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Sample records for adverse drug effects

  1. Adverse Effects of Common Drugs: Adults.

    PubMed

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

    2015-09-01

    Although drugs can be an essential and lifesaving component of the care of adult patients, their use frequently is accompanied by adverse effects and life-threatening adverse drug reactions that can result in significant disability and mortality. The potential for drug-related severe morbidity and mortality is compounded during periods of hospitalization, when high-risk drugs such as anticoagulants or insulin are used, and when care in an intensive care unit is required. Patient factors in adults that can increase the risk of drug harms include immunosuppression, cognitive impairment, depression, alcoholism and other substance abuse disorders, chronic kidney disease, hepatic dysfunction, coagulopathies, limited English proficiency, institutional/nursing home care, and underinsurance or lack of insurance. Physician factors that can increase the risk of drug harms include inappropriate prescribing of drugs (including to pregnant and breastfeeding women), failure to appropriately discontinue/deprescribe drugs, insufficient drug reconciliation, failure to coordinate care among multiple prescribing clinicians, and failure to elicit and incorporate into health histories and clinical decision-making the widespread use of nonprescription drugs, herbal products, and dietary supplements. PMID:26375995

  2. [Adverse drug effects in the community pharmacy].

    PubMed

    Arnet, Isabelle; Seidling, Hanna M; Hersberger, Kurt E

    2015-12-01

    Community pharmacists represent an important pillar for the identification and the reporting of adverse drug effects (ADE}. Thanks to their broad view on the pharmacotherapy, over-the-counter medication included, they contribute greatly to the improvement of drug safety. In principle, the community pharmacy will face three groups of ADE which require specific attention. This article deals with these specific ADE groups and presents some illustrative examples from daily practice. Furthermore, we suggest some solutions to identify potential relevant interactions - including herbal-drug interactions - and give tips for daily practice, along with some often overseen cutaneous ADE. PMID:26654812

  3. Adverse immunologic effects of antithyroid drugs.

    PubMed Central

    Wing, S S; Fantus, I G

    1987-01-01

    Propylthiouracil and methimazole are frequently used in the management of hyperthyroidism. Two patients in whom adverse immunologic effects other than isolated agranulocytosis developed during treatment with propylthiouracil are described. A review of the literature revealed 53 similar cases over a 35-year period. Rash, fever, arthralgias and granulocytopenia were the most common manifestations. Vasculitis, particularly with cutaneous manifestations, occurs and may be fatal. The clinical evidence suggests that an immunologic mechanism is involved. A number of different autoantibodies were reported, but antinuclear antibodies were infrequent, and none of the cases met the criteria for a diagnosis of systemic lupus erythematosus. Thus, the reactions do not represent a true drug-induced lupus syndrome. Current hypotheses and experimental data regarding the cause of the reactions are reviewed. No specific clinical subgroup at high risk can be identified, and manifestations may occur at any dosage and at any time during therapy. Cross-reactivity between the two antithyroid drugs can be expected. Except for minor symptoms (e.g., mild arthralgias or transient rash), such reactions are an indication for withdrawal of the drug and the use of alternative methods to control the hyperthyroidism. In rare cases of severe vasculitis a short course of high-dose glucocorticoid therapy may be helpful. PMID:3539299

  4. Adverse Effects of Common Drugs: General Concepts.

    PubMed

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

    2015-09-01

    Adverse drug reactions (ADRs) contribute to substantial morbidity and mortality and add to rising health care costs. Many ADRs are preventable with appropriate prescribing and monitoring because they often occur as an extension of a drug's mechanism of action or known drug interactions. Patients at higher risk of ADRs include those at the extremes of age, those with multiple comorbidities, those taking multiple drugs, and patients admitted to intensive care units or experiencing transitions of care. Because the risk of ADRs becomes greater as the number of drugs and dietary supplements taken increases, it is imperative that prescribers be vigilant about the prescribing cascade and take steps to discontinue drugs that are likely to be more harmful than helpful. Pharmacists serve as important partners in clinical care environments by conducting comprehensive drug reviews, aiding in drug/dosage selection, and developing therapeutic monitoring plans. Although the potential exists for clinicians to use electronic health record systems to aid in clinical decision making through drug safety decision support tools, computer systems should never replace clinical judgment. Clinicians also are encouraged to report ADRs to the Food and Drug Administration Adverse Event Reporting System. PMID:26375993

  5. [Haematological adverse effects caused by psychiatric drugs].

    PubMed

    Mazaira, Silvina

    2008-01-01

    Almost all clases of psychiatric drugs (typical and atypical antipsychotics, antidepressants, mood stabilizers, benzodiazepines) have been reported as possible causes of haematological toxicity. This is a review of the literature in which different clinical situations involving red blood cells, white blood cells, platelets and impaired coagulation are detailed and the drugs more frequently involved are listed. The haematological adverse reactions detailed here include: aplastic anemia, haemolitic anemia, leukopenia, agranulocytosis, leukocytosis, eosinophilia, thrombocytosis, thrombocytopenia, disordered platelet function and impaired coagulation. The haematologic toxicity profile of the drugs more frequently involved: lithium, clozapine, carbamazepine, valproic acid and SSRI antidepressants is mentioned. PMID:19424521

  6. Nonlinear neural mapping analysis of the adverse effects of drugs.

    PubMed

    Domine, D; Guillon, C; Devillers, J; Lacroix, R; Lacroix, J; Doré, J C

    1998-01-01

    Numerous drugs have been identified as presenting adverse effects towards the driving of vehicles. A large set of these drugs was compiled and classified into ten categories. Nonlinear neural mapping (N2M) was used to derive a typology of these molecules and also to link their adverse effects to therapeutic categories and structural information. PMID:9517012

  7. Using Literature-Based Discovery to Explain Adverse Drug Effects.

    PubMed

    Hristovski, Dimitar; Kastrin, Andrej; Dinevski, Dejan; Burgun, Anita; Žiberna, Lovro; Rindflesch, Thomas C

    2016-08-01

    We report on our research in using literature-based discovery (LBD) to provide pharmacological and/or pharmacogenomic explanations for reported adverse drug effects. The goal of LBD is to generate novel and potentially useful hypotheses by analyzing the scientific literature and optionally some additional resources. Our assumption is that drugs have effects on some genes or proteins and that these genes or proteins are associated with the observed adverse effects. Therefore, by using LBD we try to find genes or proteins that link the drugs with the reported adverse effects. These genes or proteins can be used to provide insight into the processes causing the adverse effects. Initial results show that our method has the potential to assist in explaining reported adverse drug effects. PMID:27318993

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

    PubMed Central

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

    2016-01-01

    Objective 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. Methods 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. Results 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. Conclusions 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. PMID:27366123

  9. Pharmacology, Toxicology, and Adverse Effects of Synthetic Cannabinoid Drugs.

    PubMed

    Gurney, S M R; Scott, K S; Kacinko, S L; Presley, B C; Logan, B K

    2014-01-01

    Synthetic cannabinoid drugs have become an established part of the recreational drug landscape in the United States and internationally. These drugs are manufactured in clandestine laboratories internationally and distributed in the United States in smoking mixtures, use of which produces effects very similar to use of marijuana. The adverse-effect profile of the drugs has not been studied in humans and infrequently in animal models, so much of the information about their toxicity comes from emergency department and treatment reports and forensic case studies. This review considers the discovery and characterization of the endocannabinoid system, approaches to receptor-binding studies of various synthetic cannabinoids from the first wave of naphthoylindoles (e.g., JWH-018) to the emerging adamantoylindole drugs (e.g., AKB-48), and their analogs, to evaluate the potential activity of drugs in this class. Currently employed approaches to assessing functional activity of the drugs using in vitro and in vivo models is also described, and comparisons made to the effects of THC. The physiological effects of activation of the endocannabinoid system in humans are reviewed, and the physiological effects of cannabinoid use are described. Case reports of adverse events including emergency department admissions, mental health admissions, and clinical and forensic case reports are presented in detail and discussed to summarize the current state of knowledge of adverse effects, both clinical and forensic in humans, including effects on driving ability, and tissue injury and death. The greatest weight is accorded to those reports that include toxicological confirmation of use. Finally, we discuss the current status of attempts to schedule and control the distribution of synthetic cannabinoids and the relevance of receptor binding and functional activity in this context. There is growing toxicological and pharmacological evidence of impairment, psychosis, tissue injury, and

  10. Adverse effects of drugs on the immature kidney.

    PubMed

    Guignard, J P; Gouyon, J B

    1988-01-01

    The immature kidney may be adversely affected by a variety of vasoactive or diuretic drugs, either administered to the mother during pregnancy, or to the neonate. Inhibitors of the angiotensin-converting enzyme administered to the hypertensive pregnant woman can severely and sometimes definitely impair renal function in the fetus, leading to postnatal anuria. Pathogenesis involves interference with the renin-angiotensin system and the prostaglandins. Beta-adrenergic agents administered during labor depress glomerular filtration rate transiently. Tolazoline, an alpha-adrenergic blocking agent useful in the treatment of persistent pulmonary hypertension of the neonate induces intense renal vasoconstriction with consequent hypoperfusion. Indomethacin, a prostaglandin synthetase inhibitor used for the pharmacological closure of a patent ductus arteriosus, also increases renal vascular resistance, and decreases urine output. Furosemide, the drug most often used in oliguric neonates, may also adversely affect the newborn infant. Its use has been associated with an increase in the incidence of patent ductus arteriosus, hypercalciuria, nephrocalcinosis and secondary hyperparathyroidism. These observations demonstrate that the proper use of drugs requires that the therapeutic endpoint be clearly defined and the predictable side effects be anticipated. PMID:2901276

  11. Potential adverse effects of discontinuing psychotropic drugs. Part 3: Antipsychotic, dopaminergic, and mood-stabilizing drugs.

    PubMed

    Howland, Robert H

    2010-08-01

    Abrupt discontinuation of antipsychotic drugs in patients with schizophrenia is associated with earlier, and often more severe, illness episodes than are seen with gradual discontinuation. Antipsychotic drugs can cause various abnormal motor syndromes, but abruptly stopping them has been associated with the seemingly paradoxical development of similar motor syndromes, such as withdrawal dyskinesias, parkinsonian symptoms, dystonias, and neuroleptic malignant syndrome. Dopamine-releasing and dopamine-agonist drugs are used to treat some of the motor syndromes caused by antipsychotic drugs, but their abrupt discontinuation can also be associated with abnormal syndromes. When antipsychotic drugs, lithium, or certain anticonvulsant drugs are used for treatment of bipolar disorder, rapid versus gradual discontinuation is more likely to lead to greater mood instability and manic relapse. If necessary, these medications should be gradually tapered to minimize all types of adverse discontinuation effects. Patients should be educated about the possible adverse effects of abrupt medication discontinuation. PMID:20669865

  12. Adverse Effects of Common Drugs: Children and Adolescents.

    PubMed

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

    2015-09-01

    Drug use and harms are increasingly common among newborns, infants, children, and adolescents during ambulatory practice, emergency department, and in-hospital treatment, including treatment in pediatric intensive care units. The pharmacokinetic and pharmacodynamic parameters of drugs often are different for children compared with adults and must be considered before prescribing. Drug exposure and the potential for harms also should be considered for fetuses and breastfeeding infants. As with adult patients, a thorough drug and allergy history (including nonprescription drugs and herbal and dietary supplements) should be obtained and reviewed at each medical visit. Children and adolescents are increasingly at risk of drug harm/overdose through accidental or intentional ingestion of nonprescription and prescription drugs (eg, cough and cold preparations, candy-appearing vitamins, stimulants, narcotics). Parents and caregivers should receive training in the proper use, storage, and administration of all drugs. Prescribing clinicians should be vigilant in withholding unnecessary drugs, such as antibiotics for viral infections. When prescribing, clinicians should be aware of common drugs frequently associated with adverse reactions, including stimulants, antipsychotics, analgesics, asthma therapies, acne therapies, and tumor necrosis factor inhibitors. Scientifically based prescribing practices should be used and consultation with evidence-based resources and pharmacists sought as needed. PMID:26375994

  13. Adverse antibiotic drug interactions.

    PubMed

    Bint, A J; Burtt, I

    1980-07-01

    There is enormous potential for drug interactions in patients who, today, often receive many drugs. Antibiotics are prominent amongst the groups of drugs commonly prescribed. Many interactions take place at the absorption stage. Antacids and antidiarrhoeal preparations, in particular, can delay and reduce the absorption of antibiotics such as tetracyclines and clindamycin, by combining with them in the gastrointestinal tract to form chelates or complexes. Other drugs can affect gastric motility, which in turn often controls the rate at which antibiotics are absorbed. Some broad spectrum antibiotics can alter the bacterial flora of the gut which may be related to malabsorption states. The potentiation of toxic side effects of one drug by another is a common type of interaction. Antibiotics which are implicated in this type of interaction are those which themselves possess some toxicity such as aminoglycosides, some cephalosporins, tetracyclines and colistin. Some of the most important adverse interactions with antibiotics are those which involve other drugs which have a low toxicity/efficacy ratio. These include anticoagulants such as warfarin, anticonvulsants such as phenytoin and phenobarbitone and oral antidiabetic drugs like tolbutamide. Risk of interaction arises when the metabolism of these drugs is inhibited by liver microsomal enzyme inhibitors such as some sulphonamides and chloramphenicol, or is enhanced by enzyme inducers such as rifampicin. PMID:6995091

  14. ADVERSE CUTANEOUS DRUG REACTION

    PubMed Central

    Nayak, Surajit; Acharjya, Basanti

    2008-01-01

    In everyday clinical practice, almost all physicians come across many instances of suspected adverse cutaneous drug reactions (ACDR) in different forms. Although such cutaneous reactions are common, comprehensive information regarding their incidence, severity and ultimate health effects are often not available as many cases go unreported. It is also a fact that in the present world, almost everyday a new drug enters market; therefore, a chance of a new drug reaction manifesting somewhere in some form in any corner of world is unknown or unreported. Although many a times, presentation is too trivial and benign, the early identification of the condition and identifying the culprit drug and omit it at earliest holds the keystone in management and prevention of a more severe drug rash. Therefore, not only the dermatologists, but all practicing physicians should be familiar with these conditions to diagnose them early and to be prepared to handle them adequately. However, we all know it is most challenging and practically difficult when patient is on multiple medicines because of myriad clinical symptoms, poorly understood multiple mechanisms of drug-host interaction, relative paucity of laboratory testing that is available for any definitive and confirmatory drug-specific testing. Therefore, in practice, the diagnosis of ACDR is purely based on clinical judgment. In this discussion, we will be primarily focusing on pathomechanism and approach to reach a diagnosis, which is the vital pillar to manage any case of ACDR. PMID:19967009

  15. [Adverse or toxic effects of drugs in medical practice: a one-year follow-up].

    PubMed

    Grange, J C

    1990-01-01

    In order to analyse the response of pharmaceutical companies to adverse drug reaction reports, 37 suspected side effects were sent by mail to the 30 companies concerned. The time period involved was 1 year and corresponded to a total of 3341 consultations in general practice. Companies answered in 29 cases (78.3%), sent 21 reply forms and returned 3 evaluations of adverse drugs reactions to the reporting doctor. The high percentage of adverse drug reactions (1.07 per one hundred consultations), the doctor's work-load and poor feed-back lead one to reflect on the usefulness of systematic adverse drug reaction reporting by general practitioners. PMID:2399517

  16. 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…

  17. Adverse ocular reactions to drugs.

    PubMed Central

    Spiteri, M. A.; James, D. G.

    1983-01-01

    Drugs acting on various parts of the body may also affect the eye insidiously. Increased awareness of such drug toxicity by the prescribing doctor should encourage him to consider effects on the cornea, lens, retina, optic nerve and elsewhere when checking the patient's progress. The following review concerns adverse ocular effects of systemic drug administration. PMID:6356101

  18. [Cutaneous adverse drug reactions].

    PubMed

    Lebrun-Vignes, B; Valeyrie-Allanore, L

    2015-04-01

    Cutaneous adverse drug reactions (CADR) represent a heterogeneous field including various clinical patterns without specific features suggesting drug causality. Exanthematous eruptions, urticaria and vasculitis are the most common forms of CADR. Fixed eruption is uncommon in western countries. Serious reactions (fatal outcome, sequelae) represent 2% of CADR: bullous reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), DRESS (drug reaction with eosinophilia and systemic symptoms or drug-induced hypersensitivity syndrome) and acute generalized exanthematous pustulosis (AGEP). These forms must be quickly diagnosed to guide their management. The main risk factors are immunosuppression, autoimmunity and some HLA alleles in bullous reactions and DRESS. Most systemic drugs may induce cutaneous adverse reactions, especially antibiotics, anticonvulsivants, antineoplastic drugs, non-steroidal anti-inflammatory drugs, allopurinol and contrast media. Pathogenesis includes immediate or delayed immunologic mechanism, usually not related to dose, and pharmacologic/toxic mechanism, commonly dose-dependent or time-dependent. In case of immunologic mechanism, allergologic exploration is possible to clarify drug causality, with a variable sensitivity according to the drug and to the CADR type. It includes epicutaneous patch testing, prick test and intradermal test. However, no in vivo or in vitro test can confirm the drug causality. To determine the cause of the eruption, a logical approach based on clinical characteristics, chronologic factors and elimination of differential diagnosis is required, completed with a literature search. A reporting to pharmacovigilance network is essential in case of a serious CADR whatever the suspected drug and in any case if the involved drug is a newly marketed one or unusually related to cutaneous reactions. PMID:25458866

  19. Comprehensive evaluations of the adverse effects of drugs: importance of appropriate study selection and data sources

    PubMed Central

    Golder, Su P.; Vandenbroucke, Jan P.

    2011-01-01

    While systematic reviews and meta-analyses are at the top of the evidence hierarchy, most of the methodology has focused on assessing treatment benefit. Hence, we propose a structured framework for the initial steps of searching and identifying relevant data sources so that adverse effects can be evaluated in a comprehensive, unbiased manner. The unique methodological challenges stem from the difficulties of addressing diverse outcomes encompassing common, mild symptoms to rare, fatal events. Retrieval of the most appropriate studies should be specifically tailored to fit the nature of the adverse effects, according to the primary objective and study question. In our framework, the structure of the review takes different forms depending on whether the main aim is on scoping/hypothesis generation, or evaluating statistically the magnitude of risk (hypothesis testing), or clarifying characteristics and risk factors of the adverse effect. The wide range of data sources covering adverse effects all have distinct strengths and limitations, and selection of appropriate sources depends on characteristics of the adverse effect (e.g. background incidence and effect size of the drug, clinical presentation, time of onset after drug exposure). Reviewers need to retrieve particular study designs that are most likely to yield robust data on the adverse effects of interest, rather than rely on studies that cannot reliably detect adverse effects, and may yield ‘false negatives’. Type II errors (a particular problem when evaluating rare adverse effects) can lull us into a false sense of security (e.g. wrongly concluding that there was no significant difference in harm between drug and control, with the drug erroneously judged as safe). Given the rapid rate at which methodological improvements occur, this proposed framework is by no means definitive, but aims to stimulate further debate and discussion amongst the pharmacoepidemiological and systematic review communities to reach

  20. ISMP Adverse Drug Reactions

    PubMed Central

    2013-01-01

    The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration’s (FDA’s) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA’s MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner. PMID:24421544

  1. 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

  2. A screening study of drug-drug interactions in cerivastatin users: an adverse effect of clopidogrel.

    PubMed

    Floyd, J S; Kaspera, R; Marciante, K D; Weiss, N S; Heckbert, S R; Lumley, T; Wiggins, K L; Tamraz, B; Kwok, P-Y; Totah, R A; Psaty, B M

    2012-05-01

    An analysis of a case-control study of rhabdomyolysis was conducted to screen for previously unrecognized cytochrome P450 enzyme (CYP) 2C8 inhibitors that may cause other clinically important drug-drug interactions. Medication use in cases of rhabdomyolysis using cerivastatin (n = 72) was compared with that in controls using atorvastatin (n = 287) for the period 1998-2001. The use of clopidogrel was strongly associated with rhabdomyolysis (odds ratio (OR) 29.6; 95% confidence interval (CI), 6.1-143). In a replication effort that used the US Food and Drug Administration (FDA) Adverse Event Reporting System (AERS), it was found that clopidogrel was used more commonly in patients with rhabdomyolysis receiving cerivastatin (17%) than in those receiving atorvastatin (0%, OR infinity; 95% CI = 5.2-infinity). Several medications were tested in vitro for their potential to cause drug-drug interactions. Clopidogrel, rosiglitazone, and montelukast were the most potent inhibitors of cerivastatin metabolism. Clopidogrel and its metabolites also inhibited cerivastatin metabolism in human hepatocytes. These epidemiological and in vitro findings suggest that clopidogrel may cause clinically important, dose-dependent drug-drug interactions with other medications metabolized by CYP2C8. PMID:22419147

  3. Adverse effects of the antimalaria drug, mefloquine: due to primary liver damage with secondary thyroid involvement?

    PubMed Central

    Croft, Ashley M; Herxheimer, Andrew

    2002-01-01

    Background Mefloquine is a clinically important antimalaria drug, which is often not well tolerated. We critically reviewed 516 published case reports of mefloquine adverse effects, to clarify the phenomenology of the harms associated with mefloquine, and to make recommendations for safer prescribing. Presentation We postulate that many of the adverse effects of mefloquine are a post-hepatic syndrome caused by primary liver damage. In some users we believe that symptomatic thyroid disturbance occurs, either independently or as a secondary consequence of the hepatocellular injury. The mefloquine syndrome presents in a variety of ways including headache, gastrointestinal disturbances, nervousness, fatigue, disorders of sleep, mood, memory and concentration, and occasionally frank psychosis. Previous liver or thyroid disease, and concurrent insults to the liver (such as from alcohol, dehydration, an oral contraceptive pill, recreational drugs, and other liver-damaging drugs) may be related to the development of severe or prolonged adverse reactions to mefloquine. Implications We believe that people with active liver or thyroid disease should not take mefloquine, whereas those with fully resolved neuropsychiatric illness may do so safely. Mefloquine users should avoid alcohol, recreational drugs, hormonal contraception and co-medications known to cause liver damage or thyroid damage. With these caveats, we believe that mefloquine may be safely prescribed in pregnancy, and also to occupational groups who carry out safety-critical tasks. Testing Mefloquine's adverse effects need to be investigated through a multicentre cohort study, with small controlled studies testing specific elements of the hypothesis. PMID:11914150

  4. Evaluating the potential effectiveness of using computerized information systems to prevent adverse drug events.

    PubMed Central

    Anderson, J. G.; Jay, S. J.; Anderson, M.; Hunt, T. J.

    1997-01-01

    In this study a dynamic computer simulation model is used to estimate the effectiveness of various information systems applications designed to detect and prevent medication errors that result in adverse drug events (ADEs). The model simulates the four stages of the drug ordering and delivery system: prescribing, transcribing, dispensing and administering drugs. In this study we simulated interventions that have been demonstrated in prior studies to decrease error rates. The results demonstrated that a computerized information system that detected 26% of medication errors and prevented associated ADEs could save 1,226 days of excess hospitalization and $1.4 million in hospital costs annually. Those results suggest that such systems are potentially a cost-effective means of preventing ADEs in hospitals. The results demonstrated the importance of viewing adverse drug events from a systems perspective. Prevention efforts that focus on a single stage of the process had limited impact on the overall error rate. This study suggests that system-wide changes to the drug-ordering and delivery system are required to significantly reduce adverse drug events in a hospital setting. PMID:9357622

  5. Statistical Mining of Potential Drug Interaction Adverse Effects in FDA's Spontaneous Reporting System.

    PubMed

    Harpaz, Rave; Haerian, Krystl; Chase, Herbert S; Friedman, Carol

    2010-01-01

    Many adverse drug effects (ADEs) can be attributed to drug interactions. Spontaneous reporting systems (SRS) provide a rich opportunity to detect novel post-marketed drug interaction adverse effects (DIAEs), as they include populations not well represented in clinical trials. However, their identification in SRS is nontrivial. Most existing research have addressed the statistical issues used to test or verify DIAEs, but not their identification as part of a systematic large scale database-wide mining process as discussed in this work. This paper examines the application of a highly optimized and tailored implementation of the Apriori algorithm, as well as methods addressing data quality issues, to the identification of DIAEs in FDAs SRS. PMID:21346985

  6. 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. PMID:14746774

  7. Identifying Adverse Effects of HIV Drug Treatment and Associated Sentiments Using Twitter

    PubMed Central

    Adrover, Cosme; Bodnar, Todd; Huang, Zhuojie

    2015-01-01

    Background Social media platforms are increasingly seen as a source of data on a wide range of health issues. Twitter is of particular interest for public health surveillance because of its public nature. However, the very public nature of social media platforms such as Twitter may act as a barrier to public health surveillance, as people may be reluctant to publicly disclose information about their health. This is of particular concern in the context of diseases that are associated with a certain degree of stigma, such as HIV/AIDS. Objective The objective of the study is to assess whether adverse effects of HIV drug treatment and associated sentiments can be determined using publicly available data from social media. Methods We describe a combined approach of machine learning and crowdsourced human assessment to identify adverse effects of HIV drug treatment solely on individual reports posted publicly on Twitter. Starting from a large dataset of 40 million tweets collected over three years, we identify a very small subset (1642; 0.004%) of individual reports describing personal experiences with HIV drug treatment. Results Despite the small size of the extracted final dataset, the summary representation of adverse effects attributed to specific drugs, or drug combinations, accurately captures well-recognized toxicities. In addition, the data allowed us to discriminate across specific drug compounds, to identify preferred drugs over time, and to capture novel events such as the availability of preexposure prophylaxis. Conclusions The effect of limited data sharing due to the public nature of the data can be partially offset by the large number of people sharing data in the first place, an observation that may play a key role in digital epidemiology in general. PMID:27227141

  8. [Analysis of the cardiac side effects of antipsychotics: Japanese Adverse Drug Event Report Database (JADER)].

    PubMed

    Ikeno, Takashi; Okumara, Yasuyuki; Kugiyama, Kiyotaka; Ito, Hiroto

    2013-08-01

    We analyzed the cases of side effects due to antipsychotics reported to Japan's Pharmaceuticals and Medical Devices Agency (PMDA) from Jan. 2004 to Dec. 2012. We used the Japanese Adverse Drug Event Report Database (JADER) and analyzed 136 of 216,945 cases using the defined terms. We also checked the cardiac adverse effects listed in the package inserts of the antipsychotics involved. We found cases of Ikr blockade resulting in sudden death (49 cases), electrocardiogram QT prolonged (29 cases), torsade de pointes (TdP, 19 cases), ventricular fibrillation (VF, 10 cases). M2 receptor blockade was observed in tachycardia (8 cases) and sinus tachycardia (3 cases). Calmodulin blockade was involved in reported cardiomyopathy (3 cases) and myocarditis (1 case). Multiple adverse events were reported simultaneously in 14 cases. Our search of package inserts revealed warnings regarding electrocardiogram QT prolongation (24 drugs), tachycardia (23), sudden death (18), TdP (14), VF (3), myocarditis (1) and cardiomyopathy (1). We suggest that when an antipsychotic is prescribed, the patient should be monitored regularly with ECG, blood tests, and/or biochemical tests to avoid adverse cardiac effects. PMID:25069255

  9. Epigenetics and transcriptomics to detect adverse drug effects in model systems of human development.

    PubMed

    Balmer, Nina V; Leist, Marcel

    2014-07-01

    Prenatal exposure to environmental chemicals or drugs has been associated with functional or structural deficits and the development of diseases in later life. For example, developmental neurotoxicity (DNT) is triggered by lead, and this compound may predispose to neurodegenerative diseases in later life. The molecular memory for such late consequences of early exposure is not known, but epigenetic mechanisms (modification of the chromatin structure) could take this role. Examples and underlying mechanisms have been compiled here for the field of DNT. Moreover, we addressed the question as to what readout is suitable for addressing drug memory effects. We summarize how complex developmental processes can be modelled in vitro by using the differentiation of human stem cells. Although cellular models can never replicate the final human DNT phenotype, they can model the adverse effect that a chemical has on key biological processes essential for organ formation and function. Highly information-rich transcriptomics data may inform on these changes and form the bridge from in vitro models to human prediction. We compiled data showing that transcriptome analysis can indicate toxicity patterns of drugs. A crucial question to be answered in our systems is when and how transcriptome changes indicate adversity (as opposed to transient adaptive responses), and how drug-induced changes are perpetuated over time even after washout of the drug. We present evidence for the hypothesis that changes in the histone methylation pattern could represent the persistence detector of an early insult that is transformed to an adverse effect at later time-points in life. PMID:24476462

  10. Adverse drug reactions in dermatology.

    PubMed

    Ferner, R E

    2015-03-01

    Adverse drug reactions (ADRs) - that is, unintended and harmful responses to medicines - are important to dermatologists because many present with cutaneous signs and because dermatological treatments can cause serious ADRs. The detection of ADRs to new drugs is often delayed because they have a long latency or are rare or unexpected. This means that ADRs to newer agents emerge only slowly after marketing. ADRs are part of the differential diagnosis of unusual rashes. A good drug history that includes details of drug dose, time-course of the reaction and factors that may make the patient more susceptible, will help. For example, Stevens-Johnson syndrome with abacavir is much commoner in patients with HLA-B*5701, and has a characteristic time course. Newer agents have brought newer reactions; for example, acneiform rashes associated with epidermal growth factor receptor inhibitors such as erlotinib. Older systemic agents used to treat skin disease, including corticosteroids and methotrexate, cause important ADRs. The adverse effects of newer biological agents used in dermatology are becoming clearer; for example, hypersensitivity reactions or loss of efficacy from antibody formation and progressive multifocal leucoencephalopathy due to reactivation of latent JC (John Cunningham) virus infections during efalizumab treatment. Unusual or serious harm from medicines, including ADRs, medication errors and overdose, should be reported. The UK Yellow Card scheme is online, and patients can report their own ADRs. PMID:25622648

  11. Adverse Drug Interactions

    PubMed Central

    Becker, Daniel E.

    2011-01-01

    The potential for interactions with current medications should always be considered when administering or prescribing any drug. Considering the staggering number of drugs patients may be taking, this task can be daunting. Fortunately, drug classes employed in dental practice are relatively few in number and therapy is generally brief in duration. While this reduces the volume of potential interactions, there are still a significant number to be considered. This article will review basic principles of drug interactions and highlight those of greatest concern in dental practice. PMID:21410363

  12. Adverse Drug Effects and Preoperative Medication Factors Related to Perioperative Low-Dose Ketamine Infusions.

    PubMed

    Schwenk, Eric S; Goldberg, Stephen F; Patel, Ronak D; Zhou, Jon; Adams, Douglas R; Baratta, Jaime L; Viscusi, Eugene R; Epstein, Richard H

    2016-01-01

    High-dose opioid administration is associated with significant adverse events. Evidence suggests that low-dose ketamine infusions improve perioperative analgesia over conventional opioid management, but usage is highly variable. Ketamine's adverse drug effects (ADEs) are well known, but their prevalence during low-dose infusions in a clinical setting and how often they lead to infusion discontinuation are unknown. The purposes of this study were 3-fold: (1) to identify patient factors associated with initiation of ketamine infusions during spine surgery, (2) to identify specific spine procedures in which ketamine has been used most frequently, and (3) to identify ADEs associated with postoperative ketamine infusions and which ADEs most frequently led to discontinuation. Spine surgery was chosen because of its association with moderate to severe pain and a relatively high use of ketamine infusions in this population at our hospital. PMID:27281730

  13. 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

  14. Tramadol hydrochloride: pharmacokinetics, pharmacodynamics, adverse side effects, co-administration of drugs and new drug delivery systems.

    PubMed

    Vazzana, M; Andreani, T; Fangueiro, J; Faggio, C; Silva, C; Santini, A; Garcia, M L; Silva, A M; Souto, E B

    2015-03-01

    Tramadol hydrochloride (TrHC) is a synthetic analgesic drug exhibiting opioid and non-opioid properties, acting mainly on the central nervous system. It has been mostly used to treat pain, although its use to treat anxiety and depression has also been documented. These properties arise from the fact that they inhibit serotonin (5-HT) reuptake augmenting 5-HT concentration on the synaptic cleft. Despite this, TrHC has also been described to have several side effects which are mainly due to its fast metabolization and excretion which in turn requires multiple doses per day. To surpass this limitation, new pharmaceutical formulations are being developed intending the protection, target and sustained delivery as well as a reduction on daily dose aiming a reduction on the side effects. In the present work we have revised the efficacy, safety, biological and adverse effects of TrHC, and the added value of developing a novel drug delivery system for topical administration. PMID:25776506

  15. Multi-omic landscape of rheumatoid arthritis: re-evaluation of drug adverse effects

    PubMed Central

    Tieri, Paolo; Zhou, XiaoYuan; Zhu, Lisha; Nardini, Christine

    2014-01-01

    Objective: To provide a frame to estimate the systemic impact (side/adverse events) of (novel) therapeutic targets by taking into consideration drugs potential on the numerous districts involved in rheumatoid arthritis (RA) from the inflammatory and immune response to the gut-intestinal (GI) microbiome. Methods: We curated the collection of molecules from high-throughput screens of diverse (multi-omic) biochemical origin, experimentally associated to RA. Starting from such collection we generated RA-related protein-protein interaction (PPI) networks (interactomes) based on experimental PPI data. Pharmacological treatment simulation, topological and functional analyses were further run to gain insight into the proteins most affected by therapy and by multi-omic modeling. Results: Simulation on the administration of MTX results in the activation of expected (apoptosis) and adverse (nitrogenous metabolism alteration) effects. Growth factor receptor-bound protein 2 (GRB2) and Interleukin-1 Receptor Associated Kinase-4 (IRAK4, already an RA target) emerge as relevant nodes. The former controls the activation of inflammatory, proliferative and degenerative pathways in host and pathogens. The latter controls immune alterations and blocks innate response to pathogens. Conclusions: This multi-omic map properly recollects in a single analytical picture known, yet complex, information like the adverse/side effects of MTX, and provides a reliable platform for in silico hypothesis testing or recommendation on novel therapies. These results can support the development of RA translational research in the design of validation experiments and clinical trials, as such we identify GRB2 as a robust potential new target for RA for its ability to control both synovial degeneracy and dysbiosis, and, conversely, warn on the usage of IRAK4-inhibitors recently promoted, as this involves potential adverse effects in the form of impaired innate response to pathogens. PMID:25414848

  16. Nurses must report adverse drug reactions.

    PubMed

    Griffith, Richard

    There is renewed determination throughout the European Union (EU) to reduce the economic cost and high death rate associated with adverse drug reactions through better pharmacovigilance. Timely reporting and sharing of information concerning adverse drug reactions is vital to the success of this initiative. In the UK, the reporting of serious adverse drug reactions is facilitated by the Yellow Card Scheme, yet despite being well placed to monitor the effect of medicines on patients, nurses do not make full use of the scheme. This article sets out the impact of adverse drug reactions in the EU and argues that it is essential that nurses must be at the vanguard of adverse reaction reporting if the EU's pharmacovigilance initiative is to be a success. PMID:23905231

  17. Severe cutaneous adverse drug reactions.

    PubMed

    Chung, Wen-Hung; Wang, Chuang-Wei; Dao, Ro-Lan

    2016-07-01

    The clinical manifestations of drug eruptions can range from mild maculopapular exanthema to severe cutaneous adverse drug reactions (SCAR), including drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) which are rare but occasionally fatal. Some pathogens may induce skin reactions mimicking SCAR. There are several models to explain the interaction of human leukocyte antigen (HLA), drug and T-cell receptor (TCR): (i) the "hapten/prohapten" theory; (ii) the "p-i concept"; (iii) the "altered peptide repertoire"; and (iv) the "altered TCR repertoire". The checkpoints of molecular mechanisms of SCAR include specific drug antigens interacting with the specific HLA loci (e.g. HLA-B*15:02 for carbamazepine-induced SJS/TEN and HLA-B*58:01 for allopurinol-induced SCAR), involvement of specific TCR, induction of T-cell-mediated responses (e.g. granulysin, Fas ligand, perforin/granzyme B and T-helper 1/2-associated cytokines) and cell death mechanism (e.g. miR-18a-5p-induced apoptosis; annexin A1 and formyl peptide receptor 1-induced necroptosis in keratinocytes). In addition to immune mechanism, metabolism has been found to play a role in the pathogenesis of SCAR, such as recent findings of strong association of CYP2C9*3 with phenytoin-induced SCAR and impaired renal function with allopurinol SCAR. With a better understanding of the mechanisms, effective therapeutics and prevention for SCAR can be improved. PMID:27154258

  18. 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. PMID:25987241

  19. Assessing the sedative (adverse) effects of antiallergic drugs by quantitative electroencephalography: effects of setastine a non-sedating antihistaminic drug.

    PubMed

    Rajna, P; Veres, J

    1994-01-01

    In order to assess the effects of Loderix (setastine) on the EEG ten healthy male volunteers were investigated in double-blind, placebo-controlled, cross-over arrangement. In addition to the test compound (Loderix) volunteers were treated with vehicle and with two referent drugs (terfenadine, Teldane, and chloropyramine HCl, Suprastin) possessing sedative effects of very different degrees. The different effects of the referent drugs on the central nervous system (CNS) were precisely indicated by the posterior alpha/theta ratio in the EEG. This marker parameter was affected by Loderix in the same direction as by Teldane and in the opposite direction as compared to Suprastin. In addition, Loderix increased the beta frequency range in the median areas of both hemispheres, moreover, it increased the total EEG power. The latter changes raise the question if Loderix has an "own" action on the EEG. (The observed "own" effect could not even be brought into connection with decrease of the vigilance level). The results strengthen the view that the action of Loderix on the EEG is similar to that of induced by Teldane, a drug very favourable in respect of the sedative side effects. Moreover, the drug did not affect the EEG power spectra in a direction that referred to sedative action. The spectral parameters in the "pharmaco" EEG recordings seem to be useful in the objective definition of the central (psychotropic) side-effects of drugs. This is a methodical achievement of the present study. PMID:7761959

  20. Characterization of a novel mechanism accounting for the adverse cholinergic effects of the anticancer drug irinotecan

    PubMed Central

    Blandizzi, Corrado; De Paolis, Barbara; Colucci, Rocchina; Lazzeri, Gloria; Baschiera, Fabio; Del Tacca, Mario

    2001-01-01

    This study investigates the mechanisms accounting for the adverse cholinergic effects of the antitumour drug irinotecan. The activity of irinotecan and its active metabolite, 7-ethyl-10-hydroxy-camptothecin (SN-38), was assayed in models suitable for pharmacological studies on cholinergic system. Irinotecan moderately inhibited human or electric eel acetylcholinesterase activity, SN-38 had no effect, whereas physostigmine blocked both the enzymes with high potency and efficacy. Irinotecan and SN-38 did not affect spontaneous or electrically-induced contractile activity of human colonic muscle. Acetylcholine and dimethylphenylpiperazinium (DMPP) caused phasic contractions or relaxations, respectively. Physostigmine enhanced the motor responses elicited by electrical stimulation. Although irinotecan and SN-38 did not modify the basal contractile activity of guinea-pig ileum longitudinal muscle strips, irinotecan 100 μM moderately enhanced cholinergic twitch contractions. Acetylcholine or DMPP caused phasic contractions, whereas physostigmine enhanced the twitch responses. Electrically-induced [3H]-acetylcholine release was reduced by irinotecan (100 μM) or physostigmine (0.1 μM). Intravenous irinotecan stimulated gastric acid secretion in rats, but no effects were obtained with SN-38, physostigmine or i.c.v. irinotecan. Hypersecretion induced by irinotecan was partly prevented by ondansetron, and unaffected by capsazepine. In the presence of atropine, vagotomy and systemic or vagal ablation of capsaicin-sensitive afferent fibres, irinotecan did not stimulate gastric secretion. The present results indicate that irinotecan and SN-38 do not act as specific acetylcholinesterase blockers or acetylcholine receptor agonists. It is rather suggested that irinotecan promotes a parasympathetic discharge to peripheral organs, mediated by capsaicin-sensitive vagal afferent fibres, and that serotonin 5-HT3 receptors are implicated in the genesis of vago-vagal reflex

  1. The Combined Effects of Prenatal Drug Exposure and Early Adversity on Neurobehavioral Disinhibition in Childhood and Adolescence

    PubMed Central

    Fisher, Philip A.; Lester, Barry M.; DeGarmo, David S.; LaGasse, Linda L.; Lin, Hai; Shankaran, Seetha; Bada, Henrietta S.; Bauer, Charles R.; Hammond, Jane; Whitaker, Toni; Higgins, Rosemary

    2012-01-01

    The negative effects of prenatal substance exposure on neurobiological and psychological development and of early adversity are clear, but little is known about their combined effects. In this study, multilevel analyses of the effects of prenatal substance exposure and early adversity on the emergence of neurobehavioral disinhibition in adolescence were conducted. Neurobehavioral disinhibition has previously been observed to occur frequently in multiproblem youth from high-risk backgrounds. In the present study, neurobehavioral disinhibition was assessed via behavioral dysregulation and poor executive function composite measures. Data were drawn from a prospective longitudinal investigation of prenatal substance exposure that included 1073 participants followed from birth through adolescence. The results from latent growth modeling analyses showed mean stability but significant individual differences in behavioral dysregulation and mean decline with individual differences in executive function difficulties. Prior behavioral dysregulation predicted increased executive function difficulties. Prenatal drug use predicted the emergence and growth in neurobehavioral disinhibition across adolescence (directly for behavioral dysregulation and indirectly for executive function difficulties via early adversity and behavioral dysregulation). Prenatal drug use and early adversity exhibited unique effects on growth in behavioral dysregulation; early adversity uniquely predicted executive function difficulties. These results are discussed in terms of implications for theory development, social policy, and prevention science. PMID:21756431

  2. [Adverse events of psychotropic drugs].

    PubMed

    Watanabe, Koichiro; Kikuchi, Toshiaki

    2014-01-01

    The authors discuss adverse events which are often missed but clinicians should pay attention to in order to preserve patients'quality of life(QOL). Among mood stabilizers, lithium may cause a urinary volume increase, hyperparathyroidism, and serum calcium elevation; sodium valproate possibly increases androgenic hormone levels and the risk of polycystic ovary syndrome (PCOS) as well as hypothyroidism. Moreover, in addition to teratogenesis, it has been reported that fetal exposure to a higher dose of valproate is associated with a lower intelligence quotient and higher incidence of autism spectrum disorders in children. Antidepressants with a higher affinity for serotonin transporters might induce gastrointestinal bleeding, and some antidepressants cause sexual dysfunction more frequently than others. Activation syndrome is still a key side effect which should be noted. Regarding the adverse events of antipsychotics, subjective side effects unpleasant to patients such as dysphoria and a lower subjective well-being should not be overlooked. We clinicians have to cope with adverse events worsening the QOL of patients with psychiatric disorders and, therefore, we need to adopt appropriate counter-measures. PMID:24864567

  3. Adverse events associated with incretin-based drugs in Japanese spontaneous reports: a mixed effects logistic regression model

    PubMed Central

    Narushima, Daichi; Kawasaki, Yohei; Takamatsu, Shoji

    2016-01-01

    Background: Spontaneous Reporting Systems (SRSs) are passive systems composed of reports of suspected Adverse Drug Events (ADEs), and are used for Pharmacovigilance (PhV), namely, drug safety surveillance. Exploration of analytical methodologies to enhance SRS-based discovery will contribute to more effective PhV. In this study, we proposed a statistical modeling approach for SRS data to address heterogeneity by a reporting time point. Furthermore, we applied this approach to analyze ADEs of incretin-based drugs such as DPP-4 inhibitors and GLP-1 receptor agonists, which are widely used to treat type 2 diabetes. Methods: SRS data were obtained from the Japanese Adverse Drug Event Report (JADER) database. Reported adverse events were classified according to the MedDRA High Level Terms (HLTs). A mixed effects logistic regression model was used to analyze the occurrence of each HLT. The model treated DPP-4 inhibitors, GLP-1 receptor agonists, hypoglycemic drugs, concomitant suspected drugs, age, and sex as fixed effects, while the quarterly period of reporting was treated as a random effect. Before application of the model, Fisher’s exact tests were performed for all drug-HLT combinations. Mixed effects logistic regressions were performed for the HLTs that were found to be associated with incretin-based drugs. Statistical significance was determined by a two-sided p-value <0.01 or a 99% two-sided confidence interval. Finally, the models with and without the random effect were compared based on Akaike’s Information Criteria (AIC), in which a model with a smaller AIC was considered satisfactory. Results: The analysis included 187,181 cases reported from January 2010 to March 2015. It showed that 33 HLTs, including pancreatic, gastrointestinal, and cholecystic events, were significantly associated with DPP-4 inhibitors or GLP-1 receptor agonists. In the AIC comparison, half of the HLTs reported with incretin-based drugs favored the random effect, whereas HLTs

  4. 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

  5. Adverse cutaneous drug eruptions: current understanding.

    PubMed

    Hoetzenecker, W; Nägeli, M; Mehra, E T; Jensen, A N; Saulite, I; Schmid-Grendelmeier, P; Guenova, E; Cozzio, A; French, L E

    2016-01-01

    Adverse cutaneous drug reactions are recognized as being major health problems worldwide causing considerable costs for health care systems. Most adverse cutaneous drug reactions follow a benign course; however, up to 2% of all adverse cutaneous drug eruptions are severe and life-threatening. These include acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Physicians should be aware of specific red flags to rapidly identify these severe cutaneous drug eruptions and initiate appropriate treatment. Besides significant progress in clinical classification and treatment, recent studies have greatly enhanced our understanding in the pathophysiology of adverse cutaneous drug reactions. Genetic susceptibilities to certain drugs have been identified in SJS/TEN patients, viral reactivation in DRESS has been elucidated, and the discovery of tissue resident memory T cells helps to better understand the recurrent site-specific inflammation in patients with fixed drug eruption. PMID:26553194

  6. Standardizing drug adverse event reporting data.

    PubMed

    Wang, Liwei; Jiang, Guoqian; Li, Dingcheng; Liu, Hongfang

    2013-01-01

    Normalizing data in the Adverse Event Reporting System (AERS), an FDA database, would improve the mining capacity of AERS for drug safety signal detection. In this study, we aim to normalize AERS and build a publicly available normalized Adverse drug events (ADE) data source.he drug information in AERS is normalized to RxNorm, a standard terminology source for medication. Drug class information is then obtained from the National Drug File - Reference Terminology (NDF-RT). Adverse drug events (ADE) are aggregated through mapping with the PT (Preferred Term) and SOC (System Organ Class) codes of MedDRA. Our study yields an aggregated knowledge-enhanced AERS data mining set (AERS-DM). The AERS-DM could provide more perspectives to mine AERS database for drug safety signal detection and could be used by research community in the data mining field. PMID:23920875

  7. Toxicity and adverse effects of Tamoxifen and other anti-estrogen drugs.

    PubMed

    Yang, Geniey; Nowsheen, Somaira; Aziz, Khaled; Georgakilas, Alexandros G

    2013-09-01

    Breast cancer is a heterogeneous disease affecting thousands of people every year. Multiple factors are responsible in causing breast cancer while a number of treatment options are also available for the disease. Tamoxifen is the most widely used anti-estrogen for the treatment of hormone-dependent breast cancer. The specific drug is used as a hormonal therapy for patients who exhibit estrogen receptor positive breast cancer. The pharmacological activity of Tamoxifen is dependent on its conversion to its active metabolite, endoxifen, by CYP2D6. Tamoxifen reduces the risk of recurrence and death from breast cancer when given as adjuvant therapy and provides effective palliation for patients with metastatic breast cancer. In this review we focus on the role of Tamoxifen in breast cancer treatment including mechanisms and side-effects. Finally, we discuss in detail the exciting prospects that lie ahead. PMID:23711794

  8. Pharmacogenetics of idiosyncratic adverse drug reactions.

    PubMed

    Pirmohamed, Munir

    2010-01-01

    Idiosyncratic adverse drug reactions are unpredictable and thought to have an underlying genetic etiology. With the completion of the human genome and HapMap projects, together with the rapid advances in genotyping technologies, we have unprecedented capabilities in identifying genetic predisposing factors for these relatively rare, but serious, reactions. The main roadblock to this is the lack of sufficient numbers of well-characterized samples from patients with such reactions. This is now beginning to be solved through the formation of international consortia, including developing novel ways of identifying and recruiting patients affected by these reactions, both prospectively and retrospectively. This has been led by the research on abacavir hypersensitivity - its association with HLA-B*5701 forms the gold standard of how we need to identify associations and implement them in clinical practice. Strong genetic predisposing factors have also been identified for hypersensitivity reactions such as are associated with carbamazepine, allopurinol, flucloxacillin, and statin-induced myopathy. However, for most other idiosyncratic adverse drug reactions, the genetic effect sizes have been low to moderate, although this may partly be due to the fact that only small numbers have been investigated and limited genotyping strategies have been utilized. It may also indicate that genetic predisposition will be dependent on multiple genes, with complex interactions with environmental factors. Irrespective of the strength of the genetic associations identified with individual idiosyncratic adverse drug reactions, it is important to undertake functional investigations to provide insights into the mechanism(s) of how the drug interacts with the gene variant to lead to a phenotype, which can take a multitude of clinical forms with variable severity. Such investigations will be essential in preventing the burden caused by idiosyncratic reactions, both in healthcare and in industry

  9. Identifying Adverse Drug Events by Relational Learning

    PubMed Central

    Page, David; Costa, Vítor Santos; Natarajan, Sriraam; Barnard, Aubrey; Peissig, Peggy; Caldwell, Michael

    2013-01-01

    The pharmaceutical industry, consumer protection groups, users of medications and government oversight agencies are all strongly interested in identifying adverse reactions to drugs. While a clinical trial of a drug may use only a thousand patients, once a drug is released on the market it may be taken by millions of patients. As a result, in many cases adverse drug events (ADEs) are observed in the broader population that were not identified during clinical trials. Therefore, there is a need for continued, post-marketing surveillance of drugs to identify previously-unanticipated ADEs. This paper casts this problem as a reverse machine learning task, related to relational subgroup discovery and provides an initial evaluation of this approach based on experiments with an actual EMR/EHR and known adverse drug events. PMID:24955289

  10. Investigation of adverse effects of interactions between herbal drugs and natural blood clotting mechanism.

    PubMed

    Adhyapak, M S; Kachole, M S

    2016-05-01

    Throughout the world, herbal medicines are consumed by most of the patients without considering their adverse effects. Many herbal medicines/plant extracts have been reported to interact with the natural blood clotting system. In continuation to this effort, thirty medicinal plant extracts were allowed to interact with citrated human blood and the clotting time was measured after re-calcification in vitro using Lee and White method. The aq. leaf ext. of Syzygium cumini and Camellia sinensis significantly prolonged the clotting time. In response to the prothrombin time and activated partial thromboplastin time tests, the ext. of C. sinensis showed normal APTT and marginally prolonged the PT to 16.7 s (control-15.2 s) while S. cumini showed normal PT but significantly prolonged the APTT to 66.9 s (control-20.7 s). This suggests that, C. sinensis acts on the extrinsic pathway while S. cumini on the intrinsic pathway. There are some common herbal formulations that are frequently used by the patients which contain above plant materials, like, Syzygium cumin in anti-diabetic formulations, while the ext. of C. sinensis is consumed frequently as beverage in many part of the world. Hence, patients having known bleeding tendency or haemophilia disease should take into account the interaction potential of these plants with the natural blood clotting system while taking herbal formulations containing above plants; specially, the patients suffering from intrinsic pathway factor deficiency should keep a limit on the consumption of S. cumini while extrinsic pathway factor deficiency patients should limit C. sinensis. Also, the medical practitioners should consider the patient's food consumption history before doing any major surgical procedures. PMID:26340850

  11. Biologics in dermatology: adverse effects.

    PubMed

    Sehgal, Virendra N; Pandhi, Deepika; Khurana, Ananta

    2015-12-01

    Biologics are a group of drugs that precisely affect certain specific steps in the immune response and are an extremely useful group when used in an appropriate setting. However, their use can often be a double-edged sword. Careful patient selection and thorough knowledge of adverse effects is a key to their successful use in various disorders. The initial enthusiasm has gradually given way to a more cautious approach wherein a balance is sought between clinical usefulness and expected side effects. The adverse effects of the biologics most commonly used in dermatology have been carefully listed for ready reference. The plausible causes of the adverse reactions are succinctly outlined along with their incriminating factor(s). Besides, in brief, the attention has been focused on their management. The content should provide an essential didactic content for educating the practitioner. PMID:26147909

  12. 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

  13. Pharmacogenomics and adverse drug reactions in children

    PubMed Central

    Rieder, Michael J.; Carleton, Bruce

    2014-01-01

    Adverse drug reactions are a common and important complication of drug therapy in children. Over the past decade it has become increasingly apparent that genetically controlled variations in drug disposition and response are important determinants of adverse events for many important adverse events associated with drug therapy in children. While this research has been difficult to conduct over the past decade technical and ethical evolution has greatly facilitated the ability of investigators to conduct pharmacogenomic studies in children. Some of this research has already resulted in changes in public policy and clinical practice, for example in the case of codeine use by mothers and children. It is likely that the use of pharmacogenomics to enhance drug safety will first be realized among selected groups of children with high rates of drug use such as children with cancer, but it also likely that this research will be extended to other groups of children who have high rates of drug utilization and as well as providing insights into the mechanisms and pathophysiology of adverse drug reactions in children. PMID:24795743

  14. Adverse Drug Reactions of the Lower Extremities.

    PubMed

    Adigun, Chris G

    2016-07-01

    Adverse drug reactions (ADRs) are a common cause of dermatologic consultation, involving 2 to 3 per 100 medical inpatients in the United States. Female patients are 1.3 to 1.5 times more likely to develop ADRs, except in children less than 3 years of age, among whom boys are more often affected. Certain drugs are more frequent causes, including aminopenicillins, trimethoprim-sulfamethoxazole, and nonsteroidal antiinflammatory drugs. Chemotherapeutic agents commonly cause adverse reactions to the skin and nails, with certain agents causing particular patterns of reactions. ADRs can involve any area of the skin; the appendages, including hair and nails; as well as mucosa. PMID:27215159

  15. Pharmacogenetic analysis of adverse drug effect reveals genetic variant for susceptibility to liver toxicity.

    PubMed

    Acuña, Gonzalo; Foernzler, Dorothee; Leong, Diane; Rabbia, Michael; Smit, Ralf; Dorflinger, Ernest; Gasser, Rodolfo; Hoh, Josephine; Ott, Jürg; Borroni, Edilio; To, Zung; Thompson, Annick; Li, Jia; Hashimoto, Lara; Lindpaintner, Klaus

    2002-01-01

    A retrospective pharmacogenetic study was conducted to identify possible genetic susceptibility factors in patients in whom the administration of the anti-Parkinson drug, tolcapone (TASMAR), was associated with hepatic toxicity. We studied 135 cases of patients with elevated liver transaminase levels (ELT) of >/=1.5 times above the upper limit of normal, in comparison with matched controls that had also received the drug but had not experienced ELT. DNA samples were genotyped for 30 previously described or newly characterized bi-allelic single nucleotide polymorphisms (SNPs), representing 12 candidate genes selected based on the known metabolic pathways involved in the tolcapone elimination. SNPs located within the UDP-glucuronosyl transferase 1A gene complex, which codes for the enzymes involved in the main elimination pathway of the drug, were found to be significantly associated with the occurrence of tolcapone-associated ELTs. PMID:12439739

  16. 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…

  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. 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. PMID:26645393

  19. [Gold antirheumatic drug: desired and adverse effects of Au(I) and Au(III) [corrected] on the immune system.

