish clinical narrative text

    PubMed Central

    Eriksson, Robert; Jensen, Peter Bjødstrup; Frankild, Sune; Jensen, Lars Juhl; Brunak, Søren

    2013-01-01

    Objective Drugs have tremendous potential to cure and relieve disease, but the risk of unintended effects is always present. Healthcare providers increasingly record data in electronic patient records (EPRs), in which we aim to identify possible adverse events (AEs) and, specifically, possible adverse drug events (ADEs). Materials and methods Based on the undesirable effects section from the summary of product characteristics (SPC) of 7446 drugs, we have built a Danish ADE dictionary. Starting from this dictionary we have developed a pipeline for identifying possible ADEs in unstructured clinical narrative text. We use a named entity recognition (NER) tagger to identify dictionary matches in the text and post-coordination rules to construct ADE compound terms. Finally, we apply post-processing rules and filters to handle, for example, negations and sentences about subjects other than the patient. Moreover, this method allows synonyms to be identified and anatomical location descriptions can be merged to allow appropriate grouping of effects in the same location. Results The method identified 1 970 731 (35 477 unique) possible ADEs in a large corpus of 6011 psychiatric hospital patient records. Validation was performed through manual inspection of possible ADEs, resulting in precision of 89% and recall of 75%. Discussion The presented dictionary-building method could be used to construct other ADE dictionaries. The complication of compound words in Germanic languages was addressed. Additionally, the synonym and anatomical location collapse improve the method. Conclusions The developed dictionary and method can be used to identify possible ADEs in Danish clinical narratives. PMID:23703825

  9. Adverse drug reaction prediction using scores produced by large-scale drug-protein target docking on high-performance computing machines.

    PubMed

    LaBute, Montiago X; Zhang, Xiaohua; Lenderman, Jason; Bennion, Brian J; Wong, Sergio E; Lightstone, Felice C

    2014-01-01

    Late-stage or post-market identification of adverse drug reactions (ADRs) is a significant public health issue and a source of major economic liability for drug development. Thus, reliable in silico screening of drug candidates for possible ADRs would be advantageous. In this work, we introduce a computational approach that predicts ADRs by combining the results of molecular docking and leverages known ADR information from DrugBank and SIDER. We employed a recently parallelized version of AutoDock Vina (VinaLC) to dock 906 small molecule drugs to a virtual panel of 409 DrugBank protein targets. L1-regularized logistic regression models were trained on the resulting docking scores of a 560 compound subset from the initial 906 compounds to predict 85 side effects, grouped into 10 ADR phenotype groups. Only 21% (87 out of 409) of the drug-protein binding features involve known targets of the drug subset, providing a significant probe of off-target effects. As a control, associations of this drug subset with the 555 annotated targets of these compounds, as reported in DrugBank, were used as features to train a separate group of models. The Vina off-target models and the DrugBank on-target models yielded comparable median area-under-the-receiver-operating-characteristic-curves (AUCs) during 10-fold cross-validation (0.60-0.69 and 0.61-0.74, respectively). Evidence was found in the PubMed literature to support several putative ADR-protein associations identified by our analysis. Among them, several associations between neoplasm-related ADRs and known tumor suppressor and tumor invasiveness marker proteins were found. A dual role for interstitial collagenase in both neoplasms and aneurysm formation was also identified. These associations all involve off-target proteins and could not have been found using available drug/on-target interaction data. This study illustrates a path forward to comprehensive ADR virtual screening that can potentially scale with increasing number

  10. High-throughput identification of off-targets for the mechanistic study of severe adverse drug reactions induced by analgesics

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

    Pan, Jian-Bo; Ji, Nan; Pan, Wen

    2014-01-01

    Drugs may induce adverse drug reactions (ADRs) when they unexpectedly bind to proteins other than their therapeutic targets. Identification of these undesired protein binding partners, called off-targets, can facilitate toxicity assessment in the early stages of drug development. In this study, a computational framework was introduced for the exploration of idiosyncratic mechanisms underlying analgesic-induced severe adverse drug reactions (SADRs). The putative analgesic-target interactions were predicted by performing reverse docking of analgesics or their active metabolites against human/mammal protein structures in a high-throughput manner. Subsequently, bioinformatics analyses were undertaken to identify ADR-associated proteins (ADRAPs) and pathways. Using the pathways and ADRAPsmore » that this analysis identified, the mechanisms of SADRs such as cardiac disorders were explored. For instance, 53 putative ADRAPs and 24 pathways were linked with cardiac disorders, of which 10 ADRAPs were confirmed by previous experiments. Moreover, it was inferred that pathways such as base excision repair, glycolysis/glyconeogenesis, ErbB signaling, calcium signaling, and phosphatidyl inositol signaling likely play pivotal roles in drug-induced cardiac disorders. In conclusion, our framework offers an opportunity to globally understand SADRs at the molecular level, which has been difficult to realize through experiments. It also provides some valuable clues for drug repurposing. - Highlights: • A novel computational framework was developed for mechanistic study of SADRs. • Off-targets of drugs were identified in large scale and in a high-throughput manner. • SADRs like cardiac disorders were systematically explored in molecular networks. • A number of ADR-associated proteins were identified.« less

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

    PubMed Central

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

    2011-01-01

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

  12. Building a time-saving and adaptable tool to report adverse drug events.

    PubMed

    Parès, Yves; Declerck, Gunnar; Hussain, Sajjad; Ng, Romain; Jaulent, Marie-Christine

    2013-01-01

    The difficult task of detecting adverse drug events (ADEs) and the tedious process of building manual reports of ADE occurrences out of patient profiles result in a majority of adverse reactions not being reported to health regulatory authorities. The SALUS individual case safety report (ICSR) reporting tool, a component currently developed within the SALUS project, aims to support semi-automatic reporting of ADEs to regulatory authorities. In this paper, we present an initial design and current state of of our ICSR reporting tool that features: (i) automatic pre-population of reporting forms through extraction of the patient data contained in an Electronic Health Record (EHR); (ii) generation and electronic submission of the completed ICSRs by the physician to regulatory authorities; and (iii) integration of the reporting process into the physician's work-flow to limit the disturbance. The objective is to increase the rates of ADE reporting and the quality of the reported data. The SALUS interoperability platform supports patient data extraction independently of the EHR data model in use and allows generation of reports using the format expected by regulatory authorities.

  13. A case report: using SNOMED CT for grouping Adverse Drug Reactions Terms

    PubMed Central

    Alecu, Iulian; Bousquet, Cedric; Jaulent, Marie-Christine

    2008-01-01

    Background WHO-ART and MedDRA are medical terminologies used for the coding of adverse drug reactions in pharmacovigilance databases. MedDRA proposes 13 Special Search Categories (SSC) grouping terms associated to specific medical conditions. For instance, the SSC "Haemorrhage" includes 346 MedDRA terms among which 55 are also WHO-ART terms. WHO-ART itself does not provide such groupings. Our main contention is the possibility of classifying WHO-ART terms in semantic categories by using knowledge extracted from SNOMED CT. A previous paper presents the way WHO-ART term definitions have been automatically generated in a description logics formalism by using their corresponding SNOMED CT synonyms. Based on synonymy and relative position of WHO-ART terms in SNOMED CT, specialization or generalization relationships could be inferred. This strategy is successful for grouping the WHO-ART terms present in most MedDRA SSCs. However the strategy failed when SSC were organized on other basis than taxonomy. Methods We propose a new method that improves the previous WHO-ART structure by integrating the associative relationships included in SNOMED CT. Results The new method improves the groupings. For example, none of the 55 WHO-ART terms in the Haemorrhage SSC were matched using the previous method. With the new method, we improve the groupings and obtain 87% coverage of the Haemorrhage SSC. Conclusion SNOMED CT's terminological structure can be used to perform automated groupings in WHO-ART. This work proves that groupings already present in the MedDRA SSCs (e.g. the haemorrhage SSC) may be retrieved using classification in SNOMED CT. PMID:19007441

  14. Design of the Anti-tuberculosis Drugs induced Adverse Reactions in China National Tuberculosis Prevention and Control Scheme Study (ADACS)

    PubMed Central

    2010-01-01

    Background More than 1 million tuberculosis (TB) patients are receiving the standard anti-TB treatment provided by China National Tuberculosis Prevention and Control Scheme (CNTS) in China every year. Adverse reactions (ADRs) induced by anti-TB drugs could both do harm to patients and lead to anti-TB treatment failure. The ADACS aimed to explore ADRs' incidences, prognoses, economical and public health impacts for TB patients and TB control, and build a DNA bank of TB patients. Methods/Design Multiple study designs were adopted. Firstly, a prospective cohort with 4488 sputum smears positive pulmonary tuberculosis patients was established. Patients were followed up for 6-9 months in 52 counties of four regions. Those suspected ADRs should be checked and confirmed by Chinese State Food and Drug Administration (SFDA). Secondly, if the suspected ADR was anti-TB drug induced liver injury (ATLI), a nested case-control study would be performed which comprised choosing a matched control and doing a plus questionnaire inquiry. Thirdly, health economical data of ADRs would be collected to analyze financial burdens brought by ADRs and cost-effectiveness of ADRs' treatments. Fourthly, a drop of intravenous blood for each patient was taken and saved in FTA card for DNA banking and genotyping. Finally, the demographic, clinical, environmental, administrative and genetic data would be merged for the comprehensive analysis. Discussion ADACS will give an overview of anti-TB drugs induced ADRs' incidences, risk factors, treatments, prognoses, and clinical, economical and public health impacts for TB patients applying CNTS regimen in China, and provide suggestions for individualized health care and TB control policy. PMID:20492672

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

    PubMed

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

    2017-01-06

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

  16. Prevalence of Adverse Drug Reactions to Highly Active Antiretroviral Therapy (HAART) among HIV Positive Patients in Imam Khomeini Hospital of Tehran, Iran.

    PubMed

    Koochak, Hamid E; Babaii, Azita; Pourdast, Alia; Golrokhy, Raheleh; Rasoolinejad, Mehrnaz; Khodaei, Sepideh; Moghadam, Saeed R J; Taheri, Reza R; Seyed Alinaghi, Seyed Ahmad

    2017-01-01

    The present study assessed the prevalence of adverse drug reactions (ADRs) among HIV positive patients taking antiretroviral therapy referred to Imam Khomeini Hospital in Tehran, Iran. This is a cross sectional study regarding side effects of Highly Active Antiretroviral Therapy (HAART) in HIV positive patients referred to Voluntary Counseling and Testing (VCT) center in Imam Khomeini Hospital of Tehran, Iran during a period of the year 2009 to 2010. Two hundred patients under antiretroviral treatment evaluated for the side effects of drug based on available records, face to face interviews and written lab data. Data was collected from a sample of 200 HIV positive patients (72% male). Injection drug use was the most common route of HIV transmission. Co-Infections with Hepatitis C virus (HCV) found in the majority of patients (60.5%). Tuberculosis was the most prevalent opportunistic infection. One hundred eighty eight (94%) patients experienced at least one adverse drug reaction. The most frequent clinical and paraclinical findings were skin rash (28%) and abnormal liver function tests (36%). Given the high prevalence of adverse drug reactions among HIV positive patients taking antiretroviral therapy (ART) in this study, clinicians should be aware of ADRs at the initiation of ART as complications can affect patients' adherence to the therapy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

    PubMed

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

    2007-02-01

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

  18. Adverse drug reactions and adverse events of 33 varieties of traditional Chinese medicine injections on National Essential medicines List (2004 edition) of China: an overview on published literatures.

    PubMed

    Wang, Li; Yuan, Qiang; Marshall, Gareth; Cui, Xiaohua; Cheng, Lan; Li, Yuanyuan; Shang, Hongcai; Zhang, Boli; Li, Youping

    2010-05-01

    We conducted a literature review on adverse drug reactions (ADRs) related to 33 kinds of traditional Chinese medicine injections (CMIs) on China's National Essential medicines List (2004 edition). We aimed to retrieve basic ADR information, identify trends related to CMIs, and provide evidence for the research, development, and application of CMIs. We electronically searched the Chinese Biomedical Literature Database (CBM, January 1978-April 2009), the China National Knowledge Infrastructure Database (CNKI, January 1979-April 2009), the Chinese Science and Technology Periodical Database (January 1989-April 2009) and the Traditional Chinese Medicine Database (January 1984-April 2009). We used the terms of 'adverse drug reaction', 'adverse event', 'side effects', 'side reaction', 'toxicity', and 'Chinese medicine injections', as well as the names of the 33 CMIs to search. We also collected CMI-related ADR reports and regulations from the Chinese Food and Drug Administration's 'Newsletter of Adverse Drug Reactions' (Issue 1 to 22). Then we descriptively analyzed all the articles by year published, periodical, and study design. We also analyzed regulations relevants to ADRs. (1) We found 5405 relevant citations, of which 1010 studies met the eligibility criteria. (2) The rate of publishing of research articles on CMI-linked ADRs has risen over time. (3) The included 1010 articles were scattered among 297 periodicals. Of these, 55 journals on pharmaceutical medicine accounted for 39.5% of the total (399/1010); the 64 journals on traditional Chinese medicine, accounted for only 19.5% (197/1010). Only 22 periodicals with relevant articles were included on the core journals of the Beijing University List (2008 edition); these published 129 articles (12.8% of the included articles). (4) The relevant articles consisted of 348 case reports (34.5%), 254 case series (25.2%), 119 reviews (11.8%), 116 randomized controlled trials (11.5%), 78 cross-sectional studies (7.7%), 61

  19. [Irrational use of drugs as a source of drug - induced diseases].

    PubMed

    Woroń, Jarosław; Porebski, Grzegorz; Kostka-Trabka, Elzbieta; Goszcz, Aleksandra

    2007-01-01

    The irrational use of medication, by which we understand the administration of drugs for indications where their effectiveness has not been confirmed, the disregard of restrictions and warnings against their use, and the use of drug combinations which do not increase the therapeutic effect but to the contrary increase the risk of adverse drug reactions, is a serious problem encountered in paediatric pharmacotherapy. Each year the centres for monitoring of adverse drug reactions receive many reports, the analysis of which show that the reasons of occurrence of adverse drug reactions after drug administration, are specifically due to irrational use of medications. In order to prevent in an active way the occurrence, of adverse drug reactions following drug administration it is worthwhile to bring to attention the reasons for their occurrence which not infrequently bring about pathological effects. Our work which is based on reports received by the Regional Centre for Adverse Drug Reactions Monitoring in Krakow concerning the occurrence of adverse drug reactions in an attempt to bring to attention in our view important problems in current pharmacotherapy.

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

    PubMed

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

    2016-04-01

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

  1. Ascertainment of risk of serious adverse reactions associated with chemoprophylactic antimalarial drugs.

    PubMed Central

    Phillips-Howard, P. A.; Bjorkman, A. B.

    1990-01-01

    Serious adverse reactions during malaria chemoprophylaxis are reviewed. Three drugs considered to have caused serious reactions in recent years are pyrimethamine/sulfadoxine (Fansidar), pyrimethamine/dapsone (Maloprim) and amodiaquine. These reactions are principally independent of dose and cannot be determined during screening for optimal doses. However, host factors may precipitate dose-dependent reactions, some of which could be avoided with improvements in drug licensing. Since serious and life-threatening reactions are relatively rare (between 1:1000 and 1:20,000), Phase I to III trials cannot identify them. Reliance must therefore be placed on Phase IV post-marketing studies, including ongoing reviews of national registers, and specially tailored studies to identify the risk using prescription-event monitoring in high-risk populations. Occasionally, medical-record linkage, case-control and cohort studies may provide supportive data. Although large numbers of travellers must, of necessity, be exposed to a drug before relatively rare reactions are identified, the ascertainment of risk using post-marketing surveillance was prevented by the following five deficiencies: lack of awareness of early alerts, inadequate use of national registers, poor attention to epidemiological and statistical rigour, inadequate verification of denominators, and inadequacy of data records. Recommendations are given for minimizing such errors in the future. PMID:2208562

  2. A Drug Safety Rating System Based on Postmarketing Costs Associated with Adverse Events and Patient Outcomes.

    PubMed

    Hoffman, Keith B; Dimbil, Mo; Kyle, Robert F; Tatonetti, Nicholas P; Erdman, Colin B; Demakas, Andrea; Chen, Dingguo; Overstreet, Brian M

    2015-12-01

    Given the multiple limitations associated with relatively homogeneous preapproval clinical trials, inadequate data disclosures, slow reaction times from regulatory bodies, and deep-rooted bias against disclosing and publishing negative results, there is an acute need for the development of analytics that reflect drug safety in heterogeneous, real-world populations. To develop a drug safety statistic that estimates downstream medical costs associated with serious adverse events (AEs) and unfavorable patient outcomes associated with the use of 706 FDA-approved drugs. All primary suspect case reports for each drug were collected from the FDA's Adverse Event Reporting System database (FAERS) from 2010-2014. The Medical Dictionary for Regulatory Activities (MedDRA) was used to code serious AEs and outcomes, which were tallied for each case report. Medical costs associated with AEs and poor patient outcomes were derived from Agency for Healthcare Research and Quality (AHRQ) survey data, and their corresponding ICD-9-CM codes were mapped to MedDRA terms. Nonserious AEs and outcomes were not included. For each case report, either the highest AE cost or, if no eligible AE was listed, the highest outcome cost was used. All costed cases were aggregated for each drug and divided by the number of patients exposed to obtain a downstream estimated direct medical cost burden per exposure. Each drug was assigned a corresponding 1-100 point total. The 706 drugs showed an exponential distribution of downstream costs, and the data were transformed using the natural log to approximate a normal distribution. The minimum score was 8.29, and the maximum score was 99.25, with a mean of 44.32. Drugs with the highest individual scores tended to be kinase inhibitors, thalidomide analogs, and endothelin receptor antagonists. When scores were analyzed across Established Pharmacologic Class (EPC), the kinase inhibitor and endothelin receptor antagonist classes had the highest total. However

  3. A Retrospective Analysis of Spontaneous Adverse Drug Reactions Reports Relating to Paediatric Patients

    PubMed Central

    Rosli, Rosliana; Abd Aziz, Noorizan; Manan, Mohamed Mansor

    2016-01-01

    Background Spontaneous reporting on adverse drug reactions (ADR) has been established in Malaysia since 1987, and although these reports are monitored by the Malaysia drug monitoring authority, the National Pharmaceutical Control Bureau, information about ADRs in the paediatric patient population still remains unexplored. The aims of this study, therefore, were to characterize the ADRs reported in respect to the Malaysian paediatric population and to relate the data to specific paediatric age groups. Methods Data on all ADRs reported to the National Pharmaceutical Control Bureau between 2000 and 2013 for individuals aged from birth to 17 years old were analysed with respect to age and gender, type of reporter, suspected medicines (using the Anatomical Therapeutic Chemical classification), category of ADR (according to system organ class) as well as the severity of the ADR. Results In total, 11,523 ADR reports corresponding to 22,237 ADRs were analysed, with half of these reporting one ADR per report. Vaccines comprised 55.7% of the 11,523 ADR reports with the remaining being drug related ADRs. Overall, 63.9% of ADRs were reported for paediatric patients between 12 and 17 years of age, with the majority of ADRs reported in females (70.7%). The most common ADRs reported were from the following system organ classes: application site disorders (32.2%), skin and appendages disorders (20.6%), body as a whole general disorders (12.8%) and central and peripheral nervous system disorders (11.2%). Meanwhile, ADRs in respect to anti-infectives for systemic use (2194/5106; 43.0%) were the most frequently reported across all age groups, followed by drugs from the nervous system (1095/5106; 21.4%). Only 0.28% of the ADR cases were reported as fatal. A large proportion of the reports were received from healthcare providers in government health facilities. Discussion ADR reports concerning vaccines and anti-infectives were the most commonly reported in children, and are mainly

  4. 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.

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

    PubMed Central

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

    2012-01-01

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

  6. Factors Associated with Anti-Tuberculosis Medication Adverse Effects: A Case-Control Study in Lima, Peru

    PubMed Central

    Chung-Delgado, Kocfa; Revilla-Montag, Alejandro; Guillen-Bravo, Sonia; Velez-Segovia, Eduardo; Soria-Montoya, Andrea; Nuñez-Garbin, Alexandra; Silva-Caso, Wilmer; Bernabe-Ortiz, Antonio

    2011-01-01

    Background Long-term exposure to anti-tuberculosis medication increases risk of adverse drug reactions and toxicity. The objective of this investigation was to determine factors associated with anti-tuberculosis adverse drug reactions in Lima, Peru, with special emphasis on MDR-TB medication, HIV infection, diabetes, age and tobacco use. Methodology and Results A case-control study was performed using information from Peruvian TB Programme. A case was defined as having reported an anti-TB adverse drug reaction during 2005–2010 with appropriate notification on clinical records. Controls were defined as not having reported a side effect, receiving anti-TB therapy during the same time that the case had appeared. Crude, and age- and sex-adjusted models were calculated using odds ratios (OR) and 95% confidence intervals (95%CI). A multivariable model was created to look for independent factors associated with side effect from anti-TB therapy. A total of 720 patients (144 cases and 576 controls) were analyzed. In our multivariable model, age, especially those over 40 years (OR = 3.93; 95%CI: 1.65–9.35), overweight/obesity (OR = 2.13; 95%CI: 1.17–3.89), anemia (OR = 2.10; IC95%: 1.13–3.92), MDR-TB medication (OR = 11.1; 95%CI: 6.29–19.6), and smoking (OR = 2.00; 95%CI: 1.03–3.87) were independently associated with adverse drug reactions. Conclusions Old age, anemia, MDR-TB medication, overweight/obesity status, and smoking history are independent risk factors associated with anti-tuberculosis adverse drug reactions. Patients with these risk factors should be monitored during the anti-TB therapy. A comprehensive clinical history and additional medical exams, including hematocrit and HIV-ELISA, might be useful to identify these patients. PMID:22110689

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

    PubMed

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

    2018-04-01

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

  8. Adverse Drug Reactions to Antiretroviral Therapy in HIV-Infected Patients at the Largest Public Hospital in Nicaragua.

    PubMed

    Lorío, Marco; Colasanti, Jonathan; Moreira, Sumaya; Gutierrez, Gamaliel; Quant, Carlos

    2014-01-01

    Adverse drug reactions (ADRs) to antiretroviral therapy (ART) are an important cause of hospitalization, treatment discontinuation, and regimen changes in both developed and developing countries. This study is the first to examine and understand ADRs in HIV-infected patients in Nicaragua. A retrospective descriptive study was conducted from May 2010 to March 2011, in a cohort of HIV-infected patients receiving ART at the largest public hospital in Managua, Nicaragua. Patients were identified based on ADRs reporting on a standardized antiretroviral pharmacotherapy form. Subsequently, chart reviews of these patients were performed in order to document the specific ADRs. Six hundred ninety-two patients on ART were included. The incidence of ADRs was 6.4% (95% confidence interval [CI] 4.5-8.2). Females demonstrated a higher incidence, that is, 10.2% (95% CI 5.3-15.1, P = .020). Patients treated with combinations of zidovudine (ZDV)/lamivudine (3TC) and emtricitabine (FTC)/tenofovir (TDF) had fewer ADRs (P < .01) than those using other combinations. Five patients were hospitalized or had a prolonged hospitalization secondary to ADRs, with no mortality attributed to ADR. The most common manifestations of ADRs were central nervous system (20 of 44), gastrointestinal (12 of 44), and dermatologic (8 of 44) reactions. Adverse drug reactions were classified as "likely ADRs" (25 of 44) and "possible ADRs" (19 of 44). No ADRs were preventable. Adverse drug reactions most frequently affected the central nervous system. No ADR was life threatening. The frequency of ADRs in this Nicaraguan patient population was less than that reported from other studies in resource-limited settings. © The Author(s) 2014.

  9. How to promote adverse drug reaction reports using information systems - a systematic review and meta-analysis.

    PubMed

    Ribeiro-Vaz, Inês; Silva, Ana-Marta; Costa Santos, Cristina; Cruz-Correia, Ricardo

    2016-03-01

    Adverse drug reactions (ADRs) are a well-recognized public health problem and a major cause of death and hospitalization in developed countries. The safety of a new drug cannot be established until it has been on the market for several years. Keeping drug reactions under surveillance through pharmacovigilance systems is indispensable. However, underreporting is a major issue that undermines the effectiveness of spontaneous reports. Our work presents a systematic review on the use of information systems for the promotion of ADR reporting. The aim of this work is to describe the state of the art information systems used to promote adverse drug reaction reporting. A systematic review was performed with quantitative analysis of studies describing or evaluating the use of information systems to promote adverse drug reaction reporting. Studies with data related to the number of ADRs reported before and after each intervention and the follow-up period were included in the quantitative analysis. From a total of 3865 articles, 33 articles were included in the analysis; these articles described 29 different projects. Most of the projects were on a regional scale (62 %) and were performed in a hospital context (52 %). A total of 76 % performed passive promotion of ADR reporting and used web-based software (55 %). A total of 72 % targeted healthcare professionals and 24 % were oriented to patient ADR reporting. We performed a meta-analysis of 7 of the 29 projects to calculate the aggregated measure of the ADR reporting increase, which had an overall measure of 2.1 (indicating that the interventions doubled the number of ADRs reported). We found that most of the projects performed passive promotion of ADR reporting (i.e., facilitating the process). They were developed in hospitals and were tailored to healthcare professionals. These interventions doubled the number of ADR reports. We believe that it would be useful to develop systems to assist healthcare professionals

  10. A review and assessment of drug-induced parotitis.

    PubMed

    Brooks, Krista G; Thompson, Dennis F

    2012-12-01

    To review the current literature on drug-induced parotitis. Literature was accessed through MEDLINE/PubMed (1980-May 2012), using the search terms sialadenitis/chemically induced and parotitis/chemically induced. EMBASE (1980-May 2012) was searched using the terms parotitis/diagnosis, sialadenitis/side effect, and parotitis/side effect. International Pharmaceutical Abstracts (1970-May 2012) was searched using the search terms parotitis and sialadenitis. All searches were limited to articles on humans written in English. Inclusion criteria were published letters, case reports, reviews, and clinical trials involving drugs that may be associated with parotitis. Articles pertaining to parotitis induced by iodine-containing drugs were excluded. References of all relevant articles were reviewed for additional citations. Review articles, clinical trials, background data, and case reports of drug-induced parotitis were collected and case reports were assessed for causality. Parotitis is an uncommon adverse effect; however, signs and symptoms of parotitis have been noted in case reports as an adverse drug reaction related to various medications. Assessing causality of an adverse drug reaction such as parotitis is challenging. To help determine the probability of causality for these events, algorithms such as the Naranjo probability scale have been developed. Eighty-four case reports of drug-induced parotitis from 40 different drugs were reviewed using a modified Naranjo probability scale that included criteria specific for parotitis. Medications that met the criteria for establishing causality included l-asparaginase with 7 case reports, clozapine with 13 case reports, and phenylbutazone with 13 case reports. Drug-induced parotitis is a rare adverse drug reaction. Based on the quantitative and qualitative evidence collected from the case reports, medications that are associated with drug-induced parotitis include l-asparaginase, clozapine, and phenylbutazone. Many other

  11. Adverse Drug Event Causality Analysis (ADECA): A Process for Evaluating Evidence and Assigning Drugs to Risk Categories for Sudden Death.

    PubMed

    Woosley, Raymond L; Romero, Klaus; Heise, Craig W; Gallo, Tyler; Tate, Jared; Woosley, Raymond David; Ward, Sophie

    2017-06-01

    Growing evidence indicates that many drugs have the ability to cause a potentially lethal cardiac arrhythmia, torsades de pointes (TdP). This necessitates the development of a compilation of drugs that have this potential toxicity. Such a list is helpful in identifying the etiology of TdP in patients taking multiple drugs and assists decision making by those caring for patients at high risk of TdP. The Arizona Center for Education and Research on Therapeutics (AZCERT) has developed a process to standardize the identification of drugs and place them in risk categories for their clinical ability to cause TdP and QT prolongation. AZCERT's Adverse Drug Event Causality Analysis (ADECA) utilizes 16 types of data drawn from four sources to compile an open-source knowledge base, QTdrugs, which is maintained on the CredibleMeds.org website. Because the evidence for most drugs is incomplete, the ADECA process is used to place drugs into one of three categories that represent different levels of certainty: known TdP risk, possible TdP risk, and conditional TdP risk. Each category has strict evidentiary requirements for clinical evidence of TdP and/or QT prolongation. These are described in this paper. Because evidence can evolve over time, the ADECA process includes the continuous gathering and analysis of newly emerging evidence to revise the lists. The QTdrugs lists have proven to be a valued, readily available, commercial influence-free resource for healthcare providers, patients, researchers, and authors of consensus guidelines for the safe use of medicines.

  12. Large-scale combining signals from both biomedical literature and the FDA Adverse Event Reporting System (FAERS) to improve post-marketing drug safety signal detection

    PubMed Central

    2014-01-01

    Background Independent data sources can be used to augment post-marketing drug safety signal detection. The vast amount of publicly available biomedical literature contains rich side effect information for drugs at all clinical stages. In this study, we present a large-scale signal boosting approach that combines over 4 million records in the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and over 21 million biomedical articles. Results The datasets are comprised of 4,285,097 records from FAERS and 21,354,075 MEDLINE articles. We first extracted all drug-side effect (SE) pairs from FAERS. Our study implemented a total of seven signal ranking algorithms. We then compared these different ranking algorithms before and after they were boosted with signals from MEDLINE sentences or abstracts. Finally, we manually curated all drug-cardiovascular (CV) pairs that appeared in both data sources and investigated whether our approach can detect many true signals that have not been included in FDA drug labels. We extracted a total of 2,787,797 drug-SE pairs from FAERS with a low initial precision of 0.025. The ranking algorithm combined signals from both FAERS and MEDLINE, significantly improving the precision from 0.025 to 0.371 for top-ranked pairs, representing a 13.8 fold elevation in precision. We showed by manual curation that drug-SE pairs that appeared in both data sources were highly enriched with true signals, many of which have not yet been included in FDA drug labels. Conclusions We have developed an efficient and effective drug safety signal ranking and strengthening approach We demonstrate that large-scale combining information from FAERS and biomedical literature can significantly contribute to drug safety surveillance. PMID:24428898

  13. Patch testing in non-immediate cutaneous adverse drug reactions: value of extemporaneous patch tests.

    PubMed

    Assier, Haudrey; Valeyrie-Allanore, Laurence; Gener, Gwendeline; Verlinde Carvalh, Muriel; Chosidow, Olivier; Wolkenstein, Pierre

    2017-11-01

    Patch testing following a standardized protocol is reliable for identifying the culprit drug in cutaneous adverse drug reactions (CADRs). However, these patch tests (PTs) require pharmaceutical material and staff, which are not always easily available. To evaluate an extemporaneous PT method in CADRs. We retrospectively analysed data for all patients referred to our department between March 2009 and June 2013 for patch testing after a non-immediate CADR. The patients who supplied their own suspected drugs were tested both with extemporaneous PTs and with conventional PTs. Extemporaneous PTs involved a nurse crushing and diluting the drug in pet. in a ratio of approximately one-third to two-thirds. Standardized PTs were performed according to guidelines, with commercial drugs diluted to 30% or with active ingredients diluted to 10%. We analysed the data for the two PT methods in terms of the number of positive test reactions, drugs tested, and type of CADR for patients in whom the two PT methods were used. In total, 75 of 156 patients underwent the two PT procedures, including 91 double tests. Overall, 21 tests gave positive reactions with the two methods, and 69 other tests gave negative results with the two methods. Our series yielded results similar to those of published series concerning the types of CADR and the drugs responsible. Our results suggest that, for CADRs, if a patient supplies a suspected drug but if the pharmaceutical material and staff are not available for conventional PTs, extemporaneous PTs performed by the nurse with the commercial drug used by the patient can be useful and reliable. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Pattern of adverse drug reactions reported by the community pharmacists in Nepal

    PubMed Central

    Palaian, Subish; Ibrahim, Mohamed I.M.; Mishra, Pranaya

    2010-01-01

    The pharmacovigilance program in Nepal is less than a decade old, and is hospital centered. This study highlights the findings of a community based pharmacovigilance program involving the community pharmacists. Objectives: To collect the demographic details of the patients experiencing adverse drug reactions (ADR) reported by the community pharmacists; to identify the common drugs causing the ADRs, the common types of ADRs; and to carry out the causality, severity and preventability assessments of the reported ADRs. Methods: The baseline Knowledge-Attitude-Practices (KAP) of 116 community pharmacists from Pokhara valley towards drug safety was evaluated using a validated (Cronbach alpha=0.61) KAP questionnaire having 20 questions [(knowledge 11, attitude 5 and practice 4) maximum possible score 40]. Thirty community pharmacists with high scores were selected for three training sessions, each session lasting for one to two hours, covering the basic knowledge required for the community pharmacists for ADR reporting. Pharmacist from the regional pharmacovigilance center visited the trained community pharmacists every alternate day and collected the filled ADR reporting forms. Results: Altogether 71 ADRs, from 71 patients (37 males) were reported. Antibiotics/ antibacterials caused 42% (n=37) of the total ADRs followed by non steroidal anti-inflammatory drugs [25% (n=22)]. Ibuprofen/paracetamol combination accounted for ten ADRs. The most common type of ADR was itching [17.2 % (n=20), followed by generalized edema [8.6 % (n=10)]. In order to manage the ADRs, the patients needed medical treatment in 69% (n=49) of the cases. Over two third (69%) of the ADRs had a ‘possible’ association with the suspected drugs and a high percentage (70.4%) were of ‘mild (level 2)’ type. Nearly two third [64.7 % (n=46)] of the ADRs were ‘definitely preventable’. Conclusion: The common class of drugs known to cause ADRs was antibacterial/ antibiotics. Ibuprofen/ Paracetamol

  15. Filtering big data from social media--Building an early warning system for adverse drug reactions.

    PubMed

    Yang, Ming; Kiang, Melody; Shang, Wei

    2015-04-01

    Adverse drug reactions (ADRs) are believed to be a leading cause of death in the world. Pharmacovigilance systems are aimed at early detection of ADRs. With the popularity of social media, Web forums and discussion boards become important sources of data for consumers to share their drug use experience, as a result may provide useful information on drugs and their adverse reactions. In this study, we propose an automated ADR related posts filtering mechanism using text classification methods. In real-life settings, ADR related messages are highly distributed in social media, while non-ADR related messages are unspecific and topically diverse. It is expensive to manually label a large amount of ADR related messages (positive examples) and non-ADR related messages (negative examples) to train classification systems. To mitigate this challenge, we examine the use of a partially supervised learning classification method to automate the process. We propose a novel pharmacovigilance system leveraging a Latent Dirichlet Allocation modeling module and a partially supervised classification approach. We select drugs with more than 500 threads of discussion, and collect all the original posts and comments of these drugs using an automatic Web spidering program as the text corpus. Various classifiers were trained by varying the number of positive examples and the number of topics. The trained classifiers were applied to 3000 posts published over 60 days. Top-ranked posts from each classifier were pooled and the resulting set of 300 posts was reviewed by a domain expert to evaluate the classifiers. Compare to the alternative approaches using supervised learning methods and three general purpose partially supervised learning methods, our approach performs significantly better in terms of precision, recall, and the F measure (the harmonic mean of precision and recall), based on a computational experiment using online discussion threads from Medhelp. Our design provides

  16. Clopidogrel-Proton Pump Inhibitor Drug-Drug Interaction and Risk of Adverse Clinical Outcomes Among PCI-Treated ACS Patients: A Meta-analysis.