    PubMed

    Griem, P; Gleichmann, E

    1996-01-01

    Three new findings are reviewed that help to understand the mechanisms of action of anti-rheumatic gold drugs, such as disodium aurothiomalate (Na2Au(I)TM): i) We found that Na2Au(I)TM selectively inhibits T-cell receptor-mediated antigen recognition by murine CD4+ T-cell hybridomas specific for antigenic peptides containing at least two cysteine residues. Presumably, Au(I) acts as a chelating agent forming linear complexes (Cys-Au(I)-Cys) which prevents correct antigen-processing and/or peptide recognition by the T-cell receptor, ii) We were able to show that Au(I) is oxidized to Au(III) in mononuclear phagocytes, such as macrophages. Because Au(III) rapidly oxidizes protein and itself is re-reduced to Au(I), this may introduce an Au(I)/Au(III) redox system into phagocytes which scavenges reactive oxygen species, such as hypochlorous acid (HOCl) and inactivates lysosomal enzymes, iii) Pretreatment with Au(III) of a model protein antigen, bovine ribonuclease A (RNase A), induced novel antigenic determinants recognized by CD4+ T lymphocytes. Analysis of the fine specificity of these "Au(III)-specific" T-cells revealed that they react to RNase peptides that are not presented to T-cells when the native protein, i.e., not treated with Au(III), is used as antigen. The T-cell recognition of these cryptic peptides did not require the presence of gold. This finding has important implications for understanding the pathogenesis of allergic and autoimmune responses induced by gold drugs. Taken together, our findings indicate that Au(I) and Au(III) each exert specific effects on several distinct functions of macrophages and the activation of T-cells. These effects may explain both the desired anti-inflammatory and the adverse effects of antirheumatic gold drugs. PMID:9036720

  20. Tamoxifen nanostructured lipid carriers: enhanced in vivo antitumor efficacy with reduced adverse drug effects.

    PubMed

    Shete, Harshad K; Selkar, Nilakash; Vanage, Geeta R; Patravale, Vandana B

    2014-07-01

    A novel approach of enhancing the Tamoxifen uptake via Intestinal Lymphatic System is executed by developing long chain lipid and oil based nanostructured lipid carrier system (Tmx-NLC). The aim was to achieve improved systemic bioavailability of Tamoxifen, prevent systemic and hepatotoxicity and enhance antitumor efficacy. Following the proof of concept achieved in cell culture experiments and in vivo pharmacokinetic and biodistribution study, the current work focuses on investigation of antitumor efficacy and treatment associated toxicity in murine mammary tumor mice model. The efficacy study demonstrated greater tumor suppression and 100% survival with 1.5 and 3 mg/kg Tmx-NLC compared to 3 mg/kg Tamoxifen suspension and Mamofen(®) (Khandelwal Pharmaceuticals, Mumbai, India). Tmx-NLC treatment for a month demonstrated improved systemic toxicity profile and no evidences of hepatotoxicity. Thus, developed Tmx-NLC could prove to be a promising delivery strategy to confer superior therapeutic efficacy and ability to address the biopharmaceutical and toxicity associated issues of drug. PMID:24704438

  1. Cadec: A corpus of adverse drug event annotations.

    PubMed

    Karimi, Sarvnaz; Metke-Jimenez, Alejandro; Kemp, Madonna; Wang, Chen

    2015-06-01

    CSIRO Adverse Drug Event Corpus (Cadec) is a new rich annotated corpus of medical forum posts on patient-reported Adverse Drug Events (ADEs). The corpus is sourced from posts on social media, and contains text that is largely written in colloquial language and often deviates from formal English grammar and punctuation rules. Annotations contain mentions of concepts such as drugs, adverse effects, symptoms, and diseases linked to their corresponding concepts in controlled vocabularies, i.e., SNOMED Clinical Terms and MedDRA. The quality of the annotations is ensured by annotation guidelines, multi-stage annotations, measuring inter-annotator agreement, and final review of the annotations by a clinical terminologist. This corpus is useful for studies in the area of information extraction, or more generally text mining, from social media to detect possible adverse drug reactions from direct patient reports. The corpus is publicly available at https://data.csiro.au.(1). PMID:25817970

  2. Adverse Events in Healthy Individuals and MDR-TB Contacts Treated with Anti-Tuberculosis Drugs Potentially Effective for Preventing Development of MDR-TB: A Systematic Review

    PubMed Central

    Langendam, Miranda W.; Tiemersma, Edine W.; van der Werf, Marieke J.; Sandgren, Andreas

    2013-01-01

    A recent systematic review concluded that there is insufficient evidence on the effectiveness to support or reject preventive therapy for treatment of contacts of patients with multidrug resistant tuberculosis (MDR-TB). Whether preventive therapy is favorable depends both on the effectiveness and the adverse events of the drugs used. We performed a systematic review to assess adverse events in healthy individuals and MDR-TB contacts treated with anti-tuberculosis drugs potentially effective for preventing development of MDR-TB. We searched MEDLINE, EMBASE, and other databases (August 2011). Record selection, data extraction, and study quality assessment were done in duplicate. The quality of evidence was assessed using the GRADE approach. Of 6,901 identified references, 20 studies were eligible. Among the 16 studies in healthy volunteers (a total of 87 persons on either levofloxacin, moxifloxacin, ofloxacin, or rifabutin, mostly for 1 week), serious adverse events and treatment discontinuation due to adverse events were rare (<1 and <5%, respectively), but mild adverse events frequently occurred. Due to small sample sizes of the levofloxacin and ofloxacin studies an increased frequency of mild adverse events compared to placebo could not be demonstrated or excluded. For moxifloxacin the comparative results were inconsistent. In four studies describing preventive therapy of MDR-TB contacts, therapy was stopped for 58–100% of the included persons because of the occurrence of adverse events ranging from mild adverse events such as nausea and dizziness to serious events requiring treatment. The quality of the evidence was very low. Although the number of publications and quality of evidence are low, the available evidence suggests that shortly after starting treatment the occurrence of serious adverse events is rare. Mild adverse events occur more frequently and may be of importance because these may provoke treatment interruption. PMID:23326464

  3. Standardizing adverse drug event reporting data

    PubMed Central

    2014-01-01

    Background The Adverse Event Reporting System (AERS) is an FDA database providing rich information on voluntary reports of adverse drug events (ADEs). Normalizing data in the AERS would improve the mining capacity of the AERS for drug safety signal detection and promote semantic interoperability between the AERS and other data sources. In this study, we normalize the AERS and build a publicly available normalized ADE data source. The drug information in the AERS is normalized to RxNorm, a standard terminology source for medication, using a natural language processing medication extraction tool, MedEx. Drug class information is then obtained from the National Drug File-Reference Terminology (NDF-RT) using a greedy algorithm. Adverse events are aggregated through mapping with the Preferred Term (PT) and System Organ Class (SOC) codes of Medical Dictionary for Regulatory Activities (MedDRA). The performance of MedEx-based annotation was evaluated and case studies were performed to demonstrate the usefulness of our approaches. Results Our study yields an aggregated knowledge-enhanced AERS data mining set (AERS-DM). In total, the AERS-DM contains 37,029,228 Drug-ADE records. Seventy-one percent (10,221/14,490) of normalized drug concepts in the AERS were classified to 9 classes in NDF-RT. The number of unique pairs is 4,639,613 between RxNorm concepts and MedDRA Preferred Term (PT) codes and 205,725 between RxNorm concepts and SOC codes after ADE aggregation. Conclusions We have built an open-source Drug-ADE knowledge resource with data being normalized and aggregated using standard biomedical ontologies. The data resource has the potential to assist the mining of ADE from AERS for the data mining research community. PMID:25157320

  4. Adverse drug reactions and safety considerations of NSAIDs: clinical analysis.

    PubMed

    Bahadur, Shiv; Keshri, Lav; Pathak, Kamla

    2011-11-01

    NSAIDs are the most frequently used drugs for treatment, in Europe and the United States, accounting for approximately 5% of all prescriptions. Moreover, the use of NSAIDs is increasing because these constitute the first-line drug therapy for a wide range of rheumatic conditions. This increase is in part the result of the increasing population of elderly patients, who constitute the group of patients with greatest demand for these agents. There are many types of NSAIDs that vary in potency, action and potential side effects. Thus various efforts have been made to determine the safety considerations including adverse drug effects, duration of drug therapy, drug interactions, precautions and other drugs applied to reduce side effects. Researchers have introduced some novel techniques to diagnose NSAIDs related adverse effects on the gastrointestinal mucosa. The researchers dealing with the development of drug delivery system for these drugs should aim at designing a therapeutically efficacious dosage form with reduced side/adverse effects. Thus an effort has been made in this review to deal with the safety parameters of various NSAIDs with a special emphasis on preclinical and clinical safety analysis and various attempts to minimize the side effects by structural modification or by drug delivery system. PMID:22424538

  5. A New Alternative Drug With Fewer Adverse Effects in the Treatment of Sydenham Chorea: Levetiracetam Efficacy in a Child.

    PubMed

    Şahin, Sevim; Cansu, Ali

    2015-01-01

    Levetiracetam (LEV) efficacy in the treatment of chorea in Huntington disease, paroxysmal nonkinesigenic dyskinesia, paroxysmal kinesigenic choreoathetosis, and dyskinetic cerebral palsy was reported in some studies. We described a case of a child with Sydenham chorea treated with LEV. A 7.5-year-old male patient presented with chorea, orofacial dyskinesia, speech impairment, and irritability. Echocardiographic examination revealed mitral insufficiency. Sydenham chorea was diagnosed after excluding other diseases causing chorea. Although his choreiform movements were decreased substantially with haloperidol treatment, speech impairment, orofacial dyskinesia, and light chorea were continued. Therefore, on day 9, LEV was added, and his complaints resolved in a few days. The severity of the chorea according to the Universidade Federal de Minas Gerais Sydenham's Chorea Rating Scale decreased from 47 to 5 points after LEV treatment. Thus, on day 13, the dose of haloperidol was reduced and gradually discontinued within 4 days. Symptoms did not reoccur. The follow-up at 1.5 months revealed recurrence of complaints due to discontinuation of LEV by parents. Signs and symptoms were regressed completely within 1 week after LEV retreatment. We suggest that LEV with fewer adverse effects comparing to other drugs may be considered to be a good alternative in the treatment of Sydenham chorea. PMID:26166232

  6. 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. PMID:27507394

  7. Ranking Adverse Drug Reactions With Crowdsourcing

    PubMed Central

    Gottlieb, Assaf; Hoehndorf, Robert; Dumontier, Michel

    2015-01-01

    Background There is no publicly available resource that provides the relative severity of adverse drug reactions (ADRs). Such a resource would be useful for several applications, including assessment of the risks and benefits of drugs and improvement of patient-centered care. It could also be used to triage predictions of drug adverse events. Objective The intent of the study was to rank ADRs according to severity. Methods We used Internet-based crowdsourcing to rank ADRs according to severity. We assigned 126,512 pairwise comparisons of ADRs to 2589 Amazon Mechanical Turk workers and used these comparisons to rank order 2929 ADRs. Results There is good correlation (rho=.53) between the mortality rates associated with ADRs and their rank. Our ranking highlights severe drug-ADR predictions, such as cardiovascular ADRs for raloxifene and celecoxib. It also triages genes associated with severe ADRs such as epidermal growth-factor receptor (EGFR), associated with glioblastoma multiforme, and SCN1A, associated with epilepsy. Conclusions ADR ranking lays a first stepping stone in personalized drug risk assessment. Ranking of ADRs using crowdsourcing may have useful clinical and financial implications, and should be further investigated in the context of health care decision making. PMID:25800813

  8. 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

  9. Systematic Analysis of Adverse Event Reports for Sex Differences in Adverse Drug Events

    PubMed Central

    Yu, Yue; Chen, Jun; Li, Dingcheng; Wang, Liwei; Wang, Wei; Liu, Hongfang

    2016-01-01

    Increasing evidence has shown that sex differences exist in Adverse Drug Events (ADEs). Identifying those sex differences in ADEs could reduce the experience of ADEs for patients and could be conducive to the development of personalized medicine. In this study, we analyzed a normalized US Food and Drug Administration Adverse Event Reporting System (FAERS). Chi-squared test was conducted to discover which treatment regimens or drugs had sex differences in adverse events. Moreover, reporting odds ratio (ROR) and P value were calculated to quantify the signals of sex differences for specific drug-event combinations. Logistic regression was applied to remove the confounding effect from the baseline sex difference of the events. We detected among 668 drugs of the most frequent 20 treatment regimens in the United States, 307 drugs have sex differences in ADEs. In addition, we identified 736 unique drug-event combinations with significant sex differences. After removing the confounding effect from the baseline sex difference of the events, there are 266 combinations remained. Drug labels or previous studies verified some of them while others warrant further investigation. PMID:27102014

  10. 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

  11. Hepatic drug metabolism and adverse hepatic drug reactions.

    PubMed

    Schaffner, F

    1975-01-01

    Drugs and other chemicals are usually metabolized in the liver in the drug-metabolizing enzyme system. The metabolites sometimes bind with cellular macromolecules and injure the cell directly or serve as new antigens to create immunologic injury in a delayed fashion. The immediate or toxic injury is dose-dependent, predictable and zonal in the liver lobule, usually in the central region. Carbon tetrachloride intoxication and acetaminophen overdose are examples of injury resulting from microsomal metabolism. Other injuries related to microsomal metabolism are those produced by vinyl chloride in polymerization plant workers and by methotrexate in psoriatics or leukemic children. Most adverse drug reactions affecting the liver and producing jaundice are unpredictable, delayed in onset, and only hypothetically related to microsomal metabolism in some instances. The two main types are cholestasis and viral-hepatitis-like. The former may be in a pure form, in which case it may be partly dose-dependent, or in a form mixed with hepatitis. Many drugs produce cholestasis in a small percentage of persons, and because the reaction is benign, albeit prolonged at times, such drugs continue to be used. The viral-hepatitis-like reaction involves few drugs and affects few persons, but can be fatal. The recognition that chronic hepatitis can be caused by drugs such as oxyphenisatin, alpha-methyldopa, and isoniazid has added a new dimension to the clinical problem of adverse drug reactions, which may extend to widely used and commonly available agents like aspirin. PMID:171822

  12. Adverse reactions to new anticonvulsant drugs.

    PubMed

    Wong, I C; Lhatoo, S D

    2000-07-01

    A lack of systematic pharmacoepidemiological studies investigating adverse drug reactions (ADRs) to anticonvulsants makes it difficult to assess accurately the incidence of anticonvulsant-related ADRs. Most of the available information in this regard stems from clinical trial experience, case reports and postmarketing surveillance, sources that are not, by any means, structured to provide precise data on adverse event epidemiology. For various ethical, statistical and logistical reasons, the organisation of structured clinical trials that are likely to provide substantial data on ADRs is extremely difficult. This review concentrates on current literature concerning serious and life-threatening ADRs. As with the older anticonvulsants, the majority of ADRs to newer anticonvulsants are CNS-related, although there are several that are apparently unique to some of these new drugs. Gabapentin has been reported to cause aggravation of seizures, movement disorders and psychiatric disturbances. Felbamate should only be prescribed under close medical supervision because of aplastic anaemia and hepatotoxicity. Lamotrigine causes hypersensitivity reactions that range from simple morbilliform rashes to multi-organ failure. Psychiatric ADRs and deterioration of seizure control have also been reported with lamotrigine treatment. Oxcarbazepine has a safety profile similar to that of carbamazepine. Hyponatraemia associated with oxcarbazepine is also a problem; however, it is less likely to cause rash than carbamazepine. Nonconvulsive status epilepticus has been reported frequently with tiagabine, although there are insufficient data at present to identify risk factors for this ADR. Topiramate frequently causes cognitive ADRs and, in addition, also appears to cause word-finding difficulties, renal calculi and bodyweight loss. Vigabatrin has been reported to cause seizure aggravation, especially in myoclonic seizures. There have been rare reports of other neurological ADRs to

  13. Learning Lessons from Adverse Drug Reactions in Children

    PubMed Central

    Sammons, Helen M.; Choonara, Imti

    2016-01-01

    Drug toxicity is, unfortunately, a significant problem in children both in the hospital and in the community. Drug toxicity in children is different to that seen in adults. At least one in 500 children will experience an adverse drug reaction each year. For children in hospital, the risk is far greater (one in ten). Additionally, different and sometimes unique adverse drug reactions are seen in the paediatric age groups. Some of the major cases of drug toxicity historically have occurred in neonates. It is important that we understand the mechanism of action of adverse drug reactions. Greater understanding alongside rational prescribing should hopefully reduce drug toxicity in children in the future. PMID:27417239

  14. Extraction of potential adverse drug events from medical case reports

    PubMed Central

    2012-01-01

    The sheer amount of information about potential adverse drug events published in medical case reports pose major challenges for drug safety experts to perform timely monitoring. Efficient strategies for identification and extraction of information about potential adverse drug events from free‐text resources are needed to support pharmacovigilance research and pharmaceutical decision making. Therefore, this work focusses on the adaptation of a machine learning‐based system for the identification and extraction of potential adverse drug event relations from MEDLINE case reports. It relies on a high quality corpus that was manually annotated using an ontology‐driven methodology. Qualitative evaluation of the system showed robust results. An experiment with large scale relation extraction from MEDLINE delivered under‐identified potential adverse drug events not reported in drug monographs. Overall, this approach provides a scalable auto‐assistance platform for drug safety professionals to automatically collect potential adverse drug events communicated as free‐text data. PMID:23256479

  15. Proposed actions for the US Food and Drug Administration to implement to minimize adverse effects associated with energy drink consumption.

    PubMed

    Thorlton, Janet; Colby, David A; Devine, Paige

    2014-07-01

    Energy drink sales are expected to reach $52 billion by 2016. These products, often sold as dietary supplements, typically contain stimulants. The Dietary Supplement Protection Act claims an exemplary public health safety record. However, in 2011 the number of emergency department visits related to consumption of energy drinks exceeded 20,000. Nearly half of these visits involved adverse effects occurring from product misuse. Political, social, economic, practical, and legal factors shape the landscape surrounding this issue. In this policy analysis, we examine 3 options: capping energy drink caffeine levels, creating a public education campaign, and increasing regulatory scrutiny regarding the manufacture and labeling of energy drinks. Increased regulatory scrutiny may be in order, especially in light of wrongful death lawsuits related to caffeine toxicity resulting from energy drink consumption. PMID:24832439

  16. 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

    2016-10-01

    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. PMID:25365228

  17. Pattern of Adverse Drug Reactions Reported with Cardiovascular Drugs in a Tertiary Care Teaching Hospital

    PubMed Central

    Palaniappan, Muthiah; George, Melvin; Subramaniyan, Ganesan; Dkhar, Steven Aibor; Pillai, Ajith Ananthakrishna; Jayaraman, Balachander; Chandrasekaran, Adithan

    2015-01-01

    Background Cardiovascular diseases (CVD) are one of the leading causes of non-communicable disease related deaths globally. Patients with cardiovascular diseases are often prescribed multiple drugs and have higher risk for developing more adverse drug reactions due to polypharmacy. Aim To evaluate the pattern of adverse drug reactions reported with cardiovascular drugs in an adverse drug reaction monitoring centre (AMC) of a tertiary care hospital. Settings and Design Adverse drug reactions related to cardiovascular drugs reported to an AMC of a tertiary care hospital were included in this prospective observational study. Materials and Methods All cardiovascular drugs related adverse drug reactions (ADRs) received in AMC through spontaneous reporting system and active surveillance method from January 2011 to March 2013 were analysed for demographic profile, ADR pattern, severity and causality assessment. Statistical Analysis used The study used descriptive statistics and the values were expressed in numbers and percentages. Results During the study period, a total of 463 ADRs were reported from 397 patients which included 319 males (80.4%) and 78 females (19.6%). The cardiovascular drug related reports constituted 18.1% of the total 2188 ADR reports. In this study, the most common ADRs observed were cough (17.3%), gastritis (7.5%) and fatigue (6.5%). Assessment of ADRs using WHO-causality scale revealed that 62% of ADRs were possible, 28.2% certain and 6.8% probable. As per Naranjo’s scale most of the reports were possible (68.8%) followed by probable (29.7%). According to Hartwig severity scale majority of the reports were mild (95%) followed by moderate (4.5%). A system wise classification of ADRs showed that gastrointestinal system (20.7%) related reactions were the most frequently observed adverse reactions followed by respiratory system (18.4%) related adverse effects. From the reported ADRs, the drugs most commonly associated with ADRs were found to be

  18. Managing adverse effects of glaucoma medications

    PubMed Central

    Inoue, Kenji

    2014-01-01

    Glaucoma is a chronic, progressive disease in which retinal ganglion cells disappear and subsequent, gradual reductions in the visual field ensues. Glaucoma eye drops have hypotensive effects and like all other medications are associated with adverse effects. Adverse reactions may either result from the main agent or from preservatives used in the drug vehicle. The preservative benzalkonium chloride, is one such compound that causes frequent adverse reactions such as superficial punctate keratitis, corneal erosion, conjunctival allergy, and conjunctival injection. Adverse reactions related to main hypotensive agents have been divided into those affecting the eye and those affecting the entire body. In particular, β-blockers frequently cause systematic adverse reactions, including bradycardia, decrease in blood pressure, irregular pulse and asthma attacks. Prostaglandin analogs have distinctive local adverse reactions, including eyelash bristling/lengthening, eyelid pigmentation, iris pigmentation, and upper eyelid deepening. No systemic adverse reactions have been linked to prostaglandin analog eye drop usage. These adverse reactions may be minimized when they are detected early and prevented by reducing the number of different eye drops used (via fixed combination eye drops), reducing the number of times eye drops are administered, using benzalkonium chloride-free eye drops, using lower concentration eye drops, and providing proper drop instillation training. Additionally, a one-time topical medication can be given to patients to allow observation of any adverse reactions, thereafter the preparation of a topical medication with the fewest known adverse reactions can be prescribed. This does require precise patient monitoring and inquiries about patient symptoms following medication use. PMID:24872675

  19. Predicting adverse drug events from personal health messages.

    PubMed

    Chee, Brant W; Berlin, Richard; Schatz, Bruce

    2011-01-01

    Adverse drug events (ADEs) remain a large problem in the United States, being the fourth leading cause of death, despite post market drug surveillance. Much post consumer drug surveillance relies on self-reported "spontaneous" patient data. Previous work has performed datamining over the FDA's Adverse Event Reporting System (AERS) and other spontaneous reporting systems to identify drug interactions and drugs correlated with high rates of serious adverse events. However, safety problems have resulted from the lack of post marketing surveillance information about drugs, with underreporting rates of up to 98% within such systems. We explore the use of online health forums as a source of data to identify drugs for further FDA scrutiny. In this work we aggregate individuals' opinions and review of drugs similar to crowd intelligence3. We use natural language processing to group drugs discussed in similar ways and are able to successfully identify drugs withdrawn from the market based on messages discussing them before their removal. PMID:22195073

  20. Risk factors for seizures and antiepileptic drug-associated adverse effects in high-grade glioma patients: A multicentre, retrospective study in Hong Kong

    PubMed Central

    Woo, Peter Yat-Ming; Chan, Danny Tat-Ming; Chan, Kwong-Yau; Wong, Wai-Kei; Po, Yin-Chung; Kwok, John Ching-Kong; Poon, Wai-Sang

    2015-01-01

    Aim The aim of this present study was to determine the frequency, as well as risk factors, for seizures and antiepileptic drug (AED)-associated adverse effects among high-grade glioma (HGG) patients. Patients and Methods A multicentre, retrospective study of adult Chinese Hong Kong patients from three neurosurgical centres diagnosed with supratentorial HGG between 1 January 2001 and 31 December 2010 was performed. Results A total of 198 patients, with a mean age of 55 years (range: 18–88) and a mean follow up of 15 months, was recruited. Most suffered from glioblastoma multiforme (GBM) (63 per cent) followed by anaplastic astrocytoma (25 per cent). Median overall survival for patients with GBM was 8 months, and 11 months for those with grade III gliomas. Prophylactic AED was prescribed in 165 patients (83 per cent), and 64 per cent of patients were continued until end of life or last follow up. A total of 112 patients (57 per cent) experienced seizures at a mean duration of 8 months postoperatively (range: 1 day–75 months). Independent predictors for seizures were a diagnosis of GBM [adjusted odds ratio (OR): 2.33, 95 per cent confidence interval (CI): 1.21–4.52] and adjuvant radiotherapy (adjusted OR: 2.97, 95 per cent CI: 1.49–6.62). One-fifth of patients (21 per cent) experienced AED adverse effects, with idiosyncratic cutaneous reactions and hepatotoxicity most frequently observed. An independent predictor for adverse effects was exposure to aromatic AED, such as phenytoin, carbamazepine and phenobarbital (adjusted OR: 3.32, 95 per cent CI: 1.32–8.40). Conclusions Antiepileptic drug prescription for primary seizure prophylaxis is both pervasive and prolonged for HGG patients. Seizures occur frequently, but most were delayed and none were life threatening. Judicious prescription of AED is required, especially when a significant proportion of patients experience adverse effects. Patients with a diagnosis of GBM and exposure to radiotherapy

  1. Valproic acid in amygdala-kindled rats: alterations in anticonvulsant efficacy, adverse effects and drug and metabolite levels in various brain regions during chronic treatment.

    PubMed

    Löscher, W; Fisher, J E; Nau, H; Hönack, D

    1989-09-01

    Amygdala-kindled rats were treated with valproic acid (VPA; administered as its sodium salt) 3 times daily at 200 mg/kg i.p. for 6 weeks, and anticonvulsant and adverse effects during this period were studied. Groups of nonkindled rats were treated in parallel for determination of VPA and its major active metabolites in various brain regions after different durations of treatment. After the first injection of VPA, 200 mg/kg, seizure severity, seizure duration and duration of electrical afterdischarges recorded from the stimulated amygdala were reduced significantly, but only one of nine animals was protected completely from kindled seizures. At day 3 of chronic treatment, the anticonvulsant activity of VPA had increased markedly so that seven of nine animals were totally protected from seizures. However, this potent anticonvulsant effect was only transitory so that after 1 week of treatment the anticonvulsant effect of the medication was similar to that obtained after the first dosing. The effect of VPA remained at this level for the subsequent weeks, but there was a second, more permanent increase in the number of protected animals after 4 to 6 weeks. Plasma and brain levels of VPA and its metabolites remained relatively constant throughout the chronic treatment although there was a moderate accumulation of some metabolites, e.g., trans isomer of 2-propyl-2-pentenoic acid, in specific brain nuclei. The most prominent adverse effects of VPA were ataxia, muscle relaxation, wet-dog shake behavior and an increase in body temperature. Except for body temperature, tolerance developed to these adverse effects, but escape from wet-dog shake behavior occurred much more rapidly than reduction of other adverse effects. Pathohistological examination of liver sections from animals treated with VPA for 6 weeks showed no indication of any hepatotoxic effects. After drug withdrawal, kindled seizure parameters returned toward control values without evidence of significant carry

  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. Post-surgical analgesia in rainbow trout: is reduced cardioventilatory activity a sign of improved animal welfare or the adverse effects of an opioid drug?

    PubMed

    Gräns, Albin; Sandblom, Erik; Kiessling, Anders; Axelsson, Michael

    2014-01-01

    The use of fish models in biomedical research is increasing. Since behavioural and physiological consequences of surgical procedures may affect experimental results, these effects should be defined and, if possible, ameliorated. Thus, the use of post-surgical analgesia should be considered after invasive procedures also in fish, but presently, little information exists on the effects of analgesics in fish. This study assessed the effects of an opioid drug, buprenorphine (0.05 mg/kg IM), on resting ventilation and heart rates during 7 days of postsurgical recovery in rainbow trout (Oncorhynchus mykiss) at 10°C by non-invasively recording bioelectric potentials from the fish via electrodes in the water. Baseline ventilation and heart rates were considerably lower compared to previously reported values for rainbow trout at 10°C, possibly due to the non-invasive recording technique. Buprenorphine significantly decreased both ventilation and heart rates further, and the effects were most pronounced at 4-7 days after anaesthesia, surgical procedures and administration of the drug. Somewhat surprisingly, the same effects of buprenorphine were seen in the two control groups that had not been subject to surgery. These results indicate that the reductions in ventilation and heart rates are not caused by an analgesic effect of the drug, but may instead reflect a general sedative effect acting on both behaviour as well as e.g. central control of ventilation in fishes. This resembles what has previously been demonstrated in mammals, although the duration of the drug effect is considerably longer in this ectothermic animal. Thus, before using buprenorphine for postoperative analgesic treatment in fish, these potentially adverse effects need further characterisation. PMID:24736526

  4. Post-Surgical Analgesia in Rainbow Trout: Is Reduced Cardioventilatory Activity a Sign of Improved Animal Welfare or the Adverse Effects of an Opioid Drug?

    PubMed Central

    Gräns, Albin; Sandblom, Erik; Kiessling, Anders; Axelsson, Michael

    2014-01-01

    The use of fish models in biomedical research is increasing. Since behavioural and physiological consequences of surgical procedures may affect experimental results, these effects should be defined and, if possible, ameliorated. Thus, the use of post-surgical analgesia should be considered after invasive procedures also in fish, but presently, little information exists on the effects of analgesics in fish. This study assessed the effects of an opioid drug, buprenorphine (0.05 mg/kg IM), on resting ventilation and heart rates during 7 days of postsurgical recovery in rainbow trout (Oncorhynchus mykiss) at 10°C by non-invasively recording bioelectric potentials from the fish via electrodes in the water. Baseline ventilation and heart rates were considerably lower compared to previously reported values for rainbow trout at 10°C, possibly due to the non-invasive recording technique. Buprenorphine significantly decreased both ventilation and heart rates further, and the effects were most pronounced at 4–7 days after anaesthesia, surgical procedures and administration of the drug. Somewhat surprisingly, the same effects of buprenorphine were seen in the two control groups that had not been subject to surgery. These results indicate that the reductions in ventilation and heart rates are not caused by an analgesic effect of the drug, but may instead reflect a general sedative effect acting on both behaviour as well as e.g. central control of ventilation in fishes. This resembles what has previously been demonstrated in mammals, although the duration of the drug effect is considerably longer in this ectothermic animal. Thus, before using buprenorphine for postoperative analgesic treatment in fish, these potentially adverse effects need further characterisation. PMID:24736526

  5. Factors affecting the development of adverse drug reactions (Review article)

    PubMed Central

    Alomar, Muaed Jamal

    2013-01-01

    Objectives To discuss the effect of certain factors on the occurrence of Adverse Drug Reactions (ADRs). Data Sources A systematic review of the literature in the period between 1991 and 2012 was made based on PubMed, the Cochrane database of systematic reviews, EMBASE and IDIS. Key words used were: medication error, adverse drug reaction, iatrogenic disease factors, ambulatory care, primary health care, side effects and treatment hazards. Summary Many factors play a crucial role in the occurrence of ADRs, some of these are patient related, drug related or socially related factors. Age for instance has a very critical impact on the occurrence of ADRs, both very young and very old patients are more vulnerable to these reactions than other age groups. Alcohol intake also has a crucial impact on ADRs. Other factors are gender, race, pregnancy, breast feeding, kidney problems, liver function, drug dose and frequency and many other factors. The effect of these factors on ADRs is well documented in the medical literature. Taking these factors into consideration during medical evaluation enables medical practitioners to choose the best drug regimen. Conclusion Many factors affect the occurrence of ADRs. Some of these factors can be changed like smoking or alcohol intake others cannot be changed like age, presence of other diseases or genetic factors. Understanding the different effects of these factors on ADRs enables healthcare professionals to choose the most appropriate medication for that particular patient. It also helps the healthcare professionals to give the best advice to patients. Pharmacogenomics is the most recent science which emphasizes the genetic predisposition of ADRs. This innovative science provides a new perspective in dealing with the decision making process of drug selection. PMID:24648818

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

    PubMed

    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

  7. Quality of life in patients with schizophrenia: the impact of socio-economic factors and adverse effects of atypical antipsychotics drugs.

    PubMed

    de Araújo, Aurigena Antunes; de Araújo Dantas, Diego; do Nascimento, Gemma Galgani; Ribeiro, Susana Barbosa; Chaves, Katarina Melo; de Lima Silva, Vanessa; de Araújo, Raimundo Fernandes; de Souza, Dyego Leandro Bezerra; de Medeiros, Caroline Addison Carvalho Xavier

    2014-09-01

    This cross-sectional study compared the effects of treatment with atypical antipsychotic drugs on quality of life (QoL) and side effects in 218 patients with schizophrenia attending the ambulatory services of psychiatric in Rio Grande do Norte, Brazil. Socio-economic variables were compared. The five-dimension EuroQoL (EQ-5D) was used to evaluate QoL, and side effects were assessed using the Udvalg for Kliniske Undersøgelser (UKU) Side Effect Rating Scale and the Simpson-Angus Scale. Data were analysed using the χ (2) test and Student's t test, with a significance level of 5 %. Average monthly household incomes in the medication groups were 1.1-2.1 minimum wages ($339-$678). UKU Scale scores showed significant differences in side effects, mainly, clozapine, quetiapine and ziprasidone (p < 0.05). EQ-5D scores showed that all drugs except olanzapine significantly impacted mobility (p < 0.05), and proportions of individuals reporting problems in other dimensions were high: 63.6 % of clozapine users reported mobility problems, 63.7 and 56.3 % of clozapine and ziprasidone users, respectively, had difficulties with usual activities, 68.8 and 54.5 % of ziprasidone and clozapine users, respectively, experienced pain and/or discomfort, and 72.8 % of clozapine users reported anxiety and/or depression. Psychiatric, neurological, and autonomous adverse effects, as well as other side effects, were prevalent in users of atypical antipsychotic drugs, especially clozapine and ziprasidone. Olanzapine had the least side effects. QoL was impacted by side effects and economic conditions in all groups. Thus, the effects of these antipsychotic agents appear to have been masked by aggravating social and economic situations. PMID:24789610

  8. 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

  9. (1)H-Nuclear magnetic resonance-based metabolic profiling of nonsteroidal anti-inflammatory drug-induced adverse effects in rats.

    PubMed

    Um, So Young; Park, Jung Hyun; Chung, Myeon Woo; Choi, Ki Hwan; Lee, Hwa Jeong

    2016-09-10

    Nonsteroidal anti-inflammatory drugs (NSAIDs), which are globally prescribed, exhibit mainly anti-inflammatory and analgesic effects but also can cause adverse effects including gastrointestinal erosions, ulceration, bleeding, and perforation. The purpose of this study was to investigate surrogate biomarkers associated with the gastrointestinal (GI) damage caused by NSAID treatment using pattern recognition analysis of (1)H-nuclear magnetic resonance ((1)H NMR) spectra of rat urine. Urine was collected for 5h after oral administration of the following NSAIDs at low or high doses: acetylsalicylic acid (10 or 200mgkg(-1)), diclofenac (0.5 or 15mgkg(-1)), piroxicam (1 or 10mgkg(-1)), indomethacin (1 or 25mgkg(-1)), or ibuprofen (10, or 150mgkg(-1)) as nonselective COX inhibitors and celecoxib (10 or 100mgkg(-1)) as a COX-2 selective inhibitor. The urine was analyzed using 500MHz (1)H NMR for spectral binning and targeted profiling and the level of gastric damage was examined. The nonselective COX inhibitors caused severe gastric damage while no lesions were observed in the celecoxib-treated rats. The (1)H NMR urine spectra were divided into spectral bins (0.04ppm) for global profiling, and a total of 44 endogenous metabolites were assigned for targeted profiling. Multivariate data analyses were performed to recognize the spectral pattern of endogenous metabolites related to NSAIDs using partial least square-discrimination analysis (PLS-DA). The (1)H NMR spectra clustered differently according to gastric damage score in global profiling. In targeted profiling, the endogenous metabolites of citrate, allantoin, 2-oxoglutarate, acetate, benzoate, glycine, and trimethylamine N-oxide were selected as putative biomarkers for gastric damage caused by NSAIDs. These putative biomarkers might be useful for predicting the risk of adverse effects caused by NSAIDs in the early stage of drug development process. PMID:27497650

  10. Adverse drug reactions and organ damage: The skin.

    PubMed

    Marzano, Angelo V; Borghi, Alessandro; Cugno, Massimo

    2016-03-01

    Cutaneous adverse drug reactions are frequent, affecting 2-3% of hospitalized patients and in one twentieth of them are potentially life-threatening. Almost any pharmacologic agent can induce skin reactions, and certain drug classes, such as non-steroidal anti-inflammatory drugs, antibiotics and antiepileptics, have drug eruption rates ranging from 1% to 5%. Cutaneous drug reactions recognize several different pathomechanisms: some skin manifestations are immune-mediated like allergic reactions while others are the result of non immunological causes such as cumulative toxicity, photosensitivity, interaction with other drugs or different metabolic pathways. Cutaneous adverse drug reactions can be classified into two groups: common non-severe and rare life-threatening adverse drug reactions. Non-severe reactions are often exanthematous or urticarial whereas life-threatening reactions typically present with skin detachment or necrosis of large areas of the body and mucous membrane involvement, as in the Stevens-Johnson syndrome or toxic epidermal necrolysis. Clinicians should carefully evaluate the signs and symptoms of all cutaneous adverse drug reactions thought to be due to drugs and immediately discontinue drugs that are not essential. Short cycles of systemic corticosteroids in combination with antihistamines may be necessary for widespread exanthematous rashes, while more aggressive corticosteroid regimens or intravenous immunoglobulins associated with supportive treatment should be used for patients with Stevens-Johnson syndrome or toxic epidermal necrolysis. PMID:26674736

  11. [Adverse ocular effects of vaccinations].

    PubMed

    Ness, T; Hengel, H

    2016-07-01

    Vaccinations are very effective measures for prevention of infections but are also associated with a long list of possible side effects. Adverse ocular effects following vaccination have been rarely reported or considered to be related to vaccinations. Conjunctivitis is a frequent sequel of various vaccinations. Oculorespiratory syndrome and serum sickness syndrome are considered to be related to influenza vaccinations. The risk of reactivation or initiation of autoimmune diseases (e. g. uveitis) cannot be excluded but has not yet been proven. Overall the benefit of vaccination outweighs the possible but very low risk of ocular side effects. PMID:27357302

  12. Adverse drug reactions in veterinary patients associated with drug transporters.

    PubMed

    Mealey, Katrina L

    2013-09-01

    For many drugs used in veterinary practice, plasma and tissue concentrations are highly dependent on the activity of drug transporters. This article describes how functional changes in drug transporters, whether mediated by genetic variability or drug-drug interactions, affect drug disposition and, ultimately, drug safety and efficacy in veterinary patients. A greater understanding of species, breed, and individual (genetic) differences in drug transporter function, as well as drug-drug interactions involving drug transporters, will result in improved strategies for drug design and will enable veterinarians to incorporate individualized medicine in their practices. PMID:23890239

  13. [Frequency of drug adverse reactions among hospitalized patients].

    PubMed

    González Martínez, L

    1995-01-01

    This article describes the frequency of adverse reactions to drugs in a sample of hospitalized patients in the internal medicine ward seen during a year's term. Of 61 medical charts, we found 8 patients with adverse reactions to drugs during their hospital stay and another 4 patients hospitalized due to adverse reactions to drugs. The majority of the adverse reactions were of moderate degree (75%) and were related to drugs of cardiovascular action (58%). The frequency of reactions in hospitalized patients (13%) is comparable with the results obtained from other hospitals. Yet, the real magnitude of the problem is probably greater since the source of information (hospital charts) the totality of the clinical manifestations are not registered. PMID:8581452

  14. [Adverse drug reaction - Definitions, risk factors and pharmacovigilance].

    PubMed

    Krähenbühl, Stephan

    2015-12-01

    Adverse drug reactions (ADR} are the downside of active pharmacotherapies and can only partially be avoided. Risk factors have been identified for certain ADR which should be taken into account for the choice and dosing of critical drugs. Medical staff have a legal obligation to report severe ADR and ADR caused by newly licensed drugs. Such reports are important for monitoring the safety of drugs that are on the market. PMID:26654809

  15. [Adverse drug reactions in multidrug-resistant tuberculosis].

    PubMed

    Palmero, Domingo; Cruz, Víctor; Museli, Tomás; Pavlovsky, Hernán; Fernández, Juan; Waisman, Jaime

    2010-01-01

    Multidrug-resistant tuberculosis (MDRTB) poses difficulties in diagnosis and treatment, including increased frequency of adverse reactions to antituberculosis drugs (ADRAs), which compromise the effectiveness of treatment. This is specially complicated in the treatment of patients co-infected with HIV which includes the antiretroviral therapy plus the treatment of eventual comorbidities. A total of 121 MDRTB patients, 87 HIV-negative and 34 HIV positive, assisted in the Hospital F. J. Muñiz, Buenos Aires, during the period 2003-2007 were retrospectively studied. The incidence of ADRAs among the two groups of patients was compared. All the patients with adherence to treatment (no more than one abandon, recovered) were included in the study. Antituberculosis drugs used were: ethambutol, pyrazinamide, ofloxacin, moxifloxacin, cycloserine, ethionamide, PAS, streptomycin, kanamycin, amikacin and linezolid. The emergence of ADRAs and the proportion of severe reactions attributed to antituberculosis drugs were similar in both groups: 44.8% in HIV negative and 44.1% in HIV positive, but it was observed an additional 23.5% of adverse reactions to antiretroviral therapy in the second group. There were differences in the type of reactions and time of occurrence between the two groups. One HIV positive patient died of epidermolysis. The proportion of adverse reactions in HIV/AIDS patients increased 50% when those attributed to antiretroviral treatment were included. We conclude that the studied population showed a frequency of ADRAs higher than it would be expected in the treatment of susceptible TB, but there was no difference in its frequency among HIV-negative and positive patients. PMID:20920959

  16. Cutaneous Adverse Effects of Neurologic Medications.

    PubMed

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

    2016-03-01

    Life-threatening and benign drug reactions occur frequently in the skin, affecting 8 % of the general population and 2-3 % of all hospitalized patients, emphasizing the need for physicians to effectively recognize and manage patients with drug-induced eruptions. Neurologic medications represent a vast array of drug classes with cutaneous side effects. Approximately 7 % of the United States (US) adult population is affected by adult-onset neurological disorders, reflecting a large number of patients on neurologic drug therapies. This review elucidates the cutaneous reactions associated with medications approved by the US Food and Drug Administration (FDA) to treat the following neurologic pathologies: Alzheimer disease, amyotrophic lateral sclerosis, epilepsy, Huntington disease, migraine, multiple sclerosis, Parkinson disease, and pseudobulbar affect. A search of the literature was performed using the specific FDA-approved drug or drug classes in combination with the terms 'dermatologic,' 'cutaneous,' 'skin,' or 'rash.' Both PubMed and the Cochrane Database of Systematic Reviews were utilized, with side effects ranging from those cited in randomized controlled trials to case reports. It behooves neurologists, dermatologists, and primary care physicians to be aware of the recorded cutaneous adverse reactions and their severity for proper management and potential need to withdraw the offending medication. PMID:26914914

  17. 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.

  18. [Adverse effects of drugs in intensive care units: analysis of the administration of electrolyte solutions and antibiotics].

    PubMed

    Manenti, S; Chaves, A B; Leopoldino, R S; Padilha, K G

    1998-12-01

    The aims of this study were: 1) to verify the incidence of adverse occurrences (AOs) with medication related to the time of electrolyte solutions infusion and the frequency of doses of antibiotics prescribed and administered to the patients; 2) to characterize the nature of those occurrences. The study was developed in two ICUs of a general hospital of São Paulo City. The population was composed by 51 patients that were in the ICUs in August of 1996. Sixty percent of the patients were older than 60 years, 58.8% were women, 49.1% remained in ICU from 1 to 4 days and 41.2% went to the Intermediate Care Units after ICU. Regarding the incidence of AOs related to the time of administration of the electrolyte solutions and the frequency of doses of antibiotics the non execution of the patient's medical prescriptions was verified in 76.3% and 38.8% respectively. The largest frequency of irregularities with the electrolyte solutions (60.2%) was the infusion faster than the prescribed time followed by the reduction of the number of doses of antibiotics administered. Taking these into consideration we have to invest in preventive measures to reduce those occurrences. PMID:10614484

  19. Fingolimod-Associated Peripheral Vascular Adverse Effects.

    PubMed

    Russo, Margherita; Guarneri, Claudio; Mazzon, Emanuela; Sessa, Edoardo; Bramanti, Placido; Calabrò, Rocco Salvatore

    2015-10-01

    Fingolimod is the first oral disease-modifying drug approved for the treatment of multiple sclerosis. The drug is usually well tolerated, and common adverse effects include bradycardia, headache, influenza, diarrhea, back pain, increased liver enzyme levels, and cough. Fingolimod is thought to provide therapeutic benefit by preventing normal lymphocyte egress from lymphoid tissues, thus reducing the infiltration of autoaggressive lymphocytes into the central nervous system. However, because the drug acts on different sphingosine-1-phosphate receptors, it may induce several biological effects by influencing endothelial cell-cell adhesion, angiogenesis, vascular development, and cardiovascular function. We describe a patient with multiple sclerosis who, after 3 weeks of fingolimod administration, developed purplish blotches over the dorsal surface of the distal phalanges of the second and fifth digits and the middle phalanx of the fourth ray, itching, and edema on his left hand, without other evident clinical manifestations. When fingolimod therapy was discontinued, the clinical picture regressed within a few days but reappeared after a rechallenge test. Physicians should be aware of unexpected peripheral vascular adverse effects due to fingolimod use, and patients with vascular-based acropathies should be carefully screened and monitored when taking this drug. PMID:26349949

  20. Adverse Effects of Electroconvulsive Therapy.

    PubMed

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

    2016-09-01

    Electroconvulsive therapy (ECT) is an effective treatment commonly used for depression and other major psychiatric disorders. We discuss potential adverse effects (AEs) associated with ECT and strategies for their prevention and management. Common acute AEs include headache, nausea, myalgia, and confusion; these are self-limiting and are managed symptomatically. Serious but uncommon AEs include cardiovascular, pulmonary, and cerebrovascular events; these may be minimized with screening for risk factors and by physiologic monitoring. Although most cognitive AEs of ECT are short-lasting, troublesome retrograde amnesia may rarely persist. Modifications of and improvements in treatment techniques minimize cognitive and other AEs. PMID:27514303

  1. A Survey of Adverse Drug Reactions in Family Practice

    PubMed Central

    Reynolds, J. L.

    1984-01-01

    In this study, 232 Canadian family physicians recorded suspected adverse drug reactions (SADRs) in their practices for five months. Patients' age and sex, the drug(s) implicated, type of reaction and any disability were recorded on a card and sent to a central coordinating office each week. The number of SADRs in clinical practice seems to be small. An estimated 300,000 patients were involved in the study, and a total of 314 suspected adverse drug reactions in 314 patients were reported. A proposal is made for a surveillance system for new drugs. Family physicians would monitor all patients taking a drug or group of drugs and matched controls. The status of patients and controls would be recorded regularly and any SADRs reported to a central coordinating centre. PMID:21283495

  2. Predicting Adverse Drug Events from Personal Health Messages

    PubMed Central

    Chee, Brant W.; Berlin, Richard; Schatz, Bruce

    2011-01-01

    Adverse drug events (ADEs) remain a large problem in the United States, being the fourth leading cause of death, despite post market drug surveillance. Much post consumer drug surveillance relies on self-reported “spontaneous” patient data. Previous work has performed datamining over the FDA’s Adverse Event Reporting System (AERS) and other spontaneous reporting systems to identify drug interactions and drugs correlated with high rates of serious adverse events. However, safety problems have resulted from the lack of post marketing surveillance information about drugs, with underreporting rates of up to 98% within such systems1,2. We explore the use of online health forums as a source of data to identify drugs for further FDA scrutiny. In this work we aggregate individuals’ opinions and review of drugs similar to crowd intelligence3. We use natural language processing to group drugs discussed in similar ways and are able to successfully identify drugs withdrawn from the market based on messages discussing them before their removal. PMID:22195073

  3. Adverse effects of plasma transfusion.

    PubMed

    Pandey, Suchitra; Vyas, Girish N

    2012-05-01

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

  4. [Novel oral anticancer drugs: a review of adverse drug reactions, interactions and patient adherence].

    PubMed

    Bartal, Alexandra; Mátrai, Zoltán; Szucs, Attila; Belinszkaja, Galina; Langmár, Zoltán; Rosta, András

    2012-01-15

    Each aspect of oncological care is widely affected by the spread of oral anticancer agents, which raises several questions in terms of safe medication use and patient adherence. Over the past decade targeted therapies have appeared in clinical practice and revolutionized the pharmacological treatment of malignancies. Regular patient - doctor visits and proper patient education is crucial in order to comply with the therapy previously agreed upon with the oncologist, to increase patient adherence, to detect and to treat adverse effects in early stages. Since the information on the new medicines in Hungarian language is sparse it is the intention of the authors to give an overview of the basic knowledge, patient safety issues, adverse effects and interactions. Official drug information summaries and data on pharmacokinetics, interactions and adverse effects from the literature are reviewed as the basis for this overview. PMID:22217686

  5. Adverse Outcome Pathways and Drug-Induced Liver Injury Testing.

    PubMed

    Vinken, Mathieu

    2015-07-20

    Drug-induced liver injury is a prominent reason for premarketing and postmarketing drug withdrawal and can be manifested in a number of ways, such as cholestasis, steatosis, and fibrosis. The mechanisms driving these toxicological processes have been well characterized and have been emdedded in adverse outcome pathway frameworks in recent years. This review evaluates these constructs and simultaneously illustrates their use in the preclinical testing of drug-induced liver injury. PMID:26119269

  6. Adverse outcome pathways and drug-induced liver injury testing

    PubMed Central

    Vinken, Mathieu

    2015-01-01

    Drug-induced liver injury is a prominent reason for premarketing and postmarketing drug withdrawal and can be manifested in a number of ways, such as cholestasis, steatosis and fibrosis. The mechanisms driving these toxicological processes have been well characterized and have been emdedded in adverse outcome pathway frameworks in recent years. This paper reviews these constructs and simultaneously illustrates their use in the preclinical testing of drug-induced liver injury. PMID:26119269

  7. Medical marijuana patient counseling points for health care professionals based on trends in the medical uses, efficacy, and adverse effects of cannabis-based pharmaceutical drugs.

    PubMed

    Parmar, Jayesh R; Forrest, Benjamin D; Freeman, Robert A

    2016-01-01

    The purpose of this report is to present a review of the medical uses, efficacy, and adverse effects of the three approved cannabis-based medications and ingested marijuana. A literature review was conducted utilizing key search terms: dronabinol, nabilone, nabiximols, cannabis, marijuana, smoke, efficacy, toxicity, cancer, multiple sclerosis, nausea, vomiting, appetite, pain, glaucoma, and side effects. Abstracts of the included literature were reviewed, analyzed, and organized to identify the strength of evidence in medical use, efficacy, and adverse effects of the approved cannabis-based medications and medical marijuana. A total of 68 abstracts were included for review. Dronabinol's (Marinol) most common medical uses include weight gain, chemotherapy-induced nausea and vomiting (CINV), and neuropathic pain. Nabiximol's (Sativex) most common medical uses include spasticity in multiple sclerosis (MS) and neuropathic pain. Nabilone's (Cesamet) most common medical uses include CINV and neuropathic pain. Smoked marijuana's most common medical uses include neuropathic pain and glaucoma. Orally ingested marijuana's most common medical uses include improving sleep, reducing neuropathic pain, and seizure control in MS. In general, all of these agents share similar medical uses. The reported adverse effects of the three cannabis-based medications and marijuana show a major trend in central nervous system (CNS)-related adverse effects along with cardiovascular and respiratory related adverse effects. Marijuana shares similar medical uses with the approved cannabis-based medications dronabinol (Marinol), nabiximols (Sativex), and nabilone (Cesamet), but the efficacy of marijuana for these medical uses has not been fully determined due to limited and conflicting literature. Medical marijuana also has similar adverse effects as the FDA-approved cannabis-based medications mainly consisting of CNS related adverse effects but also including cardiovascular and respiratory

  8. Genetic polymorphisms affect efficacy and adverse drug reactions of DMARDs in rheumatoid arthritis.

    PubMed

    Zhang, Ling Ling; Yang, Sen; Wei, Wei; Zhang, Xue Jun

    2014-11-01

    Disease-modifying antirheumatic drugs (DMARDs) and biological agents are critical in preventing the severe complications of rheumatoid arthritis (RA). However, the outcome of treatment with these drugs in RA patients is quite variable and unpredictable. Drug-metabolizing enzymes (dihydrofolate reductase, cytochrome P450 enzymes, N-acetyltransferases, etc.), drug transporters (ATP-binding cassette transporters), and drug targets (tumor necrosis factor-α receptors) are coded for by variant alleles. These gene polymorphisms may influence the pharmacokinetics, pharmacodynamics, and side effects of medicines. The cause for differences in efficacy and adverse drug reactions may be genetic variation in drug metabolism among individuals. Polymorphisms in drug transporter genes may change the distribution and excretion of medicines, and the sensitivity of the targets to drugs is strongly influenced by genetic variations. In this article, we review the genetic polymorphisms that affect the efficacy of DMARDs or the occurrence of adverse drug reactions associated with DMARDs in RA. PMID:25144752

  9. Pharmacoepidemiological characterization of drug-induced adverse reaction clusters towards understanding of their mechanisms.

    PubMed

    Mizutani, Sayaka; Noro, Yousuke; Kotera, Masaaki; Goto, Susumu

    2014-06-01

    A big challenge in pharmacology is the understanding of the underlying mechanisms that cause drug-induced adverse reactions (ADRs), which are in some cases similar to each other regardless of different drug indications, and are in other cases different regardless of same drug indications. The FDA Adverse Event Reporting System (FAERS) provides a valuable resource for pharmacoepidemiology, the study of the uses and the effects of drugs in large human population. However, FAERS is a spontaneous reporting system that inevitably contains noise that deviates the application of conventional clustering approaches. By performing a biclustering analysis on the FAERS data we identified 163 biclusters of drug-induced adverse reactions, counting for 691 ADRs and 240 drugs in total, where the number of ADR occurrences are consistently high across the associated drugs. Medically similar ADRs are derived from several distinct indications for use in the majority (145/163=88%) of the biclusters, which enabled us to interpret the underlying mechanisms that lead to similar ADRs. Furthermore, we compared the biclusters that contain same drugs but different ADRs, finding the cases where the populations of the patients were different in terms of age, sex, and body weight. We applied a biclustering approach to catalogue the relationship between drugs and adverse reactions from a large FAERS data set, and demonstrated a systematic way to uncover the cases different drug administrations resulted in similar adverse reactions, and the same drug can cause different reactions dependent on the patients' conditions. PMID:24534381

  10. Predicting adverse drug events using pharmacological network models.

    PubMed

    Cami, Aurel; Arnold, Alana; Manzi, Shannon; Reis, Ben

    2011-12-21

    Early and accurate identification of adverse drug events (ADEs) is critically important for public health. We have developed a novel approach for predicting ADEs, called predictive pharmacosafety networks (PPNs). PPNs integrate the network structure formed by known drug-ADE relationships with information on specific drugs and adverse events to predict likely unknown ADEs. Rather than waiting for sufficient post-market evidence to accumulate for a given ADE, this predictive approach relies on leveraging existing, contextual drug safety information, thereby having the potential to identify certain ADEs earlier. We constructed a network representation of drug-ADE associations for 809 drugs and 852 ADEs on the basis of a snapshot of a widely used drug safety database from 2005 and supplemented these data with additional pharmacological information. We trained a logistic regression model to predict unknown drug-ADE associations that were not listed in the 2005 snapshot. We evaluated the model's performance by comparing these predictions with the new drug-ADE associations that appeared in a 2010 snapshot of the same drug safety database. The proposed model achieved an AUROC (area under the receiver operating characteristic curve) statistic of 0.87, with a sensitivity of 0.42 given a specificity of 0.95. These findings suggest that predictive network methods can be useful for predicting unknown ADEs. PMID:22190238

  11. Completeness of adverse drug reactions reports of the Saudi adverse event reporting system

    PubMed Central

    Alshammari, Thamir M.; Al-Kathiri, Wa’ad H.; Louet, Hervé Le; Aljadhey, Hisham S.