    PubMed

    Serbin, Michael A; Guzauskas, Gregory F; Veenstra, David L

    2016-08-01

    Uncertainty regarding clopidogrel effectiveness attenuation because of a drug-drug interaction with proton pump inhibitors (PPI) has led to conflicting guidelines on concomitant therapy. In particular, the effect of this interaction in patients who undergo a percutaneous coronary intervention (PCI), a population known to have increased risk of adverse cardiovascular events, has not been systematically evaluated. To synthesize the evidence of the effect of clopidogrel-PPI drug interaction on adverse cardiovascular outcomes in a PCI patient population. We conducted a systematic literature review for studies reporting clinical outcomes in patients who underwent a PCI and were initiated on clopidogrel with or without a PPI. Studies were included in the analysis if they reported at least 1 of the clinical outcomes of interest (major adverse cardiovascular event [MACE], cardiovascular death, all-cause death, myocardial infarction, stroke, stent thrombosis, and bleed events). We excluded studies that were not exclusive to PCI patients or had no PCI subgroup analysis and/or did not report at least a 6-month follow-up. Statistical and clinical heterogeneity were evaluated and HRs and 95% CIs for adverse clinical events were pooled using the DerSimonian and Laird random-effects meta-analysis method. We identified 12 studies comprising 50,277 PCI patients that met our inclusion and exclusion criteria. Our analysis included retrospective analyses of randomized controlled trials (2), health registries (3), claims databases (2), and institutional records (5); no prospective studies of PCI patients were identified. On average, patients were in their mid-60s, male, and had an array of comorbidities, including hyperlipidemia, diabetes, hypertension, and smoking history. Concomitant therapy following PCI resulted in statistically significant increases in composite MACE (HR = 1.28; 95% CI = 1.24-1.32), myocardial infarction (HR = 1.51; 95% CI = 1.40-1.62), and stroke (HR = 1.46; 95

  17. Drugs and Medical Devices: Adverse Events and the Impact on Women's Health.

    PubMed

    Carey, Jennifer L; Nader, Nathalie; Chai, Peter R; Carreiro, Stephanie; Griswold, Matthew K; Boyle, Katherine L

    2017-01-01

    A large number of medications and medical devices removed from the market by the US Food and Drug Administration over the past 4 decades specifically posed greater health risks to women. This article reviews the historical background of sex and gender in clinical research policy and describes several approved drugs and devices targeted for use in women that have caused major morbidity and mortality. The intended population for the medications and devices, population affected, approval process, and the basic and legal actions taken against the medication/drug company are also discussed. It is recognized that women are still at risk for harm from unsafe medications and devices, and continued improvements in legislation that promotes inclusion of sex and gender into the design and analysis of research will improve safety for both men and women. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

  18. A retrospective study on the incidences of adverse drug events and analysis of the contributing trigger factors

    PubMed Central

    Sam, Aaseer Thamby; Lian Jessica, Looi Li; Parasuraman, Subramani

    2015-01-01

    Objectives: To retrospectively determine the extent and types of adverse drug events (ADEs) from the patient cases sheets and identify the contributing factors of medication errors. To assess causality and severity using the World Health Organization (WHO) probability scale and Hartwig's scale, respectively. Methods: Hundred patient case sheets were randomly selected, modified version of the Institute for Healthcare Improvement (IHI) Global Trigger Tool was utilized to identify the ADEs; causality and severity were calculated utilizing the WHO probability scale and Hartwig's severity assessment scale, respectively. Results: In total, 153 adverse events (AEs) were identified using the IHI Global Trigger Tool. Majority of the AEs are due to medication errors (46.41%) followed by 60 adverse drug reactions (ADRs), 15 therapeutic failure incidents, and 7 over-dose cases. Out of the 153 AEs, 60 are due to ADRs such as rashes, nausea, and vomiting. Therapeutic failure contributes 9.80% of the AEs, while overdose contributes to 4.58% of the total 153 AEs. Using the trigger tools, we were able to detect 45 positive triggers in 36 patient records. Among it, 19 AEs were identified in 15 patient records. The percentage of AE/100 patients is 17%. The average ADEs/1000 doses is 2.03% (calculated). Conclusion: The IHI Global Trigger Tool is an effective method to aid provisionally-registered pharmacists to identify ADEs quicker. PMID:25767366

  19. Disentangling incentives effects of insurance coverage from adverse selection in the case of drug expenditure: a finite mixture approach.

    PubMed

    Munkin, Murat K; Trivedi, Pravin K

    2010-09-01

    This paper takes a finite mixture approach to model heterogeneity in incentive and selection effects of drug coverage on total drug expenditure among the Medicare elderly US population. Evidence is found that the positive drug expenditures of the elderly population can be decomposed into two groups different in the identified selection effects and interpreted as relatively healthy with lower average expenditures and relatively unhealthy with higher average expenditures, accounting for approximately 25 and 75% of the population, respectively. Adverse selection into drug insurance appears to be strong for the higher expenditure component and weak for the lower expenditure group. Copyright (c) 2010 John Wiley & Sons, Ltd.

  20. Methodology for computing the burden of disease of adverse events following immunization.

    PubMed

    McDonald, Scott A; Nijsten, Danielle; Bollaerts, Kaatje; Bauwens, Jorgen; Praet, Nicolas; van der Sande, Marianne; Bauchau, Vincent; de Smedt, Tom; Sturkenboom, Miriam; Hahné, Susan

    2018-03-24

    Composite disease burden measures such as disability-adjusted life-years (DALY) have been widely used to quantify the population-level health impact of disease or injury, but application has been limited for the estimation of the burden of adverse events following immunization. Our objective was to assess the feasibility of adapting the DALY approach for estimating adverse event burden. We developed a practical methodological framework, explicitly describing all steps involved: acquisition of relative or absolute risks and background event incidence rates, selection of disability weights and durations, and computation of the years lived with disability (YLD) measure, with appropriate estimation of uncertainty. We present a worked example, in which YLD is computed for 3 recognized adverse reactions following 3 childhood vaccination types, based on background incidence rates and relative/absolute risks retrieved from the literature. YLD provided extra insight into the health impact of an adverse event over presentation of incidence rates only, as severity and duration are additionally incorporated. As well as providing guidance for the deployment of DALY methodology in the context of adverse events associated with vaccination, we also identified where data limitations potentially occur. Burden of disease methodology can be applied to estimate the health burden of adverse events following vaccination in a systematic way. As with all burden of disease studies, interpretation of the estimates must consider the quality and accuracy of the data sources contributing to the DALY computation. © 2018 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd.

  1. Recognizing Severe Adverse Drug Reactions: Two Case Reports After Switching Therapies to the Same Generic Company.

    PubMed

    Gallelli, Luca; Gallelli, Giuseppe; Codamo, Giuseppe; Argentieri, Angela; Michniewicz, Andzelika; Siniscalchi, Antonio; Stefanelli, Roberta; Cione, Erika; Caroleo, Maria C; Longo, Paola; De Sarro, Giovambattista

    2016-01-01

    Generic formulations represent a way to reduce the costs of brand compounds when their patent is expired. While, the bio-equivalence in generic drugs is guaranteed, some excipients as well as dyes could be different and this could reduce the drug safety. Herein, we report the development of Adverse Drug Reactions (ADRs) in two patients after the switch from brand to generic formulations. We have tested cytochrome P450 enzymes expression as well as drug serum levels. None of these markers were altered. Checking deeply into both patient's medical history, they harbored poly-sensitivity or allergy to pollen and graminacea and used different active ingredients for different health problems coming from the same generic company Almus(®). This company used different dyes and excipients compared to the branded drugs made by distinguished companies. In conclusion, we strongly suggest to both pharmacists and physicians to be careful in giving the advice to change the drug, thinking to reduce health sanitary costs without considering the personal clinical history of each one. Paradoxically this behavior is causing other health issues, bringing to an increase of the overall costs for patients as well as for National Health System.

  2. [Active surveillance of adverse drug reaction in the era of big data: challenge and opportunity for control selection].

    PubMed

    Wang, S F; Zhan, S Y

    2016-07-01

    Electronic healthcare databases have become an important source for active surveillance of drug safety in the era of big data. The traditional epidemiology research designs are needed to confirm the association between drug use and adverse events based on these datasets, and the selection of the comparative control is essential to each design. This article aims to explain the principle and application of each type of control selection, introduce the methods and parameters for method comparison, and describe the latest achievements in the batch processing of control selection, which would provide important methodological reference for the use of electronic healthcare databases to conduct post-marketing drug safety surveillance in China.

  3. Willingness to pay for adverse drug event regulatory actions.

    PubMed

    Bouvy, Jacoline; Weemers, Just; Schellekens, Huub; Koopmanschap, Marc

    2011-11-01

    . This study is, as far as we know, one of the first attempts to analyse the WTP for drug regulation and should in future be used in studies of the societal costs of drug regulation for epoetin alpha use. Our results indicate that the Dutch general public, especially Dutch dialysis patients, are willing to pay limited amounts to reduce the risk of serious adverse events associated with drug use.

  4. Nicorandil, Gastrointestinal Adverse Drug Reactions and Ulcerations: A Systematic Review.

    PubMed

    Pisano, Umberto; Deosaran, Jordanna; Leslie, Stephen J; Rushworth, Gordon F; Stewart, Derek; Ford, Ian; Watson, Angus J M

    2016-03-01

    Nicorandil is a popular anti-anginal drug in Europe and Japan. Apart from some common adverse drug reactions (ADR), its safety is satisfactory. Several reports have suggested a link between nicorandil, gastrointestinal (GI) ulceration and fistulas. The review aims to critically appraise, synthesize and present the available evidence of all known GI ADR per anatomical location. The study complied with the PRISMA statement. Literature and pharmacovigilance databases were used to provide rate and/or calculate parameters (median age, median dose, history of symptoms, length of therapy and healing time after withdrawal of the drug). Differences in distribution of quantitative variables were analyzed via Mann-Whitney test. Correlation between quantitative variables was assessed with a Spearman's correlation coefficient. A p value <0.05 was significant. Oral ulcerations occur in 0.2% of the subjects, anal ulcerations are present between 0.07% and 0.37% of patients. Oral and distal GI involvements are the most common ADR (28-29% and 27-31% of all GI ADR, respectively). The hepatobiliary system, the pancreas and salivary glands are not affected by nicorandil exposure. The time to develop oral ulcerations is 74 weeks among people on <30 mg/day compared to only 7.5 weeks in individuals on higher regimens (p = 0.47). There is a significant correlation between dose and ulcer healing time (Spearman's 0.525, p < 0.001). Ulcerative disease is a very commonly reported GI ADR. A delayed ulcerative tendency supports the hypothesis of an ulcerogenic metabolite. Nicorandil seems to act as a cause of the ulcerations, but appears to also work in synergy with other promoting factors. Whether the action of the metabolites relies on a specific mechanism or a simple chemical ulceration is still to be established.

  5. 21 CFR 606.170 - Adverse reaction file.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Adverse reaction file. 606.170 Section 606.170... Adverse reaction file. (a) Records shall be maintained of any reports of complaints of adverse reactions... thorough investigation of each reported adverse reaction shall be made. A written report of the...

  6. Fatigue during treatment with antiepileptic drugs: A levetiracetam-specific adverse event?

    PubMed

    Mula, Marco; von Oertzen, Tim J; Cock, Hannah R; Yogarajah, Mahinda; Lozsadi, Dora A; Agrawal, Niruj

    2017-07-01

    To examine the prevalence and clinical correlates of fatigue as an adverse event (AE) of antiepileptic drug (AED) treatment in patients with epilepsy. Data from 443 adult outpatients with epilepsy assessed with the Adverse Event Profile (AEP) and the Neurological Disorder Depression Inventory for Epilepsy (NDDIE) were analysed. Fatigue is reported by 36.6% of patients as always a problem during AED treatment. Fatigue is more likely to be reported by females (64.8% vs. 35.2%; Chi-Square=16.762; df=3; p=0.001) and during treatment with levetiracetam (42.3% vs. 33.2%; Chi-Square=11.462; df=3; p=0.009). The associations with the female gender and levetiracetam treatment were not mediated by depression, as identified with the NDDIE, and could not be simply explained by the large number of subjects on levetiracetam treatment, as analogous figures resulted from the analysis of a monotherapy subsample (41.7% vs. 30.3%; Chi-Square=11.547; df=3; p=0.009). One third of patients with epilepsy reports fatigue as a significant problem during AED treatment. Fatigue is more likely to be reported by females and seems to be specifically associated with LEV treatment. However, fatigue is not mediated by a negative effect of LEV on mood. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    PubMed Central

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

    2005-01-01

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

  8. Teledermatologist expert skin advice: A unique model of care for managing skin disorders and adverse drug reactions in hepatitis C patients.

    PubMed

    Charlston, Samuel; Siller, Gregory

    2018-03-23

    To conduct an audit of teledermatologist expert skin advice, a store and forward tele-dermatological service, to determine its effectiveness and user satisfaction in managing cutaneous adverse drug reactions in patients with hepatitis C, and to demonstrate a unique collaborative model of care for patients receiving specialised drug therapy. A retrospective analysis of data on teledermatologist expert skin advice referrals from January 2014 to December 2015 was performed. The primary outcomes assessed included number of referrals, referral locations, diagnoses, response times, quality of clinical information provided and user satisfaction ratings. Altogether 43 consultations from 29 referring sites were received from Australian metropolitan and rural settings. Of the patients, 43 were diagnosed with an adverse drug reaction related to the use of either telaprevir or simeprevir. The average time taken for the dermatologist to reply electronically with a final diagnosis and management plan was 1 h 57 min. As many as 26% of referrals required additional photos to establish a diagnosis due to poor-quality images or insufficient detail. Altogether 18 clinicians completed the customer satisfaction survey, all of whom rated teledermatologist expert skin advice nine or above on a scale of one to 10. Teledermatologist expert skin advice was regarded by clinicians as a valuable patient care service. The platform is a novel modality that supports patients undergoing specialised treatments at risk of cutaneous adverse drug reaction. © 2018 The Australasian College of Dermatologists.

  9. Stimulated reporting: the impact of US food and drug administration-issued alerts on the adverse event reporting system (FAERS).

    PubMed

    Hoffman, Keith B; Demakas, Andrea R; Dimbil, Mo; Tatonetti, Nicholas P; Erdman, Colin B

    2014-11-01

    The US Food and Drug Administration (FDA) uses the Adverse Event Reporting System (FAERS) to support post-marketing safety surveillance programs. Currently, almost one million case reports are submitted to FAERS each year, making it a vast repository of drug safety information. Sometimes cited as a limitation of FAERS, however, is the assumption that "stimulated reporting" of adverse events (AEs) occurs in response to warnings, alerts, and label changes that are issued by the FDA. To determine the extent of "stimulated reporting" in the modern-day FAERS database. One hundred drugs approved by the FDA between 2001 and 2010 were included in this analysis. FDA alerts were obtained by a comprehensive search of the FDA's MedWatch and main websites. Publicly available FAERS data were used to assess the "primary suspect" AE reporting pattern for up to four quarters before, and after, the issuance of an FDA alert. A few drugs did demonstrate "stimulated reporting" trends. A majority of the drugs, however, showed little evidence for significant reporting changes associated with the issuance of alerts. When we compared the percentage changes in reporting after an FDA alert with those after a sham "control alert", the overall reporting trends appeared to be quite similar. Of 100 drugs analyzed for short-term reporting trends, 21 real alerts and 25 sham alerts demonstrated an increase (greater than or equal to 1 %) in reporting. The long-term analysis of 91 drugs showed that 24 real alerts and 28 sham alerts demonstrated a greater than or equal to 1 % increase. Our results suggest that most of modern day FAERS reporting is not significantly affected by the issuance of FDA alerts.

  10. The ADE scorecards: a tool for adverse drug event detection in electronic health records.

    PubMed

    Chazard, Emmanuel; Băceanu, Adrian; Ferret, Laurie; Ficheur, Grégoire

    2011-01-01

    Although several methods exist for Adverse Drug events (ADE) detection due to past hospitalizations, a tool that could display those ADEs to the physicians does not exist yet. This article presents the ADE Scorecards, a Web tool that enables to screen past hospitalizations extracted from Electronic Health Records (EHR), using a set of ADE detection rules, presently rules discovered by data mining. The tool enables the physicians to (1) get contextualized statistics about the ADEs that happen in their medical department, (2) see the rules that are useful in their department, i.e. the rules that could have enabled to prevent those ADEs and (3) review in detail the ADE cases, through a comprehensive interface displaying the diagnoses, procedures, lab results, administered drugs and anonymized records. The article shows a demonstration of the tool through a use case.

  11. Surveying Teens in School to Assess the Prevalence of Problematic Drug Use

    ERIC Educational Resources Information Center

    Falck, Russel S.; Nahhas, Ramzi W.; Li, Linna; Carlson, Robert G.

    2012-01-01

    Background: Illicit drug use by school-aged teens can adversely affect their health and academic achievement. This study used a survey administered in schools to assess the prevalence of problematic drug use among teenagers in a Midwestern community. Methods: Self-report data were collected from 11th- and 12th-grade students (N = 3974) in 16…

  12. AOP: An R Package For Sufficient Causal Analysis in Pathway-based Screening of Drugs and Chemicals for Adversity

    EPA Science Inventory

    Summary: How can I quickly find the key events in a pathway that I need to monitor to predict that a/an beneficial/adverse event/outcome will occur? This is a key question when using signaling pathways for drug/chemical screening in pharma-cology, toxicology and risk assessment. ...

  13. Patient Drug Safety Reporting: Diabetes Patients' Perceptions of Drug Safety and How to Improve Reporting of Adverse Events and Product Complaints.

    PubMed

    Patel, Puja; Spears, David; Eriksen, Betina Østergaard; Lollike, Karsten; Sacco, Michael

    2018-03-01

    Global health care manufacturer Novo Nordisk commissioned research regarding awareness of drug safety department activities and potential to increase patient feedback. Objectives were to examine patients' knowledge of pharmaceutical manufacturers' responsibilities and efforts regarding drug safety, their perceptions and experiences related to these efforts, and how these factors influence their thoughts and behaviors. Data were collected before and after respondents read a description of a drug safety department and its practices. We conducted quantitative survey research across 608 health care consumers receiving treatment for diabetes in the United States, Germany, United Kingdom, and Italy. This research validated initial, exploratory qualitative research (across 40 comparable consumers from the same countries) which served to guide design of the larger study. Before reading a drug safety department description, 55% of respondents were unaware these departments collect safety information on products and patients. After reading the description, 34% reported the department does more than they expected to ensure drug safety, and 56% reported "more confidence" in the industry as a whole. Further, 66% reported themselves more likely to report an adverse event or product complaint, and 60% reported that they were more likely to contact a drug safety department with questions. The most preferred communication methods were websites/online forums (39%), email (27%), and telephone (25%). Learning about drug safety departments elevates consumers' confidence in manufacturers' safety efforts and establishes potential for patients to engage in increased self-monitoring and reporting. Study results reveal potentially actionable insights for the industry across patient and physician programs and communications.

  14. Polysensitivity in delayed cutaneous adverse drug reactions to macrolides, clindamycin, and pristinamycin: clinical history and patch testing.

    PubMed

    El Khoury, M; Assier, H; Gener, G; Paul, M; Haddad, C; Chosidow, O; Wolkenstein, P; Ingen-Housz-Oro, S

    2018-05-10

    Although they have different biochemical structures, macrolides, lincosamides (including clindamycin) and streptogramins (including pristinamycin) share a similar mechanism of action on Gram-positive bacteria and are grouped into the MLS family. 1 Cross-allergies induced by drugs of similar mechanism of action but different chemical structure (polysensitivity) are poorly described. Our objectives were to investigate the possibility of polysensitivity among MLS antibiotics, and to compare the value of patch tests (PTs) in MLS-induced delayed-cutaneous adverse drug reactions (D-CADRs). This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  15. Association of HLA-A and HLA-B Alleles with Lamotrigine-Induced Cutaneous Adverse Drug Reactions in the Thai Population

    PubMed Central

    Koomdee, Napatrupron; Pratoomwun, Jirawat; Jantararoungtong, Thawinee; Theeramoke, Voralaksana; Tassaneeyakul, Wichittra; Klaewsongkram, Jettanong; Rerkpattanapipat, Ticha; Santon, Siwalee; Puangpetch, Apichaya; Intusoma, Utcharee; Tempark, Therdpong; Deesudchit, Tayard; Satapornpong, Patompong; Visudtibhan, Anannit; Sukasem, Chonlaphat

    2017-01-01

    Background: Lamotrigine (LTG) is commonly used for treatment of epilepsy and bipolar disorder. It is one of the common cause of cutaneous adverse drug reactions (CADR). Clinical symptoms of LTG-induced CADR range from maculopapular exanthema (MPE) to severe cutaneous adverse reactions (SCAR). This study aimed to determine the association of the LTG-induced CADR with human leukocyte antigen (HLA) alleles in Thai patients. Methods: Fifteen patients with LTG-induced CADR [10 MPE; 4 Stevens–Johnson syndrome; and 1 drug reaction with eosinophilia and systemic symptoms] and 50 LTG-tolerant controls were included in the study. HLA-A and HLA-B genotyping was performed using polymerase chain reaction-sequence-specific oligonucleotides probes. Results: The proportion of HLA-A∗02:07 and HLA-B∗15:02 allele carriers were significantly higher in the LTG-induced CADR group than in the tolerant controls [odds ratio (OR): 7.83; 95% confidence interval (CI): 1.60–38.25; P = 0.013, and OR: 4.89; 95% CI: 1.28–18.67; P = 0.014]. In addition, subjects with HLA-A∗33:03, HLA-B∗15:02, and HLA-B∗44:03 were significantly higher in the LTG-induced MPE group than in the tolerant controls (OR: 8.27; 95% CI: 1.83–37.41; P = 0.005, OR: 7.33; 95% CI: 1.63–33.02; P = 0.005; and OR: 10.29; 95% CI: 1.45–72.81; P = 0.029). In contrast to the LTG-induced MPE group, there were no significant differences between HLA alleles and LTG-induced SCAR group. Conclusion: HLA-A∗02:07 and HLA-B∗15:02 were associated with LTG-induced CADR in Thai patients. We also identified an association between HLA-A∗33:03, HLA-B∗15:02, and HLA-B∗44:03 and LTG-induced MPE in this population. These results suggest that these alleles could be useful screening markers for preventing CADR before LTG treatment in Thai patients, but further replication studies with larger sample sizes are needed. PMID:29238301

  16. 21 CFR 606.170 - Adverse reaction file.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Adverse reaction file. 606.170 Section 606.170 Food... reaction file. (a) Records shall be maintained of any reports of complaints of adverse reactions regarding... investigation of each reported adverse reaction shall be made. A written report of the investigation of adverse...

  17. 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.

  18. Dose-specific adverse drug reaction identification in electronic patient records: temporal data mining in an inpatient psychiatric population.

    PubMed

    Eriksson, Robert; Werge, Thomas; Jensen, Lars Juhl; Brunak, Søren

    2014-04-01

    Data collected for medical, filing and administrative purposes in electronic patient records (EPRs) represent a rich source of individualised clinical data, which has great potential for improved detection of patients experiencing adverse drug reactions (ADRs), across all approved drugs and across all indication areas. The aim of this study was to take advantage of techniques for temporal data mining of EPRs in order to detect ADRs in a patient- and dose-specific manner. We used a psychiatric hospital's EPR system to investigate undesired drug effects. Within one workflow the method identified patient-specific adverse events (AEs) and links these to specific drugs and dosages in a temporal manner, based on integration of text mining results and structured data. The structured data contained precise information on drug identity, dosage and strength. When applying the method to the 3,394 patients in the cohort, we identified AEs linked with a drug in 2,402 patients (70.8 %). Of the 43,528 patient-specific drug substances prescribed, 14,736 (33.9 %) were linked with AEs. From these links we identified multiple ADRs (p < 0.05) and found them to occur at similar frequencies, as stated by the manufacturer and in the literature. We showed that drugs displaying similar ADR profiles share targets, and we compared submitted spontaneous AE reports with our findings. For nine of the ten most prescribed antipsychotics in the patient population, larger doses were prescribed to sedated patients than non-sedated patients; five antipsychotics [corrected] exhibited a significant difference (p<0.05). Finally, we present two cases (p < 0.05) identified by the workflow. The method identified the potentially fatal AE QT prolongation caused by methadone, and a non-described likely ADR between levomepromazine and nightmares found among the hundreds of identified novel links between drugs and AEs (p < 0.05). The developed method can be used to extract dose-dependent ADR information from

  19. Associations of Adverse Clinical Course and Ingested Substances among Patients with Deliberate Drug Poisoning: A Cohort Study from an Intensive Care Unit in Japan.

    PubMed

    Ichikura, Kanako; Okumura, Yasuyuki; Takeuchi, Takashi

    2016-01-01

    Some patients with deliberate drug poisoning subsequently have an adverse clinical course. The present study aimed to examine whether the type of drugs ingested and psychiatric diagnoses were related to an adverse clinical course. We conducted a cohort study of patients with deliberate drug poisoning admitted to the intensive care unit of a university hospital located in Tokyo, Japan, between September 2006 and June 2013. Intensive care unit (ICU) stay of ≥4 days was used as a primary outcome measure, while the incidence of aspiration pneumonitis was used as a secondary outcome measure. Ingested substances and psychiatric diagnoses were used as explanatory variables. Of the 676 patients with deliberate drug poisoning, 88% had a history of psychiatric treatment and 82% had ingested psychotropic drugs. Chlorpromazine-promethazine-phenobarbital combination drug (Vegetamin®) ranked fifth among the most frequently ingested substances in cases of deliberate drug poisoning and had the highest incidence of prolonged ICU stay (20%) and aspiration pneumonitis (29%). The top three major classes consisted of benzodiazepines (79%), new-generation antidepressants (25%), and barbiturates/non-barbiturates (23%). Barbiturate overdose was independently associated with increased odds of both prolonged ICU stay (8% vs. 17%; odds ratio [OR], 2.97; 95% confidence interval [CI], 1.60-5.55) and aspiration pneumonitis (8% vs. 24%; OR, 3.83; 95% CI, 2.18-6.79) relative to those associated with overdose of only other sedative-hypnotics (i.e., benzodiazepines). These results suggest that judicious prescribing of barbiturates by psychiatrists could reduce the risk of an adverse clinical course when a patient attempts an overdose.

  20. Drugs and Medical Devices: Adverse Events and the Impact on Women’s Health

    PubMed Central

    Carey, Jennifer L.; Nader, Nathalie; Chai, Peter R.; Carreiro, Stephanie; Griswold, Matthew K.; Boyle, Katherine L.

    2018-01-01

    A large number of medications and medical devices removed from the market by the US Food and Drug Administration over the past 4 decades specifically posed greater health risks to women. This article reviews the historical background of sex and gender in clinical research policy and describes several approved drugs and devices targeted for use in women that have caused major morbidity and mortality. The intended population for the medications and devices, population affected, approval process, and the basic and legal actions taken against the medication/drug company are also discussed. It is recognized that women are still at risk for harm from unsafe medications and devices, and continued improvements in legislation that promotes inclusion of sex and gender into the design and analysis of research will improve safety for both men and women. PMID:28069260

  1. Nonsteroidal, antiinflammatory drug-induced gastrointestinal injuries and related adverse reactions: epidemiology, pathogenesis and management.

    PubMed

    Al Mofleh, Ibrahim A; Al Rashed, Rashed S

    2007-01-01

    A large proportion of the population all over the world consumes acetylsalicylic acid (ASA: aspirin) or other nonsteroidal, antiinflammatory drugs (NSAIDs). This is associated with a considerable morbidity and mortality. Elderly patients, patients with prior history of peptic ulcer disease (PUD) or its complications, those who require high doses of NSAIDs and those undergoing concomitant therapy with corticosteroids or anticoagulants, are at particularly high risk of developing gastroduodenal injuries and related adverse reactions. Gastroduodenal mucosal injuries induced by NSAIDs vary from subtle microscopic to gross macroscopic changes including ulcers. These injuries are induced by both topical and systemic actions of NSAIDs. Inhibition of gastroduodenal cyclooxygenase (COX) enzyme by NSAIDs is considered to be a major pathogenetic factor. Reactive oxygen species (ROS) appear also to play a significant role in the pathogenesis of mucosal injury. Withdrawal of NSAIDs is preferably the first therapeutic option; however, it is not feasible in the majority of patients. Therefore, several drugs including antisecretory drugs (ASDs-proton pump inhibitors and Histamine-2 receptor antagonists) and misoprostol, a prostaglandin analog are used for the prevention and treatment of NSAID-induced gastroduodenal injuries. Among ASDs, proton pump inhibitors (PPIs) are the most commonly used drugs. The antiulcerogenic effect of PPIs is similar to that of misoprostol and superior to standard doses of histamine-2 receptor antagonists (H2-RAs). The adverse effects of m, isoprostol such as diarrhea, abdominal pain, nausea, flatulence, headache, dyspepsia, vomiting, constipation, abortifacient and teratogenicity limit its general use. Aside from their antisecretory action, PPIs also possess an antioxidative effect. PPI maintenance is recommended in chronic NSAID treatment in those with an increased risk of complications and is more effective than Helicobacter pylori eradication. Low

  2. Chemical Leukoderma Associated with Methylphenidate Transdermal System: Data From the US Food and Drug Administration Adverse Event Reporting System.

    PubMed

    Cheng, Carmen; La Grenade, Lois; Diak, Ida-Lina; Brinker, Allen; Levin, Robert L

    2017-01-01

    To identify and characterize cases of chemical leukoderma, an underrecognized adverse event, associated with the methylphenidate transdermal system (MTS) reported to the US Food and Drug Administration Adverse Event Reporting System (FAERS). We searched the Food and Drug Administration Adverse Event Reporting System for reports of chemical leukoderma associated with MTS, received by the Food and Drug Administration from April 6, 2006 to December 23, 2014. We identified 51 cases of chemical leukoderma reported with the use of MTS. The median age was 11 years; 43 cases reported leukoderma at or near the application site only, and 7 reported leukoderma at other parts of the body in addition to the application site; 1 case did not provide enough information to confirm the affected site. The time to onset ranged from 2 months to 4 years after the initiation of MTS. MTS was discontinued in 31 cases. Thirteen patients were prescribed treatment for repigmentation. Three cases reported continued spread of leukoderma after MTS was discontinued. Nineteen cases were diagnosed as vitiligo, including 5 cases reporting histologic features consistent with vitiligo. Leukoderma was persistent in all cases. The median follow-up interval after the discontinuation of MTS in 23 cases was 14 months. As outlined in recent changes to the prescribing information for MTS, health care professionals need to be aware of the potential risk of chemical leukoderma caused by MTS, especially given that chemical leukoderma is often misdiagnosed as idiopathic vitiligo. MTS should be discontinued at the earliest sign of pigment loss and other treatment options considered. Published by Elsevier Inc.

  3. Filing Sources after Oral P2Y12 Platelet Inhibitors to the Food and Drug Administration Adverse Event Reporting System (FAERS).

    PubMed

    Serebruany, Victor L; Cherepanov, Vasily; Kim, Moo Hyun; Litvinov, Oleg; Cabrera-Fuentes, Hector A; Marciniak, Thomas A

    The US Food and Drug Administration Adverse Event Reporting System (FAERS) is a global passive surveillance database that relies on voluntary reporting by health care professionals and consumers as well as required mandatory reporting by pharmaceutical manufacturers. However, the initial filers and comparative patterns for oral P2Y12 platelet inhibitor reporting are unknown. We assessed who generated original FAERS reports for clopidogrel, prasugrel, and ticagrelor in 2015. From the FAERS database we extracted and examined adverse event cases coreported with oral P2Y12 platelet inhibitors. All adverse event filing originating sources were dichotomized into consumers, lawyers, pharmacists, physicians, other health care professionals, and unknown. Overall, 2015 annual adverse events were more commonly coreported with clopidogrel (n = 13,234) with known source filers (n = 12,818, or 96.9%) than with prasugrel (2,896; 98.9% out of 2,927 cases) or ticagrelor (2,163, or 82.3%, out of 2,627 cases, respectively). Overall, most adverse events were filed by consumers (8,336, or 44.4%), followed by physicians (5,290, or 28.2%), other health care professionals (2,997, or 16.0%), pharmacists (1,125, or 6.0%), and finally by lawyers (129, or 0.7%). The origin of 811 (4.7%) initial reports remains unknown. The adverse event filing sources differ among drugs. While adverse events coreported with clopidogrel and prasugrel were commonly originated by patients (40.4 and 84.3%, respectively), most frequently ticagrelor reports (42.5%) were filed by physicians. The reporting quality and initial sources differ among oral P2Y12 platelet inhibitors in FAERS. The ticagrelor surveillance in 2015 was inadequate when compared to clopidogrel and prasugrel. Patients filed most adverse events for clopidogrel and prasugrel, while physicians originated most ticagrelor complaints. These differences justify stricter compliance control for ticagrelor manufacturers and may be attributed to the

  4. 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.

  5. SSEL-ADE: A semi-supervised ensemble learning framework for extracting adverse drug events from social media.

    PubMed

    Liu, Jing; Zhao, Songzheng; Wang, Gang

    2018-01-01

    With the development of Web 2.0 technology, social media websites have become lucrative but under-explored data sources for extracting adverse drug events (ADEs), which is a serious health problem. Besides ADE, other semantic relation types (e.g., drug indication and beneficial effect) could hold between the drug and adverse event mentions, making ADE relation extraction - distinguishing ADE relationship from other relation types - necessary. However, conducting ADE relation extraction in social media environment is not a trivial task because of the expertise-dependent, time-consuming and costly annotation process, and the feature space's high-dimensionality attributed to intrinsic characteristics of social media data. This study aims to develop a framework for ADE relation extraction using patient-generated content in social media with better performance than that delivered by previous efforts. To achieve the objective, a general semi-supervised ensemble learning framework, SSEL-ADE, was developed. The framework exploited various lexical, semantic, and syntactic features, and integrated ensemble learning and semi-supervised learning. A series of experiments were conducted to verify the effectiveness of the proposed framework. Empirical results demonstrate the effectiveness of each component of SSEL-ADE and reveal that our proposed framework outperforms most of existing ADE relation extraction methods The SSEL-ADE can facilitate enhanced ADE relation extraction performance, thereby providing more reliable support for pharmacovigilance. Moreover, the proposed semi-supervised ensemble methods have the potential of being applied to effectively deal with other social media-based problems. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Serious adverse events and compensation in registration trials: a review of data from a Japanese university hospital

    PubMed Central

    2014-01-01

    Background Clinical trials leading to regulatory approval, or registration trials, play a central role in the development of drugs and medical devices. The contribution of support staff, such as the clinical research coordinator (CRC) and administrative officers, in registration trials is now widely recognized. Attending to serious adverse events is an important duty of the CRC and investigators alike, and managing these complications and compensation constitutes a key responsibility. We retrospectively examined the frequency of serious adverse events and compensation events reported from 2007 through 2011 at Tokushima University Hospital, an academic hospital in rural Japan. We present herein the results of our analysis. Results Over the five-year period, 284 subjects participating in 106 registration trials experienced a total of 43 serious adverse events, and eight compensation events were documented. Among the serious adverse events, 35 (81.4%) were considered not related to the investigational drug, and 17 (39.5%) resulted in withdrawal of the study drug. Patients with malignant diseases experienced serious adverse events significantly more frequently compared to those with non-malignant diseases (28.3% versus 8.2%, respectively; P < 0.01). Conclusions The CRC should be vigilant for serious adverse events in oncology clinical trials due to the generally higher frequency of these complications in subjects with malignancy. However, on an individual basis, the CRC may be seldom involved in the process for compensating serious adverse events. Therefore, the CRC’s ability to share such experiences may serve as an opportunity for educating clinical trial support staff at the study site as well as those at other sites. However, further study is warranted to determine the role of the clinical trial support staff in optimizing methods for managing adverse events requiring compensation in registration trials. PMID:24742228

  7. Adverse and Advantageous Selection in the Medicare Supplemental Market: A Bayesian Analysis of Prescription drug Expenditure.

    PubMed

    Li, Qian; Trivedi, Pravin K

    2016-02-01

    This paper develops an extended specification of the two-part model, which controls for unobservable self-selection and heterogeneity of health insurance, and analyzes the impact of Medicare supplemental plans on the prescription drug expenditure of the elderly, using a linked data set based on the Medicare Current Beneficiary Survey data for 2003-2004. The econometric analysis is conducted using a Bayesian econometric framework. We estimate the treatment effects for different counterfactuals and find significant evidence of endogeneity in plan choice and the presence of both adverse and advantageous selections in the supplemental insurance market. The average incentive effect is estimated to be $757 (2004 value) or 41% increase per person per year for the elderly enrolled in supplemental plans with drug coverage against the Medicare fee-for-service counterfactual and is $350 or 21% against the supplemental plans without drug coverage counterfactual. The incentive effect varies by different sources of drug coverage: highest for employer-sponsored insurance plans, followed by Medigap and managed medicare plans. Copyright © 2014 John Wiley & Sons, Ltd.

  8. ClinicalTrials.gov and Drugs@FDA: A comparison of results reporting for new drug approval trials

    PubMed Central

    Schwartz, Lisa M.; Woloshin, Steven; Zheng, Eugene; Tse, Tony; Zarin, Deborah A.

    2016-01-01

    Background Pharmaceutical companies and other trial sponsors must submit certain trial results to ClinicalTrials.gov. The validity of these results is unclear. Purpose To validate results posted on ClinicalTrials.gov against publicly-available FDA reviews on Drugs@FDA. Data sources ClinicalTrials.gov (registry and results database) and Drugs@FDA (medical/statistical reviews). Study selection 100 parallel-group, randomized trials for new drug approvals (1/2013 – 7/2014) with results posted on ClinicalTrials.gov (3/15/2015). Data extraction Two assessors systematically extracted, and another verified, trial design, primary/secondary outcomes, adverse events, and deaths. Results The 100 trials were mostly phase 3 (90%) double-blind (92%), placebo-controlled (73%), representing 32 drugs from 24 companies. Of 137 primary outcomes from ClinicalTrials.gov, 134 (98%) had corresponding data in Drugs@FDA, 130 (95%) had concordant definitions, and 107 (78%) had concordant results; most differences were nominal (i.e. relative difference < 10%). Of 100 trials, primary outcome results in 14 could not be validated . Of 1,927 secondary outcomes from ClinicalTrials.gov, 1,061 (55%) definitions could be validated and 367 (19%) had results. Of 96 trials with ≥ 1 serious adverse event in either source, 14 could be compared and 7 were discordant. Of 62 trials with ≥ 1 death in either source, 25 could be compared and 17 were discordant. Limitations Unknown generalizability to uncontrolled or crossover trial results. Conclusion Primary outcome definitions and results were largely concordant between ClinicalTrials.gov and Drugs@FDA. Half of secondary outcomes could not be validated because Drugs@FDA only includes “key outcomes” for regulatory decision-making; nor could serious adverse events and deaths because Drugs@FDA frequently only includes results aggregated across multiple trials. PMID:27294570

  9. A rare adverse effect of metronidazole: nervous system symptoms.

    PubMed

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

    2013-06-01

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

  10. Adverse Drug Event Discovery Using Biomedical Literature: A Big Data Neural Network Adventure

    PubMed Central

    Badger, Jonathan; LaRose, Eric; Shirzadi, Ehsan; Mahnke, Andrea; Mayer, John; Ye, Zhan; Page, David; Peissig, Peggy

    2017-01-01

    Background The study of adverse drug events (ADEs) is a tenured topic in medical literature. In recent years, increasing numbers of scientific articles and health-related social media posts have been generated and shared daily, albeit with very limited use for ADE study and with little known about the content with respect to ADEs. Objective The aim of this study was to develop a big data analytics strategy that mines the content of scientific articles and health-related Web-based social media to detect and identify ADEs. Methods We analyzed the following two data sources: (1) biomedical articles and (2) health-related social media blog posts. We developed an intelligent and scalable text mining solution on big data infrastructures composed of Apache Spark, natural language processing, and machine learning. This was combined with an Elasticsearch No-SQL distributed database to explore and visualize ADEs. Results The accuracy, precision, recall, and area under receiver operating characteristic of the system were 92.7%, 93.6%, 93.0%, and 0.905, respectively, and showed better results in comparison with traditional approaches in the literature. This work not only detected and classified ADE sentences from big data biomedical literature but also scientifically visualized ADE interactions. Conclusions To the best of our knowledge, this work is the first to investigate a big data machine learning strategy for ADE discovery on massive datasets downloaded from PubMed Central and social media. This contribution illustrates possible capacities in big data biomedical text analysis using advanced computational methods with real-time update from new data published on a daily basis. PMID:29222076

  11. Detection of adverse drug reactions among ordinary users of liraglutide on the occasion of drug dispensing in the community pharmacy setting.

    PubMed

    Christensen, Søren Troels; Bjerrum, Ole Jannik

    2013-12-01

    Postmarketing studies of drugs forms an essential part of safety surveillance. In particular, this concerns new drugs as safety information of these by large rests on randomized clinical studies conducted on a limited number of subjects before licensing. Pharmacists in community pharmacies are in a unique position for detection of user experienced adverse drug reactions (ADRs) in relation to drug dispensing. The study reports from a research initiative exploring prompt and proactive ADR detection of liraglutide and reporting facilitated by pharmacy students undertaking internship in a community pharmacy in Denmark. Nineteen pharmacy students undertaking regular 6 months' internship--eighth semester--in a Danish community pharmacy participated in the data collection. Before the data collection, students attended an interactive training seminar addressing ADRs in general, organ symptoms, diagnostic classification, and pharmacovigilance systems. Pharmacy students approached recurrent drug users purchasing liraglutide. Participating users were asked about experienced ADRs linked to liraglutide use. Reported ADRs were collected and analyzed. Sixty-two liraglutide users participated in the study, of whom, 38 reported 84 ADRs possibly linked to liraglutide usage. Nausea was by far the most reported ADR followed by decreased appetite, diarrhea, fatigue, and abdominal pain (upper). The reported ADRs are in accordance with previously reported ADRs. The study has demonstrated the feasibility of community pharmacy driven pharmacovigilance. The study supports the thesis that community pharmacists in the future may play a proactive and prominent role in patient-centered pharmacovigilance.

  12. Filtering Entities to Optimize Identification of Adverse Drug Reaction From Social Media: How Can the Number of Words Between Entities in the Messages Help?

    PubMed

    Abdellaoui, Redhouane; Schück, Stéphane; Texier, Nathalie; Burgun, Anita

    2017-06-22

    With the increasing popularity of Web 2.0 applications, social media has made it possible for individuals to post messages on adverse drug reactions. In such online conversations, patients discuss their symptoms, medical history, and diseases. These disorders may correspond to adverse drug reactions (ADRs) or any other medical condition. Therefore, methods must be developed to distinguish between false positives and true ADR declarations. The aim of this study was to investigate a method for filtering out disorder terms that did not correspond to adverse events by using the distance (as number of words) between the drug term and the disorder or symptom term in the post. We hypothesized that the shorter the distance between the disorder name and the drug, the higher the probability to be an ADR. We analyzed a corpus of 648 messages corresponding to a total of 1654 (drug and disorder) pairs from 5 French forums using Gaussian mixture models and an expectation-maximization (EM) algorithm . The distribution of the distances between the drug term and the disorder term enabled the filtering of 50.03% (733/1465) of the disorders that were not ADRs. Our filtering strategy achieved a precision of 95.8% and a recall of 50.0%. This study suggests that such distance between terms can be used for identifying false positives, thereby improving ADR detection in social media. ©Redhouane Abdellaoui, Stéphane Schück, Nathalie Texier, Anita Burgun. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 22.06.2017.

  13. Improving Pediatric Adverse Drug Event Reporting through Clinical Pharmacy Services

    PubMed Central

    Crowther, David M.; Buck, Marcia L.; McCarthy, Michelle W.; Barton, Virginia W.

    2011-01-01

    OBJECTIVES The purpose of this study was to summarize adverse drug event (ADE) reporting and to characterize the type of healthcare practitioners involved in reporting over a 10-year period at a 120-bed university-affiliated children's hospital. METHODS The University of Virginia Children's Hospital ADE database was analyzed for records involving pediatric patients. Data from patients <18 years of age who were admitted to the University of Virginia Children's Hospital between January 1, 2000, and December 31, 2009, were analyzed. Data collected included drug name and therapeutic class of the suspected causative agent, description of the event, severity, causality, outcome, and the type of healthcare practitioner reporting the event. RESULTS A total of 863 ADEs were reported over the 10-year period. The 5 most common types reported were extravasation injury (10%), rash (8%), hypotension (5%), pruritus (5%), and renal failure (3%). A total of 196 (21%) cases were categorized as mild, 436 (47%) cases as moderate, and 296 (32%) cases as severe. Further characterization of extravasations was performed to identify trends relating to potential causes. In 45 (57%) reports, parenteral nutrition was identified as the causative agent. Full recovery was documented in 21 (47%) extravasations. Of the total events reported, 83% were reported by pharmacists, 16% by nurses, and <1% by other healthcare practitioners. CONCLUSIONS Results of this study are consistent with those of previous studies involving ADE reporting in children's hospitals. This consistency is due in part to system design and use of unit-based pharmacists as the primary reporters. PMID:22768013

  14. Herb-drug, food-drug, nutrient-drug, and drug-drug interactions: mechanisms involved and their medical implications.

    PubMed

    Sørensen, Janina Maria

    2002-06-01

    Adverse drug reactions (ADRs) and iatrogenic diseases have been identified as significant factors responsible for patient morbidity and mortality. Significant studies on drug metabolism in humans have been published during the last few years, offering a deeper comprehension of the mechanisms underlying adverse drug reactions and interactions. More understanding of these mechanisms, and of recent advances in laboratory technology, can help to evaluate potential drug interactions when drugs are prescribed concurrently. Increasing knowledge of interindividual variation in drug breakdown capacity and recent findings concerning the influence of environment, diet, nutrients, and herbal products can be used to reduce ADRs and iatrogenic diseases. Reviewed data suggest that drug treatment should be increasingly custom tailored to suit the individual patient and that appropriately co-prescribed diet and herbal remedies, could increase drug efficacy and lessen drug toxicity. This review focuses mainly on recently published research material. The cytochrome p450 enzymes, their role in metabolism, and their mechanisms of action are reviewed, and their role in drug-drug interactions are discussed. Drug-food and drug-herb interactions have garnered attention. Interdisciplinary communication among medical herbalists, medical doctors, and dietetic experts needs to be improved and encouraged. Internet resources for obtaining current information regarding drug-drug, drug-herb, and drug-nutrient interactions are provided.

  15. Patterns of drug treatment entry by Latino male injection drug users from different national/geographical backgrounds.

    PubMed

    Reynoso-Vallejo, Humberto; Chassler, Deborah; Witas, Julie; Lundgren, Lena M

    2008-02-01

    This study examined patterns of treatment entry by Puerto Rican, Central American, Dominican, and other Latino male injection drug users (IDUs) in the state of Massachusetts over the time period 1996-2002. Specifically, it explored whether these populations had different patterns relative to three paths: entry into detoxification only, entry into residential treatment, or entry into methadone maintenance. Using a state-level MIS dataset on all substance abuse treatment entries to all licensed treatment programs, bi-variate and logistic regression methods were employed to examine patterns of drug treatment utilization among Latino men residing in Massachusetts. Three logistic regression models, which controlled for age, education, homelessness, employment, history of mental health treatment, health insurance, criminal justice involvement, having injected drugs in the past month, and number of treatment entries, indicated that Puerto Rican men were significantly less likely to only use detoxification services and residential treatment services, and significantly more likely to enter methadone maintenance compared to Latino men from Central American, Dominican, or other Latino backgrounds. For example, Central American men were 2.4 times more likely to enter only detoxification programs and 54% less likely to enter methadone maintenance programs than Puerto Rican male IDUs. For program planning, include the need to (a) develop varied drug treatment services to meet the needs of non-homogenous Latino groups within the population, (b) tailor outreach efforts to effectively reach all Latino groups, and (c) increase awareness among practitioners of differential patterns of treatment utilization.

  16. Can social media data lead to earlier detection of drug-related adverse events?

    PubMed

    Duh, Mei Sheng; Cremieux, Pierre; Audenrode, Marc Van; Vekeman, Francis; Karner, Paul; Zhang, Haimin; Greenberg, Paul

    2016-12-01

    To compare the patient characteristics and the inter-temporal reporting patterns of adverse events (AEs) for atorvastatin (Lipitor ® ) and sibutramine (Meridia ® ) in social media (AskaPatient.com) versus the FDA Adverse Event Reporting System (FAERS). We identified clinically important AEs associated with atorvastatin (muscle pain) and sibutramine (cardiovascular AEs), compared their patterns in social media postings versus FAERS and used Granger causality tests to assess whether social media postings were useful in forecasting FAERS reports. We analyzed 998 and 270 social media postings between 2001 and 2014, 69 003 and 7383 FAERS reports between 1997 and 2014 for atorvastatin and sibutramine, respectively. Social media reporters were younger (atorvastatin: 53.9 vs. 64.0 years, p < 0.001; sibutramine: 36.8 vs. 43.8 years, p < 0.001). Social media reviews contained fewer serious AEs (atorvastatin, pain: 2.5% vs. 38.2%; sibutramine, cardiovascular issues: 7.9% vs. 63.0%; p < 0.001 for both) and concentrated on fewer types of AEs (proportion comprising the top 20 AEs: atorvastatin, 88.7% vs. 55.4%; sibutramine, 86.3% vs. 65.4%) compared with FAERS. While social media sibutramine reviews mentioning cardiac issues helped predict those in FAERS 11 months later (p < 0.001), social media atorvastatin reviews did not help predict FAERS reports. Social media AE reporters were younger and focused on less-serious and fewer types of AEs than FAERS reporters. The potential for social media to provide earlier indications of AEs compared with FAERS is uncertain. Our findings highlight some of the promises and limitations of online social media versus conventional pharmacovigilance sources and the need for careful interpretation of the results. © 2016 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd. © 2016 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.

  17. The expert explorer: a tool for hospital data visualization and adverse drug event rules validation.

    PubMed

    Băceanu, Adrian; Atasiei, Ionuţ; Chazard, Emmanuel; Leroy, Nicolas

    2009-01-01

    An important part of adverse drug events (ADEs) detection is the validation of the clinical cases and the assessment of the decision rules to detect ADEs. For that purpose, a software called "Expert Explorer" has been designed by Ideea Advertising. Anonymized datasets have been extracted from hospitals into a common repository. The tool has 3 main features. (1) It can display hospital stays in a visual and comprehensive way (diagnoses, drugs, lab results, etc.) using tables and pretty charts. (2) It allows designing and executing dashboards in order to generate knowledge about ADEs. (3) It finally allows uploading decision rules obtained from data mining. Experts can then review the rules, the hospital stays that match the rules, and finally give their advice thanks to specialized forms. Then the rules can be validated, invalidated, or improved (knowledge elicitation phase).

  18. Targeted therapies and adverse drug reactions in oncology: the role of clinical pharmacist in pharmacovigilance.

    PubMed

    Fornasier, G; Taborelli, M; Francescon, S; Polesel, J; Aliberti, M; De Paoli, P; Baldo, P

    2018-05-21

    Background The majority of adverse drug reactions (ADRs) reported in the summary of product characteristics (SPCs) are based on pivotal clinical trials, performed under controlled conditions and with selected patients. Objectives (1) to observe ADRs in the real-world setting and to evaluate if the supervision of the pharmacist impacts on the management of ADRs and on the satisfaction of patients; (2) to sensitise health professionals and patients on the need to increase the reporting of ADRs, in compliance with Pharmacovigilance. Setting CRO Aviano, Italian National Cancer Institute. Method From February 2013 to April 2015, we conducted an observational study enrolling 154 patients (≥ 18 years) undergoing treatment with at least one of ten targeted-therapies included in the study. Main outcome ADR reporting in the real-world setting. Patient satisfaction with clinical pharmacist support. Results Reported ADRs in the real setting do not always correspond with data described in the respective SPCs. Unknown ADRs were also identified such as hyperglycaemia with lenalidomide and sorafenib; and hypomagnesaemia with bevacizumab. We also observed a 124.3% increase in spontaneous reports. Conclusion This study shows the high value of active pharmacovigilance programs, and our results might be a starting point for developing a randomised trial which should aim to demonstrate the impact of the pharmacist on improving patient's adherence and in measuring the difference in ADRs reports in the different arms followed or not by the pharmacist.

  19. [PHARMACOLOGICAL TREATMENT IN PALLIATIVE CARE. DRUG ADMINISTRATION ROUTE, CONTINUOUS SUBCUTANEOUS INFUSION, ADVERSE SIDE EFFECTS, SYMPTOM MANAGEMENT].

    PubMed

    Dominguez Álvarez, Rocío; Calderón Carrasco, Justo; García Colchero, Francisco; Postigo Mota, Salvador; Alburquerque Medina, Eulalia

    2015-01-01

    To achieve well-being in patients in Palliative Care is required to know which are the most common symptoms, which are the drugs used for relief, which are the routes of administration of drugs that are suitable, how effective the drugs are and what incompatibilities, interactions and adverse effects occur. The aim of this article is to review the relevant issues in the management of the drugs commonly used by nursing in Palliative Care and presenting recommendations to clinical practice. Management interventions drugs for nurses in Palliative Care recommended by the scientific literature after a search of Scopus, CINAHL, Medline, PubMed, UpToDate and Google Scholar are selected. The oral route is the choice for patients in palliative situation and subcutaneous route when the first is not available. The symptoms, complex, intense and moody, should be systematically reevaluated by the nurse, to predict when a possible decompensation of it needing extra dose of medication. Nurses must be able to recognize the imbalance of well-being and act quickly and effectively, to get relief to some unpleasant situations for the patient as the pain symptoms, dyspnea or delirium. For the proper administration of rescue medication, the nurse should know the methods of symptomatic evaluation, pharmacokinetics and pharmacodynamics of drugs, the time intervals to elapse between different rescues and nccocc rocnnnco t thocm

  20. Acute drug prescribing to children on chronic antiepilepsy therapy and the potential for adverse drug interactions in primary care

    PubMed Central

    Novak, Philipp H; Ekins-Daukes, Suzie; Simpson, Colin R; Milne, Robert M; Helms, Peter; McLay, James S

    2005-01-01

    Aims To investigate the extent of acute coprescribing in primary care to children on chronic antiepileptic therapy, which could give rise to potentially harmful drug–drug interactions. Design Acute coprescribing to children on chronic antiepileptic drug therapy in primary care was assessed in 178 324 children aged 0–17 years for the year 1 November 1999 to 31 October 2000. Computerized prescribing data were retrieved from 161 representative general practices in Scotland. Setting One hundred and sixty-one general practices throughout Scotland. Results During the study year 723 (0.41%) children chronically prescribed antiepileptic therapy were identified. Fourteen antiepileptic agents were prescribed, with carbamazepine, sodium valproate and lamotrigine accounting for 80% of the total. During the year children on chronic antiepileptic therapy were prescribed 4895 acute coprescriptions for 269 different medicines. The average number of acute coprescriptions for non-epileptic drug therapy were eight, 11, six, and six for the 0–1, 2–4, 5–11, and 12–17-year-olds, respectively. Of these acute coprescriptions 72 (1.5%) prescribed to 22 (3.0%) children were identified as a potential source of clinically serious interactions. The age-adjusted prevalence rates for potentially serious coprescribing were 86, 26, 22, and 33/1000 children chronically prescribed antiepileptic therapy in the 0–1, 2–4, 5–11, and 12–17-year-old age groups, respectively. The drugs most commonly coprescribed which could give rise to such interactions were antacids, erythromycin, ciprofloxacin, theophylline and the low-dose oral contraceptive. For 10 (45.5%0 of the 20 children identified at risk of a potentially clinically serious adverse drug interaction, the acute coprescription was prescribed off label because of age or specific contraindication/warning. Conclusions In primary care, 3.0% of children on chronic antiepileptic therapy are coprescribed therapeutic agents, which could

  1. [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.

  2. Retrospective analysis of drug photosensitivity in Norway

    NASA Astrophysics Data System (ADS)

    Selvaag, Edgar

    1999-02-01

    Reports on adverse drug reactions, as they were recorded at the Norwegian Medicines Control Authority beginning in the year 1970 up to 1994 were analyzed especially with regard to cutaneous reactions and photosensitivity reactions. During the time period, almost 13.000 side effects were reported. Out of these 799 reports involved the skin and appendages, and 64 out of these reports (8%) were classified as photosensitivity reactions. Tetracyclines, diuretics, antihypertensive agents, and urologicals were the drugs which most often caused photosensitivity reactions. In addition, a number of uncommon photosensitizing drugs were reported. The risk for photosensitization is discussed on the background of experimental data and the prescription rates of these substances.

  3. OAE: The Ontology of Adverse Events.

    PubMed

    He, Yongqun; Sarntivijai, Sirarat; Lin, Yu; Xiang, Zuoshuang; Guo, Abra; Zhang, Shelley; Jagannathan, Desikan; Toldo, Luca; Tao, Cui; Smith, Barry

    2014-01-01

    A medical intervention is a medical procedure or application intended to relieve or prevent illness or injury. Examples of medical interventions include vaccination and drug administration. After a medical intervention, adverse events (AEs) may occur which lie outside the intended consequences of the intervention. The representation and analysis of AEs are critical to the improvement of public health. The Ontology of Adverse Events (OAE), previously named Adverse Event Ontology (AEO), is a community-driven ontology developed to standardize and integrate data relating to AEs arising subsequent to medical interventions, as well as to support computer-assisted reasoning. OAE has over 3,000 terms with unique identifiers, including terms imported from existing ontologies and more than 1,800 OAE-specific terms. In OAE, the term 'adverse event' denotes a pathological bodily process in a patient that occurs after a medical intervention. Causal adverse events are defined by OAE as those events that are causal consequences of a medical intervention. OAE represents various adverse events based on patient anatomic regions and clinical outcomes, including symptoms, signs, and abnormal processes. OAE has been used in the analysis of several different sorts of vaccine and drug adverse event data. For example, using the data extracted from the Vaccine Adverse Event Reporting System (VAERS), OAE was used to analyse vaccine adverse events associated with the administrations of different types of influenza vaccines. OAE has also been used to represent and classify the vaccine adverse events cited in package inserts of FDA-licensed human vaccines in the USA. OAE is a biomedical ontology that logically defines and classifies various adverse events occurring after medical interventions. OAE has successfully been applied in several adverse event studies. The OAE ontological framework provides a platform for systematic representation and analysis of adverse events and of the factors (e

  4. Thromboembolic adverse event study of combined estrogen-progestin preparations using Japanese Adverse Drug Event Report database

    PubMed Central

    Hasegawa, Shiori; Matsui, Toshinobu; Hane, Yuuki; Abe, Junko; Hatahira, Haruna; Motooka, Yumi; Sasaoka, Sayaka; Fukuda, Akiho; Naganuma, Misa; Hirade, Kouseki; Takahashi, Yukiko; Kinosada, Yasutomi

    2017-01-01

    Combined estrogen-progestin preparations (CEPs) are associated with thromboembolic (TE) side effects. The aim of this study was to evaluate the incidence of TE using the Japanese Adverse Drug Event Report (JADER) database. Adverse events recorded from April 2004 to November 2014 in the JADER database were obtained from the Pharmaceuticals and Medical Devices Agency (PMDA) website (www.pmda.go.jp). We calculated the reporting odds ratios (RORs) of suspected CEPs, analyzed the time-to-onset profile, and assessed the hazard type using Weibull shape parameter (WSP). Furthermore, we used the applied association rule mining technique to discover undetected relationships such as the possible risk factors. The total number of reported cases in the JADER contained was 338,224. The RORs (95% confidential interval, CI) of drospirenone combined with ethinyl estradiol (EE, Dro-EE), norethisterone with EE (Ne-EE), levonorgestrel with EE (Lev-EE), desogestrel with EE (Des-EE), and norgestrel with EE (Nor-EE) were 56.2 (44.3–71.4), 29.1 (23.5–35.9), 42.9 (32.3–57.0), 44.7 (32.7–61.1), and 38.6 (26.3–56.7), respectively. The medians (25%–75%) of the time-to-onset of Dro-EE, Ne-EE, Lev-EE, Des-EE, and Nor-EE were 150.0 (75.3–314.0), 128.0 (27.0–279.0), 204.0 (44.0–660.0), 142.0 (41.3–344.0), and 16.5 (8.8–32.0) days, respectively. The 95% CIs of the WSP-β for Ne-EE, Lev-EE, and Nor-EE were lower and excluded 1. Association rule mining indicated that patients with anemia had a potential risk of developing a TE when using CEPs. Our results suggest that it is important to monitor patients administered CEP for TE. Careful observation is recommended, especially for those using Nor-EE, and this information may be useful for efficient therapeutic planning. PMID:28732067

  5. Differences by Veteran/civilian status and gender in associations between childhood adversity and alcohol and drug use disorders.

    PubMed

    Evans, Elizabeth A; Upchurch, Dawn M; Simpson, Tracy; Hamilton, Alison B; Hoggatt, Katherine J

    2018-04-01

    To examine differences by US military Veteran status and gender in associations between childhood adversity and DSM-5 lifetime alcohol and drug use disorders (AUD/DUD). We analyzed nationally representative data from 3119 Veterans (n = 379 women; n = 2740 men) and 33,182 civilians (n = 20,066 women; n = 13,116 men) as provided by the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III). We used weighted multinomial logistic regression, tested interaction terms, and calculated predicted probabilities by Veteran status and gender, controlling for covariates. To test which specific moderation contrasts were statistically significant, we conducted pairwise comparisons. Among civilians, women had lower AUD and DUD prevalence than men; however, with more childhood adversity, this gender gap narrowed for AUD and widened for DUD. Among Veterans, in contrast, similar proportions of women and men had AUD and DUD; with more childhood adversity, AUD-predicted probability among men surpassed that of women. Childhood adversity elevated AUD probability among civilian women to levels exhibited by Veteran women. Among men, Veterans with more childhood adversity were more likely than civilians to have AUD, and less likely to have DUD. Childhood adversity alters the gender gap in AUD and DUD risk, and in ways that are different for Veterans compared with civilians. Department of Defense, Veterans Affairs, and community health centers can prevent and ameliorate the harmful effects of childhood adversity by adapting existing behavioral health efforts to be trauma informed, Veteran sensitive, and gender tailored.

  6. Oral antibiotic adverse reactions after penicillin skin testing: multi-year follow-up.

    PubMed

    Macy, E; Burchette, R J

    2002-12-01

    Long-term follow-up data on adverse drug reactions after oral antibiotic use in penicillin allergy history positive individuals with penicillin skin test done in advance of need are rare. Oral antibiotic associated adverse drug reactions in 83 penicillin skin test positive individuals were compared to a sex, age, and length of follow-up matched sample of 166 penicillin skin test negative individuals, all of whom had at least one post penicillin skin test oral antibiotic. The mean post penicillin skin test follow-up interval was 34.5 +/- 16.6 months. There were 1655 total oral antibiotic exposures. In penicillin skin test positive individuals, the adverse drug reaction rate was not significantly different with cephalosporin or non-beta-lactam use (P = 0.12). In penicillin skin test negative individuals the adverse drug reaction rate was significantly lower with cephalosporin vs. non-beta-lactam use (P = 0.005). Penicillin was safely used in penicillin skin test negative individuals. Overall cephalosporins caused fewer adverse drug reactions independent of penicillin skin test status (P = 0.005). Penicillin skin testing was only able to predict penicillin associated adverse drug reactions in penicillin skin test positive individuals. Excluding accidental penicillin exposure in penicillin skin test positive individuals, non-beta-lactams were associated with adverse drug reactions more often than penicillins or cephalosporins, independent of the penicillin skin test result. Cephalosporins were used as or more safely than non-beta-lactams in both penicillin skin test positive and negative individuals.

  7. Detecting, Monitoring, and Reporting Possible Adverse Drug Events Using an Arden-Syntax-based Rule Engine.

    PubMed

    Fehre, Karsten; Plössnig, Manuela; Schuler, Jochen; Hofer-Dückelmann, Christina; Rappelsberger, Andrea; Adlassnig, Klaus-Peter

    2015-01-01

    The detection of adverse drug events (ADEs) is an important aspect of improving patient safety. The iMedication system employs predefined triggers associated with significant events in a patient's clinical data to automatically detect possible ADEs. We defined four clinically relevant conditions: hyperkalemia, hyponatremia, renal failure, and over-anticoagulation. These are some of the most relevant ADEs in internal medical and geriatric wards. For each patient, ADE risk scores for all four situations are calculated, compared against a threshold, and judged to be monitored, or reported. A ward-based cockpit view summarizes the results.

  8. Campania preventability assessment committee: a focus on the preventability of the contrast media adverse drug reactions.

    PubMed

    Sessa, Maurizio; Rossi, Claudia; Rafaniello, Concetta; Mascolo, Annamaria; Cimmaruta, Daniela; Scavone, Cristina; Fiorentino, Sonia; Grassi, Enrico; Reginelli, Alfonso; Rotondo, Antonio; Sportiello, Liberata

    2016-12-01

    The current study aims to assess the preventability of the contrast media adverse drug reactions reported through the Campania spontaneous reporting system, identifying the possible limitations emerged in this type of evaluation. All the individual case safety reports validated by the Campania Pharmacovigilance Regional Centre from July 2012 to September 2015 were screened to select those that reported contrast media as suspected drug. Campania Preventability Assessment Committee, in collaboration with clinicians specialized in Radiology, assessed the preventability according to the P-Method, through a case-by-case approach. From July 2012 to September 2015, 13798 cases were inserted by pharmacovigilance managers in the Italian Pharmacovigilance Network database (in the geographical contest of the Campania Region), of which 67 reported contrast media as suspected drug. Five preventable cases were found. The most reported causes for preventability were the inappropriate drug use for the case clinical conditions and the absence of the preventive measure administrated prior to the contrast media administration. Several limitations were found in the evaluation of the critical criteria for the preventability assessment. Educational initiatives will be organized directly to the healthcare professionals involved in the contrast media administration, to promote an appropriate use of the contrast media.

  9. Modelling the adverse effects associated with ecstasy use.

    PubMed

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

    2011-04-01

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

  10. Adverse effects of oral amiodarone therapy.

    PubMed

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

    1992-04-01

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

  11. Adverse Effects of GLP-1 Receptor Agonists

    PubMed Central

    Filippatos, Theodosios D.; Panagiotopoulou, Thalia V.; Elisaf, Moses S.

    2014-01-01

    Glucagon-like peptide-1 (GLP-1) receptor agonists are a class of injective anti-diabetic drugs that improve glycemic control and many other atherosclerosis-related parameters in patients with type 2 diabetes (T2D). However, the use of this relatively new class of drugs may be associated with certain adverse effects. Concerns have been expressed regarding the effects of these drugs on pancreatic and thyroid tissue, since animal studies and analyses of drug databases indicate an association of GLP-1 receptor agonists with pancreatitis, pancreatic cancer, and thyroid cancer. However, several meta-analyses failed to confirm a cause-effect relation between GLP-1 receptor agonists and the development of these adverse effects. One benefit of GLP-1 receptor agonists is that they do not cause hypoglycemia when combined with metformin or thiazolidinediones, but the dose of concomitant sulphonylurea or insulin may have to be decreased to reduce the risk of hypoglycemic episodes. On the other hand, several case reports have linked the use of these drugs, mainly exenatide, with the occurrence of acute kidney injury, primarily through hemodynamic derangement due to nausea, vomiting, and diarrhea. The most common symptoms associated with the use of GLP-1 receptor agonists are gastrointestinal symptoms, mainly nausea. Other common adverse effects include injection site reactions, headache, and nasopharyngitis, but these effects do not usually result in discontinuation of the drug. Current evidence shows that GLP-1 receptor agonists have no negative effects on the cardiovascular risk of patients with T2D. Thus, GLP-1 receptor agonists appear to have a favorable safety profile, but ongoing trials will further assess their cardiovascular effects. The aim of this review is to analyze critically the available data regarding adverse events of GLP-1 receptor agonists in different anatomic systems published in Pubmed and Scopus. Whenever possible, certain differences between GLP-1

  12. Clinical Risk Factors for In-Hospital Adverse Cardiovascular Events After Acute Drug Overdose

    PubMed Central

    Manini, Alex F.; Hoffman, Robert S.; Stimmel, Barry; Vlahov, David

    2015-01-01

    Objectives It was recently demonstrated that adverse cardiovascular events (ACVE) complicate a high proportion of hospitalizations for patients with acute drug overdoses. The aim of this study was to derive independent clinical risk factors for ACVE in patients with acute drug overdoses. Methods This prospective cohort study was conducted over 3 years at two urban university hospitals. Patients were adults with acute drug overdoses enrolled from the ED. In-hospital ACVE was defined as any of myocardial injury, shock, ventricular dysrhythmia, or cardiac arrest. Results There were 1,562 patients meeting inclusion/exclusion criteria (mean age, 41.8 years; female, 46%; suicidal, 38%). ACVE occurred in 82 (5.7%) patients (myocardial injury, 61; shock, 37; dysrhythmia, 23; cardiac arrests, 22) and there were 18 (1.2%) deaths. On univariate analysis, ACVE risk increased with age, lower serum bicarbonate, prolonged QTc interval, prior cardiac disease, and altered mental status. In a multivariable model adjusting for these factors as well as patient sex and hospital site, independent predictors were: QTc > 500 msec (3.8% prevalence, odds ratio [OR] 27.6), bicarbonate < 20 mEql/L (5.4% prevalence, OR 4.4), and prior cardiac disease (7.1% prevalence, OR 9.5). The derived prediction rule had 51.6% sensitivity, 93.7% specificity, and 97.1% negative predictive value; while presence of two or more risk factors had 90.9% positive predictive value. Conclusions The authors derived independent clinical risk factors for ACVE in patients with acute drug overdose, which should be validated in future studies as a prediction rule in distinct patient populations and clinical settings. PMID:25903997

  13. Caffeic Acid Phenethyl Ester: A Review of Its Antioxidant Activity, Protective Effects against Ischemia-reperfusion Injury and Drug Adverse Reactions.