    2015-01-01

    Objectives: To assess completeness of reports in the Saudi Adverse Event Reporting System (SAERS), which is a part of the Saudi Food and Drug Authority pharmacovigilance system for monitoring the safety of medications. Methods: A cross-sectional study was conducted in Riyadh, Saudi Arabia using the reports that were received between December 2009 and June 2012 in the SAERS. The completeness was assessed by reviewing the components of the adverse drug reactions (ADRs) form, and how many fields were completed. Descriptive statistics are reported. Result: There were 14,783 reports during the study period. Eighty percent of these reports were spontaneous reports. Information related to the drug (99%) and adverse events (98%) of the reports were completed. While the patient’s demographic data were completed only in 38% of all reports, the least completed item in the ADRs form was the reporter information (15%). The most reported drug class was tumor necrosis factor inhibitors (7%), whereas events involving the respiratory organ system were the most frequently reported (4.5%). Conclusion: Although the SAERS is considered new, it has a high number of reports. More efforts are needed to improve the completeness of the SAERS to be a good source to assess the signals between events and suspected drugs, especially when there is a high number of reports. PMID:26108586

  12. Pharmacogenetic markers of severe cutaneous adverse drug reactions.

    PubMed

    Borroni, R G

    2014-04-01

    Different responses, in terms both of efficacy and toxicity, are commonly observed for any drug administered to apparently homogeneous groups of patients. It is estimated that adverse drug reactions (ADRs) cause 3-6% of all hospitalizations, accounting for 5% to 9% of hospital admission costs. The skin is often involved in ADRs and although most cutaneous ADRs have a favorable course, they may present as severe adverse cutaneous drug reactions (SCARs), such as Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (also referred to as drug-induced hypersensitivity syndrome), and acute generalized exanthematous pustulosis. SCARs are associated with significant mortality and require prompt diagnosis and adequate treatment. Pharmacogenetics studies individual variants in the DNA sequence associated with drug efficacy and toxicity, allowing prescription of a drug to patients expected to benefit from it, and excluding from treatment those who are at risk of developing ADRs. Pharmacogenetics already achieved several important results in the prevention of SCARs, and pharmacogenetic testing is now recommended by regulatory agencies before administration of abacavir and carbamazepine, leading to reduced incidence of SCARs. In this review, the pharmacogenetic associations of SCARs that have been validated in independent, case-control association studies will be presented. By familiarizing with principles of pharmacogenetics, dermatologists should be able to correlate specific cutaneous ADR phenotypes to the underlying genotype, thus contributing to better drug safety and facilitating drug discovery, development and approval. PMID:24819643

  13. Signal Detection of Adverse Drug Reaction of Amoxicillin Using the Korea Adverse Event Reporting System Database.

    PubMed

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

    2016-09-01

    We conducted pharmacovigilance data mining for a β-lactam antibiotics, amoxicillin, and compare the adverse events (AEs) with the drug labels of 9 countries including Korea, USA, UK, Japan, Germany, Swiss, Italy, France, and Laos. We used the Korea Adverse Event Reporting System (KAERS) database, a nationwide database of AE reports, between December 1988 and June 2014. Frequentist and Bayesian methods were used to calculate disproportionality distribution of drug-AE pairs. The AE which was detected by all the three indices of proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC) was defined as a signal. The KAERS database contained a total of 807,582 AE reports, among which 1,722 reports were attributed to amoxicillin. Among the 192,510 antibiotics-AE pairs, the number of amoxicillin-AE pairs was 2,913. Among 241 AEs, 52 adverse events were detected as amoxicillin signals. Comparing the drug labels of 9 countries, 12 adverse events including ineffective medicine, bronchitis, rhinitis, sinusitis, dry mouth, gastroesophageal reflux, hypercholesterolemia, gastric carcinoma, abnormal crying, induration, pulmonary carcinoma, and influenza-like symptoms were not listed on any of the labels of nine countries. In conclusion, we detected 12 new signals of amoxicillin which were not listed on the labels of 9 countries. Therefore, it should be followed by signal evaluation including causal association, clinical significance, and preventability. PMID:27510377

  14. Signal Detection of Adverse Drug Reaction of Amoxicillin Using the Korea Adverse Event Reporting System Database

    PubMed Central

    2016-01-01

    We conducted pharmacovigilance data mining for a β-lactam antibiotics, amoxicillin, and compare the adverse events (AEs) with the drug labels of 9 countries including Korea, USA, UK, Japan, Germany, Swiss, Italy, France, and Laos. We used the Korea Adverse Event Reporting System (KAERS) database, a nationwide database of AE reports, between December 1988 and June 2014. Frequentist and Bayesian methods were used to calculate disproportionality distribution of drug-AE pairs. The AE which was detected by all the three indices of proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC) was defined as a signal. The KAERS database contained a total of 807,582 AE reports, among which 1,722 reports were attributed to amoxicillin. Among the 192,510 antibiotics-AE pairs, the number of amoxicillin-AE pairs was 2,913. Among 241 AEs, 52 adverse events were detected as amoxicillin signals. Comparing the drug labels of 9 countries, 12 adverse events including ineffective medicine, bronchitis, rhinitis, sinusitis, dry mouth, gastroesophageal reflux, hypercholesterolemia, gastric carcinoma, abnormal crying, induration, pulmonary carcinoma, and influenza-like symptoms were not listed on any of the labels of nine countries. In conclusion, we detected 12 new signals of amoxicillin which were not listed on the labels of 9 countries. Therefore, it should be followed by signal evaluation including causal association, clinical significance, and preventability. PMID:27510377

  15. [Photodegradation of chlorpromazine, a drug-related adverse event].

    PubMed

    Chabi, Yossounon; Brahim, Kheira; Da Costa, Maryline; Caffin, Anne-Gaëlle; Camus, Gisèle; Paillet, Michel; Bohand, Xavier

    2016-04-01

    The photodegradation of an active substance during treatment is a rare drug-related adverse event which can sometimes have serious consequences. Health professionals must be aware of the specific storage and administration instructions with regard to chlorpromazine and ensure that they are respected. PMID:27085925

  16. A pipeline to extract drug-adverse event pairs from multiple data sources

    PubMed Central

    2014-01-01

    Background Pharmacovigilance aims to uncover and understand harmful side-effects of drugs, termed adverse events (AEs). Although the current process of pharmacovigilance is very systematic, the increasing amount of information available in specialized health-related websites as well as the exponential growth in medical literature presents a unique opportunity to supplement traditional adverse event gathering mechanisms with new-age ones. Method We present a semi-automated pipeline to extract associations between drugs and side effects from traditional structured adverse event databases, enhanced by potential drug-adverse event pairs mined from user-comments from health-related websites and MEDLINE abstracts. The pipeline was tested using a set of 12 drugs representative of two previous studies of adverse event extraction from health-related websites and MEDLINE abstracts. Results Testing the pipeline shows that mining non-traditional sources helps substantiate the adverse event databases. The non-traditional sources not only contain the known AEs, but also suggest some unreported AEs for drugs which can then be analyzed further. Conclusion A semi-automated pipeline to extract the AE pairs from adverse event databases as well as potential AE pairs from non-traditional sources such as text from MEDLINE abstracts and user-comments from health-related websites is presented. PMID:24559132

  17. A time-indexed reference standard of adverse drug reactions

    PubMed Central

    Harpaz, Rave; Odgers, David; Gaskin, Greg; DuMouchel, William; Winnenburg, Rainer; Bodenreider, Olivier; Ripple, Anna; Szarfman, Ana; Sorbello, Alfred; Horvitz, Eric; White, Ryen W.; Shah, Nigam H.

    2014-01-01

    Undetected adverse drug reactions (ADRs) pose a major burden on the health system. Data mining methodologies designed to identify signals of novel ADRs are of deep importance for drug safety surveillance. The development and evaluation of these methodologies requires proper reference benchmarks. While progress has recently been made in developing such benchmarks, our understanding of the performance characteristics of the data mining methodologies is limited because existing benchmarks do not support prospective performance evaluations. We address this shortcoming by providing a reference standard to support prospective performance evaluations. The reference standard was systematically curated from drug labeling revisions, such as new warnings, which were issued and communicated by the US Food and Drug Administration in 2013. The reference standard includes 62 positive test cases and 75 negative controls, and covers 44 drugs and 38 events. We provide usage guidance and empirical support for the reference standard by applying it to analyze two data sources commonly mined for drug safety surveillance. PMID:25632348

  18. Mining for adverse drug events with formal concept analysis.

    PubMed

    Estacio-Moreno, Alexander; Toussaint, Yannick; Bousquet, Cédric

    2008-01-01

    The pharmacovigilance databases consist of several case reports involving drugs and adverse events (AEs). Some methods are applied consistently to highlight all signals, i.e. all statistically significant associations between a drug and an AE. These methods are appropriate for verification of more complex relationships involving one or several drug(s) and AE(s) (e.g; syndromes or interactions) but do not address the identification of them. We propose a method for the extraction of these relationships based on Formal Concept Analysis (FCA) associated with disproportionality measures. This method identifies all sets of drugs and AEs which are potential signals, syndromes or interactions. Compared to a previous experience of disproportionality analysis without FCA, the addition of FCA was more efficient for identifying false positives related to concomitant drugs. PMID:18487830

  19. Successful Drug Development Despite Adverse Preclinical Findings Part 2: Examples

    PubMed Central

    Kuroda, Junji; Plassmann, Stephanie; Hayashi, Makoto; Prentice, David E.

    2010-01-01

    To illustrate the process of addressing adverse preclinical findings (APFs) as outlined in the first part of this review, a number of cases with unexpected APF in toxicity studies with drug candidates is discussed in this second part. The emphasis is on risk characterization, especially regarding the mode of action (MoA), and risk evaluation regarding relevance for man. While severe APFs such as retinal toxicity may turn out to be of little human relevance, minor findings particularly in early toxicity studies, such as vasculitis, may later pose a real problem. Rodents are imperfect models for endocrine APFs, non-rodents for human cardiac effects. Liver and kidney toxicities are frequent, but they can often be monitored in man and do not necessarily result in early termination of drug candidates. Novel findings such as the unusual lesions in the gastrointestinal tract and the bones presented in this review can be difficult to explain. It will be shown that well known issues such as phospholipidosis and carcinogenicity by agonists of peroxisome proliferator-activated receptors (PPAR) need to be evaluated on a case-by-case basis. The latter is of particular interest because the new PPAR α and dual α/γ agonists resulted in a change of the safety paradigm established with the older PPAR α agonists. General toxicologists and pathologists need some understanding of the principles of genotoxicity and reproductive toxicity testing. Both types of preclinical toxicities are major APF and clinical monitoring is difficult, generally leading to permanent use restrictions. PMID:22272032

  20. The effectiveness of computerized order entry at reducing preventable adverse drug events and medication errors in hospital settings: a systematic review and meta-analysis

    PubMed Central

    2014-01-01

    Background The Health Information Technology for Economic and Clinical Health (HITECH) Act subsidizes implementation by hospitals of electronic health records with computerized provider order entry (CPOE), which may reduce patient injuries caused by medication errors (preventable adverse drug events, pADEs). Effects on pADEs have not been rigorously quantified, and effects on medication errors have been variable. The objectives of this analysis were to assess the effectiveness of CPOE at reducing pADEs in hospital-related settings, and examine reasons for heterogeneous effects on medication errors. Methods Articles were identified using MEDLINE, Cochrane Library, Econlit, web-based databases, and bibliographies of previous systematic reviews (September 2013). Eligible studies compared CPOE with paper-order entry in acute care hospitals, and examined diverse pADEs or medication errors. Studies on children or with limited event-detection methods were excluded. Two investigators extracted data on events and factors potentially associated with effectiveness. We used random effects models to pool data. Results Sixteen studies addressing medication errors met pooling criteria; six also addressed pADEs. Thirteen studies used pre-post designs. Compared with paper-order entry, CPOE was associated with half as many pADEs (pooled risk ratio (RR) = 0.47, 95% CI 0.31 to 0.71) and medication errors (RR = 0.46, 95% CI 0.35 to 0.60). Regarding reasons for heterogeneous effects on medication errors, five intervention factors and two contextual factors were sufficiently reported to support subgroup analyses or meta-regression. Differences between commercial versus homegrown systems, presence and sophistication of clinical decision support, hospital-wide versus limited implementation, and US versus non-US studies were not significant, nor was timing of publication. Higher baseline rates of medication errors predicted greater reductions (P < 0.001). Other context and

  1. [ Preventing adverse drug events using clinical decision support systems].

    PubMed

    Salili, Ali Reza; Hammann, Felix; Taegtmeyer, Anne B

    2015-12-01

    Adverse drug events pose a great risk to patients, are an everyday clinical problem and can have potential/ega/ consequences. Computerized physician order entry or computerized provider order entry (CPOE} in combination with clinical decision support systems {CDSS) are popular and aim to reduce prescribing errors as well as identifying potentially harmful drug drug interactions. The quantifiable benejit these systems bring to patients, has however, yet to be definitively proven. This article focusses on the current standpoint of CPOE-/CDSS, their risks and benefits, the potential for improvement and their perspectives for the future. PMID:26654813

  2. Bioactivation and bioinactivation of drugs and drug metabolites: Relevance to adverse drug reactions.

    PubMed

    Park, B K; Pirmohamed, M; Tingle, M D; Madden, S; Kitteringham, N R

    1994-08-01

    Adverse drug reactions that cannot be predicted from the pharmacological properties of the drug and which are not easily reproduced in laboratory animals are a major complication of drug therapy. It is necessary to investigate the mechanisms of such reactions in order to (1) define structural features within a given drug molecule which are responsible for causing toxicity and (2) to identify those individuals who are particularly sensitive to a given drug reaction. In theory, drug toxicity may arise by direct toxicity, genotoxicity or immune-mediated toxicity caused by either parent drug or chemical. In this respect chemically reactive metabolites are of particular importance and the balance between bioactivation and bioinactivation pathways of drug metabolism will be a critical factor in both the type and extent of toxicity. We have therefore developed in vitro techniques that incorporate human cells for the detection and characterization of stable, chemically reactive and cytotoxic metabolites. In such experiments bioactivation (by CYP1A, CYP2D6, CYP3A, etc.) can be investigated by use of a liver bank, while lymphocytes provide accessible human cells, which can be obtained from both patients and volunteers, genotyped and/or phenotyped for particular drug-metabolizing enzymes (eg. glutathione transferase mu). The relevance of in vitro experiments to drug toxicity observed in humans will be illustrated by reference to studies with anticonvulsants and antimalarials. PMID:20692973

  3. Unity from diversity: the evidential use of anecdotal reports of adverse drug reactions and interactions.

    PubMed

    Aronson, Jeffrey K

    2005-04-01

    Anecdotal case reports contribute about one-third of the published literature on adverse drug reactions and interactions, but are regarded as providing poor-quality evidence. However, they can occasionally provide proof of cause and effect, and there are many other reasons for publishing them. Because an anecdote is a narrative, narratological paradigms from literature, art, and music can show how we can make evidential use of anecdotes. Useful paradigms are the dramatic unities (of time, place, and action), comprehensive catalogues, and pattern formations. Here I give examples of each of these types of paradigm and show how they can be used to interpret anecdotes about adverse drug reactions and interactions. The dramatic unities show how a proper classification of adverse drug reactions can be achieved, according to dose-relation, time-course, and susceptibility factors; use of this classification should improve the evidential use of anecdotal reports. A high background incidence of the effect (the medical equivalent of subplots, which violate the unity of action) makes it more difficult to detect adverse drug effects using anecdotal reports. To make best evidential use of the corpus of anecdotal reports of adverse drug reactions, comprehensiveness is important: each suspected adverse reaction should be reported in detail and reactions should be reported in sufficient numbers for proper classification and for patterns to be recognized. One form of pattern recognition, teleoanalysis of data, should, when possible, include not only randomized controlled trials and observational studies, but also case series and anecdotal reports. PMID:15813716

  4. Comparing probabilistic and descriptive analyses of time-dose-toxicity relationship for determining no-observed-adverse-effect level in drug development.

    PubMed

    Glatard, Anaïs; Berges, Aliénor; Sahota, Tarjinder; Ambery, Claire; Osborne, Jan; Smith, Randall; Hénin, Emilie; Chen, Chao

    2015-10-15

    The no-observed-adverse-effect level (NOAEL) of a drug defined from animal studies is important for inferring a maximal safe dose in human. However, several issues are associated with its concept, determination and application. It is confined to the actual doses used in the study; becomes lower with increasing sample size or dose levels; and reflects the risk level seen in the experiment rather than what may be relevant for human. We explored a pharmacometric approach in an attempt to address these issues. We first used simulation to examine the behaviour of the NOAEL values as determined by current common practice; and then fitted the probability of toxicity as a function of treatment duration and dose to data collected from all applicable toxicology studies of a test compound. Our investigation was in the context of an irreversible toxicity that is detected at the end of the study. Simulations illustrated NOAEL's dependency on experimental factors such as dose and sample size, as well as the underlying uncertainty. Modelling the probability as a continuous function of treatment duration and dose simultaneously to data from multiple studies allowed the estimation of the dose, along with its confidence interval, for a maximal risk level that might be deemed as acceptable for human. The model-based data integration also reconciled between-study inconsistency and explicitly provided maximised estimation confidence. Such alternative NOAEL determination method should be explored for its more efficient data use, more quantifiable insight to toxic doses, and the potential for more relevant animal-to-human translation. PMID:26232187

  5. Management of adverse effects of mood stabilizers.

    PubMed

    Murru, Andrea; Popovic, Dina; Pacchiarotti, Isabella; Hidalgo, Diego; León-Caballero, Jordi; Vieta, Eduard

    2015-08-01

    Mood stabilizers such as lithium and anticonvulsants are still standard-of-care for the acute and long-term treatment of bipolar disorder (BD). This systematic review aimed to assess the prevalence of their adverse effects (AEs) and to provide recommendations on their clinical management. We performed a systematic research for studies reporting the prevalence of AEs with lithium, valproate, lamotrigine, and carbamazepine/oxcarbazepine. Management recommendations were then developed. Mood stabilizers have different tolerability profiles and are eventually associated to cognitive, dermatological, endocrine, gastrointestinal, immunological, metabolic, nephrogenic, neurologic, sexual, and teratogenic AEs. Most of those can be transient or dose-related and can be managed by optimizing drug doses to the lowest effective dose. Some rare AEs can be serious and potentially lethal, and require abrupt discontinuation of medication. Integrated medical attention is warranted for complex somatic AEs. Functional remediation and psychoeducation may help to promote awareness on BD and better medication management. PMID:26084665

  6. Analysis of Adverse Drug Reactions of Atypical Antipsychotic Drugs in Psychiatry OPD

    PubMed Central

    Piparva, Kiran G.; Buch, J. G.; Chandrani, Kalpesh V.

    2011-01-01

    Background: Novel atypical antipsychotics are superior to conventional antipsychotics as they significantly reduce both positive and negative symptoms of schizophrenia and have lower risk of extrapyramidal symptoms (EPS). However, these drugs have separate set of adverse drug reactions (ADRs). Therefore, this study was carried out to assess these ADRs, which can have impact on long-term compliance and achieving successful treatment. Materials and Methods: A prospective study of analysis of ADR of atypical antipsychotic drugs was carried out in the psychiatry outpatient department. Patients of psychotic disorder (any age, either sex), who were prescribed atypical antipsychotic drugs, were included. Those who were prescribed conventional antipsychotics or combinations of antipsychotics were excluded from the study. Apart from spontaneously reported ADRs, a questionnaire related to the likely ADR was used and patients’ responses were recorded in the case record form. Results: Totally 93 ADRs were recorded from 84 prescriptions. Majority of the ADRs (82 out of 93) were seen with risperidone and olanzepine, as they were the commonly prescribed drugs. Weight gain, dizziness, sleep disturbance and appetite disturbance accounted for nearly 78% of the total events. With risperidone (at 4–6 mg/day) and olanzepine (at 10–15 mg/day), gastrointestinal and sleep disturbance were observed in the initial (within 7 days to 2–3 months after treatment) course of treatment, while EPS, fatigue, seizure, increased frequency of micturition and dizziness were observed after long-term (3–9 months) use. Conclusion: The present study adds to the existing information on the prevalence of adverse effects of atypical antipsychotic drugs. Role of active surveillance in post-marketing phase is also emphasized. PMID:22345840

  7. Mixed-effects Poisson regression analysis of adverse event reports

    PubMed Central

    Gibbons, Robert D.; Segawa, Eisuke; Karabatsos, George; Amatya, Anup K.; Bhaumik, Dulal K.; Brown, C. Hendricks; Kapur, Kush; Marcus, Sue M.; Hur, Kwan; Mann, J. John

    2008-01-01

    SUMMARY A new statistical methodology is developed for the analysis of spontaneous adverse event (AE) reports from post-marketing drug surveillance data. The method involves both empirical Bayes (EB) and fully Bayes estimation of rate multipliers for each drug within a class of drugs, for a particular AE, based on a mixed-effects Poisson regression model. Both parametric and semiparametric models for the random-effect distribution are examined. The method is applied to data from Food and Drug Administration (FDA)’s Adverse Event Reporting System (AERS) on the relationship between antidepressants and suicide. We obtain point estimates and 95 per cent confidence (posterior) intervals for the rate multiplier for each drug (e.g. antidepressants), which can be used to determine whether a particular drug has an increased risk of association with a particular AE (e.g. suicide). Confidence (posterior) intervals that do not include 1.0 provide evidence for either significant protective or harmful associations of the drug and the adverse effect. We also examine EB, parametric Bayes, and semiparametric Bayes estimators of the rate multipliers and associated confidence (posterior) intervals. Results of our analysis of the FDA AERS data revealed that newer antidepressants are associated with lower rates of suicide adverse event reports compared with older antidepressants. We recommend improvements to the existing AERS system, which are likely to improve its public health value as an early warning system. PMID:18404622

  8. 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

  9. 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. PMID:19482095

  10. Ocular and systemic adverse effects of ophthalmic and non ophthalmic medications.

    PubMed

    Izazola-Conde, C; Zamora-de la Cruz, D; Tenorio-Guajardo, G

    2011-01-01

    Information related to adverse drug effects caused by ocular medications and ocular adverse effects of systemically administered drugs has increased over the last several decades. Here we review the medical literature over the last four decades to both quantitatively and qualitatively determine the adverse effects of ocular drugs and ocular toxicity of non-ocular drugs. A systematic bibliographic review of the literature was performed with the following terms: "drug treatment", "drug therapy", "ocular adverse effects", "ocular side effects", "ocular toxicity", "systemic side effects", "systemic adverse effects", "systemic toxicity", "ocular drug" and "ophthalmic drug" using the Boolean operators or, and, not. Searches focused on: (1) Ocular side/adverse effects of ophthalmic drugs; (2) Ocular side/adverse effects of systemic drugs; (3) Systemic side/adverse effects of ophthalmic drugs. PubMed was used to perform searches. Limits included: species, human and field tag, abstract/title, dates from 01/01/1971 to 31/12/2010. A sub-selection of references was made by discarding articles that were irrelevant for the topics listed above. Adverse effects of alpha2-adrenergic agonists, beta-adrenergic antagonists, quinine derivatives and antituberculosis agents appear in the literature throughout the period of the review. Adverse effects of newer drugs such as amiodarone, phosphodiesterase 5 inhibitors, antiepileptics, tamoxifen, and its interactions have been published principally in the last two decades. It is imperative for patient safety that knowledge of the adverse effects of drugs on the eye whether topically or systemically administered, and the possible systemic effects of drugs given as ophthalmic medications be emphasized to clinicians. PMID:22423585

  11. 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

  12. Adverse drug reactions in elderly patients: alternative approaches to postmarket surveillance.

    PubMed

    Noah, B A; Brushwood, D B

    2000-01-01

    In the last three years, the Food and Drug Administration has withdrawn seven prescription drugs from the market, and it has required intensified warnings for a number of others, all due to the discovery of previously unforeseen side effects associated with their use. Adverse drug reactions are a leading cause of death in the United States. For a variety of physiological and socio-medical reasons, the elderly are particularly susceptible to adverse drug reactions. Because the pre-approval process cannot expose all potential risks associated with a drug, the authors assert that policymakers should consider implementing a more extensive, and more integrated, post-approval surveillance and testing system. They conclude that the recent cluster of drug withdrawals due to safety problems raises legitimate questions about the rigor and effectiveness of the post-approval monitoring system for new drugs, and these questions extend beyond the obvious difficulties associated with the collection and analysis of risk data. Traditionally viewed as a regulatory problem for the FDA, the problem of adverse drug reactions implicates patient welfare and the provision of medical care more broadly, and a purely regulatory mind set unnecessarily constrains thinking about possible approaches to improving drug safety. Possible solutions to the problem ought to contemplate more formalized involvement of the medical community, pharmacists, and patients. This Article introduces a proposed systems approach to detecting and preventing adverse drug reactions, and discusses several other incremental reforms to existing systems that may help the medical community to improve the overall safety of prescription drug therapy for the elderly, and ultimately for all patients. PMID:11184355

  13. [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. PMID:26152872

  14. Neuropsychiatric Adverse Effects of Interferon-α

    PubMed Central

    Raison, Charles L.; Demetrashvili, Marina; Capuron, Lucile; Miller, Andrew H.

    2005-01-01

    subjects to complete treatment successfully. Recent data suggest that IFNα-induced depression may be composed of two overlapping syndromes: a depression-specific syndrome characterised by mood, anxiety and cognitive complaints, and a neurovegetative syndrome characterised by fatigue, anorexia, pain and psychomotor slowing. Depression-specific symptoms are highly responsive to serotonergic antidepressants, whereas neurovegetative symptoms are significantly less responsive to these agents. These symptoms may he more effectively treated by agents that modulate catecholaminergic functioning, such as combined serotonin-noradrenaline (norepinephrine) antidepressants, bupropion, psychostimulants or modafinil. Additional factors to consider in selecting an antidepressant include potential drug-drug interactions and adverse effect profile. Finally. IFNα appears capable of inducing manic symptoms. Mania, especially when severe, is a clinical emergency. When this occurs, IFNα and antidepressants should be stopped, an emergency psychiatric consultation should he obtained, and treatment with a mood stabiliser should be initiated. PMID:15697325

  15. 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

  16. Cutaneous adverse drug reactions in Indian population: A systematic review

    PubMed Central

    Patel, Tejas K; Thakkar, Sejal H; Sharma, DC

    2014-01-01

    Background: Epidemiological data is limited for cutaneous adverse drug reactions (CADRs) in India. Most of the Indian studies have small sample size and are of limited duration. Aims: The aim of this study is to analyze CADRs with reference to the causative drugs and their clinical characteristics in Indian population. Materials and Methods: As per selection criteria, electronic databases were searched for publications describing CADRs from January-1995 to April-2013 by two independent investigators. Data of the causative drugs and clinical characteristics were extracted and summarized by absolute numbers, percentages, ranges, and means as presented by the authors. The subgroup analysis of causative drugs was performed for causality assessment, severe or nonsevere reactions and occurrence of common CADRs. Studies showing “definite” and “probable” categories of causality analysis were labeled as “definite and probable causality (DPC) studies”. The other included studies were labeled as “non-DPC studies”. Results: Of 8337 retrieved references, 18 prospective studies were selected for analysis. The pooled incidence was 9.22/1000 total among outpatient and inpatient cases. Commonly observed reactions were maculopapular rash (32.39%), fixed drug eruptions (FDEs) (20.13%), urticaria (17.49%) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) (6.84%). The major causative drug groups were antimicrobials (45.46%), nonsteroidal anti-inflammatory drugs (NSAIDs) (20.87%) and anti-epileptic drugs (14.57%). Commonly implicated drugs were sulfa (13.32%), β-lactams (8.96%) and carbamazepine (6.65%). High frequency of CADRs is observed with anti-epileptic drugs in DPC studies only. Carbamazepine, phenytoin and fluoroquinolones had higher severe to nonsevere cutaneous reaction ratio than other drugs. Antimicrobials were the main causative drugs for maculopapular rash, FDEs and SJS/TEN, and NSAIDs for the urticaria. The mortality for overall CADRs, SJS

  17. 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

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Records and reports concerning adverse drug experiences on marketed prescription drugs for human use without approved new drug applications. 310.305 Section 310.305 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE NEW DRUGS...

  18. 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

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Records and reports concerning adverse drug experiences on marketed prescription drugs for human use without approved new drug applications. 310.305 Section 310.305 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE NEW DRUGS...

  19. 21 CFR 310.305 - Records and reports concerning adverse drug experiences on marketed prescription drugs for human...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Records and reports concerning adverse drug experiences on marketed prescription drugs for human use without approved new drug applications. 310.305 Section 310.305 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE NEW DRUGS...

  20. 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

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Records and reports concerning adverse drug experiences on marketed prescription drugs for human use without approved new drug applications. 310.305 Section 310.305 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE NEW DRUGS...

  1. 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

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Records and reports concerning adverse drug experiences on marketed prescription drugs for human use without approved new drug applications. 310.305 Section 310.305 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE NEW DRUGS...

  2. Automatic adverse drug events detection using letters to the editor.

    PubMed

    Yang, Chao; Srinivasan, Padmini; Polgreen, Philip M

    2012-01-01

    We present and test the intuition that letters to the editor in journals carry early signals of adverse drug events (ADEs). Surprisingly these letters have not yet been exploited for automatic ADE detection unlike for example, clinical records and PubMed. Part of the challenge is that it is not easy to access the full-text of letters (for the most part these do not appear in PubMed). Also letters are likely underrated in comparison with full articles. Besides demonstrating that this intuition holds we contribute techniques for post market drug surveillance. Specifically, we test an automatic approach for ADE detection from letters using off-the-shelf machine learning tools. We also involve natural language processing for feature definitions. Overall we achieve high accuracy in our experiments and our method also works well on a second new test set. Our results encourage us to further pursue this line of research. PMID:23304379

  3. Automatic Adverse Drug Events Detection Using Letters to the Editor

    PubMed Central

    Yang, Chao; Srinivasan, Padmini; Polgreen, Philip M.

    2012-01-01

    We present and test the intuition that letters to the editor in journals carry early signals of adverse drug events (ADEs). Surprisingly these letters have not yet been exploited for automatic ADE detection unlike for example, clinical records and PubMed. Part of the challenge is that it is not easy to access the full-text of letters (for the most part these do not appear in PubMed). Also letters are likely underrated in comparison with full articles. Besides demonstrating that this intuition holds we contribute techniques for post market drug surveillance. Specifically, we test an automatic approach for ADE detection from letters using off-the-shelf machine learning tools. We also involve natural language processing for feature definitions. Overall we achieve high accuracy in our experiments and our method also works well on a second new test set. Our results encourage us to further pursue this line of research. PMID:23304379

  4. [Acute adverse effects of dialysis].

    PubMed

    Opatrný, K

    2003-02-01

    Adverse reactions to dialyzers are a not very frequent, but because of the serious, sometimes fatal course, a dreaded complication of haemodialysis treatment. Most important among these reactions are hypersensitive reactions (anaphylactoid, reaction type A to dialyzer), which develop as a rule within the 10th minute of the procedure, and the reaction caused by the action of perfluorohydrocarbon which develop hours after onset or even completion of haemodialysis. Explanation of the development of hypersensitive reactions (HSR) by complement activation and formation of anaphylatoxins C3a and C5a during contact of blood with the bioincompatible dialysis membrane has been abandoned. Evidence of the etiological role of ethylene oxide (ETO) in the development of HSR influenced the selection of materials for the production of dialyzers and sterilization during manufacture, it emphasized the importance of rinsing of the dialyzer in the dialysis centre and led to the wide application of alternative methods of sterilization by gamma radiation and steam. HSR may be also caused by overproduction of bradykinin and inhibition of its degradation or degradation of its metabolites. Excessive bradykinin production caused by dialysis membranes with a negative charge is potentiated e.g. by a lower pH and increased plasma dilution in the initial stage of haemodialysis. Inhibition of bradykinin degradation develops during treatment with angiotensin converting enzyme inhibitors (ACEI). In prevention of HSR associated with bradykinin in addition to elimination of a combination of a negatively charged dialysis membrane and ACEI treatment a part is played also by rinsing of the dialyzer before haemodialysis with a bicarbonate solution and the modification of the membrane surface (implemented by the manufacturer) which reduces its negative charge. The first reaction to the dialyzer in conjunction with perfluorohydrocarbon (PF-5070), used in production of some dialyzers for testing the

  5. 3D Pharmacophoric Similarity improves Multi Adverse Drug Event Identification in Pharmacovigilance

    NASA Astrophysics Data System (ADS)

    Vilar, Santiago; Tatonetti, Nicholas P.; Hripcsak, George

    2015-03-01

    Adverse drugs events (ADEs) detection constitutes a considerable concern in patient safety and public health care. For this reason, it is important to develop methods that improve ADE signal detection in pharmacovigilance databases. Our objective is to apply 3D pharmacophoric similarity models to enhance ADE recognition in Offsides, a pharmacovigilance resource with drug-ADE associations extracted from the FDA Adverse Event Reporting System (FAERS). We developed a multi-ADE predictor implementing 3D drug similarity based on a pharmacophoric approach, with an ADE reference standard extracted from the SIDER database. The results showed that the application of our 3D multi-type ADE predictor to the pharmacovigilance data in Offsides improved ADE identification and generated enriched sets of drug-ADE signals. The global ROC curve for the Offsides ADE candidates ranked with the 3D similarity score showed an area of 0.7. The 3D predictor also allows the identification of the most similar drug that causes the ADE under study, which could provide hypotheses about mechanisms of action and ADE etiology. Our method is useful in drug development, screening potential adverse effects in experimental drugs, and in drug safety, applicable to the evaluation of ADE signals selected through pharmacovigilance data mining.

  6. Impact of New Genomic Technologies on Understanding Adverse Drug Reactions.

    PubMed

    Maggo, Simran D S; Savage, Ruth L; Kennedy, Martin A

    2016-04-01

    It is well established that variations in genes can alter the pharmacokinetic and pharmacodynamic profile of a drug and immunological responses to it. Early advances in pharmacogenetics were made with traditional genetic techniques such as functional cloning of genes using knowledge gained from purified proteins, and candidate gene analysis. Over the past decade, techniques for analysing the human genome have accelerated greatly as knowledge and technological capabilities have grown. These techniques were initially focussed on understanding genetic factors of disease, but increasingly they are helping to clarify the genetic basis of variable drug responses and adverse drug reactions (ADRs). We examine genetic methods that have been applied to the understanding of ADRs, review the current state of knowledge of genetic factors that influence ADR development, and discuss how the application of genome-wide association studies and next-generation sequencing approaches is supporting and extending existing knowledge of pharmacogenetic processes leading to ADRs. Such approaches have identified single genes that are major contributing genetic risk factors for an ADR, (such as flucloxacillin and drug-induced liver disease), making pre-treatment testing a possibility. They have contributed to the identification of multiple genetic determinants of a single ADR, some involving both pharmacologic and immunological processes (such as phenytoin and severe cutaneous adverse reactions). They have indicated that rare genetic variants, often not previously reported, are likely to have more influence on the phenotype than common variants that have been traditionally tested for. The problem of genotype/phenotype discordance affecting the interpretation of pharmacogenetic screening and the future of genome-based testing applied to ADRs are also discussed. PMID:26369774

  7. Attitudinal survey of voluntary reporting of adverse drug reactions

    PubMed Central

    Eland, I A; Belton, K J; van Grootheest, A C; Meiners, A P; Rawlins, M D; Stricker, B H Ch

    1999-01-01

    Aims Voluntary adverse drug reaction (ADR) reporting schemes have operated since the early sixties in many Western countries. It is generally recognized, however, that only a small proportion of ADRs is actually reported. The current survey was conducted to assess attitudes towards reporting of ADRs, and to study which types of ADRs are reported. Methods A questionnaire seeking reasons for nonreporting was sent to a random sample of 10% of medical practitioners in The Netherlands in October 1997. After 6 weeks, a reminder was sent to those who had not responded. Results One thousand four hundred and forty-two (73%) questionnaires were returned, of which 94% were complete. The percentage of GPs (51%) which had ever reported an ADR to the national reporting centre was significantly higher than the percentage of specialists (35%), who reported more often to the pharmaceutical industry (34%vs 48%). 86% of GPs, 72% of surgical specialists and 81% of medical specialists had ever diagnosed an ADR, which they had not reported. Uncertainty as to whether the reaction was caused by a drug (72%), the ADR being trivial (75%) or too well known (93%) were the most important reasons for not reporting. 18% were not aware of the need to report ADRs, 22% did not know how to report ADRs, 38% did not have enough time, 36% thought that reporting was too bureaucratic and only 26% of Dutch physicians knew which ADRs to report. A serious ADR, an unlabelled ADR, an ADR to a new drug, history of reporting of one or more ADRs, and specialty were all independently associated with reporting of 16 hypothetical ADRs. Surgical and medical specialists tended to report less often than GPs. Conclusions There is a considerable degree of underreporting, which might partly be explained by lack of knowledge and misconceptions about spontaneous reporting of adverse drug reactions. PMID:10583035

  8. Adverse drug reactions in special populations - the elderly.

    PubMed

    Davies, E A; O'Mahony, M S

    2015-10-01

    The International Conference on Harmonization considers older people a 'special population', as they differ from younger adults in terms of comorbidity, polypharmacy, pharmacokinetics and greater vulnerability to adverse drug reactions (ADRs). Medical practice is often based on single disease guidelines derived from clinical trials that have not included frail older people or those with multiple morbidities. This presents a challenge caring for older people, as drug doses in trials may not be achievable in real world patients and risks of ADRs are underestimated in clinical trial populations. The majority of ADRs in older people are Type A, potentially avoidable and associated with commonly prescribed medications. Several ADRs are particularly associated with major adverse consequences in the elderly and their reduction is therefore a clinical priority. Falls are strongly associated with benzodiazepines, neuroleptics, antidepressants and antihypertensives. There is good evidence for medication review as part of a multifactorial intervention to reduce falls risk in community dwelling elderly. Multiple medications also contribute to delirium, another multifactorial syndrome resulting in excess mortality particularly in frail older people. Clostridium difficile associated with use of broad spectrum antibiotics mainly affects frail older people and results in prolonged hospital stay with substantial morbidity and mortality. Antipsychotics increase the risk of stroke by more than three-fold in patients with dementia. Inappropriate prescribing can be reduced by adherence to prescribing guidelines, suitable monitoring and regular medication review. Given the heterogeneity within the older population, providing individualized care is pivotal to preventing ADRs. PMID:25619317

  9. Predicting risk of adverse drug reactions in older adults.

    PubMed

    Lavan, Amanda Hanora; Gallagher, Paul

    2016-02-01

    Adverse drug reactions (ADRs) are common in older adults, with falls, orthostatic hypotension, delirium, renal failure, gastrointestinal and intracranial bleeding being amongst the most common clinical manifestations. ADR risk increases with age-related changes in pharmacokinetics and pharmacodynamics, increasing burden of comorbidity, polypharmacy, inappropriate prescribing and suboptimal monitoring of drugs. ADRs are a preventable cause of harm to patients and an unnecessary waste of healthcare resources. Several ADR risk tools exist but none has sufficient predictive value for clinical practice. Good clinical practice for detecting and predicting ADRs in vulnerable patients includes detailed documentation and regular review of prescribed and over-the-counter medications through standardized medication reconciliation. New medications should be prescribed cautiously with clear therapeutic goals and recognition of the impact a drug can have on multiple organ systems. Prescribers should regularly review medication efficacy and be vigilant for ADRs and their contributory risk factors. Deprescribing should occur at an individual level when drugs are no longer efficacious or beneficial or when safer alternatives exist. Inappropriate prescribing and unnecessary polypharmacy should be minimized. Comprehensive geriatric assessment and the use of explicit prescribing criteria can be useful in this regard. PMID:26834959

  10. Predicting risk of adverse drug reactions in older adults

    PubMed Central

    Lavan, Amanda Hanora; Gallagher, Paul

    2016-01-01

    Adverse drug reactions (ADRs) are common in older adults, with falls, orthostatic hypotension, delirium, renal failure, gastrointestinal and intracranial bleeding being amongst the most common clinical manifestations. ADR risk increases with age-related changes in pharmacokinetics and pharmacodynamics, increasing burden of comorbidity, polypharmacy, inappropriate prescribing and suboptimal monitoring of drugs. ADRs are a preventable cause of harm to patients and an unnecessary waste of healthcare resources. Several ADR risk tools exist but none has sufficient predictive value for clinical practice. Good clinical practice for detecting and predicting ADRs in vulnerable patients includes detailed documentation and regular review of prescribed and over-the-counter medications through standardized medication reconciliation. New medications should be prescribed cautiously with clear therapeutic goals and recognition of the impact a drug can have on multiple organ systems. Prescribers should regularly review medication efficacy and be vigilant for ADRs and their contributory risk factors. Deprescribing should occur at an individual level when drugs are no longer efficacious or beneficial or when safer alternatives exist. Inappropriate prescribing and unnecessary polypharmacy should be minimized. Comprehensive geriatric assessment and the use of explicit prescribing criteria can be useful in this regard. PMID:26834959

  11. Migraine treatment: a chain of adverse effects.

    PubMed

    Veloso, Tiago Sousa; Cambão, Mariana Seixas

    2015-01-01

    This clinical vignette presents a 14 years old female, with a past medical history relevant only for migraine with typical aura of less than monthly frequency, complaining of a severe unilateral headache with rising intensity for the previous 4 h, associated with nausea, vomiting, photophobia and phonophobia. This episode of migraine with aura in a patient with recurrent migraine was complicated by side effects of medical diagnostic and therapeutic procedures (extrapyramidal symptoms, delirium, post-lumbar puncture headache, hospital admission) all of which could have been prevented-quaternary prevention. This case illustrates several important messages in migraine management: (1) use of acetaminophen is not based in high-quality evidence and better options exist; (2) among youngsters, domperidone should be preferred over metoclopramide because it does not cross the blood-brain barrier; (3) moderate to severe migraine crisis can be managed with triptans in teenagers over 12 years old; (4) it is important to recognize adverse drug effects; (5) harmful consequences of medical interventions do occur; (6) the school community must be informed about chronic diseases of the young. PMID:26266080

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

    PubMed Central

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

    2016-01-01

    Background 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. Objective 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. Methods 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. Results 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. Conclusions 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. PMID:27036325

  13. Perspective on Lithotripsy Adverse Effects

    NASA Astrophysics Data System (ADS)

    Knoll, Thomas; Wendt-Nordahl, Gunnar

    2008-09-01

    Shock wave lithotripsy (SWL) is an effective and without any doubt the least invasive procedure to treat upper urinary tract calculi. Acute complications are rarely reported and do not require specific treatment in most cases. However, one should be aware that energy levels sufficient for stone breakage are capable of damaging tissue as well, and significant hematoma—not only in the kidney but as well in surrounding organs—has been observed. Furthermore, only little is known about the long-term effects of SWL. Some authors have reported an increased incidence of hypertension and possibly also diabetes mellitus. Such chronic diseases—if indeed related to prior SWL—may be a late result of acute SWL-related trauma but the discussion on the underlying pathogenesis is controversial. Many factors have to be considered, such as the natural history of recurrent stone formers, technical principles of SWL, and differences in treatment protocols. Promising studies are currently underway to optimize stone breakage while limiting potential collateral damage. With this progress, SWL remains a safe treatment option for most urinary calculi.

  14. Adverse effects of IgG therapy.

    PubMed

    Berger, Melvin

    2013-01-01

    IgG is widely used for patients with immune deficiencies and in a broad range of autoimmune and inflammatory disorders. Up to 40% of intravenous infusions of IgG may be associated with adverse effects (AEs), which are mostly uncomfortable or unpleasant but often are not serious. The most common infusion-related AE is headache. More serious reactions, including true anaphylaxis and anaphylactoid reactions, occur less frequently. Most reactions are related to the rate of infusion and can be prevented or treated just by slowing the infusion rate. Medications such as nonsteroidal anti-inflammatory drugs, antihistamines, or corticosteroids also may be helpful in preventing or treating these common AEs. IgA deficiency with the potential of IgG or IgE antibodies against IgA increases the risk of some AEs but should not be viewed as a contraindication if IgG therapy is needed. Potentially serious AEs include renal dysfunction and/or failure, thromboembolic events, and acute hemolysis. These events usually are multifactorial, related to combinations of constituents in the IgG product as well as risk factors for the recipient. Awareness of these factors should allow minimization of the risks and consequences of these AEs. Subcutaneous IgG is absorbed more slowly into the circulation and has a lower incidence of AEs, but awareness and diligence are necessary whenever IgG is administered. PMID:24565701

  15. An overview on adverse drug reactions to traditional Chinese medicines.

    PubMed

    Chan, Kelvin; Zhang, Hongwei; Lin, Zhi-Xiu

    2015-10-01

    The safe use of Chinese materia medica (CMM) and products in traditional Chinese medicine (TCM) practice conventionally relies on correct pharmacognostic identification, good agricultural and manufacturing practices based on pharmacopoeia standards and rational/correct CMM combinations with TCM-guided clinical prescribing. These experience-based principles may not absolutely ensure safety without careful toxicological investigations when compared with development of new pharmaceutical drugs. Clinically observed toxicity reports remain as guidance for gathering toxicological evidence, though essential as pharmacovigilance, but are considered as late events for ensuring safety. The overview focuses on the following factors: global development of TCM that has affected conventional healthcare; examples of key toxic substances in CMM; reported adverse drug reactions (ADRs) consequential to taking CMM and TCM products; and proposals on rational approaches to integrate the knowledge of biomedical science and the principles of TCM practice for detecting early ADRs if both TCM products and orthodox drugs are involved. It is envisaged that good control of the quality and standards of CMM and proprietary Chinese medicines can certainly reduce the incidence of ADRs in TCM practice when these medications are used. PMID:25619530

  16. 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

  17. Adverse Effects of Psychotropic Medications on Sleep.

    PubMed

    Doghramji, Karl; Jangro, William C

    2016-09-01

    Psychotropic medications such as antidepressants, antipsychotics, stimulants, and benzodiazepines are widely prescribed. Most of these medications are thought to exert their effects through modulation of various monoamines as well as interactions with receptors such as histamine and muscarinic cholinergic receptors. Through these interactions, psychotropics can also have a significant impact on sleep physiology, resulting in both beneficial and adverse effects on sleep. PMID:27514301

  18. Adverse effects of fillers and their histopathology.

    PubMed

    Haneke, Eckart

    2014-12-01

    Injectable fillers nowadays represent a pillar in facial rejuvenation and make a significant contribution to the success of the treatment. Despite their obvious benefits, a wide range of possible complications such as immediate, late, delayed, temporary, or irreversible adverse effects have to be respected. Differentiating the various filler materials, these effects are assigned to histopathology findings and currently available treatment options. PMID:25536126

  19. Pharmacovigilance on Twitter? Mining Tweets for Adverse Drug Reactions

    PubMed Central

    O’Connor, Karen; Pimpalkhute, Pranoti; Nikfarjam, Azadeh; Ginn, Rachel; Smith, Karen L; Gonzalez, Graciela

    2014-01-01

    Recent research has shown that Twitter data analytics can have broad implications on public health research. However, its value for pharmacovigilance has been scantly studied – with health related forums and community support groups preferred for the task. We present a systematic study of tweets collected for 74 drugs to assess their value as sources of potential signals for adverse drug reactions (ADRs). We created an annotated corpus of 10,822 tweets. Each tweet was annotated for the presence or absence of ADR mentions, with the span and Unified Medical Language System (UMLS) concept ID noted for each ADR present. Using Cohen’s kappa1, we calculated the inter-annotator agreement (IAA) for the binary annotations to be 0.69. To demonstrate the utility of the corpus, we attempted a lexicon-based approach for concept extraction, with promising success (54.1% precision, 62.1% recall, and 57.8% F-measure). A subset of the corpus is freely available at: http://diego.asu.edu/downloads. PMID:25954400

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

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Postmarketing reporting of adverse drug experiences. 314.80 Section 314.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications § 314.80 Postmarketing reporting of...

  1. 21 CFR 314.80 - Postmarketing reporting of adverse drug experiences.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Postmarketing reporting of adverse drug experiences. 314.80 Section 314.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications § 314.80 Postmarketing reporting of...

  2. 21 CFR 314.80 - Postmarketing reporting of adverse drug experiences.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Postmarketing reporting of adverse drug experiences. 314.80 Section 314.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications § 314.80 Postmarketing reporting of...

  3. 21 CFR 314.80 - Postmarketing reporting of adverse drug experiences.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Postmarketing reporting of adverse drug experiences. 314.80 Section 314.80 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG Applications § 314.80 Postmarketing reporting of...

  4. Identifying plausible adverse drug reactions using knowledge extracted from the literature.

    PubMed

    Shang, Ning; Xu, Hua; Rindflesch, Thomas C; Cohen, Trevor

    2014-12-01

    Pharmacovigilance involves continually monitoring drug safety after drugs are put to market. To aid this process; algorithms for the identification of strongly correlated drug/adverse drug reaction (ADR) pairs from data sources such as adverse event reporting systems or Electronic Health Records have been developed. These methods are generally statistical in nature, and do not draw upon the large volumes of knowledge embedded in the biomedical literature. In this paper, we investigate the ability of scalable Literature Based Discovery (LBD) methods to identify side effects of pharmaceutical agents. The advantage of LBD methods is that they can provide evidence from the literature to support the plausibility of a drug/ADR association, thereby assisting human review to validate the signal, which is an essential component of pharmacovigilance. To do so, we draw upon vast repositories of knowledge that has been extracted from the biomedical literature by two Natural Language Processing tools, MetaMap and SemRep. We evaluate two LBD methods that scale comfortably to the volume of knowledge available in these repositories. Specifically, we evaluate Reflective Random Indexing (RRI), a model based on concept-level co-occurrence, and Predication-based Semantic Indexing (PSI), a model that encodes the nature of the relationship between concepts to support reasoning analogically about drug-effect relationships. An evaluation set was constructed from the Side Effect Resource 2 (SIDER2), which contains known drug/ADR relations, and models were evaluated for their ability to "rediscover" these relations. In this paper, we demonstrate that both RRI and PSI can recover known drug-adverse event associations. However, PSI performed better overall, and has the additional advantage of being able to recover the literature underlying the reasoning pathways it used to make its predictions. PMID:25046831

  5. Identifying plausible adverse drug reactions using knowledge extracted from the literature

    PubMed Central

    Shang, Ning; Xu, Hua; Rindflesch, Thomas C.; Cohen, Trevor

    2014-01-01

    Pharmacovigilance involves continually monitoring drug safety after drugs are put to market. To aid this process; algorithms for the identification of strongly correlated drug/adverse drug reaction (ADR) pairs from data sources such as adverse event reporting systems or Electronic Health Records have been developed. These methods are generally statistical in nature, and do not draw upon the large volumes of knowledge embedded in the biomedical literature. In this paper, we investigate the ability of scalable Literature Based Discovery (LBD) methods to identify side effects of pharmaceutical agents. The advantage of LBD methods is that they can provide evidence from the literature to support the plausibility of a drug/ ADR association, thereby assisting human review to validate the signal, which is an essential component of pharmacovigilance. To do so, we draw upon vast repositories of knowledge that has been extracted from the biomedical literature by two Natural Language Processing tools, MetaMap and SemRep. We evaluate two LBD methods that scale comfortably to the volume of knowledge available in these repositories. Specifically, we evaluate Reflective Random Indexing (RRI), a model based on concept-level co-occurrence, and Predication-based Semantic Indexing (PSI), a model that encodes the nature of the relationship between concepts to support reasoning analogically about drug-effect relationships. An evaluation set was constructed from the Side Effect Resource 2 (SIDER2), which contains known drug/ADR relations, and models were evaluated for their ability to “rediscover” these relations. In this paper, we demonstrate that both RRI and PSI can recover known drug-adverse event associations. However, PSI performed better overall, and has the additional advantage of being able to recover the literature underlying the reasoning pathways it used to make its predictions. PMID:25046831

  6. [Evaluation of the Association of Hand-Foot Syndrome with Anticancer Drugs Using the US Food and Drug Administration Adverse Event Reporting System (FAERS) and Japanese Adverse Drug Event Report (JADER) Databases].

    PubMed

    Sasaoka, Sayaka; Matsui, Toshinobu; Abe, Junko; Umetsu, Ryogo; Kato, Yamato; Ueda, Natsumi; Hane, Yuuki; Motooka, Yumi; Hatahira, Haruna; Kinosada, Yasutomi; Nakamura, Mitsuhiro

    2016-01-01

    The Japanese Ministry of Health, Labor, and Welfare lists hand-foot syndrome as a serious adverse drug event. Therefore, we evaluated its association with anticancer drug therapy using case reports in the Japanese Adverse Drug Event Report (JADER) and the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). In addition, we calculated the reporting odds ratio (ROR) of anticancer drugs potentially associated with hand-foot syndrome, and applied the Weibull shape parameter to time-to-event data from JADER. We found that JADER contained 338224 reports from April 2004 to November 2014, while FAERS contained 5821354 reports from January 2004 to June 2014. In JADER, the RORs [95% confidence interval (CI)] of hand-foot syndrome for capecitabine, tegafur-gimeracil-oteracil, fluorouracil, sorafenib, and regorafenib were 63.60 (95%CI, 56.19-71.99), 1.30 (95%CI, 0.89-1.89), 0.48 (95%CI, 0.30-0.77), 26.10 (95%CI, 22.86-29.80), and 133.27 (95%CI, 112.85-157.39), respectively. Adverse event symptoms of hand-foot syndrome were observed with most anticancer drugs, which carry warnings of the propensity to cause these effects in their drug information literature. The time-to-event analysis using the Weibull shape parameter revealed differences in the time-dependency of the adverse events of each drug. Therefore, anticancer drugs should be used carefully in clinical practice, and patients may require careful monitoring for symptoms of hand-foot syndrome. PMID:26935094

  7. The role of the clinical pharmacologist in the management of adverse drug reactions.

    PubMed

    Moore, N

    2001-01-01

    The classical definition of clinical pharmacology is the study or the knowledge of the effects of drugs in humans. The activities of a clinical pharmacologist can vary from country to country, usually ranging from involvement in clinical trials, especially fundamental pharmacodynamic studies, to studies of pharmacokinetics and drug metabolism, to pharmacogenetics. Most clinical pharmacologists outside industry are in hospitals or university hospitals and research centres. In addition to research, this implies teaching of clinical pharmacology, and interacting with other medical staff: in the field of research, giving advice on clinical trials methodology and often managing a therapeutic drug monitoring centre. Some clinical pharmacologists have clinical departments with beds or consulting offices. Can there be another role for the clinical pharmacologist that would increase his or her usefulness for the medical community? Adverse drug reactions (ADRs) are remarkably complex events, related to drug effects, patient characteristics (background diseases, genetics), and drug/disease interactions. Evaluation of ADRs requires understanding of drug mechanisms and interactions, and of disease diagnostics, especially in the discussion of alternative diagnoses. This implies expertise as a pharmacologist and a clinician. In addition, because not all adverse reactions or interactions are in the Summary of Product Characteristics, and because problems arise long before they report in the literature, it is necessary for the clinical pharmacologist to have knowledge of ongoing regulatory processes, in addition to having access to the published literature. Helping clinicians cope with individual patient problems will also improve the clinical pharmacologist's integration into the healthcare process. PMID:11219484

  8. Adverse drug interactions with nonsteroidal anti-inflammatory drugs (NSAIDs). Recognition, management and avoidance.

    PubMed

    Johnson, A G; Seideman, P; Day, R O

    1993-02-01

    The prevalence and incidence of adverse drug interactions involving nonsteroidal anti-inflammatory drugs (NSAIDs) remains unknown. To identify those proposed drug interactions of greatest clinical significance, it is appropriate to focus on interactions between commonly used and/or commonly coprescribed drugs, interactions for which there are numerous well documented case reports in reputable journals, interactions validated by well designed in vivo human studies and those affecting high-risk drugs and/or high-risk patients. While most interactions between NSAIDs and other drugs are pharmacokinetic, NSAID-related pharmacodynamic interactions may be considerably more important in the clinical context, and prescriber ignorance is likely to be a major determinant of many adverse drug interactions. Prescribing NSAIDs is relatively contraindicated for patients on oral anticoagulants due to the risk of haemorrhage, and for patients taking high-dose methotrexate due to the dangers of bone marrow toxicity, renal failure and hepatic dysfunction. Combination NSAID therapy cannot be justified as toxicity may be increased without any improvement in efficacy. Where lithium or anti-hypertensives are coprescribed with NSAIDs, close monitoring is mandatory for lithium toxicity and hypertension, respectively, and aspirin (acetylsalicylic acid) or sulindac are preferred. Phenytoin or oral hypoglycaemic agents may be administered with NSAIDs other than pyrazoles and salicylates provided that patients are monitored carefully at the initiation and cessation of NSAID treatment. Digoxin, aminoglycosides and probenecid may be coprescribed with NSAIDs, but close monitoring is required, particularly for high-risk patients such as the elderly. Indomethacin and triamterene should be avoided due to the risk of renal failure. High dose aspirin should be replaced by naproxen in patients on valproic acid (sodium valproate) and care is required when corticosteroids are administered to patients

  9. Adverse Drug Reactions Causing Admission to Medical Wards

    PubMed Central

    Mouton, Johannes P.; Njuguna, Christine; Kramer, Nicole; Stewart, Annemie; Mehta, Ushma; Blockman, Marc; Fortuin-De Smidt, Melony; De Waal, Reneé; Parrish, Andy G.; Wilson, Douglas P.K.; Igumbor, Ehimario U.; Aynalem, Getahun; Dheda, Mukesh; Maartens, Gary; Cohen, Karen

    2016-01-01

    Abstract Limited data exist on the burden of serious adverse drug reactions (ADRs) in sub-Saharan Africa, which has high HIV and tuberculosis prevalence. We determined the proportion of adult admissions attributable to ADRs at 4 hospitals in South Africa. We characterized drugs implicated in, risk factors for, and the preventability of ADR-related admissions. We prospectively followed patients admitted to 4 hospitals’ medical wards over sequential 30-day periods in 2013 and identified suspected ADRs with the aid of a trigger tool. A multidisciplinary team performed causality, preventability, and severity assessment using published criteria. We categorized an admission as ADR-related if the ADR was the primary reason for admission. There were 1951 admissions involving 1904 patients: median age was 50 years (interquartile range 34–65), 1057 of 1904 (56%) were female, 559 of 1904 (29%) were HIV-infected, and 183 of 1904 (10%) were on antituberculosis therapy (ATT). There were 164 of 1951 (8.4%) ADR-related admissions. After adjustment for age and ATT, ADR-related admission was independently associated (P ≤ 0.02) with female sex (adjusted odds ratio [aOR] 1.51, 95% confidence interval [95% CI] 1.06–2.14), increasing drug count (aOR 1.14 per additional drug, 95% CI 1.09–1.20), increasing comorbidity score (aOR 1.23 per additional point, 95% CI 1.07–1.41), and use of antiretroviral therapy (ART) if HIV-infected (aOR 1.92 compared with HIV-negative/unknown, 95% CI 1.17–3.14). The most common ADRs were renal impairment, hypoglycemia, liver injury, and hemorrhage. Tenofovir disoproxil fumarate, insulin, rifampicin, and warfarin were most commonly implicated, respectively, in these 4 ADRs. ART, ATT, and/or co-trimoxazole were implicated in 56 of 164 (34%) ADR-related admissions. Seventy-three of 164 (45%) ADRs were assessed as preventable. In our survey, approximately 1 in 12 admissions was because of an ADR. The range of ADRs and implicated drugs reflect

  10. Amiodarone-induced hypothyroidism and other adverse effects.

    PubMed

    Mosher, Mary C

    2011-01-01

    Amiodarone is a class III antiarrhythmic agent that is frequently prescribed today for the treatment of ventricular and atrial arrhythmias. Amiodarone has many adverse effects, and one of them is thyroid dysfunction. Advanced practice and staff nurses need to be vigilant, recognizing early signs and symptoms of thyroid dysfunction to prevent adverse drug reactions. Often, the signs and symptoms of amiodarone-induced hypothyroidism are overlooked because of the complexity of the patient's condition. The purpose of this article was to review a case study, present differential diagnoses and testing, discuss risk factors associated with amiodarone-induced hypothyroidism, discuss its pathogenesis, and review clinical management. PMID:21307683

  11. 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

  12. Some adverse effects of antipsychotics: prevention and treatment.

    PubMed

    Lader, M

    1999-01-01

    Antipsychotic medication causes a wide range of adverse effects, which can be serious and may further imperil both the physical and psychological health of schizophrenic patients. The range of side effects patients commonly encounter includes weight gain, endocrine disturbances, sedation, anticholinergic effects, hypotension, seizures, and extrapyramidal symptoms. Less common and unpredictable reactions are blood dyscrasias, cardiotoxicity, sudden death, and the neuroleptic malignant syndrome. Antipsychotic drugs differ significantly regarding their propensity to cause these reactions. Patients should undergo comprehensive health checks before an antipsychotic is prescribed, and drug therapy should be individualized to take account of any preexisting symptoms. Side effects and the wider implications of drug treatment, such as effects on occupational and social functioning, should be discussed with the patient before initiating therapy. Patients should be regularly monitored for side effects during treatment and switched to alternative therapy if side effects are serious and/or persistent. PMID:10372605

  13. Possible adverse drug events leading to hospital admission in a Brazilian teaching hospital

    PubMed Central

    Varallo, Fabiana Rossi; Capucho, Helaine Carneiro; da Silva Planeta, Cleópatra; de Carvalho Mastroianni, Patrícia

    2014-01-01

    OBJECTIVES: Drug safety problems can lead to hospital admission. In Brazil, the prevalence of hospitalization due to adverse drug events is unknown. This study aims to estimate the prevalence of hospitalization due to adverse drug events and to identify the drugs, the adverse drug events, and the risk factors associated with hospital admissions. METHOD: A cross-sectional study was performed in the internal medicine ward of a teaching hospital in São Paulo State, Brazil, from August to December 2008. All patients aged ≥18 years with a length of stay ≥24 hours were interviewed about the drugs used prior to hospital admission and their symptoms/complaints/causes of hospitalization. RESULTS: In total, 248 patients were considered eligible. The prevalence of hospitalization due to potential adverse drug events in the ward was 46.4%. Overprescribed drugs and those indicated for prophylactic treatments were frequently associated with possible adverse drug events. Frequently reported symptoms were breathlessness (15.2%), fatigue (12.3%), and chest pain (9.0%). Polypharmacy was a risk factor for the occurrence of possible adverse drug events. CONCLUSION: Possible adverse drug events led to hospitalization in a high-complexity hospital, mainly in polymedicated patients. The clinical outcomes of adverse drug events are nonspecific, which delays treatment, hinders causality analysis, and contributes to the underreporting of cases. PMID:24626940

  14. A curated and standardized adverse drug event resource to accelerate drug safety research

    PubMed Central

    Banda, Juan M.; Evans, Lee; Vanguri, Rami S.; Tatonetti, Nicholas P.; Ryan, Patrick B.; Shah, Nigam H.