    PubMed

    Tolba, Mai F; Omar, Hany A; Azab, Samar S; Khalifa, Amani E; Abdel-Naim, Ashraf B; Abdel-Rahman, Sherif Z

    2016-10-02

    Propolis, a honey bee product, has been used in folk medicine for centuries for the treatment of abscesses, canker sores and for wound healing. Caffeic acid phenethyl ester (CAPE) is one of the most extensively investigated active components of propolis which possess many biological activities, including antibacterial, antiviral, antioxidant, anti-inflammatory, and anti-cancer effects. CAPE is a polyphenolic compound characterized by potent antioxidant and cytoprotective activities and protective effects against ischemia-reperfusion (I/R)-induced injury in multiple tissues such as brain, retina, heart, skeletal muscles, testis, ovaries, intestine, colon, and liver. Furthermore, several studies indicated the protective effects of CAPE against chemotherapy-induced adverse drug reactions (ADRs) including several antibiotics (streptomycin, vancomycin, isoniazid, ethambutol) and chemotherapeutic agents (mitomycin, doxorubicin, cisplatin, methotrexate). Due to the broad spectrum of pharmacological activities of CAPE, this review makes a special focus on the recently published data about CAPE antioxidant activity as well as its protective effects against I/R-induced injury and many adverse drug reactions.

  14. Study of adverse drug reactions in patients with diabetes attending a tertiary care hospital in New Delhi, India.

    PubMed

    Singh, Abhishank; Dwivedi, Shridhar

    2017-02-01

    The present prospective observational study was carried out in a tertiary care hospital in New Delhi, India from May 2014 to June 2015 to report adverse drug reactions (ADRs) in patients with type 2 diabetes mellitus (T2DM) using antidiabetic drugs. A total of 220 patients (121 males, 99 females) were enrolled. ADRs were recorded on the prescribed form. Causality and severity assessment was done using Naranjo's probability scale and modified Hartwig and Siegel's severity scale, respectively. Commonly prescribed drugs were biguanides, peptide hormone and sulphonylurea. A total of 26 ADRs were recorded (16 in males and 10 in females). Most commonly observed ADRs were related to endocrine and gastrointestinal system. Severity assessment of ADRs showed seven (26.9%) ADRs as moderate, and 19 (73.1%) as mild. No severe reactions were observed. ADRs were mostly related to endocrine and gastrointestinal system. More information on prescribed drugs and their side effects is required for ensuring patient safety.

  15. [Adverse drug reactions of hydroxymethylglutaryl-CoA reductase inhibitors reported to agency for medicinal products and medical devices].

    PubMed

    Skvrce, Nikica Mirosević; Bozina, Nada; Sarinić, Viola Macolić; Tomić, Sinisa

    2010-01-01

    Hydroxymethylglutaryl-CoA reductase inhibitors (statins) are drugs used in the treatment of chronic diseases and frequently in concomitant therapy with many other drugs. Therefore, the risk of adverse drug reactions (ADRs), especially those caused by interactions is high. Aim of the study was to describe and analyze ADRs caused by statins reported to Croatian Agency from March 2005 to December 2008, and to emphasize reasons of their occurrence. 136 of statin ADRs were reported. 12 % of all reported statins' ADRs were caused by interactions, which is higher than percent (5.6%) of interactions caused by all other drugs in 2005 and 2006. Proportion of serious ADRs related to administered dose and thus preventable was higher than proportion of all ADRs caused by statins (p = 0.003). Most serious ADRs could have been prevented with better understanding of interactions and by use of pharmacogenomics in identifying patients that are because of genetic predisposition more sensitive to standard doses.

  16. What's the hospitalisation's impact on background treatments of patients over 65 years.

    PubMed

    Gasperini, Guillaume; Molinier, Sylvain; Marimoutou, Catherine; Denormandie, Philippe; Sanchez, Stéphane

    2016-12-01

    As our population aging increases, it requires a particular attention from the health system. Indeed, elderly are often frail, with several diseases and presenting high risk of adverse drug accident. Prescribing appropriately to the elderly has become an important matter. Hospitalization and consultation with the general practitioner are key moments for drug prescription. However, their real impact on background treatments of this population has been barely evaluated. A retrospective descriptive study was conducted with 300 patients over 65 years old, hospitalized at the Laveran military hospital in Marseille. Treatment modifications, consecutive to hospitalization and to the first consultation with the general practitioner, were identified and analyzed. We found an average prescription of 5.93 drugs in prehospital period and 66% of the patients with polypharmacy. Drugs for cardiovascular system were the most prescribed and the most modified. Hospitalization generated a rate of modification by prescription of 28.5% and the consultation with the general practitioner following this hospitalization led to further change in 48% of cases. Beside the important prevalence of patients with polypharmacy, this study shows that hospitalization entails a significant change in background treatments in that population at risk. Therefore, it is important to have a consensus in the re-evaluation of these treatments, in order to prevent the iatrogenic risk.

  17. Adverse childhood experiences and consumption of alcohol, tobacco and illicit drugs among adolescents of a Brazilian birth cohort.

    PubMed

    Gonçalves, Helen; Soares, Ana Luiza Gonçalves; Santos, Ana Paula Gomes Dos; Ribeiro, Camila Garcez; Bierhals, Isabel Oliveira; Vieira, Luna Strieder; Hellwig, Natália Limões; Wehrmeister, Fernando C; Menezes, Ana M B

    2016-11-03

    The objective of this study was to investigate the association between adverse childhood experiences (ACEs) and the use of alcohol, tobacco and illicit drugs among adolescents from a Brazilian cohort. The occurrence of five ACEs, the use of alcohol and tobacco and trying illicit drugs were investigated in the 1993 Pelotas birth cohort at the age of 15 (n = 4,230). A score was created for the ACEs and their association with the use of substances was evaluated. Around 25% of adolescents consumed alcohol, 6% smoked and 2.1% reported having used drugs at least once in their lives. The ACEs were associated with the use of alcohol, tobacco and illicit drugs. A dose-response relation between the number of ACEs and the substance use was found, particularly with regard to illicit drugs. The occurrence of ACEs was positively associated with the use of alcohol, tobacco and illicit drugs among adolescents and the risk may be different for men and women. These results point to the fact that strategies for preventing the use of substances should include interventions both among adolescents and within the family environment.

  18. Acute Kidney Injury and Bisphosphonate Use in Cancer: A Report From the Research on Adverse Drug Events and Reports (RADAR) Project

    PubMed Central

    Edwards, Beatrice J.; Usmani, Sarah; Raisch, Dennis W.; McKoy, June M.; Samaras, Athena T.; Belknap, Steven M.; Trifilio, Steven M.; Hahr, Allison; Bunta, Andrew D.; Abu-Alfa, Ali; Langman, Craig B.; Rosen, Steve T.; West, Dennis P.

    2013-01-01

    Purpose: To determine whether acute kidney injury (AKI) is identified within the US Food and Drug Administration's Adverse Events and Reporting System (FDA AERS) as an adverse event resulting from bisphosphonate (BP) use in cancer therapy. Methods: A search of the FDA AERS records from January 1998 through June 2009 was performed; search terms were “renal problems” and all drug names for BPs. The search resulted in 2,091 reports. We analyzed for signals of disproportional association by calculating the proportional reporting ratio for zoledronic acid (ZOL) and pamidronate. Literature review of BP-associated renal injury within the cancer setting was conducted. Results: Four hundred eighty cases of BP-associated acute kidney injury (AKI) were identified in patients with cancer. Two hundred ninety-eight patients (56%) were female; mean age was 66 ± 10 years. Multiple myeloma (n = 220, 46%), breast cancer (n = 98, 20%), and prostate cancer (n = 24, 5%) were identified. Agents included ZOL (n = 411, 87.5%), pamidronate (n = 8, 17%), and alendronate (n = 36, 2%). Outcomes included hospitalization (n = 304, 63.3%) and death (n = 68, 14%). The proportional reporting ratio for ZOL was 1.22 (95% CI, 1.13 to 1.32) and for pamidronate was 1.55 (95% CI, 1.25 to 1.65), reflecting a nonsignificant safety signal for both drugs. Conclusion: AKI was identified in BP cancer clinical trials, although a safety signal for BPs and AKI within the FDA AERS was not detected. Our findings may be attributed, in part, to clinicians who believe that AKI occurs infrequently; ascribe the AKI to underlying premorbid disease, therapy, or cancer progression; or consider that AKI is a known adverse drug reaction of BPs and thus under-report AKI to the AERS. PMID:23814519

  19. Adverse Events Involving Radiation Oncology Medical Devices: Comprehensive Analysis of US Food and Drug Administration Data, 1991 to 2015

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

    Connor, Michael J.; Department of Radiation Oncology, University of California Irvine School of Medicine, Irvine, California; Marshall, Deborah C.

    Purpose: Radiation oncology relies on rapidly evolving technology and highly complex processes. The US Food and Drug Administration collects reports of adverse events related to medical devices. We sought to characterize all events involving radiation oncology devices (RODs) from the US Food and Drug Administration's postmarket surveillance Manufacturer and User Facility Device Experience (MAUDE) database, comparing these with non–radiation oncology devices. Methods and Materials: MAUDE data on RODs from 1991 to 2015 were sorted into 4 product categories (external beam, brachytherapy, planning systems, and simulation systems) and 5 device problem categories (software, mechanical, electrical, user error, and dose delivery impact).more » Outcomes included whether the device was evaluated by the manufacturer, adverse event type, remedial action, problem code, device age, and time since 510(k) approval. Descriptive statistics were performed with linear regression of time-series data. Results for RODs were compared with those for other devices by the Pearson χ{sup 2} test for categorical data and 2-sample Kolmogorov-Smirnov test for distributions. Results: There were 4234 ROD and 4,985,698 other device adverse event reports. Adverse event reports increased over time, and events involving RODs peaked in 2011. Most ROD reports involved external beam therapy (50.8%), followed by brachytherapy (24.9%) and treatment planning systems (21.6%). The top problem types were software (30.4%), mechanical (20.9%), and user error (20.4%). RODs differed significantly from other devices in each outcome (P<.001). RODs were more likely to be evaluated by the manufacturer after an event (46.9% vs 33.0%) but less likely to be recalled (10.5% vs 37.9%) (P<.001). Device age and time since 510(k) approval were shorter among RODs (P<.001). Conclusions: Compared with other devices, RODs may experience adverse events sooner after manufacture and market approval. Close postmarket surveillance

  20. Statin-associated muscular and renal adverse events: data mining of the public version of the FDA adverse event reporting system.

    PubMed

    Sakaeda, Toshiyuki; Kadoyama, Kaori; Okuno, Yasushi

    2011-01-01

    Adverse event reports (AERs) submitted to the US Food and Drug Administration (FDA) were reviewed to assess the muscular and renal adverse events induced by the administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) and to attempt to determine the rank-order of the association. After a revision of arbitrary drug names and the deletion of duplicated submissions, AERs involving pravastatin, simvastatin, atorvastatin, or rosuvastatin were analyzed. Authorized pharmacovigilance tools were used for quantitative detection of signals, i.e., drug-associated adverse events, including the proportional reporting ratio, the reporting odds ratio, the information component given by a Bayesian confidence propagation neural network, and the empirical Bayes geometric mean. Myalgia, rhabdomyolysis and an increase in creatine phosphokinase level were focused on as the muscular adverse events, and acute renal failure, non-acute renal failure, and an increase in blood creatinine level as the renal adverse events. Based on 1,644,220 AERs from 2004 to 2009, signals were detected for 4 statins with respect to myalgia, rhabdomyolysis, and an increase in creatine phosphokinase level, but these signals were stronger for rosuvastatin than pravastatin and atorvastatin. Signals were also detected for acute renal failure, though in the case of atorvastatin, the association was marginal, and furthermore, a signal was not detected for non-acute renal failure or for an increase in blood creatinine level. Data mining of the FDA's adverse event reporting system, AERS, is useful for examining statin-associated muscular and renal adverse events. The data strongly suggest the necessity of well-organized clinical studies with respect to statin-associated adverse events.

  1. Exploring Spanish health social media for detecting drug effects

    PubMed Central

    2015-01-01

    Background Adverse Drug reactions (ADR) cause a high number of deaths among hospitalized patients in developed countries. Major drug agencies have devoted a great interest in the early detection of ADRs due to their high incidence and increasing health care costs. Reporting systems are available in order for both healthcare professionals and patients to alert about possible ADRs. However, several studies have shown that these adverse events are underestimated. Our hypothesis is that health social networks could be a significant information source for the early detection of ADRs as well as of new drug indications. Methods In this work we present a system for detecting drug effects (which include both adverse drug reactions as well as drug indications) from user posts extracted from a Spanish health forum. Texts were processed using MeaningCloud, a multilingual text analysis engine, to identify drugs and effects. In addition, we developed the first Spanish database storing drugs as well as their effects automatically built from drug package inserts gathered from online websites. We then applied a distant-supervision method using the database on a collection of 84,000 messages in order to extract the relations between drugs and their effects. To classify the relation instances, we used a kernel method based only on shallow linguistic information of the sentences. Results Regarding Relation Extraction of drugs and their effects, the distant supervision approach achieved a recall of 0.59 and a precision of 0.48. Conclusions The task of extracting relations between drugs and their effects from social media is a complex challenge due to the characteristics of social media texts. These texts, typically posts or tweets, usually contain many grammatical errors and spelling mistakes. Moreover, patients use lay terminology to refer to diseases, symptoms and indications that is not usually included in lexical resources in languages other than English. PMID:26100267

  2. Risk factors for adverse drug reactions in pediatric inpatients: A cohort study.

    PubMed

    Andrade, Paulo Henrique Santos; Lobo, Iza Maria Fraga; da Silva, Wellington Barros

    2017-01-01

    The present study aims to identify the risk factors for adverse drug reactions (ADR) in pediatric inpatients. A prospective cohort study in one general pediatric ward in a hospital in Northeast Brazil was conducted in two stages: the first stage was conducted between August 17th and November 6th, 2015, and the second one between March 1st and August 25th, 2016. We included children aged 0-14 years 11 months hospitalized with a minimum stay of 48 hours. Observed outcomes were the ADR occurrence and the time until the first ADR observed. In the univariate analysis, the time to the first ADR was compared among groups using a log-rank test. For the multivariate analysis, the Cox regression model was used. A total of 173 children (208 admissions) and 66 ADR classified as "definite" and "probable" were identified. The incidence rate was 3/100 patient days. The gastro-intestinal system disorders were the main ADR observed (28.8%). In addition, 22.7% of the ADR were related to antibacterials for systemic use and 15.2% to general anesthesia. Prior history of ADR of the child [hazard ratio (HR) 2.44; 95% confidence interval (CI) 1.19-5.00], the use of meglumine antimonate (HR 4.98; 95% CI 1.21-20.54), antibacterial for systemic use (HR 2.75; 95% CI 1.08-6.98) and antiepileptic drugs (HR 3.84; 95% CI 1.40-10.56) were identified risk factors for ADR. We identified as risk factors the prior history of ADR of the child and the use of meglumine antimonate, antibacterial for systemic use and antiepileptic drugs.

  3. Severe adverse drug reaction following Crotalidae Polyvalent Immune Fab (Ovine) administration for copperhead snakebite.

    PubMed

    Lepak, Maryjoy R; Bochenek, Samantha H; Bush, Sean P

    2015-01-01

    To present the case of a severe anaphylactic/anaphylactoid reaction to Crotalidae Polyvalent Immune Fab (Ovine) in a patient bitten by a copperhead snake. A 68-year-old man presented with progressive envenomation after receiving a copperhead snakebite on each hand. Crotalinae Fab antivenom was administered. While the initial and only dose was partially infusing, the patient developed an adverse drug reaction (ADR) of urticaria and hypotension, which resolved with cessation of the infusion, recurred with resumption of the infusion, and ultimately was completed with supportive care. An additional episode of hypotension, urticaria, and angioedema occurred shortly after antivenom therapy completion. Epinephrine was administered, resolving the reaction with complete patient recovery. The event received a Naranjo score of 10, indicating a definite ADR. Treating copperhead snakebites with antivenom is a matter of debate. Concern over adverse events and cost induce some physicians to manage copperhead bites without antivenom because they are generally milder in severity. As demonstrated in this case, severe ADR can occur with Crotalinae Fab antivenom, and its efficacy for copperhead envenoming needs to be better established via placebo-controlled, randomized trials. © The Author(s) 2014.

  4. Evaluation of thromboembolic events in cancer patients receiving bevacizumab according to the Japanese Adverse Drug Event Report database.

    PubMed

    Matsumura, Chikako; Chisaki, Yugo; Sakimoto, Satoko; Sakae, Honoka; Yano, Yoshitaka

    2018-01-01

    Purpose We aimed to examine the risk factors, time of onset, incidence rates, and outcomes of thromboembolic events induced by bevacizumab in patients with cancer using the Japanese Adverse Drug Event Report (JADER) database of the Pharmaceuticals and Medical Devices Agency. Methods Adverse event data recorded in the JADER database between January 2004 and January 2015 were used. After screening the data using the generic drug name bevacizumab, patient data were classified into two groups by age and five groups by cancer type. The histories of disorders were also categorized. Arterial thromboembolic event and venous thromboembolic event were classified as "favorable" or "unfavorable" outcomes. Results In total, 6076 patients were reported to have developed adverse events during the sample period, of which 233 and 453 developed arterial thromboembolic event and venous thromboembolic event, respectively. Logistic analysis suggested that the presence of cancer was a significant risk factor for both arterial thromboembolic event and venous thromboembolic event. Age (≥70 years), histories of either hypertension or diabetes mellitus were also risk factors for arterial thromboembolic event. Median cumulative times of onset for arterial thromboembolic event and venous thromboembolic event were 60 and 80 days, respectively, and were not significantly different by the log-rank test. By the chi-square test, the rate of unfavorable outcomes was found to be higher after developing arterial thromboembolic event than after venous thromboembolic event. Conclusion Thromboembolism is a leading cause of mortality in patients with cancer. Patients should be monitored for the symptoms of thromboembolic events right from the initial stages of bevacizumab treatment.

  5. Defining Catastrophic Costs and Comparing Their Importance for Adverse Tuberculosis Outcome with Multi-Drug Resistance: A Prospective Cohort Study, Peru

    PubMed Central

    Wingfield, Tom; Boccia, Delia; Tovar, Marco; Gavino, Arquímedes; Zevallos, Karine; Montoya, Rosario; Lönnroth, Knut; Evans, Carlton A.

    2014-01-01

    Background Even when tuberculosis (TB) treatment is free, hidden costs incurred by patients and their households (TB-affected households) may worsen poverty and health. Extreme TB-associated costs have been termed “catastrophic” but are poorly defined. We studied TB-affected households' hidden costs and their association with adverse TB outcome to create a clinically relevant definition of catastrophic costs. Methods and Findings From 26 October 2002 to 30 November 2009, TB patients (n = 876, 11% with multi-drug-resistant [MDR] TB) and healthy controls (n = 487) were recruited to a prospective cohort study in shantytowns in Lima, Peru. Patients were interviewed prior to and every 2–4 wk throughout treatment, recording direct (household expenses) and indirect (lost income) TB-related costs. Costs were expressed as a proportion of the household's annual income. In poorer households, costs were lower but constituted a higher proportion of the household's annual income: 27% (95% CI = 20%–43%) in the least-poor houses versus 48% (95% CI = 36%–50%) in the poorest. Adverse TB outcome was defined as death, treatment abandonment or treatment failure during therapy, or recurrence within 2 y. 23% (166/725) of patients with a defined treatment outcome had an adverse outcome. Total costs ≥20% of household annual income was defined as catastrophic because this threshold was most strongly associated with adverse TB outcome. Catastrophic costs were incurred by 345 households (39%). Having MDR TB was associated with a higher likelihood of incurring catastrophic costs (54% [95% CI = 43%–61%] versus 38% [95% CI = 34%–41%], p<0.003). Adverse outcome was independently associated with MDR TB (odds ratio [OR] = 8.4 [95% CI = 4.7–15], p<0.001), previous TB (OR = 2.1 [95% CI = 1.3–3.5], p = 0.005), days too unwell to work pre-treatment (OR = 1.01 [95% CI = 1.00–1.01], p = 0.02), and catastrophic costs (OR = 1

  6. LimTox: a web tool for applied text mining of adverse event and toxicity associations of compounds, drugs and genes

    PubMed Central

    Cañada, Andres; Rabal, Obdulia; Oyarzabal, Julen; Valencia, Alfonso

    2017-01-01

    Abstract A considerable effort has been devoted to retrieve systematically information for genes and proteins as well as relationships between them. Despite the importance of chemical compounds and drugs as a central bio-entity in pharmacological and biological research, only a limited number of freely available chemical text-mining/search engine technologies are currently accessible. Here we present LimTox (Literature Mining for Toxicology), a web-based online biomedical search tool with special focus on adverse hepatobiliary reactions. It integrates a range of text mining, named entity recognition and information extraction components. LimTox relies on machine-learning, rule-based, pattern-based and term lookup strategies. This system processes scientific abstracts, a set of full text articles and medical agency assessment reports. Although the main focus of LimTox is on adverse liver events, it enables also basic searches for other organ level toxicity associations (nephrotoxicity, cardiotoxicity, thyrotoxicity and phospholipidosis). This tool supports specialized search queries for: chemical compounds/drugs, genes (with additional emphasis on key enzymes in drug metabolism, namely P450 cytochromes—CYPs) and biochemical liver markers. The LimTox website is free and open to all users and there is no login requirement. LimTox can be accessed at: http://limtox.bioinfo.cnio.es PMID:28531339

  7. ADEpedia: a scalable and standardized knowledge base of Adverse Drug Events using semantic web technology.

    PubMed

    Jiang, Guoqian; Solbrig, Harold R; Chute, Christopher G

    2011-01-01

    A source of semantically coded Adverse Drug Event (ADE) data can be useful for identifying common phenotypes related to ADEs. We proposed a comprehensive framework for building a standardized ADE knowledge base (called ADEpedia) through combining ontology-based approach with semantic web technology. The framework comprises four primary modules: 1) an XML2RDF transformation module; 2) a data normalization module based on NCBO Open Biomedical Annotator; 3) a RDF store based persistence module; and 4) a front-end module based on a Semantic Wiki for the review and curation. A prototype is successfully implemented to demonstrate the capability of the system to integrate multiple drug data and ontology resources and open web services for the ADE data standardization. A preliminary evaluation is performed to demonstrate the usefulness of the system, including the performance of the NCBO annotator. In conclusion, the semantic web technology provides a highly scalable framework for ADE data source integration and standard query service.

  8. Factors associated with fatigue in acquired immunodeficiency syndrome patients with antiretroviral drug adverse reactions: a retrospective study.

    PubMed

    Liu, Zhibin; Yang, Jiping; Liu, Huijuan; Jin, Yantao

    2013-06-01

    To retrospectively study the prevalence of fatigue and factors associated with fatigue among acquired immunodeficiency syndrome (AIDS) patients with antiretroviral drug adverse reactions. Data were collected from case report forms (CRFs) for a project funded by the 11th National 5-year Special Science and Technology Program on Major Infectious Diseases. Fatigue was defined by patient self-report. The outcomes were the prevalence of fatigue and the potential risk factors of fatigue. Univariate and multivariate logistic regression analyses were conducted to identify the factors associated with fatigue. Among the 228 subjects, the prevalence of fatigue was 86.8%. In univariate analysis, the significant differences in demographic characteristics between patients with and without fatigue were: gender [OR = 2.29; 95% CI (1.05-4.98)], education level [OR = 0.40; 95% CI (0.18-0.85)], anemia [OR = 3.80; 95% CI (1.27-11.31)], time of HIV diagnosis [OR = 0.29; 95% CI (0.13-0.65)], and route of infection [OR = 0.14; 95% CI (0.06-0.32)]. Abnormal taste and rapid pulse were more commonly seen in patients with fatigue (P < 0.05), while abdominal distension and lumbar soreness were encountered less often in patients with fatigue (P < 0.05). Multivariate analysis showed that the four main factors associated with fatigue were anemia [OR = 3.50; 95% CI (1.01-12.15)], route of infection [OR = 3.40; 95% CI (1.21-9.58); P = 0.02 < 0.05], lumbar soreness [OR = 0.06; 95% CI (0.02-0.18); P = 0.000 < 0.05], and rapid pulse [OR = 10.58; 95% CI (2.16-51.75); P = 0.004 < 0.05]. This study demonstrated that fatigue is common (86.8% prevalence) in AIDS patients with antiretroviral drug adverse reactions, and that anemia, route of infection (i.e., non-commercial blood donation) and rapid pulse were risk factors, while lumbar soreness was a protective factor related to fatigue. More attention should be paid to fatigue and more efforts should be made to find ways to prevent, control and eliminate

  9. Cardiovascular adverse effects of phenytoin.

    PubMed

    Guldiken, B; Rémi, J; Noachtar, Soheyl

    2016-05-01

    Phenytoin is an established drug in the treatment of acute repetitive seizures and status epilepticus. One of its main advantages over benzodiazepines is the less sedative effect. However, the possibility of cardiovascular adverse effects with the intravenous use of phenytoin cause a reluctance to its usage, and this has lead to a search for safer anticonvulsant drugs. In this study, we aimed to review the studies which evaluated the safety of phenytoin with respect to cardiovascular adverse effects. The original clinical trials and case reports listed in PUBMED in English language between the years of 1946-2014 were evaluated. As the key words, "phenytoin, diphenylhydantoin, epilepsy, seizure, cardiac toxicity, asystole, arrhythmia, respiratory arrest, hypotension, death" were used. Thirty-two clinical trials and ten case reports were identified. In the case reports, a rapid infusion rate (>50 mg/min) of phenytoin appeared as the major cause of increased mortality. In contrast, no serious cardiovascular adverse effects leading to death were met in the clinical trials which applied the recommended infusion rate and dosages. An infusion rate of 50 mg/min was reported to be safe for young patients. For old patients and patients with a cardiovascular co-morbidity, a slower infusion rate was recommended with a careful follow-up of heart rhythm and blood pressure. No cardiovascular adverse effect was reported in oral phenytoin overdoses except one case with a very high serum phenytoin level and hypoalbuminemia. Phenytoin is an effective and well tolerated drug in the treatment of epilepsy. Intravenous phenytoin is safe when given at recommended infusion rates and doses.

  10. 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.

  11. Using technology to prevent adverse drug events in the intensive care unit.

    PubMed

    Hassan, Erkan; Badawi, Omar; Weber, Robert J; Cohen, Henry

    2010-06-01

    Critically ill patients are particularly susceptible to adverse drug events (ADEs) due to their rapidly changing and unstable physiology, complex therapeutic regimens, and large percentage of medications administered intravenously. There are a wide variety of technologies that can help prevent the points of failure commonly associated with ADEs (i.e., the five "Rights": right patient; right drug; right route; right dose; right frequency). These technologies are often categorized by their degree of complexity to design and engineer and the type of error they are designed to prevent. Focusing solely on the software and hardware design of technology may over- or underestimate the degree of difficulty to avoid ADEs at the bedside. Alternatively, we propose categorizing technological solutions by identifying the factors essential for success. The two major critical success factors are: 1) the degree of clinical assessment required by the clinician to appropriately evaluate and disposition the issue identified by a technology; and 2) the complexity associated with effective implementation. This classification provides a way of determining how ADE-preventing technologies in the intensive care unit can be successfully integrated into clinical practice. Although there are limited data on the effectiveness of many technologies in reducing ADEs, we will review the technologies currently available in the intensive care unit environment. We will also discuss critical success factors for implementation, common errors made during implementation, and the potential errors using these systems.

  12. A Decade of Gabapentinoid Misuse: An Analysis of the European Medicines Agency's 'Suspected Adverse Drug Reactions' Database.

    PubMed

    Chiappini, Stefania; Schifano, Fabrizio

    2016-07-01

    The gabapentinoids pregabalin and gabapentin are being increasingly prescribed for a range of clinical conditions. Recently, although gabapentinoids at therapeutic dosages may present with low addictive liability levels, cases of misuse and rising numbers of related fatalities have been reported. The aim of the study was to identify and assess cases of gabapentinoid misuse or dependence as reported to the European Medicines Agency's EudraVigilance database, to identify the magnitude of this problem and the characteristics of these reactions. All spontaneous reports of both gabapentin- (2004-2015) and pregabalin- (2006-2015) related misuse/abuse/dependence were retrieved. A descriptive analysis by source, sex, age, and type of report was performed. From the EudraVigilance database 7639 (6.6 % of a total of 115,616) and 4301 (4.8 % of 90,166) adverse drug reaction reports of misuse/abuse/dependence were, respectively, associated with pregabalin and gabapentin, with an overall reporting frequency increasing over time. For both molecules, subjects typically involved were female adults. A total of 27 and 86 fatalities, respectively, associated with pregabalin and gabapentin, and mostly in combination with opioids, were identified. Analysis of proportional reporting ratios for drug abuse/dependence/intentional product misuse values seem to indicate that these adverse drug reactions were more frequently reported for pregabalin (1.25, 1.39, and 1.58, respectively) compared with gabapentin. Despite data collection/methodological approach limitations, the present data seem to suggest that gabapentinoid misuse may be a cause for concern, especially in patients with a history of substance misuse. Hence, healthcare professionals should be vigilant when prescribing these molecules.

  13. Distant Supervision with Transductive Learning for Adverse Drug Reaction Identification from Electronic Medical Records

    PubMed Central

    Ikeda, Mitsuru

    2017-01-01

    Information extraction and knowledge discovery regarding adverse drug reaction (ADR) from large-scale clinical texts are very useful and needy processes. Two major difficulties of this task are the lack of domain experts for labeling examples and intractable processing of unstructured clinical texts. Even though most previous works have been conducted on these issues by applying semisupervised learning for the former and a word-based approach for the latter, they face with complexity in an acquisition of initial labeled data and ignorance of structured sequence of natural language. In this study, we propose automatic data labeling by distant supervision where knowledge bases are exploited to assign an entity-level relation label for each drug-event pair in texts, and then, we use patterns for characterizing ADR relation. The multiple-instance learning with expectation-maximization method is employed to estimate model parameters. The method applies transductive learning to iteratively reassign a probability of unknown drug-event pair at the training time. By investigating experiments with 50,998 discharge summaries, we evaluate our method by varying large number of parameters, that is, pattern types, pattern-weighting models, and initial and iterative weightings of relations for unlabeled data. Based on evaluations, our proposed method outperforms the word-based feature for NB-EM (iEM), MILR, and TSVM with F1 score of 11.3%, 9.3%, and 6.5% improvement, respectively. PMID:29090077

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

    PubMed

    Cuena Boy, R; Maciá Martínez, M A

    1998-03-31

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

  15. Incidence, characteristics and risk factors of adverse drug reactions in hospitalized children – a prospective observational cohort study of 6,601 admissions

    PubMed Central

    2013-01-01

    Background Adverse drug reactions (ADRs) are an important cause of harm in children. Current data are incomplete due to methodological differences between studies: only half of all studies provide drug data, incidence rates vary (0.6% to 16.8%) and very few studies provide data on causality, severity and risk factors of pediatric ADRs. We aimed to determine the incidence of ADRs in hospitalized children, to characterize these ADRs in terms of type, drug etiology, causality and severity and to identify risk factors. Methods We undertook a year-long, prospective observational cohort study of admissions to a single UK pediatric medical and surgical secondary and tertiary referral center (Alder Hey, Liverpool, UK). Children between 0 and 16 years 11 months old and admitted for more than 48 hours were included. Observed outcomes were occurrence of ADR and time to first ADR for the risk factor analysis. Results A total of 5,118 children (6,601 admissions) were included, 17.7% of whom experienced at least one ADR. Opiate analgesics and drugs used in general anesthesia (GA) accounted for more than 50% of all drugs implicated in ADRs. Of these ADRs, 0.9% caused permanent harm or required admission to a higher level of care. Children who underwent GA were at more than six times the risk of developing an ADR than children without a GA (hazard ratio (HR) 6.40; 95% confidence interval (CI) 5.30 to 7.70). Other factors increasing the risk of an ADR were increasing age (HR 1.06 for each year; 95% CI 1.04 to 1.07), increasing number of drugs (HR 1.25 for each additional drug; 95% CI 1.22 to 1.28) and oncological treatment (HR 1.90; 95% CI 1.40 to 2.60). Conclusions ADRs are common in hospitalized children and children who had undergone a GA had more than six times the risk of developing an ADR. GA agents and opiate analgesics are a significant cause of ADRs and have been underrepresented in previous studies. This is a concern in view of the increasing number of pediatric short

  16. Exploration of the Anti-Inflammatory Drug Space Through Network Pharmacology: Applications for Drug Repurposing

    PubMed Central

    de Anda-Jáuregui, Guillermo; Guo, Kai; McGregor, Brett A.; Hur, Junguk

    2018-01-01

    The quintessential biological response to disease is inflammation. It is a driver and an important element in a wide range of pathological states. Pharmacological management of inflammation is therefore central in the clinical setting. Anti-inflammatory drugs modulate specific molecules involved in the inflammatory response; these drugs are traditionally classified as steroidal and non-steroidal drugs. However, the effects of these drugs are rarely limited to their canonical targets, affecting other molecules and altering biological functions with system-wide effects that can lead to the emergence of secondary therapeutic applications or adverse drug reactions (ADRs). In this study, relationships among anti-inflammatory drugs, functional pathways, and ADRs were explored through network models. We integrated structural drug information, experimental anti-inflammatory drug perturbation gene expression profiles obtained from the Connectivity Map and Library of Integrated Network-Based Cellular Signatures, functional pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome databases, as well as adverse reaction information from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). The network models comprise nodes representing anti-inflammatory drugs, functional pathways, and adverse effects. We identified structural and gene perturbation similarities linking anti-inflammatory drugs. Functional pathways were connected to drugs by implementing Gene Set Enrichment Analysis (GSEA). Drugs and adverse effects were connected based on the proportional reporting ratio (PRR) of an adverse effect in response to a given drug. Through these network models, relationships among anti-inflammatory drugs, their functional effects at the pathway level, and their adverse effects were explored. These networks comprise 70 different anti-inflammatory drugs, 462 functional pathways, and 1,175 ADRs. Network-based properties, such as degree

  17. Exploration of the Anti-Inflammatory Drug Space Through Network Pharmacology: Applications for Drug Repurposing.

    PubMed

    de Anda-Jáuregui, Guillermo; Guo, Kai; McGregor, Brett A; Hur, Junguk

    2018-01-01

    The quintessential biological response to disease is inflammation. It is a driver and an important element in a wide range of pathological states. Pharmacological management of inflammation is therefore central in the clinical setting. Anti-inflammatory drugs modulate specific molecules involved in the inflammatory response; these drugs are traditionally classified as steroidal and non-steroidal drugs. However, the effects of these drugs are rarely limited to their canonical targets, affecting other molecules and altering biological functions with system-wide effects that can lead to the emergence of secondary therapeutic applications or adverse drug reactions (ADRs). In this study, relationships among anti-inflammatory drugs, functional pathways, and ADRs were explored through network models. We integrated structural drug information, experimental anti-inflammatory drug perturbation gene expression profiles obtained from the Connectivity Map and Library of Integrated Network-Based Cellular Signatures, functional pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome databases, as well as adverse reaction information from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). The network models comprise nodes representing anti-inflammatory drugs, functional pathways, and adverse effects. We identified structural and gene perturbation similarities linking anti-inflammatory drugs. Functional pathways were connected to drugs by implementing Gene Set Enrichment Analysis (GSEA). Drugs and adverse effects were connected based on the proportional reporting ratio (PRR) of an adverse effect in response to a given drug. Through these network models, relationships among anti-inflammatory drugs, their functional effects at the pathway level, and their adverse effects were explored. These networks comprise 70 different anti-inflammatory drugs, 462 functional pathways, and 1,175 ADRs. Network-based properties, such as degree

  18. Types, frequencies, and burden of nonspecific adverse events of drugs: analysis of randomized placebo-controlled clinical trials.