    2016-01-01

    Identification of adverse drug reactions (ADRs) during the post-marketing phase is one of the most important goals of drug safety surveillance. Spontaneous reporting systems (SRS) data, which are the mainstay of traditional drug safety surveillance, are used for hypothesis generation and to validate the newer approaches. The publicly available US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) data requires substantial curation before they can be used appropriately, and applying different strategies for data cleaning and normalization can have material impact on analysis results. We provide a curated and standardized version of FAERS removing duplicate case records, applying standardized vocabularies with drug names mapped to RxNorm concepts and outcomes mapped to SNOMED-CT concepts, and pre-computed summary statistics about drug-outcome relationships for general consumption. This publicly available resource, along with the source code, will accelerate drug safety research by reducing the amount of time spent performing data management on the source FAERS reports, improving the quality of the underlying data, and enabling standardized analyses using common vocabularies. PMID:27193236

  15. A curated and standardized adverse drug event resource to accelerate drug safety research.

    PubMed

    Banda, Juan M; Evans, Lee; Vanguri, Rami S; Tatonetti, Nicholas P; Ryan, Patrick B; Shah, Nigam H

    2016-01-01

    Identification of adverse drug reactions (ADRs) during the post-marketing phase is one of the most important goals of drug safety surveillance. Spontaneous reporting systems (SRS) data, which are the mainstay of traditional drug safety surveillance, are used for hypothesis generation and to validate the newer approaches. The publicly available US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) data requires substantial curation before they can be used appropriately, and applying different strategies for data cleaning and normalization can have material impact on analysis results. We provide a curated and standardized version of FAERS removing duplicate case records, applying standardized vocabularies with drug names mapped to RxNorm concepts and outcomes mapped to SNOMED-CT concepts, and pre-computed summary statistics about drug-outcome relationships for general consumption. This publicly available resource, along with the source code, will accelerate drug safety research by reducing the amount of time spent performing data management on the source FAERS reports, improving the quality of the underlying data, and enabling standardized analyses using common vocabularies. PMID:27193236

  16. [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 PMID:27245013

  17. Perception of Nigerian medical students on adverse drug reaction reporting.

    PubMed

    Abubakar, Abdullahi Rabiu; Chedi, Bashir A Z; Mohammed, Khalid Garba; Haque, Mainul

    2015-01-01

    Spontaneous reporting (SPR) and intensive monitoring are the conventional systems used for detecting, recording, and reporting adverse drug reactions (ADRs). Using spontaneous reporting a lot of successes has been made as existing ADRs were identified and new ones prevented through this methods. The aim of this appraisal was to evaluate the knowledge, attitude, and the practice of medical students with regards to ADRs reporting and to see if differences exist between the level of study and genders. The questionnaire was adopted, modified, and validated from previous studies. It comprised of 25 questions. It was administered year-IV and V medical students of Bayero University Kano, Nigeria. The data collected were coded and analyzed using the Statistical Package for the Social Sciences (SPSS) version 20, currently known as IBM SPSS Statistics. The response rate was 74%. Among the 108 participants, 80% got the definition of ADRs correct; 63% of them knew the precise functions of pharmacovigilance (PV). In addition, 82% strongly agreed that ADR reporting is health care workers responsibility; 82% also said PV should be taught in detail. Meanwhile, 99% have noticed patient experiencing ADRs; 67% said even mild ADRs should be reported. The outcome of this study showed good knowledge and attitude with respect to ADRs and PV among the medical students surveyed. Unfortunately, the practice of medical students was found to be unsatisfactory. There is a need to upgrade the students teaching the curriculum with respect to ADRs monitoring. PMID:26605155

  18. 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. PMID:14734438

  19. Enduring psychobiological effects of childhood adversity.

    PubMed

    Ehlert, Ulrike

    2013-09-01

    This mini-review refers to recent findings on psychobiological long-term consequences of childhood trauma and adverse living conditions. The continuum of trauma-provoked aftermath reaches from healthy adaptation with high resilience, to severe maladjustment with co-occurring psychiatric and physical pathologies in children, adolescents and adults. There is increasing evidence of a strong interconnectivity between genetic dispositions, epigenetic processes, stress-related hormonal systems and immune parameters in all forms of (mal)-adjustment to adverse living conditions. Unfavorable constellations of these dispositions and systems, such as low cortisol levels and elevated markers of inflammation in maltreated children, seem to promote the (co)-occurrence of psychiatric and physical pathologies such as posttraumatic stress disorder, obesity, or diabetes. Although findings from prospective study designs support a deepened understanding of causal relations between adverse living conditions, including traumatic experiences, during childhood and its psychobiological effects, so far, little is known about the temporal coincidence of stress-sensitive developmental stages during childhood and adolescence and trauma consequences. Taken together, childhood adversity is a severe risk factor for the onset of psychobiological (mal)-adjustment, which has to be explained under consideration of diverse physiological systems and developmental stages of childhood and adolescence. PMID:23850228

  20. Does Illicit Drug Use Influence Inpatient Adverse Events, Death, Length of Stay, and Discharge After Orthopaedic Trauma?

    PubMed

    Babatunde, Victor D; Menendez, Mariano E; Ring, David

    2016-01-01

    Illicit drug use among adults is increasing, but its associated risk following orthopaedic trauma remains largely unexplored. This study assessed the relationship of illicit drug use with inpatient adverse events, in-hospital mortality, prolonged length of stay, and nonroutine discharge. With the use of the Nationwide Inpatient Sample database, 7,118,720 orthopaedic trauma inpatients from 2002 to 2011 were identified and separated into illicit drug users (1.5%) and non-illicit drug users (98.5%). Multivariable regression modeling was used to determine the association between illicit drug use and each outcome variable. Illicit drug use was associated with higher odds of inpatient adverse events, but not greater likelihood of inpatient death. Illicit drug users were also more likely to experience prolonged hospital stay and nonroutine discharge. Prompt recognition and effective treatment interventions for orthopaedic trauma patients with a history of illicit drug use may improve inpatient outcomes. PMID:27082887

  1. Adverse Outcome Pathways as Tools to Assess Drug-Induced Toxicity.

    PubMed

    Vinken, Mathieu

    2016-01-01

    Adverse outcome pathways (AOPs) are novel tools in toxicology and human risk assessment with broad potential. AOPs are designed to provide a clear-cut mechanistic representation of toxicological effects that span over different layers of biological organization. AOPs share a common structure consisting of a molecular initiating event, a series of key events connected by key event relationships, and an adverse outcome. Development and evaluation of AOPs ideally complies with guidelines issued by the Organization for Economic Cooperation and Development. AOP frameworks have yet been proposed for major types of drug-induced injury, especially in the liver, including steatosis, fibrosis, and cholestasis. These newly postulated AOPs can serve a number of purposes pertinent to safety assessment of drugs, in particular the establishment of quantitative structure-activity relationships, the development of novel in vitro toxicity screening tests, and the elaboration of prioritization strategies. PMID:27311472

  2. Neuropsychiatric Adverse Effects of Amphetamine and Methamphetamine.

    PubMed

    Harro, Jaanus

    2015-01-01

    Administration of amphetamine and methamphetamine can elicit psychiatric adverse effects at acute administration, binge use, withdrawal, and chronic use. Most troublesome of these are psychotic states and aggressive behavior, but a large variety of undesirable changes in cognition and affect can be induced. Adverse effects occur more frequently with higher dosages and long-term use. They can subside over time but some persist long-term. Multiple alterations in the gray and white matter of the brain assessed as changes in tissue volume or metabolism, or at molecular level, have been associated with amphetamine and methamphetamine use and the psychiatric adverse effects, but further studies are required to clarify their causal role, specificity, and relationship with preceding states and traits and comorbidities. The latter include other substance use disorders, mood and anxiety disorders, attention deficit hyperactivity disorder, and antisocial personality disorder. Amphetamine- and methamphetamine-related psychosis is similar to schizophrenia in terms of symptomatology and pathogenesis, and these two disorders share predisposing genetic factors. PMID:26070758

  3. Adverse health effects of anabolic-androgenic steroids.

    PubMed

    van Amsterdam, Jan; Opperhuizen, Antoon; Hartgens, Fred

    2010-06-01

    Anabolic-androgenic steroids (AAS) are synthetic drugs derived from testosterone. Illegally, these drugs are regularly self-administered by body builders and power lifters to enhance their sportive performance. Adverse side effects of AAS include sexual dysfunction, alterations of the cardiovascular system, psyche and behavior, and liver toxicity. However, severe side effects appear only following prolonged use of AAS at high dose and their occurrence is limited. Occasionally, AAS abuse may be linked to certain social and psychological traits of the user, like low self-esteem, low self-confidence, suffered hostility, childhood conduct disorder, and tendency to high-risk behavior. The overwhelming stereotype about AAS is that these compounds cause aggressive behavior in males. However, the underlying personality traits of a specific subgroup of the AAS abusers, who show aggression and hostility, may be relevant, as well. Use of AAS in combination with alcohol largely increases the risk of violence and aggression. The dependence liability of AAS is very low, and withdrawal effects are relatively mild. Based on the scores for acute and chronic adverse health effects, the prevalence of use, social harm and criminality, AAS were ranked among 19 illicit drugs as a group of drugs with a relatively low harm. PMID:20153798

  4. Non-steroidal anti-inflammatory drugs with adverse psychiatric reactions: five case reports.

    PubMed

    Jiang, H K; Chang, D M

    1999-01-01

    Adverse drug reactions of non-steroidal anti-inflammatory drugs (NSAIDs) are quite prevalent, but there are few reports about possible adverse psychiatric reactions, which may be ignored or underestimated. We describe here five psychiatric outpatients, two with major depressive disorders, one bipolar disorder, one schizophrenic disorder and one anxiety disorder, who were treated with NSAIDs for pain due to rheumatoid arthritis, osteoarthritis or other painful neuromuscular conditions. All five patients developed a moderate to severe depressive state, three patients became obviously paranoid, and four had either thoughts of suicide or an attempt while undergoing co-administration of NSAIDs. The psychiatric symptoms remitted when the NSAIDs were stopped. The depressive and paranoid symptoms returned on seven occasions of re-use or re-challenge with the same or a different type of NSAID in all five patients. When the NSAIDs were stopped again, the patients had another remission of the adverse psychiatric reactions, and eventually recovered to their baseline mental states in clear temporal relationships. The cases presented suggest that NSAIDs can induce or exacerbate idiosyncratic reproducible adverse psychiatric symptoms in certain vulnerable patients, including those with a variety of psychotic or neurotic disorders, and also in elderly persons, but these undesirable side-effects were generally transient and disappeared on withdrawal of the NSAIDs. PMID:10468178

  5. Quality check of spontaneous adverse drug reaction reporting forms of different countries.

    PubMed

    Bandekar, M S; Anwikar, S R; Kshirsagar, N A

    2010-11-01

    Adverse drug reactions (ADRs) are considered as one of the leading causes of death among hospitalized patients. Thus reporting of adverse drug reactions become an important phenomenon. Spontaneous adverse drug reaction reporting form is an essential component and a major tool of the pharmacovigilance system of any country. This form is a tool to collect information of ADRs which helps in establishing the causal relationship between the suspected drug and the reaction. As different countries have different forms, our aim was to study, analyze the suspected adverse drug reaction reporting form of different countries, and assess if these forms can capture all the data regarding the adverse drug reaction. For this analysis we identified 18 points which are essential to make a good adverse drug reaction report, enabling proper causality assessment of adverse reaction to generate a safety signal. Adverse drug reaction reporting forms of 10 different countries were collected from the internet and compared for 18 points like patient information, information about dechallenge-rechallenge, adequacy of space and columns to capture necessary information required for its causality assessment, etc. Of the ADR forms that we analyzed, Malaysia was the highest scorer with 16 out of 18 points. This study reveals that there is a need to harmonize the ADR reporting forms of all the countries because there is a lot of discrepancy in data captured by the existing ADR reporting forms as the design of these forms is different for different countries. These incomplete data obtained result in inappropriate causality assessment. PMID:20845409

  6. Environmental Perchlorate Exposure: Potential Adverse Thyroid Effects

    PubMed Central

    Leung, Angela M.; Pearce, Elizabeth N.; Braverman, Lewis E.

    2014-01-01

    Purpose of review This review will present a general overview of the sources, human studies, and proposed regulatory action regarding environmental perchlorate exposure. Recent findings Some recent studies have reported significant associations between urinary perchlorate concentrations, thyroid dysfunction, and decreased infant IQ in groups who would be particularly susceptible to perchlorate effects. An update regarding the recent proposed regulatory actions and potential costs surrounding amelioration of perchlorate contamination is provided. Summary The potential adverse thyroidal effects of environmental perchlorate exposure remain controversial, and further research is needed to further define its relationship to human health among pregnant and lactating women and their infants. PMID:25106002

  7. The validation of an invitro colonic motility assay as a biomarker for gastrointestinal adverse drug reactions

    SciTech Connect

    Keating, Christopher; Martinez, Vicente; Ewart, Lorna; Gibbons, Stephen; Grundy, Luke; Valentin, Jean-Pierre; Grundy, David

    2010-06-15

    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, 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.

  8. Knowledge-based extraction of adverse drug events from biomedical text

    PubMed Central

    2014-01-01

    Background Many biomedical relation extraction systems are machine-learning based and have to be trained on large annotated corpora that are expensive and cumbersome to construct. We developed a knowledge-based relation extraction system that requires minimal training data, and applied the system for the extraction of adverse drug events from biomedical text. The system consists of a concept recognition module that identifies drugs and adverse effects in sentences, and a knowledge-base module that establishes whether a relation exists between the recognized concepts. The knowledge base was filled with information from the Unified Medical Language System. The performance of the system was evaluated on the ADE corpus, consisting of 1644 abstracts with manually annotated adverse drug events. Fifty abstracts were used for training, the remaining abstracts were used for testing. Results The knowledge-based system obtained an F-score of 50.5%, which was 34.4 percentage points better than the co-occurrence baseline. Increasing the training set to 400 abstracts improved the F-score to 54.3%. When the system was compared with a machine-learning system, jSRE, on a subset of the sentences in the ADE corpus, our knowledge-based system achieved an F-score that is 7 percentage points higher than the F-score of jSRE trained on 50 abstracts, and still 2 percentage points higher than jSRE trained on 90% of the corpus. Conclusion A knowledge-based approach can be successfully used to extract adverse drug events from biomedical text without need for a large training set. Whether use of a knowledge base is equally advantageous for other biomedical relation-extraction tasks remains to be investigated. PMID:24593054

  9. Could chiropractors screen for adverse drug events in the community? Survey of US chiropractors

    PubMed Central

    2010-01-01

    Background The "Put Prevention into Practice" campaign of the US Public Health Service (USPHS) was launched with the dissemination of the Clinician's Handbook of Preventive Services that recommended standards of clinical care for various prevention activities, including preventive clinical strategies to reduce the risk of adverse drug events. We explored whether nonprescribing clinicians such as chiropractors may contribute to advancing drug safety initiatives by identifying potential adverse drug events in their chiropractic patients, and by bringing suspected adverse drug events to the attention of the prescribing clinicians. Methods Mail survey of US chiropractors about their detection of potential adverse drug events in their chiropractic patients. Results Over half of responding chiropractors (62%) reported having identified a suspected adverse drug event occurring in one of their chiropractic patients. The severity of suspected drug-related events detected ranged from mild to severe. Conclusions Chiropractors or other nonprescribing clinicians may be in a position to detect potential adverse drug events in the community. These detection and reporting mechanisms should be standardized and policies related to clinical case management of suspected adverse drug events occurring in their patients should be developed. PMID:21083911

  10. 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

  11. Adverse health consequences of performance-enhancing drugs: an Endocrine Society scientific statement.

    PubMed

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

    2014-06-01

    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

  12. Managing the adverse effects of radiation therapy.

    PubMed

    Berkey, Franklin J

    2010-08-15

    Nearly two thirds of patients with cancer will undergo radiation therapy as part of their treatment plan. Given the increased use of radiation therapy and the growing number of cancer survivors, family physicians will increasingly care for patients experiencing adverse effects of radiation. Selective serotonin reuptake inhibitors have been shown to significantly improve symptoms of depression in patients undergoing chemotherapy, although they have little effect on cancer-related fatigue. Radiation dermatitis is treated with topical steroids and emollient creams. Skin washing with a mild, unscented soap is acceptable. Cardiovascular disease is a well-established adverse effect in patients receiving radiation therapy, although there are no consensus recommendations for cardiovascular screening in this population. Radiation pneumonitis is treated with oral prednisone and pentoxifylline. Radiation esophagitis is treated with dietary modification, proton pump inhibitors, promotility agents, and viscous lidocaine. Radiation-induced emesis is ameliorated with 5-hydroxytryptamine3 receptor antagonists and steroids. Symptomatic treatments for chronic radiation cystitis include anticholinergic agents and phenazopyridine. Sexual dysfunction from radiation therapy includes erectile dysfunction and vaginal stenosis, which are treated with phosphodiesterase type 5 inhibitors and vaginal dilators, respectively. PMID:20704169

  13. [Thyrostatic treatment and its adverse effects].

    PubMed

    Dokupilová, A; Payer, J

    2013-11-01

    Antithyroid drugs are relatively simple molecules known as thionamides, which contain a sulfhydryl group and a thiourea moiety within a heterocyclic structure. Propylthiouracil (6- propyl 2- sulfanylidene 1,2,3,4- tetrahydropyrimidin4- one) and methimazole (1- metyl 2,3- dihydro1H imidazole 2- thione) are the antithyroid drugs used in the United States. Methimazole is used in most of Europe and Asia, and carbimazole -  methimazole analogue, is used in the United Kingdom and parts of the former British Commonwealth. Their primary effect is to inhibit thyroid hormone synthesis by interfering with thyroid peroxidase mediated iodination of tyrosine residues in thyroglobulin and is an important step in the synthesis of thyroxine and triiodothyronine. Propylthiouracil (but not methimazole or carbimazole), can block the conversion of thyroxine to triiodothyronine within the thyroid and in peripheral tissues. Antithyroid drugs may have clinically important immunosuppressive effects. Side effects of thionamides are usually mild, serious untoward effects are observed in < 5% of cases, more frequently during the initial phases of treatment, when the drug daily dose is higher. PMID:24279443

  14. Automated Summarization of Publications Associated with Adverse Drug Reactions from PubMed

    PubMed Central

    Finkelstein, Joseph; Chen, Qinlang; Adams, Hayden; Friedman, Carol

    2016-01-01

    Academic literature provides rich and up-to-date information concerning adverse drug reactions (ADR), but it is time consuming and labor intensive for physicians to obtain information of ADRs from academic literature because they would have to generate queries, review retrieved articles and summarize the results. In this study, a method is developed to automatically detect and summarize ADRs from journal articles, rank them and present them to physicians in a user-friendly interface. The method studied ADRs for 6 drugs and returned on average 4.8 ADRs that were correct. The results demonstrated this method was feasible and effective. This method can be applied in clinical practice for assisting physicians to efficiently obtain information about ADRs associated with specific drugs. Automated summarization of ADR information from recent publications may facilitate translation of academic research into actionable information at point of care. PMID:27570654

  15. Automated Determination of Publications Related to Adverse Drug Reactions in PubMed

    PubMed Central

    Adams, Hayden; Friedman, Carol; Finkelstein, Joseph

    2015-01-01

    Timely dissemination of up-to-date information concerning adverse drug reactions (ADRs) at the point of care can significantly improve medication safety and prevent ADRs. Automated methods for finding relevant articles in MEDLINE which discuss ADRs for specific medications can facilitate decision making at the point of care. Previous work has focused on other types of clinical queries and on retrieval for specific ADRs or drug-ADR pairs, but little work has been published on finding ADR articles for a specific medication. We have developed a method to generate a PubMED query based on MESH, supplementary concepts, and textual terms for a particular medication. Evaluation was performed on a limited sample, resulting in a sensitivity of 90% and precision of 93%. Results demonstrated that this method is highly effective. Future work will integrate this method within an interface aimed at facilitating access to ADR information for specified drugs at the point of care. PMID:26306227

  16. Adverse Drug Reactions Associated with Antipsychotics, Antidepressants, Mood Stabilizers, and Stimulants.

    PubMed

    Givens, Courtney J

    2016-06-01

    The advent of psychotropic medications in the 1950s greatly impacted the practice of psychiatry. Since then, efforts have been made to produce effective medications with few side effects (SEs) or adverse drug reactions (ADRs). Newer psychotropics have been developed but are not without risk. ADRs and SEs can lead to medication noncompliance, morbidity, and mortality. In many cases, ADRs can be prevented and common SEs relieved through proper interventions. Nursing interventions are vital to improving patient safety and outcomes in mental health populations. This article discusses ADRs and SEs of antipsychotics, antidepressants, mood stabilizers, and stimulants. PMID:27229284

  17. [The undesirable, psychologically adverse effects of screening].

    PubMed

    Döbrössy, Bence; Kovács, Attila; Budai, András; Cornides, Agnes; Döbrössy, Lajos

    2007-09-01

    The psychological adverse effects might play an important role in the non-compliance with the offered screening examination. The possible sources of them are three-fold: 1. The general human attitude, such as the rejection of health interventions, particularly those aiming at the prevention of eventual future health problems instead of handling existing complaints and symptoms at present; the screening can be seen as a "future-oriented" intervention. 2. The cultural image of cancer and the disbelief of its curability. 3. The subjective experiences in relation to the screening process. The providers have to do their best to eliminate these causes: by means of a) health education addressing people of various ages, social classes and cultural levels, promoting the understanding of the importance of disease prevention, and, changing their negative, defeatist attitude towards cancer; b) minimizing the psychological adverse effects of all kinds. This can be done by proper organisation of the screening process; optimizing the quality of work, and, provision of good quality of information and advice to the screenees before, during and after the screening. PMID:17766222

  18. EMPADE Study: Evaluation of Medical Prescriptions and Adverse Drug Events in COPD Patients Admitted to Intensive Care Unit

    PubMed Central

    Khan, M. Amer; Khan, M. Nematullah; Sultan, Ihtisham; Khan, M. Aamer; Ali, S. Amir; Farooqui, Afroze

    2015-01-01

    Introduction Inappropriate drug usage may preclude ideal benefit due to increased medical cost, antimicrobial resistance, adverse effects and mortality. Therefore drug utilization studies have become a plausible means in evaluating the healthcare systems. COPD management usually involves more than one drug which may escalate the risk of ADEs (adverse drug events). Aim The present study was aimed at assessing the current drug practice and ADEs in COPD management in ICU. Materials and Methods A total of 1,044 patients admitted for the treatment of COPD were included in the study. Their prescriptions were recorded for evaluation of drug utilization and patients were counseled for assessing ADEs. Results were evaluated by Chi-square test and percentages. Result All-embracing 15,360 drugs were prescribed at an average of 14.71 drugs per patient, wherein β2-agonists were extensively prescribed agents followed by inhaled-corticosteroids and anti-cholinergics. 372 ADEs were reported in 252 patients, wherein restlessness was the most frequent ADE and theophylline was found to be associated with highest cases of ADEs. Conclusion Practitioners should prescribe least number of drugs to mitigate the likelihood of adverse outcomes in patients due to numerous drugs usage, which may be achieved by following GOLD guidelines. The present work may help in improving the current management of COPD by rectifying the flaws delineated in this article. PMID:26675667

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

    SciTech Connect

    Hirsch, Michael J.; Meneses, Claudio N.; Pardalos, Panos M.; Ragle, Michelle; Resende, Mauricio G. C.

    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.

  20. [Adverse drug events of older patients presenting in the emergency department].

    PubMed

    Malinovska, Alexandra; Bingisser, Roland; Nickel, Christian H

    2015-12-01

    The effect of medication is always a balance between their beneficial effects and any adverse reactions they might elicit. The main risk for adverse drug events {ADEs) is polypharmacy, which is the simultaneous use of multiple drugs.This often applies to older patients, who suffer from multiple diseases and therefore take multiple medications. Thus, itis not surprising, that ADEs are frequention older patients and account up to 16% of emergency visits. It is still under discussion, whether age is an independent risk factor for ADEs. However, there are some age-related changes in the pharmacokinetic and pharmacodynamics properties of many drugs, which may influence the highly fragile balance between benefit and harm in older patients. Though there are multiple risk factors for and causes of ADEs, it could be shown that a lot of ADEs are preventable and even predictable: Budnitz eta/. showed that almost two thirds of emergency hospitalisations occur due to four medication classes: warfarin, oral antiplatelet agents, insulin and oral hypoglycaemic agents. Nevertheless, only 40-60% ofA DEs are recognized in the emergency department. This might be explained by the broad clinical symptoms, ranging from bleeding due to anticoagulants to the more nonspecific symptom of weakness due to hyponatraemia secondary to thiazide diuretics. Detecting and avoiding ADEs could be aided by using lists such as Beers criteria or STOPP/FART which list medications which are potentially inappropriate for older patients. PMID:26654810

  1. Prospective Observational Study of Adverse Drug Reactions of Anticancer Drugs Used in Cancer Treatment in a Tertiary Care Hospital

    PubMed Central

    Saini, V. K.; Sewal, R. K.; Ahmad, Yusra; Medhi, B.

    2015-01-01

    Adverse drug reactions associated with the use of anticancer drugs are a worldwide problem and cannot be ignored. Adverse drug reactions can range from nausea, vomiting or any other mild reaction to severe myelosuppression. The study was planned to observe the suspected adverse drug reactions of cancer chemotherapy in patients aged >18 years having cancer attending Postgraduate Institute of Medical Education and Research, Chandigarh. During the study period, 101 patients of breast cancer and 73 patients of lung cancer were screened for occurrence of adverse drug reactions during their treatment with chemotherapy. About 87.36% patients experienced adverse drug reactions, 90.09% and 83.56% of breast and lung cancer patients experienced at least one adverse drug reaction respectively. In breast cancer patients, 41.58% patients were prescribed fluorouracil+doxorubicin+cyclophosphamide while paclitaxel was prescribed to 22.77% patients. Alopecia (54.94%), nail discolouration (43.96%), dysgeusia (38.46%), anorexia (30.77%), nausea (29.67%), and neuropathy (29.67%) were found to be very common in breast cancer patients treated with single/combined regimen. In lung cancer group of patients, cisplatin with docetaxel, cisplatin with pemetrexed and cisplatin with irinotecan were prescribed to 30.14, 24.65 and 17.81% patients, respectively. Dysgeusia (40.98%), diarrhoea (39.34%), anorexia (32.77%) and constipation (31.15%) and alopecia (31.15%) were commonly observed adverse drug reactions having lung cancer patients. Causality assessments using World Health Organization causality assessment scale showed that observed adverse drug reactions were of probable (64.67%) and possible (35.33%) categories. Alopecia, dysgeusia, anorexia, constipation diarrhoea, nausea, nail discoloration were more prevalent amongst the cancer patients undergoing chemotherapy. PMID:26997696

  2. Prospective Observational Study of Adverse Drug Reactions of Anticancer Drugs Used in Cancer Treatment in a Tertiary Care Hospital.

    PubMed

    Saini, V K; Sewal, R K; Ahmad, Yusra; Medhi, B

    2015-01-01

    Adverse drug reactions associated with the use of anticancer drugs are a worldwide problem and cannot be ignored. Adverse drug reactions can range from nausea, vomiting or any other mild reaction to severe myelosuppression. The study was planned to observe the suspected adverse drug reactions of cancer chemotherapy in patients aged >18 years having cancer attending Postgraduate Institute of Medical Education and Research, Chandigarh. During the study period, 101 patients of breast cancer and 73 patients of lung cancer were screened for occurrence of adverse drug reactions during their treatment with chemotherapy. About 87.36% patients experienced adverse drug reactions, 90.09% and 83.56% of breast and lung cancer patients experienced at least one adverse drug reaction respectively. In breast cancer patients, 41.58% patients were prescribed fluorouracil+doxorubicin+cyclophosphamide while paclitaxel was prescribed to 22.77% patients. Alopecia (54.94%), nail discolouration (43.96%), dysgeusia (38.46%), anorexia (30.77%), nausea (29.67%), and neuropathy (29.67%) were found to be very common in breast cancer patients treated with single/combined regimen. In lung cancer group of patients, cisplatin with docetaxel, cisplatin with pemetrexed and cisplatin with irinotecan were prescribed to 30.14, 24.65 and 17.81% patients, respectively. Dysgeusia (40.98%), diarrhoea (39.34%), anorexia (32.77%) and constipation (31.15%) and alopecia (31.15%) were commonly observed adverse drug reactions having lung cancer patients. Causality assessments using World Health Organization causality assessment scale showed that observed adverse drug reactions were of probable (64.67%) and possible (35.33%) categories. Alopecia, dysgeusia, anorexia, constipation diarrhoea, nausea, nail discoloration were more prevalent amongst the cancer patients undergoing chemotherapy. PMID:26997696

  3. Adverse Psychiatric Effects Associated with Herbal Weight-Loss Products

    PubMed Central

    Bersani, F. Saverio; Coviello, Marialuce; Imperatori, Claudio; Francesconi, Marta; Hough, Christina M.; Valeriani, Giuseppe; De Stefano, Gianfranco; Bolzan Mariotti Posocco, Flaminia; Santacroce, Rita; Minichino, Amedeo; Corazza, Ornella

    2015-01-01

    Obesity and overeating are among the most prevalent health concerns worldwide and individuals are increasingly using performance and image-enhancing drugs (PIEDs) as an easy and fast way to control their weight. Among these, herbal weight-loss products (HWLPs) often attract users due to their health claims, assumed safety, easy availability, affordable price, extensive marketing, and the perceived lack of need for professional oversight. Reports suggest that certain HWLPs may lead to onset or exacerbation of psychiatric disturbances. Here we review the available evidence on psychiatric adverse effects of HWLPs due to their intrinsic toxicity and potential for interaction with psychiatric medications. PMID:26457296

  4. Palmar-plantar erythrodysesthesia: An uncommon adverse effect of everolimus

    PubMed Central

    Arora, Shalabh; Akhil, Rajendra; Chacko, Raju Titus; George, Renu

    2016-01-01

    Mammalian target of rapamycin inhibitor everolimus is a novel agent used in endocrine therapy resistant hormone receptor positive metastatic breast cancer. Its use has been associated with clinically significant improvement in the otherwise dismal outcomes of this subset of patients. Rash is a common adverse effect associated with everolimus. However, Hand-foot syndrome is an uncommon toxicity with the use of this drug. We report a case of Grade 3 hand-foot syndrome following institution of everolimus therapy and describe its successful management. PMID:27168711

  5. Adverse Psychiatric Effects Associated with Herbal Weight-Loss Products.

    PubMed

    Bersani, F Saverio; Coviello, Marialuce; Imperatori, Claudio; Francesconi, Marta; Hough, Christina M; Valeriani, Giuseppe; De Stefano, Gianfranco; Bolzan Mariotti Posocco, Flaminia; Santacroce, Rita; Minichino, Amedeo; Corazza, Ornella

    2015-01-01

    Obesity and overeating are among the most prevalent health concerns worldwide and individuals are increasingly using performance and image-enhancing drugs (PIEDs) as an easy and fast way to control their weight. Among these, herbal weight-loss products (HWLPs) often attract users due to their health claims, assumed safety, easy availability, affordable price, extensive marketing, and the perceived lack of need for professional oversight. Reports suggest that certain HWLPs may lead to onset or exacerbation of psychiatric disturbances. Here we review the available evidence on psychiatric adverse effects of HWLPs due to their intrinsic toxicity and potential for interaction with psychiatric medications. PMID:26457296

  6. The NAS Perchlorate Review: Adverse Effects?

    SciTech Connect

    Johnston, Richard B.; Corley, Richard; Cowan, Linda; Utiger, Robert D.

    2005-11-01

    To the editor: Drs. Ginsberg and Rice argue that the reference dose for perchlorate of 0.0007 mg/kg per day recommended by the National Academies’ Committee to Assess the Health Implications of Perchlorate Ingestion is not adequately protective. As members of the committee, we disagree. Ginsberg and Rice base their conclusion on three points. The first involves the designation of the point of departure as a NOEL (no-observed-effect level) versus a LOAEL (lowest-observed-adverse- effect level). The committee chose as its point of departure a dose of perchlorate (0.007 mg/kg per day) that when given for 14 days to 7 normal subjects did not cause a significant decrease in the group mean thyroid iodide uptake (Greer et al. 2002). Accordingly, the committee considered it a NOEL. Ginsberg and Rice focus on the fact that only 7 subjects were given that dose, and they 1seem to say that attention should be paid only to the results in those subjects in whom there was a 1fall in thyroid iodide uptake, and that the results in those in whom there was no fall or an increase should be ignored. They consider the dose to be a LOAEL because of the fall in uptake in those few subjects. It is important to note that a statistically significant decrease of, for example, 5% or even 10%, would not be biologically important and, more important, would not be sustained. For example, in another study (Braverman et al. 2004), administration of 0.04 mg/kg per day to normal subjects for 6 months had no effect on thyroid iodide uptake when measured at 3 and 6 months, and no effect on serum thyroid hormone or thyrotropin concentrations measured monthly (inspection of Figure 5A in the paper by Greer et al. suggests that this dose would inhibit thyroid iodide uptake by about 25% if measured at 2 weeks). The second issue involves database uncertainty. In clinical studies, perchlorate has been administered prospectively to 68 normal subjects for 2 weeks to 6 months. In one study (Brabant et al. 1992

  7. 10 CFR 1017.10 - Adverse effect test.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Adverse effect test. 1017.10 Section 1017.10 Energy... Adverse effect test. In order for information to be identified as UCNI, it must be determined that the... significant adverse effect on the health and safety of the public or the common defense and security...

  8. 20 CFR 655.207 - Adverse effect rates.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... adverse effect rate (computed pursuant to 20 CFR 655.207(b)(1), 43 FR 10317; March 10, 1978) by the... at 20 CFR 655.207(b)(2) (1985). (c) In no event shall an adverse effect rate for any year be lower... listed in paragraph (b)(2) of this section, and for Florida sugarcane work, the adverse effect rate...

  9. 20 CFR 655.207 - Adverse effect rates.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... adverse effect rate (computed pursuant to 20 CFR 655.207(b)(1), 43 FR 10317; March 10, 1978) by the... at 20 CFR 655.207(b)(2) (1985). (c) In no event shall an adverse effect rate for any year be lower... listed in paragraph (b)(2) of this section, and for Florida sugarcane work, the adverse effect rate...

  10. 20 CFR 655.207 - Adverse effect rates.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... adverse effect rate (computed pursuant to 20 CFR 655.207(b)(1), 43 FR 10317; March 10, 1978) by the... at 20 CFR 655.207(b)(2) (1985). (c) In no event shall an adverse effect rate for any year be lower... listed in paragraph (b)(2) of this section, and for Florida sugarcane work, the adverse effect rate...

  11. 20 CFR 655.207 - Adverse effect rates.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... adverse effect rate (computed pursuant to 20 CFR 655.207(b)(1), 43 FR 10317; March 10, 1978) by the... at 20 CFR 655.207(b)(2) (1985). (c) In no event shall an adverse effect rate for any year be lower... listed in paragraph (b)(2) of this section, and for Florida sugarcane work, the adverse effect rate...

  12. 36 CFR 800.6 - Resolution of adverse effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  13. 36 CFR 800.6 - Resolution of adverse effects.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Resolution of adverse effects... PROTECTION OF HISTORIC PROPERTIES The section 106 Process § 800.6 Resolution of adverse effects. (a) Continue... the undertaking that could avoid, minimize, or mitigate adverse effects on historic properties....

  14. 10 CFR 1017.10 - Adverse effect test.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Adverse effect test. 1017.10 Section 1017.10 Energy... Adverse effect test. In order for information to be identified as UCNI, it must be determined that the... significant adverse effect on the health and safety of the public or the common defense and security...

  15. 10 CFR 1017.10 - Adverse effect test.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Adverse effect test. 1017.10 Section 1017.10 Energy... Adverse effect test. In order for information to be identified as UCNI, it must be determined that the... significant adverse effect on the health and safety of the public or the common defense and security...

  16. 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. PMID:26518315

  17. 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. PMID:25670505

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

    PubMed

    Wang, Kejian; Weng, Zuquan; Sun, Liya; Sun, Jiazhi; Zhou, Shu-Feng; He, Lin

    2015-02-13

    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. In 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. PMID:25576362

  19. 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

  20. Genetics of Common Antipsychotic-Induced Adverse Effects.

    PubMed

    MacNeil, Raymond R; Müller, Daniel J

    2016-07-01

    The effectiveness of antipsychotic drugs is limited due to accompanying adverse effects which can pose considerable health risks and lead to patient noncompliance. Pharmacogenetics (PGx) offers a means to identify genetic biomarkers that can predict individual susceptibility to antipsychotic-induced adverse effects (AAEs), thereby improving clinical outcomes. We reviewed the literature on the PGx of common AAEs from 2010 to 2015, placing emphasis on findings that have been independently replicated and which have additionally been listed to be of interest by PGx expert panels. Gene-drug associations meeting these criteria primarily pertain to metabolic dysregulation, extrapyramidal symptoms (EPS), and tardive dyskinesia (TD). Regarding metabolic dysregulation, results have reaffirmed HTR2C as a strong candidate with potential clinical utility, while MC4R and OGFR1 gene loci have emerged as new and promising biomarkers for the prediction of weight gain. As for EPS and TD, additional evidence has accumulated in support of an association with CYP2D6 metabolizer status. Furthermore, HSPG2 and DPP6 have been identified as candidate genes with the potential to predict differential susceptibility to TD. Overall, considerable progress has been made within the field of psychiatric PGx, with inroads toward the development of clinical tools that can mitigate AAEs. Going forward, studies placing a greater emphasis on multilocus effects will need to be conducted. PMID:27606321

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

    SciTech Connect

    Wang, Kejian; Weng, Zuquan; Sun, Liya; Sun, Jiazhi; Zhou, Shu-Feng; He, Lin

    2015-02-13

    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. In 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.

  2. Adverse drug reactions and organ damage: The liver.

    PubMed

    Licata, Anna

    2016-03-01

    Drug-induced liver injury (DILI) is among the most challenging acute or chronic liver conditions to be handled by physicians. Despite its low incidence in the general population, DILI is a frequent cause of acute liver failure. As such, the possibility of DILI should be considered in all patients who present with acute liver damage, independent of any known pre-existing liver disease. DILI can be classified as intrinsic/dose-dependent (e.g., acetaminophen toxicity) or idiosyncratic/dose-independent, with the latter form being relatively uncommon. Amoxicillin-clavulanate is the antimicrobial that is most frequently associated with idiosyncratic DILI. Large, ongoing, prospective studies in western countries have reported other drugs associated with DILI, including nonsteroidal anti-inflammatory drugs, statins, and herbal and dietary supplements. An important safety issue, DILI is one of the most frequently cited reasons for cessation of drug development during or after preclinical studies and for withdrawal of a drug from the market. This review summarizes the epidemiology, risk factors, commonly implicated drugs, clinical features, and diagnosis of DILI, with the aim of aiding physicians in the management of this debated problem. Old and new biomarkers for DILI and pharmacogenetic studies are also described. PMID:26827101

  3. Chloroquine cardiomyopathy: beyond ocular adverse effects

    PubMed Central

    Lopez-Ruiz, Nilson; Uribe, Carlos Esteban

    2014-01-01

    A 36-year-old woman who had received long-term treatment with chloroquine for systemic lupus erythematosus developed a third degree atrioventricular block and required a permanent pacemaker. Notably, left ventricular thickening and mild systolic dysfunction were noticed on echocardiography as well as on cardiac MRI. As there was no clear explanation for myocardial findings, the patient underwent an endomyocardial biopsy that demonstrated vacuolar degeneration of myocytes on light microscopy and curvilinear bodies on electron microscopy, both findings consistent with chloroquine toxicity. The drug was withheld and treatment with candesartan and carvedilol was prescribed. At 2-year follow-up, the patient remained asymptomatic and left ventricular systolic function had improved. Physicians who prescribe antimalarial drugs for rheumatic diseases should be aware of the potentially life-threatening effects of chloroquine on the heart. PMID:25225192

  4. Adverse effects of common medications on male fertility.

    PubMed

    Samplaski, Mary K; Nangia, Ajay K

    2015-07-01

    An increasing number of patients require long-term medication regimens at a young age, but the adverse effects of medications on male reproduction are often inadequately considered, recognized and investigated. Medications can affect male reproduction through central hormonal effects, direct gonadotoxic effects, effects on sperm function or on sexual function. For example, exogenous testosterone inhibits spermatogenesis through central suppression of the hypothalamic-pituitary-gonadal hormonal axis. 5α-reductase inhibitors can impair sexual function, decrease semen volume and negatively affect sperm parameters, depending on dose and treatment duration. α-Blockers might decrease seminal emission and cause retrograde ejaculation, depending on the receptor specificity and dose of the agent. Phosphodiesterase inhibitors seem to have variable effects based on the isoform inhibited and evidence is conflicting. Antihypertensive and psychotropic agents can affect sperm, sexual function and hormonal parameters. For antibiotics, the literature on effects on sperm and sperm function is limited and dated. Many chemotherapeutic agents have a direct gonadotoxic effect, depending on agents used, dosing and number of treatment cycles. Overall, many medications commonly used in urology can have effects on male fertility (mostly reversible) but conclusive evidence in humans is often limited. Men should be counselled appropriately about potential drug-related adverse effects on their fertility. PMID:26101108

  5. 78 FR 54469 - Solicitation of Written Comments on Draft National Action Plan for Adverse Drug Event Prevention

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-04

    ... HUMAN SERVICES Solicitation of Written Comments on Draft National Action Plan for Adverse Drug Event... Action Plan for Adverse Drug Event Prevention. DATES: Comments on the draft National Action Plan for Adverse Drug Event Prevention must be received no later than 5 p.m. on October 4, 2013. This...

  6. Evaluation of neuroprotection by melatonin against adverse effects of prenatal exposure to a nonsteroidal anti-inflammatory drug during peripheral nerve development.

    PubMed

    Keskin, Ilknur; Kaplan, Suleyman; Kalkan, Serpil; Sutcu, Mustafa; Ulkay, M Basak; Esener, O Burak

    2015-04-01

    The potential ability of melatonin to protect against impairment of the fetal peripheral nerve system due to maternal consumption of diclofenac sodium (DS) was investigated. Eighty-four pregnant rats were divided into seven groups: control (CONT), saline administered (PS), DS administered (DS), DS with low-dose melatonin administered (DS+MLT10), DS with high-dose melatonin administered (DS+MLT50), low-dose melatonin administered (MLT10), and high-dose melatonin administered (MLT50). After the pregnancy, six male newborn rats from each group were sacrificed at 4 and 20 weeks of age. Their right sciatic nerves were harvested, and nerve fibers were evaluated using stereological techniques. Mean numbers of myelinated axons, axon cross-section areas and the mean thickness of the myelin sheet were estimated. Four-week-old prenatally DS-exposed rats had significantly fewer axons, a smaller myelinated axonal area, and a thinner myelin sheath compared to CONT group (p<0.05). Although melatonin at both doses significantly increased axon numbers, only a high dose of melatonin increased the diameter of those axons (p<0.05). At 20-weeks of age, myelinated axon number in the DS group was not only significantly lower than all other groups (p<0.05) but also the cross-sectional area of these axons was smaller than all other groups (p<0.05). There were no differences between the groups regarding the mean thickness of the myelin sheet. The current study indicates that prenatal exposure to DS decreases the number and the diameter of sciatic nerve axons and that melatonin prophylaxis can prevent these effects. PMID:25485952

  7. Identifying potential adverse effects using the web: a new approach to medical hypothesis generation

    PubMed Central

    Benton, Adrian; Ungar, Lyle; Hill, Shawndra; Hennessy, Sean; Mao, Jun; Chung, Annie; Leonard, Charles E.; Holmes, John H.

    2011-01-01

    Medical message boards are online resources where users with a particular condition exchange information, some of which they might not otherwise share with medical providers. Many of these boards contain a large number of posts and contain patient opinions and experiences that would be potentially useful to clinicians and researchers. We present an approach that is able to collect a corpus of medical message board posts, de-identify the corpus, and extract information on potential adverse drug effects discussed by users. Using a corpus of posts to breast cancer message boards, we identified drug event pairs using co-occurrence statistics. We then compared the identified drug event pairs with adverse effects listed on the package labels of tamoxifen, anastrozole, exemestane, and letrozole. Of the pairs identified by our system, 75–80% were documented on the drug labels. Some of the undocumented pairs may represent previously unidentified adverse drug effects. PMID:21820083

  8. 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

  9. 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. PMID:25504934

  10. [Methodology for Estimating the Risk of Adverse Drug Reactions in Pregnant Women: Analysis of the Japanese Adverse Drug Event Report Database].

    PubMed

    Sakai, Takamasa; Ohtsu, Fumiko; Sekiya, Yasuaki; Mori, Chiyo; Sakata, Hiroshi; Goto, Nobuyuki

    2016-01-01

    Safety information regarding drug use during pregnancy is insufficient. The present study aimed to establish an optimal signal detection method to identify adverse drug reactions in pregnant women and to evaluate information in the Japanese Adverse Drug Event Report (JADER) database between April 2004 and November 2014. We identified reports on pregnant women using the Standardised MedDRA Queries. We calculated the proportional reporting ratio (PRR) and reporting odds ratio (ROR) of the risk factors for the two known risks of antithyroid drugs and methimazole (MMI) embryopathy, and ritodrine and fetal/infant cardiovascular events. The PRR and ROR values differed between all reports in the JADER database and those on pregnant women, affecting whether signal detection criteria were met. Therefore we considered that reports on pregnant women should be used when risks associated with pregnancy were determined using signal detection. Analyses of MMI embryopathy revealed MMI signals [PRR, 159.7; ROR, 669.9; 95% confidence interval (CI), 282.4-1588.7] but no propylthiouracil signals (PRR, 1.98; ROR, 2.0; 95%CI, 0.3-15.4). These findings were consistent with those of reported risks. Analyses of fetal/infant cardiovascular events revealed ritodrine signals (PRR, 2.1; ROR, 2.1; 95%CI, 1.4-3.3). These findings were also consistent with reported risks. Mining the JADER database was helpful for analyzing adverse drug reactions in pregnant women. PMID:26935093

  11. 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

  12. Adverse effects of gentamicin in scarlet macaws and galahs.

    PubMed

    Flammer, K; Clark, C H; Drewes, L A; Wilson, R C; Fiorello-Barrett, J

    1990-03-01

    The adverse effects of administration of gentamicin (5 mg/kg of body weight, IM, q 12 h) for 7 days were studied in healthy scarlet macaws (Ara macao) and galahs (Eolophus roseicapillus; cockatoos). Polydipsia and polyuria developed in each species, but were greater and persisted longer in the cockatoos. Peak water intake in the cockatoos more than quadrupled, and remained increased for 23 days after cessation of gentamicin administration. Plasma aspartate transaminase activity increased significantly (P less than 0.05) after treatment in the macaws, and plasma aspartate transaminase and lactate dehydrogenase activities increased in the cockatoos. Single IM administration of gentamicin (5 mg/kg) resulted in mean (+/- SEM) plasma concentration of 20.6 (+/- 1.85) micrograms/ml at 0.5 hour for either species of birds. There were no significant differences between mean plasma gentamicin concentrations for cockatoos and macaws at any time after drug administration, except at 12 hours, when values for cockatoos were significantly (P less than 0.05) greater than those for macaws. The elimination half-life for gentamicin after IM administration of 5 and 10 mg/kg was 1.17 and 1.07 hours, respectively, for macaws and 1.23 and 1.44 hours, respectively, for cockatoos. Correlation between drug disposition and adverse side effects could not be detected. PMID:2316918

  13. Reporting of adverse events for marketed drugs: Need for strengthening safety database

    PubMed Central

    Apte, Aditi Anand

    2016-01-01

    Pharmacovigilance is an evolving discipline in the Indian context. However, there is limited regulatory guidance for adverse event reporting outside the purview of clinical trials. There are number of deficiencies in the framework for adverse event reporting from the perspective of pharma industry, health-care professional and general public due to which adverse events for marketed drugs are highly underreported. This article discusses the need to strengthen national safety database by promoting and mandating reporting of adverse events by all the stakeholders. PMID:27453826

  14. Reporting of adverse events for marketed drugs: Need for strengthening safety database.

    PubMed

    Apte, Aditi Anand

    2016-01-01

    Pharmacovigilance is an evolving discipline in the Indian context. However, there is limited regulatory guidance for adverse event reporting outside the purview of clinical trials. There are number of deficiencies in the framework for adverse event reporting from the perspective of pharma industry, health-care professional and general public due to which adverse events for marketed drugs are highly underreported. This article discusses the need to strengthen national safety database by promoting and mandating reporting of adverse events by all the stakeholders. PMID:27453826

  15. Adverse Drug Reactions of Spontaneous Reports in Shanghai Pediatric Population

    PubMed Central

    Du, Wen-Min; Xu, Jin-Fang; Zhang, Xin-Ji; He, Jia

    2014-01-01

    Background Knowledge of drug safety in the pediatric population of China is limited. This study was designed to evaluate ADRs in children reported to the spontaneous reporting system (SRS) of Shanghai in 2009. Methodology and Principal Findings Crude ADR reports submitted to Shanghai SRS in 2009 for individuals aged from birth to 17 years (including 17 years) were included. Data were analyzed with respect to age, gender, category of ADR (System Organ Class [SOC]), the severity of reports and type of reporter. Results A male overrepresentation was observed regarding the total number of reports. The most frequently reported group of drugs were vaccines (42.15%). Skin rash and fever were the commonest symptoms reported in the total pediatric dataset. The proportion of children that suffered from a serious ADR was 2.16% and that for drug related deaths was 0.34%. And we found that the multiple drug exposure experienced a high proportion of serious ADRs compared with the single drug use (χ2 = 15.99, P<0.0001). Sixty-five percent of ADRs were for children less than 6 years of age. And more than half of reports were from doctors. Conclusions In our study, consumers were more likely to report new ADRs though they appear to contribute a relatively small percentage of total reports. We propose that patients would take an active role in reporting ADRs. More researches are needed in order to achieve better understanding the characteristics of ADRs in pediatric population of China. PMID:24587066

  16. The radiology of adverse drug reactions and toxic hazards

    SciTech Connect

    Ansell, G.

    1985-01-01

    Dr. Ansell has produced a scholarly review of the radiology of drug reactions and toxic hazards in his latest book, which is based on over 1,200 articles in the world literature. About 800 of these articles are taken from outside the radiology literature, which indicates the need for this subject to be brought to the attention of the radiologist, particularly as concern about drug reactions and toxic hazards is always increasing. The book includes sections covering the chest, gastrointestinal tract, renal tract, skeletal system and soft tissues, and skull and central nervous system. Each section treats specific substances, such as steroids and heavy metals; specific radiologic signs, such as ureteric dilation; specific symptoms, such as dysphagia; industrial toxins; radiographic abnormalities are discussed; and numerous high-quality radiographs.