    PubMed

    Mahr, Alfred; Golmard, Clara; Pham, Emilie; Iordache, Laura; Deville, Laure; Faure, Pierre

    2017-07-01

    Scarce studies analyzing adverse event (AE) data from randomized placebo-controlled clinical trials (RPCCTs) of selected illnesses suggested that a substantial proportion of collected AEs are unrelated to the drug taken. This study analyzed the nonspecific AEs occurring with active-drug exposure in RPCCTs for a large range of medical conditions. Randomized placebo-controlled clinical trials published in five prominent medical journals during 2006-2012 were searched. Only trials that evaluated orally or parenterally administered active drugs versus placebo in a head-to-head setting were selected. For AEs reported from ≥10 RPCCTs, Pearson's correlation coefficients (r) were calculated to determine the relationship between AE rates in placebo and active-drug recipients. Random-effects meta-analyses were used to compute proportions of nonspecific AEs, which were truncated at a maximum of 100%, in active-drug recipients. We included 231 trials addressing various medical domains or healthy participants. For the 88 analyzed AE variables, AE rates for placebo and active-drug recipients were in general strongly correlated (r > 0.50) or very strongly correlated (r > 0.80). The pooled proportions of nonspecific AEs for the active-drug recipients were 96.8% (95%CI: 95.5-98.1) for any AEs, 100% (97.9-100) for serious AEs, and 77.7% (72.7-83.2) for drug-related AEs. Results were similar for individual medical domains and healthy participants. The pooled proportion of nonspecificity of 82 system organ class and individual AE types ranged from 38% to 100%. The large proportion of nonspecific AEs reported in active-drug recipients of RPCCTs, including serious and drug-related AEs, highlights the limitations of clinical trial data to determine the tolerability of drugs. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  19. The changing face of antihistamines and cardiac adverse drug reactions: a clinical perspective.

    PubMed

    Shaikh, W A

    2000-07-01

    Recent times have witnessed a qualitative shift in the recognition and management of adverse drug effects. Many of them occur in organs that are unconnected to the primary target of pharmacological action. Out of these, cardiac side-effects have drawn particular attention because of their potential to cause death. Starting with the early observations on antibiotics such as macrolides, followed by fluoroquinolones and others, the focus has now shifted to the antihistamine class of drugs which are used extensively by patients all over the world, thanks to the ever increasing levels of environmental pollution. The occurrence of prolonged QTc interval following treatment with terfenadine leading to ventricular tachycardia of torsades de points variety with a potentially fatal outcome has forced many regulatory authorities of the world to clamp a ban the use of this drug. Alerted by these developments, studies on a new member, followed by fluoroquinolones and others, the focus has now shifted to the antihistamine class of drugs which are used extensively by patients all over the world, thanks to the ever incresing levels of envrionmental pollution. The occurrence of prolonged QTc interval following treatment with terfenadine leading to ventricular tachycardia of torsades de points variety with a potentially fatal outcome has forced many regulatory authorities of the world to clamp a ban use of this drug. Alerted by these developments, studies on a new member of non-sedating antihistamine class viz, fexofenadine, have been reviewed especially because of the structural similarity between terfenadine and fexofenadine. It is now clear that despite the closeness of its chemical structure to terfenadine fexofenadine behaves in a different manner and does not affect the electrophysiology of the heart muscle tissue, as proved by data from extensive clinical trials as well as membrane models in vitro. Interestingly, the solitary false alarm that was sounded on the drug by a

  20. [Use of Nadis(®) software to improve adverse drug reaction reporting of antiretroviral drugs: experience in south west of France (midi-pyrénées)].

    PubMed

    Pochard, Liselotte; Hauviller, Laurent; Cuzin, Lise; Eyvrard, Fréderic; Sommet, Agnès; Montastruc, Jean-Louis; Bagheri, Haleh

    2014-01-01

    To study the value of the module of pharmacovigilance in Nadis® to improve the antiretroviral (ARV) drugs-induced adverse drug reactions (ADRs) reporting. We collected the ADRs reported for 17 months from November 2010 until April 2012. Following data were recorded: characteristics of patients, ADRs, ARV drugs. The number of ADRs was compared to those collected in the same period (17 months) before use of Nadis®. The 119 ADRs reported (an increase of 183%) for 109 patients ADRs were mainly gastrointestinal (21.8%) followed by renal (20.2%), neuro-psychiatric (16.8%), hepatic (13.5%), cutaneous (8.4%), metabolic (6.7%) and others (12.6%). The repartition of ARV drugs was: nucleoside (31.8%), nucleotide (13.6%) reverse transcriptase inhibitors respectively, non-nucleoside reverse transcriptase inhibitors (13.1%), protease inhibitors (36.4%), and integrase inhibitors (5.1%). Our results show the improvement of ARV-induced ADRs reporting by Nadis® which could be used to reduce the rate of under-reporting in patients exposed to these drugs. © 2014 Société Française de Pharmacologie et de Thérapeutique.

  1. Persistence of transmitted HIV-1 drug resistance mutations associated with fitness costs and viral genetic backgrounds.

    PubMed

    Yang, Wan-Lin; Kouyos, Roger D; Böni, Jürg; Yerly, Sabine; Klimkait, Thomas; Aubert, Vincent; Scherrer, Alexandra U; Shilaih, Mohaned; Hinkley, Trevor; Petropoulos, Christos; Bonhoeffer, Sebastian; Günthard, Huldrych F

    2015-03-01

    Transmission of drug-resistant pathogens presents an almost-universal challenge for fighting infectious diseases. Transmitted drug resistance mutations (TDRM) can persist in the absence of drugs for considerable time. It is generally believed that differential TDRM-persistence is caused, at least partially, by variations in TDRM-fitness-costs. However, in vivo epidemiological evidence for the impact of fitness costs on TDRM-persistence is rare. Here, we studied the persistence of TDRM in HIV-1 using longitudinally-sampled nucleotide sequences from the Swiss-HIV-Cohort-Study (SHCS). All treatment-naïve individuals with TDRM at baseline were included. Persistence of TDRM was quantified via reversion rates (RR) determined with interval-censored survival models. Fitness costs of TDRM were estimated in the genetic background in which they occurred using a previously published and validated machine-learning algorithm (based on in vitro replicative capacities) and were included in the survival models as explanatory variables. In 857 sequential samples from 168 treatment-naïve patients, 17 TDRM were analyzed. RR varied substantially and ranged from 174.0/100-person-years;CI=[51.4, 588.8] (for 184V) to 2.7/100-person-years;[0.7, 10.9] (for 215D). RR increased significantly with fitness cost (increase by 1.6[1.3,2.0] per standard deviation of fitness costs). When subdividing fitness costs into the average fitness cost of a given mutation and the deviation from the average fitness cost of a mutation in a given genetic background, we found that both components were significantly associated with reversion-rates. Our results show that the substantial variations of TDRM persistence in the absence of drugs are associated with fitness-cost differences both among mutations and among different genetic backgrounds for the same mutation.

  2. Concealed renal failure and adverse drug reactions in older patients with type 2 diabetes mellitus.

    PubMed

    Corsonello, Andrea; Pedone, Claudio; Corica, Francesco; Mazzei, Bruno; Di Iorio, Angelo; Carbonin, Pierugo; Incalzi, Raffaele Antonelli

    2005-09-01

    In elderly patients serum creatinine may be normal despite decreased glomerular filtration rate (GFR). The aim of this study was to evaluate the prevalence of this "concealed" renal failure, i.e., renal failure with normal serum creatinine levels, in elderly diabetic patients, and to verify whether it is a risk factor for adverse drug reactions (ADR) to hydrosoluble drugs. We used data on 2257 hospitalized patients with type 2 diabetes mellitus enrolled in the Gruppo Italiano di Farmacovigilanza nell'Anziano study. On the basis of serum creatinine and calculated GFR, patients were grouped as follows: normal renal function (normal serum creatinine levels and normal GFR), concealed (normal serum creatinine levels and reduced GFR), or overt (increased creatinine levels and reduced GFR) renal failure. GFR was calculated using the Modification of Diet in Renal Disease (MDRD) equation. The outcome of the study was the incidence of ADR to hydrosoluble drugs during the hospital stay. The relationship between renal function and ADR was evaluated using Cox regression analysis including potential confounders. Concealed renal failure was observed in 363 (16.1%) of patients studied. Patients with concealed or overt renal failure were older, had more frequently cognitive impairment and polypharmacy, and had lower serum albumin levels than did those with normal renal function. Both concealed (hazard ratio = 1.90; 95% confidence interval, 1.04-3.48; p =.036) and overt (hazard ratio = 2.23; 95% confidence interval, 1.40-3.55; p =.001) renal failure were significantly associated with ADR to hydrosoluble drugs. The use of more than four drugs also qualified as an independent risk factor for ADRs to hydrosoluble drugs during hospital stay. Older diabetic patients should be systematically screened to ascertain the presence of concealed renal failure in an attempt to optimize the pharmacological treatment and reduce the risk of ADRs.

  3. The effect size of type 2 diabetes mellitus on tuberculosis drug resistance and adverse treatment outcomes.

    PubMed

    Perez-Navarro, Lucia Monserrat; Restrepo, Blanca I; Fuentes-Dominguez, Francisco Javier; Duggirala, Ravindranath; Morales-Romero, Jaime; López-Alvarenga, Juan Carlos; Comas, Iñaki; Zenteno-Cuevas, Roberto

    2017-03-01

    To evaluate the effect size of type 2 diabetes mellitus (T2DM) on tuberculosis (TB) treatment outcomes and multi drug resistance (MDR). A cohort with 507 individuals with diagnosed TB included 183 with coexistence of T2DM and TB (TB-T2DM). Participants were identified at the time of TB diagnosis and followed during the course of TB treatment. Then we computed relative risks and adjustments by Cox proportional hazards for outcome variables (drug resistance, death, relapse, treatment failure), and the size of their effect as Cohen's-d. Patients with TB-T2DM were more likely to remain positive for acid-fast bacilli after two months of anti-TB treatment RR = [2.01 (95% CI: 1.3, 3.1)], to have drug resistant (DR) [OR 3.5 (95% CI: 1.8, 6.7)] and multi-drug resistant (MDR) TB [OR 3.5 (95% CI: 1.8, 7.1)]. The Cohen's-d for DR or MDR in T2DM was 0.69 when compared with non-DM subjects. The T2DM patients had higher odds of resistance to isoniazid (OR 3.9, 95% CI: 2.01, 7.9), rifampicin (OR 3.4, 95% CI: 1.6, 7.2) and pyrazinamide (OR 9.4, 95% CI: 2.8, 25.6), and their effect sizes were ≥0.67. Patients with TB-T2DM (versus no DM) were more likely to present with MDR TB (HR 3.1; 95% CI: 1.7, 5.8; p < 0.001), treatment failure (HR 2.04; 95% CI: 1.07, 3.8; p = 0.02) and relapse (HR 1.86; 95% CI: 1.09, 3.1; p = 0.02), with effect size ≥0.34. T2DM showed a substantial contribution to the presence of DR or MDR-TB and to adverse clinical outcomes during and after TB treatment. Our findings support the importance for routine screening of T2DM among newly-diagnosed TB patients in order to stratify them for immediate DR assessment, and highlight the need for clinical trials to evaluate variations to the standard TB treatment in TB-T2DM to prevent adverse treatment outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Food and Drug Administration (FDA) postmarket reported side effects and adverse events associated with pulmonary hypertension therapy in pediatric patients.

    PubMed

    Maxey, Dawn M; Ivy, D Dunbar; Ogawa, Michelle T; Feinstein, Jeffrey A

    2013-10-01

    Because most medications for pediatric pulmonary hypertension (PH) are used off label and based on adult trials, little information is available on pediatric-specific adverse events (AEs). Although drug manufacturers are required to submit postmarket AE reports to the Food and Drug Administration (FDA), this information is rarely transmitted to practitioners. In the setting of a recent FDA warning for sildenafil, the authors sought to give a better description of the AEs associated with current therapies in pediatric PH. In January 2010, a written request was made to the Food and Drug Administration for AE records of commonly used PH medications. Reports were screened for pediatric patients, analyzed in terms of AEs, and compared with the medical literature. Arbitrarily, AEs that could be attributed to concomitant medications were not attributed to the PH medication in question. Adverse events occurring in more than 5 % of events for each drug were assumed to be associated with the targeted PH medication. Between November 1997 and December 2009, 588 pediatric AE reports (death in 257 cases) were reported for the three most commonly used therapies: bosentan, epoprostenol, and sildenafil. Many of the AEs were similar to those reported previously. However, 27 AEs not previously reported in the literature (e.g., pulmonary hemorrhage, hemoptysis, and pneumonia) were found. The FDA postmarket records for PH medications in pediatric patients show a significant number of AEs. The discovery of AEs not previously reported will better inform those caring for these complex and critically ill children, and the large number of deaths suggest they may be underreported in current literature.

  5. Incidence and nature of adverse reactions to antibiotics used as endocarditis prophylaxis

    PubMed Central

    Thornhill, Martin H.; Dayer, Mark J.; Prendergast, Bernard; Baddour, Larry M.; Jones, Simon; Lockhart, Peter B.

    2015-01-01

    Objectives Antibiotic prophylaxis (AP) administration prior to invasive dental procedures has been a leading focus of infective endocarditis prevention. However, there have been long-standing concerns about the risk of adverse drug reactions as a result of this practice. The objective of this study was to identify the incidence and nature of adverse reactions to amoxicillin and clindamycin prophylaxis to prevent infective endocarditis. Methods We obtained AP prescribing data for England from January 2004 to March 2014 from the NHS Business Services Authority, and adverse drug reaction data from the Medicines and Healthcare Products Regulatory Agency's Yellow Card reporting scheme for prescriptions of the standard AP protocol of a single 3 g oral dose of amoxicillin or a single 600 mg oral dose of clindamycin for those allergic to penicillin. Results The reported adverse drug reaction rate for amoxicillin AP was 0 fatal reactions/million prescriptions (in fact 0 fatal reactions for nearly 3 million prescriptions) and 22.62 non-fatal reactions/million prescriptions. For clindamycin, it was 13 fatal and 149 non-fatal reactions/million prescriptions. Most clindamycin adverse drug reactions were Clostridium difficile infections. Conclusions AP adverse drug reaction reporting rates in England were low, particularly for amoxicillin, and lower than previous estimates. This suggests that amoxicillin AP is comparatively safe for patients without a history of amoxicillin allergy. The use of clindamycin AP was, however, associated with significant rates of fatal and non-fatal adverse drug reactions associated with C. difficile infections. These were higher than expected and similar to those for other doses, durations and routes of clindamycin administration. PMID:25925595

  6. LimTox: a web tool for applied text mining of adverse event and toxicity associations of compounds, drugs and genes.

    PubMed

    Cañada, Andres; Capella-Gutierrez, Salvador; Rabal, Obdulia; Oyarzabal, Julen; Valencia, Alfonso; Krallinger, Martin

    2017-07-03

    A considerable effort has been devoted to retrieve systematically information for genes and proteins as well as relationships between them. Despite the importance of chemical compounds and drugs as a central bio-entity in pharmacological and biological research, only a limited number of freely available chemical text-mining/search engine technologies are currently accessible. Here we present LimTox (Literature Mining for Toxicology), a web-based online biomedical search tool with special focus on adverse hepatobiliary reactions. It integrates a range of text mining, named entity recognition and information extraction components. LimTox relies on machine-learning, rule-based, pattern-based and term lookup strategies. This system processes scientific abstracts, a set of full text articles and medical agency assessment reports. Although the main focus of LimTox is on adverse liver events, it enables also basic searches for other organ level toxicity associations (nephrotoxicity, cardiotoxicity, thyrotoxicity and phospholipidosis). This tool supports specialized search queries for: chemical compounds/drugs, genes (with additional emphasis on key enzymes in drug metabolism, namely P450 cytochromes-CYPs) and biochemical liver markers. The LimTox website is free and open to all users and there is no login requirement. LimTox can be accessed at: http://limtox.bioinfo.cnio.es. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  7. Sex Differences in Reported Adverse Drug Reactions of Selective Serotonin Reuptake Inhibitors.

    PubMed

    Ekhart, Corine; van Hunsel, Florence; Scholl, Joep; de Vries, Sieta; van Puijenbroek, Eugene

    2018-02-26

    Several studies have investigated sex as a risk factor for the occurrence of adverse drug reactions (ADRs) and found that women are more likely to experience ADRs than men. The aim of this explorative study was to investigate whether differences exist in reported ADRs of selective serotonin reuptake inhibitors (SSRIs) for men and women in the database of the Netherlands Pharmacovigilance Centre Lareb. A ratio of reports concerning women and men, corrected for the number of users, was calculated for all the ADRs reported on SSRIs. We found that 16 ADRs were statistically significantly more reported in women than men, and four ADRS were reported more in men than women. ADRs more reported in women than men when using SSRIs were usually dose-related ADRs or commonly occurring ADRs. Differences in the pharmacokinetics of SSRIs between men and women may explain why these reports of dose-related ADRs when using SSRIs concern women more than men.

  8. A Framework of Knowledge Integration and Discovery for Supporting Pharmacogenomics Target Predication of Adverse Drug Events: A Case Study of Drug-Induced Long QT Syndrome.

    PubMed

    Jiang, Guoqian; Wang, Chen; Zhu, Qian; Chute, Christopher G

    2013-01-01

    Knowledge-driven text mining is becoming an important research area for identifying pharmacogenomics target genes. However, few of such studies have been focused on the pharmacogenomics targets of adverse drug events (ADEs). The objective of the present study is to build a framework of knowledge integration and discovery that aims to support pharmacogenomics target predication of ADEs. We integrate a semantically annotated literature corpus Semantic MEDLINE with a semantically coded ADE knowledgebase known as ADEpedia using a semantic web based framework. We developed a knowledge discovery approach combining a network analysis of a protein-protein interaction (PPI) network and a gene functional classification approach. We performed a case study of drug-induced long QT syndrome for demonstrating the usefulness of the framework in predicting potential pharmacogenomics targets of ADEs.

  9. Patch testing and cross sensitivity study of adverse cutaneous drug reactions due to anticonvulsants: A preliminary report.

    PubMed

    Shiny, T N; Mahajan, Vikram K; Mehta, Karaninder S; Chauhan, Pushpinder S; Rawat, Ritu; Sharma, Rajni

    2017-03-26

    To evaluate the utility of patch test and cross-sensitivity patterns in patients with adverse cutaneous drug reactions (ACDR) from common anticonvulsants. Twenty-four (M:F = 13:11) patients aged 18-75 years with ACDR from anticonvulsants were patch tested 3-27 mo after complete recovery using carbamazepine, phenytoin, phenobarbitone, lamotrigine, and sodium valproate in 10%, 20% and 30% conc. in pet. after informed consent. Positive reactions persisting on D3 and D4 were considered significant. Clinical patterns were exanthematous drug rash with or without systemic involvement (DRESS) in 18 (75%), Stevens-Johnsons syndrome/toxic epidermal necrolysis (SJS/TEN) overlap and TEN in 2 (8.3%) patients each, SJS and lichenoid drug eruption in 1 (4.2%) patient each, respectively. The implicated drugs were phenytoin in 14 (58.3%), carbamazepine in 9 (37.5%), phenobarbitone in 2 (8.3%), and lamotrigine in 1 (4.7%) patients, respectively. Twelve (50%) patients elicited positive reactions to implicated drugs; carbamazepine in 6 (50%), phenytoin alone in 4 (33.3%), phenobarbitone alone in 1 (8.3%), and both phenytoin and phenobarbitone in 1 (8.33%) patients, respectively. Cross-reactions occurred in 11 (92%) patients. Six patients with carbamazepine positive patch test reaction showed cross sensitivity with phenobarbitone, sodium valproate and/or lamotrigine. Three (75%) patients among positive phenytoin patch test reactions had cross reactions with phenobarbitone, lamotrigine, and/or valproate. Carbamazepine remains the commonest anticonvulsant causing ACDRs and cross-reactions with other anticonvulsants are possible. Drug patch testing appears useful in DRESS for drug imputability and cross-reactions established clinically.

  10. Patch testing and cross sensitivity study of adverse cutaneous drug reactions due to anticonvulsants: A preliminary report

    PubMed Central

    Shiny, T N; Mahajan, Vikram K; Mehta, Karaninder S; Chauhan, Pushpinder S; Rawat, Ritu; Sharma, Rajni

    2017-01-01

    AIM To evaluate the utility of patch test and cross-sensitivity patterns in patients with adverse cutaneous drug reactions (ACDR) from common anticonvulsants. METHODS Twenty-four (M:F = 13:11) patients aged 18-75 years with ACDR from anticonvulsants were patch tested 3-27 mo after complete recovery using carbamazepine, phenytoin, phenobarbitone, lamotrigine, and sodium valproate in 10%, 20% and 30% conc. in pet. after informed consent. Positive reactions persisting on D3 and D4 were considered significant. RESULTS Clinical patterns were exanthematous drug rash with or without systemic involvement (DRESS) in 18 (75%), Stevens-Johnsons syndrome/toxic epidermal necrolysis (SJS/TEN) overlap and TEN in 2 (8.3%) patients each, SJS and lichenoid drug eruption in 1 (4.2%) patient each, respectively. The implicated drugs were phenytoin in 14 (58.3%), carbamazepine in 9 (37.5%), phenobarbitone in 2 (8.3%), and lamotrigine in 1 (4.7%) patients, respectively. Twelve (50%) patients elicited positive reactions to implicated drugs; carbamazepine in 6 (50%), phenytoin alone in 4 (33.3%), phenobarbitone alone in 1 (8.3%), and both phenytoin and phenobarbitone in 1 (8.33%) patients, respectively. Cross-reactions occurred in 11 (92%) patients. Six patients with carbamazepine positive patch test reaction showed cross sensitivity with phenobarbitone, sodium valproate and/or lamotrigine. Three (75%) patients among positive phenytoin patch test reactions had cross reactions with phenobarbitone, lamotrigine, and/or valproate. CONCLUSION Carbamazepine remains the commonest anticonvulsant causing ACDRs and cross-reactions with other anticonvulsants are possible. Drug patch testing appears useful in DRESS for drug imputability and cross-reactions established clinically. PMID:28396847

  11. Days lost due to disability of diclofenac-induced adverse drug reactions.

    PubMed

    Thomas, Dixon; Mathew, Molly; Raghavan, C Vijaya; Mohanta, Guru P; Reddy, Y Padmanabha

    2012-01-01

    Disability Adjusted Life Years (DALY) is a widely used measure to quantify the burden of diseases or illness. DALYs for a disease is calculated as the sum of the Years of Life Lost (YLL) due to premature mortality in the population and the equivalent healthy Years Lost due to Disability (YLD). The only difference from the YLD and Days Lost due to Disability (DLD) calculation is that instead of considering the duration of Adverse Drug Reaction (ADR) in years, it is calculated in days. DLD was measured for diclofenac tablets to prepare the ADR profile. The study was done on the patients (18-65 years old) attending the community pharmacy at Kasaragod district, South India, with prescription of diclofenac tablets. Patients reported ADRs on their next visit to the pharmacy or they had called to the provided phone number and reported it. Disability Weight (DW) was calculated in an analogue scale from 0-1. Zero represent complete health and 1 represent death or equivalent condition. DW was multiplied with occurrence and duration of ADRs in days. About 943 patients received diclofenac tablets in 1000 prescriptions were successfully followed up for possible, probable and definite ADRs. A total of 561 reactions reported in 2010 for diclofenac tablet in the study population. There were 34 different types of ADRs under 12 physiological systems/organs. Most common reactions were on gastrointestinal (GI) system (48%), followed by skin (14%), Central Nervous System (10%), renal (7%), and cardiovascular (7%). Abdominal pain, cramps or flatulence was the highest occurring GI ADR (107), followed by 43 rashes, 42 nausea/vomiting, 37 indigestion, 34 peptic ulcers, 31 edema etc. DLD for peptic ulcer was considerably high (0.078) per 1000 of the study population on diclofenac. The most damaging ADR were peptic ulcer with or without perforation, followed by rash 0.036 DLD and edema 0.027 DLD. There was considerable DLD by acute renal failure (0.012) Steven-Johnson syndrome (0.013) even

  12. Monitoring drug safety in Astrakhan, Russia.

    PubMed

    Kirilochev, O O; Dorfman, I P; Umerova, A R

    2015-01-01

    The problem of drug safety will never disappear as new drugs are delivered in increasing numbers. They have high biological activity and adverse drug reactions (ADR) [1]. Currently, adverse drug reactions are the fourth leading cause of death for patients.There are databases of ADRs (Vigibase, Eudravigilance), but we know that ADR manifestations may vary in different countries and regions, due to the demographic, genetic characteristics of the population and the quality of manufactured drugs [2]. In this regard, the study of the ADR at the regional level is very relevant. We aimed to optimize the work on monitoring drug safety in Astrakhan region through pharmacoepidemiological research and development of computer database for analysis of information coming to the center for drug safety monitoring (CDSM). 1. To study the rates of ADR reporting and the structure in the Astrakhan region at the regional center for drug safety monitoring.2. To analyze the outcomes of registered adverse drug reactions.3. To determine the causality of adverse drug reactions.4. To identify reports on the ineffectiveness of drugs.5. To analyze the rates and structure of ADR reporting for drugs prescribed off-label. We studied spontaneous adverse event reporting. The adverse event reports received by the regional CDSM for the period of 2010 to 2014 was analyzed. The groups of drugs were categorized according by Anatomical Therapeutic Chemical classification system. The data were analyzed using Microsoft Office Excel. The likelihood of whether an ADR was actually due to the drugs was assessed with the Naranjo algorithm. The analysis of the results showed that the establishment of the CDSM in September 2010, contributed to improvement of drug safety monitoring in health facilities of the region. Noteworthy was the increasing the number of adverse event reports in 2011 and 2012, compared with the beginning of the year 2010, when the CDSM was not yet functioning.The decrease of adverse event

  13. Ocular Adverse Events Associated with Antibody–Drug Conjugates in Human Clinical Trials

    PubMed Central

    Miller, Paul E.; Mannis, Mark J.

    2015-01-01

    Abstract This article reviews ocular adverse events (AEs) reported in association with administration of antibody–drug conjugates (ADCs) in human clinical trials. References reporting ocular toxicity or AEs associated with ADCs were collected using online publication searches. Articles, abstracts, or citations were included if they cited ocular toxicities or vision-impairing AEs with a confirmed or suspected association with ADC administration. Twenty-two references were found citing ocular or vision-impairing AEs in association with ADC administration. All references reported use of ADCs in human clinical trials for treatment of various malignancies. The molecular target and cytotoxic agent varied depending on the ADC used. Ocular AEs affected a diversity of ocular tissues. The most commonly reported AEs involved the ocular surface and included blurred vision, dry eye, and corneal abnormalities (including microcystic corneal disease). Most ocular AEs were not severe (≤ grade 2) or dose limiting. Clinical outcomes were not consistently reported, but when specified, most AEs improved or resolved with cessation of treatment or with ameliorative therapy. A diverse range of ocular AEs are reported in association with administration of ADCs for the treatment of cancer. The toxicologic mechanism(s) and pathogenesis of such events are not well understood, but most are mild in severity and reversible. Drug development and medical professionals should be aware of the clinical features of these events to facilitate early recognition and intervention in the assessment of preclinical development programs and in human clinical trials. PMID:26539624

  14. ADEPt, a semantically-enriched pipeline for extracting adverse drug events from free-text electronic health records.

    PubMed

    Iqbal, Ehtesham; Mallah, Robbie; Rhodes, Daniel; Wu, Honghan; Romero, Alvin; Chang, Nynn; Dzahini, Olubanke; Pandey, Chandra; Broadbent, Matthew; Stewart, Robert; Dobson, Richard J B; Ibrahim, Zina M

    2017-01-01

    Adverse drug events (ADEs) are unintended responses to medical treatment. They can greatly affect a patient's quality of life and present a substantial burden on healthcare. Although Electronic health records (EHRs) document a wealth of information relating to ADEs, they are frequently stored in the unstructured or semi-structured free-text narrative requiring Natural Language Processing (NLP) techniques to mine the relevant information. Here we present a rule-based ADE detection and classification pipeline built and tested on a large Psychiatric corpus comprising 264k patients using the de-identified EHRs of four UK-based psychiatric hospitals. The pipeline uses characteristics specific to Psychiatric EHRs to guide the annotation process, and distinguishes: a) the temporal value associated with the ADE mention (whether it is historical or present), b) the categorical value of the ADE (whether it is assertive, hypothetical, retrospective or a general discussion) and c) the implicit contextual value where the status of the ADE is deduced from surrounding indicators, rather than explicitly stated. We manually created the rulebase in collaboration with clinicians and pharmacists by studying ADE mentions in various types of clinical notes. We evaluated the open-source Adverse Drug Event annotation Pipeline (ADEPt) using 19 ADEs specific to antipsychotics and antidepressants medication. The ADEs chosen vary in severity, regularity and persistence. The average F-measure and accuracy achieved by our tool across all tested ADEs were 0.83 and 0.83 respectively. In addition to annotation power, the ADEPT pipeline presents an improvement to the state of the art context-discerning algorithm, ConText.

  15. An Adverse Drug Event and Medication Error Reporting System for Ambulatory Care (MEADERS)

    PubMed Central

    Zafar, Atif; Hickner, John; Pace, Wilson; Tierney, William

    2008-01-01

    The Institute of Medicine (IOM) has identified the mitigation of Adverse Drug Events (ADEs) and Medication Errors (MEs) as top national priorities. Currently available reporting tools are fraught with inefficiencies that prevent widespread adoption into busy primary care practices. Using expert panel input we designed and built a new reporting tool that could be used in these settings with a variety of information technology capabilities. We pilot tested the system in four Practice Based Research Networks (PBRNs) comprising 24 practices. Over 10 weeks we recorded 507 reports, of which 370 were MEs and 137 were ADEs. Clinicians found the system easy to use, with the average time to generating a report under 4 minutes. By using streamlined interface design techniques we were successfully able to improve reporting rates of ADEs and MEs in these practices. PMID:18999053

  16. Rare and very rare adverse effects of clozapine

    PubMed Central

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

    2015-01-01

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

  17. Adverse drug reactions in Germany: direct costs of internal medicine hospitalizations.

    PubMed

    Rottenkolber, Dominik; Schmiedl, Sven; Rottenkolber, Marietta; Farker, Katrin; Saljé, Karen; Mueller, Silke; Hippius, Marion; Thuermann, Petra A; Hasford, Joerg

    2011-06-01

    German hospital reimbursement modalities changed as a result of the introduction of Diagnosis Related Groups (DRG) in 2004. Therefore, no data on the direct costs of adverse drug reactions (ADRs) resulting in admissions to departments of internal medicine are available. The objective was to quantify the ADR-related economic burden (direct costs) of hospitalizations in internal medicine wards in Germany. Record-based study analyzing the patient records of about 57,000 hospitalizations between 2006 and 2007 of the Net of Regional Pharmacovigilance Centers (Germany). All ADRs were evaluated by a team of experts in pharmacovigilance for severity, causality, and preventability. The calculation of accurate person-related costs for ADRs relied on the German DRG system (G-DRG 2009). Descriptive and bootstrap statistical methods were applied for data analysis. The incidence of hospitalization due to at least 'possible' serious outpatient ADRs was estimated to be approximately 3.25%. Mean age of the 1834 patients was 71.0 years (SD 14.7). Most frequent ADRs were gastrointestinal hemorrhage (n = 336) and drug-induced hypoglycemia (n = 270). Average inpatient length-of-stay was 9.3 days (SD 7.1). Average treatment costs of a single ADR were estimated to be approximately €2250. The total costs sum to €434 million per year for Germany. Considering the proportion of preventable cases (20.1%), this equals a saving potential of €87 million per year. Preventing ADRs is advisable in order to realize significant nationwide savings potential. Our cost estimates provide a reliable benchmark as they were calculated based on an intensified ADR surveillance and an accurate person-related cost application. Copyright © 2011 John Wiley & Sons, Ltd.

  18. Drug-induced liver injury is frequently associated with severe cutaneous adverse drug reactions: experience from two Australian tertiary hospitals.

    PubMed

    Fang, Wendy C; Adler, Nikki R; Graudins, Linda V; Goldblatt, Caitlin; Goh, Michelle S Y; Roberts, Stuart K; Trubiano, Jason A; Aung, Ar Kar

    2018-05-01

    Drug-induced liver injury (DILI) can be associated with certain cutaneous adverse drug reaction (cADR). To demonstrate the prevalence of DILI in patients with cADRs. Severity and patterns of liver injury, risk factors, causal medications and outcomes are also examined. A retrospective cohort study of patients with cADRs was conducted across two hospitals in Australia. Patients were identified through cross-linkage of multiple databases. One hundred and four patients with cADRs were identified. Of these, 33 (31.7%) had liver injury, representing 50% of patients with drug reaction with eosinophilia and systemic symptoms, and 30.2% of patients with Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Most cases of liver injury (69.7%) were of a cholestatic/mixed pattern with severe disease in 18.2%. No significant risk factors for development of liver injury were noted, but peripheral lymphocytosis may represent a risk in patients with SJS (odds ratio, OR = 6.0, 95% confidence interval, CI: 1.8-19.7, P = 0.003). Antimicrobials were the most common class to be implicated in DILI. The median length of inpatient stay was longer in patients with liver injury compared to those without (19 vs 11 days, P = 0.002). The mortality rate in those with liver injury was 15.2% and 9.9% in those without. No patients required liver transplantation. DILI commonly occurs in patients with cADRs and is associated with longer inpatient stay. Patients with SJS/TEN and peripheral lymphocytosis appear to be at higher risk for developing associated liver injury. © 2018 Royal Australasian College of Physicians.

  19. Species differences in drug glucuronidation: Humanized UDP-glucuronosyltransferase 1 mice and their application for predicting drug glucuronidation and drug-induced toxicity in humans

    PubMed Central

    Fujiwara, Ryoichi; Yoda, Emiko; Tukey, Robert H.

    2018-01-01

    More than 20% of clinically used drugs are glucuronidated by a microsomal enzyme UDP-glucuronosyltransferase (UGT). Inhibition or induction of UGT can result in an increase or decrease in blood drug concentration. To avoid drug-drug interactions and adverse drug reactions in individuals, therefore, it is important to understand whether UGTs are involved in metabolism of drugs and drug candidates. While most of glucuronides are inactive metabolites, acyl-glucuronides that are formed from compounds with a carboxylic acid group can be highly toxic. Animals such as mice and rats are widely used to predict drug metabolism and drug-induced toxicity in humans. However, there are marked species differences in the expression and function of drug-metabolizing enzymes including UGTs. To overcome the species differences, mice in which certain drug-metabolizing enzymes are humanized have been recently developed. Humanized UGT1 (hUGT1) mice were created in 2010 by crossing Ugt1-null mice with human UGT1 transgenic mice in a C57BL/6 background. hUGT1 mice can be promising tools to predict human drug glucuronidation and acyl-glucuronide-associated toxicity. In this review article, studies of drug metabolism and toxicity in the hUGT1 mice are summarized. We further discuss research and strategic directions to advance the understanding of drug glucuronidation in humans. PMID:29079228

  20. Exposure to Prescription Drugs Labeled for Risk of Adverse Effects of Suicidal Behavior or Ideation among 100 Air Force Personnel Who Died by Suicide, 2006-2009

    ERIC Educational Resources Information Center

    Lavigne, Jill E.; McCarthy, Michael; Chapman, Richard; Petrilla, Allison; Knox, Kerry L.

    2012-01-01

    Prescription drugs for many indications are labeled with warnings for potential risk of suicidal ideation or behavior. Exposures to prescription drugs labeled for adverse effects of suicidal behavior or ideation among 100 Air Force personnel who died by suicide between 2006 and 2009 are described. Air Force registry data were linked to…

  1. 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.

  2. Adverse Effects of Nutraceuticals and Dietary Supplements.

    PubMed

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

    2018-01-06

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

  3. Methodological Considerations for Comparison of Brand Versus Generic Versus Authorized Generic Adverse Event Reports in the US Food and Drug Administration Adverse Event Reporting System (FAERS).

    PubMed

    Rahman, Md Motiur; Alatawi, Yasser; Cheng, Ning; Qian, Jingjing; Peissig, Peggy L; Berg, Richard L; Page, David C; Hansen, Richard A

    2017-12-01

    The US Food and Drug Administration Adverse Event Reporting System (FAERS), a post-marketing safety database, can be used to differentiate brand versus generic safety signals. To explore the methods for identifying and analyzing brand versus generic adverse event (AE) reports. Public release FAERS data from January 2004 to March 2015 were analyzed using alendronate and carbamazepine as examples. Reports were classified as brand, generic, and authorized generic (AG). Disproportionality analyses compared reporting odds ratios (RORs) of selected known labeled serious adverse events stratifying by brand, generic, and AG. The homogeneity of these RORs was compared using the Breslow-Day test. The AG versus generic was the primary focus since the AG is identical to brand but marketed as a generic, therefore minimizing generic perception bias. Sensitivity analyses explored how methodological approach influenced results. Based on 17,521 US event reports involving alendronate and 3733 US event reports involving carbamazepine (immediate and extended release), no consistently significant differences were observed across RORs for the AGs versus generics. Similar results were obtained when comparing reporting patterns over all time and just after generic entry. The most restrictive approach for classifying AE reports yielded smaller report counts but similar results. Differentiation of FAERS reports as brand versus generic requires careful attention to risk of product misclassification, but the relative stability of findings across varying assumptions supports the utility of these approaches for potential signal detection.

  4. A 3-armed randomized controlled trial of nurses' continuing education meetings on adverse drug reactions.

    PubMed

    Sarayani, Amir; Naderi-Behdani, Fahimeh; Hadavand, Naser; Javadi, Mohammadreza; Farsad, Fariborz; Hadjibabaie, Molouk; Gholami, Kheirollah

    2015-01-01

    Nurses' insufficient knowledge of adverse drug reactions is reported as a barrier to spontaneous reporting. Therefore, CE meetings could be utilized to enhance nurses' competencies. In a 3-armed randomized controlled trial, 496 nurses, working in a tertiary medical center, were randomly allocated to a didactic lecture, brainstorming workshop, or the control group (delayed education). Similar instructors (2 clinical pharmacists) prepared and delivered the educational content to all 3 groups. Outcomes were declarative/procedural knowledge (primary outcome), participation rate, and satisfaction. Knowledge was evaluated using a validated researcher-made questionnaire in 3 time points: immediately before, immediately after, and 3 months after each session. Participants' satisfaction was assessed immediately after each meeting via a standard tool. Data were analyzed using appropriate parametric and nonparametric tests. Rate of participation was 37.7% for the lecture group and 47.5% for the workshop group. The workshop participants were significantly more satisfied in comparison with the lecture group (p < .05). Mean knowledge scores were similar at baseline in the 3 study groups (43-47). Immediately after the meeting, knowledge was significantly higher in the lecture group (79.1 ± 11.9 vs 73.7 ± 11.3; p = .01). At the follow-up, knowledge scores of the lecture and workshop groups were similar, while significantly higher than the control group. However, the reduction of knowledge score was significantly higher in the lecture group (-13.0 ± 15.9% vs -5.7 ± 15.1%, p = .02). Educational interventions can improve nurses' knowledge of adverse drug reactions. Short-term learning could be achieved with lecture, but the retention of knowledge will be enhanced by simple interactive techniques. © 2015 The Alliance for Continuing Education in the Health Professions, the Society for Academic Continuing Medical Education, and the Council on Continuing Medical Education

  5. Drug metabolism and hypersensitivity reactions to drugs.

    PubMed

    Agúndez, José A G; Mayorga, Cristobalina; García-Martin, Elena

    2015-08-01

    The aim of the present review was to discuss recent advances supporting a role of drug metabolism, and particularly of the generation of reactive metabolites, in hypersensitivity reactions to drugs. The development of novel mass-spectrometry procedures has allowed the identification of reactive metabolites from drugs known to be involved in hypersensitivity reactions, including amoxicillin and nonsteroidal antiinflammatory drugs such as aspirin, diclofenac or metamizole. Recent studies demonstrated that reactive metabolites may efficiently bind plasma proteins, thus suggesting that drug metabolites, rather than - or in addition to - parent drugs, may elicit an immune response. As drug metabolic profiles are often determined by variability in the genes coding for drug-metabolizing enzymes, it is conceivable that an altered drug metabolism may predispose to the generation of reactive drug metabolites and hence to hypersensitivity reactions. These findings support the potential for the use of pharmacogenomics tests in hypersensitivity (type B) adverse reactions, in addition to the well known utility of these tests in type A adverse reactions. Growing evidence supports a link between genetically determined drug metabolism, altered metabolic profiles, generation of highly reactive metabolites and haptenization. Additional research is required to developing robust biomarkers for drug-induced hypersensitivity reactions.

  6. Adverse effects of antiretroviral therapy for HIV infection.

    PubMed

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

    2004-01-20

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

  7. Adverse effects of antiretroviral therapy for HIV infection

    PubMed Central

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

    2004-01-01

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

  8. Dietary Supplement Adverse Event Report Data From the FDA Center for Food Safety and Applied Nutrition Adverse Event Reporting System (CAERS), 2004-2013.

    PubMed

    Timbo, Babgaleh B; Chirtel, Stuart J; Ihrie, John; Oladipo, Taiye; Velez-Suarez, Loy; Brewer, Vickery; Mozersky, Robert

    2018-05-01

    The Food and Drug Administration (FDA)'s Center for Food Safety and Applied Nutrition (CFSAN) oversees the safety of the nation's foods, dietary supplements, and cosmetic products. To present a descriptive analysis of the 2004-2013 dietary supplement adverse event report (AER) data from CAERS and evaluate the 2006 Dietary Supplements and Nonprescription Drug Consumer Protection Act as pertaining to dietary supplements adverse events reporting. We queried CAERS for data from the 2004-2013 AERs specifying at least 1 suspected dietary supplement product. We extracted the product name(s), the symptom(s) reported, age, sex, and serious adverse event outcomes. We examined time trends for mandatory and voluntary reporting and performed analysis using SAS v9.4 and R v3.3.0 software. Of the total AERs (n = 15 430) received from January 1, 2004, through December 31, 2013, indicating at least 1 suspected dietary supplement product, 66.9% were mandatory, 32.2% were voluntary, and 0.9% were both mandatory and voluntary. Reported serious outcomes included death, life-threatening conditions, hospitalizations, congenital anomalies/birth defects and events requiring interventions to prevent permanent impairments (5.1%). The dietary supplement adverse event reporting rate in the United States was estimated at ~2% based on CAERS data. This study characterizes CAERS dietary supplement adverse event data for the 2004-2013 period and estimates a reporting rate of 2% for dietary supplement adverse events based on CAERS data. The findings show that the 2006 Dietary Supplements and Nonprescription Drug Consumer Protection Act had a substantial impact on the reporting of adverse events.

  9. Drug skin tests in cutaneous adverse drug reactions to pristinamycin: 29 cases with a study of cross-reactions between synergistins.

    PubMed

    Barbaud, A; Trechot, P; Weber-Muller, F; Ulrich, G; Commun, N; Schmutz, J L

    2004-01-01

    The present study was made to determine the value of drug skin tests in patients with cutaneous adverse drug reactions (CADRs) due to a synergistin (pristinamycin) and to determine the frequency of cross-reactions between synergistins. 29 patients were referred during the onset of the CADR due to pristinamycin: 18 with maculopapular rash, 9 erythrodermas, 1 angioedema and 1 Stevens-Johnson syndrome. They all had patch tests with pristinamycin and, in most cases, with other synergistins [virginiamycin and dalfopristin-quinupristin (DQ)], prick tests (10 cases) and intradermal tests (IDT) (5 cases). Skin tests with synergistins were positive in 27 cases, patch tests with pristinamycin in 20/29 cases (69%), prick tests with pristinamycin in 3/9 cases on immediate (1 case) or on delayed (2 cases) readings, and IDT with DQ in 4/5 cases. Cross-reactions between synergistins occurred in 9/22 with virginiamycin and in 7/8 cases with DQ. Skin tests with synergistins are useful in investigating CADR due to pristinamycin. Synergistins are composed of 2 chains (1 depsipeptide and 1 macrocyclic lactone) with many structural analogies between all synergistins. According to the chemical structures and our results, it seems advisable to avoid all synergistins in patients with CADR due to pristinamycin.

  10. Suspected adverse drug reaction reports with oral anticoagulants in Portugal: a pharmacovigilance study.

    PubMed

    Caldeira, Daniel; Rodrigues, Raquel; Abreu, Daisy; Anes, Ana Marta; Rosa, Mário M; Ferreira, Joaquim J

    2018-04-01

    In this pharmacovigilance study, we aimed to determine the incidence of spontaneously reported suspected adverse drug reactions (ADRs) related to oral anticoagulants: non-vitamin K antagonist oral anticoagulants (NOACs; apixaban, dabigatran, edoxaban, rivaroxaban) and vitamin K antagonists (VKA) Research design and methods: In this retrospective observational study, we extracted all the individual case safety reports related to oral anticoagulants recorded in the Portuguese Pharmacovigilance Database (January 2010 to April 2015). The annual incidence of suspected ADRs was estimated using drug exposure data. Disproportionality of reporting ADR was addressed through reporting odds ratio (ROR) and 99% confidence intervals. We appraised 794 suspected ADR (78% related to NOACs). The annual number of ADRs increased overtime with 9 ADRs/million Defined Daily Dose (DDD) at the end of 2014. The incidence of NOACs ADRs decreased from 2012 onwards. VKA showed a disproportion in 'Investigation' (ROR 0.10, 99%CI 0.05-0.22) and 'Injury, poisoning and procedural complications' (ROR 0.36, 99%CI 0.19-0.69) ADRs compared with NOACs. NOACs had a higher significant disproportion of 'Nervous system disorders' related ADRs (ROR 3.98, 99%CI 1.50-10.53). Reporting of ADRs associated with oral anticoagulants (mainly NOACs), is increasing. Exploratory disproportion analyses showed an increase of reports of nervous system ADRs with NOACs, and INR-related ADRs with VKA.

  11. Attitudes and knowledge of hospital pharmacists to adverse drug reaction reporting

    PubMed Central

    Green, Christopher F; Mottram, David R; Rowe, Philip H; Pirmohamed, Munir

    2001-01-01

    Aims To investigate the attitudes of UK hospital pharmacists towards, and their understanding, of adverse drug reaction (ADR) reporting. Methods A postal questionnaire survey of 600 randomly selected hospital pharmacists was conducted. Results The response rate was 53.7% (n = 322). A total of 217 Yellow Cards had been submitted to the CSM/MCA by 78 (25.6%) of those responding. Half of those responding felt that ADR reporting should be compulsory and over three-quarters felt it was a professional obligation. However, almost half were unclear as to what should be reported, while the time available in clinical practice and time taken to complete forms were deemed to be major deterrents to reporting. Pharmacists were not dissuaded from reporting by the need to consult a medical colleague or by the absence of a fee. Education and training had a significant influence on pharmacists' participation in the Yellow Card Scheme. Conclusions Pharmacists have a reasonable knowledge and are supportive of the Yellow Card spontaneous ADR reporting scheme. However, education and training will be important in maintaining and increasing ADR reports from pharmacists. PMID:11167664

  12. Adverse drug events with hyperkalaemia during inpatient stays: evaluation of an automated method for retrospective detection in hospital databases.

    PubMed

    Ficheur, Grégoire; Chazard, Emmanuel; Beuscart, Jean-Baptiste; Merlin, Béatrice; Luyckx, Michel; Beuscart, Régis

    2014-09-12

    Adverse drug reactions and adverse drug events (ADEs) are major public health issues. Many different prospective tools for the automated detection of ADEs in hospital databases have been developed and evaluated. The objective of the present study was to evaluate an automated method for the retrospective detection of ADEs with hyperkalaemia during inpatient stays. We used a set of complex detection rules to take account of the patient's clinical and biological context and the chronological relationship between the causes and the expected outcome. The dataset consisted of 3,444 inpatient stays in a French general hospital. An automated review was performed for all data and the results were compared with those of an expert chart review. The complex detection rules' analytical quality was evaluated for ADEs. In terms of recall, 89.5% of ADEs with hyperkalaemia "with or without an abnormal symptom" were automatically identified (including all three serious ADEs). In terms of precision, 63.7% of the automatically identified ADEs with hyperkalaemia were true ADEs. The use of context-sensitive rules appears to improve the automated detection of ADEs with hyperkalaemia. This type of tool may have an important role in pharmacoepidemiology via the routine analysis of large inter-hospital databases.

  13. Prediction of Hospitalization due to Adverse Drug Reactions in Elderly Community-Dwelling Patients (The PADR-EC Score)

    PubMed Central

    Parameswaran Nair, Nibu; Chalmers, Leanne; Connolly, Michael; Bereznicki, Bonnie J.; Peterson, Gregory M.; Curtain, Colin; Castelino, Ronald L.; Bereznicki, Luke R.

    2016-01-01

    Background Adverse drug reactions (ADRs) are the major cause of medication-related hospital admissions in older patients living in the community. This study aimed to develop and validate a score to predict ADR-related hospitalization in people aged ≥65 years. Methods ADR-related hospitalization and its risk factors were determined using a prospective, cross-sectional study in patients aged ≥65 years admitted to two hospitals. A predictive model was developed in the derivation cohort (n = 768) and the model was applied in the validation cohort (n = 240). ADR-related hospital admission was determined through expert consensus from comprehensive reviews of medical records and patient interviews. The causality and preventability of the ADR were assessed based on the Naranjo algorithm and modified Schumock and Thornton criteria, respectively. Results In the derivation sample (mean [±SD] age, 80.1±7.7 years), 115 (15%) patients were admitted due to a definite or probable ADR; 92.2% of these admissions were deemed preventable. The number of antihypertensives was the strongest predictor of an ADR followed by presence of dementia, renal failure, drug changes in the preceding 3 months and use of anticholinergic medications; these variables were used to derive the ADR prediction score. The predictive ability of the score, assessed from calculation of the area under the receiver operator characteristic (ROC) curve, was 0.70 (95% confidence interval (CI) 0.65–0.75). In the validation sample (mean [±SD] age, 79.6±7.6 years), 30 (12.5%) patients’ admissions were related to definite or probable ADRs; 80% of these admissions were deemed preventable. The area under the ROC curve in this sample was 0.67 (95% CI 0.56–0.78). Conclusions This study proposes a practical and simple tool to identify elderly patients who are at an increased risk of preventable ADR-related hospital admission. Further refinement and testing of this tool is necessary to implement the score in

  14. Ci4SeR--curation interface for semantic resources--evaluation with adverse drug reactions.

    PubMed

    Souvignet, Julien; Asfari, Hadyl; Declerck, Gunnar; Lardon, Jérémy; Trombert-Paviot, Béatrice; Jaulent, Marie-Christine; Bousquet, Cédric

    2014-01-01

    Evaluation and validation have become a crucial problem for the development of semantic resources. We developed Ci4SeR, a Graphical User Interface to optimize the curation work (not taking into account structural aspects), suitable for any type of resource with lightweight description logic. We tested it on OntoADR, an ontology of adverse drug reactions. A single curator has reviewed 326 terms (1020 axioms) in an estimated time of 120 hours (2.71 concepts and 8.5 axioms reviewed per hour) and added 1874 new axioms (15.6 axioms per hour). Compared with previous manual endeavours, the interface allows increasing the speed-rate of reviewed concepts by 68% and axiom addition by 486%. A wider use of Ci4SeR would help semantic resources curation and improve completeness of knowledge modelling.

  15. Synthetic cannabinoids: the hidden side of Spice drugs.

    PubMed

    Pintori, Nicholas; Loi, Barbara; Mereu, Maddalena

    2017-09-01

    Spice drugs are herbal mixtures sprayed with synthetic cannabinoids designed to mimic the psychoactive ingredient in marijuana [Δ-tetrahydrocannabinol (Δ-THC)] and synthesized by introducing modifications to the chemical structure of parental compounds aiming to circumvent legal regulations. Synthetic cannabinoid use/abuse can be devastating as toxicological effects and adverse reactions cannot be entirely predicted and may vary with the dose, route of administration, individual vulnerability and concomitant intake with other drugs. The absence of validated testing procedures in the clinical field makes difficult the adoption of a therapeutic approach effective in coping with the synthetic cannabinoid phenomenon, posing a significant challenge for prevention, treatment and public health in general. The aim of this review is to gain insights into the epidemiological, pharmacological and toxicological properties of synthetic cannabinoids, aiming to provide a reliable background needed for the management of synthetic cannabinoid-related adverse effects. Consumers, competent authorities and medical care professionals should be aware of the risks associated with synthetic cannabinoid use.

  16. Adverse drug event-related emergency department visits associated with complex chronic conditions.

    PubMed

    Feinstein, James A; Feudtner, Chris; Kempe, Allison

    2014-06-01

    Outpatient adverse drug events (ADEs) can result in serious outcomes requiring emergency department (ED) visits and hospitalizations. The incidence and severity of ADEs in children with complex chronic conditions (CCCs), who often take multiple medications, is unknown. We sought to describe the characteristics of ADE-related ED visits, including association with CCC status; determine the implicated medications; and determine if CCC status increased the risk of ADE-related admission. Retrospective cohort study of ED visits by patients aged 0 to 18 years using a national sample. ADEs were identified by external cause of injury codes; cases with overdose, wrongful administration, self-harm, or diagnosis of malignancy were excluded. Multivariable logistic regression was used to test outcomes of having an ADE-related ED visit and of subsequent admission. All statistics accounted for the complex survey design. Of 144 million ED visits, 0.5% were associated with ADEs. Adjusting for age, gender, insurance type, day of week, and location of hospital, ADEs were associated with the presence of a CCC (odds ratio 4.76; 95% confidence interval: 4.45-5.10). The implicated medications differed significantly by CCC status. Adjusting for the same variables, ADEs were associated with subsequent inpatient admission (odds ratio 2.18; 95% confidence interval: 2.04-2.32) for all children; an interaction between ADE and CCC status was not significant. ED visits associated with ADEs were more likely to occur for children with CCCs, and the implicated drugs differed, but ADE-related admissions were not differentially affected by CCC status. Copyright © 2014 by the American Academy of Pediatrics.

  17. Adverse Drug Reaction Identification and Extraction in Social Media: A Scoping Review.

    PubMed

    Lardon, Jérémy; Abdellaoui, Redhouane; Bellet, Florelle; Asfari, Hadyl; Souvignet, Julien; Texier, Nathalie; Jaulent, Marie-Christine; Beyens, Marie-Noëlle; Burgun, Anita; Bousquet, Cédric

    2015-07-10

    The underreporting of adverse drug reactions (ADRs) through traditional reporting channels is a limitation in the efficiency of the current pharmacovigilance system. Patients' experiences with drugs that they report on social media represent a new source of data that may have some value in postmarketing safety surveillance. A scoping review was undertaken to explore the breadth of evidence about the use of social media as a new source of knowledge for pharmacovigilance. Daubt et al's recommendations for scoping reviews were followed. The research questions were as follows: How can social media be used as a data source for postmarketing drug surveillance? What are the available methods for extracting data? What are the different ways to use these data? We queried PubMed, Embase, and Google Scholar to extract relevant articles that were published before June 2014 and with no lower date limit. Two pairs of reviewers independently screened the selected studies and proposed two themes of review: manual ADR identification (theme 1) and automated ADR extraction from social media (theme 2). Descriptive characteristics were collected from the publications to create a database for themes 1 and 2. Of the 1032 citations from PubMed and Embase, 11 were relevant to the research question. An additional 13 citations were added after further research on the Internet and in reference lists. Themes 1 and 2 explored 11 and 13 articles, respectively. Ways of approaching the use of social media as a pharmacovigilance data source were identified. This scoping review noted multiple methods for identifying target data, extracting them, and evaluating the quality of medical information from social media. It also showed some remaining gaps in the field. Studies related to the identification theme usually failed to accurately assess the completeness, quality, and reliability of the data that were analyzed from social media. Regarding extraction, no study proposed a generic approach to easily

  18. Pharmacy student perceptions of adverse event reporting.

    PubMed

    Kalari, Sirisha; Dormarunno, Matthew; Zvenigorodsky, Oleg; Mohan, Aparna

    2011-09-10

    To assess US pharmacy students' knowledge and perceptions of adverse event reporting. To gauge pharmacy students' impressions of adverse event reporting, a 10-question survey instrument was administered that addressed student perceptions of the reporting procedures of the Food and Drug Administration (FDA) and pharmaceutical manufacturers, as well as student understanding of the Health Insurance Portability and Accountability Act (HIPAA) and its relationship to adverse event reporting. Two hundred twenty-eight pharmacy students responded to the survey. The majority of respondents believed that the FDA is more likely than a pharmaceutical company to take action regarding an adverse event. There were misconceptions relating to the way adverse event reports are handled and the influence of HIPAA regulations on reporting. Communication between the FDA and pharmaceutical manufacturers regarding adverse event reports is not well understood by pharmacy students. Education about adverse event reporting should evolve so that by the time pharmacy students become practitioners, they are well acquainted with the relevance and importance of adverse event reporting.

  19. Adverse drug reactions of non-opioid and opioid analgesics reported to Croatian national authority from 2007 to 2014.

    PubMed

    Sunara, Petra; Krnic, Darko; Puljak, Livia

    2017-11-01

    Adverse drug reactions (ADRs) are commonly observed in the health services because of system weaknesses and individual errors. Analgesics are widely used and it can be expected that with the increased use one can expect increased number of ADRs of analgesics. The aim of this study was to analyze ADRs of non-opioid and opioid analgesics reported to the Croatian Agency for Medicinal Products and Medical Devices (HALMED) from 2007 to 2014. HALMED provided data on generic drug name, year of the ADR report, type of report, institution, reporting person, patient's age, sex and ADR type. In the analyzed period 796 ADRs of analgesics were reported, of which 367 (46%) were serious ADRs. Number of ADR reports was continuously increasing during the analyzed period. There were 20 analgesics that had ≥5 reports, making 597 (75%) of all ADR reports for analgesics. The most common adverse reaction reports of those 20 analgesics referred to individual drugs (n=16; 80%). Most of the ADR reports were filed by physicians (n=257; 43%), followed by pharmacists (n=252; 42%). Most side effects (n=572; 96%) were reported spontaneously through appropriate forms by patients or health professionals. ADRs were most commonly reported in women (n=352; 59%) and most of them have occurred in adults (n=354; 59%). The most common ADRs of opioid and non-opioid analgesics have been reported on the skin and mucous membranes. Most serious ADRs were result of action of opioid analgesics. Number of ADR reports in Croatia is continuously increasing and a considerable number of them refers to serious ADRs. To keep better track of medications and ADRs it is necessary to educate and encourage health professionals and patients in reporting side effects. Copyright © 2017 by Academy of Sciences and Arts of Bosnia and Herzegovina.

  20. 10-Year analysis of adverse event reports to the Food and Drug Administration for phosphodiesterase type-5 inhibitors.

    PubMed

    Lowe, Gregory; Costabile, Raymond A

    2012-01-01

    To ensure public safety all Food and Drug Administration (FDA)-approved medications undergo postapproval safety analysis. Phosphodiesterase type-5 inhibitors (PDE5-i) are generally regarded as safe and effective. We performed a nonindustry-sponsored analysis of FDA reports for sildenafil, tadalafil, and vardenafil to evaluate the reported cardiovascular and mortality events over the past 10 years. Summarized reports of adverse events (AEs) for each PDE5-i were requested from the Center for Drug Evaluation and Research within the FDA. These data are available under the Freedom of Information Act and document industry and nonindustry reports of AEs entered into the computerized system maintained by the Office of Surveillance and Epidemiology. The data were analyzed for the number of AE reports, number of objective cardiovascular events, and reported deaths. Overall, 14,818 AEs were reported for sildenafil. There were 1,824 (12.3%) reported deaths, and reports of cardiovascular AEs numbered 2,406 (16.2%). Tadalafil was associated with 5,548 AEs and 236 deaths were reported. Vardenafil was associated with 6,085 AEs and 121 reports of deaths. The percentage of reported severe cardiovascular disorders has stabilized at 10% to 15% of all AE reports for sildenafil and tadalafil and 5% to 10% for vardenafil. Only 10% of AE reports sent to the FDA for PDE5-i were from pharmaceutical manufacturers. Reports of deaths associated with PDE5-i remain around 5% of total reported events. Despite inherent limitations from evaluating FDA reports of AEs, it is important that these reports be reviewed outside pharmaceutical industry support in order to provide due diligence and transparency. Lowe G and Costabile RA. 10-year analysis of adverse event reports to the Food and Drug Administration for phosphodiesterase type-5 inhibitors. J Sex Med 2012;9:265-270. © 2011 International Society for Sexual Medicine.

  1. Adverse drug events-Analysis of a decade. A Portuguese case-study, from 2004 to 2013 using hospital database.

    PubMed

    Scripcaru, Gianina; Mateus, Ceu; Nunes, Carla

    2017-01-01

    The goal of this study was to characterise adverse drug events (ADE), including both adverse drug reaction (ADR) and accidental poisoning by drugs (AP), considering age, gender, length of stay (LOS), number of deaths and year, during the period 2004-2013. Additionally distributions of the ten's most frequent ADR and AP were characterized, considering age-group and gender. A retrospective descriptive nationwide study was conducted, based on the hospital discharges database in Portugal from 2004 to 2013, using ICD-9. Events were identified based on the following codes: from E930 to E949.9 and from E850 to E858.9. A total of 9 320 076 patients were discharged within this period, with 133 688 patients (1.46%) having at least one ADE, 4% of them related with AP. The mean age of these patients was 63.79 years (SD 21.31), 54.50% were female and the mean LOS was 14.05 days (SD 22.19). Patient with AP had a mean age of 41.06 years (SD 34.05), 54.70% were female and LOS was 7.15 days (SD 19.42). We have identified 10.691 deaths that represent 8.00% from the total of patients with an ADE. The patients above 65 years were more affected by ADR and children below 18 were more affected by AP. In the last decade an increasing trend of ADR were observed and an AP pattern relatively stable. Elderly people and children were the age groups most affected. Antibiotics (in ADR) and benzodiazepine-based tranquilizers (in AP) were the major problems. This is a huge, increasing and challenging problem. Further research, using individual and contextual risk factors should be developed to understand spatiotemporal variability, promoting tailored interventions, within and across countries.

  2. E-pharmacovigilance: development and implementation of a computable knowledge base to identify adverse drug reactions.

    PubMed

    Neubert, Antje; Dormann, Harald; Prokosch, Hans-Ulrich; Bürkle, Thomas; Rascher, Wolfgang; Sojer, Reinhold; Brune, Kay; Criegee-Rieck, Manfred

    2013-09-01

    Computer-assisted signal generation is an important issue for the prevention of adverse drug reactions (ADRs). However, due to poor standardization of patients' medical data and a lack of computable medical drug knowledge the specificity of computerized decision support systems for early ADR detection is too low and thus those systems are not yet implemented in daily clinical practice. We report on a method to formalize knowledge about ADRs based on the Summary of Product Characteristics (SmPCs) and linking them with structured patient data to generate safety signals automatically and with high sensitivity and specificity. A computable ADR knowledge base (ADR-KB) that inherently contains standardized concepts for ADRs (WHO-ART), drugs (ATC) and laboratory test results (LOINC) was built. The system was evaluated in study populations of paediatric and internal medicine inpatients. A total of 262 different ADR concepts related to laboratory findings were linked to 212 LOINC terms. The ADR knowledge base was retrospectively applied to a study population of 970 admissions (474 internal and 496 paediatric patients), who underwent intensive ADR surveillance. The specificity increased from 7% without ADR-KB up to 73% in internal patients and from 19.6% up to 91% in paediatric inpatients, respectively. This study shows that contextual linkage of patients' medication data with laboratory test results is a useful and reasonable instrument for computer-assisted ADR detection and a valuable step towards a systematic drug safety process. The system enables automated detection of ADRs during clinical practice with a quality close to intensive chart review. © 2013 The Authors. British Journal of Clinical Pharmacology © 2013 The British Pharmacological Society.

  3. Pattern of adverse events of antiepileptic drugs: results of the aESCAPE study in Poland

    PubMed Central

    Chmielewska, Barbara; Lis, Krystyna; Rejdak, Konrad; Balcerzak, Marcin

    2013-01-01

    Introduction The Adverse Event Scale in Patients With Epilepsy (aESCAPE) European study (NCT00394927) explored and analyzed adverse events (AEs) and reasons for modifying treatment in patients treated with newer and older antiepileptic drugs (AEDs) used in monotherapy or polytherapy. The present analysis concerns the results of patients recruited in Poland. Material and methods Multicentre, international, observational, cross-sectional study investigating AEs in patients with epilepsy (aged ≥ 4 years), on stable AED treatment with one or two AED(s) for ≥ 3 months, using standardized questionnaires completed by a physician during a single study visit. Results Out of 309 patients, 24.6% were treated exclusively with newer AED(s) in monotherapy or in combination, while 75.4% were treated with older AED(s) or a combination of older and newer AED(s). 60.8% were on monotherapy, and 39.9% on polytherapy. In general, 73.8% of patients reported ≥ 1 AE(s). There were no significant differences in the frequency of reported AEs in compared groups. The most common were disturbances in cognitive function (40.5%), psychological problems (36.2%), and sedation (32.7%). Some AEs were found to be more specific for particular types and treatment regimens. Changes in treatment or dose during the study visit occurred in 22.3% of the patients, mainly due to lack of efficacy (10.7%), AEs (5.2%) or absence of seizures (4.5%). Conclusions A detailed structured interview revealed high frequency of AEs in patients treated with AEDs. The main reasons for treatment modifications at the study visit were lack of efficacy, adverse events and absence of seizures. PMID:24273570

  4. Experiences from consumer reports on psychiatric adverse drug reactions with antidepressant medication: a qualitative study of reports to a consumer association.

    PubMed

    Vilhelmsson, Andreas; Svensson, Tommy; Meeuwisse, Anna; Carlsten, Anders

    2012-12-23

    The new European pharmacovigilance legislation has been suggested as marking the beginning of a new chapter in drug safety, making patients an important part of pharmacovigilance. In Sweden since 2008 it has been possible for consumers to report adverse drug reactions (ADRs) to the Medical Products Agency (MPA), and these reports are now understood as an increasingly valuable contribution in the monitoring of safety aspects in medicines. Already in 2002 it was possible to report experiences with medicines to the non-profit and independent organization Consumer Association for Medicines and Health (KILEN) through a web-based report form with an opportunity to describe ADR experiences in free text comments. The aim of this study was to qualitatively analyze the free text comments appended to consumer reports on antidepressant medication. All reports of suspected adverse reactions regarding antidepressant medications submitted from January 2002 to April 2009 to KILEN's Internet-based reporting system in Sweden were analyzed according to reported narrative experience(s). Content analysis was used to interpret the content of 181 reports with free text comments. Three main categories emerged from the analyzed data material: (1) Experiences of drug treatment with subcategories (a) Severe psychiatric adverse reactions, and (b) Discontinuation symptoms; (2) Lack of communication and (3) Trust and distrust. A majority of the reports to KILEN were from patients experiencing symptoms of mental disturbances (sometimes severe) affecting them in many different ways, especially during discontinuation. Several report included narratives of patients not receiving information of potential ADRs from their doctor, but also that there were no follow-ups of the treatment. Trust was highlighted as especially important and some patients reported losing confidence in their doctor when they were not believed about the suspected ADRs they experienced, making them attempt to discontinue their

  5. Adverse drug reaction reporting among health care workers at Mulago National Referral and Teaching hospital in Uganda.

    PubMed

    Katusiime, Barbra; Semakula, Daniel; Lubinga, Solomon J

    2015-12-01

    Adverse Drug Reactions (ADRs) are an important contributor to patient morbidity and hospitalisation in Uganda. Under-reporting of ADRs may increase medicine-induced morbidity and mortality among patients. This study determined the extent of ADR reporting, and associated factors, among healthcare workers in Uganda. A quantitative, cross-sectional, study was conducted. Pretested, semi-structured questionnaires were administered to 289 randomly sampled healthcare workers over a three-month period in Mulago National Referral Hospital, Uganda. The primary outcome was the proportion of healthcare workers who had ever reported an ADR. Data was double-entered in Epidata version 3.0, cleaned and exported to STATA version 10.1 for analysis. The overall response rate was 77.2% (n=223). The majority of the respondents were females (139, 62.3%). The median age of all respondents was 32.6 years (min-23; max-65). Only about 16.6% (n=37) of healthcare workers had ever reported an ADR. Very few (n= 84, 37.7%) healthcare workers knew the tools used in ADR reporting. Less than a quarter (n=41, 18.4%) of the healthcare workers knew where to report ADRs. Lack of training was reported as the major (56.5%, 126) deterrent to reporting ADRs by healthcare workers. Adverse drug reactions are under-reported in Uganda, and healthcare workers have insufficient knowledge of existing pharmacovigilance systems, including ADR reporting systems. To address these challenges, there is need to sensitize and train healthcare workers in patient-centred aspects of medicine surveillance, so as to provide appropriate care while optimising patient safety.