  17. Confirming false adverse reactions to drugs by performing individualized, randomized trials.

    PubMed

    Knowles, Sandra R; Uetrecht, Jack P; Shear, Neil H

    2002-01-01

    One-patient, randomized, double-blind, controlled trials (N-of-1 RCTs) have traditionally been used to assess the efficacy of treatment. At the Drug Safety Clinic, Toronto, this methodology is used to evaluate adverse effects related to medication use, specifically when the symptoms are vague and are in response to more than one medication. Two patients are described with histories of drug allergies to multiple medications; as well, guidelines for conducting N-of-1 trials are summarized. The first patient had a history of prolonged periorbital and generalized weakness lasting up to one week after exposure to a variety of drugs. Because of the ambiguous results of local anesthetic skin testing, an N-of-1 trial was performed using lidocaine without preservative. Two short-lived episodes of blepharospasm and lethargy were observed with placebo; no subjective or objective reaction occurred with active drug. The second patient had a history of prolonged weakness and drowsiness after exposure to many medications; she had been told that she was allergic to all drugs with a benzene ring. During the first N-of-1 trial, generalized weakness was observed with 10 mg of dimenhydrinate and all four placebo doses. During the second N-of-1 challenge using codeine, no unwarranted reactions occurred with either active or placebo drug. Traditional testing of these patients to disprove the clinical symptoms is often difficult because of the anxiety level associated with the patients' past experiences. N-of-1 trials provide a useful alternative for the management of patients with nonspecific symptomatology attributed to drug ingestion. PMID:12422252

  18. Salicylate intolerance: a masquerader of multiple adverse drug reactions

    PubMed Central

    Fernando, Suran Loshana; Clarke, Lesley R

    2009-01-01

    A female in her early 50s presented with a long-standing history of episodic urticaria and angioedema. She also reported urticarial reactions after ingestion of aspirin, prednisone and multiple antibiotics. These medications were all taken during upper respiratory tract infections. An elimination diet followed by a series of open challenges to food chemicals demonstrated an urticarial eruption following the ingestion of mints, which contain high levels of salicylates. A double-blinded placebo-controlled challenge to salicylate confirmed her sensitivity and explained her reaction to aspirin. The patient informed her treating physician of her copious ingestion of mints during upper respiratory tract infections. Drug hypersensitivity to antibiotics and prednisone was excluded on the basis of negative radioallergosorbent tests (RASTs) and/or absent skin-test responses and/or tolerance to oral challenges. This patient had a salicylate intolerance that caused her episodic urticaria and angioedema, and also masqueraded as a drug allergy due to the concurrent ingestion of mints. PMID:21918670

  19. Adverse effects associated with selective serotonin reuptake inhibitors and tricyclic antidepressants: a meta-analysis

    PubMed Central

    Trindade, E; Menon, D; Topfer, L A; Coloma, C

    1998-01-01

    BACKGROUND: The use of antidepressant medications and the resulting costs have increased dramatically in recent years, partly because of the introduction of selective serotonin reuptake inhibitors (SSRIs). An assessment of the clinical and economic aspects of SSRIs compared with the older tricyclic antidepressants (TCAs) was initiated to generate information for purchasers of these drugs as well as clinicians. One component of this study was an examination of the adverse effects associated with the use of these drugs. METHODS: Searches of bibliographic databases (for January 1980 through May 1996) and manual scanning of both peer-reviewed publications and other documents were used to identify double-blind, randomized controlled trials involving at least one SSRI and one TCA. For the study of adverse effects, only trials that had at least 20 patients in each trial arm and that reported rates of adverse effects in both arms were retained. In total 84 trials reporting on 18 adverse effects were available. Meta-analyses were undertaken to calculate pooled differences in rates of adverse effects. The question of whether the method of eliciting information from patients about adverse effects made a difference in the findings was also examined. Finally, differences in drop-out rates due to adverse effects were calculated. RESULTS: The crude rates of occurrence of adverse effects ranged from 4% (palpitations) to 26% (nausea) for SSRIs and from 4% (diarrhea) to 27% (dry mouth) for TCAs. The differences in the rates of adverse effects between the 2 types of drugs ranged from 14% more with SSRIs (for nausea) to 11% more with TCAs (for constipation). The results did not depend on the method of eliciting information from patients. There were no statistically significant differences between drug classes in terms of drop-outs due to adverse effects. INTERPRETATION: SSRIs and TCAs are both associated with adverse effects, although the key effects differ between the drug classes

  20. Adverse drug reactions caused by drug-drug interactions reported to Croatian Agency for Medicinal Products and Medical Devices: a retrospective observational study

    PubMed Central

    Mirošević Skvrce, Nikica; Macolić Šarinić, Viola; Mucalo, Iva; Krnić, Darko; Božina, Nada; Tomić, Siniša

    2011-01-01

    Aim To analyze potential and actual drug-drug interactions reported to the Spontaneous Reporting Database of the Croatian Agency for Medicinal Products and Medical Devices (HALMED) and determine their incidence. Methods In this retrospective observational study performed from March 2005 to December 2008, we detected potential and actual drug-drug interactions using interaction programs and analyzed them. Results HALMED received 1209 reports involving at least two drugs. There were 468 (38.7%) reports on potential drug-drug interactions, 94 of which (7.8% of total reports) were actual drug-drug interactions. Among actual drug-drug interaction reports, the proportion of serious adverse drug reactions (53 out of 94) and the number of drugs (n = 4) was significantly higher (P < 0.001) than among the remaining reports (580 out of 1982; n = 2, respectively). Actual drug-drug interactions most frequently involved nervous system agents (34.0%), and interactions caused by antiplatelet, anticoagulant, and non-steroidal anti-inflammatory drugs were in most cases serious. In only 12 out of 94 reports, actual drug-drug interactions were recognized by the reporter. Conclusion The study confirmed that the Spontaneous Reporting Database was a valuable resource for detecting actual drug-drug interactions. Also, it identified drugs leading to serious adverse drug reactions and deaths, thus indicating the areas which should be in the focus of health care education. PMID:21990078

  1. Does Cannabidiol Protect Against Adverse Psychological Effects of THC?

    PubMed

    Niesink, Raymond J M; van Laar, Margriet W

    2013-01-01

    The recreational use of cannabis can have persistent adverse effects on mental health. Delta-9-tetrahydrocannabinol (THC) is the main psychoactive constituent of cannabis, and most, if not all, of the effects associated with the use of cannabis are caused by THC. Recent studies have suggested a possible protective effect of another cannabinoid, cannabidiol (CBD). A literature search was performed in the bibliographic databases PubMed, PsycINFO, and Web of Science using the keyword "cannabidiol." After removing duplicate entries, 1295 unique titles remained. Based on the titles and abstracts, an initial selection was made. The reference lists of the publications identified in this manner were examined for additional references. Cannabis is not a safe drug. Depending on how often someone uses, the age of onset, the potency of the cannabis that is used and someone's individual sensitivity, the recreational use of cannabis may cause permanent psychological disorders. Most recreational users will never be faced with such persistent mental illness, but in some individuals cannabis use leads to undesirable effects: cognitive impairment, anxiety, paranoia, and increased risks of developing chronic psychosis or drug addiction. Studies examining the protective effects of CBD have shown that CBD can counteract the negative effects of THC. However, the question remains of how the laboratory results translate to the types of cannabis that are encountered by real-world recreational users. PMID:24137134

  2. Does Cannabidiol Protect Against Adverse Psychological Effects of THC?

    PubMed Central

    Niesink, Raymond J. M.; van Laar, Margriet W.

    2013-01-01

    The recreational use of cannabis can have persistent adverse effects on mental health. Delta-9-tetrahydrocannabinol (THC) is the main psychoactive constituent of cannabis, and most, if not all, of the effects associated with the use of cannabis are caused by THC. Recent studies have suggested a possible protective effect of another cannabinoid, cannabidiol (CBD). A literature search was performed in the bibliographic databases PubMed, PsycINFO, and Web of Science using the keyword “cannabidiol.” After removing duplicate entries, 1295 unique titles remained. Based on the titles and abstracts, an initial selection was made. The reference lists of the publications identified in this manner were examined for additional references. Cannabis is not a safe drug. Depending on how often someone uses, the age of onset, the potency of the cannabis that is used and someone’s individual sensitivity, the recreational use of cannabis may cause permanent psychological disorders. Most recreational users will never be faced with such persistent mental illness, but in some individuals cannabis use leads to undesirable effects: cognitive impairment, anxiety, paranoia, and increased risks of developing chronic psychosis or drug addiction. Studies examining the protective effects of CBD have shown that CBD can counteract the negative effects of THC. However, the question remains of how the laboratory results translate to the types of cannabis that are encountered by real-world recreational users. PMID:24137134

  3. [Understanding and reducing the risk of adverse drug reactions in pediatric patients].

    PubMed

    Gotta, Verena; van den Anker, Johannes; Pfister, Marc

    2015-12-01

    Developmental pharmacology influences the safety profile of drugs in pediatrics. Altered pharmacokinetics and/ or pharmacodynamics of drugs make pediatric patients susceptible to adverse drug reactions (ADRs), especially infants and newborns. Since the efficacy/ safety balance of most available drugs has not been formally evaluated in pediatric clinical trials, optimal dosing is rarely known in pediatrics. Suboptimal pediatric drug formulations make dose optimization even more difficult exposing pediatric patients to medication errors like overdosing and associated ADRs. We provide an overview of pediatric ADRs and discuss recent regulatory and pharmacological measures to understand and reduce risk of ADRs in pediatric patients. PMID:26654811

  4. 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. PMID:26951484

  5. 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

  6. The adverse health effects of chronic cannabis use.

    PubMed

    Hall, Wayne; Degenhardt, Louisa

    2014-01-01

    This paper summarizes the most probable of the adverse health effects of regular cannabis use sustained over years, as indicated by epidemiological studies that have established an association between cannabis use and adverse outcomes; ruled out reverse causation; and controlled for plausible alternative explanations. We have also focused on adverse outcomes for which there is good evidence of biological plausibility. The focus is on those adverse health effects of greatest potential public health significance--those that are most likely to occur and to affect a substantial proportion of regular cannabis users. These most probable adverse effects of regular use include a dependence syndrome, impaired respiratory function, cardiovascular disease, adverse effects on adolescent psychosocial development and mental health, and residual cognitive impairment. PMID:23836598

  7. Semantic Processing to Identify Adverse Drug Event Information from Black Box Warnings

    PubMed Central

    Culbertson, Adam; Fiszman, Marcelo; Shin, Dongwook; Rindflesch, Thomas C.

    2014-01-01

    Adverse drug events account for two million combined injuries, hospitalizations, or deaths each year. Furthermore, there are few comprehensive, up-to-date, and free sources of drug information. Clinical decision support systems may significantly mitigate the number of adverse drug events. However, these systems depend on up-to-date, comprehensive, and codified data to serve as input. The DailyMed website, a resource managed by the FDA and NLM, contains all currently approved drugs. We used a semantic natural language processing approach that successfully extracted information for adverse drug events, at-risk conditions, and susceptible populations from black box warning labels on this site. The precision, recall, and F-score were, 94%, 52%, 0.67 for adverse drug events; 80%, 53%, and 0.64 for conditions; and 95%, 44%, 0.61 for populations. Overall performance was 90% precision, 51% recall, and 0.65 F-Score. Information extracted can be stored in a structured format and may support clinical decision support systems. PMID:25954348

  8. Weighing the adverse cardiac effects of fluoroquinolones: A risk perspective.

    PubMed

    Mehrzad, Raman; Barza, Michael

    2015-11-01

    A rare side effect of fluoroquinolone (FQ) antibiotics is QT prolongation, which may result in serious arrhythmias. Most published comparative trials describe the relative risks among the drug class but do not focus on the incidence of serious arrhythmias. It is important for the prescriber to have a sense not only of relative risk but also of incidence to balance the risks against the other attributes of the individual members of the drug class. A review of English-language literature was performed to identify trials that provide data on the relative risk and, when able to be calculated, the incidence of adverse cardiac events among the commonly used FQs. Moxifloxacin had a several-fold higher risk of cardiac arrhythmias than levofloxacin or ciprofloxacin in randomized trials. However, the actual event rate was low in 2 of 3 studies. Given inconsistencies among the studies and the relative rarity of the events, the clinician need not base the choice of drug primarily on concern for a cardiac arrhythmia except in patients at the highest risk of such an event. PMID:26011799

  9. 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. PMID:26941185

  10. 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. PMID:26928768

  11. Adverse effects of human immunoglobulin therapy.

    PubMed

    Stiehm, E Richard

    2013-07-01

    Human immunoglobulin (IG) is used for IgG replacement therapy in primary and secondary immunodeficiency, for prevention and treatment of certain infections, and as an immunomodulatory agent for autoimmune and inflammatory disorders. IG has a wide spectrum of antibodies to microbial and human antigens. Several high-titered IGs are also available enriched in antibodies to specific viruses or bacterial toxins. IG can be given intravenously (IGIV), intramuscularly (IGIM) or by subcutaneous infusions (SCIG). Local adverse reactions such as persistent pain, bruising, swelling and erythema are rare with IGIV infusions but common (75%) with SCIG infusions. By contrast, adverse systemic reactions are rare with SCIG infusions but common with IGIV infusions, occurring as often as 20% to 50% of patients and 5% to 15% of all IGIV infusions. Systemic adverse reactions can be immediate (60% of reactions) occurring within 6 hours of an infusion, delayed (40% of reactions) occurring 6 hours-1 week after an infusion, and late (less than 1% of reactions), occurring weeks and months after an infusion. Immediate systemic reactions such as head and body aches, chills and fever are usually mild and readily treatable. Immediate anaphylactic and anaphylactoid reactions are uncommon. The most common delayed systemic reaction is persistent headache. Less common but more serious delayed reactions include aseptic meningitis, renal failure, thromboembolism, and hemolytic reactions. Late reactions are uncommon but often severe, and include lung disease, enteritis, dermatologic disorders and infectious diseases. The types, incidence, causes, prevention, and management of these reactions are discussed. PMID:23835249

  12. Mixed-effects Poisson regression analysis of adverse event reports: the relationship between antidepressants and suicide.

    PubMed

    Gibbons, Robert D; Segawa, Eisuke; Karabatsos, George; Amatya, Anup K; Bhaumik, Dulal K; Brown, C Hendricks; Kapur, Kush; Marcus, Sue M; Hur, Kwan; Mann, J John

    2008-05-20

    A new statistical methodology is developed for the analysis of spontaneous adverse event (AE) reports from post-marketing drug surveillance data. The method involves both empirical Bayes (EB) and fully Bayes estimation of rate multipliers for each drug within a class of drugs, for a particular AE, based on a mixed-effects Poisson regression model. Both parametric and semiparametric models for the random-effect distribution are examined. The method is applied to data from Food and Drug Administration (FDA)'s Adverse Event Reporting System (AERS) on the relationship between antidepressants and suicide. We obtain point estimates and 95 per cent confidence (posterior) intervals for the rate multiplier for each drug (e.g. antidepressants), which can be used to determine whether a particular drug has an increased risk of association with a particular AE (e.g. suicide). Confidence (posterior) intervals that do not include 1.0 provide evidence for either significant protective or harmful associations of the drug and the adverse effect. We also examine EB, parametric Bayes, and semiparametric Bayes estimators of the rate multipliers and associated confidence (posterior) intervals. Results of our analysis of the FDA AERS data revealed that newer antidepressants are associated with lower rates of suicide adverse event reports compared with older antidepressants. We recommend improvements to the existing AERS system, which are likely to improve its public health value as an early warning system. PMID:18404622

  13. 15 CFR 970.701 - Significant adverse environmental effects.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 15 Commerce and Foreign Trade 3 2012-01-01 2012-01-01 false Significant adverse environmental... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Environmental Effects § 970.701 Significant adverse environmental effects. (a) Activities with no...

  14. 15 CFR 970.701 - Significant adverse environmental effects.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 15 Commerce and Foreign Trade 3 2014-01-01 2014-01-01 false Significant adverse environmental... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Environmental Effects § 970.701 Significant adverse environmental effects. (a) Activities with no...

  15. 15 CFR 970.701 - Significant adverse environmental effects.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 15 Commerce and Foreign Trade 3 2013-01-01 2013-01-01 false Significant adverse environmental... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES Environmental Effects § 970.701 Significant adverse environmental effects. (a) Activities with no...

  16. 40 CFR 350.21 - Adverse health effects.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  17. 40 CFR 350.21 - Adverse health effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  18. 40 CFR 350.21 - Adverse health effects.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  19. 40 CFR 350.21 - Adverse health effects.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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

  20. 40 CFR 350.21 - Adverse health effects.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  1. Paradoxical bronchospasm: a potentially life threatening adverse effect of albuterol.

    PubMed

    Raghunathan, Kalpana; Nagajothi, Nagapradeep

    2006-03-01

    We report a case of paradoxical bronchospasm to both levalbuterol and albuterol. While the exact mechanism for this known adverse effect of albuterol is not known, awareness of this adverse effect can be life saving to the patient. To our knowledge, this is the first reported case of paradoxical bronchospasm to levalbuterol inhalation solution. PMID:16553105

  2. Multiple adverse effects of pyridium: a case report.

    PubMed

    Haigh, Charles; Dewar, James C

    2006-01-01

    Pyridium (phenazopyridine hydrochloride) is often prescribed as an analgesic in patients following trauma, surgery, or infections of the urinary tract. Pyridium toxicity has been previously reported, however, most cases result in a single adverse effect. Herein the authors describe an elderly patient who presented with simultaneous multiple adverse effects, including a previously undocumented myelosuppressive pancytopenia. PMID:16466130

  3. Adverse Effects of Systemic Immunosuppression in Keratolimbal Allograft

    PubMed Central

    Krakauer, M.; Welder, J. D.; Pandya, H. K.; Nassiri, N.; Djalilian, A. R.

    2012-01-01

    Purpose. Keratolimbal allograft (KLAL) is a treatment for limbal stem cell deficiency. One disadvantage is systemic immunosuppression to avoid rejection. Our purpose was to examine the adverse effects of systemic immunosuppression in KLAL. Methods. A retrospective case review of 16 patients with KLAL who received systemic immunosuppression consisting of a corticosteroid, an antimetabolite, and/or a calcineurin inhibitor was performed. Patients were monitored for signs, symptoms, or laboratory evidence of toxicity. Results. Eleven of 16 patients (68%) experienced an adverse effect. The average age of those with adverse effects was 43.5 years and without was 31.4 years. Ten of 11 patients (91%) had resolution during mean followup of 16.4 months. No serious adverse effects occurred. The most common included anemia, hyperglycemia, elevated creatinine, and elevated liver function tests. Prednisone and tacrolimus were responsible for the most adverse effects. Patients with comorbidities were more likely to experience an adverse effect (82% versus 20%, P = 0.036). Conclusions. KLAL requires prolonged systemic immunosuppression. Our data demonstrated that systemic immunosuppression did not result in serious adverse effects in our population and is relatively safe with monitoring for toxicity. In addition, we demonstrated that adverse effects are more likely in older patients with comorbidities. PMID:22523651

  4. A review of the adverse effects and safety of noradrenergic antidepressants.

    PubMed

    Whiskey, Eromona; Taylor, David

    2013-08-01

    There are a variety of noradrenergic antidepressants available, most of which act by inhibiting neuronal noradrenaline re-uptake, although few drugs are specific for this action. Where drugs have numerous actions the adverse effects of noradrenaline reuptake may be difficult to isolate, although in this respect the adverse effects of reboxetine, a specific noradrenaline re-uptake inhibitor, are illuminating. Noradrenergic antidepressants typically cause minor changes in blood and heart rate, sweating and insomnia. Other pharmacological actions shown by non-specific antidepressants may act to worsen or mitigate these adverse effects. Noradrenergic drugs are less likely than selective serotonin reuptake inhibitors (SSRIs) to cause sexual dysfunction but more likely to cause urinary hesitancy. Doubts remain over the relative propensity for antidepressants with different modes of action to cause diabetes and hyponatraemia. Noradrenergic actions do not seem to confer a risk of death in overdose. PMID:23784737

  5. A Critical Approach to Evaluating Clinical Efficacy, Adverse Events and Drug Interactions of Herbal Remedies.

    PubMed

    Izzo, Angelo A; Hoon-Kim, Sung; Radhakrishnan, Rajan; Williamson, Elizabeth M

    2016-05-01

    Systematic reviews and meta-analyses represent the uppermost ladders in the hierarchy of evidence. Systematic reviews/meta-analyses suggest preliminary or satisfactory clinical evidence for agnus castus (Vitex agnus castus) for premenstrual complaints, flaxseed (Linum usitatissimum) for hypertension, feverfew (Tanacetum partenium) for migraine prevention, ginger (Zingiber officinalis) for pregnancy-induced nausea, ginseng (Panax ginseng) for improving fasting glucose levels as well as phytoestrogens and St John's wort (Hypericum perforatum) for the relief of some symptoms in menopause. However, firm conclusions of efficacy cannot be generally drawn. On the other hand, inconclusive evidence of efficacy or contradictory results have been reported for Aloe vera in the treatment of psoriasis, cranberry (Vaccinium macrocarpon) in cystitis prevention, ginkgo (Ginkgo biloba) for tinnitus and intermittent claudication, echinacea (Echinacea spp.) for the prevention of common cold and pomegranate (Punica granatum) for the prevention/treatment of cardiovascular diseases. A critical evaluation of the clinical data regarding the adverse effects has shown that herbal remedies are generally better tolerated than synthetic medications. Nevertheless, potentially serious adverse events, including herb-drug interactions, have been described. This suggests the need to be vigilant when using herbal remedies, particularly in specific conditions, such as during pregnancy and in the paediatric population. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26887532

  6. Nifedipine versus terbutaline, tocolytic effectiveness and maternal and neonatal adverse effects: a randomized, controlled pilot trial.

    PubMed

    Padovani, Tania Regina; Guyatt, Gordon; Lopes, Luciane Cruz

    2015-03-01

    Although previous evidence suggests advantages of nifedipine over terbutaline as tocolytic agents, in some jurisdictions, terbutaline is approved for use and nifedipine is not. In women in preterm labour, we compared the impact of terbutaline versus nifedipine on inhibition of uterine contractions, preterm birth, neonatal sepsis, intracranial haemorrhage or necrotizing enterocolitis, death or admission to a neonatal intensive care unit and maternal adverse reactions. We randomized 32 women to nifedipine and 34 to terbutaline. We found no difference between groups in tocolysis or preterm birth. No serious maternal adverse effects or serious neonatal adverse outcome occurred in either group. Less serious maternal adverse effects less common with terbutaline included flushing (2.94% versus 43.7%) and headache (5.9% versus 31.2%). The administration of terbutaline increased tremor (76.4% versus 0%), nausea (58.8% versus 9.4%) and dizziness (29.4% versus 6.25%). The total number of side effects, and the proportion of women experiencing one or more side effects, proved greater with terbutaline. In this study, terbutaline and nifedipine performed similarly in their tocolytic effects. Each drug has specific side effects, although overall, nifedipine was associated with fewer adverse effects. PMID:25146233

  7. Benznidazole-Related Adverse Drug Reactions and Their Relationship to Serum Drug Concentrations in Patients with Chronic Chagas Disease

    PubMed Central

    Guerrero, Laura; Posada, Elizabeth; Rodríguez, Elena; Soy, Dolors; Gascon, Joaquim

    2013-01-01

    For treating Chagas disease (CD), a current worldwide health problem, only benznidazole and nifurtimox have been approved to be used. In both cases, unwanted drug-related adverse events (ADRs) are frequent when these drugs are used in adults in the chronic stage. The main objective of this study was to establish benznidazole ADRs and their relationship to serum concentrations in patients with chronic Trypanosoma cruzi infection in order to perform more accurate dosages to minimize ADRs. A total of 54 patients were recruited over 12 months. Of these 54 patients, 53 (98%) experienced at least one ADR during follow-up, and the overall average ADR incidence was 2.4 episodes/patient/month. Benznidazole treatment was discontinued in 11 patients, 7 among them due to severe adverse effects. The mean duration of treatment before withdrawal was 11 days. Benznidazole serum concentrations were recorded on days 15, 30, 45, and 60 of follow-up and evaluated according to clinical and epidemiological variables and ADR severity. No relationship was found between the benznidazole serum concentration and the ADRs. The mean (standard deviation) trough serum benznidazole concentrations (all below 20 mcg/ml) on days 15, 30, 45, and 60 were 6.4 (1.9), 6.1 (1.8), 6.2 (2.2), and 5.7 (1.7) μg/ml, respectively. Benznidazole serum concentrations do not appear to be related to the appearance of serious ADRs. Further, well-controlled studies are necessary to establish the optimal regimen for benznidazole in adults with chronic CD. PMID:23114763

  8. ADReCS: an ontology database for aiding standardization and hierarchical classification of adverse drug reaction terms.

    PubMed

    Cai, Mei-Chun; Xu, Quan; Pan, Yan-Jing; Pan, Wen; Ji, Nan; Li, Yin-Bo; Jin, Hai-Jing; Liu, Ke; Ji, Zhi-Liang

    2015-01-01

    Adverse drug reactions (ADRs) are noxious and unexpected effects during normal drug therapy. They have caused significant clinical burden and been responsible for a large portion of new drug development failure. Molecular understanding and in silico evaluation of drug (or candidate) safety in laboratory is thus so desired, and unfortunately has been largely hindered by misuse of ADR terms. The growing impact of bioinformatics and systems biology in toxicological research also requires a specialized ADR term system that works beyond a simple glossary. Adverse Drug Reaction Classification System (ADReCS; http://bioinf.xmu.edu.cn/ADReCS) is a comprehensive ADR ontology database that provides not only ADR standardization but also hierarchical classification of ADR terms. The ADR terms were pre-assigned with unique digital IDs and at the same time were well organized into a four-level ADR hierarchy tree for building an ADR-ADR relation. Currently, the database covers 6544 standard ADR terms and 34,796 synonyms. It also incorporates information of 1355 single active ingredient drugs and 134,022 drug-ADR pairs. In summary, ADReCS offers an opportunity for direct computation on ADR terms and also provides clues to mining common features underlying ADRs. PMID:25361966

  9. Musculoskeletal adverse drug reactions: a review of literature and data from ADR spontaneous reporting databases.

    PubMed

    Conforti, Anita; Chiamulera, Christian; Moretti, Ugo; Colcera, Sonia; Fumagalli, Guido; Leone, Roberto

    2007-01-01

    The musculoskeletal system can be a target organ for adverse drug reactions (ADRs). Drug-induced muscle, bone or connective tissue injuries may be due to, i), primary direct drug action, or, ii), undirected consequence of generalized drug-induced disease. Musculoskeletal ADRs may be only temporarily disabling, such as muscle cramps, as well as in other cases may be serious and life-threatening, such as rhabdomyolysis. In the last few years there has been an increasing awareness of musculoskeletal ADRs. Some recent drug safety issues dealt with serious or uncommon musculoskeletal reactions like rhabdomyolysis associated to statins and tendon rupture associated to fluoroquinolones. In this review, we firstly selected those drug classes having a significantly high percentage of musculoskeletal disorder reports in the WHO adverse drug reaction database, maintained by the Uppsala Monitoring Centre. Secondly, the different musculoskeletal ADRs were closely analyzed through the data obtained from an Italian interregional ADRs spontaneous reporting database. The findings on drugs associated to different musculoskeletal disorders, have been integrated with a review of the epidemiological data available in the literature. For the most involved drugs (HMG-CoA reductase inhibitors, fluoroquinolones, corticosteroids, bisphosphonates, retinoids) the underlying musculoskeletal ADR mechanisms were also reviewed and discussed. PMID:18690950

  10. Use of internet search logs to evaluate potential drug adverse events.

    PubMed

    Sarntivijai, S; Abernethy, D R

    2014-08-01

    Internet search logs provide an abundant source of data that can be explored for purposes such as identifying drug exposure-adverse event relationships. The methodology to rigorously conduct such evaluations is not well characterized, and the utility of such analyses is not well defined. In this issue, White and colleagues propose an approach using Internet search logs for this purpose and compare it to parallel analyses conducted using the US Food and Drug Administration's spontaneous reporting database. PMID:25056395

  11. [Drug-induced adverse events in the elderly: a traveler's guide].

    PubMed

    Barez, Thierry; Monod, Stéfanie; Livio, Françoise; Renard, Delphine

    2013-11-01

    Elderly people are prone to drug-induced adverse events (AEs), which often manifest as an atypical clinical picture. The differential diagnosis of any new symptom or alteration in the general state of health in the elderly must, therefore, include AEs. This article offers a practical tool designed to help clinicians to rapidly identify which drugs may induce which kind of frequent symptoms or syndromes. PMID:24308143

  12. 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. PMID:20502181

  13. Prevalence, nature and potential preventability of adverse drug events – a population-based medical record study of 4970 adults

    PubMed Central

    Hakkarainen, Katja M; Gyllensten, Hanna; Jönsson, Anna K; Andersson Sundell, Karolina; Petzold, Max; Hägg, Staffan

    2014-01-01

    Aims To estimate the 3 month prevalence of adverse drug events (ADEs), categories of ADEs and preventable ADEs, and the preventability of ADEs among adults in Sweden. Further, to identify drug classes and organ systems associated with ADEs and estimate their seriousness. Methods A random sample of 5025 adults in a Swedish county council in 2008 was drawn from the Total Population Register. All their medical records in 29 inpatient care departments in three hospitals, 110 specialized outpatient clinics and 51 primary care units were reviewed retrospectively in a stepwise manner, and complemented with register data on dispensed drugs. ADEs, including adverse drug reactions (ADRs), sub-therapeutic effects of drug therapy (STEs), drug dependence and abuse, drug intoxications from overdose, and morbidities due to drug-related untreated indication, were detected during a 3 month study period, and assessed for preventability. Results Among 4970 included individuals, the prevalence of ADEs was 12.0% (95% confidence interval (CI) 11.1, 12.9%), and preventable ADEs 5.6% (95% CI 5.0, 6.2%). ADRs (6.9%; 95% CI 6.2, 7.6%) and STEs (6.4%; 95% CI 5.8, 7.1%) were more prevalent than the other ADEs. Of the ADEs, 38.8% (95% CI 35.8–41.9%) was preventable, varying by ADE category and seriousness. ADEs were frequently associated with nervous system and cardiovascular drugs, but the associated drugs and affected organs varied by ADE category. Conclusions The considerable burden of ADEs and preventable ADEs from commonly used drugs across care settings warrants large-scale efforts to redesign safer, higher quality healthcare systems. The heterogeneous nature of the ADE categories should be considered in research and clinical practice for preventing, detecting and mitigating ADEs. PMID:24372506

  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. PMID:26291578

  15. 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

  16. 21 CFR 314.80 - Postmarketing reporting of adverse drug experiences.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... scientific and medical journals either as case reports or as the result of a formal clinical trial. (2) As... experience, postmarketing clinical investigations, postmarketing epidemiological/surveillance studies... adverse drug experiences that occurred in clinical trials if they were previously submitted as part of...

  17. 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...

  18. Drug target prediction using adverse event report systems: a pharmacogenomic approach

    PubMed Central

    Takarabe, Masataka; Kotera, Masaaki; Nishimura, Yosuke; Goto, Susumu; Yamanishi, Yoshihiro

    2012-01-01

    Motivation: Unexpected drug activities derived from off-targets are usually undesired and harmful; however, they can occasionally be beneficial for different therapeutic indications. There are many uncharacterized drugs whose target proteins (including the primary target and off-targets) remain unknown. The identification of all potential drug targets has become an important issue in drug repositioning to reuse known drugs for new therapeutic indications. Results: We defined pharmacological similarity for all possible drugs using the US Food and Drug Administration's (FDA's) adverse event reporting system (AERS) and developed a new method to predict unknown drug–target interactions on a large scale from the integration of pharmacological similarity of drugs and genomic sequence similarity of target proteins in the framework of a pharmacogenomic approach. The proposed method was applicable to a large number of drugs and it was useful especially for predicting unknown drug–target interactions that could not be expected from drug chemical structures. We made a comprehensive prediction for potential off-targets of 1874 drugs with known targets and potential target profiles of 2519 drugs without known targets, which suggests many potential drug–target interactions that were not predicted by previous chemogenomic or pharmacogenomic approaches. Availability: Softwares are available upon request. Contact: yamanishi@bioreg.kyushu-u.ac.jp Supplementary Information: Datasets and all results are available at http://cbio.ensmp.fr/~yyamanishi/aers/. PMID:22962489

  19. 36 CFR 800.5 - Assessment of adverse effects.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... CFR part 68) and applicable guidelines, to avoid adverse effects. (c) Consulting party review. If the... (36 CFR part 68) and applicable guidelines; (iii) Removal of the property from its historic location... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Assessment of adverse...

  20. 36 CFR 800.5 - Assessment of adverse effects.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... CFR part 68) and applicable guidelines, to avoid adverse effects. (c) Consulting party review. If the... (36 CFR part 68) and applicable guidelines; (iii) Removal of the property from its historic location... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Assessment of adverse...

  1. Second-Generation Antipsychotics and Extrapyramidal Adverse Effects

    PubMed Central

    Jakovcevski, Igor

    2014-01-01

    Antipsychotic-induced extrapyramidal adverse effects are well recognized in the context of first-generation antipsychotic drugs. However, the introduction of second-generation antipsychotics, with atypical mechanism of action, especially lower dopamine receptors affinity, was met with great expectations among clinicians regarding their potentially lower propensity to cause extrapyramidal syndrome. This review gives a brief summary of the recent literature relevant to second-generation antipsychotics and extrapyramidal syndrome. Numerous studies have examined the incidence and severity of extrapyramidal syndrome with first- and second-generation antipsychotics. The majority of these studies clearly indicate that extrapyramidal syndrome does occur with second-generation agents, though in lower rates in comparison with first generation. Risk factors are the choice of a particular second-generation agent (with clozapine carrying the lowest risk and risperidone the highest), high doses, history of previous extrapyramidal symptoms, and comorbidity. Also, in comparative studies, the choice of a first-generation comparator significantly influences the results. Extrapyramidal syndrome remains clinically important even in the era of second-generation antipsychotics. The incidence and severity of extrapyramidal syndrome differ amongst these antipsychotics, but the fact is that these drugs have not lived up to the expectation regarding their tolerability. PMID:24995318

  2. Computerized Detection of Adverse Drug Reactions in the Medical Intensive Care Unit

    PubMed Central

    Kane-Gill, Sandra L.; Visweswaran, Shyam; Saul, Melissa I.; Wong, An-Kwok Ian; Penrod, Louis E.; Handler, Steven M.

    2011-01-01

    Objective Clinical event monitors are a type of active medication monitoring system that can use signals to alert clinicians to possible adverse drug reactions. The primary goal was to evaluate the positive predictive values of select signals used to automate the detection of ADRs in the medical intensive care unit. Method This is a prospective, case series of adult patients in the medical intensive care unit during a six-week period who had one of five signals presents: an elevated blood urea nitrogen, vancomycin, or quinidine concentration, or a low sodium or glucose concentration. Alerts were assessed using 3 objective published adverse drug reaction determination instruments. An event was considered an adverse drug reaction when 2 out of 3 instruments had agreement of possible, probable or definite. Positive predictive values were calculated as the proportion of alerts that occurred, divided by the number of times that alerts occurred and adverse drug reactions were confirmed. Results 145 patients were eligible for evaluation. For the 48 patients (50% male) having an alert, the mean ± SD age was 62 ± 19 years. A total of 253 alerts were generated. Positive predictive values were 1.0, 0.55, 0.38 and 0.33 for vancomycin, glucose, sodium, and blood urea nitrogen, respectively. A quinidine alert was not generated during the evaluation. Conclusions Computerized clinical event monitoring systems should be considered when developing methods to detect adverse drug reactions as part of intensive care unit patient safety surveillance systems, since they can automate the detection of these events using signals that have good performance characteristics by processing commonly available laboratory and medication information. PMID:21621453

  3. Adverse effects of spinal manipulation: a systematic review

    PubMed Central

    Ernst, E

    2007-01-01

    Objective To identify adverse effects of spinal manipulation. Design Systematic review of papers published since 2001. Setting Six electronic databases. Main outcome measures Reports of adverse effects published between January 2001 and June 2006. There were no restrictions according to language of publication or research design of the reports. Results The searches identified 32 case reports, four case series, two prospective series, three case-control studies and three surveys. In case reports or case series, more than 200 patients were suspected to have been seriously harmed. The most common serious adverse effects were due to vertebral artery dissections. The two prospective reports suggested that relatively mild adverse effects occur in 30% to 61% of all patients. The case-control studies suggested a causal relationship between spinal manipulation and the adverse effect. The survey data indicated that even serious adverse effects are rarely reported in the medical literature. Conclusions Spinal manipulation, particularly when performed on the upper spine, is frequently associated with mild to moderate adverse effects. It can also result in serious complications such as vertebral artery dissection followed by stroke. Currently, the incidence of such events is not known. In the interest of patient safety we should reconsider our policy towards the routine use of spinal manipulation. PMID:17606755

  4. 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. PMID:23920604

  5. A prospective study on Adverse Drug Reactions of antibiotics in a tertiary care hospital

    PubMed Central

    Shamna, M.; Dilip, C.; Ajmal, M.; Linu Mohan, P.; Shinu, C.; Jafer, C.P.; Mohammed, Yahiya

    2013-01-01

    Adverse reactions are the recognized hazards of drug therapy and they can occur with any class of drugs and many studies revealed that the incidence is more in case of antibiotics. The main aim of this study was to detect and analyze Adverse Drug Reactions of antibiotics in inpatients of a tertiary care hospital. A prospective spontaneous reporting study by active and passive methods was carried out for a period of six months. A total of 49 ADRs were reported during the study period with male predominance (53.06%) and geriatric age group. More number of ADRs was from General Medicine and Pediatric departments in which the most affected organ systems were the GIT (38.77%) and the skin (30.61%). The antibiotic classes mostly accounted were cephalosporins (34.69%) followed by fluoroquinolones and others in which type A reactions were more compared to type B and 59.18% of them were predictable. The severity assessment revealed that most of them were moderate (63.26%) followed by mild and severe reactions. Of the reported reactions, 55.10% were definitely preventable and causality assessment was done which showed that 71.42% of the reactions were probable, possible (18.36%), definite (10.20%) and no reactions were unlikely. The study concluded that Adverse Drug Reactions to antibiotics are common and some of them resulted in increased healthcare cost due to the need of some interventions and increased length of hospital stay. The health system should promote the spontaneous reporting of Adverse Drug Reactions to antibiotics, proper documentation and periodic reporting to regional pharmacovigilance centers to ensure drug safety. PMID:25161373

  6. Misuse of the Naranjo Adverse Drug Reaction Probability Scale in toxicology

    PubMed Central

    Seger, Donna; BARKER, Kimberly; McNAUGHTON, Candace D.

    2014-01-01

    Context When an adverse event occurs in an overdose patient, it may be difficult to determine whether the event was caused by the ingested drug or by medical therapy. Naranjo and colleagues developed a probability scale, the Naranjo Adverse Drug Reaction Probability Scale (Naranjo Scale), to assess the probability that a drug administered in therapeutic doses caused an adverse event thereby classifying the event as an adverse drug reaction (ADR). Although Naranjo et al. specifically excluded the application of this scale to adverse events in overdose patients, case reports demonstrate that authors continue to apply the Naranjo Scale to events in these patients. Objective The World Health Organization defines an ADR as occurring only when drugs are administered in therapeutic doses. Yet ADRs continue to be reported in overdose patients. We sought to examine the use of the Naranjo scale in case reports of overdose patients to assess the potential consequences of that application. Methods A Medline search via PubMed without language limits, through September 2012, using the search terms “Naranjo” and “overdose” or “poisoning” yielded 146 publications. Additional searches were performed to find articles with keywords of the Naranjo Scale development, current applications and validity of application in specific populations such as critically ill and overdose patients. Results From the 146 publications, we identified 17 case reports or series of overdose patients in which the Naranjo Scale was applied to a clinical complication to support a causal relationship between an administered drug and the clinical complication and thereby classify the clinical complication as an ADR. We also identified a recent publication in which the Naranjo Scale was applied to a new treatment modality (lipid emulsion) that is currently administered to overdose patients. Conclusion Adverse events that occur in overdose patients are excluded from the definition of ADR. Yet in case

  7. Integrating Multiple Evidence Sources to Predict Adverse Drug Reactions Based on a Systems Pharmacology Model

    PubMed Central

    Cao, D-S; Xiao, N; Li, Y-J; Zeng, W-B; Liang, Y-Z; Lu, A-P; Xu, Q-S; Chen, AF

    2015-01-01

    Identifying potential adverse drug reactions (ADRs) is critically important for drug discovery and public health. Here we developed a multiple evidence fusion (MEF) method for the large-scale prediction of drug ADRs that can handle both approved drugs and novel molecules. MEF is based on the similarity reference by collaborative filtering, and integrates multiple similarity measures from various data types, taking advantage of the complementarity in the data. We used MEF to integrate drug-related and ADR-related data from multiple levels, including the network structural data formed by known drug–ADR relationships for predicting likely unknown ADRs. On cross-validation, it obtains high sensitivity and specificity, substantially outperforming existing methods that utilize single or a few data types. We validated our prediction by their overlap with drug–ADR associations that are known in databases. The proposed computational method could be used for complementary hypothesis generation and rapid analysis of potential drug–ADR interactions. PMID:26451329

  8. 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

  9. Role of adverse effects in medication nonadherence in bipolar disorder.

    PubMed

    Mago, Rajnish; Borra, Dileep; Mahajan, Rajeev

    2014-01-01

    Nonadherence to medications is common and associated with poor or limited clinical outcomes in the treatment of bipolar disorder. A review of the literature discloses that adverse effects are one of the commonly reported reasons for nonadherence to mood stabilizers by patients with bipolar disorder. Nevertheless, other than such broad summaries, relatively little attention has been given to the role of adverse effects in relation to nonadherence. This review article is the first to consolidate the available data on this topic. Weight gain, perceived cognitive impairment, tremors, and sedation are the adverse effects most likely to lead to nonadherence. Further research is needed to anticipate, identify, manage, and potentially minimize the impact of adverse effects. PMID:25377611

  10. Correlation of adverse effects of cisplatin administration in patients affected by solid tumours: A retrospective evaluation

    PubMed Central

    ASTOLFI, LAURA; GHISELLI, SARA; GUARAN, VALERIA; CHICCA, MILVIA; SIMONI, EDI; OLIVETTO, ELENA; LELLI, GIORGIO; MARTINI, ALESSANDRO

    2013-01-01

    Cisplatin is the most common antineoplastic drug used for the therapy of solid tumours. To date, researchers have focused on the dosage to be administered for each specific tumour, mainly considering the local adverse effects. The aim of this study was to correlate the severity of the adverse effects with: i) the dosage of cisplatin; ii) the specific site of the tumour; iii) the association with other drugs; and iv) the symptoms. We analysed data from 123 patients with 11 different tumour classes undergoing therapy from 2007 to 2008 at St. Anna Hospital (Ferrara, Italy), using the Spearman non-parametric correlation index. Even though significant correlations were found among the variables, the overall results showed that the main factor influencing the severity of the adverse effects was the dosage of cisplatin administered. PMID:23404427

  11. Adverse effects and safety of SGLT-2 inhibitors.

    PubMed

    Halimi, S; Vergès, B

    2014-12-01

    In type 2 diabetes (T2DM), glycaemic control delays the development and slows the progression of complications. Although there are numerous glucose-lowering agents in clinical use, only approximately half of T2DM patients achieve glycaemic control, while undesirable side-effects, such as hypoglycaemia and body weight gain, often impede treatment in those taking these medications. Thus, there is a need for novel agents and treatment options. Sodium-glucose cotransporter-2 inhibitors (SGLT-2-i) have recently been developed for the treatment of T2DM. The available data suggest a good tolerability profile for the three available drugs - canagliflozin, dapagliflozin and empagliflozin - approved by the US Food and Drug Administration (FDA) for the American market as well as in other countries. The most frequently reported adverse events with SGLT-2-i are female genital mycotic infections, urinary tract infections and increased urination. The pharmacodynamic response to SGLT-2-i declines with increasing severity of renal impairment, requiring dosage adjustments or restrictions with moderate-to-severe renal dysfunction. Most patients treated with SGLT-2-i also have a modest reduction in blood pressure and modest effects on serum lipid profiles, some of which are beneficial (increased high-density lipoprotein cholesterol and decreased triglycerides) and others which are not (increased low-density lipoprotein cholesterol, LDL-C). A number of large-scale and longer-term cardiovascular trials are now ongoing. In patients treated with dapagliflozin, a non-significant excess number of breast and bladder cancers has been reported; considered as due to a bias, this is nevertheless being followed in the ongoing trials. No other significant safety issues have been reported so far. Although there is some benefit for several cardiovascular risk factors such as HbA1c, high blood pressure, obesity and increases in LDL-C, adequately powered trials are still required to determine the

  12. Torsadogenic Risk of Antipsychotics: Combining Adverse Event Reports with Drug Utilization Data across Europe

    PubMed Central

    Raschi, Emanuel; Poluzzi, Elisabetta; Godman, Brian; Koci, Ariola; Moretti, Ugo; Kalaba, Marija; Bennie, Marion; Barbui, Corrado; Wettermark, Bjorn; Sturkenboom, Miriam; De Ponti, Fabrizio

    2013-01-01

    Background Antipsychotics (APs) have been associated with risk of torsade de Pointes (TdP). This has important public health implications. Therefore, (a) we exploited the public FDA Adverse Event Reporting System (FAERS) to characterize their torsadogenic profile; (b) we collected drug utilization data from 12 European Countries to assess the population exposure over the 2005-2010 period. Methods FAERS data (2004-2010) were analyzed based on the following criteria: (1) ≥4 cases of TdP/QT abnormalities; (2) Significant Reporting Odds Ratio, ROR [Lower Limit of the 95% confidence interval>1], for TdP/QT abnormalities, adjusted and stratified (Arizona CERT drugs as effect modifiers); (3) ≥4 cases of ventricular arrhythmia/sudden cardiac death (VA/SCD); (4) Significant ROR for VA/SCD; (5) Significant ROR, combined by aggregating TdP/QT abnormalities with VA and SCD. Torsadogenic signals were characterized in terms of signal strength: from Group A (very strong torsadogenic signal: all criteria fulfilled) to group E (unclear/uncertain signal: only 2/5 criteria). Consumption data were retrieved from 12 European Countries and expressed as defined daily doses per 1,000 inhabitants per day (DID). Results Thirty-five antipsychotics met at least one criterium: 9 agents were classified in Group A (amisulpride, chlorpromazine, clozapine, cyamemazine, haloperidol, olanzapine, quetiapine, risperidone, ziprasidone). In 2010, the overall exposure to antipsychotics varied from 5.94 DID (Estonia) to 13.99 (France, 2009). Considerable increment of Group A agents was found in several Countries (+3.47 in France): the exposure to olanzapine increased across all Countries (+1.84 in France) and peaked 2.96 in Norway; cyamemazine was typically used only in France (2.81 in 2009). Among Group B drugs, levomepromazine peaked 3.78 (Serbia); fluphenazine 1.61 (Slovenia). Conclusions This parallel approach through spontaneous reporting and drug utilization analyses highlighted drug- and

  13. Adverse drug reaction monitoring: support for pharmacovigilance at a tertiary care hospital in Northern Brazil

    PubMed Central

    2013-01-01

    Background Adverse drug reactions (ADRs) are recognised as a common cause of hospital admissions, and they constitute a significant economic burden for hospitals. Hospital-based ADR monitoring and reporting programmes aim to identify and quantify the risks associated with the use of drugs provided in a hospital setting. This information may be useful for identifying and minimising preventable ADRs and may enhance the ability of prescribers to manage ADRs more effectively. The main objectives of this study were to evaluate ADRs that occurred during inpatient stays at the Hospital Geral de Palmas (HGP) in Tocantins, Brazil, and to facilitate the development of a pharmacovigilance service. Methods A prospective study was conducted at HGP over a period of 8 months, from January 2009 to August 2009. This observational, cross-sectional, descriptive study was based on an analysis of medical records. Several parameters were utilised in the data evaluation, including patient demographics, drug and reaction characteristics, and reaction outcomes. The reaction severity and predisposing factors were also assessed. Results The overall incidence of ADRs in the patient population was 3.1%, and gender was not found to be a risk factor. The highest ADR rate (75.8%) was found in the adult age group 15 to 50 years, and the lowest ADR rate was found in children aged 3 to 13 years (7.4%). Because of the high frequency of ADRs in orthopaedic (25%), general medicine (22%), and oncology (16%) patients, improved control of the drugs used in these specialties is required. Additionally, the nurse team (52.7%) registered the most ADRs in medical records, most likely due to the job responsibilities of nurses. As expected, the most noticeable ADRs occurred in skin tissues, with such ADRs are more obvious to medical staff, with rashes being the most common reactions. Metamizole, tramadol, and vancomycin were responsible for 21, 11.6, and 8.4% of ADRs, respectively. The majority of ADRs had

  14. DRAR-CPI: a server for identifying drug repositioning potential and adverse drug reactions via the chemical-protein interactome.

    PubMed

    Luo, Heng; Chen, Jian; Shi, Leming; Mikailov, Mike; Zhu, Huang; Wang, Kejian; He, Lin; Yang, Lun

    2011-07-01

    Identifying new indications for existing drugs (drug repositioning) is an efficient way of maximizing their potential. Adverse drug reaction (ADR) is one of the leading causes of death among hospitalized patients. As both new indications and ADRs are caused by unexpected chemical-protein interactions on off-targets, it is reasonable to predict these interactions by mining the chemical-protein interactome (CPI). Making such predictions has recently been facilitated by a web server named DRAR-CPI. This server has a representative collection of drug molecules and targetable human proteins built up from our work in drug repositioning and ADR. When a user submits a molecule, the server will give the positive or negative association scores between the user's molecule and our library drugs based on their interaction profiles towards the targets. Users can thus predict the indications or ADRs of their molecule based on the association scores towards our library drugs. We have matched our predictions of drug-drug associations with those predicted via gene-expression profiles, achieving a matching rate as high as 74%. We have also successfully predicted the connections between anti-psychotics and anti-infectives, indicating the underlying relevance of anti-psychotics in the potential treatment of infections, vice versa. This server is freely available at http://cpi.bio-x.cn/drar/. PMID:21558322

  15. Adverse effects of herbal medicines: an overview of systematic reviews.

    PubMed

    Posadzki, Paul; Watson, Leala K; Ernst, Edzard

    2013-02-01

    This overview of systematic reviews (SRs) aims to evaluate critically the evidence regarding the adverse effects of herbal medicines (HMs). Five electronic databases were searched to identify all relevant SRs, with 50 SRs of 50 different HMs meeting our inclusion criteria. Most had only minor weaknesses in methods. Serious adverse effects were noted only for four HMs: Herbae pulvis standardisatus, Larrea tridentate, Piper methysticum and Cassia senna. The most severe adverse effects were liver or kidney damage, colon perforation, carcinoma, coma and death. Moderately severe adverse effects were noted for 15 HMs: Pelargonium sidoides, Perna canaliculus, Aloe vera, Mentha piperita, Medicago sativa, Cimicifuga racemosa, Caulophyllum thalictroides, Serenoa repens, Taraxacum officinale, Camellia sinensis, Commifora mukul, Hoodia gordonii, Viscum album, Trifolium pratense and Stevia rebaudiana. Minor adverse effects were noted for 31 HMs: Thymus vulgaris, Lavandula angustifolia Miller, Boswellia serrata, Calendula officinalis, Harpagophytum procumbens, Panax ginseng, Vitex agnus-castus, Crataegus spp., Cinnamomum spp., Petasites hybridus, Agave americana, Hypericum perforatum, Echinacea spp., Silybum marianum, Capsicum spp., Genus phyllanthus, Ginkgo biloba, Valeriana officinalis, Hippocastanaceae, Melissa officinalis, Trigonella foenum-graecum, Lagerstroemia speciosa, Cnicus benedictus, Salvia hispanica, Vaccinium myrtillus, Mentha spicata, Rosmarinus officinalis, Crocus sativus, Gymnema sylvestre, Morinda citrifolia and Curcuma longa. Most of the HMs evaluated in SRs were associated with only moderately severe or minor adverse effects. PMID:23472485

  16. Adverse Effect of Child Abuse Victimization among Substance-Using Women in Treatment.

    ERIC Educational Resources Information Center

    Kang, Sung-Yeon; Magura, Stephen; Laudet, Alexandre; Whitney, Shirley

    1999-01-01

    Study examined adverse effects of childhood sexual/physical abuse among substance-abusing women with children. Several significant differences between abused and nonabused women were found in service outcomes. Abused women had more problems relating to drug use and psychiatric/psychological adjustment at follow-up. Findings support a need for…

  17. Adverse Health Effects of Nighttime Lighting

    NASA Astrophysics Data System (ADS)

    Motta, M.

    2012-06-01

    The effects of poor lighting and glare on public safety are well-known, as are the harmful environmental effects on various species and the environment in general. What is less well-known is the potential harmful medical effects of excessive poor nighttime lighting. A significant body of research has been developed over the last few years regarding this problem. One of the most significant effects is the startling increased risk for breast cancer by excessive exposure to nighttime lighting. The mechanism is felt to be by disruption of the circadian rhythm and suppression of melatonin production from the pineal gland. Melatonin has an anticancer effect that is lost when its production is disrupted. I am in the process of developing a monograph that will summarize this important body of research, to be presented and endorsed by the American Medical Association, and its Council of Science and Public health. This paper is a brief overall summary of this little known potential harmful effect of poor and excessive nighttime lighting.