  6. Use and Perceived Benefits of Mobile Devices by Physicians in Preventing Adverse Drug Events in the Nursing Home

    PubMed Central

    Handler, Steven M.; Boyce, Richard D.; Ligons, Frank; Perera, Subashan; Nace, David A.; Hochheiser, Harry

    2015-01-01

    Objective Although mobile devices equipped with drug reference software may help prevent adverse drug events (ADEs) in the nursing home (NH) by providing medication information at the point-of-care, little is known about their use and perceived benefits. The goal of this study was to conduct a survey of a nationally representative sample of NH physicians to quantify the use and perceived benefits of mobile devices in preventing ADEs in the NH setting. Design/Setting/Participants We surveyed physicians who attended the 2010 the AMDA Annual Symposium about their use of mobile devices and beliefs about the effectiveness of drug reference software in preventing ADEs. Results The overall net valid response rate was 70% (558/800) with 42% (236/558) using mobile devices to assist with prescribing in the NH. Physicians with ≤15 years clinical experience were 67% more likely to be mobile device users, compared to those with >15 years of clinical experience (odds ratio=1.68; 95% confidence interval=1.17-2.41; p=0.005). For those who used a mobile device to assist with prescribing, almost all (98%) reported performing an average of one or more drug look-ups per day, performed an average of 1-2 lookups per day for potential drug-drug interactions (DDIs), and most (88%) believed that drug reference software had helped to prevent at least one potential ADE in the preceding four-week period. Conclusions The proportion of NH physicians who use mobile devices with drug reference software, while significant, is lower than in other clinical environments. Our results suggest that NH physicians who use mobile devices equipped with drug reference software believe they are helpful for reducing ADEs. Further research is needed to better characterize the facilitators and barriers to adoption of the technology in the NH and its precise impact on NH ADEs. PMID:24094901

  7. Species differences in drug glucuronidation: Humanized UDP-glucuronosyltransferase 1 mice and their application for predicting drug glucuronidation and drug-induced toxicity in humans.

    PubMed

    Fujiwara, Ryoichi; Yoda, Emiko; Tukey, Robert H

    2018-02-01

    More than 20% of clinically used drugs are glucuronidated by a microsomal enzyme UDP-glucuronosyltransferase (UGT). Inhibition or induction of UGT can result in an increase or decrease in blood drug concentration. To avoid drug-drug interactions and adverse drug reactions in individuals, therefore, it is important to understand whether UGTs are involved in metabolism of drugs and drug candidates. While most of glucuronides are inactive metabolites, acyl-glucuronides that are formed from compounds with a carboxylic acid group can be highly toxic. Animals such as mice and rats are widely used to predict drug metabolism and drug-induced toxicity in humans. However, there are marked species differences in the expression and function of drug-metabolizing enzymes including UGTs. To overcome the species differences, mice in which certain drug-metabolizing enzymes are humanized have been recently developed. Humanized UGT1 (hUGT1) mice were created in 2010 by crossing Ugt1-null mice with human UGT1 transgenic mice in a C57BL/6 background. hUGT1 mice can be promising tools to predict human drug glucuronidation and acyl-glucuronide-associated toxicity. In this review article, studies of drug metabolism and toxicity in the hUGT1 mice are summarized. We further discuss research and strategic directions to advance the understanding of drug glucuronidation in humans. Copyright © 2017 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

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

    PubMed

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

    2014-08-06

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

  9. Towards a standardised representation of a knowledge base for adverse drug event prevention.

    PubMed

    Koutkias, Vassilis; Lazou, Katerina; de Clercq, Paul; Maglaveras, Nicos

    2011-01-01

    Knowledge representation is an important part of knowledge engineering activities that is crucial for enabling knowledge sharing and reuse. In this regard, standardised formalisms and technologies play a significant role. Especially for the medical domain, where knowledge may be tacit, not articulated and highly diverse, the development and adoption of standardised knowledge representations is highly challenging and of outmost importance to achieve knowledge interoperability. To this end, this paper presents a research effort towards the standardised representation of a Knowledge Base (KB) encapsulating rule-based signals and procedures for Adverse Drug Event (ADE) prevention. The KB constitutes an integral part of Clinical Decision Support Systems (CDSSs) to be used at the point of care. The paper highlights the requirements at the domain of discourse with respect to knowledge representation, according to which GELLO (an HL7 and ANSI standard) has been adopted. Results of our prototype implementation are presented along with the advantages and the limitations introduced by the employed approach.

  10. Cost-effectiveness of one-time genetic testing to minimize lifetime adverse drug reactions.

    PubMed

    Alagoz, O; Durham, D; Kasirajan, K

    2016-04-01

    We evaluated the cost-effectiveness of one-time pharmacogenomic testing for preventing adverse drug reactions (ADRs) over a patient's lifetime. We developed a Markov-based Monte Carlo microsimulation model to represent the ADR events in the lifetime of each patient. The base-case considered a 40-year-old patient. We measured health outcomes in life years (LYs) and quality-adjusted LYs (QALYs) and estimated costs using 2013 US$. In the base-case, one-time genetic testing had an incremental cost-effectiveness ratio (ICER) of $43,165 (95% confidence interval (CI) is ($42,769,$43,561)) per additional LY and $53,680 per additional QALY (95% CI is ($53,182,$54,179)), hence under the base-case one-time genetic testing is cost-effective. The ICER values were most sensitive to the average probability of death due to ADR, reduction in ADR rate due to genetic testing, mean ADR rate and cost of genetic testing.

  11. Text mining for adverse drug events: the promise, challenges, and state of the art.

    PubMed

    Harpaz, Rave; Callahan, Alison; Tamang, Suzanne; Low, Yen; Odgers, David; Finlayson, Sam; Jung, Kenneth; LePendu, Paea; Shah, Nigam H

    2014-10-01

    Text mining is the computational process of extracting meaningful information from large amounts of unstructured text. It is emerging as a tool to leverage underutilized data sources that can improve pharmacovigilance, including the objective of adverse drug event (ADE) detection and assessment. This article provides an overview of recent advances in pharmacovigilance driven by the application of text mining, and discusses several data sources-such as biomedical literature, clinical narratives, product labeling, social media, and Web search logs-that are amenable to text mining for pharmacovigilance. Given the state of the art, it appears text mining can be applied to extract useful ADE-related information from multiple textual sources. Nonetheless, further research is required to address remaining technical challenges associated with the text mining methodologies, and to conclusively determine the relative contribution of each textual source to improving pharmacovigilance.

  12. Text Mining for Adverse Drug Events: the Promise, Challenges, and State of the Art

    PubMed Central

    Harpaz, Rave; Callahan, Alison; Tamang, Suzanne; Low, Yen; Odgers, David; Finlayson, Sam; Jung, Kenneth; LePendu, Paea; Shah, Nigam H.

    2014-01-01

    Text mining is the computational process of extracting meaningful information from large amounts of unstructured text. Text mining is emerging as a tool to leverage underutilized data sources that can improve pharmacovigilance, including the objective of adverse drug event detection and assessment. This article provides an overview of recent advances in pharmacovigilance driven by the application of text mining, and discusses several data sources—such as biomedical literature, clinical narratives, product labeling, social media, and Web search logs—that are amenable to text-mining for pharmacovigilance. Given the state of the art, it appears text mining can be applied to extract useful ADE-related information from multiple textual sources. Nonetheless, further research is required to address remaining technical challenges associated with the text mining methodologies, and to conclusively determine the relative contribution of each textual source to improving pharmacovigilance. PMID:25151493

  13. Spontaneous Adverse Event Reports Associated with Zolpidem in the United States 2003-2012.

    PubMed

    Wong, Carmen K; Marshall, Nathaniel S; Grunstein, Ronald R; Ho, Samuel S; Fois, Romano A; Hibbs, David E; Hanrahan, Jane R; Saini, Bandana

    2017-02-15

    Stimulated reporting occurs when patients and healthcare professionals are influenced or "stimulated" by media publicity to report specific drug-related adverse reactions, significantly biasing pharmacovigilance analyses. Among countries where the non-benzodiazepine hypnotic drug zolpidem is marketed, the United States experienced a comparable surge of media reporting during 2006-2009 linking the above drug with the development of complex neuropsychiatric sleep-related behaviors. However, the effect of this stimulated reporting in the United States Food and Drug Administration Adverse Event Reporting System has not been explored. Using disproportionality analyses, reporting odds ratios for zolpidem exposure and the following adverse events; parasomnia, movement-based parasomnia, nonmovement-based parasomnia, amnesia, hallucination, and suicidality were determined and compared to all other medications in the database, followed by specific comparison to the benzodiazepine hypnotic class, year-by-year from 2003 to 2012. Odds ratios were increased significantly during and after the period of media publicity for parasomnias, movement-based parasomnias, amnesias and hallucinations. We also observed that zolpidem adverse drug reaction (ADR) reports have higher odds for parasomnias, movement-based parasomnias, amnesias, hallucinations, and suicidality compared to all other drugs, even before the media publicity cluster. Although our results indicate that zolpidem reports have higher odds for the ADR of interest even before the media publicity cluster, negative media coverage greatly exacerbated the reporting of these adverse reactions. The effect of such reporting must be borne in mind when decisions around drugs which have been the subject of intense media publicity are made by health professionals or regulatory bodies. © 2017 American Academy of Sleep Medicine

  14. Drug-drug interactions and adverse drug reactions in polypharmacy among older adults: an integrative review.

    PubMed

    Rodrigues, Maria Cristina Soares; Oliveira, Cesar de

    2016-09-01

    to identify and summarize studies examining both drug-drug interactions (DDI) and adverse drug reactions (ADR) in older adults polymedicated. an integrative review of studies published from January 2008 to December 2013, according to inclusion and exclusion criteria, in MEDLINE and EMBASE electronic databases were performed. forty-seven full-text studies including 14,624,492 older adults (≥ 60 years) were analyzed: 24 (51.1%) concerning ADR, 14 (29.8%) DDI, and 9 studies (19.1%) investigating both DDI and ADR. We found a variety of methodological designs. The reviewed studies reinforced that polypharmacy is a multifactorial process, and predictors and inappropriate prescribing are associated with negative health outcomes, as increasing the frequency and types of ADRs and DDIs involving different drug classes, moreover, some studies show the most successful interventions to optimize prescribing. DDI and ADR among older adults continue to be a significant issue in the worldwide. The findings from the studies included in this integrative review, added to the previous reviews, can contribute to the improvement of advanced practices in geriatric nursing, to promote the safety of older patients in polypharmacy. However, more research is needed to elucidate gaps. identificar e sintetizar estudos que examinam as interações medicamentosas (IM) e reações adversas a medicamentos (RAM) em idosos polimedicados. revisão integrativa de estudos publicados de janeiro de 2008 a dezembro de 2013, de acordo com critérios de inclusão e exclusão, nas bases de dados eletrônicas MEDLINE e EMBASE. foram analisados 47 estudos de texto completo, incluindo 14,624,492 idosos (≥ 60 anos): 24 (51,1%) sobre RAM, 14 (29,8%) sobre IM e 9 estudos (19,1%) que investigaram tanto IM como RAM. Encontramos uma variedade de desenhos metodológicos. Os estudos revisados reforçaram que a polifarmácia é um processo multifatorial, e os preditores e a prescrição inadequada estão associados a

  15. 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

  16. Reducing Adverse Effects During Drug Development: The Example of Lesogaberan and Paresthesia.

    PubMed

    Rydholm, Hans; von Corswant, Christian; Denison, Hans; Jensen, Jörgen M; Lehmann, Anders; Ruth, Magnus; Söderlind, Erik; Aurell-Holmberg, Ann

    2016-04-01

    Lesogaberan, a γ-aminobutyric acid (GABA)B receptor agonist, was developed for the treatment of gastroesophageal reflux disease in patients with a partial response to proton pump inhibitor therapy. A high prevalence of paresthesia was observed in healthy individuals after dosing with lesogaberan in early-phase clinical trials. The aim of this review was to gain further insight into paresthesia caused by lesogaberan by summarizing the relevant preclinical and clinical data. This study was a narrative review of the literature and unpublished data. The occurrence of paresthesia may depend on the route or rate of drug administration; several studies were conducted to test this hypothesis, and formulations were developed to minimize the occurrence of paresthesia. Phase I clinical studies showed that, in healthy individuals, paresthesia occurred soon after administration of lesogaberan in a dose-dependent manner regardless of the route of administration. The occurrence of paresthesia could be decreased by fractionating the dose or reducing the rate of administration. These findings suggest that the initial rate of absorption plays an important part in the development of paresthesia. Modified-release formulations minimize the occurrence of paresthesia while retaining the anti-reflux activity of the drug, as measured by esophageal pH and the number of transient lower esophageal sphincter relaxations. The development of lesogaberan was halted because the effect on gastroesophageal reflux disease symptoms observed in Phase II studies was not considered clinically meaningful in the target patient population. Nevertheless, it is an example of successful formulation development designed to minimize the occurrence of a compound's adverse effect while retaining its pharmacodynamic action. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.

  17. [Perioperative adverse events related to antidepressive agents use].

    PubMed

    Rozec, B; Cinotti, R; Blanloeil, Y

    2011-11-01

    Depression is the most common psychiatric disease, which is treated by the use of antidepressive agents possessing various mechanisms of action. Thus, the use in preoperative period of antidepressive agents is frequent (7% of patients scheduled for surgery). The objective of this review was to update the knowledge on the drug interactions between antidepressive agents and drugs used in perioperative period. (i) Medline and Ovid databases using combination of antidepressive agent and perioperative period as keywords; (ii) national and European epidemiologic database; (iii) expert recommendation and official French health agency; (iv) reference book chapters. The clinical practice showed a limited risk of adverse event related to antidepressant agents interaction with perioperative used drugs. In the two past decades, few relevant observations of adverse event related with imipramine and monoamine oxidase inhibitors use was reported. The most recent antidepressive agents had no serious adverse interaction. Nevertheless, the serotonin syndrome has to be known as far as it is more and more reported. In case of hypotension, the use of vasopressive agent has to be careful because of excessive response. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  18. A comparison of patterns of spontaneous adverse drug reaction reporting with St. John's Wort and fluoxetine during the period 2000-2013.

    PubMed

    Hoban, Claire L; Byard, Roger W; Musgrave, Ian F

    2015-07-01

    Herbal medicines are perceived to be safe by the general public and medical practitioners, despite abundant evidence from clinical trials and case reports that show herbal preparations can have significant adverse effects. The overall impact of adverse events to herbal medicines in Australia is currently unknown. Post marketing surveillance of medications through spontaneous adverse drug reaction (ADR) reports to the Therapeutic Goods Administration (TGA) is one way to estimate this risk. The patterns of spontaneously reported ADRs provide insight to herbal dangers, especially when compared with patterns of a mechanistically similar conventional drug. The study compared the pattern of spontaneously reported ADRs to St. John's Wort (Hypericum perforatum), a common herbal treatment for depression which contains selective serotonin reuptake inhibitors (SSRI), to fluoxetine, a commonly prescribed synthetic SSRI antidepressant. Spontaneous ADR reports sent to the TGA between 2000-2013 for St. John's Wort (n = 84) and fluoxetine (n = 447) were obtained and analysed. The demographic information, types of interaction, severity of the ADR, and the body systems affected (using the Anatomical Therapeutic Chemical classification system) were recorded for individual ADR cases. The majority of spontaneously reported ADRs for St. John's Wort and fluoxetine were concerning females aged 26-50 years (28.6%, 22.8%). The organ systems affected by ADRs to St John's Wort and fluoxetine have a similar profile, with the majority of cases affecting the central nervous system (45.2%, 61.7%). This result demonstrates that herbal preparations can result in ADRs similar to those of prescription medications. © 2015 Wiley Publishing Asia Pty Ltd.

  19. Thrombotic events associated with C1 esterase inhibitor products in patients with hereditary angioedema: investigation from the United States Food and Drug Administration adverse event reporting system database.

    PubMed

    Gandhi, Pranav K; Gentry, William M; Bottorff, Michael B

    2012-10-01

    To investigate reports of thrombotic events associated with the use of C1 esterase inhibitor products in patients with hereditary angioedema in the United States. Retrospective data mining analysis. The United States Food and Drug Administration (FDA) adverse event reporting system (AERS) database. Case reports of C1 esterase inhibitor products, thrombotic events, and C1 esterase inhibitor product-associated thrombotic events (i.e., combination cases) were extracted from the AERS database, using the time frames of each respective product's FDA approval date through the second quarter of 2011. Bayesian statistical methodology within the neural network architecture was implemented to identify potential signals of a drug-associated adverse event. A potential signal is generated when the lower limit of the 95% 2-sided confidence interval of the information component, denoted by IC₀₂₅ , is greater than zero. This suggests that the particular drug-associated adverse event was reported to the database more often than statistically expected from reports available in the database. Ten combination cases of thrombotic events associated with the use of one C1 esterase inhibitor product (Cinryze) were identified in patients with hereditary angioedema. A potential signal demonstrated by an IC₀₂₅ value greater than zero (IC₀₂₅ = 2.91) was generated for these combination cases. The extracted cases from the AERS indicate continuing reports of thrombotic events associated with the use of one C1 esterase inhibitor product among patients with hereditary angioedema. The AERS is incapable of establishing a causal link and detecting the true frequency of an adverse event associated with a drug; however, potential signals of C1 esterase inhibitor product-associated thrombotic events among patients with hereditary angioedema were identified in the extracted combination cases. © 2012 Pharmacotherapy Publications, Inc.

  20. Adverse Drug Events in U.S. Adult Ambulatory Medical Care

    PubMed Central

    Sarkar, Urmimala; López, Andrea; Maselli, Judith H; Gonzales, Ralph

    2011-01-01

    Objective To estimate the incidence of adverse drug events (ADEs) associated with health care visits among U.S. adults across all ambulatory settings. Data Source We analyzed data from two nationally representative probability sample surveys: the National Ambulatory Medical Care Survey and the National Hospital and Ambulatory Medical Care Survey. From 2005 to 2007, the presence of an ADE was specifically defined, requested, and recorded in these surveys. Study Design Secondary data analysis. Principal Findings An estimated 13.5 million ADE-related visits occurred between 2005 and 2007 (0.5 percent of all visits), the large majority (72 percent) occurring in outpatient practice settings, and the remaining in emergency departments. Older patients (age ≥65 years) had the highest age-specific ADE rate, 3.8 ADEs per 10,000 persons per year. In adjusted analyses of outpatient visits, there was an increased odds of an ADE-related visit with increased medication burden (odds ratio [OR] for six to eight medications compared with no medications, OR 3.83 [2.20, 6.65]), and increased odds of ADEs associated with primary care visits compared with specialty visits (OR 2.22 [1.70, 2.89]). Conclusions Approximately 4.5 million ambulatory visits related to ADEs occur each year, the majority of these in outpatient office practices. A greater focus on ADE prevention and detection is warranted among patients receiving multiple medications in primary care practices. PMID:21554271

  1. Adverse Reactions Associated With Cannabis Consumption as Evident From Search Engine Queries.

    PubMed

    Yom-Tov, Elad; Lev-Ran, Shaul

    2017-10-26

    Cannabis is one of the most widely used psychoactive substances worldwide, but adverse drug reactions (ADRs) associated with its use are difficult to study because of its prohibited status in many countries. Internet search engine queries have been used to investigate ADRs in pharmaceutical drugs. In this proof-of-concept study, we tested whether these queries can be used to detect the adverse reactions of cannabis use. We analyzed anonymized queries from US-based users of Bing, a widely used search engine, made over a period of 6 months and compared the results with the prevalence of cannabis use as reported in the US National Survey on Drug Use in the Household (NSDUH) and with ADRs reported in the Food and Drug Administration's Adverse Drug Reporting System. Predicted prevalence of cannabis use was estimated from the fraction of people making queries about cannabis, marijuana, and 121 additional synonyms. Predicted ADRs were estimated from queries containing layperson descriptions to 195 ICD-10 symptoms list. Our results indicated that the predicted prevalence of cannabis use at the US census regional level reaches an R 2 of .71 NSDUH data. Queries for ADRs made by people who also searched for cannabis reveal many of the known adverse effects of cannabis (eg, cough and psychotic symptoms), as well as plausible unknown reactions (eg, pyrexia). These results indicate that search engine queries can serve as an important tool for the study of adverse reactions of illicit drugs, which are difficult to study in other settings. ©Elad Yom-Tov, Shaul Lev-Ran. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 26.10.2017.

  2. Review of adverse reactions to injections of Chinese materia medica.

    PubMed

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

    2010-05-01

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

  3. Hybrid Semantic Analysis for Mapping Adverse Drug Reaction Mentions in Tweets to Medical Terminology.

    PubMed

    Emadzadeh, Ehsan; Sarker, Abeed; Nikfarjam, Azadeh; Gonzalez, Graciela

    2017-01-01

    Social networks, such as Twitter, have become important sources for active monitoring of user-reported adverse drug reactions (ADRs). Automatic extraction of ADR information can be crucial for healthcare providers, drug manufacturers, and consumers. However, because of the non-standard nature of social media language, automatically extracted ADR mentions need to be mapped to standard forms before they can be used by operational pharmacovigilance systems. We propose a modular natural language processing pipeline for mapping (normalizing) colloquial mentions of ADRs to their corresponding standardized identifiers. We seek to accomplish this task and enable customization of the pipeline so that distinct unlabeled free text resources can be incorporated to use the system for other normalization tasks. Our approach, which we call Hybrid Semantic Analysis (HSA), sequentially employs rule-based and semantic matching algorithms for mapping user-generated mentions to concept IDs in the Unified Medical Language System vocabulary. The semantic matching component of HSA is adaptive in nature and uses a regression model to combine various measures of semantic relatedness and resources to optimize normalization performance on the selected data source. On a publicly available corpus, our normalization method achieves 0.502 recall and 0.823 precision (F-measure: 0.624). Our proposed method outperforms a baseline based on latent semantic analysis and another that uses MetaMap.

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

    PubMed

    Gosch, Markus

    2015-07-01

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

  5. Adverse Drug Reactions Reported by Healthcare Professionals: Reaction Characteristics and Time to Reporting.

    PubMed

    Aung, Ar Kar; Tang, Mei Jie; Adler, Nikki Rae; de Menezes, Sara Lee; Goh, Michelle Sue Yen; Tee, Hui Wen; Trubiano, Jason Anthony; Puy, Robert; Zubrinich, Celia Mary; Graudins, Linda Velta

    2018-05-07

    We describe adverse drug reaction (ADR) reporting characteristics and factors contributing to length of time to report by healthcare professionals. This is a retrospective study of voluntary reports to an Australian healthcare ADR Review Committee over a 2-year period (2015-2016). Descriptive and univariate models were used for outcomes, employing standardized ADR definitions. Hospital pharmacists reported 84.8% of the 555 ADRs: 70.3% were hospital onset reactions, and 71.7% were at least of moderate severity. Immunologically mediated reactions were most commonly reported (409, 73.7%). The median time to submit an ADR report was 3 (interquartile range 1-10) days. Longer median times to reporting were associated with multiple implicated agents and delayed hypersensitivity reactions, especially severe cutaneous adverse reactions. A total of 650 medications were implicated that involved multiple agents in 165/555 (29.7%) reports. Antimicrobials were the most commonly implicated agents. Immunologically mediated reactions were most commonly associated with antimicrobials and radiocontrast agents (P < .0001, odds ratio [OR] 3.6, 95%CI 2.4-5.5, and P = .04, OR 4.2, 95%CI 1.2-18.2, respectively). Opioids and psychoactive medications were more commonly implicated in nonimmunological reported ADRs (P = .0002, OR 3.9, 95%CI 1.9-7.9, and P < .0001, OR 11.4, 95%CI 4.6-27.8, respectively). Due to the predominant reporting of immunologically mediated reactions, a targeted education program is being planned to improve identification and accuracy of ADR reports, with the overall aim of improved management to ensure quality service provision and patient safety. © 2018, The American College of Clinical Pharmacology.

  6. Influence of attitudes on pharmacists' intention to report serious adverse drug events to the Food and Drug Administration

    PubMed Central

    Gavaza, Paul; Brown, Carolyn M; Lawson, Kenneth A; Rascati, Karen L; Wilson, James P; Steinhardt, Mary

    2011-01-01

    AIM To investigate the influence of pharmacists' attitudes on intention to report serious adverse drug events (ADEs) to the Food and Drug Administration (FDA). METHODS This cross-sectional study used a mail survey to collect data from hospital and community pharmacists practicing in Texas, United States. Three and 16 items were used to measure intention and attitudes, respectively, using a seven-point bipolar scale. Pharmacists' demographic and practice characteristics, and past reporting were also measured. RESULTS The response rate was 26.4% (n = 377/1500 pharmacists). Most pharmacists intended (n = 297, 78.8%) to report serious ADEs that they will encounter to the FDA through MedWatch. Overall, pharmacists held favourable attitudes towards reporting serious ADEs (mean = 24.5, SD = 6.7, possible range 1–49, neutral = 16). Pharmacists intending to report serious ADEs had more favourable attitudes than those who did not (P < 0.001). About 90% of the pharmacists believed that reporting serious ADEs would improve patient safety. However, 72.6% indicated that reporting serious ADEs was time consuming and over half (55.5%) of the respondents believed that reporting serious ADEs disrupted the normal workflow. Non-intenders held stronger beliefs that ADE reporting would disrupt the normal workflow and was time consuming compared with intenders. Years of experience, number of hours worked and practice setting were associated with pharmacists' attitudes towards reporting (P < 0.05). CONCLUSIONS Most pharmacists held moderately favourable attitudes and high intentions toward reporting serious ADEs to the FDA. This study's findings contribute to an increased understanding of individual factors that influence pharmacists' attitude and intention towards reporting serious ADEs to the FDA. PMID:21332572

  7. Spontaneous Adverse Event Reports Associated with Zolpidem in the United States 2003–2012

    PubMed Central

    Wong, Carmen K.; Marshall, Nathaniel S.; Grunstein, Ronald R.; Ho, Samuel S.; Fois, Romano A.; Hibbs, David E.; Hanrahan, Jane R.; Saini, Bandana

    2017-01-01

    Study Objectives: Stimulated reporting occurs when patients and healthcare professionals are influenced or “stimulated” by media publicity to report specific drug-related adverse reactions, significantly biasing pharmacovigilance analyses. Among countries where the non-benzodiazepine hypnotic drug zolpidem is marketed, the United States experienced a comparable surge of media reporting during 2006–2009 linking the above drug with the development of complex neuropsychiatric sleep-related behaviors. However, the effect of this stimulated reporting in the United States Food and Drug Administration Adverse Event Reporting System has not been explored. Methods: Using disproportionality analyses, reporting odds ratios for zolpidem exposure and the following adverse events; parasomnia, movement-based parasomnia, nonmovement-based parasomnia, amnesia, hallucination, and suicidality were determined and compared to all other medications in the database, followed by specific comparison to the benzodiazepine hypnotic class, year-by-year from 2003 to 2012. Results: Odds ratios were increased significantly during and after the period of media publicity for parasomnias, movement-based parasomnias, amnesias and hallucinations. We also observed that zolpidem adverse drug reaction (ADR) reports have higher odds for parasomnias, movement-based parasomnias, amnesias, hallucinations, and suicidality compared to all other drugs, even before the media publicity cluster. Conclusions: Although our results indicate that zolpidem reports have higher odds for the ADR of interest even before the media publicity cluster, negative media coverage greatly exacerbated the reporting of these adverse reactions. The effect of such reporting must be borne in mind when decisions around drugs which have been the subject of intense media publicity are made by health professionals or regulatory bodies. Citation: Wong CK, Marshall NS, Grunstein RR, Ho SS, Fois RA, Hibbs DE, Hanrahan JR, Saini B

  8. DITOP: drug-induced toxicity related protein database.

    PubMed

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

    2007-07-01

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

  9. Bioactivation of drugs in the skin: relationship to cutaneous adverse drug reactions.

    PubMed

    Sharma, Amy M; Uetrecht, Jack

    2014-02-01

    Drug-induced skin rashes are poorly understood idiosyncratic reactions, and current methods cannot predict their occurrence. Most idiosyncratic drug reactions are thought to be caused by chemically reactive metabolites, and the skin is a frequent site of idiosyncratic reactions; however, the skin has a very limited capacity to metabolize drugs. To balance this, the skin represents a protective barrier with a very active immune response against pathogens and other types of skin injury. Therefore its response to reactive metabolites is quite different from that of the liver. The purpose of this review is to integrate emerging findings into proposed mechanisms of drug and carcinogen metabolism in the skin that are likely responsible for rashes and other immune responses of the skin. Current evidence suggests the skin possesses significant sulfotransferase and flavin monooxygenases activities, but very low cytochromes P450 activity. However, there are skin-specific P450s that are not present in the liver. The manner in which the skin responds to neoantigens through local antigen presentation and innate immune sensing is reviewed with a focus on insights gained from the contact hypersensitivity (CHS) field. The roles of keratinocytes and Langerhans cells, and the emerging function of NOD-like receptors, are highlighted.

  10. [Adverse reactions to drugs reported by the primary care physicians of Andalusia. Analysis of underreporting].

    PubMed

    Torelló Iserte, J; Castillo Ferrando, J R; Laínez, M M; García Morillas, M; Arias González, A

    1994-04-15

    To discover the sort of adverse reactions to medication (ARM) notified by Primary Care doctors and identify the under-notification of those cases having special clinical-epidemiological interest. Retrospective study in which 2,597 ARM corresponding to 1,467 Yellow Cards (YC) were analysed. These were notified by Primary Care doctors to the Centro Andaluz de Farmacovigilancia (Andalusian Drug-watch centre) during the period from 1/6/90 to 31/12/92. To assess the seriousness of the ARM, their terminological classification and imputability, the criteria used in the WHO's international "Yellow Card" programme of spontaneous notification were followed. 77.2% of all notifications were from Primary Care, of which 7.4% were of special interest due to their serious or novel character. However an undernotification of serious and well-known ARM was detected, such as digestive haemorrhages (1.07/10(6) inhibitants per year), anaphylactic shock (0.34/10(6) inhab/year), agranulocytosis (0.23/10(6) inhab/year) and aplastic anaemia (0.05/10(6) inhab/year), among others. Most of the main under-notified ARM are generated in the community but treated in hospital Casualty departments. Therefore it would be useful to develop specific Drug-watch programmes in the hospitals themselves.

  11. Use and perceived benefits of mobile devices by physicians in preventing adverse drug events in the nursing home.

    PubMed

    Handler, Steven M; Boyce, Richard D; Ligons, Frank M; Perera, Subashan; Nace, David A; Hochheiser, Harry

    2013-12-01

    Although mobile devices equipped with drug reference software may help prevent adverse drug events (ADEs) in the nursing home (NH) by providing medication information at the point of care, little is known about their use and perceived benefits. The goal of this study was to conduct a survey of a nationally representative sample of NH physicians to quantify the use and perceived benefits of mobile devices in preventing ADEs in the NH setting. We surveyed physicians who attended the 2010 American Medical Directors Association Annual Symposium about their use of mobile devices, and beliefs about the effectiveness of drug reference software in preventing ADEs. The overall net valid response rate was 70% (558/800) with 42% (236/558) using mobile devices to assist with prescribing in the NH. Physicians with 15 or fewer years of clinical experience were 67% more likely to be mobile device users, compared with those with more than 15 years of clinical experience (odds ratio = 1.68; 95% confidence interval = 1.17-2.41; P = .005). For those who used a mobile device to assist with prescribing, almost all (98%) reported performing an average of 1 or more drug look-ups per day, performed an average of 1 to 2 lookups per day for potential drug-drug interactions (DDIs), and most (88%) believed that drug reference software had helped to prevent at least 1 potential ADE in the preceding 4-week period. The proportion of NH physicians who use mobile devices with drug reference software, although significant, is lower than in other clinical environments. Our results suggest that NH physicians who use mobile devices equipped with drug reference software believe they are helpful for reducing ADEs. Further research is needed to better characterize the facilitators and barriers to adoption of the technology in the NH and its precise impact on NH ADEs. Copyright © 2013 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.

  12. Pharmacist's knowledge, practice and attitudes toward pharmacovigilance and adverse drug reactions reporting process.

    PubMed

    Suyagh, Maysa; Farah, Doaa; Abu Farha, Rana

    2015-04-01

    Adverse drug reactions (ADRs) are a major cause of drug related morbidity and mortality. Pharmacovigilance is the science that plays an essential role in the reduction of ADRs, thus the evolution and growth of this science are critical for effective and safe clinical practice. This study is considered the first study in the region to evaluate pharmacist's knowledge, practice and attitudes toward ADRs reporting after establishing the national ADRs reporting center in Jordan. A cross sectional study was used to evaluate pharmacist knowledge and attitude toward ADRs reporting. A structured validated questionnaire was developed for this purpose and a total of 208 pharmacists were recruited to participate in this study. The majority of pharmacists have insufficient awareness and lack of knowledge about pharmacovigilance and ADRs reporting. Also the rate of reporting of ADRs was extremely poor. Several factors were found to discourage pharmacists from reporting ADRs, which include inadequate information available from the patient, unavailability of pharmacist ADRs form when needed, unawareness of the existence of the national ADRs reporting system. Also pharmacists think that ADRs are unimportant or they did not know how to report them. The results of this study suggest that pharmacists have insufficient knowledge about the concept of pharmacovigilance and spontaneous ADRs reporting. On the other hand, pharmacists had positive attitudes toward pharmacovigilance, despite their little experience with ADRs reporting. Educational programs are needed to increase pharmacist's role in the reporting process, and thus to have a positive impact on the overall patient caring process.

  13. Impact of the HLA-B(*)58:01 Allele and Renal Impairment on Allopurinol-Induced Cutaneous Adverse Reactions.

    PubMed

    Ng, Chau Yee; Yeh, Yu-Ting; Wang, Chuang-Wei; Hung, Shuen-Iu; Yang, Chih-Hsun; Chang, Ya-Ching; Chang, Wan-Chun; Lin, Yu-Jr; Chang, Chee-Jen; Su, Shih-Chi; Fan, Wen-Lang; Chen, Der-Yuan; Wu, Yeong-Jian Jan; Tian, Ya-Chung; Hui, Rosaline Chung-Yee; Chung, Wen-Hung

    2016-07-01

    Allopurinol, a common drug for treating hyperuricemia, is associated with cutaneous adverse drug reactions ranging from mild maculopapular exanthema to life-threatening severe cutaneous adverse reactions, including drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. We have previously reported that HLA-B*58:01 is strongly associated with allopurinol-induced severe cutaneous adverse reactions in Han Chinese, but the associations of the HLA-B*58:01 genotype in an allopurinol-induced hypersensitivity phenotype remain unclear. To investigate the comprehensive associations of HLA-B*58:01, we enrolled 146 patients with allopurinol-induced cutaneous adverse drug reactions (severe cutaneous adverse reactions, n = 106; maculopapular exanthema, n = 40) and 285 allopurinol-tolerant control subjects. Among these allopurinol-induced cutaneous adverse drug reactions, HLA-B*58:01 was strongly associated with severe cutaneous adverse reactions (odds ratio [OR] = 44.0; 95% confidence interval = 21.5-90.3; P = 2.6 × 10(-41)), and the association was correlated with disease severity (OR = 44.0 for severe cutaneous adverse reactions, OR = 8.5 for maculopapular exanthema). The gene dosage effect of HLA-B*58:01 also influenced the development of allopurinol-induced cutaneous adverse drug reactions (OR = 15.25 for HLA-B*58:01 heterozygotes and OR = 72.45 for homozygotes). Furthermore, coexistence of HLA-B*58:01 and renal impairment increased the risk and predictive accuracy of allopurinol-induced cutaneous adverse drug reactions (heterozygous HLA-B*58:01 and normal renal function: OR = 15.25, specificity = 82%; homozygous HLA-B*58:01 and severe renal impairment: OR = 1269.45, specificity = 100%). This HLA-B*58:01 correlation study suggests that patients with coexisting HLA-B*58:01 and renal impairment (especially estimated glomerular filtration rate < 30ml/minute/1.73 m(2)) should be cautious and avoid using

  14. Psychotic and Bipolar Disorders: Antipsychotic Drugs.

    PubMed

    Holder, Sarah D; Edmunds, Alaina L; Morgan, Sherri

    2017-04-01

    Antipsychotic drugs block dopamine receptors and are used to manage psychosis as well as other mental illnesses that may or may not have psychotic features, such as bipolar disorders and major depressive disorder. First-generation antipsychotic drugs are more likely to cause adverse effects such as extrapyramidal symptoms and tardive dyskinesia. Adverse effects of second-generation antipsychotic drugs typically are related to metabolic abnormalities such as weight gain, abnormal blood glucose levels, and elevated lipid levels. Neuroleptic malignant syndrome is a rare but serious adverse effect of antipsychotic drugs that causes mental status changes, hyperthermia, and generalized rigidity. Timely diagnosis is essential due to a high risk of related morbidities if the syndrome remains untreated. Some adverse effects of antipsychotics can be identified and managed so that patients can continue beneficial therapy while minimizing the physiologic consequences. Patients taking antipsychotic drugs should be monitored regularly for adverse effects. Antipsychotics are also associated with potential drug interactions, the most lethal being prolongation of the QT interval, which can lead to fatal arrhythmias. Antipsychotic drugs can be used in special populations, such as pregnant women, children, and elderly patients, per recommendation from a mental health subspecialist. 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.

  15. Nonsteroidal Anti-Inflammatory Drugs and Analgesics Use by Kidney Transplant Recipients.

    PubMed

    Mulka-Gierek, Maria; Foroncewicz, Bartosz; Pączek, Leszek; Wawiórko, Elżbieta; Kamińska, Joanna; Kosieradzki, Maciej; Małkowski, Piotr; Małczuk, Bianka; Nazarewski, Sławomir; Mucha, Krzysztof

    2018-03-02

    BACKGROUND Nonsteroidal anti-inflammatory drugs (NSAIDs) and analgesics are the most commonly used drugs and are increasingly available over-the-counter (OTC). In certain groups of patients, including kidney transplant recipients, their use may be complicated by adverse effects or drug interactions. The aim of our study was to assess the causes and frequency of OTC NSAIDs or analgesics use, as well as the awareness of related side effects. MATERIAL AND METHODS We enrolled 94 randomly selected kidney transplant recipients, who represented 5% of all kidney transplant recipients at our center. An anonymous survey consisting of 23 multiple-choice questions was administered voluntarily and anonymously. RESULTS In all, 63% of study patients confirmed taking the OTC painkillers; 22% of these patients took these drugs at least several times a week, and 4% took these drugs daily. For 38% of the study kidney transplant recipients, NSAIDs or analgesics were reported to be the only way to manage their pain. In addition, 30% of study patients were unaware of the risks associated with these drugs, despite the fact that 89% of the study patients consider physicians the best source of information. CONCLUSIONS Our study found that 63% of kidney transplant recipients regularly took OTC painkillers and 30% were unaware of the potential adverse effects. This necessitates continuous, ongoing education of kidney transplant recipients about the risks of OTC NSAIDs or analgesics use.

  16. Efficacy of intravenous hydrocortisone administered 2-4 h prior to antivenom as prophylaxis against adverse drug reactions to snake antivenom in Sri Lanka: An open labelled randomized controlled trial.

    PubMed

    Kularatne, Senanayake A M; Weerakoon, Kosala; Silva, Anjana; Maduwage, Kalana; Walathara, Chamara; Rathnayake, Ishani; Medagedara, Senal; Paranagama, Ranjith; Mendis, Suresh; Kumarasiri, P V R

    2016-09-15

    The prevention of adverse drug reactions to antivenom serum poses a formidable challenge in the management of snakebite. Hydrocortisone is being used concurrently with antivenom in order to prevent these adverse drug reactions without a proven benefit. However, all previous studies seemed to ignore the testing of effectiveness of hydrocortisone therapy during its pharmacological effects, which come hours later. On this principle, we aimed to test the effectiveness of intravenous hydrocortisone given 2 h or more prior to the commencement of antivenom therapy to reduce adverse drug reactions to antivenom. In an open-labelled randomized controlled trial, patients with a history of snakebite were randomly assigned to receive either 500 mg intravenous hydrocortisone bolus given 2 h or more prior to antivenom therapy (Group A) or at the time of antivenom therapy (Group B). The primary endpoint was the reduction of adverse drug reactions to antivenom of any grade of severity within the first 48 h. This trial has been registered with the "Sri Lanka Clinical Trials Registry", number SLCTR/2010/005. A total of 236 patients were randomized to group A or Group B. In the group A, 38 participants received hydrocortisone 2 h before administration of antivenom whilst 33 received hydrocortisone less than 2 h before administration of antivenom. In the Group B, 84 participants received hydrocortisone at the time of antivenom therapy. In Group A (n, 38), and Group B (n, 84), 15 patients (39%) and 29 patients (35%) developed reactions respectively and the difference is not significant (p = 0.598). Moreover, hydrocortisone therapy did not significantly reduce the occurrence of antievnom reactions of any grade of severity. Further, it didn't delay the occurrence of antivenom reactions in patients who received hydrocortisone either more than 2 h or less than 2 h before the antivenom as opposed to the control group (group B). Intravenous hydrocortisone shows no difference in the

  17. Machine Learning to Predict, Detect, and Intervene Older Adults Vulnerable for Adverse Drug Events in the Emergency Department.

    PubMed

    Ouchi, Kei; Lindvall, Charlotta; Chai, Peter R; Boyer, Edward W

    2018-06-01

    Adverse drug events (ADEs) are common and have serious consequences in older adults. ED visits are opportunities to identify and alter the course of such vulnerable patients. Current practice, however, is limited by inaccurate reporting of medication list, time-consuming medication reconciliation, and poor ADE assessment. This manuscript describes a novel approach to predict, detect, and intervene vulnerable older adults at risk of ADE using machine learning. Toxicologists' expertise in ADE is essential to creating the machine learning algorithm. Leveraging the existing electronic health records to better capture older adults at risk of ADE in the ED may improve their care.

  18. Adverse events attributed to traditional Korean medical practices: 1999–2010

    PubMed Central

    Shin, Hyeun-Kyoo; Jeong, Soo-Jin; Ernst, Edzard

    2013-01-01

    Abstract Objective To investigate adverse events attributed to traditional medical treatments in the Republic of Korea. Methods Adverse events recorded in the Republic of Korea between 1999 and 2010 – by the Food and Drug Administration, the Consumer Agency or the Association of Traditional Korean Medicine – were reviewed. Records of adverse events attributed to the use of traditional medical practices, including reports of medicinal accidents and consumers’ complaints, were investigated. Findings Overall, 9624 records of adverse events attributed to traditional medical practices – including 522 linked to herbal treatments – were identified. Liver problems were the most frequently reported adverse events. Only eight of the adverse events were recorded by the pharmacovigilance system run by the Food and Drug Administration. Of the 9624 events, 1389 – mostly infections, cases of pneumothorax and burns – were linked to physical therapy (n = 285) or acupuncture/moxibustion (n = 1104). Conclusion In the Republic of Korea, traditional medical practices often appear to have adverse effects, yet almost all of the adverse events attributed to such practices between 1999 and 2010 were missed by the national pharmacovigilance system. The Consumer Agency and the Association of Traditional Korean Medicine should be included in the national pharmacovigilance system. PMID:23940404

  19. [Club drugs].

    PubMed

    Guerreiro, Diogo Frasquilho; Carmo, Ana Lisa; da Silva, Joaquim Alves; Navarro, Rita; Góis, Carlos

    2011-01-01

    Club drugs are the following substances: Methylenedioxymethamphetamine (MDMA); Methamphetamine; Lysergic Acid Diethylamide (LSD); Ketamine; Gamma-hydroxybutyrate (GHB) and Flunitrazepam. These substances are mainly used by adolescents and young adults, mostly in recreational settings like dance clubs and rave parties. These drugs have diverse psychotropic effects, are associated with several degrees of toxicity, dependence and long term adverse effects. Some have been used for several decades, while others are relatively recent substances of abuse. They have distinct pharmacodynamic and pharmacokinetic properties, are not easy to detect and, many times, the use of club drugs is under diagnosed. Although the use of these drugs is increasingly common, few health professionals feel comfortable with the diagnosis and treatment. The authors performed a systematic literature review, with the goal of synthesising the existing knowledge about club drugs, namely epidemiology, mechanism of action, detection, adverse reactions and treatment. The purpose of this article is creating in Portuguese language a knowledge data base on club drugs, that health professionals of various specialties can use as a reference when dealing with individual with this kind of drug abuse.

  20. Managing drugs safely.

    PubMed

    van den Anker, John N

    2005-02-01

    There is hard data to show that newborn infants are more likely than adults to experience adverse reactions to drugs. Paradoxically, drug-related legislation to ensure safe and effective drug use in humans neglected neonates until 2002, when the Best Pharmaceuticals Act for Children was signed into law in the USA. The situation for neonates should now catch up with that for adults and neonates will be prescribed more licensed drugs in the near future. If we are to be able to analyze the underlying system errors to improve the safe use of drugs in the studied patient population, reporting of adverse drug events and reactions needs to happen in a blame free environment. In addition, computerized physician order entry will certainly further improve the current situation by preventing errors in ordering, transcribing, verifying, and transmitting medication orders.

  1. Adverse effects of neuromuscular blockers and their antagonists.

    PubMed

    Naguib, M; Magboul, M M

    1998-02-01

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

  2. Adverse effects of neuromuscular blockers and their antagonists.

    PubMed

    Naguib, M; Magboul, M M

    1998-06-01

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

  3. [Serious adverse drug reactions with tramadol reported to the French pharmacovigilance database between 2011 and 2015].

    PubMed

    Moulis, Florence; Rousseau, Vanessa; Abadie, Delphine; Masmoudi, Kamel; Micallef, Joëlle; Vigier, Caroline; Pierre, Sabrina; Dautriche, Anne; Montastruc, François; Montastruc, Jean-Louis

    2017-12-01

    Tramadol is an opioid and a serotonin reuptake inhibitor drug. It is approved for moderate to severe pain in adults. The aim of this study was to assess tramadol safety through a national pharmacovigilance study in France since dextropropoxyphen withdrawal in 2011. We described all serious adverse drug reactions (SADRs) reported with tramadol in adults in the French National PharmacoVigilance Database from August 1st, 2011 to December 31st, 2015. We identified 1512 SADRs during the study period. The most frequently reported SADRs were neurological (29.4%, including troubles of consciousness [13.2%] and seizures [6.7%]), psychiatric (22.8%, including confusions [14.6%] and hallucinations [7.3%]) and gastrointestinal (17.0%, mostly nausea and vomiting [9.6%]). Unexpected SADRs were also reported: hyponatremia, cholestatic hepatitis, serotonin syndrome. This study demonstrates new unexpected hepatic and metabolic SADRs. Tramadol alone can induce serotonin syndrome in overdose situations. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  4. Biomedical Informatics Approaches to Identifying Drug-Drug Interactions: Application to Insulin Secretagogues

    PubMed Central

    Han, Xu; Chiang, ChienWei; Leonard, Charles E.; Bilker, Warren B.; Brensinger, Colleen M.; Li, Lang; Hennessy, Sean

    2017-01-01

    Background Drug-drug interactions with insulin secretagogues are associated with increased risk of serious hypoglycemia in patients with type 2 diabetes. We aimed to systematically screen for drugs that interact with the five most commonly used secretagogues―glipizide, glyburide, glimepiride, repaglinide, and nateglinide―to cause serious hypoglycemia. Methods We screened 400 drugs frequently co-prescribed with the secretagogues as candidate interacting precipitants. We first predicted the drug–drug interaction potential based on the pharmacokinetics of each secretagogue–precipitant pair. We then performed pharmacoepidemiologic screening for each secretagogue of interest, and for metformin as a negative control, using an administrative claims database and the self-controlled case series design. The overall rate ratios (RRs) and those for four predefined risk periods were estimated using Poisson regression. The RRs were adjusted for multiple estimation using semi-Bayes method, and then adjusted for metformin results to distinguish native effects of the precipitant from a drug–drug interaction. Results We predicted 34 pharmacokinetic drug–drug interactions with the secretagogues, nine moderate and 25 weak. There were 140 and 61 secretagogue–precipitant pairs associated with increased rates of serious hypoglycemia before and after the metformin adjustment, respectively. The results from pharmacokinetic prediction correlated poorly with those from pharmacoepidemiologic screening. Conclusions The self-controlled case series design has the potential to be widely applicable to screening for drug–drug interactions that lead to adverse outcomes identifiable in healthcare databases. Coupling pharmacokinetic prediction with pharmacoepidemiologic screening did not notably improve the ability to identify drug–drug interactions in this case. PMID:28169935

  5. Multi-Exposure and Clustering of Adverse Childhood Experiences, Socioeconomic Differences and Psychotropic Medication in Young Adults

    PubMed Central

    Björkenstam, Emma; Hjern, Anders; Mittendorfer-Rutz, Ellenor; Vinnerljung, Bo; Hallqvist, Johan; Ljung, Rickard

    2013-01-01

    Purpose Stressful childhood experiences have negative long-term health consequences. The present study examines the association between adverse childhood experiences, socioeconomic position, and risk of psychotropic medication in young adulthood. Methods This register-based cohort study comprises the birth cohorts between 1985 and 1988 in Sweden. We followed 362 663 individuals for use of psychotropic medication from January 2006 until December 2008. Adverse childhood experiences were severe criminality among parents, parental alcohol or drug abuse, social assistance recipiency, parental separation or single household, child welfare intervention before the age of 12, mentally ill or suicidal parents, familial death, and number of changes in place of residency. Estimates of risk of psychotropic medication were calculated as odds ratio (OR) with 95% confidence intervals (CIs) using logistic regression analysis. Results Adverse childhood experiences were associated with increased risks of psychotropic medication. The OR for more than three adverse childhood experiences and risk of psychotropic medication was for women 2.4 (95% CI 2.3–2.5) and for men 3.1 (95% CI 2.9–3.2). The risk of psychotropic medication increased with a higher rate of adverse childhood experiences, a relationship similar in all socioeconomic groups. Conclusions Accumulation of adverse childhood experiences increases the risk of psychotropic medication in young adults. Parental educational level is of less importance when adjusting for adverse childhood experiences. The higher risk for future mental health problems among children from lower socioeconomic groups, compared to peers from more advantaged backgrounds, seems to be linked to a higher rate of exposure to adverse childhood experiences. PMID:23341951

  6. Multi-exposure and clustering of adverse childhood experiences, socioeconomic differences and psychotropic medication in young adults.

    PubMed

    Björkenstam, Emma; Hjern, Anders; Mittendorfer-Rutz, Ellenor; Vinnerljung, Bo; Hallqvist, Johan; Ljung, Rickard

    2013-01-01

    Stressful childhood experiences have negative long-term health consequences. The present study examines the association between adverse childhood experiences, socioeconomic position, and risk of psychotropic medication in young adulthood. This register-based cohort study comprises the birth cohorts between 1985 and 1988 in Sweden. We followed 362 663 individuals for use of psychotropic medication from January 2006 until December 2008. Adverse childhood experiences were severe criminality among parents, parental alcohol or drug abuse, social assistance recipiency, parental separation or single household, child welfare intervention before the age of 12, mentally ill or suicidal parents, familial death, and number of changes in place of residency. Estimates of risk of psychotropic medication were calculated as odds ratio (OR) with 95% confidence intervals (CIs) using logistic regression analysis. Adverse childhood experiences were associated with increased risks of psychotropic medication. The OR for more than three adverse childhood experiences and risk of psychotropic medication was for women 2.4 (95% CI 2.3-2.5) and for men 3.1 (95% CI 2.9-3.2). The risk of psychotropic medication increased with a higher rate of adverse childhood experiences, a relationship similar in all socioeconomic groups. Accumulation of adverse childhood experiences increases the risk of psychotropic medication in young adults. Parental educational level is of less importance when adjusting for adverse childhood experiences. The higher risk for future mental health problems among children from lower socioeconomic groups, compared to peers from more advantaged backgrounds, seems to be linked to a higher rate of exposure to adverse childhood experiences.

  7. Monitoring adverse drug reactions in children using community pharmacies: a pilot study

    PubMed Central

    Stewart, Derek; Helms, Peter; McCaig, Dorothy; Bond, Christine; McLay, James

    2005-01-01

    Aims To determine the feasibility of a community pharmacy-based parental adverse drug reaction (ADR) reporting system for children. Design Prospective study of parent-reported ADRs using a questionnaire issued to the parent or guardians of children 0–11 years of age collecting prescribed medicine for amoxicillin, and/or salbutamol, and collecting prescribed medicine for, or purchasing, paracetamol or ibuprofen suspension. Setting Seven community pharmacies in Grampian, Scotland. Results During a 4-week period 360 prescriptions or purchases for the study medications occurred. Two hundred and sixty-seven parents (85.5%) agreed to participate in the study. One hundred and six participants (40%) returned a total of 122 questionnaires. The demographics of responders and nonresponders including medication, age of child, and social status as assessed by the Depcat score were similar. There was no evidence of under-representation of any socio-economic group. Possible adverse events were detected using a symptom tick list and perceived ADRs using free text entry. Using the symptom tick list approach the most commonly reported symptoms were diarrhoea (28.9%) and tiredness (31.6%) for amoxicillin. The levels of diarrhoea and tiredness reported for ibuprofen, paracetamol and salbutamol were 15% and 20%, 7.4% and 18.5%, and 20% and 0%, respectively. Using the freehand section of the questionnaire 15 specific ADRs were reported by parents (12.3%). Eight children (21.2%) reported ADRs attributed to amoxicilin [diarrhoea (n = 4), fever (n = 1), anorexia (n = 1), hyperactivity (n = 1) and nonspecific (n = 1)], five to paracetamol [diarrhoea (n = 3), anorexia, irritability, crying and very angry (n = 1) and not stated (n = 1)], two to ibuprofen [diarrhoea (n = 1), not stated (n =)]. Only one off-label prescription was identified and this was for salbutamol syrup prescribed to a child under 2 years of age. Conclusions The prospective monitoring of paediatric ADRs, using a

  8. DL-ADR: a novel deep learning model for classifying genomic variants into adverse drug reactions.

    PubMed

    Liang, Zhaohui; Huang, Jimmy Xiangji; Zeng, Xing; Zhang, Gang

    2016-08-10

    Genomic variations are associated with the metabolism and the occurrence of adverse reactions of many therapeutic agents. The polymorphisms on over 2000 locations of cytochrome P450 enzymes (CYP) due to many factors such as ethnicity, mutations, and inheritance attribute to the diversity of response and side effects of various drugs. The associations of the single nucleotide polymorphisms (SNPs), the internal pharmacokinetic patterns and the vulnerability of specific adverse reactions become one of the research interests of pharmacogenomics. The conventional genomewide association studies (GWAS) mainly focuses on the relation of single or multiple SNPs to a specific risk factors which are a one-to-many relation. However, there are no robust methods to establish a many-to-many network which can combine the direct and indirect associations between multiple SNPs and a serial of events (e.g. adverse reactions, metabolic patterns, prognostic factors etc.). In this paper, we present a novel deep learning model based on generative stochastic networks and hidden Markov chain to classify the observed samples with SNPs on five loci of two genes (CYP2D6 and CYP1A2) respectively to the vulnerable population of 14 types of adverse reactions. A supervised deep learning model is proposed in this study. The revised generative stochastic networks (GSN) model with transited by the hidden Markov chain is used. The data of the training set are collected from clinical observation. The training set is composed of 83 observations of blood samples with the genotypes respectively on CYP2D6*2, *10, *14 and CYP1A2*1C, *1 F. The samples are genotyped by the polymerase chain reaction (PCR) method. A hidden Markov chain is used as the transition operator to simulate the probabilistic distribution. The model can perform learning at lower cost compared to the conventional maximal likelihood method because the transition distribution is conditional on the previous state of the hidden Markov

  9. 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.

  10. Liability and ophthalmic drug use.

    PubMed

    Classé, J G

    1992-01-01

    Ophthalmic drug use has been an aspect of optometry for more than two decades. Although utilization of these drugs has produced significant changes in the clinical and legal responsibilities of optometrists, the liability posture of the profession has remained unaltered. Studies of malpractice claims against optometrists and ophthalmologists have demonstrated that ophthalmologists are much more likely to be charged with negligence for adverse drug reactions and that drug-related malpractice claims are not a liability issue for optometrists. Based on the experiences of both professions, this paper describes the adverse effects of common ophthalmic drugs, with emphasis on those drug reactions that have resulted in litigation.

  11. Impact of Drug Cost Sharing on Service Use and Adverse Clinical Outcomes In Elderly Receiving Antidepressants

    PubMed Central

    Wang, Philip S.; Patrick, Amanda R.; Dormuth, Colin; Maclure, Malcolm; Avorn, Jerry; Canning, Claire F.; Schneeweiss, Sebastian

    2010-01-01

    Background Depression imposes enormous burdens on the elderly. Despite this, rates of initiation of and adherence to recommended pharmacotherapy are frequently low in this population. Although initiatives such as the Medicare Modernization Act (MMA) in have improved seniors' access to antidepressants, there are concerns that the patient cost-sharing incorporated in the MMA may have unintended consequences if it reduces essential drug use. Age-related pharmacokinetic and pharmacodynamic changes could make seniors particularly vulnerable to antidepressant regimens used inappropriately to save costs, increasing their risks of morbidity, hospitalizations, and nursing home placements. Two sequential large-scale “natural experiments” in British Columbia provide a unique opportunity to evaluate the effect of cost sharing on outcomes and mental health service use among seniors. In January 2002 the province introduced a $25 Canadian copay ($10 for low-income seniors). In May 2003 this copay policy was replaced by a second policy consisting of an income-based deductible, 25% coinsurance once the deductible was met, and full coverage once an out-of-pocket ceiling was met. The transition between the two policies is analogous to what many U.S. seniors experience when they transition from private insurance requiring copays to Medicare Part D requiring deductibles and coinsurance. Aims To evaluate whether declines in antidepressant initiation after the introduction of two drug cost-sharing policies in British Columbia were associated with increased use of physician services, hospitalizations, and nursing home admissions among all British Columbia residents aged 65+. Methods Records of physician service use, inpatient hospitalizations, and residential care admissions were obtained from administrative databases. Population-level patterns over time were plotted, and effects of implementing the cost-sharing policies examined in segmented linear regression models. Results Neither

  12. Background Papers on Student Drug Involvement.

    ERIC Educational Resources Information Center

    Hollander, Charles, Ed.

    The National Student Association (NSA) presents its position on student drug involvement in part 1 of this collection. A resolution calling for re-investigation of existing marijuana laws and guaranteed rights to the privacy of students was passed by NSA in August, 1966. This resolution is discussed. In part 2, papers presented at the National…

  13. Drug-Food Interactions

    MedlinePlus

    ... article was contributed by: familydoctor.org editorial staff Categories: Drugs, Procedures & Devices, Prescription Medicines, Your Health ResourcesTags: adverse reactions, Food-Drug Interactions, patient education, patient information September 1, ...

  14. From ultrasocial to antisocial: a role for oxytocin in the acute reinforcing effects and long-term adverse consequences of drug use?

    PubMed

    McGregor, I S; Callaghan, P D; Hunt, G E

    2008-05-01

    Addictive drugs can profoundly affect social behaviour both acutely and in the long-term. Effects range from the artificial sociability imbued by various intoxicating agents to the depressed and socially withdrawn state frequently observed in chronic drug users. Understanding such effects is of great potential significance in addiction neurobiology. In this review we focus on the 'social neuropeptide' oxytocin and its possible role in acute and long-term effects of commonly used drugs. Oxytocin regulates social affiliation and social recognition in many species and modulates anxiety, mood and aggression. Recent evidence suggests that popular party drugs such as MDMA and gamma-hydroxybutyrate (GHB) may preferentially activate brain oxytocin systems to produce their characteristic prosocial and prosexual effects. Oxytocin interacts with the mesolimbic dopamine system to facilitate sexual and social behaviour, and this oxytocin-dopamine interaction may also influence the acquisition and expression of drug-seeking behaviour. An increasing body of evidence from animal models suggests that even brief exposure to drugs such as MDMA, cannabinoids, methamphetamine and phencyclidine can cause long lasting deficits in social behaviour. We discuss preliminary evidence that these adverse effects may reflect long-term neuroadaptations in brain oxytocin systems. Laboratory studies and preliminary clinical studies also indicate that raising brain oxytocin levels may ameliorate acute drug withdrawal symptoms. It is concluded that oxytocin may play an important, yet largely unexplored, role in drug addiction. Greater understanding of this role may ultimately lead to novel therapeutics for addiction that can improve mood and facilitate the recovery of persons with drug use disorders.

  15. Language does not come "in boxes": Assessing discrepancies between adverse drug reactions spontaneous reporting and MedDRA® codes in European Portuguese.

    PubMed

    Inácio, Pedro; Airaksinen, Marja; Cavaco, Afonso

    2015-01-01

    The description of adverse drug reactions (ADRs) by health care professionals (HCPs) can be highly variable. This variation can affect the coding of a reaction with the Medical Dictionary for Regulatory Activities (MedDRA(®)), the gold standard for pharmacovigilance database entries. Ultimately, the strength of a safety signal can be compromised. The objective of this study was to assess: 1) participation of different HCPs in ADR reporting, and 2) variation of language used by HCPs when describing ADRs, and to compare it with the corresponding MedDRA(®) codes. A retrospective content analysis was performed, using the database of spontaneous reports submitted by HCPs in the region of the Southern Pharmacovigilance Unit, Portugal. Data retrieved consisted of the idiomatic description of all ADRs occurring in 2004 (first year of the Unit activity, n = 53) and in 2012 (n = 350). The agreement between the language used by HCPs and the MedDRA(®) dictionary codes was quantitatively assessed. From a total of 403 spontaneous reports received in the two years, 896 words describing ADRs were collected. HCPs presented different levels of pharmacovigilance participation and ADR idiomatic descriptions, with pharmacists providing the greatest overall contribution. The agreement between the language used in spontaneous reports and the corresponding MedDRA(®) terms varied by HCP background, with nurses presenting the poorer results than medical doctors and pharmacists when considering the dictionary as the gold standard in ADRs' language. Lexical accuracy and semantic variations exist between different HCP groups. These differences may interfere with the strength of a generated safety signal. Clinical and MedDRA(®) terminology training should be targeted to increase not only the frequency, but also the quality of spontaneous reports, in accordance with HCPs' experience and background. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. A systematic review of adverse drug events associated with administration of common asthma medications in children

    PubMed Central

    Johnson, David W.; Sperou, Arissa J.; Crotts, Jennifer; Saude, Erik; Hartling, Lisa; Stang, Antonia

    2017-01-01

    Objective To systematically review the literature and determine frequencies of adverse drug events (ADE) associated with pediatric asthma medications. Methods Following PRISMA guidelines, we systematically searched six bibliographic databases between January 1991 and January 2017. Study eligibility, data extraction and quality assessment were independently completed and verified by two reviewers. We included randomized control trials (RCT), case-control, cohort, or quasi-experimental studies where the primary objective was identifying ADE in children 1 month– 18 years old exposed to commercial asthma medications. The primary outcome was ADE frequency. Findings Our search identified 14,540 citations. 46 studies were included: 24 RCT, 15 cohort, 4 RCT pooled analyses, 1 case-control, 1 open-label trial and 1 quasi-experimental study. Studies examined the following drug classes: inhaled corticosteroids (ICS) (n = 24), short-acting beta-agonists (n = 10), long-acting beta-agonists (LABA) (n = 3), ICS + LABA (n = 3), Leukotriene Receptor Antagonists (n = 3) and others (n = 3). 29 studies occurred in North America, and 29 were industry funded. We report a detailed index of 406 ADE descriptions and frequencies organized by drug class. The majority of data focuses on ICS, with 174 ADE affecting 13 organ systems including adrenal and growth suppression. We observed serious ADE, although they were rare, with frequency ranging between 0.9–6% per drug. There were no confirmed deaths, except for 13 potential deaths in a LABA study including combined adult and pediatric participants. We identified substantial methodological concerns, particularly with identifying ADE and determining severity. No studies utilized available standardized causality, severity or preventability assessments. Conclusion The majority of studies focus on ICS, with adrenal and growth suppression described. Serious ADE are relatively uncommon, with no confirmed pediatric deaths. We identify substantial

  17. Public awareness and perception toward Adverse Drug Reactions reporting in Riyadh, Saudi Arabia.

    PubMed

    Sales, Ibrahim; Aljadhey, Hisham; Albogami, Yasser; Mahmoud, Mansour A

    2017-09-01

    Purpose: To assess the general public awareness and perception about Adverse Drug Reactions (ADRs) reporting and pharmacovigilance. Method: A cross-sectional study conducted on June 2012 during awareness campaign held in two malls in Riyadh city for two days. A self-administered questionnaire consisting of three parts was distributed to the attendees who accepted to participate in the study. Results: A total of 204 questionnaires were collected with a response rate of 68%. Twenty-three percent could correctly define ADRs. Only 13(15.7%) of responders were familiar with the term "Pharmacovigilance" and only 78.6% were aware about the Saudi Pharmacovigilance Center. Sixty-seventy percent indicated that their physicians or pharmacists don't actively encourage them to report ADRs that may occur when they take their medications. The majority of responders (73.2%) believed that the medical team, rather than consumers, should report ADRs. When asked why patients do not report ADRs, 19.1(48.5%) believed that patients do not know whether the ADR is from the medication or not, 18.1(46.1%) stated that the reason was because patients don't know about the Pharmacovigilance Center, 16(40.7%) think that patients don't know about the importance of ADRs reporting, and 14(36.3%) responded that patients probably don't know how to report ADRs. Conclusion: The general public in Saudi Arabia are not aware about ADRs reporting and the pharmacovigilance system. The Saudi Food and Drug Authorities (FDA) need to put more efforts to increasing public awareness about the importance of ADRs reporting process and the importance of pharmacovigilance system in promoting patient safety.

  18. Various pharmacogenetic aspects of antiepileptic drug therapy: a review.

    PubMed

    Mann, Michael W; Pons, Gerard

    2007-01-01

    Pharmacogenetics concerns the influence of an individual's genetic background on the pharmacokinetics and pharmacodynamics of xenobiotics. Much of the pharmacogenetic data in the field of epilepsy deals with the pharmacokinetics of antiepileptic drugs (AEDs). In particular, two polymorphisms of cytochrome P450 2C9 are known to slow down the metabolism of phenytoin to a degree that increases the risk of the neurotoxic adverse effects of this drug among carriers of these polymorphisms. A significant number of patients with epilepsy do not respond to AEDs and such pharmacoresistance is a major, largely unsolved, problem that is likely to be multifactorial in nature. In this regard, genetic factors may influence transmembrane drug transporter proteins, thereby modifying the intracerebral penetration of AEDs. Monogenic idiopathic epilepsies are rare and frequently associated with ion channel mutations; however, to date, a consistent relationship between changes in channel properties and clinical phenotype has not been established nor has any association between genotype and response to specific treatment options. Polymorphisms of drug targets may represent another genetic facet in epilepsy: a recent study demonstrated for the first time a polymorphism of a drug target (the alpha-subunit of a voltage-gated sodium channel) associated in clinical practice with differing response to two classic AEDs. Adverse drug reactions and teratogenicity of AEDs remain a major concern. Whole-genome single nucleotide polymorphism profiling might in the future help to determine genetic predisposing factors for adverse drug reactions. Recently, in Han Chinese treated with carbamazepine and presenting with Stevens-Johnson syndrome, a strong association was found with HLA B*1502. If genetically targeted drug development becomes more affordable/cost efficient in the near future, the development of new drugs for relatively rare diseases could become economically viable for the pharmaceutical

  19. Is polypharmacy an independent risk factor for adverse outcomes after an emergency department visit?

    PubMed

    Salvi, Fabio; Rossi, Lorena; Lattanzio, Fabrizia; Cherubini, Antonio

    2017-03-01

    This study aimed at verifying the role of polypharmacy as an independent risk factor for adverse health outcomes in older emergency department (ED) patients. This was a large (n = 2057) sample of older ED patients (≥65 years) participating in an observational cohort study. Polypharmacy and excessive polypharmacy were defined as having 6-9 drug prescriptions and 10 or more drug prescriptions in the last 3 months, respectively. The total number of medication prescriptions was also available. Outcome measures were in-hospital mortality; 30-day ED return; ED revisit, hospital admission, and mortality at 6 months. Logistic and Cox regression models as well as receiver operating characteristic curves using the Youden index and the area under the curve were calculated. Polypharmacy and excessive polypharmacy were present in 624 (30.3 %) and 367 (17.8 %) subjects, respectively. The mean number of prescriptions in the last 3 months was 5.7 (range 0-25) drugs. Polypharmacy and, particularly, excessive polypharmacy were constantly and independently associated with worse outcomes. A cut-off of 6 had the highest value of the Youden Index in predicting the majority of the adverse outcomes considered. Polypharmacy and excessive polypharmacy are independent risk factors for adverse health outcomes after an ED visit. Further studies are needed to clarify whether drug related issues (such as non-compliance, inappropriate or suboptimal prescribing, adverse drug reactions, and drug-drug or drug-disease interactions) or underlying multimorbidity and disease severity, as well as clinical complexity and frailty, are responsible for the negative outcomes associated with polypharmacy.

  20. Is There a Potential of Misuse for Quetiapine?: Literature Review and Analysis of the European Medicines Agency/European Medicines Agency Adverse Drug Reactions' Database.

    PubMed

    Chiappini, Stefania; Schifano, Fabrizio

    2018-02-01

    A recent years' increase in both prescribing and availability of second-generation antipsychotics (SGAs) has been observed. According to the literature, typically made up by case studies/series, quetiapine seems to be the most commonly misused SGA, with both intranasal and intravenous intake modalities having been described. Another SGA that has been anecdotally reported to be misused is olanzapine. For these molecules, both a previous history of drug misuse and being an inmate have been described as factors associated with misuse. Hence, while providing here an updated literature review of the topic, we aimed at assessing all cases of quetiapine misuse/abuse/dependence/withdrawal as reported to the European Medicines Agency's EudraVigilance (EV) database; this was carried out in comparison with the reference drug olanzapine. All spontaneous, European Medicines Agency database reports relating to both quetiapine (2005-2016) and olanzapine (2004-2016) misuse/abuse/dependence/withdrawal issues were retrieved, and a descriptive analysis was performed. From the EV database, 18,112 (8.64% of 209,571) and 4178 (7.58% of 55,100) adverse drug reaction reports of misuse/abuse/dependence/withdrawal were associated with quetiapine and olanzapine, respectively. The resulting proportional reporting ratio values suggested that the misuse/abuse-, dependence-, and withdrawal-related adverse drug reactions were more frequently reported for quetiapine (1.07, 1.01, and 5.25, respectively) in comparison with olanzapine. Despite data collection limitations, present EV data may suggest that, at least in comparison with olanzapine, quetiapine misuse may be a cause for concern.