  18. An educational intervention to improve nurses’ knowledge, attitude, and practice toward reporting of adverse drug reactions

    PubMed Central

    Hanafi, Somayeh; Torkamandi, Hassan; Hayatshahi, Alireza; Gholami, Kheirollah; Shahmirzadi, Nikinaz Ashrafi; Javadi, Mohammad Reza

    2014-01-01

    Background: The reporting of adverse drug reactions (ADRs) by nurses in hospitals is very important. Aims: This study was aimed at investigating the impact of an educational intervention to improve ADR reporting and whether trained nurses had better knowledge, attitude, and practice toward ADR reporting. Materials and Methods: A total of 300 nurses in a tertiary care teaching hospital in Tehran, Iran were evaluated with a knowledge, attitude, and practice (KAP) questionnaire regarding ADR reporting in March 2010. After this, an educational program about ADR was provided to nurses. Then the nurses were re-evaluated by the same questionnaire. Comparisons were made of the attitude and knowledge within nurses, before and after education. Data were analyzed using SPSS software. P < 0.05 was considered as significant level. Independent-sample t-test was used to measure the intervention effect. Results: The response rate was 61.3% (N = 184). Knowledge of nurses before the intervention was significantly less than the knowledge after the intervention (P = 0.001). Also, there was a significant effect on attitude (P = 0.002). During the follow-up period of 4 months after the intervention, 26 spontaneous reports were received. Conclusion: Continuous ADR educational program, training, and integration of ADRs’ reporting into the activities of the nurses would likely improve ADR reporting. PMID:24554968

  19. Adverse respiratory reactions to aspirin and nonsteroidal anti-inflammatory drugs.

    PubMed

    Simon, Ronald A

    2004-01-01

    Aspirin-exacerbated respiratory disease (AERD) is an adult-onset condition that manifests as asthma, rhinosinusitis/nasal polyps, and sensitivity to aspirin and other cyclooxygenase-1 (COX-1)-inhibitor nonsteroidal anti-inflammatory drugs (NSAIDs). There is no cross-sensitivity to highly selective COX-2 inhibitors. AERD is chronic and does not improve with avoidance of COX-1 inhibitors. The diagnosis of AERD is made through provocative challenge testing. Following a positive aspirin challenge, patients can be desensitized to aspirin and NSAIDs. The desensitized state can be maintained indefinitely with continued daily administration. After desensitization, there is an approximately 48-hour refractory period to adverse effects from aspirin. The pathogenesis of AERD remains unknown, but these patients have been shown to have multiple abnormalities in arachidonic acid metabolism and in cysteinyl leukotriene 1 receptors. AERD patients can take up to 650 mg of acetaminophen for analgesic or antipyretic relief. Patients can also use weak COX-1 inhibitors, such as sodium salicylate or choline magnesium trisalicylate. Treatment of AERD patients with antileukotriene medications has been helpful but not preferential when compared with non-AERD patients. An alternative treatment for many AERD patients is aspirin desensitization. This is particularly effective in reducing upper-airway mucosal congestion, nasal polyp formation, and systemic steroids. PMID:14680616

  20. Adverse drug reaction and concepts of drug safety in Ayurveda: An overview

    PubMed Central

    Ajanal, Manjunath; Nayak, Shradda; Prasad, Buduru Sreenivasa; Kadam, Avinash

    2013-01-01

    Drug safety is a very basic and fundamental concept in medical practice. ADRs play an important role in assessing patient safety in any system of medicine. Pharmacovigilance study is thus significant to understand treatment outcomes. Current raised issue with respect to complementary and alternative system medicine (CAM) like Ayurveda is increased in number of safety reports along with report misinterpretation; this generates the negative impact on system. Although, Ayurveda which is holistic system of medicine from India has elaborated the causes and methods of drug-induced consequences along with preventive measures the available data in classical texts is scattered. The compilation and analysis along with modern concept drug safety is need of the hour. Present literature review was conducted from various compendium of Ayurveda and electronic data base with search terms of ‘Vyapad’, ‘Viruddha’, ‘Ahita’, ‘herb–herb interaction’, ‘idiosyncrasy’, ‘Prakritiviruddha’ etc. The reported information was analysed for the possible correlation on concept of ADR and Pharmacovigilance of current science. Overall review demonstrated that drug interaction, iatrogenic, over dose, administration of unsuitable drugs, reprehensive drug administration with respect to disease, complication from five procedural therapies (Panchakarma) and reprehensible preparation of mineral drug are nearer to the modern causes of ADR. Thus, concept of drug safety and ADR is not new to the Ayurveda. The concept “Drug which is not appropriate to be used as medicine”(Abheshaja) of Ayurveda sounds similar as that of modern pharmacovigilance. PMID:24563588

  1. Preventive Effects of Multi-Lamellar Emulsion on Low Potency Topical Steroid Induced Local Adverse Effect

    PubMed Central

    Sul, Geun Dong; Park, Hyun Jung; Bae, Jong Hwan; Hong, Keum Duck; Park, Byeong Deog; Chun, Jaesun; Jeong, Se Kyoo; Lee, Seung Hun; Ahn, Sung Ku

    2013-01-01

    Background Topical steroid treatment induces diverse local Wand systemic adverse effects. Several approaches have been tried to reduce the steroid-induced adverse effects. Simultaneous application of physiological lipid mixture is also suggested. Objective Novel vehicles for topical glucocorticoids formulation were evaluated for the efficacy of reducing side-effects and the drug delivery properties of desonide, a low potency topical steroid. Methods Transcutaneous permeation and skin residual amount of desonide were measured using Franz diffusion cells. The in vivo anti-inflammatory activity was evaluated using murine model. Results Topical steroids formulation containing desonide, in either cream or lotion form, were prepared using multi-lamellar emulsion (MLE), and conventional desonide formulations were employed for comparison. MLE formulations did not affect the anti-inflammatory activity of the desonide in phobol ester-induced skin inflammation model, compared with conventional formulations. While the penetrated amounts of desonide were similar for all the tested formulations at 24 hours after application, the increased lag time was observed for the MLE formulations. Interestingly, residual amount of desonide in epidermis was significantly higher in lotion type MLE formulation. Steroid-induced adverse effects, including permeability barrier function impairment, were partially prevented by MLE formulation. Conclusion Topical desonide formulation using MLE as a vehicle showed a better drug delivery with increased epidermal retention. MLE also partially prevented the steroid-induced side effects, such as skin barrier impairment. PMID:23467730

  2. Biclustering of Adverse Drug Events in FDA’s Spontaneous Reporting System

    PubMed Central

    Harpaz, Rave; Perez, Hector; Chase, Herbert S.; Rabadan, Raul; Hripcsak, George; Friedman, Carol

    2012-01-01

    In this paper we present a new pharmacovigilance data mining technique based on the biclustering paradigm, which is designed to identify drug groups that share a common set of adverse events in FDA’s spontaneous reporting system. A taxonomy of biclusters is developed, revealing that a significant number of bone fide adverse drug event (ADE) biclusters are identified. Statistical tests indicate that it is extremely unlikely that the discovered bicluster structures as well as their content arose by chance. Some of the biclusters classified as indeterminate provide support for previously unrecognized and potentially novel ADEs. In addition, we demonstrate the importance of the proposed methodology to several important aspects of pharmacovigilance such as: providing insight into the etiology of ADEs, facilitating the identification of novel ADEs, suggesting methods and rational for aggregating terminologies, highlighting areas of focus, and as a data exploratory tool. PMID:21191383

  3. Recent Literature on Medication Errors and Adverse Drug Events in Older Adults.

    PubMed

    Naples, Jennifer G; Hanlon, Joseph T; Schmader, Kenneth E; Semla, Todd P

    2016-02-01

    Medication errors and adverse drug events are common in older adults, but locating literature addressing these issues is often challenging. The objective of this article is to summarize recent studies addressing medication errors and adverse drug events in a single location to improve accessibility for individuals working with older adults. A comprehensive literature search for studies published in 2014 was conducted, and 51 potential articles were identified. After critical review, 17 studies were selected for inclusion based on innovation; rigorous observational or experimental study designs; and use of reliable, valid measures. Four articles characterizing potentially inappropriate prescribing and interventions to optimize medication regimens were annotated and critiqued in detail. The authors hope that health policy-makers and clinicians find this information helpful in improving the quality of care for older adults. PMID:26804210

  4. Ontological representation of adverse drug reactions using the Foundational Model of Anatomy.

    PubMed

    Bousquet, Cédric; Gasperina, Philippe; Trombert, Béatrice; Clavel, Lucienne; Kumar, Anand; Rodrigues, Jean Marie

    2009-01-01

    In a previous work we proposed a categorial structure for the representation of adverse drug reactions consisting of 16 semantic categories and 20 relations. We present an implementation of this categorial structure in Protégé based on four WHO-ART system organ classes: Gastro-intestinal system disorders, Liver and biliary system disorders, Central & peripheric nervous system disorders, and Psychiatric disorders. We compared classification according to anatomy using SNOMED CT within the PharmARTS tool and the FMA with the Pellet reasoner. This ontology contains 210 concepts for Gastroenterology, 66 concepts for Psychiatry and 85 concepts for Neurology. Classification of disorders located in the upper gastro intestinal tract was similar using both SNOMED CT and the FMA. This work is a first step towards the comparison of two models of anatomy within a common ontology of adverse drug reactions. PMID:19745363

  5. Developing a taxonomy for research in adverse drug events: potholes and signposts.

    PubMed

    Nebeker, J R; Hurdle, J F; Hoffman, J; Roth, B; Weir, C R; Samore, M H

    2001-01-01

    Computerized decision support and order entry shows great promise for reducing adverse drug events (ADEs). The evaluation of these solutions depends on a framework of definitions and classifications that is clear and practical. Unfortunately the literature does not always provide a clear path to defining and classifying adverse drug events. While not a systematic review, this paper uses examples from the literature to illustrate problems that investigators will confront as they develop a conceptual framework for their research. It also proposes a targeted taxonomy that can facilitate a clear and consistent approach to the research of ADEs and aid in the comparison to results of past and future studies. The taxonomy addresses the definition of ADE, types, seriousness, error, and causality. PMID:11825237

  6. Recent Literature on Medication Errors and Adverse Drug Events in Older Adults

    PubMed Central

    Naples, Jennifer G.; Hanlon, Joseph T.; Schmader, Kenneth E.; Semla, Todd P.

    2015-01-01

    Medication errors and adverse drug events are common in older adults, but locating literature addressing these issues is often challenging. The objective of this article was to summarize recent studies addressing medication errors and adverse drug events in a single location to improve accessibility for individuals working with older adults. The authors conducted a comprehensive literature search for studies published in 2014 and identified 51 potential articles. After critical review, 17 studies were selected for inclusion based on innovation, rigorous observational or experimental study designs, and use of reliable, valid measures. Four articles characterizing potentially inappropriate prescribing and interventions to optimize medication regimens were annotated and critiqued in detail. We hope that health policy makers and clinicians find this information helpful in improving the quality of care for older adults. PMID:26804210

  7. 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. PMID:22506106

  8. 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

  9. Novel data-mining methodologies for adverse drug event discovery and analysis.

    PubMed

    Harpaz, R; DuMouchel, W; Shah, N H; Madigan, D; Ryan, P; Friedman, C

    2012-06-01

    An important goal of the health system is to identify new adverse drug events (ADEs) in the postapproval period. Datamining methods that can transform data into meaningful knowledge to inform patient safety have proven essential for this purpose. New opportunities have emerged to harness data sources that have not been used within the traditional framework. This article provides an overview of recent methodological innovations and data sources used to support ADE discovery and analysis. PMID:22549283

  10. Novel Data Mining Methodologies for Adverse Drug Event Discovery and Analysis

    PubMed Central

    Harpaz, Rave; DuMouchel, William; Shah, Nigam H.; Madigan, David; Ryan, Patrick; Friedman, Carol

    2013-01-01

    Introduction Discovery of new adverse drug events (ADEs) in the post-approval period is an important goal of the health system. Data mining methods that can transform data into meaningful knowledge to inform patient safety have proven to be essential. New opportunities have emerged to harness data sources that have not been used within the traditional framework. This article provides an overview of recent methodological innovations and data sources used in support of ADE discovery and analysis. PMID:22549283

  11. Identifying genetic risk factors for serious adverse drug reactions: current progress and challenges

    PubMed Central

    Wilke, Russell A.; Lin, Debbie W.; Roden, Dan M.; Watkins, Paul B.; Flockhart, David; Zineh, Issam; Giacomini, Kathleen M.; Krauss, Ronald M.

    2009-01-01

    Serious adverse drug reactions (SADRs) are a major cause of morbidity and mortality worldwide. Some SADRs may be predictable, based upon a drug's pharmacodynamic and pharmacokinetic properties. Many, however, appear to be idiosyncratic. Genetic factors may underlie susceptibility to SADRs and the identification of predisposing genotypes may improve patient management through the prospective selection of appropriate candidates. Here we discuss three specific SADRs with an emphasis on genetic risk factors. These SADRs, selected based on wide-sweeping clinical interest, are drug-induced liver injury, statin-induced myotoxicity and drug-induced long QT and torsades de pointes. Key challenges for the discovery of predictive risk alleles for these SADRs are also considered. PMID:17971785

  12. Updating the French method for the causality assessment of adverse drug reactions.

    PubMed

    Arimone, Yannick; Bidault, Irène; Dutertre, Jean-Paul; Gérardin, Marie; Guy, Claire; Haramburu, Françoise; Hillaire-Buys, Dominique; Meglio, Carmine; Penfornis, Catherine; Théophile, Hélène; Valnet-Rabier, Marie-Blanche

    2013-01-01

    The Imputability Working Group (CRI) updated the French drug reaction causality assessment method. This tripartite group is made up of staff from the French network of regional pharmacovigilance centres, pharmaceutical companies, and the French National Agency for the Safety of Medicines and Health Products (ANSM). After reviewing the strengths and weaknesses of the previous method, several ideas for improvement were proposed: a better-worded and more discriminating scale for certain chronological and semiological criteria, a larger scale for the intrinsic score (increased from 5 to 7 levels), a new bibliographical scale to differentiate between expected and unexpected adverse drug reactions, and a new informativeness scale. PMID:23773347

  13. 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. PMID:22512705

  14. Potential adverse health effects of wood smoke.

    PubMed

    Pierson, W E; Koenig, J Q; Bardana, E J

    1989-09-01

    The use of wood stoves has increased greatly in the past decade, causing concern in many communities about the health effects of wood smoke. Wood smoke is known to contain such compounds as carbon monoxide, nitrogen oxides, sulfur oxides, aldehydes, polycyclic aromatic hydrocarbons, and fine respirable particulate matter. All of these have been shown to cause deleterious physiologic responses in laboratory studies in humans. Some compounds found in wood smoke--benzo[a]pyrene and formaldehyde--are possible human carcinogens. Fine particulate matter has been associated with decreased pulmonary function in children and with increased chronic lung disease in Nepal, where exposure to very high amounts of wood smoke occurs in residences. Wood smoke fumes, taken from both outdoor and indoor samples, have shown mutagenic activity in short-term bioassay tests. Because of the potential health effects of wood smoke, exposure to this source of air pollution should be minimal. PMID:2686171

  15. Potential adverse health effects of wood smoke.

    PubMed Central

    Pierson, W E; Koenig, J Q; Bardana, E J

    1989-01-01

    The use of wood stoves has increased greatly in the past decade, causing concern in many communities about the health effects of wood smoke. Wood smoke is known to contain such compounds as carbon monoxide, nitrogen oxides, sulfur oxides, aldehydes, polycyclic aromatic hydrocarbons, and fine respirable particulate matter. All of these have been shown to cause deleterious physiologic responses in laboratory studies in humans. Some compounds found in wood smoke--benzo[a]pyrene and formaldehyde--are possible human carcinogens. Fine particulate matter has been associated with decreased pulmonary function in children and with increased chronic lung disease in Nepal, where exposure to very high amounts of wood smoke occurs in residences. Wood smoke fumes, taken from both outdoor and indoor samples, have shown mutagenic activity in short-term bioassay tests. Because of the potential health effects of wood smoke, exposure to this source of air pollution should be minimal. PMID:2686171

  16. Prevalence and Perceived Preventability of Self-Reported Adverse Drug Events – A Population-Based Survey of 7099 Adults

    PubMed Central

    Hakkarainen, Katja Marja; Andersson Sundell, Karolina; Petzold, Max; Hägg, Staffan

    2013-01-01

    Purpose Adverse drug events (ADEs) are common and often preventable among inpatients, but self-reported ADEs have not been investigated in a representative sample of the general public. The objectives of this study were to estimate the 1-month prevalence of self-reported ADEs among the adult general public, and the perceived preventability of 2 ADE categories: adverse drug reactions (ADRs) and sub-therapeutic effects (STEs). Methods In this cross-sectional study, a postal survey was sent in October 2010 to a random sample of 13 931 Swedish residents aged ≥18 years. Self-reported ADEs experienced during the past month included ADRs, STEs, drug dependence, drug intoxications and morbidity due to drug-related untreated indication. ADEs could be associated with prescription, non-prescription or herbal drugs. The respondents estimated whether ADRs and STEs could have been prevented. ADE prevalences in age groups (18–44, 45–64, or ≥65 years) were compared. Results Of 7099 respondents (response rate 51.0%), ADEs were reported by 19.4% (95% confidence interval, 18.5–20.3%), and the prevalence did not differ by age group (p>0.05). The prevalences of self-reported ADRs, STEs, and morbidities due to drug-related untreated indications were 7.8% (7.2–8.4%), 7.6% (7.0–8.2%) and 8.1% (7.5–8.7%), respectively. The prevalence of self-reported drug dependence was 2.2% (1.9–2.6%), and drug intoxications 0.2% (0.1–0.3%). The respondents considered 19.2% (14.8–23.6%) of ADRs and STEs preventable. Although reported drugs varied between ADE categories, most ADEs were attributable to commonly dispensed drugs. Drugs reported for all and preventable events were similar. Conclusions One-fifth of the adult general public across age groups reported ADEs during the past month, indicating a need for prevention strategies beyond hospitalised patients. For this, the underlying causes of ADEs should increasingly be investigated. The high burden of ADEs and preventable ADEs

  17. Adverse health effects of indoor moulds.

    PubMed

    Piecková, Elena

    2012-12-01

    Building associated illnesses - sick building syndrome (SBS) as a common example - are associated with staying in buildings with poor indoor air quality. The importance of indoor fungal growth in this phenomenon continues to be evident, even though no causative relation has been established so far. Indoor humidity is strongly associated with the symptoms of SBS. Fungal metabolites that may induce ill health in susceptible occupants comprise beta-D-glucan, mycotoxins, and volatile organic compounds as known irritants and/or immunomodulators. Indoor toxic fungal metabolites might be located in micromycetal propagules (endometabolites), in (bio-)aerosol, detritus, and house dust (exometabolites) as their particular carriers. It is highly probable that hyphal fragments, dust, and particles able to reach the alveoli have the strongest depository and toxic potential. Most fungal spores are entrapped by the upper respiratory tract and do not reach further than the bronchi because of their size, morphology, and the mode of propagation (such as slime heads and aggreggation). This is why studies of the toxic effects of fungal spores prefer directly applying metabolite mixtures over mimicking real exposure. Chronic low-level exposure to a mixture of fungal toxicants and other indoor stressors may have synergistic effects and lead to severe neuroendocrineimmune changes. PMID:23334050

  18. Chemical Hair Relaxers Have Adverse Effects a Myth or Reality

    PubMed Central

    Shetty, Vinma H; Shetty, Narendra J; Nair, Dhanya Gopinath

    2013-01-01

    Context: Hair plays an important role in one's personality and builds confidence. Now-a-days, chemical hair relaxers are used very commonly in the society. We document the adverse effects reported by the sample that have used any one of the professional chemical hair relaxers. Aim: To study the adverse effects reported by the sample who underwent repeated chemical hair relaxing. Settings and Design: Cross-sectional questionnaire based study done on a sample taken from a medical college and hospital campus in Mangalore. Materials and Methods: The sample was restricted to females and to those who underwent it more than once. A questionnaire was given to a sample of 90, which matched our criteria. Statistical Analysis: SPSS software 17. Results: Adverse effects reported by the sample after undergoing the procedure were found to be a high 95.56%, out of which the following are the common adverse effects reported; frizzy hair in 67%, dandruff in 61%, hair loss in 47%, thinning and weakening of hair in 40%, greying of hair 22%, and split ends in only 17%. Conclusions: Very few studies have been conducted on the adverse effects of hair straightening products in India. From our study, it can be stated that most of the samples had adverse effects, which was as high as 95.56%. Hence from the details elicited from this study, we can conclude that, usage of chemical hair relaxers does cause adverse effects and is “not a myth.” Thus, it is necessary to make available a less harmful chemical hair relaxer to the society. PMID:23960393

  19. Patients' Induced Pluripotent Stem Cells to Model Drug Induced Adverse Events: A Role in Predicting Thiopurine Induced Pancreatitis?

    PubMed

    Stocco, Gabriele; Lanzi, Gaetana; Yue, Fengming; Giliani, Silvia; Sasaki, Katsunori; Tommasini, Alberto; Pelin, Marco; Martelossi, Stefano; Ventura, Alessandro; Decorti, Giuliana

    2015-01-01

    Induced pluripotent stem cells (iPSC) can be produced from adult cells by transfecting them with a definite set of pluripotency-associated genes. Under adequate growth conditions and stimulation iPSC can differentiate to almost every somatic lineage in the body. Patients' derived iPSC are an innovative model to study mechanisms of adverse drug reactions in individual patients and in cell types that cannot be easily obtained from human subjects. Proof-of concept studies with known toxicants have been performed for liver, cardiovascular and central nervous system cells: neurons obtained from iPSC have been used to elucidate the mechanism of chemotherapy-induced peripheral neuropathy by evaluating the effects of neurotoxic drugs such as vincristine. However, no study has been performed yet on pancreatic tissue and drug induced pancreatitis. Thiopurines (azathioprine and mercaptopurine) are immunosuppressive antimetabolite drugs, commonly used to treat Crohn's disease. About 5% of Crohn's disease patients treated with thiopurines develop pancreatitis, a severe idiosyncratic adverse event; these patients have to stop thiopurine administration and may require medical treatment, with significant personal and social costs. Molecular mechanism of thiopurine induced pancreatitis (TIP) is currently unknown and no fully validated biomarker is available to assist clinicians in preventing this adverse event. Hence, in this review we have reflected upon the probable research applications of exocrine pancreatic cells generated from patient specific iPS cells. Such pancreatic cells can provide excellent insights into the molecular mechanism of TIP. In particular three hypotheses on the mechanism of TIP could be explored: drug biotransformation, innate immunity and adaptative immunity. PMID:26526832

  20. Hospitalization in older patients due to adverse drug reactions -the need for a prediction tool.

    PubMed

    Parameswaran Nair, Nibu; Chalmers, Leanne; Peterson, Gregory M; Bereznicki, Bonnie J; Castelino, Ronald L; Bereznicki, Luke R

    2016-01-01

    Adverse drug reactions (ADRs) represent a major burden on society, resulting in significant morbidity, mortality, and health care costs. Older patients living in the community are particularly susceptible to ADRs, and are at an increased risk of ADR-related hospitalization. This review summarizes the available evidence on ADR-related hospital admission in older patients living in the community, with a particular focus on risk factors for ADRs leading to hospital admission and the need for a prediction tool for risk of ADR-related hospitalization in these individuals. The reported proportion of hospital admissions due to ADRs has ranged from 6% to 12% of all admissions in older patients. The main risk factors or predictors for ADR-related admissions were advanced age, polypharmacy, comorbidity, and potentially inappropriate medications. There is a clear need to design intervention strategies to prevent ADR-related hospitalization in older patients. To ensure the cost-effectiveness of such strategies, it would be necessary to target them to those older individuals who are at highest risk of ADR-related hospitalization. Currently, there are no validated tools to assess the risk of ADRs in primary care. There is a clear need to investigate the utility of tools to identify high-risk patients to target appropriate interventions toward prevention of ADR-related hospital admissions. PMID:27194906

  1. A team agent approach to postmarketing surveillance of adverse drug reactions.

    PubMed

    Ji, Yanqing; Ying, Hao; Barth-Jones, Daniel; Yen, John; Zhu, Shizhou; Miller, Richard; Michael Massanari, R

    2005-01-01

    Current postmarketing surveillance methods largely rely on spontaneous reports which suffer from serious underreporting, latency, and inconsistent reporting. Thus they are not ideal for rapidly identifying rare adverse drug reactions (ADRs). We propose an active, multi-agent computer software system, where each agent is empowered with teamwork capabilities such as anticipating information needs, identifying relevant ADR information, and continuously monitoring and proactively sharing such information in a collaborative fashion with other agents. The main purpose of this system is to help regulatory authorities (e.g., FDA in the U.S.) find previously unrecognized ADRs as early as possible. Another objective is to promote increased filing of on-line ADR reports thereby, addressing the severe underreporting problem with the current system. The proposed system has the potential to significantly accelerate the process of ADR discovery and response by utilizing electronic patient data distributed across many different sources and locations more effectively. Our preliminary system design is presented and some issues related to it are discussed. PMID:17281878

  2. Systems biology approaches for identifying adverse drug reactions and elucidating their underlying biological mechanisms.

    PubMed

    Boland, Mary Regina; Jacunski, Alexandra; Lorberbaum, Tal; Romano, Joseph D; Moskovitch, Robert; Tatonetti, Nicholas P

    2016-01-01

    Small molecules are indispensable to modern medical therapy. However, their use may lead to unintended, negative medical outcomes commonly referred to as adverse drug reactions (ADRs). These effects vary widely in mechanism, severity, and populations affected, making ADR prediction and identification important public health concerns. Current methods rely on clinical trials and postmarket surveillance programs to find novel ADRs; however, clinical trials are limited by small sample size, whereas postmarket surveillance methods may be biased and inherently leave patients at risk until sufficient clinical evidence has been gathered. Systems pharmacology, an emerging interdisciplinary field combining network and chemical biology, provides important tools to uncover and understand ADRs and may mitigate the drawbacks of traditional methods. In particular, network analysis allows researchers to integrate heterogeneous data sources and quantify the interactions between biological and chemical entities. Recent work in this area has combined chemical, biological, and large-scale observational health data to predict ADRs in both individual patients and global populations. In this review, we explore the rapid expansion of systems pharmacology in the study of ADRs. We enumerate the existing methods and strategies and illustrate progress in the field with a model framework that incorporates crucial data elements, such as diet and comorbidities, known to modulate ADR risk. Using this framework, we highlight avenues of research that may currently be underexplored, representing opportunities for future work. PMID:26559926

  3. Probable Nootropicinduced Psychiatric Adverse Effects: A Series of Four Cases

    PubMed Central

    Ajaltouni, Jean

    2015-01-01

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

  4. Probable Nootropicinduced Psychiatric Adverse Effects: A Series of Four Cases.

    PubMed

    Talih, Farid; Ajaltouni, Jean

    2015-01-01

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

  5. A review of adverse cutaneous drug reactions resulting from the use of interferon and ribavirin

    PubMed Central

    Mistry, Nisha; Shapero, Jonathan; Crawford, Richard I

    2009-01-01

    Drug-induced cutaneous eruptions are named among the most common side effects of many medications. Thus, cutaneous drug eruptions are a common cause of morbidity and mortality, especially in hospital settings. The present article reviews different presentations of drug-induced cutaneous eruptions, with a focus on eruptions reported secondary to the use of interferon and ribavirin. Presentations include injection site reactions, psoriasis, eczematous drug reactions, alopecia, sarcoidosis, lupus, fixed drug eruptions, pigmentary changes and lichenoid eruptions. Also reviewed are findings regarding life-threatening systemic drug reactions. PMID:19826642

  6. Prospective observational study protocol to investigate long-term adverse effects of methylphenidate in children and adolescents with ADHD: the Attention Deficit Hyperactivity Disorder Drugs Use Chronic Effects (ADDUCE) study

    PubMed Central

    Inglis, S K; Carucci, S; Garas, P; Häge, A; Banaschewski, T; Buitelaar, J K; Dittmann, R W; Falissard, B; Hollis, C; Kovshoff, H; Liddle, E; McCarthy, S; Nagy, P; Neubert, A; Rosenthal, E; Sonuga-Barke, E; Wong, I; Zuddas, A; Coghill, D C

    2016-01-01

    Introduction Methylphenidate is the most frequently used medication for the treatment of attention-deficit/hyperactivity disorder (ADHD) in Europe. Following concerns about its safety, the European Commission called for research into the long-term effects of methylphenidate on children and adolescents with ADHD. The Attention Deficit Hyperactivity Disorder Drugs Use Chronic Effects (ADDUCE) research programme was designed to address this call. At the heart of this programme is a 2-year longitudinal naturalistic pharmacovigilance study being conducted in 27 European sites. Methods and analysis 3 cohorts of children and adolescents (aged 6–17) living in the UK, Germany, Italy and Hungary are being recruited: Group 1 (Medicated ADHD): 800 ADHD medication-naive children and adolescents with a clinical diagnosis of ADHD about to start methylphenidate treatment for the first time. Group 2 (Unmedicated ADHD): 400 children and adolescents with a clinical diagnosis of ADHD who have never been treated with ADHD medication and have no intention of beginning medication. Group 3 (Non-ADHD): 400 children and adolescents without ADHD who are siblings of individuals in either group 1 or 2. All participants will be assessed 5 times during their 2-year follow-up period for growth and development, psychiatric, neurological and cardiovascular health. The primary outcome measure will be the height velocity SD score. Ethics and dissemination Ethical approval for the study has been granted by the East of Scotland Research Ethics Service. Following this approval, patient information leaflets and consent forms were translated as necessary and submissions made by lead sites in each of the other 3 countries to their own ethics committees. Following ethical approval in each country, local ethical permissions at each site were sought and obtained as needed. The study's website (http://www.adhd-adduce.org/page/view/2/Home) provides information for researchers, participants and the general

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

    PubMed Central

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

    2012-01-01

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

  8. Drug adverse events and drop-out risk: a clinical case.

    PubMed

    Scoyni, R M; Aiello, L; Trani, I; Felli, B; Masin, A M R; Camponi, V; Dignazio, L; Cortese, M; Pacitti, M T; Carratelli, D; Morocutti, C

    2007-01-01

    We report a brief discussion on a clinical case of a female patient, 85 years old, affected by severe cognitive impairment and chronic obstructive pulmonary disease (COPD). The patient was not taking drugs at home (apart from promazine: 10 drops when necessary to control her behavioral diseases). A previous neuropsychological evaluation had shown a severe cognitive impairment MMSE=16/30; ADL=3/6; IADL=0/8) due to multiple brain ischemic areas (confirmed in 2003 by MRI neuroimaging). When the patient was admitted to our center she was able to perform some basic activities of daily living such as eating and walking and was not too confused. She was included in cognitive rehabilitation groups. Since she showed signs of Parkinsonism, a therapy based on omeprazol 20mg, acetylsalicylic acid, donepezil 10mg, pramipexol 0.18 mg, nimodipine 10 drops, levodopa+carbidopa 100/25mg was started. A few days later she became sleepy during daytime and, once, she lost her balance and fell. She was not self-sufficient any more. At first this was attributed to a lung infection that the patient had, but her state continue after the infection was completely cured with appropriate antibiotics therapy. At that point an adverse drug reaction was suspected and therapy with pramipexol 0.18 mg was interrupted. In a few days the patient regained her previous level of consciousness and self-sufficiency. We consider this a typical case of complex management in a patient with dementia and comorbidity in which adverse drug reactions can play an important role in lowering the level of cognitive functions. In this case the relationship with the family of the patient was made difficult by the attitude of the patient's daughter who decided, after the onset of the adverse drug reaction, to interrupt her mother's stay in our center even at risk of the worst consequences. PMID:17317475

  9. 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

  10. Quality of Reporting of Serious Adverse Drug Events to an Institutional Review Board

    PubMed Central

    Dorr, David A.; Burdon, Rachel; West, Dennis P.; Lagman, Jennifer; Georgopoulos, Christina; Belknap, Steven M.; McKoy, June M.; Djulbegovic, Benjamin; Edwards, Beatrice J.; Weitzman, Sigmund A.; Boyle, Simone; Tallman, Martin S.; Talpaz, Moshe; Sartor, Oliver; Bennett, Charles L.

    2009-01-01

    Purpose Serious adverse drug event (sADE) reporting to Institutional Review Boards (IRB) is essential to ensure pharmaceutical safety. However, the quality of these reports has not been studied. Safety reports are especially important for cancer drugs that receive accelerated Food and Drug Administration approval, like imatinib, as preapproval experience with these drugs is limited. We evaluated the quality, accuracy, and completeness of sADE reports submitted to an IRB. Experimental Design sADE reports submitted to an IRB from 14 clinical trials with imatinib were reviewed. Structured case report forms, containing detailed clinical data fields and a validated causality assessment instrument, were developed. Two forms were generated for each ADE, the first populated with data abstracted from the IRB reports, and the second populated with data from the corresponding clinical record. Completeness and causality assessments were evaluated for each of the two sources, and then compared. Accuracy (concordance between sources) was also assessed. Results Of 115 sADEs reported for 177 cancer patients to the IRB, overall completeness of adverse event descriptions was 2.4-fold greater for structured case report forms populated with information from the clinical record versus the corresponding forms from IRB reports (95.0% versus 40.3%, P < 0.05). Information supporting causality assessments was recorded 3.5-fold more often in primary data sources versus IRB adverse event descriptions (93% versus 26%, P < 0.05). Some key clinical information was discrepant between the two sources. Conclusions The use of structured syndrome-specific case report forms could enhance the quality of reporting to IRBs, thereby improving the safety of pharmaceuticals administered to cancer patients. PMID:19458059

  11. Determining molecular predictors of adverse drug reactions with causality analysis based on structure learning

    PubMed Central

    Liu, Mei; Cai, Ruichu; Hu, Yong; Matheny, Michael E; Sun, Jingchun; Hu, Jun; Xu, Hua

    2014-01-01

    Objective Adverse drug reaction (ADR) can have dire consequences. However, our current understanding of the causes of drug-induced toxicity is still limited. Hence it is of paramount importance to determine molecular factors of adverse drug responses so that safer therapies can be designed. Methods We propose a causality analysis model based on structure learning (CASTLE) for identifying factors that contribute significantly to ADRs from an integration of chemical and biological properties of drugs. This study aims to address two major limitations of the existing ADR prediction studies. First, ADR prediction is mostly performed by assessing the correlations between the input features and ADRs, and the identified associations may not indicate causal relations. Second, most predictive models lack biological interpretability. Results CASTLE was evaluated in terms of prediction accuracy on 12 organ-specific ADRs using 830 approved drugs. The prediction was carried out by first extracting causal features with structure learning and then applying them to a support vector machine (SVM) for classification. Through rigorous experimental analyses, we observed significant increases in both macro and micro F1 scores compared with the traditional SVM classifier, from 0.88 to 0.89 and 0.74 to 0.81, respectively. Most importantly, identified links between the biological factors and organ-specific drug toxicities were partially supported by evidence in Online Mendelian Inheritance in Man. Conclusions The proposed CASTLE model not only performed better in prediction than the baseline SVM but also produced more interpretable results (ie, biological factors responsible for ADRs), which is critical to discovering molecular activators of ADRs. PMID:24334612

  12. Clinically Inconsequential Alerts: The Characteristics of Opioid Drug Alerts and Their Utility in Preventing Adverse Drug Events in the Emergency Department

    PubMed Central

    Genco, Emma K.; Forster, Jeri E.; Flaten, Hanna; Goss, Foster; Heard, Kennon J.; Hoppe, Jason; Monte, Andrew A.

    2016-01-01

    Study objective We examine the characteristics of clinical decision support alerts triggered when opioids are prescribed, including alert type, override rates, adverse drug events associated with opioids, and preventable adverse drug events. Methods This was a retrospective chart review study assessing adverse drug event occurrences for emergency department (ED) visits in a large urban academic medical center using a commercial electronic health record system with clinical decision support. Participants include those aged 18 to 89 years who arrived to the ED every fifth day between September 2012 and January 2013. The main outcome was characteristics of opioid drug alerts, including alert type, override rates, opioid-related adverse drug events, and adverse drug event preventability by clinical decision support. Results Opioid drug alerts were more likely to be overridden than nonopioid alerts (relative risk 1.35; 95% confidence interval [CI] 1.21 to 1.50). Opioid drug-allergy alerts were twice as likely to be overridden (relative risk 2.24; 95% CI 1.74 to 2.89). Opioid duplicate therapy alerts were 1.57 times as likely to be overridden (95% CI 1.30 to 1.89). Fourteen of 4,581 patients experienced an adverse drug event (0.31%; 95% CI 0.15% to 0.47%), and 8 were due to opioids (57.1%). None of the adverse drug events were preventable by clinical decision support. However, 46 alerts were accepted for 38 patients that averted a potential adverse drug event. Overall, 98.9% of opioid alerts did not result in an actual or averted adverse drug event, and 96.3% of opioid alerts were overridden. Conclusion Overridden opioid alerts did not result in adverse drug events. Clinical decision support successfully prevented adverse drug events at the expense of generating a large volume of inconsequential alerts. To prevent 1 adverse drug event, providers dealt with more than 123 unnecessary alerts. It is essential to refine clinical decision support alerting systems to eliminate

  13. Adverse Health Effects in Relation to Urban Residential Soundscapes

    NASA Astrophysics Data System (ADS)

    SKÅNBERG, A.; ÖHRSTRÖM, E.

    2002-02-01

    Noise pollution from road traffic in residential areas is a growing environmental problem. New approaches to turn the negative trend are needed. The programme “Soundscape Support to Health” will achieve new knowledge about the adverse health effects of noise pollution on humans and will investigate the link between well-being and health and perceived soundscapes for optimizing the acoustic soundscapes in urban residential areas. This paper will briefly present the programme and presents preliminary results from the first study of how various adverse health effects are related to individual noise exposures among individuals in residential areas with and without access to a quiet side of the dwelling.

  14. 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

  15. 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. PMID:26141794

  16. Successful Drug Development Despite Adverse Preclinical Findings Part 1: Processes to Address Issues and Most Important Findings

    PubMed Central

    Kuroda, Junji; Plassmann, Stephanie; Prentice, David E.

    2010-01-01

    Unexpected adverse preclinical findings (APFs) are not infrequently encountered during drug development. Such APFs can be functional disturbances such as QT prolongation, morphological toxicity or carcinogenicity. The latter is of particular concern in conjunction with equivocal genotoxicity results. The toxicologic pathologist plays an important role in recognizing these effects, in helping to characterize them, to evaluate their risk for man, and in proposing measures to mitigate the risk particularly in early clinical trials. A careful scientific evaluation is crucial while termination of the development of a potentially useful drug must be avoided. This first part of the review discusses processes to address unexpected APFs and provides an overview over typical APFs in particular classes of drugs. If the mode of action (MoA) by which a drug candidate produces an APF is known, this supports evaluation of its relevance for humans. Tailor-made mechanistic studies, when needed, must be planned carefully to test one or several hypotheses regarding the potential MoA and to provide further data for risk evaluation. Safety considerations are based on exposure at no-observed-adverse-effect levels (NOAEL) of the most sensitive and relevant animal species and guide dose escalation in clinical trials. The availability of early markers of toxicity for monitoring of humans adds further safety to clinical studies. Risk evaluation is concluded by a weight of evidence analysis (WoE) with an array of parameters including drug use, medical need and alternatives on the market. In the second part of this review relevant examples of APFs will be discussed in more detail. PMID:22272031

  17. Patterns of Adverse Drug Reactions in Different Age Groups: Analysis of Spontaneous Reports by Community Pharmacists

    PubMed Central

    Yu, Yun Mi; Shin, Wan Gyoon; Lee, Ju-Yeun; Choi, Soo An; Jo, Yun Hee; Youn, So Jung; Lee, Mo Se; Choi, Kwang Hoon

    2015-01-01

    Purpose To evaluate the clinical manifestations and causative drugs associated with adverse drug reactions (ADRs) spontaneously reported by community pharmacists and to compare the ADRs by age. Methods ADRs reported to the Regional Pharmacovigilance Center of the Korean Pharmaceutical Association by community pharmacists from January 2013 to June 2014 were included. Causality was assessed using the WHO-Uppsala Monitoring Centre system. The patient population was classified into three age groups. We analyzed 31,398 (74.9%) ADRs from 9,705 patients, identified as having a causal relationship, from a total pool of 41,930 ADRs from 9,873 patients. Median patient age was 58.0 years; 66.9% were female. Results Gastrointestinal system (34.4%), nervous system (14.4%), and psychiatric (12.1%) disorders were the most frequent symptoms. Prevalent causative drugs were those for acid-related disorders (11.4%), anti-inflammatory products (10.5%), analgesics (7.2%), and antibacterials (7.1%). Comparisons by age revealed diarrhea and antibacterials to be most commonly associated with ADRs in children (p < 0.001), whereas dizziness was prevalent in the elderly (p < 0.001). Anaphylactic reaction was the most frequent serious event (19.7%), mainly associated with cephalosporins and non-steroidal anti-inflammatory drugs. Among 612 ADRs caused by nonprescription drugs, the leading symptoms and causative drugs were skin disorders (29.6%) and non-steroidal anti-inflammatory drugs (16.2%), respectively. Conclusions According to the community pharmacist reports, the leading clinical manifestations and causative drugs associated with ADRs in outpatients differed among age groups. PMID:26172050

  18. Development and Validation of a Risk Model for Predicting Adverse Drug Reactions in Older People during Hospital Stay: Brighton Adverse Drug Reactions Risk (BADRI) Model

    PubMed Central

    Tangiisuran, Balamurugan; Scutt, Greg; Stevenson, Jennifer; Wright, Juliet; Onder, G.; Petrovic, M.; van der Cammen, T. J.; Rajkumar, Chakravarthi; Davies, Graham

    2014-01-01

    Background Older patients are at an increased risk of developing adverse drug reactions (ADR). Of particular concern are the oldest old, which constitute an increasingly growing population. Having a validated clinical tool to identify those older patients at risk of developing an ADR during hospital stay would enable healthcare staff to put measures in place to reduce the risk of such an event developing. The current study aimed to (1) develop and (2) validate an ADR risk prediction model. Methods We used a combination of univariate analysis and multivariate binary logistic regression to identify clinical risk factors for developing an ADR in a population of older people from a UK teaching hospital. The final ADR risk model was then validated in a European population (European dataset). Results Six-hundred-ninety patients (median age 85 years) were enrolled in the development stage of the study. Ninety-five reports of ADR were confirmed by independent review in these patients. Five clinical variables were identified through multivariate analysis and included in our final model; each variable was attributed a score of 1. Internal validation produced an AUROC of 0.74, a sensitivity of 80%, and specificity of 55%. During the external validation stage the AUROC was 0.73, with sensitivity and specificity values of 84% and 43% respectively. Conclusions We have developed and successfully validated a simple model to use ADR risk score in a population of patients with a median age of 85, i.e. the oldest old. The model is based on 5 clinical variables (≥8 drugs, hyperlipidaemia, raised white cell count, use of anti-diabetic agents, length of stay ≥12 days), some of which have not been previously reported. PMID:25356898

  19. Rapidly Progressing Severe Cutaneous Adverse Reaction With Acute Kidney Injury After Drug Exposure: An Uncommon Presentation.

    PubMed

    Rodgers, Bradley K; Kumar, Avinash B

    2016-01-01

    Toxic epidermal necrolysis syndrome (TEN) is a rare severe cutaneous adverse drug reaction that involves skin and mucous membranes. We describe a case of TEN presenting with stage III acute kidney injury, rhabdomyolysis, and acute respiratory failure likely triggered by allopurinol for recently diagnosed gout. Prompt diagnosis, multidisciplinary management, including aggressive resuscitation, cardiorespiratory support, intravenous immunoglobulin therapy, and daily wound care resulted in a positive outcome despite a predicted mortality greater than 60%. Although allopurinol is a known triggering agent, TEN presenting with rhabdomyolysis and acute kidney injury is rare. PMID:24832386

  20. 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. PMID:26262252

  1. High Yield Research Opportunities in Geriatric Emergency Medicine: Prehospital Care, Delirium, Adverse Drug Events, and Falls

    PubMed Central

    Carpenter, Christopher R.; Shah, Manish N.; Hustey, Fredric M.; Heard, Kennon; Gerson, Lowell W.

    2011-01-01

    Emergency services constitute crucial and frequently used safety nets for older persons, an emergency visit by a senior very often indicates high vulnerability for functional decline and death, and interventions via the emergency system have significant opportunities to change the clinical course of older patients who require its services. However, the evidence base for widespread employment of emergency system-based interventions is lacking. In this article, we review the evidence and offer crucial research questions to capitalize on the opportunity to optimize health trajectories of older persons seeking emergency care in four areas: prehospital care, delirium, adverse drug events, and falls. PMID:21498881

  2. Building an ontology of adverse drug reactions for automated signal generation in pharmacovigilance.

    PubMed

    Henegar, Corneliu; Bousquet, Cédric; Lillo-Le Louët, Agnès; Degoulet, Patrice; Jaulent, Marie-Christine

    2006-01-01

    Automated signal generation in pharmacovigilance implements unsupervised statistical machine learning techniques in order to discover unknown adverse drug reactions (ADR) in spontaneous reporting systems. The impact of the terminology used for coding ADRs has not been addressed previously. The Medical Dictionary for Regulatory Activities (MedDRA) used worldwide in pharmacovigilance cases does not provide formal definitions of terms. We have built an ontology of ADRs to describe semantics of MedDRA terms. Ontological subsumption and approximate matching inferences allow a better grouping of medically related conditions. Signal generation performances are significantly improved but time consumption related to modelization remains very important. PMID:16185681

  3. Dermatologic adverse effects of antiretroviral therapy: recognition and management.

    PubMed

    Luther, Jay; Glesby, Marshall J

    2007-01-01

    Despite the decrease in opportunistic infections associated with HIV in the highly active antiretroviral treatment (HAART) era, a significant number of patients still present with skin pathology, some of which can be attributed directly or indirectly to antiretroviral therapy. The non-nucleoside reverse transcriptase inhibitors exhibit a class effect with regard to skin adverse manifestations, and the spectrum of disease can vary from a mild morbilliform rash to Stevens-Johnson syndrome. Certain protease inhibitors are associated with rash, and indinavir causes retinoid-like manifestations such as paronychia, alopecia, ingrown toe-nails, and curling of straight hair. Abacavir, a nucleoside reverse transcriptase inhibitor, is notorious for causing a hypersensitivity reaction in select patients. The fusion inhibitor enfuvirtide causes injection-site reactions in the overwhelming majority of patients, although a new method of delivery has decreased the rate and severity of these reactions. A syndrome of lipoatrophy with or without lipohypertrophy, often termed lipodystrophy, has been described in patients receiving HAART. Potential management of lipoatrophy includes switching antiretrovirals and surgical treatment with facial fillers. Lastly, skin manifestations of the immune reconstitution inflammatory syndrome, including herpes zoster and warts, must be recognized and treated accordingly. In the evaluation of the individual HIV-infected patient receiving antiretroviral therapy who presents with a skin disorder, clinicians should consider the CD4 cell count as a marker of the degree of immunodeficiency, the specific antiretrovirals used, and the timing of the initiation of antiretroviral therapy in order to formulate a rational differential diagnosis. Management should be individualized based on the specific drug that is implicated and the severity of the reaction. PMID:17645377

  4. [Side effects of drugs on the oral cavity].

    PubMed

    Bascones-Martínez, Antonio; Muñoz-Corcuera, Marta; Bascones-Ilundain, Cristina

    2015-02-01

    Although drugs are the most powerful therapeutic tools we have for improving the quality of life of the population, their use is not free of adverse effects. Today there are many polymedicated patients, and it is difficult to find the cause of their adverse effects that increase exponentially when more than 4 drugs are combined. There are a large number of drugs that can result in numerous adverse effects in the oral cavity. The most common are xerostomia, altered taste, gingival enlargement and mucositis caused by cancer treatment. We also review other disorders of the salivary glands, oral mucosal changes, pigmentations, halitosis, osteonecrosis, opportunistic infections and bleeding diathesis. PMID:24629691

  5. Skin-lightening cosmetics: frequent, potentially severe adverse effects.

    PubMed

    2011-09-01

    Skin-lightening cosmetics are used by many women and men around the world. The products contain a variety of substances, which are often unknown to the users. Most of these products include topical corticosteroids, hydroquinone and mercury salts. Many other substances may be added. Several surveys and cohort studies, including several thousand individuals, have shown that regular application of skin-lightening cosmetics to large surface areas can have irreversible cutaneous adverse effects, such as patchy hyper- or hypopigmentation, skin atrophy, stretch marks and delayed wound healing, and can also mask or, on the contrary, promote or reactivate skin infections. Cases of skin cancer have been attributed to skin-lightening cosmetics. A Senegalese cohort study of 147 women showed a statistically significant increase in the risk of hypertension and diabetes linked to the use of skin-lightening agents. Other systemic adverse effects attributed to skin-lightening cosmetics include Cushing's syndrome, adrenal insufficiency, nephrotic syndrome, neurological disorders, and ocular disorders. Hypersensitivity reactions, including anaphylaxis, have also been attributed to these products. Many skin-lightening cosmetics contain substances that can harm the unborn child. For example, tretinoin is teratogenic while salicylic acid is feto-toxic. In practice, users are often unaware of the risk of severe adverse effects associated with skin-lightening cosmetics. Users should be informed of these adverse effects and encouraged to stop using these products, especially when skin disorders appear. PMID:21954516

  6. 15 CFR 971.602 - Significant adverse environmental effects.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... no significant adverse environmental effect. NOAA believes that exploration-type activities, as listed in the license regulations (15 CFR 970.701), require no further environmental assessment. (e... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR COMMERCIAL RECOVERY...

  7. 15 CFR 971.602 - Significant adverse environmental effects.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... no significant adverse environmental effect. NOAA believes that exploration-type activities, as listed in the license regulations (15 CFR 970.701), require no further environmental assessment. (e... REGULATIONS OF THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR COMMERCIAL RECOVERY...

  8. 15 CFR 971.602 - Significant adverse environmental effects.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... significant adverse environmental effect or impact (for the purposes of sections 103(a)(2)(D), 105(a)(4), 106.... Determinations will be based upon the best information available, including relevant environmental impact... listed in the license regulations (15 CFR 970.701), require no further environmental assessment....

  9. 15 CFR 971.602 - Significant adverse environmental effects.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... significant adverse environmental effect or impact (for the purposes of sections 103(a)(2)(D), 105(a)(4), 106.... Determinations will be based upon the best information available, including relevant environmental impact... listed in the license regulations (15 CFR 970.701), require no further environmental assessment....

  10. 15 CFR 971.602 - Significant adverse environmental effects.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... significant adverse environmental effect or impact (for the purposes of sections 103(a)(2)(D), 105(a)(4), 106.... Determinations will be based upon the best information available, including relevant environmental impact... listed in the license regulations (15 CFR 970.701), require no further environmental assessment....

  11. A Prospective, Observational Study of Adverse Reactions to Drug Regimen for Multi-Drug Resistant Pulmonary Tuberculosis in Central India

    PubMed Central

    Hire, Rohan; Kale, A. S.; Dakhale, G. N.; Gaikwad, Nilesh

    2014-01-01

    Objective 1) To assess the adverse drug reactions (ADRs) of second-line anti-tubercular drugs used to treat Multi-drug resistant Tuberculosis (MDR-TB) in central India on the basis of causality, severity and avoidability scales. 2) To investigate the relationship of MDR-TB (primary or secondary) and the presence of diabetes mellitus (DM) with mean smear conversion time. Material and Methods: A prospective, observational study was carried out on diagnosed multidrug-resistant tuberculosis patients enrolled for DOTS-Plus regimen at TB and Chest Disease Department from January 2012 to December 2012 with a follow-up of nine months. Encountered ADRs were noted along with the time of sputum conversion. Results Total 64 ADRs were reported in 55 patients out of total 110 patients (n=110). As per the Naranjo causality assessment of ADRs, seven patients had definite, 45 had probable, and 3 had possible causal relation with drugs of DOTS-Plus regimen. As per the Hartwig’s severity assessment scale, there were total 7 ADRs in Level 1, 6 in Level 2, 33 in Level 3 and 9 in Level 4. Hallas avoidability assessment scale divided the ADRs as 3 being definitely avoidable, 26 possibly avoidable, 23 not avoidable and three not evaluable. Mean sputum smear conversion time was significantly higher in patients with a secondary type than that of primary type of MDR TB and in patients with DM than those without DM. Conclusion ADRs were common in patients of MDR-TB on DOTs-Plus drug regimen. It was due to lack of availability of safer and equally potent drugs in DOTs-Plus drug regimen compared to DOTS regimen in non-resistant TB. The frequency and severity of ADRs can be reduced by strict vigilance about known and unknown ADRs, monitoring their laboratory and clinical parameters and instituting appropriate measures. PMID:25237474

  12. Adverse psychosocial outcomes associated with drug use among US high school seniors: a comparison of alcohol and marijuana

    PubMed Central

    Palamar, Joseph J.; Fenstermaker, Michael; Kamboukos, Dimitra; Ompad, Danielle C.; Cleland, Charles M.; Weitzman, Michael

    2015-01-01

    Objectives There is debate about whether marijuana (cannabis) use is more dangerous than alcohol use. Although difficult to make objective comparisons, research is needed to compare relative dangers in order to help inform preventive efforts and policy. Methods Data were analyzed from a nationally representative sample of high school seniors in the Monitoring the Future study (2007–2011; Weighted n = 7437; modal age: 18) who reported lifetime use of alcohol or marijuana. Students were asked to indicate whether they experienced various adverse psychosocial outcomes resulting from use of each substance. We examined which outcomes were more prevalent for each substance. Results Compared to alcohol use, marijuana use was more commonly reported to compromise relationships with teachers or supervisors, result in less energy or interest, and result in lower school or job performance. Compared to marijuana use, alcohol was more commonly reported to compromise relationships with friends and significant others; it was also reported to lead to more regret (particularly among females), and driving unsafely. Marijuana users were more likely to report no adverse outcomes. Females and white students were more likely to report various adverse outcomes and higher frequency use of each substance also increased occurrences of reported adverse outcomes. Conclusions Marijuana and alcohol are associated with unique adverse psychosocial outcomes. Outcomes differ by sex and race/ethnicity, and perception or experience of outcomes may also be related to legal status and associated stigma. Public health interventions may be more effective by focusing on harm reduction strategies for these drug-specific outcomes. PMID:25169838

  13. Adverse drug reactions to fluoroquinolones at a tertiary care hospital in northern India.

    PubMed

    Uppal, R; Jhaj, R; Malhotra, S

    1998-11-01

    Use of fluoroquinolones has increased considerably in the last 5-6 years in our hospitals. With a view to ascertain their safety and the type of adverse drug reactions (ADRs) in our population, spontaneous reports were collected and analysed to ciprofloxacin (the most prescribed fluoroquinolone in our hospital) over a period of three and a half years. The pattern of reactions were rash in 18, severe reactions like Steven Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in 4, gastritis and diarrhoea in 3, shivering and rigors in 2, hemorrhagic purpuric spots in 2 and oedema of eye and lids with topical application in 1 patient. Most cases recovered on stoppage of the drug and symptomatic treatment. However, one case of SJS and one of TEN proved fatal. Care needs to be exercised in their use and they do not appear to be innocuous to severe and disturbing ADRs. PMID:11229222

  14. ADEpedia: A Scalable and Standardized Knowledge Base of Adverse Drug Events Using Semantic Web Technology

    PubMed Central

    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. PMID:22195116

  15. 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. PMID:22195116

  16. Incidence of adverse cutaneous drug reactions in 22,866 Chinese inpatients: a prospective study.

    PubMed

    Tian, Xiao-Yin; Liu, Bing; Shi, Hao; Zhao, Zi-Ran; Zhou, Xi-Ping; Zhang, Tao; Sun, Qiu-Ning; Zuo, Ya-Gang

    2015-11-01

    Cutaneous adverse drug reactions (ADRs) are common. However, no prospective study assessing cutaneous ADRs is available for Chinese populations. This study aimed to assess the incidence, manifestations, causative drugs, and other factors related to cutaneous ADRs. A total of 22,866 inpatients were surveyed prospectively from January to April 2012 at the Peking Union Medical College Hospital. Only cutaneous ADRs induced by systemic drugs were considered. Fifty cases were confirmed as cutaneous ADRs, for an estimated incidence of 2.2 per 1000 during this period (95 % confidence interval 1.6-2.8). Cases of cutaneous ADRs comprised 69 % females, while 63 % of all inpatients were female (χ (2) = 0.641, P = 0.427). The department of infectious diseases was the most frequently involved department. Morbilliform exanthema (40 %) was the most frequent cutaneous ADR, followed by urticaria (23.1 %). Anti-infection drugs (36.9 %) caused most cases of cutaneous ADRs, followed by iodinated contrast media (ICM, 18.5 %) and non-steroidal anti-inflammatory drugs (NSAIDs, 18.5 %). The most frequently associated disorders were cancer (24 %), infection (22 %), cardiovascular and cerebrovascular diseases (20 %), and autoimmune diseases (18 %). In this first prospective study assessing the incidence of cutaneous ADRs in China, anti-infection drugs were the most commonly involved drugs, followed by ICM and NSAIDs. No evidence of increased cutaneous ADR incidence in AIDS or SLE patients was observed. Our findings indicate that cancer and its treatments were often related to cutaneous ADRs in China. PMID:26246330

  17. Adverse Drug Reactions: A Retrospective Review of Hospitalized Patients at a State Psychiatric Hospital

    PubMed Central

    Iuppa, Courtney A.; Nelson, Leigh Anne; Elliott, Ellie; Sommi, Roger W.

    2013-01-01

    Background: There is a paucity of information regarding adverse drug reactions (ADRs) in psychiatric patients. Information on common and preventable ADRs (pADRs) in psychiatric patients will allow for targeted improvement projects. Objective: To characterize reported ADRs and pharmacist interventions to prevent ADRs in an extended-care state psychiatric hospital. Methods: Four years of ADR reports were assessed for probability, reaction severity, pharmacological class of medication involved, preventability, change in therapy, and transfers to a medical facility. The pharmacist intervention database was queried for interventions classified as “prevention of ADR.” The interventions were assessed for type of medication and recommendation acceptance. Results: Medication classes responsible for ADRs included mood stabilizers (30%), typical antipsychotics (25%), atypical antipsychotics (25%), and antidepressants (8%). Nine percent resulted in transfer to a medical facility. Of all ADRs, 34.4% were pADRs; mood stabilizers (41%) and atypical antipsychotics (27%) were the most common pADRs. The most common causes of pADRs were supratherapeutic serum concentrations, drug-drug interactions, and history of reaction. There were 87 pharmacist interventions that were classified as “prevention of ADR,” and the acceptance rate of pharmacists’ recommendations was 96.5%. Mood stabilizers (20%), atypical antipsychotics (17%), and typical antipsychotics (11%) were commonly associated with prevented ADRs. Lithium accounted for 13.8% of prevented ADRs; these ADRs were most often due to a drug–drug interaction with a nonsteroidal anti-inflammatory drug. Conclusions: ADRs were most commonly associated with mood stabilizers and antipsychotics, and pADRs were common. There is an opportunity to provide education to medical staff on therapeutic drug monitoring and drug–drug interactions for these classes, particularly lithium. PMID:24474834

  18. Retrospective Analysis of Pattern of Cutaneous Adverse Drug Reactions in Tertiary Hospital of Pauri Garhwal

    PubMed Central

    Dimri, Deepak; Thapliyal, Swati; Thawani, Vijay

    2016-01-01

    Introduction Cutaneous Adverse Drug Reactions (CADR) are the common drug induced adverse reactions which usually have wide range of manifestations and severity. Aim To describe the prevalence and clinical spectrum of CADR’s in a tertiary hospital of the Garhwal region in Uttarakhand, India. Materials and Methods All patients suspected of having CADRs reported in the various out-patient departments, and in-patients of HNB Base & Teaching Hospital, from 1st January 2012 to 31st December 2014 were retrospectively analysed. Drug history was recorded in a format specified in Indian National Pharmacovigilance Programme. Results Total 111 cases of CADRs were reported from Jan 2012 to Dec 2014. Mean age of patients was 33.34±18.7 years and maximum ADRs were reported in the age group of 20-39 years (36.9%). Female were affected more than male (W:M :: 66:45). Most of the ADRs were exanthematous eruptions (EE) type (33.3%). Medicine department reported maximum cases of CADRs (47.7%), followed by Dermatology. Most of the CADRs were reported with antimicrobial agents (69.4%). Significant associations of different types of various cutaneous reactions were observed in relation to the duration (in days) of ADRs (p = 0.038), types of outcome (p= 0.006), different departments (p= 0.014) and between different groups of medicines (p = 0.008). Conclusion CADRs have proved a significant problem in healthcare for decades. Major bulk of CADR result from physician prescribed drugs. Hence, awareness on part of the physician can help in timely detection of cutaneous reactions, thereby restricting damage from them. PMID:27437240

  19. Implementing a pharmacovigilance program to evaluate cutaneous adverse drug reactions in an antiretroviral access program

    PubMed Central

    Mudzviti, Tinashe; Sibanda, Marvelous; Gavi, Samuel; Maponga, Charles Chiedza; Morse, Gene D.

    2012-01-01

    Background Cutaneous adverse drug reactions (cADRs) can cause significant morbidity and distress in patients especially in the HIV infected population on antiretroviral therapy. Adverse Drug Reaction monitoring and ascertaining causality in resource limited settings still remains a challenge. This study was carried out to evaluate causality and measure incidence of cADRs in HIV infected patients on highly active antiretroviral therapy. The study was also designed to test a 3-step approach in the monitoring and evaluation of ADRs in resource limited settings. Methodology A retrospective patient medical records review was carried out at the Parirenyatwa Family Care Centre, (Harare, Zimbabwe). Cases of cADRs were reported to the Medicines Control Authority of Zimbabwe (Drug regulating body in Zimbabwe) for assessment and causality classification. Results Two hundred and twenty-one patient records were randomly selected and reviewed to determine if any diagnosis of cADRs was made by clinicians. Causality assessment revealed 13.1% of cADRs which were due to an offending agent in the antiretroviral therapy against an initial incidence of 17.6% which had been determined by the physicians. Conclusions cADRs had an incidence of 13.1% within the population under study due to non nucleoside reverse transcriptase inhibitors (NNRTIs). Most reactions were due to the NNRTIs which contributed 72.4 % of all cADRs. A panel of experts from the drug regulatory authority can be used as an implementation based mechanism in ascertaining causality objectively in settings where resources are constrained. PMID:23277506

  20. Discrepancies in listed adverse drug reactions in pharmaceutical product information supplied by the regulatory authorities in Denmark and the USA.

    PubMed

    Eriksson, Robert; Aagaard, Lise; Jensen, Lars Juhl; Borisova, Liza; Hørlück, Dorte; Brunak, Søren; Hansen, Ebba Holme

    2014-06-01

    Pharmaceutical product information (PI) supplied by the regulatory authorities serves as a source of information on safe and effective use of drugs. The objectives of this study were to qualitatively and quantitatively compare PIs for selected drugs marketed in both Denmark and the USA with respect to consistency and discrepancy of listed adverse drug reaction (ADR) information. We compared individual ADRs listed in PIs from Denmark and the USA with respect to type and frequency. Consistency was defined as match of ADRs and of ADR frequency or match could not be ruled out. Discrepancies were defined as ADRs listed only in one country or listed with different frequencies. We analyzed PIs for 40 separate drugs from ten therapeutic groups and assigned the 4003 identified ADRs to System Organ Classes (Medical Dictionary for Regulatory Activities [MedDRA] terminology). Less than half of listed ADRs (n = 1874; 47%) showed consistency. Discrepancies (n = 2129; 53%) were split into ADRs listed only in the USA (n = 1558; 39%), ADRs listed only in Denmark (n = 325; 8%) and ADRs listed with different frequencies (n = 246; 6%). The majority of listed ADRs were of the type "gastrointestinal disorders" and "nervous system disorders". Our results show great differences in PIs for drugs approved in both Denmark and the USA illuminating concerns about the credibility of the publicly available PIs. The results also represent an argument for further harmonization across borders to improve consistency between authority-supplied information. PMID:25505588

  1. Sumatriptan overuse in episodic cluster headache: lack of adverse events, rebound syndromes, drug dependence and tachyphylaxis.

    PubMed

    Centonze, V; Bassi, A; Causarano, V; Dalfino, L; Cassiano, M A; Centonze, A; Fabbri, L; Albano, O

    2000-01-01

    This observational study was designed to examine the pattern of sumatriptan use in patients with cluster headache using more than the recommended daily dose of subcutaneously injected (s.c.) sumatriptan. Thirteen patients suffering from episodic cluster headache were asked to record the characteristics of their attacks and drug intake for 1 year. All reported a high daily frequency of attacks (more than 3 per day) and the related overuse of s.c. sumatriptan. The results show that the overall incidence of adverse events among patients receiving sumatriptan injections for the treatment of cluster headache is low. The extended administration of this drug in episodic cluster headache did not result in tolerance problems or tachyphylaxis. Only 4 patients experienced minor adverse events and recovered more slowly than the others. They suffered from migraine without aura and cluster headache, and showed a family history of migraine. Even though they must be viewed with caution, due to the observational nature of the study and the low number of patients included, these results suggest that the profile of sumatriptan may differ in cluster headache compared with migraine. PMID:11062845

  2. Effect of wettability on adverse mobility immiscible floods

    SciTech Connect

    Vives, M.T.; Chang, Y.C.; Mohanty, K.K.

    1995-12-31

    Many immiscible displacements in reservoirs occur at adverse mobility. Effect of wettability on these displacements is not well understood and often ignored in reservoir simulation. Recent macroscopic theories of viscous fingering treat adverse immiscible flows similar to miscible flows, the mixing in the fingered region being controlled by a Todd-Longstaff-type functional form. The wettability of the medium is taken into account only through the use of appropriate relative permeabilities. The goal of this paper is to understand the macroscopic bypassing in adverse mobility immiscible floods. Immiscible displacements are conducted in a quarter 5-spot model in both drainage and imbibition modes at similar effective mobility ratios and viscous-to-gravity numbers. The level of bypassing and gravity override is visualized and measured. Tertiary water-alternating-gas (WAG) displacements are also conducted at various WAG ratios and viscosity ratios. Fractional flow analysis and numerical simulation are used to understand these displacements. Experiments show that macroscopic viscous fingering is present in adverse viscosity immiscible displacements where no saturation shock is expected from 1-D fractional flow theory. Bypassing due to both fingering and gravity override is higher in the drainage mode than in the imbibition mode, with other key parameters being the same. Optimum WAG ratio in water-wet rock is a function of oil/solvent viscosity ratio. The macroscopic flow theory needs to include capillarity and viscous fingering to match these experimental findings.

  3. Systematic Analysis of the Associations between Adverse Drug Reactions and Pathways

    PubMed Central

    Chen, Xiaowen; Wang, Yanqiu; Wang, Pingping; Lian, Baofeng; Li, Chunquan; Wang, Jing; Li, Xia; Jiang, Wei

    2015-01-01

    Adverse drug reactions (ADRs) are responsible for drug candidate failure during clinical trials. It is crucial to investigate biological pathways contributing to ADRs. Here, we applied a large-scale analysis to identify overrepresented ADR-pathway combinations through merging clinical phenotypic data, biological pathway data, and drug-target relations. Evaluation was performed by scientific literature review and defining a pathway-based ADR-ADR similarity measure. The results showed that our method is efficient for finding the associations between ADRs and pathways. To more systematically understand the mechanisms of ADRs, we constructed an ADR-pathway network and an ADR-ADR network. Through network analysis on biology and pharmacology, it was found that frequent ADRs were associated with more pathways than infrequent and rare ADRs. Moreover, environmental information processing pathways contributed most to the observed ADRs. Integrating the system organ class of ADRs, we found that most classes tended to interact with other classes instead of themselves. ADR classes were distributed promiscuously in all the ADR cliques. These results reflected that drug perturbation to a certain pathway can cause changes in multiple organs, rather than in one specific organ. Our work not only provides a global view of the associations between ADRs and pathways, but also is helpful to understand the mechanisms of ADRs. PMID:26495310

  4. Factors Affecting the Timing of Signal Detection of Adverse Drug Reactions.

    PubMed

    Hashiguchi, Masayuki; Imai, Shungo; Uehara, Keiko; Maruyama, Junya; Shimizu, Mikiko; Mochizuki, Mayumi

    2015-01-01

    We investigated factors affecting the timing of signal detection by comparing variations in reporting time of known and unknown ADRs after initial drug release in the USA. Data on adverse event reactions (AERs) submitted to U.S. FDA was used. Six ADRs associated with 6 drugs (rosuvastatin, aripiprazole, teriparatide, telithromycin, exenatide, varenicline) were investigated: Changes in the proportional reporting ratio, reporting odds ratio, and information component as indexes of signal detection were followed every 3 months after each drugs release, and the time for detection of signals was investigated. The time for the detection of signal to be detected after drug release in the USA was 2-10 months for known ADRs and 19-44 months for unknown ones. The median lag time for known and unknown ADRs was 99.0-122.5 days and 185.5-306.0 days, respectively. When the FDA released advisory information on rare but potentially serious health risks of an unknown ADR, the time lag to report from the onset of ADRs to the FDA was shorter. This study suggested that one factor affecting signal detection time is whether an ADR was known or unknown at release. PMID:26641634

  5. Measuring the preventability of adverse drug reactions in France: A 2015 overview.

    PubMed

    Olivier-Abbal, Pascale

    2016-01-01

    In recent years, the preventability of adverse drug reactions (ADRs) has gradually gained ground as an additional criterion for assessing drug-related risk, alongside seriousness, causality mechanism of action or frequency. However, the definition of preventability itself remains a concept that needs to be defined clearly so as to compare study results. After an overview of the current methods of measuring preventability, which include a French instrument, this work proposes a synthesis of the French studies assessing the preventability of ADRs over the last 30 years. Measuring preventability is important to classify ADRs as preventable/not preventable, but the ultimate aim remains to characterize these preventable ADRs, highlighting the clinical situations and drug classes related to the risk. It is then possible to provide targeted clinical actions to correct these situations and improve the clinical use of these drugs. Thus, assessing medical preventability should address the causes of ADRs and not the responsibility of healthcare professionals. Finally, certain ideas are proposed to improve the French scale and pursue its validation. PMID:27080838

  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

    2010-01-01

    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. PMID:21347109

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

    PubMed Central

    2014-01-01

    Background 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. Methods 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). Results 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. Conclusions 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

  8. Thai traditional massage: Issues causing possible adverse effects.

    PubMed

    Wiwanitkit, Viroj

    2015-01-01

    Thai traditional massage is a widely used massage technique in Thailand and is presently accepted by local Thai Ministry of Public Health. The technique is promoted but not well accepted internationally. There is a concern about the effectiveness as well as safety of this local wisdom. After a recent episode of concurrent acute heart attack and Thai traditional massage in a patient, the issue of possible adverse effects of Thai traditional massage is being widely discussed. PMID:26865746

  9. Thai traditional massage: Issues causing possible adverse effects

    PubMed Central

    Wiwanitkit, Viroj

    2015-01-01

    Thai traditional massage is a widely used massage technique in Thailand and is presently accepted by local Thai Ministry of Public Health. The technique is promoted but not well accepted internationally. There is a concern about the effectiveness as well as safety of this local wisdom. After a recent episode of concurrent acute heart attack and Thai traditional massage in a patient, the issue of possible adverse effects of Thai traditional massage is being widely discussed. PMID:26865746

  10. A rare adverse reaction to ethambutol: drug-induced haemolytic anaemia.

    PubMed

    Nicolini, A; Perazzo, A; Gatto, P; Piroddi, I M G; Barlascini, C; Karamichali, S; Strada, P

    2016-05-01

    Anti-tuberculosis drugs seldom cause serious haematological side effects. However, among these drugs, isoniazid and rifampicin, especially when administered intermittently, may very rarely be linked to acute autoimmune haemolytic anaemia. Ethambutol (EMB) can cause dose-related retrobulbar neuritis. In this paper, we present the first reported case of acute fatal autoimmune haemolytic anaemia due to EMB. PMID:27084828

  11. Male central hypogonadism secondary to exogenous androgens: a review of the drugs and protocols highlighted by the online community of users for prevention and/or mitigation of adverse effects.

    PubMed

    Karavolos, Stamatios; Reynolds, Michael; Panagiotopoulou, Nikoletta; McEleny, Kevin; Scally, Michael; Quinton, Richard

    2015-05-01

    Androgen- or anabolic steroid-induced hypogonadism (ASIH) is no longer confined to professional athletes; its prevalence amongst young men and teenagers using androgens and/or anabolic steroids (AASs) is rising fast, and those affected can experience significant symptoms. Clinicians are increasingly encountering demanding, well-informed men affected by ASIH, yet lacking authoritative information on the subject may struggle to project a credible message. In this article, we overview the methods and drugs that men use in an attempt to counteract ASIH (with a view to either preventing its onset, or reversing it once it has developed) and summarize the scientific evidence underpinning these. The main channel for obtaining these drugs is the Internet, where they can be readily sourced without a valid prescription. An Internet search using relevant terms revealed a huge number of websites providing advice on how to buy and use products to counteract ASIH. Drugs arising repeatedly in our search included human chorionic gonadotrophin (hCG), selective oestrogen receptor modulators (SERMs) and aromatase inhibitors (AIs). The quality and accuracy of the online information was variable, but review of medical literature also highlighted a lack of scientific data to guide clinical practice. It is important for clinicians to be aware of the AAS user's self-treatment strategies with regard to ASIH side-effect mitigation. By ensuring that they are well-informed, clinicians are more likely to retain the credibility and trust of AAS users, who will in turn likely be more open to engage with appropriate management. PMID:25333666

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

    PubMed

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

    2012-04-15

    Somnambulism (sleepwalking) is a disorder of arousal that falls under "parasomnia" group and is more common in children. These phenomena occur as primary sleep events or secondary to systemic disease or can be drug induced. Medications that can cause sleepwalking include neuroleptics, hypnotics, lithium, amitriptyline, and β-blockers. This report presents an unusual adverse effect of topiramate on sleep in a patient with migraine. PMID:22505867

  13. 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. PMID:25711751

  14. The value of glucocorticoid co-therapy in different rheumatic diseases - positive and adverse effects

    PubMed Central

    2014-01-01

    Glucocorticoids play a pivotal role in the management of many inflammatory rheumatic diseases. The therapeutic effects range from pain relief in arthritides, to disease-modifying effects in early rheumatoid arthritis, and to strong immunosuppressive actions in vasculitides and systemic lupus erythematosus. There are multiple indications that adverse effects are more frequent with the longer use of glucocorticoids and use of higher dosages, but high-quality data on the occurrence of adverse effects are scarce especially for dosages above 10 mg prednisone daily. The underlying rheumatic disease, disease activity, risk factors and individual responsiveness of the patient should guide treatment decisions. Monitoring for adverse effects should also be tailored to the patient. Continuously balancing the benefits and risks of glucocorticoid therapy is recommended. There is an ongoing quest for new drugs with glucocorticoid actions without the potential to cause harmful effects, such as selective glucocorticoid receptor agonists, but the application of a new compound in clinical practice will probably not occur within the next few years. In the meantime, basic research on glucocorticoid effects and detailed reports on therapeutic efficacy and occurrence of adverse effects will be valuable in weighing benefits and risks in clinical practice. PMID:25608693

  15. Energy Drink Consumption: Beneficial and Adverse Health Effects

    PubMed Central

    Alsunni, Ahmed Abdulrahman

    2015-01-01

    Consumption of energy drinks has been increasing dramatically in the last two decades, particularly amongst adolescents and young adults. Energy drinks are aggressively marketed with the claim that these products give an energy boost to improve physical and cognitive performance. However, studies supporting these claims are limited. In fact, several adverse health effects have been related to energy drink; this has raised the question of whether these beverages are safe. This review was carried out to identify and discuss the published articles that examined the beneficial and adverse health effects related to energy drink. It is concluded that although energy drink may have beneficial effects on physical performance, these products also have possible detrimental health consequences. Marketing of energy drinks should be limited or forbidden until independent research confirms their safety, particularly among adolescents. PMID:26715927

  16. 40 CFR 159.184 - Toxic or adverse effect incident reports.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Toxic or adverse effect incident... Information § 159.184 Toxic or adverse effect incident reports. (a) General. Information about incidents... organism suffered a toxic or adverse effect, or may suffer a delayed or chronic adverse effect in...

  17. The adverse effects of sorafenib in patients with advanced cancers.

    PubMed

    Li, Ye; Gao, Zu-Hua; Qu, Xian-Jun

    2015-03-01

    Sorafenib is the first multi-kinase inhibitor (TKI) approved for the treatment of advanced hepatocellular cancer (HCC) and metastatic renal cell cancer (RCC) and is increasingly being used to treat patients with well-differentiated radioiodine-resistant thyroid cancer (DTC). Sorafenib demonstrates targeted activity on several families of receptor and non-receptor tyrosine kinases that are involved in angiogenesis, tumour growth and metastatic progression of cancer. Sorafenib treatment results in long-term efficacy and low incidence of life-threatening toxicities. Although sorafenib has demonstrated many benefits in patients, the adverse effects cannot be ignored. The most common treatment-related toxicities include diarrhoea, fatigue, hand-foot skin reaction and hypertension. Most of these toxicities are considered mild to moderate and manageable to varying degrees; however, cardiovascular events might lead to death. In this MiniReview, we summarize the adverse effects of sorafenib that commonly occur in patients with advanced cancers. PMID:25495944

  18. Spontaneous Reporting of Adverse Drug Reactions through Electronic Submission from Regional Society Healthcare Professionals in Korea

    PubMed Central

    Lee, Jae-Hyun; Park, Kyung Hee; Moon, Hyun Joo; Lee, Yong Won; Park, Jung-Won

    2012-01-01

    Purpose Pharmacovigilance Research Network built a spontaneous reporting system and collected adverse drug reactions (ADRs) by electronic submission (e-sub) in Korea. We analyzed ADRs spontaneously reported through e-sub from regional health professionals. Materials and Methods Nine hundred and thirty three ADR cases were collected and analyzed from January to December in 2008. "A matter" was defined as one symptom matched to one culprit drug included in an ADR case. We collected and analyzed e-sub ADR cases and matters to determine common culprits and organ specified ADR matters. Results There were 3,049 matters in 933 ADR cases for 1 year, and 3.3 matters per case were reported. In organ specific ADR classification, skin reactions which took the first place in 866 matters (28%) included urticaria and rash. The next cases were neurologic symptom (624 matters, 21%) and gastrointestinal symptom (581 matters, 19%). Doctor (53%) and pharmacist (31%) were the most important participants in e-sub spontaneous reporting system, and 3% of ADR cases were reported by patients or their guardians. WHO-Uppsala Monitoring Center causality assessment results showed certain 10.6%, probable 37.7%, possible 41.7% and below unlikely 10.0%. Culprit drugs were antibiotics (23.4%), neurologic agents (14.7%) and non-steroidal anti-inflammatory drugs (9.4%). Conclusion In our study, antibiotic was most common culprit drug, and skin manifestation was most common symptom in e-sub ADRs collected from regional healthcare practitioners in Korea. PMID:22869488

  19. Cutaneous adverse drug reaction type erythema multiforme major induced by eslicarbazepine

    PubMed Central

    Massot, Andreu; Gimenez-Arnau, Ana

    2014-01-01

    Severe skin reactions occur less frequently with eslicarbazepine (ESL) than with the other aromatic anticonvulsants. We report the first case of cutaneous adverse drug reaction (CADR) to ESL and co-sensitization between ESL and betalactams. A 41-year-old white woman developed focal epilepsy due to a meningioma that was removed. As post-operatory complication, she suffered meningitis as well as a maculo-papular erythema caused by the treatment with meropenem. Subsequently, ESL was started and gradually increased until 800 mg/day. Twenty-five days later, the patient developed an Erythema Multiforme Major (EMM). Strong positive immediate reaction was induced by prick test with carbamazepine (CBZ) and ESL at 0.01 and 0.1% within 15 and 30 minutes; however the delayed reading at 48 hours was negative. The patient was not carrier of the HLA alleles A3101 and B1502 associated with CBZ induced EMM. The hypersensitivity pathogenic mechanism of EMM is unclear and a delayed hypersensitivity process is speculated. However, the patch and intradermal tests in our patient did not show a delayed reaction but an immediate cutaneous one. A first allergic episode may elicit a massive nonspecific activation of the immune system, providing an enhanced expression of co-stimulatory molecules that decreases the level of tolerance to other drugs. When prescribing ESL, we suggest ruling out previous CADR, especially to CBZ and oxcarbazepine but also other chemically unrelated drugs such as beta-lactams. PMID:25422574

  20. Cutaneous adverse drug reaction type erythema multiforme major induced by eslicarbazepine.

    PubMed

    Massot, Andreu; Gimenez-Arnau, Ana

    2014-10-01

    Severe skin reactions occur less frequently with eslicarbazepine (ESL) than with the other aromatic anticonvulsants. We report the first case of cutaneous adverse drug reaction (CADR) to ESL and co-sensitization between ESL and betalactams. A 41-year-old white woman developed focal epilepsy due to a meningioma that was removed. As post-operatory complication, she suffered meningitis as well as a maculo-papular erythema caused by the treatment with meropenem. Subsequently, ESL was started and gradually increased until 800 mg/day. Twenty-five days later, the patient developed an Erythema Multiforme Major (EMM). Strong positive immediate reaction was induced by prick test with carbamazepine (CBZ) and ESL at 0.01 and 0.1% within 15 and 30 minutes; however the delayed reading at 48 hours was negative. The patient was not carrier of the HLA alleles A3101 and B1502 associated with CBZ induced EMM. The hypersensitivity pathogenic mechanism of EMM is unclear and a delayed hypersensitivity process is speculated. However, the patch and intradermal tests in our patient did not show a delayed reaction but an immediate cutaneous one. A first allergic episode may elicit a massive nonspecific activation of the immune system, providing an enhanced expression of co-stimulatory molecules that decreases the level of tolerance to other drugs. When prescribing ESL, we suggest ruling out previous CADR, especially to CBZ and oxcarbazepine but also other chemically unrelated drugs such as beta-lactams. PMID:25422574

  1. Research on Susceptible Genes and Immunological Pathogenesis of Cutaneous Adverse Drug Reactions in Chinese Hans.

    PubMed

    Yang, Fangping; Yang, Ying; Zhu, Qinyuan; Chen, Sheng-An; Fu, Xiaodan; Yan, Sijia; Meng, Chunjie; Ma, Li; Sun, Xinfen; Xu, Jinhua; Luo, Xiaoqun; Xing, Qinghe

    2015-07-01

    Cutaneous adverse drug reactions (cADRs) include mild maculopapular exanthems (MPE), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP). We used HLA high-resolution genotyping and genome wide association analysis (GWAS) to identify the genetic markers for cADRs induced by common culprit drugs in Han Chinese population. To further understand the immunopathogenesis of cADRs, and with the goal of developing treatment strategies, we compared the expression of cytoxic cytokines between the patients with cADRs and normal controls. Our data suggested that the carbamazepine induced SJS/TEN, allopurinol induced CADRs, methazolamide induced SJS/TEN and SASP induced DRESS were respectively strongly associated with HLA-B*15:02, HLA-B*58:01, HLA-B*59:01 and HLA-B*13:01. In addition, increased expression of cytotoxic cytokines in sera and tissues of cADRs patients were found, compared with healthy controls. Our findings may shed light on prediction and prevention of cADRs, provide clues to pathogenesis, and guide treatment strategies of these reactions. PMID:26067314

  2. The effects of air pollution on adverse birth outcomes

    PubMed Central

    Ha, Sandie; Hu, Hui; Roussos-Ross, Dikea; Haidong, Kan; Roth, Jeffrey; Xu, Xiaohui

    2014-01-01

    Background Air pollution has been shown to have adverse effects on many health outcomes including cardiorespiratory diseases and cancer. However, evidence on the effects of prenatal exposure is still limited. The purpose of this retrospective cohort study is to evaluate the effects of prenatal exposure to air pollutants including particulate matter with aerodynamic diameter less than 2.5 micrometer (PM2.5) and ozone (O3) on the risk of adverse birth outcomes (ABOs) including term low birth weight (LBW), preterm delivery (PTD) and very PTD (VPTD). Methods Singleton births from 2004–2005 in Florida were included in the study (N=423,719). Trimester-specific exposures to O3 and PM2.5 at maternal residence at delivery were estimated using the National Environmental Public Health Tracking Network data, which were interpolated using Hierarchical Bayesian models. Results After adjustment for potential confounders such as demographics, medical and lifestyle factors PM2.5 exposures in all trimesters were found to be significantly and positively associated with the risk of all ABOs. Second-trimester exposure had the strongest effects. For an interquartile range (IQR) increase in PM2.5 during the second trimester, the risk of term LBW, PTD and VPTD increased by 3% [95% confidence interval (CI): 1–6%)], 12% (11–14%) and 22% (18–25%), respectively. O3 was also found to be positively associated with PTD and VPTD with the strongest effects over the whole pregnancy period [3% (1–5%) for PTD and 13% (7–19%) for VPTD for each IQR increase]. However, O3 was observed to have protective effects on term LBW. Results were consistent for multi-pollutant models. Conclusion PM2.5 has consistent adverse effects on ABOs whereas O3 has inconsistent effects. These findings warrant further investigation. PMID:25173052

  3. 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

  4. 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

  5. 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

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

    PubMed

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

    2011-09-01

    Oseltamivir is the most widely used antiviral drug for the treatment and prophylaxis of influenza. However, not much is known about its adverse effects. The potential side effects were investigated in male and female rats (140-170 g). Oseltamivir was administered at 2.2 mg·kg(-1)·day(-1) for 5 days. For both genders, treatment with oseltamivir resulted in significant reductions in the hepatic activities of glutathione reductase, glutathione peroxidase, and glutathione S-transferase. Also for both genders, oseltamivir produced modest reductions in the hepatic activities of UDP-glucuronosyltransferase, quinone oxidoreductase, thioredoxin reductase, CYP1A1/2, and CYP3A, as well as hepatic glutathione content. For both genders, neither the kidney functions nor protein profile was affected by oseltamivir. Oseltamivir also caused significant elevation in serum levels of both triacylglycerols and LDL-cholesterol and in the activity of γ-glutamyl transpeptidase, in both genders. For male animals only, oseltamivir treatment elevated the serum level of total cholesterol as well as the activity of serum alanine aminotransferase, and reduced the hepatic activities of superoxide dismutase and catalase. Oseltamivir caused oxidative stress and acute toxicity in the liver, and disrupted the cholesterol and lipid metabolism but was less likely to cause serious drug interactions. There was a sexual differentiation in these adverse effects, with adverse effects being more evident in male rats. PMID:21861687

  7. Overlapping of Serotonin Syndrome with Neuroleptic Malignant Syndrome due to Linezolid-Fluoxetine and Olanzapine-Metoclopramide Interactions: A Case Report of Two Serious Adverse Drug Effects Caused by Medication Reconciliation Failure on Hospital Admission.

    PubMed

    Mazhar, Faizan; Akram, Shahzad; Haider, Nafis; Ahmed, Rafeeque

    2016-01-01

    Antipsychotic and antidepressant are often used in combination for the treatment of neuropsychiatric disorders. The concomitant use of antipsychotic and/or antidepressant with drugs that may interact can lead to rare, life-threatening conditions such as serotonin syndrome and neuroleptic malignant syndrome. We describe a patient who has a history of taking two offending drugs that interact with drugs given during the course of hospital treatment which leads to the development of serotonin syndrome overlapped with neuroleptic malignant syndrome. The physician should be aware that both NMS and SS can appear as overlapping syndrome especially when patients use a combination of both antidepressants and antipsychotics. PMID:27433163

  8. Overlapping of Serotonin Syndrome with Neuroleptic Malignant Syndrome due to Linezolid-Fluoxetine and Olanzapine-Metoclopramide Interactions: A Case Report of Two Serious Adverse Drug Effects Caused by Medication Reconciliation Failure on Hospital Admission

    PubMed Central

    Akram, Shahzad; Haider, Nafis; Ahmed, Rafeeque

    2016-01-01

    Antipsychotic and antidepressant are often used in combination for the treatment of neuropsychiatric disorders. The concomitant use of antipsychotic and/or antidepressant with drugs that may interact can lead to rare, life-threatening conditions such as serotonin syndrome and neuroleptic malignant syndrome. We describe a patient who has a history of taking two offending drugs that interact with drugs given during the course of hospital treatment which leads to the development of serotonin syndrome overlapped with neuroleptic malignant syndrome. The physician should be aware that both NMS and SS can appear as overlapping syndrome especially when patients use a combination of both antidepressants and antipsychotics. PMID:27433163

  9. Discordance between patient and clinician report of multidrug-resistant tuberculosis adverse drug reactions

    PubMed Central

    Kelly, A. M.; Smith, B.; Luo, Z.; Given, B.; Wehrwein, T.; Master, I.; Farley, J. E.

    2016-01-01

    Summary Setting An urban outpatient clinic in Durban, South Africa providing community-based treatment for drug-resistant TB. Objective Describe concordance between patient report and clinician documentation of adverse drug reactions (ADRs) from multidrug-resistant tuberculosis (MDR-TB) treatment. Design ADRs were documented by interview using an 18-item symptom checklist and medical record data abstraction during cross-sectional parent study with 121 MDR-TB patients, 75% co-infected with HIV. Concordance was analyzed using Cohen’s kappa statistic, Gwet’s AC1, and McNemar’s test. Results ADRs were reported much more frequently in the patient interviews (μ = 8.6) compared to medical records (μ = 1.4). Insomnia was most common (67 vs. 2%), followed by peripheral neuropathy (65 vs. 18%), and confusion (61 vs. 4%). Kappa scores were very low, with the highest degree of concordance found in hearing loss (kappa = 0.23), which was the only ADR not found to be significantly different between the two data sources (p = 0.34). Conclusions Our study showed a lack of concordance between patient report and clinician documentation of ADRs. These findings indicate the need for improved documentation of ADRs to better reflect the patient experience during MDR-TB treatment. These data have important implications for country-level pharmacovigilance programs that rely on clinician documentation of ADRs for MDR-TB policy formation. PMID:26970151

  10. A web resource for mining HLA associations with adverse drug reactions: HLA-ADR.

    PubMed

    Ghattaoraya, Gurpreet S; Dundar, Yenal; González-Galarza, Faviel F; Maia, Maria Helena Thomaz; Santos, Eduardo José Melo; da Silva, Andréa Luciana Soares; McCabe, Antony; Middleton, Derek; Alfirevic, Ana; Dickson, Rumona; Jones, Andrew R

    2016-01-01

    Human leukocyte antigens (HLA) are an important family of genes involved in the immune system. Their primary function is to allow the host immune system to be able to distinguish between self and non-self peptides-e.g. derived from invading pathogens. However, these genes have also been implicated in immune-mediated adverse drug reactions (ADRs), presenting a problem to patients, clinicians and pharmaceutical companies. We have previously developed the Allele Frequency Net Database (AFND) that captures the allelic and haplotype frequencies for these HLA genes across many healthy populations from around the world. Here, we report the development and release of the HLA-ADR database that captures data from publications where HLA alleles and haplotypes have been associated with ADRs (e.g. Stevens-Johnson Syndrome/toxic epidermal necrolysis and drug-induced liver injury). HLA-ADR was created by using data obtained through systematic review of the literature and semi-automated literature mining. The database also draws on data already present in AFND allowing users to compare and analyze allele frequencies in both ADR patients and healthy populations. The HLA-ADR database provides clinicians and researchers with a centralized resource from which to investigate immune-mediated ADRs.Database URL: http://www.allelefrequencies.net/hla-adr/. PMID:27189608

  11. Increasing the Number of Adverse Drug Reactions Reporting: the Role of Clinical Pharmacy Residents

    PubMed Central

    Baniasadi, Shadi; Habibi, Maryam; Haghgoo, Roodabeh; Karimi Gamishan, Masoumeh; Dabaghzadeh, Fatemeh; Farasatinasab, Maryam; Farsaei, Shadi; Gharekhani, Afshin; Kafi, Hamidreza; Karimzadeh, Iman; Kharazmkia, Ali; Najmeddin, Farhad; Nikvarz, Naemeh; Oghazian, Mohammad Bagher; Rezaee, Haleh; Sadeghi, Kourosh; Tafazzoli, Ali; Shahsavari, Nahid; Fahimi, Fanak

    2014-01-01

    Detection of adverse drug reactions (ADRs) in hospitals provides an important measure of the burden of drug related morbidity on the healthcare system. Spontaneous reporting of ADRs is scare and several obstacles to such reporting have been identified formerly. This study aimed to determine the role of clinical pharmacy residents in ADR reporting within a hospital setting. Clinical pharmacy residents were trained to report all suspected ADRs through ADR-reporting yellow cards. The incidence, pattern, seriousness, and preventability of the reported ADRs were analyzed. During the period of 12 months, for 8559 patients, 202 ADR reports were received. The most frequently reported reactions were due to anti-infective agents (38.38%). Rifampin accounted for the highest number of the reported ADRs among anti-infective agents. The gastro-intestinal system was the most frequently affected system (21.56%) of all reactions. Fifty four of the ADRs were reported as serious reactions. Eighteen of the ADRs were classified as preventable. Clinical pharmacy residents' involvement in the ADR reporting program could improve the ADR reporting system. PMID:24734083

  12. Adverse Drug Reactions for Medicines Newly Approved in Japan from 1999 to 2013: Hypertension and Hypotension.

    PubMed

    Nagayama, Takashi; Nishida, Minoru; Hizue, Masanori; Ogino, Yamato; Fujiyoshi, Masato

    2016-04-01

    In this survey, the correlation between adverse drug reactions (ADRs) in human and animal toxicities was investigated for 393 medicines which were approved in Japan from September 1999 to March 2013. ADRs were collected from each Japanese package insert. Comparable animal toxicities with ADRs were collected by thorough investigation of common technical documents. The results of this survey show that hypertension and/or hypotension were mainly observed in medicines affecting the central nervous system. Hypertension was also observed in antipyretics, analgesics, anti-inflammatory agents, vasoconstrictors and agents using antibody. Concordance between human ADRs and animal toxicities was analysed. True-positive rate for hypertension and hypotension is 0.29 and 0.52, respectively. Positive likelihood ratio and inverse negative likelihood ratio are 1.98 and 1.21, respectively, in hypertension and 1.67 and 1.44, respectively, in hypotension. Concordance between human ADRs and animal toxicities is not so high in hypertension and hypotension. Identified mechanisms as on-target for hypertension and hypotension are 29.8% and 30.5%, respectively. More than half of the causative factors of hypertension and hypotension were unable to be elucidated. Our results show that the intake of medicines is often linked to blood pressure variations that are not predicted in animal toxicity studies. Improvement of drug development processes may be necessary to provide safer medicines because current animal toxicity studies are insufficient to predict all ADRs in human beings. PMID:26407539

  13. Adverse drug reactions related to hospital admission in Slovak elderly patients.

    PubMed

    Wawruch, Martin; Zikavska, Martina; Wsolova, Ladislava; Kuzelova, Magdalena; Kahayova, Katarina; Strateny, Kamil; Kristova, Viera

    2009-01-01

    The aims of the present study were: to evaluate the prevalence of adverse drug reactions (ADRs) leading to hospitalization in elderly patients; to analyze the drugs which have been identified as having causal relationship with ADRs and to identify risk factors which predispose the patient to such ADRs. The study has been performed in 600 patients aged> or =65 years, hospitalized in a general hospital between 1 December 2003 and 31 March 2005. The ADRs recorded in patient's documentation as one of the reasons for hospital admission were evaluated. ADRs leading to hospital admission were recorded in 47 (7.8%) patients. ADRs in 43 patients represented A-type ADRs which are preventable. The most frequent ADRs were cardiovascular disorders. According to the results of multivariate analysis ischemic heart disease (odds ratio (OR)=4.50; 95% confidence interval (CI)=1.36-14.88), depression (OR, 2.49; 95% CI, 1.08-5.77) and heart failure (OR, 2.08; 95% CI, 1.13-3.81) were the most important patient-related characteristics predicting ADRs leading to hospitalization. The majority of ADRs in elderly patients could be avoided. Regular re-evaluation of the medication as well as taking into account the specific features of elderly patients represent the most important tools for ADR prevention. PMID:18313773

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

    PubMed

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

    2009-01-01

    Regulatory agencies grant product licences (marketing authorizations) for medicinal products in the light of evidence that the balance between benefit and harm in the population is favourable. Here we consider a framework for allowing regulatory agencies to make rational decisions when reviewing product licences in the light of new information about harms that change that balance. The regulator can revoke the product licence, restrict the product's availability or change the 'label' in different ways. We examine the features of the adverse effect that may be relevant in making the decision: namely, individual differences in susceptibility; the possibility of monitoring; and the availability of protective strategies. The balance of benefit and harm, and the time-course and dose relation of the adverse effect play important roles in the decision-making process. We set out how these factors can help determine the logical response to new information on the balance between benefit and harm, and provide a series of relevant examples. We believe that when regulatory agencies have to decide how to amend the product licence of a drug when new serious adverse effects cause concern, they would find it useful to adopt a framework of this kind, using different strategies for different cases. Our proposed framework could also be useful in risk management planning during drug development. PMID:19236116

  15. 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. PMID:27374969

  16. Profile of rheumatology patients willing to report adverse drug reactions: bias from selective reporting

    PubMed Central

    Protić, Dragana; Vujasinović-Stupar, Nada; Bukumirić, Zoran; Pavlov-Dolijanović, Slavica; Baltić, Snežana; Mutavdžin, Slavica; Marković-Denić, Ljiljana; Zdravković, Marija; Todorović, Zoran

    2016-01-01

    Background Adverse drug reactions (ADRs) have a significant impact on human health and health care costs. The aims of our study were to determine the profile of rheumatology patients willing to report ADRs and to identify bias in such a reporting system. Methods Semi-intensive ADRs reporting system was used in our study. Patients willing to participate (N=261) completed the questionnaire designed for the purpose of the study at the hospital admission. They were subsequently classified into two groups according to their ability to identify whether they had experienced ADRs during the previous month. Group 1 included 214 out of 261 patients who were able to identify ADRs, and group 2 consisted of 43 out of 261 patients who were not able to identify ADRs in their recent medical history. Results Group 1 patients were more significantly aware of their diagnosis than the patients from group 2. Marginal significance was found between rheumatology patients with and without neurological comorbidities regarding their awareness of ADRs. The majority of patients reported ADRs of cytotoxic drugs. The most reported ADRs were moderate gastrointestinal discomforts. Conclusion We may draw a profile of rheumatological patients willing to report ADRs: 1) The majority of them suffer from systemic inflammatory diseases and are slightly more prone to neurological comorbidities. 2) They are predominantly aware of their diagnosis but less able to identify the drugs that may cause their ADRs. 3) They tend to report mainly moderate gastrointestinal ADRs; that is, other cohorts of patients and other types of ADRs remain mainly undetected in such a reporting, which could represent a bias. Counseling and education of patients as well as developing a network for online communication might improve patients’ reporting of potential ADRs. PMID:26893547

  17. Adverse drug reactions in elderly patients with cognitive disorders: A systematic review.

    PubMed

    Kanagaratnam, Lukshe; Dramé, Moustapha; Trenque, Thierry; Oubaya, Nadia; Nazeyrollas, Pierre; Novella, Jean-Luc; Jolly, Damien; Mahmoudi, Rachid

    2016-03-01

    Elderly subjects with cognitive disorders are at particularly high risk of adverse drug reactions (ADRs). The objectives of our systematic review were to describe the prevalence of ADRs in elderly patients with cognitive disorders, the different types of ADRs and the medications suspected of involvement; to describe whether the ADRs were preventable or not, and to identify risk factors for occurrence of ADRs in this population. A bibliographic search was performed in the following databases: PubMed, Embase, Google Scholar, Opengrey and Scopus. The search included all publications up to and including 4th February 2015, with no specific start date specified. Studies concerning ADRs in elderly patients with cognitive disorders or dementia were included. Two senior authors identified eligible studies and extracted data independently. In total, 113 studies were identified by the bibliographic search, of which six full-text articles were retained and analyzed. Prevalence of ADRs ranged from 4.8 to 37%. The main ADRs reported were neurological and psychological disorders, gastro-intestinal disorders, dermatological and allergic disorders, falls, renal and urinary disorders, cardiovascular disorders, metabolic disorders and electrolyte imbalance, and hemorrhagic events. The medications most commonly suspected of involvement in the ADRs were drugs affecting the nervous system, cardiovascular drugs, anticoagulants, and painkillers. Medical prescriptions should take into account the presence of Alzheimer's disease and related syndromes. Compliance should systematically be evaluated, and cognitive disorders need to be better recognized. Therapeutic education of patients and/or their caregiver is key to management of elderly patients with cognitive disorders. PMID:26857880

  18. Countermeasures for space radiation induced adverse biologic effects

    NASA Astrophysics Data System (ADS)

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

    2011-11-01

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

  19. Olfactory drug effects approached from human-derived data.

    PubMed

    Lötsch, Jörn; Knothe, Claudia; Lippmann, Catharina; Ultsch, Alfred; Hummel, Thomas; Walter, Carmen

    2015-11-01

    The complexity of the sense of smell makes adverse olfactory effects of drugs highly likely, which can impact a patient's quality of life. Here, we present a bioinformatics approach that identifies drugs with potential olfactory effects by connecting drug target expression patterns in human olfactory tissue with drug-related information and the underlying molecular drug targets taken from publically available databases. We identified 71 drugs with listed olfactory effects and 147 different targets. Taking the target-based approach further, we found additional drugs with potential olfactory effects, including 152 different substances interacting with genes expressed in the human olfactory bulb. Our proposed bioinformatics approach provides plausible hypotheses about mechanistic drug effects for drug discovery and repurposing and, thus, would be appropriate for use during drug development. PMID:26160059

  20. Can utilizing a computerized provider order entry (CPOE) system prevent hospital medical errors and adverse drug events?

    PubMed

    Charles, Krista; Cannon, Margaret; Hall, Robert; Coustasse, Alberto

    2014-01-01

    Computerized provider order entry (CPOE) systems allow physicians to prescribe patient services electronically. In hospitals, CPOE essentially eliminates the need for handwritten paper orders and achieves cost savings through increased efficiency. The purpose of this research study was to examine the benefits of and barriers to CPOE adoption in hospitals to determine the effects on medical errors and adverse drug events (ADEs) and examine cost and savings associated with the implementation of this newly mandated technology. This study followed a methodology using the basic principles of a systematic review and referenced 50 sources. CPOE systems in hospitals were found to be capable of reducing medical errors and ADEs, especially when CPOE systems are bundled with clinical decision support systems designed to alert physicians and other healthcare providers of pending lab or medical errors. However, CPOE systems face major barriers associated with adoption in a hospital system, mainly high implementation costs and physicians' resistance to change. PMID:25593568

  1. Vaginal douching and adverse health effects: a meta-analysis.

    PubMed Central

    Zhang, J; Thomas, A G; Leybovich, E

    1997-01-01

    OBJECTIVES: The meta-analysis described here reviewed the current literature on adverse health effects of vaginal douching. METHODS: Papers published in English from 1965 through 1995 were potentially eligible. RESULTS: One third of White women and two thirds of Black women of reproductive age reported douching regularly. Analyses indicated that vaginal douching increases the overall risk of pelvic inflammatory disease by 73% and the risk of ectopic pregnancy by 76%. Frequent douching was shown to be highly associated with pelvic inflammatory disease and modestly associated with cervical cancer. CONCLUSIONS: Current literature suggests that frequent douching increases the risk of pelvic inflammatory disease, ectopic pregnancy, and, possibly, cervical cancer. PMID:9240115

  2. CN-15ADVERSE EFFECTS OF BEVACIZUMAB IN BRAIN TUMOR PATIENTS

    PubMed Central

    Pawar, Tushar; Ladha, Harshad; Mandel, Jacob; Gilbert, Mark; O'Brien, Barbara; Hamza, Mohamed; Armstrong, Terri

    2014-01-01

    BACKGROUND: Bevacizumab is humanized monoclonal antibody inhibiting angiogenesis and the only FDA approved treatment for recurrent glioblastoma. The aim of this study was to look at the occurrence of various adverse effects associated with use of bevacizumab in recurrent glioblastoma. METHODS: In this retrospective chart review, we studied 280 patients with recurrent glioblastoma treated with Bevacizumab between 2005-2011 to characterize the known adverse effects of bevacizumab including hypertension, grade 3-4 myelosuppression, wound healing complications, thrombo-embolic events, stroke, hemorrhage and gastrointestinal complications. RESULTS: The study population included 168 males and 112 females. The median age was 53.5 years(range 8.1-81.3). TREATMENT: Bevacizumab only(58), Bevacizumab + CPT(11), Bevacizumab + TMZ(32) or Bevacizumab + Other(34). Patients were treated at recurrence(1st = 96; 2nd = 126, 3rd = 58). Hypertension was the most common adverse effect occurring in 131(49%). The median duration from treatment start to development was 82 days (Range 7-1143). However, only 33(25%) were started on antihypertensive medication. Grade 3-4 Myelosuppression occurred in 52(19%)causing treatment discontinuation in 8. Thrombo-embolic events were reported in 5%(15) patients including DVT(9), PE(2), Central venous thrombosis(1) and Stroke(3). Thirty-six patients (13%) were on anti-coagulant medication at bevacizumab initiation. Median time to a thromboembolic complication was 113 days (Range 8-1145). Wound healing complications were noted in 7(3%) patients, 3 craniotomy dehiscence and 4 at soft tissue sites. Five patients (2%) developed GI complications, including perforations(3), pancreatitis(1), and diverticulitis(1). Median time to development was 92 days(Range 10-651). There was a high rate 46%(129) of grade 3-4 lymphocytopenia; median time to develop lymphocytopenia was 50 days(Range = 3-564). CONCLUSION: The range of toxicities was similar to other reports

  3. In vitro testing for diagnosis of idiosyncratic adverse drug reactions: Implications for pathophysiology.

    PubMed

    Elzagallaai, Abdelbaset A; Rieder, Michael J

    2015-10-01

    Idiosyncratic drug reactions (IDRs) represent a major health problem, as they are unpredictable, often severe and can be life threatening. The low incidence of IDRs makes their detection during drug development stages very difficult causing many post-marketing drug withdrawals and black box warnings. The fact that IDRs are always not predictable based on the drug's known pharmacology and have no clear dose-effect relationship with the culprit drug renders diagnosis of IDRs very challenging, if not impossible, without the aid of a reliable diagnostic test. The drug provocation test (DPT) is considered the gold standard for diagnosis of IDRs but it is not always safe to perform on patients. In vitro tests have the advantage of bearing no potential harm to patients. However, available in vitro tests are not commonly used clinically because of lack of validation and their complex and expensive procedures. This review discusses the current role of in vitro diagnostic testing for diagnosis of IDRs and gives a brief account of their technical and mechanistic aspects. Advantages, disadvantages and major challenges that prevent these tests from becoming mainstream diagnostic tools are also discussed here. PMID:25199801

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

    PubMed

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

    2016-01-01

    Deferasirox is a standard treatment for chronic transfusional iron overload. Adverse effects of deferasirox have been reported in large prospective studies. We report two cases of monozygotic twins manifesting with proximal muscular atrophy and weakness under deferasirox. Discontinuation of deferasirox resulted in symptom improvement and ultimately in complete remission five months after successful haematopoietic stem cell transplantation. Broad diagnostic work-up could not bring evidence of another aetiology of muscular weakness. Iron overload or beta thalassemia itself as a cause is considered unlikely in our patients because the chronological coincidence of muscular symptoms was contra-directional to serum ferritin levels and significant clinical improvement was observed promptly after cessation of deferasirox even before transplantation. These observations suggest that the development of muscular weakness in patients on deferasirox should be recognised as a possible adverse effect of the drug. PMID:27068298

  5. A severe dermatologic adverse effect related with gefitinib: case report and review of the literature.

    PubMed

    Li, Yuan-Qing; Sun, Hong; Xue, Dong

    2013-09-01

    Gefitinib, a selective inhibitor of the epidermal growth factor receptor-tyrosine kinase, it's one of the most frequent drug-related adverse effects (AEs) reported in literature is dermatologic AEs. We report, a case of severe cutaneous adverse reactions induced by gefitinib as second-line treatment in a male patient with advanced non-small cell lung cancer after 1 month of treatment. Although tumor shrunk and patient got benefit from the treatment, gefitinib had to be stopped right away. We managed the symptoms of rash with a variety of treatments, including topical ethacridine lactate, antihistamine and so on. After the rash improved, we found his tumor were progress. Then he took gefitinib again without severe skin toxicity or disease progression. We think the development of gefitinib-induced rash may be a sign of effective and administrating it again maybe relieves the degree of rash. PMID:24135241

  6. Identification of possible adverse drug reactions in clinical notes: The case of glucose-lowering medicines

    PubMed Central

    Warrer, Pernille; Jensen, Peter Bjødstrup; Aagaard, Lise; Jensen, Lars Juhl; Brunak, Søren; Krag, Malene Hammer; Rossing, Peter; Almdal, Thomas; Andersen, Henrik Ullits; Hansen, Ebba Holme

    2015-01-01

    Objective: Through manual review of clinical notes for patients with type 2 diabetes mellitus attending a Danish diabetes center, the aim of the study was to identify adverse drug reactions (ADRs) associated with three classes of glucose-lowering medicines: “Combinations of oral blood-glucose lowering medicines” (A10BD), “dipeptidyl peptidase-4 (DDP-4) inhibitors” (A10BH), and “other blood glucose lowering medicines” (A10BX). Specifically, we aimed to describe the potential of clinical notes to identify new ADRs and to evaluate if sufficient information can be obtained for causality assessment. Methods: For observed adverse events (AEs) we extracted time to onset, outcome, and suspected medicine(s). AEs were assessed according to World Health Organization-Uppsala Monitoring Centre causality criteria and analyzed with respect to suspected medicines, type of ADR (system organ class), seriousness and labeling status. Findings: A total of 207 patients were included in the study leading to the identification of 163 AEs. 14% were categorized as certain, 60% as probable/likely, and 26% as possible. 15 (9%) ADRs were unlabeled of which two were serious: peripheral edema associated with sitagliptin and stomach ulcer associated with liraglutide. Of the unlabeled ADRs, 13 (87%) were associated with “other blood glucose lowering medications,” the remaining 2 (13%) with “DDP-4 inhibitors.” Conclusion: Clinical notes could potentially reveal unlabeled ADRs associated with prescribed medicines and sufficient information is generally available for causality assessment. However, manual review of clinical notes is too time-consuming for routine use and hence there is a need for developing information technology (IT) tools for automatic screening of patient records with the purpose to detect information about potentially serious and unlabeled ADRs. PMID:25984543

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

    PubMed

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

    2015-05-01

    Carrageenan (CRG) is a family of natural polysaccharides derived from seaweeds and has widely been used as food additives. In the past decade, owing to its attractive physicochemical properties, CRG has been developed into versatile biomaterials vehicles for drug delivery. Nevertheless, studies also emerged to reveal its adverse effects on the biological system. In this review, we critically appraise the latest literature (two thirds since 2008) on the development of CRG-based pharmaceutical vehicles and the perspective of using CRG for broader biomedical applications. We focus on how current strategies exploit the unique gelling mechanisms, strong water absorption and abundant functional groups of the three major CRG varieties. Notably, CRG-based matrices are demonstrated to increase drug loading and drug solubility, enabling release of orally administrated drugs in zero-order or in a significantly prolonged period. Other amazing features, such as pH-sensitivity and adhesive property, of CRG-based formulations are also introduced. Finally, we discuss the adverse influence of CRG on the human body and then suggest some future directions for the development of CRG-based biomaterials for broader applications in biomedicine. PMID:25659668

  8. Hypomagnesemia as a potentially life-threatening adverse effect of omeprazole

    PubMed Central

    Hansen, Bent-Are; Bruserud, Øyvind

    2016-01-01

    Hypomagnesemia can be caused by a wide range of diseases (e.g. gastrointestinal disorders, kidney diseases or endocrine disorders), but it can also be a side effect of several drugs. It can be asymptomatic or cause many different clinical symptoms, and the clinical manifestations mainly depend on the rate of development rather than the actual serum magnesium concentration. We here present a 40-year-old female patient with Torsade de pointes ventricular tachycardia and cardiac arrest caused by severe hypomagnesemia as an adverse effect of the proton pump inhibitor omeprazole. PMID:27471598

  9. A side effect resource to capture phenotypic effects of drugs

    PubMed Central

    Kuhn, Michael; Campillos, Monica; Letunic, Ivica; Jensen, Lars Juhl; Bork, Peer

    2010-01-01

    The molecular understanding of phenotypes caused by drugs in humans is essential for elucidating mechanisms of action and for developing personalized medicines. Side effects of drugs (also known as adverse drug reactions) are an important source of human phenotypic information, but so far research on this topic has been hampered by insufficient accessibility of data. Consequently, we have developed a public, computer-readable side effect resource (SIDER) that connects 888 drugs to 1450 side effect terms. It contains information on frequency in patients for one-third of the drug–side effect pairs. For 199 drugs, the side effect frequency of placebo administration could also be extracted. We illustrate the potential of SIDER with a number of analyses. The resource is freely available for academic research at http://sideeffects.embl.de. PMID:20087340

  10. The drug efficacy and adverse reactions in a mouse model of oral squamous cell carcinoma treated with oxaliplatin at different time points during a day

    PubMed Central

    Yang, Kai; Zhao, Ningbo; Zhao, Dan; Chen, Dan; Li, Yadong

    2013-01-01

    Background Recent studies have shown that the growth and proliferation of cancer cells in vivo exhibit circadian rhythm, and the efficacy and adverse reactions of platinum-based anticancer drugs administered at different times of the day vary significantly on colon cancer. However, since the circadian rhythms of growth and proliferation of various cancer cells often differ, the question of whether the administration of platinum anticancer drugs at different times of the day exerts significantly different efficacy and adverse effects on oral cancers remains to be elucidated. This study has compared the efficacy and adverse effects of oxaliplatin (L-OHP) administration at different times during a day on oral squamous cell carcinoma in mice and has analyzed cellular circadian rhythms. Methods The mouse model for oral squamous cell carcinoma was established in 75 nude mice, housed in a 12 hour light/12 hour dark cycle environment. The mice were randomly divided into five groups; four experimental groups were intravenously injected with L-OHP at four time points within a 24-hour period (4, 10, 16, and 22 hours after lights on [HALO]). The control group was intravenously injected with the same volume of saline. Treatment efficacy and adverse reactions were compared on the seventh day after the injection, at 22 HALO. The existence of circadian rhythms was determined by cosine analysis. Results Only injections of L-OHP at 16 and 22 HALO significantly prolonged animal survival time. The adverse reactions in mice injected with L-OHP at 16 and 22 HALO were significantly less than those observed in mice administered L-OHP at 4 and 10 HALO. The cosine fitting curve showed that the survival time and adverse reactions exhibited circadian rhythm. Conclusion The time factor should be considered when treating patients with oral squamous cell carcinoma with L-OHP in order to achieve better efficacy, reduce the adverse reactions, and improve the patients’ survival time and quality

  11. Urging College Alcohol and Drug Policies That Target Adverse Behavior, Not Use.

    ERIC Educational Resources Information Center

    Lewis, David C.

    2001-01-01

    Although zero tolerance policies are being enacted on campuses nationwide, they may not be the most effective means of creating safer and healthier environments for students. Many historical precedents illustrate the value of moderation over prohibition. College drug and alcohol policies should focus primarily on dysfunctional and disruptive…

  12. Adverse effects of outdoor pollution in the elderly

    PubMed Central

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

    2015-01-01

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

  13. Adverse effects of outdoor pollution in the elderly.

    PubMed

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

    2015-01-01

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

  14. Mechanisms and assessment of statin-related muscular adverse effects

    PubMed Central

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

    2014-01-01

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

  15. Adverse effects associated with arginine alpha-ketoglutarate containing supplements.

    PubMed

    Prosser, J M; Majlesi, N; Chan, G M; Olsen, D; Hoffman, R S; Nelson, L S

    2009-05-01

    The athletic performance supplement industry is a multibillion-dollar business and one popular category claims to increase nitric oxide (NO) production. We report three patients presenting to the emergency department with adverse effects. A 33-year-old man presented with palpitations, dizziness, vomiting, and syncope, after the use of NO(2) platinum. His examination and electrocardiogram (ECG) were normal. The dizziness persisted, requiring admission overnight. A 21-year-old man with palpitations and near syncope had used a "nitric oxide" supplement. He was tachycardic to 115 bpm with otherwise normal examination. Laboratory values including methemoglobin, and ECG were unremarkable. He was treated with 1 L of saline with no change in heart rate. He was admitted for observation. A 24-year-old man presented after taking NO-Xplode with palpitations and a headache. His examination, laboratory values, and ECG were normal. He was discharged. The purported active ingredient in these products is arginine alpha-ketoglutarate (AAKG), which is claimed to increase NO production by supplying the precursor L-arginine. The symptoms could be due to vasodilation from increased levels of NO, though other etiologies cannot be excluded. AAKG containing supplements may be associated with adverse effects requiring hospital admission. PMID:19755457

  16. 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

  17. Evolution of pharmacological obesity treatments: focus on adverse side-effect profiles.

    PubMed

    Krentz, A J; Fujioka, K; Hompesch, M

    2016-06-01

    Pharmacotherapy directed toward reducing body weight may provide benefits for both curbing obesity and lowering the risk of obesity-associated comorbidities; however, many weight loss medications have been withdrawn from the market because of serious adverse effects. Examples include pulmonary hypertension (aminorex), cardiovascular toxicity, e.g. flenfluramine-induced valvopathy, stroke [phenylpropanolamine (PPA)], excess non-fatal cardiovascular events (sibutramine), and neuro-psychiatric issues (rimonabant; approved in Europe, but not in the USA). This negative experience has helped mould the current drug development and approval process for new anti-obesity drugs. Differences between the US Food and Drug Administration (FDA) and the European Medicines Agency, however, in perceptions of risk-benefit considerations for individual drugs have resulted in discrepancies in approval and/or withdrawal of weight-reducing medications. Thus, two drugs recently approved by the FDA, i.e. lorcaserin and phentermine + topiramate extended release, are not available in Europe. In contrast, naltrexone sustained release (SR)/bupropion SR received FDA approval, and liraglutide 3.0 mg was recently approved in both the USA and Europe. Regulatory strategies adopted by the FDA to manage the potential for uncommon but potentially serious post-marketing toxicity include: (i) risk evaluation and mitigation strategy programmes; (ii) stipulating post-marketing safety trials; (iii) considering responder rates and limiting cumulative exposure by discontinuation if weight loss is not attained within a reasonable timeframe; and (iv) requiring large cardiovascular outcome trials before or after approval. We chronicle the adverse effects of anti-obesity pharmacotherapy and consider how the history of high-profile toxicity issues has shaped the current regulatory landscape for new and future weight-reducing drugs. PMID:26936802

  18. Using Simcyp to project human oral pharmacokinetic variability in early drug research to mitigate mechanism-based adverse events.

    PubMed

    Shaffer, Christopher L; Scialis, Renato J; Rong, Haojing; Obach, R Scott

    2012-03-01

    Positive allosteric modulators ('potentiators') of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) have been shown to display a mechanism-based exposure-response continuum in preclinical species with procognitive electrophysiological and behavioral effects ('efficacy') at low exposures and motor coordination disruptions at progressively higher exposures. Due to the dose-capping nature of such motor coordination deficits, an exposure threshold-mediated adverse event (C(AE) ), the adequacy of separation between the maximal total plasma compound concentration (C(max) ) at a predicted clinically efficacious oral dose and this adverse event (AE) was explored in early drug research with three AMPAR potentiators considered potential candidates for clinical trials. In vitro metabolism studies in human liver microsomes and human hepatocytes demonstrated the metabolic clearance for each compound was predominately due to cytochromes P450 (CYP). Thus, for each compound's anticipated clinically efficacious dose, human C(max) variability following oral administration was assessed using Simcyp software, which combines its virtual human populations database using extensive demographic, physiological and genomic information with routinely collected compound-specific in vitro biochemical data to simulate and predict drug disposition. Using a combination of experimentally determined recombinant human CYP intrinsic clearances for CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4, human binding factors, expected fraction absorbed and estimated steady-state volume of distribution, Simcyp simulations demonstrated that two of the three potentiators had acceptable projected C(max) variability (i.e. the 95th percentile C(max) did not breach C(AE) ). This evaluation aided in the selection of compounds for preclinical progression, and represents a novel application of pharmacologically based pharmacokinetic (PBPK) software approaches to predict interpatient

  19. A systematic review of observational studies evaluating costs of adverse drug reactions

    PubMed Central

    Batel Marques, Francisco; Penedones, Ana; Mendes, Diogo; Alves, Carlos

    2016-01-01

    Introduction The growing evidence of the increased frequency and severity of adverse drug events (ADEs), besides the negative impact on patient’s health status, indicates that costs due to ADEs may be steadily rising. Observational studies are an important tool in pharmacovigilance. Despite these studies being more susceptible to bias than experimental designs, they are more competent in assessing ADEs and their associated costs. Objective To identify and characterize the best available evidence on ADE-associated costs. Methods MEDLINE, Cochrane Library, and Embase were searched from 1995 to 2015. Observational studies were included. The methodological quality of selected studies was assessed by Cochrane Collaboration tool for experimental and observational studies. Studies were classified according to the setting analyzed in “ambulatory”, “hospital”, or both. Costs were classified as “direct” and “indirect”. Data were analyzed using descriptive statistics. The total incremental cost per patient with ADE was estimated. Results Twenty-nine (94%) longitudinal observational studies and two (7%) cross-sectional studies were included. Twenty-three (74%) studies were assessed with the highest methodological quality score. The studies were mainly conducted in the US (61%). Twenty (65%) studies evaluated any therapeutic group. Twenty (65%) studies estimated costs of ADEs leading to or prolonging hospitalization. The “direct costs” were evaluated in all studies, whereas only two (7%) also estimated the “indirect costs”. The “direct costs” in ambulatory ranged from €702.21 to €40,273.08, and the in hospital from €943.40 to €7,192.36. Discussion Methodological heterogeneities were identified among the included studies, such as design, type of ADEs, suspected drugs, and type and structure of costs. Despite such discrepancies, the financial burden associated with ADE costs was found to be high. In the light of the present findings

  20. HLA-B*1502 and carbamazepine-induced severe cutaneous adverse drug reactions in Vietnamese

    PubMed Central

    Chu, Hieu Chi; Nguyen, Doan Van; Phan, Minh Hong; Craig, Timothy; Baumgart, Karl; van Nunen, Sheryl

    2015-01-01

    Background In Vietnam, we observed a high incidence of carbamazepine (CBZ)-induced severe cutaneous adverse drug reactions (SCARs)-Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), and drug-induced hypersensitivity rash with eosinophilia and systemic symptoms (DRESS). In other Asian countries, HLA-B*1502 is an established risk factor for SCARs. Objective The aim of our study was to determine the frequency of HLA-B*1502 in SCARs patients at a large University Medical Center in Hanoi, Vietnam. Methods Thirty-eight cases of SCARs caused by CBZ and 25 patients with epilepsy tolerating CBZ were enrolled in a case-controlled study. Clinical manifestations and laboratory findings were recorded for each subject. Genomic DNA was isolated using the QIAamp DNA purification system. The combination of polymerase chain reaction and sequence specific oligonucleotide probes with the Luminex 100×MAP flow cytometry dual laser system was then used to quantitate fluorescently labelled oligonucleotides attached to colour-coded microbeads. Results Cases comprised 20 SJS (52.6%), 7 TEN (18.4%), 8 overlap syndrome (21.1%), and 3 DRESS patients (7.9%). A strong association between HLA B*1502 and bullous skin reactions such as SJS/TEN and overlap was confirmed with an odds ratio (OR) of 33.78 (95% confidence interval [CI], 7.55-151.03), p < 0.0001, Sensitivity 91.4%, Specificity 76.0%, positive predictive value 84.2%, and negative predictive value 86.4%. We did not, however, observe any correlation between the presence of this allele and CBZ-induced nonbullous skin reactions (DRESS) (OR, 6.33; 95% CI, 0.48-82.74; p = 0.1592). Conclusion Our results indicate the presence of HLA-B*1502 in Vietnamese is a pharmacogenetic risk factor for developing CBZ-induced SJS/TEN. PMID:25938071

  1. Risk-Taking Behavior among Adolescents with Prenatal Drug Exposure and Extrauterine Environmental Adversity

    PubMed Central

    Lambert, Brittany L.; Bann, Carla M.; Bauer, Charles R.; Shankaran, Seetha; Bada, Henrietta S.; Lester, Barry M.; Whitaker, Toni M.; LaGasse, Linda L.; Hammond, Jane; Higgins, Rosemary D.

    2014-01-01

    Objective High-risk environments characterized by familial substance use, poverty, inadequate parental monitoring, and violence exposure are associated with an increased propensity for adolescents to engage in risk-taking behaviors (e.g., substance use, sexual behavior, and delinquency). However, additional factors such as drug exposure in utero and deficits in inhibitory control among drug-exposed youth may further influence the likelihood that adolescents in high-risk environments will engage in risk-taking behavior. This study examined the influence of prenatal substance exposure, inhibitory control, and sociodemographic/environmental risk factors on risk-taking behaviors in a large cohort of adolescents with and without prenatal cocaine exposure (PCE). Method Risk-taking behavior (delinquency, substance use, and sexual activity) was assessed in 963 adolescents (433 cocaine-exposed, 530 nonexposed) at 15 years of age. Results PCE predicted later arrests and early onset of sexual behavior in controlled analyses. Associations were partially mediated, however, by adolescent inhibitory control problems. PCE was not associated with substance use at this age. In addition, male gender, low parental involvement, and violence exposure were associated with greater odds of engaging in risk-taking behavior across the observed domains. Conclusions Study findings substantiate concern regarding the association between prenatal substance exposure and related risk factors and the long-term outcomes of exposed youth. Access to the appropriate social, educational, and medical services are essential in preventing and intervening with risk-taking behaviors and the potential consequences (e.g., adverse health outcomes, incarceration), especially among high-risk adolescent youth and their families. PMID:24220515

  2. Adverse testicular effects of Botox® in mature rats

    SciTech Connect

    Breikaa, Randa M.; Mosli, Hisham A.; Nagy, Ayman A.; Abdel-Naim, Ashraf B.

    2014-03-01

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

  3. Formalizing MedDRA to support semantic reasoning on adverse drug reaction terms.

    PubMed

    Bousquet, Cédric; Sadou, Éric; Souvignet, Julien; Jaulent, Marie-Christine; Declerck, Gunnar

    2014-06-01

    Although MedDRA has obvious advantages over previous terminologies for coding adverse drug reactions and discovering potential signals using data mining techniques, its terminological organization constrains users to search terms according to predefined categories. Adding formal definitions to MedDRA would allow retrieval of terms according to a case definition that may correspond to novel categories that are not currently available in the terminology. To achieve semantic reasoning with MedDRA, we have associated formal definitions to MedDRA terms in an OWL file named OntoADR that is the result of our first step for providing an "ontologized" version of MedDRA. MedDRA five-levels original hierarchy was converted into a subsumption tree and formal definitions of MedDRA terms were designed using several methods: mappings to SNOMED-CT, semi-automatic definition algorithms or a fully manual way. This article presents the main steps of OntoADR conception process, its structure and content, and discusses problems and limits raised by this attempt to "ontologize" MedDRA. PMID:24680984

  4. Designing a national combined reporting form for adverse drug reactions and medication errors.

    PubMed

    Tanti, A; Serracino-Inglott, A; Borg, J J

    2015-04-01

    The Maltese Medicines Authority was tasked with developing a reporting form that captures high-quality case information on adverse drug reactions (ADRs) and medication errors in order to fulfil its public-health obligations set by the European Union (EU) legislation on pharmacovigilance. This paper describes the process of introducing the first combined ADR/medication error reporting form in the EU for health-care professionals, the analysis of reports generated by it and the promotion of the system. A review of existing ADR forms was carried out and recommendations from the European Medicines Agency and World Health Organization audits integrated. A new, combined ADR/medication error reporting form was developed and pilot tested based on case studies. The Authority's quality system (ISO 9001 certified) was redesigned and a promotion strategy was deployed. The process used in Malta can be useful for countries that need to develop systems relative to ADR/medication error reporting and to improve the quality of data capture within their systems. PMID:26077519

  5. Adverse Drug Reactions in a Complementary Medicine Hospital: A Prospective, Intensified Surveillance Study

    PubMed Central

    Süsskind, M.; Thürmann, P. A.; Lüke, C.; Jeschke, E.; Tabali, M.; Matthes, H.; Ostermann, T.

    2012-01-01

    Background. Anthroposophic medicine is one of the widely used approaches of complementary and alternative medicine. However, few prospective studies have generated safety data on its use. Objectives. We aimed to assess adverse drug reactions (ADRs) caused by anthroposophical medicines (AMEDs) in the anthroposophical Community Hospital Havelhoehe, GERMANY. Study Design and Methods. Between May and November 2007, patients of six medical wards were prospectively assessed for ADRs. Suspected ADRs occurring during hospitalization were documented and classified in terms of organ manifestation (WHO SOC-code), causality (according to the Uppsala Monitoring Centre WHO criteria), and severity. Only those ADRs with a severity of grade 2 and higher according to the CTCAE classification system are described here. Results. Of the 3,813 patients hospitalized, 174 patients (4.6%) experienced 211 ADRs (CTCAE grade 2/3 n = 191, 90.5%, CTCAE grade 4/5 n = 20, 9.5%) of which 57 ADRs (27.0%) were serious. The median age of patients with ADRs (62.1% females) was 72.0 (IQR: 61.0; 80.0). Six patients (0.2%) experienced six ADRs (2.8% of ADRs) caused by eight suspected AMEDs, all of which were mild reactions (grade 2). Conclusion. Our data show that ADRs caused by AMEDs occur rarely and are limited to mild symptoms. PMID:22315630

  6. Patient reporting of suspected adverse drug reactions: a review of published literature and international experience

    PubMed Central

    Blenkinsopp, A; Wilkie, P; Wang, M; Routledge, P A

    2007-01-01

    Aims To synthesize data from published studies and international experience to identify evidence of potential benefits and drawbacks of direct patient reporting of suspected adverse drug reactions (ADRs) by patients. Methods Structured search of MEDLINE, CINAHL and PsycINFO supplemented by internet searches and requests for information to key contacts. Results Seven studies (eight papers) were included in the review. None of the studies concerned spontaneous reporting by patients. Information on patient reporting systems was obtained for six countries, with summary data reported by four. Patient reports identified possible new ADRs that had not previously been reported by health professionals. The quality of patient reports appears to be similar to that of health professional reports. There is some evidence that patients report an ADR when they consider their health professional has not paid attention to their concerns. Patient reports may, at least initially, be more time consuming to process. Conclusions Overall, the evidence indicates that patient reporting of suspected ADRs has more potential benefits than drawbacks. Evaluation of patient reporting systems is needed to provide further evidence. PMID:17274788

  7. Aloe vera: A review of toxicity and adverse clinical effects.

    PubMed

    Guo, Xiaoqing; Mei, Nan

    2016-04-01

    The Aloe plant is employed as a dietary supplement in a variety of foods and as an ingredient in cosmetic products. The widespread human exposure and its potential toxic and carcinogenic activities raise safety concerns. Chemical analysis reveals that the Aloe plant contains various polysaccharides and phenolic chemicals, notably anthraquinones. Ingestion of Aloe preparations is associated with diarrhea, hypokalemia, pseudomelanosis coli, kidney failure, as well as phototoxicity and hypersensitive reactions. Recently, Aloe vera whole leaf extract showed clear evidence of carcinogenic activity in rats, and was classified by the International Agency for Research on Cancer as a possible human carcinogen (Group 2B). This review presents updated information on the toxicological effects, including the cytotoxicity, genotoxicity, carcinogenicity, and adverse clinical effects of Aloe vera whole leaf extract, gel, and latex. PMID:26986231

  8. 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. ...

  9. A drug-adverse event extraction algorithm to support pharmacovigilance knowledge mining from PubMed citations.

    PubMed

    Wang, Wei; Haerian, Krystl; Salmasian, Hojjat; Harpaz, Rave; Chase, Herbert; Friedman, Carol

    2011-01-01

    Adverse drug events (ADEs) create a serious problem causing substantial harm to patients. An executable standardized knowledgebase of drug-ADE relations which is publicly available would be valuable so that it could be used for ADE detection. The literature is an important source that could be used to generate a knowledgebase of drug-ADE pairs. In this paper, we report on a method that automatically determines whether a specific adverse event (AE) is caused by a specific drug based on the content of PubMed citations. A drug-ADE classification method was initially developed to detect neutropenia based on a pre-selected set of drugs. This method was then applied to a different set of 76 drugs to determine if they caused neutropenia. For further proof of concept this method was applied to 48 drugs to determine whether they caused another AE, myocardial infarction. Results showed that AUROC was 0.93 and 0.86 respectively. PMID:22195210

  10. Measuring Adverse Drug Events on Hospital Medicine Units with the Institute for Healthcare Improvement Trigger Tool: A Chart Review

    PubMed Central

    Lau, Iris; Kirkwood, Allison

    2014-01-01

    Background: An adverse drug event (ADE) is a noxious, unintended response to a drug, occurring at doses used in humans for prophylaxis, diagnosis, or treatment of disease or for modification of physiological function. ADEs account for about one-quarter of all adverse events in Canadian hospitals. Canadian data on specific types of ADEs and commonly implicated drugs are lacking. In particular, there is a paucity of data on ADEs that occur during hospital admissions. Objectives: The primary objective was to identify the incidence of ADEs in a sample of adult general medicine inpatients over a 1-year period. The secondary objective was to identify the 5 drugs most frequently responsible for ADEs in this setting. Methods: A retrospective chart analysis was conducted for general medicine patients discharged from St Paul’s Hospital in Vancouver, British Columbia, from January to December 2011. ADEs were identified using the Institute for Healthcare Improvement (IHI) Trigger Tool for Measuring Adverse Drug Events. The Naranjo criteria were applied to assess causality, and a physician independently authenticated the ADEs for preventability and harm using the categories of harm set out by the US National Coordinating Council for Medication Error Reporting and Prevention. Results: Of the 204 patient encounters reviewed, 15 involved ADEs, which represented an incidence of 7% over the 1-year study period. The 5 drugs most frequently implicated in ADEs were vancomycin, ciprofloxacin, ceftriaxone, piperacillin–tazobactam, and moxifloxacin. Conclusions: The rate of ADEs during hospital admissions was substantial. These events may necessitate additional investigations and interventions and may prolong the hospital stay. The authors do not recommend the IHI Trigger Tool for Measuring Adverse Drug Events for efficient prospective detection of ADEs in manual chart reviews. Possible modifications to improve the utility of this tool might include incorporating it into a compatible

  11. 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

  12. Translational potential of a mouse in vitro bioassay in predicting gastrointestinal adverse drug reactions in Phase I clinical trials

    PubMed Central

    Keating, C; Ewart, L; Grundy, L; Valentin, JP; Grundy, D

    2014-01-01

    Background Motility-related gastrointestinal (GI) adverse drug reactions (GADRs) such as diarrhea and constipation are a common and deleterious feature associated with drug development. Novel biomarkers of GI function are therefore required to aid decision making on the GI liability of compounds in development. Methods Fifteen compounds associated with or without clinical GADRs were used to assess the ability of an in vitro colonic motility bioassay to predict motility-related GADRs. Compounds were examined in a blinded fashion for their effects on mouse colonic peristaltic motor complexes in vitro. For each compound concentration-response relationships were determined and the results compared to clinical data. Compounds were also assessed using GI transit measurements obtained using an in vivo rat charcoal meal model. Key Results Within a clinically relevant dosing range, the in vitro assay identified five true and three false positives, four true and three false negatives, which gave a predictive capacity of 60%. The in vivo assay detected four true and four false positives, four false and three true negatives, giving rise to a predictive capacity for this model of 47%. Conclusions & Inferences Overall these results imply that both assays are poor predictors of GADRs. Further analysis would benefit from a larger compound set, but the data show a clear need for improved models for use in safety pharmacology assessment of GI motility. PMID:24813024

  13. Adverse events of sacral neuromodulation for fecal incontinence reported to the federal drug administration

    PubMed Central

    Bielefeldt, Klaus

    2016-01-01

    AIM: To investigate the nature and severity of AE related to sacral neurostimulation (SNS). METHODS: Based on Pubmed and Embase searches, we identified published trials and case series of SNS for fecal incontinence (FI) and extracted data on adverse events, requiring an active intervention. Those problems were operationally defined as infection, device removal explant or need for lead and/or generator replacement. In addition, we analyzed the Manufacturer and User Device Experience registry of the Federal Drug Administration for the months of August - October of 2015. Events were included if the report specifically mentioned gastrointestinal (GI), bowel and FI as indication and if the narrative did not focus on bladder symptoms. The classification, reporter, the date of the recorded complaint, time between initial implant and report, the type of AE, steps taken and outcome were extracted from the report. In cases of device removal or replacement, we looked for confirmatory comments by healthcare providers or the manufacturer. RESULTS: Published studies reported adverse events and reoperation rates for 1954 patients, followed for 27 (1-117) mo. Reoperation rates were 18.6% (14.2-23.9) with device explants accounting for 10.0% (7.8-12.7) of secondary surgeries; rates of device replacement or explant or pocket site and electrode revisions increased with longer follow up. During the period examined, the FDA received 1684 reports of AE related to SNS with FI or GI listed as indication. A total of 652 reports met the inclusion criteria, with 52.7% specifically listing FI. Lack or loss of benefit (48.9%), pain or dysesthesia (27.8%) and complication at the generator implantation site (8.7%) were most commonly listed. Complaints led to secondary surgeries in 29.7% of the AE. Reoperations were performed to explant (38.2%) or replace (46.5%) the device or a lead, or revise the generator pocket (14.6%). Conservative management changes mostly involved changes in stimulation

  14. [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. PMID:27453095

  15. Prolonged Ventricular Asystole: A Rare Adverse Effect of Hydrocodone Use

    PubMed Central

    Sudhakaran, Sivakumar; Surani, Saherish S.; Surani, Salim R.

    2014-01-01

    Patient: Female, 56 Final Diagnosis: Ventricular asystole Symptoms: Dizziness, headache, near-syncope, weakness Medication: — Clinical Procedure: — Specialty: Cardiology Objective: Unusual clinical course Background: Prolonged ventricular asystole is a rare vagal reaction caused by hydrocodone use. Sinus bradycardia is a characteristic presentation of the vasovagal response; examples of other presentations include arrest or atrioventricular block. Physicians need to be aware of ventricular asystole due to vagally-mediated atrioventricular block caused by hydrocodone or other opiates. Case Report: We present a case of prolonged ventricular asystole in a young patient due to a vasovagal reaction caused by the hydrocodone found in the hydrocodone/acetaminophen combination. Conclusions: Ventricular asystole can be a rare complication of hydrocodone found in hydrocodone/acetaminophen. Physicians need to be aware of this adverse effect, rather then resorting to expensive diagnostic interventions. PMID:25330933

  16. Adverse Drug Reaction Profile in Patients on Anti-tubercular Treatment Alone and in Combination with Highly Active Antiretroviral Therapy

    PubMed Central

    Sadiq, Shamiya; Khajuria, Vijay; Mahajan, Annil; Singh, Jang B.

    2015-01-01

    Background and Objectives Adverse drug reactions are very common among patients on anti-tubercular treatment alone or in combination with highly active antiretroviral therapy but comparatively studied very less. Hence, the current study was done to evalaute the adverse drug reaction (ADR) profile in patients receiving anti-tubercular treatment (ATT) and ATT with highly active antiretroviral therapy (HAART). Materials and Methods A one year prospective, cross-sectional observational study was undertaken using suspected adverse drug data collection form available under Pharmacovigilance Programme of India. Results Seventy four patients receiving ATT & 32 patients on both ATT & HAART presented with 74 and 45 adverse drug events (ADE) respectively. Males were more affected than females in both the groups. DOTS category- 1 regimen was mostly responsible for ADE in both the groups. Epigastric pain was the most common ADE in TB patients, while anaemia was the most common presentation in TB with HIV group. On comparison, ADE rate of TB with HIV co-morbid patients was more (55.8%) than TB patients (0.36%) (p < 0.001). Urban population presented more with ADR in TB/HIV group unlike rural population in TB group (p<0.0001). Whereas, illiterate were more involved in TB group unlike literate in TB/HIV group (p<0.05). Type A reactions were more common in TB group (p < 0.001). Addition of drugs for the management of ADR events was more in TB/HIV group (p < 0.001) as compared to TB group. Rest all the parameters were comparable. Conclusion The study underscores that concomitant HAART and ATT, result in more ADRs in comparison to ATT alone demanding collaboration & integration of National AIDS Control programme and PvPI to enhance drug safety in this field. PMID:26557538

  17. Cost of illness of patient-reported adverse drug events: a population-based cross-sectional survey

    PubMed Central

    Gyllensten, Hanna; Rehnberg, Clas; Jönsson, Anna K; Petzold, Max; Carlsten, Anders; Andersson Sundell, Karolina

    2013-01-01

    Objectives To estimate the cost of illness (COI) of individuals with self-reported adverse drug events (ADEs) from a societal perspective and to compare these estimates with the COI for individuals without ADE. Furthermore, to estimate the direct costs resulting from two ADE categories, adverse drug reactions (ADRs) and subtherapeutic effects of medication therapy (STE). Design Cross-sectional study. Setting The adult Swedish general population. Participants The survey was distributed to a random sample of 14 000 Swedish residents aged 18 years and older, of which 7099 responded, 1377 reported at least one ADE and 943 reported an ADR or STE. Main outcome measures Societal COI, including direct and indirect costs, for individuals with at least one self-reported ADE, and the direct costs for prescription drugs and healthcare use resulting from self-reported ADRs and STEs were estimated during 30 days using a bottom-up approach. Results The economic burden for individuals with ADEs were (95% CI) 442.7 to 599.8 international dollars (Int$), of which direct costs were Int$ 279.6 to 420.0 (67.1%) and indirect costs were Int$ 143.0 to 199.8 (32.9%). The average COI was higher among those reporting ADEs compared with other respondents (COI: Int$ 442.7 to 599.8 versus Int$ 185.8 to 231.2). The COI of respondents reporting at least one ADR or STE was Int$ 468.9 to 652.9. Direct costs resulting from ADRs or STEs were Int$ 15.0 to 48.4. The reported resource use occurred both in hospitals and outside in primary care. Conclusions Self-reported ADRs and STEs cause resource use both in hospitals and in primary care. Moreover, ADEs seem to be associated with high overall COI from a societal perspective when comparing respondents with and without ADEs. There is a need to further examine this relationship and to study the indirect costs resulting from ADEs. PMID:23794552

  18. [Analysis on 315 cases of clinical adverse drug reaction/event induced by gastrodin].

    PubMed

    Zheng, Yang-yang; Dong, Zhi; Lu, Xiao-qin; Xia, Yong-peng; Zhu, Shu-bing

    2015-05-01

    With patients' general situation, medication use, occurrence time of adverse drug reaction/event (ADR/ADE), clinical manifestations and prognosis as reference items, a retrospective study was made for 315 cases with ADR/ADE induced by Gastrodin in Chongqing from January 2008 to June 2014, in order to analyze the characteristics of ADR/ADE and provide reference for rational clinical medication. The results showed that among the 315 cases with ADR/ADE, 143 cases (45.4%) were males and 172 cases (54.6%) were females, most of them (74.9%) were aged above 45; 60 cases (19.0%) with ADE were caused by off-label indications and 66 cases (21.0%) with ADE were caused by over dosage; ADR/ADE cases induced by intravenous drip mainly happened within 30 min (85.5%), ADR/ADE cases induced by oral administration mainly happened within 2 h (74.4%), and all of ADR/ ADE cases induced by intramuscular injection happened within 10 min. Totally 593 ADR/ADE cases were reported, which were mainly damages in gastrointestinal system, skin and its adnexa; And 61.9% of ADR/ADE cases were newly reported. It is suggested that medical workers shall learn about the regularity and characteristics of ADR/ADE induced by gastrodin, apply it in clinic with standards, pay close attention to changes of patients' situations and attach importance to the monitoring of ADR/ADE, so as to enhance the safety of medication. PMID:26390669

  19. Community pharmacists’ knowledge, behaviors and experiences about adverse drug reaction reporting in Saudi Arabia

    PubMed Central

    Mahmoud, Mansour Adam; Alswaida, Yazeed; Alshammari, Thamir; Khan, Tahir Mehmood; Alrasheedy, Alian; Hassali, Mohamad Azmi; Aljadhey, Hisham

    2013-01-01

    Objective To assess community pharmacists’ knowledge, behaviors and experiences relating to Adverse Drug Reaction (ADR) reporting in Saudi Arabia. Methods A cross-sectional study was conducted using a validated self-administered questionnaire. A convenience sample of 147 community pharmacists working in community pharmacies in Riyadh, Saudi Arabia. Results The questionnaire was distributed to 147 pharmacists, of whom 104 responded to the survey, a 70.7% response rate. The mean age of participants was 29 years. The majority (n = 101, 98.1%) had graduated with a bachelorette degree and worked in chain pharmacies (n = 68, 66.7%). Only 23 (22.1%) said they were familiar with the ADR reporting process, and only 21 (20.2%) knew that pharmacists can submit ADR reports online. The majority of the participants (n = 90, 86.5%) had never reported ADRs. Reasons for not reporting ADRs most importantly included lack of awareness about the method of reporting (n = 22, 45.9%), misconception that reporting ADRs is the duty of physician and hospital pharmacist (n = 8, 16.6%) and ADRs in community pharmacies are simple and should not be reported (n = 8, 16.6%). The most common approach perceived by community pharmacists for managing patients suffering from ADRs was to refer him/her to a physician (n = 80, 76.9%). Conclusion The majority of community pharmacists in Riyadh have poor knowledge of the ADR reporting process. Pharmacovigilance authorities should take necessary steps to urgently design interventional programs in order to increase the knowledge and awareness of pharmacists regarding the ADR reporting process. PMID:25473329

  20. Relationship between serum acetaminophen concentration and N-acetylcysteine-induced adverse drug reactions.

    PubMed

    Zyoud, Sa'ed H; Awang, Rahmat; Sulaiman, Syed Azhar Syed; Khan, Halilol Rahman Mohamed; Sawalha, Ansam F; Sweileh, Waleed M; Al-Jabi, Samah W

    2010-09-01

    Intravenous N-acetylcysteine is usually regarded as a safe antidote. However, during the infusion of the loading dose, different types of adverse drug reactions (ADR) may occur. The objective of this study was to investigate the relation between the incidence of different types of ADR and serum acetaminophen concentration in patients presenting to the hospital with acetaminophen overdose. This is a retrospective study of patients admitted to the hospital for acute acetaminophen overdose over a period of 5 years (1 January 2004 to 31 December 2008). Parametric and non-parametric tests were used to test differences between groups depending on the normality of the data. SPSS 15 was used for data analysis. Of 305 patients with acetaminophen overdose, 146 (47.9%) were treated with intravenous N-acetylcysteine and 139 (45.6%) were included in this study. Different types of ADR were observed in 94 (67.6%) patients. Low serum acetaminophen concentrations were significantly associated with cutaneous anaphylactoid reactions but not other types of ADR. Low serum acetaminophen concentration was significantly associated with flushing (p < 0.001), rash (p < 0.001) and pruritus (p < 0.001). However, there were no significant differences in serum acetaminophen concentrations between patients with and without the following ADR: gastrointestinal reactions (p = 0.77), respiratory reactions (p = 0.96), central nervous reactions (p = 0.82) and cardiovascular reactions (p = 0.37). In conclusion, low serum acetaminophen concentrations were associated with higher cutaneous anaphylactoid reactions. Such high serum acetaminophen concentrations may be protective against N-acetylcysteine-induced cutaneous ADR. PMID:20374238

  1. A Survey of Nursing Home Physicians to Determine Laboratory Monitoring Adverse Drug Event Alert Preferences

    PubMed Central

    Perera, S.; Nace, D.A.; Culley, C.M.; Handler, S.M.

    2014-01-01

    Summary Objective We conducted a survey of nursing home physicians to learn about (1) the laboratory value thresholds that clinical event monitors should use to generate alerts about potential adverse drug events (ADEs); (2) the specific information to be included in the alerts; and (3) the communication modality that should be used for communicating them. Methods Nursing home physician attendees of the 2010 Conference of AMDA: The Society for Post-Acute and Long-Term Care Medicine. Results A total of 800 surveys were distributed; 565 completed surveys were returned and seven surveys were excluded due to inability to verify that the respondents were physicians (a 70% net valid response rate). Alerting threshold preferences were identified for eight laboratory tests. For example, the majority of respondents selected thresholds of ≥ 5.5 mEq/L for hyperkalemia (63%) and ≤ 3.5 without symptoms for hypokalemia (54%). The majority of surveyed physicians thought alerts should include the complete active medication list, current vital signs, previous value of the triggering lab, medication change in the past 30 days, and medication allergies. Most surveyed physicians felt the best way to communicate an ADE alert was by direct phone/voice communication (64%), followed by email to a mobile device (59%). Conclusions This survey of nursing home physicians suggests that the majority prefer alerting thresholds that would generally lead to fewer alerts than if widely accepted standardized laboratory ranges were used. It also suggests a subset of information items to include in alerts, and the physicians’ preferred communication modalities. This information might improve the acceptance of clinical event monitoring systems to detect ADEs in the nursing home setting. PMID:25589905

  2. Knowledge, attitudes and practice of nurse regarding adverse drug reaction reporting

    PubMed Central

    Hanafi, Somayeh; Torkamandi, Hassan; Hayatshahi, Alireza; Gholami, Kheirollah; Javadi, Mohammadreza

    2012-01-01

    Background: Adverse drug reactions (ADR) are ranked as some of the major causes of patient morbidity and mortality. Spontaneous reporting of ADRs has remained the cornerstone of pharmacovigilance and is important in maintaining patient safety. This study was conducted to assess the nurses’ knowledge and attitude towards pharmacovigilance, reasons for not reporting ADRs, and their pharmacovigilance practice. Materials and Methods: A questionnaire was prepared to investigate knowledge, attitude and practice (KAP) of nurses regarding ADR reporting. In November 2009, the questionnaires were given to 500 nurses of a teaching hospital in Tehran. Findings: Knowledge and practice of participants were not satisfying; however, their attitude towards pharmacovigilance was at a high level. About 91% of the nurses had never reported an ADR. Most nurses liked to report the ADRs to the physicians (87.1%) and pharmacists in hospital's ADR center (1.8%) rather than the ADR National Center. The main cause of under-reporting of the suspected ADRs was unawareness about the existence of such a national center. Among nurses who had reported ADR for at least once, the majority preferred using phone (10 out of 50) or Yellow Cards (7 out of 50). Only 1 person out of 50 preferred using internet for submitting the reports Conclusions: Since the nurses in this study had little knowledge and poor practice regarding the pharmacovigilance and spontaneous reporting system, interventions such as holding pharmacovigilance workshops in the hospitals focusing on the aims of pharmacovigilance, completing the Yellow Card and clarifying the reporting criteria are strongly recommended. PMID:23492864

  3. Predictive Factors of Spontaneous Reporting of Adverse Drug Reactions among Community Pharmacists

    PubMed Central

    Yu, Yun Mi; Lee, Euni; Koo, Bon Sun; Jeong, Kyeong Hye; Choi, Kyung Hee; Kang, Lee Kyung; Lee, Mo Se; Choi, Kwang Hoon; Oh, Jung Mi; Shin, Wan Gyoon

    2016-01-01

    Purpose To evaluate the association between spontaneous reporting (SR) and the knowledge, attitude, and needs of community pharmacists (CPs), using a questionnaire following a conceptual model known as the mixed model of knowledge-attitude-practices and the satisfaction of needs. Methods Self-administered questionnaires were used with a nationwide convenience sample of CPs between September 1, 2014 and November 25, 2014 in Korea. The association between SR and the predictive factors was evaluated using multivariate logistic regression analysis. Results In total, 1,001 questionnaires were analyzed. The mean age of the respondents and the number of years spent in community pharmacy practice were 45.6 years and 15.3 years, respectively. CPs with experience of SR was 29.4%. Being older than 60 (ORadj, 0.16; 95% CI, 0.06–0.42), having prior experience with adverse drug reactions (ADR) (ORadj, 6.46; 95% CI, 2.46–16.98), having higher specific knowledge of SR (ORadj, 3.58; 95% CI, 1.96–6.56), and having less concern about the obstacles to SR (ORadj, 0.36; 95% CI, 0.23–0.57) were significant contributing factors to SR. The main obstacles to SR included perception of ADRs as ‘not serious ADR’ (77.9%), ‘already well known ADR’ (81.5%), and ‘uncertain about causality’ (73.3%). CPs without reporting experience had greater concerns related to the reporting method and the liability of the pharmacy than those with reporting experience (p<0.05). Conclusions Findings from our study showed around one in three CPs had ADR reporting experience in Korea, while 87.1% had prior experience with ADR cases. The knowledge of SR, prior experience of ADR, and less concern about the obstacles to SR were contributing factors for reporting levels. PMID:27192159

  4. Adverse Drug Events in the Outpatient Setting: An 11-Year National Analysis

    PubMed Central

    Bourgeois, Florence T; Shannon, Michael W; Valim, Clarissa; Mandl, Kenneth D

    2010-01-01

    Purpose Adverse drug events (ADEs) are a common complication of medical care resulting in high morbidity and medical expenditure. Population level estimates of outpatient ADEs are limited. Our objective was to provide national estimates and characterizations of outpatient ADEs and determine risk factors associated with these events. Methods Data are from the National Center for Health Statistics which collects information on patient visits to outpatient clinics and emergency departments throughout the United States. We examined visits between 1995 and 2005 and measured the national annual estimates of and risk factors for outpatient ADEs requiring medical treatment. Results The national annual number of ADE-related visits was 4,335,990 (95%CI, 4,326,872–4,345,108). Visits for ADEs to outpatient clinics increased over the study period from 9.0 to 17.0 per 1000 persons (P value for trend<0.001). In multivariate analyses, factors associated with ADE visits included patient age (OR 2.13; 95%CI 1.63–2.79 for 65 years and older), number of medications taken by patient (OR, 1.88; 95%CI, 1.58–2.25 for five medications or more), and female gender (OR, 1.51; 95%CI, 1.34–1.71). Overall, outpatient ADEs resulted in 107,468 (95%CI, 89,011–125,925) hospital admissions annually, with older patients at highest risk for hospitalization (P value for trend<0.001). Conclusions Both patient age and polypharmacy use are risk factors for ADE-related healthcare visits, which have substantially increased in outpatient clinics between 1995 and 2005. The incidence of ADEs has particularly increased among patients 65 years and older with as many as 1 in 20 persons seeking medical care for an ADE. PMID:20623513

  5. Adverse drug reactions to antiretroviral therapy: Results from spontaneous reporting system in Nigeria

    PubMed Central

    Agu, Kenneth A.; Oparah, Azuka C.

    2013-01-01

    Aim: This study evaluated the suspected adverse drug reactions (ADR) reported from a spontaneous reporting program in Human Immunodeficiency Virus (HIV) positive patients receiving antiretroviral therapy (ART) in Nigeria Materials and Methods: This descriptive study analyzed individual case safety reports (ICSRs) in HIV-positive patients receiving ART between January 2011 and December 2011 in 38 secondary hospitals. All ICSRs during this period were included. Chi-square was used to test the association between variables at 95% confidence interval. Results: From 1237 ICSRs collated, only 1119 (90.5%) were valid for analysis. Mean age of patients was 35.3 (95%CI, 35.1–35.5) years; and 67.1% were females. A total of 1679 ADR cases were reported, a mean (± Standard Deviation, SD) of 1.5 (± 0.8) ADR cases per patient. Of reported ADRs, 63.2%, 8.2% and 19.3% occurred in patients on Zidovudine-based, Stavudine-based and Tenofovir-based regimens, respectively. The commonest ADRs included (12.0%) peripheral neuropathy, (11.4%) skin rash, (10.1%) pruritus and (6.5%) dizziness. ADR occurrence was associated with ART regimens, concomitant medicines and age (P < 0.05) unlike gender. Anaemia was associated with Zidovudine (AZT)/ Lamivudine (3TC) /Nevirapine (NEV) regimen [Odds ratio, OR = 6.4 (3.0–13.8); P < 0.0001], and peripheral neuropathy with Stavudine (d4T)/3TC/NEV regimen [OR = 8.7 (5.8–30.0), P < 0.0001] and Tenofovir (TDF)/Emtricitabine (FTC)/Efavirenz (EFV) regimen [OR = 2.1 (1.0–4.1), P = 0.0446]. Skin rash and peripheral neuropathy were associated with patients aged < 15years [OR = 3.0 (1.3–6.6), P = 0.0056] and 45–59years [OR = 1.9 (1.3–2.7), P = 0.0006] respectively. Palpitation and polyuria were associated with Salbutamol [OR = 55.7 (4.9–349.6), P = 0.0000] and Nonsteroidal anti-inflammatory drugs (NSAIDS) [OR = 50.2 (0.9–562.1), P = 0.0040] respectively. Conclusion: ADRs were less likely to occur in patients on stavudine-based and tenofovir

  6. Rare, Serious, and Comprehensively Described Suspected Adverse Drug Reactions Reported by Surveyed Healthcare Professionals in Uganda

    PubMed Central

    Kiguba, Ronald; Karamagi, Charles; Waako, Paul; Ndagije, Helen B.; Bird, Sheila M.

    2015-01-01

    Background Lack of adequate detail compromises analysis of reported suspected adverse drug reactions (ADRs). We investigated how comprehensively Ugandan healthcare professionals (HCPs) described their most recent previous-month suspected ADR, and determined the characteristics of HCPs who provided comprehensive ADR descriptions. We also identified rare, serious, and unanticipated suspected ADR descriptions with medication safety-alerting potential. Methods During 2012/13, this survey was conducted in purposively selected Ugandan health facilities (public/private) including the national referral and six regional referral hospitals representative of all regions. District hospitals, health centres II to IV, and private health facilities in the catchment areas of the regional referral hospitals were conveniently selected. Healthcare professionals involved in prescribing, transcribing, dispensing, and administration of medications were approached and invited to self-complete a questionnaire on ADR reporting. Two-thirds of issued questionnaires (1,345/2,000) were returned. Results Ninety per cent (241/268) of HCPs who suspected ADRs in the previous month provided information on five higher-level descriptors as follows: body site (206), drug class (203), route of administration (127), patient age (133), and ADR severity (128). Comprehensiveness (explicit provision of at least four higher-level descriptors) was achieved by at least two-fifths (46%, 124/268) of HCPs. Received descriptions were more likely to be comprehensive from HCPs in private health facilities, regions other than central, and those not involved in teaching medical students. Overall, 106 serious and 51 rare previous-month suspected ADRs were described. The commonest serious and rare ADR was Stevens-Johnson syndrome (SJS); mostly associated with oral nevirapine or cotrimoxazole, but haemoptysis after diclofenac analgesia and paralysis after quinine injection were also described. Conclusion Surveyed Ugandan

  7. Identification and Characterization of Adverse Effects in 21st Century Toxicology

    EPA Science Inventory

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

  8. Pharmacogenetics of quetiapine in healthy volunteers: association with pharmacokinetics, pharmacodynamics, and adverse effects.

    PubMed

    Cabaleiro, Teresa; López-Rodríguez, Rosario; Román, Manuel; Ochoa, Dolores; Novalbos, Jesús; Borobia, Alberto; Carcas, Antonio; Abad-Santos, Francisco

    2015-03-01

    Quetiapine is an atypical antipsychotic used for treatment of schizophrenia. Variability in response to this drug may be associated with pharmacogenetics. The aim of this study was to identify genetic markers related to the pharmacokinetics, pharmacodynamics, and adverse effects of quetiapine. The study population comprised 79 healthy volunteers from two bioequivalence trials who were genotyped to identify polymorphisms in genes encoding enzymes, receptors, and transporters. Quetiapine plasma levels were quantified using high-performance liquid chromatography/mass spectrometry. Prolactin plasma levels were detected by indirect chemiluminescence. Possible adverse effects were recorded throughout the study. Factors with P value of 0.1 or less in the univariate analysis were included in a multiple regression analysis (logistic regression for adverse reactions). The area under the curve and clearance of quetiapine were affected by polymorphisms in CYP1A2 and DRD3, respectively. Men had a lower quetiapine area under the curve compared with women. Prolactin iC(max) was higher in volunteers harboring polymorphisms in CYP2C19 and AGT. An association was detected between polymorphisms in CYP1A1 and CYP2C9 and somnolence. Several polymorphisms are responsible for differences in the pharmacokinetics, pharmacodynamics, and safety of quetiapine in healthy individuals. PMID:25025989

  9. The Adverse Effects of Air Pollution on the Nervous System

    PubMed Central

    Genc, Sermin; Zadeoglulari, Zeynep; Fuss, Stefan H.; Genc, Kursad

    2012-01-01

    Exposure to ambient air pollution is a serious and common public health concern associated with growing morbidity and mortality worldwide. In the last decades, the adverse effects of air pollution on the pulmonary and cardiovascular systems have been well established in a series of major epidemiological and observational studies. In the recent past, air pollution has also been associated with diseases of the central nervous system (CNS), including stroke, Alzheimer's disease, Parkinson's disease, and neurodevelopmental disorders. It has been demonstrated that various components of air pollution, such as nanosized particles, can easily translocate to the CNS where they can activate innate immune responses. Furthermore, systemic inflammation arising from the pulmonary or cardiovascular system can affect CNS health. Despite intense studies on the health effects of ambient air pollution, the underlying molecular mechanisms of susceptibility and disease remain largely elusive. However, emerging evidence suggests that air pollution-induced neuroinflammation, oxidative stress, microglial activation, cerebrovascular dysfunction, and alterations in the blood-brain barrier contribute to CNS pathology. A better understanding of the mediators and mechanisms will enable the development of new strategies to protect individuals at risk and to reduce detrimental effects of air pollution on the nervous system and mental health. PMID:22523490

  10. Parenteral Lipid Tolerance and Adverse Effects: Fat Chance for Trouble?

    PubMed

    Wanten, Geert J A

    2015-09-01

    Lipid emulsions (LEs) are indispensable sources of fuel calories and (essential) fatty acids (FAs) in modern parenteral nutrition formulations. The use of LE, however, also remains associated with the development of adverse effects. Intolerance for LE mostly becomes apparent upon the development of patient complaints or disturbed blood function tests, mainly of the liver. These issues may be associated with the composition, stability, or the infusion rate of the emulsion. Also, altered balances of (anti)oxidants or the presence or absence of protective or toxic bioactive agents such as phytosterols and tocopherol in LE may lead to complications, especially in already vulnerable patients with an inflammatory condition. While the oldest available LEs are based on pure soybean oil (SO-LE), rich in the proinflammatory ω-6 polyunsaturated fatty acid linoleic acid, more recent next-generation LEs where alternative FA sources such as olive and fish oil (partially) replace soybean oil to lower the content of linoleic acid seem safe and effective. Especially LEs containing fish oil (FO-LE) have less proinflammatory characteristics that promise to convey beneficial effects on immune system and organ functions, although much of the available evidence awaits more robust clinical validation. PMID:26177663

  11. Soy isoflavones ameliorate the adverse effects of chemotherapy in children.

    PubMed

    Tacyildiz, Nurdan; Ozyoruk, Derya; Yavuz, Gulsan; Unal, Emel; Dincaslan, Handan; Dogu, Figen; Sahin, Kazim; Kucuk, Omer

    2010-01-01

    Genistein sensitizes cancer cells to chemotherapy and radiation by modulating cell survival pathways. At the same time, genistein's antioxidant and anti-inflammatory effects may protect normal tissues from adverse effects of chemotherapy and radiation, which are largely due to oxygen-free radicals and inflammation. We conducted a small pilot study with a soy isoflavone mixture containing 8 mg of genistein in children receiving chemotherapy and/or radiation to investigate genistein's potential toxicity preventive effect. We monitored clinical and laboratory parameters in children with cancer who received their first cycle of chemotherapy without genistein and the subsequent cycles with genistein. Patients served as their own controls, and the clinical-laboratory data from the first cycle were compared to the data from subsequent cycles. Nine cycles of chemotherapy were administered without genistein and 57 cycles with genistein. Patients experienced less myelosuppression, mucositis, and infection when they received genistein with chemotherapy. During supplementation, serum genistein levels were 2 to 6 times higher compared to presupplementation levels. Patients who received abdominal radiation reported less pain and diarrhea when they took the genistein supplement. Further clinical investigation of soy isoflavones in pediatric cancer patients receiving chemotherapy and/or radiation should be conducted. PMID:20924976

  12. Abuse potential and adverse cognitive effects of mitragynine (kratom).

    PubMed

    Yusoff, Nurul H M; Suhaimi, Farah W; Vadivelu, Raja K; Hassan, Zurina; Rümler, Anne; Rotter, Andrea; Amato, Davide; Dringenberg, Hans C; Mansor, Sharif M; Navaratnam, Visweswaran; Müller, Christian P

    2016-01-01

    Mitragynine is the major psychoactive alkaloid of the plant kratom/ketum. Kratom is widely used in Southeast Asia as a recreational drug, and increasingly appears as a pure compound or a component of 'herbal high' preparations in the Western world. While mitragynine/kratom may have analgesic, muscle relaxant and anti-inflammatory effects, its addictive properties and effects on cognitive performance are unknown. We isolated mitragynine from the plant and performed a thorough investigation of its behavioural effects in rats and mice. Here we describe an addictive profile and cognitive impairments of acute and chronic mitragynine administration, which closely resembles that of morphine. Acute mitragynine has complex effects on locomotor activity. Repeated administration induces locomotor sensitization, anxiolysis and conditioned place preference, enhances expression of dopamine transporter- and dopamine receptor-regulating factor mRNA in the mesencephalon. While there was no increase in spontaneous locomotor activity during withdrawal, animals showed hypersensitivity towards small challenging doses for up to 14 days. Severe somatic withdrawal signs developed after 12 hours, and increased level of anxiety became evident after 24 hours of withdrawal. Acute mitragynine independently impaired passive avoidance learning, memory consolidation and retrieval, possibly mediated by a disruption of cortical oscillatory activity, including the suppression of low-frequency rhythms (delta and theta) in the electrocorticogram. Chronic mitragynine administration led to impaired passive avoidance and object recognition learning. Altogether, these findings provide evidence for an addiction potential with cognitive impairments for mitragynine, which suggest its classification as a harmful drug. PMID:25262913

  13. A review of the adverse side effects associated with antipsychotics as related to their efficacy.

    PubMed

    Pakpoor, Jina; Agius, Mark

    2014-11-01

    Since the introduction of antipsychotic medication for the treatment of psychosis, a wide range of different types of antipsychotic drugs have been developed while their side effects have become evident. The side effects of both the typical and atypical generation of antipsychotics have important consequences for the quality of life of recipients, stigma experienced and also the level of care of patients. It is well acknowledged that the side effects of antipsychotics reduce compliance with the medication. In this review the data for an association between typical and atypical antipsychotics and the main side effects that are well-supported in the literature was explored: weight gain and associated metabolic effects; extrapyramidal symptoms and tardive dyskinesia; prolactin elevation and associated sexual effects; QTc elongation; and a group of miscellaneous side effects. It has been demonstrated that the production of adverse effects following the use of antipsychotic medication differs widely both between atypical and typical drugs but also within these subgroups. Considering the wide range of antipsychotics available amongst both groups and the differing effects they have on patients in terms of side effects, there is reason to believe that a more personalised approach to antipsychotic treatment should be considered. Additionally, screening for risk factors, screening for the appearance of side effects, as well as good communication with patients about the side effects and other options available are important tasks for clinicians in order to optimise concordance with medication. PMID:25413553

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

    PubMed Central

    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. PMID:27326858

  15. 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. PMID:27326858

  16. Drug Discontinuation Effects Are Part of the Pharmacology of a Drug

    PubMed Central

    2011-01-01

    Most reviews of drug withdrawal effects focus on drugs of potential abuse such as opioids, benzodiazepines, etc. Abrupt discontinuation of many other drugs used in medicine cause withdrawal syndromes, some of which can be fatal. Discontinuation of a number of cardiovascular drugs can increase risk of cardiovascular events above that of people not taking these drugs. These include β-adrenergic receptor antagonists, aspirin, HMG-CoA reductase inhibitors (statins), and heparin. Rebound hypertension occurs after abrupt cessation of many antihypertensive drugs. The possibility of discontinuation syndromes has usually been neglected until adverse clinical events force them to be noticed. Attention to the possibility of drug discontinuation effects is an important part of drug safety evaluation. PMID:21849624

  17. 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

  18. Cardiovascular Adverse Reactions During Antidepressant Treatment: A Drug Surveillance Report of German-Speaking Countries Between 1993 and 2010

    PubMed Central

    Spindelegger, Christoph Josef; Papageorgiou, Konstantinos; Grohmann, Renate; Engel, Rolf; Greil, Waldemar; Konstantinidis, Anastasios; Agelink, Marcus Willy; Bleich, Stefan; Ruether, Eckart; Toto, Sermin

    2015-01-01

    Background: Antidepressants (ADs) are known to have the potential to cause various cardiovascular adverse drug reactions (ADRs). The tricyclic antidepressants (TCAs) were first revealed to be a possible source of cardiovascular ADRs. In recent years, newer classes of ADs were also suggested to have a higher risk of cardiovascular adverse effects. In particular, the selective serotonin reuptake inhibitors (SSRIs) were suspected to have the potential to induce QTc interval prolongation, and therefore increase the risk of ventricular arrhythmia. This descriptive study is based on the continuous pharmacovigilance program of German-speaking countries (Austria, Germany, and Switzerland), the Arzneimittelsicherheit in der Psychiatrie (AMSP), which assesses severe ADRs occurring in clinical routine situations. Methods: Of 169 278 psychiatric inpatients treated with ADs between 1993 and 2010, 198 cases of cardiovascular ADRs (0.12%) were analyzed. Results: Our study showed that the incidence rates of cardiovascular ADRs were highest during treatment with monoamine oxidase inhibitors (0.27%), TCAs (0.15%), and serotonin noradrenaline reuptake inhibitors (0.14%); the risk of occurring during treatment with SSRIs (0.08%) was significantly lower. The noradrenergic and specific serotonergic AD mirtazapine (0.07%) had a significantly lower risk of cardiovascular ADRs than all other ADs. Severe hypotension was the most frequent ADR, followed by hypertension, arrhythmia, and in some rare cases heart failure. Conclusions: Despite certain limitations due to the AMSP study design, our observations on cardiovascular ADRs can contribute to a better knowledge of the cardiovascular risk profiles of antidepressants in the clinical routine setting. However, prospective studies are needed to verify our findings. PMID:25522416

  19. Sex-dimorphic adverse drug reactions to immune suppressive agents in inflammatory bowel disease

    PubMed Central

    Zelinkova, Zuzana; Bultman, Evelien; Vogelaar, Lauran; Bouziane, Cheima; Kuipers, Ernst J; van der Woude, C Janneke

    2012-01-01

    AIM: To analyze sex differences in adverse drug reactions (ADR) to the immune suppressive medication in inflammatory bowel disease (IBD) patients. METHODS: All IBD patients attending the IBD outpatient clinic of a referral hospital were identified through the electronic diagnosis registration system. The electronic medical records of IBD patients were reviewed and the files of those patients who have used immune suppressive therapy for IBD, i.e., thiopurines, methotrexate, cyclosporine, tacrolimus and anti-tumor necrosis factor agents (anti-TNF); infliximab (IFX), adalimumab (ADA) and/or certolizumab, were further analyzed. The reported ADR to immune suppressive drugs were noted. The general definition of ADR used in clinical practice comprised the occurrence of the ADR in the temporal relationship with its disappearance upon discontinuation of the medication. Patients for whom the required information on drug use and ADR was not available in the electronic medical record and patients with only one registered contact and no further follow-up at the outpatient clinic were excluded. The difference in the incidence and type of ADR between male and female IBD patients were analyzed statistically by χ2 test. RESULTS: In total, 1009 IBD patients were identified in the electronic diagnosis registration system. Out of these 1009 patients, 843 patients were eligible for further analysis. There were 386 males (46%), mean age 42 years (range: 16-87 years) with a mean duration of the disease of 14 years (range: 0-54 years); 578 patients with Crohn’s disease, 244 with ulcerative colitis and 21 with unclassified colitis. Seventy percent (586 pts) of patients used any kind of immune suppressive agents at a certain point of the disease course, the majority of the patients (546 pts, 65%) used thiopurines, 176 pts (21%) methotrexate, 46 pts (5%) cyclosporine and one patient tacrolimus. One third (240 pts, 28%) of patients were treated with anti-TNF, the majority of patients (227

  20. CORAL: model for no observed adverse effect level (NOAEL).

    PubMed

    Toropov, Andrey A; Toropova, Alla P; Pizzo, Fabiola; Lombardo, Anna; Gadaleta, Domenico; Benfenati, Emilio

    2015-08-01

    The in vivo repeated dose toxicity (RDT) test is intended to provide information on the possible risk caused by repeated exposure to a substance over a limited period of time. The measure of the RDT is the no observed adverse effect level (NOAEL) that is the dose at which no effects are observed, i.e., this endpoint indicates the safety level for a substance. The need to replace in vivo tests, as required by some European Regulations (registration, evaluation authorization and restriction of chemicals) is leading to the searching for reliable alternative methods such as quantitative structure-activity relationships (QSAR). Considering the complexity of the RDT endpoint, for which data quality is limited and depends anyway on the study design, the development of QSAR for this endpoint is an attractive task. Starting from a dataset of 140 organic compounds with NOAEL values related to oral short term toxicity in rats, we developed a QSAR model based on optimal descriptors calculated with simplified molecular input-line entry systems and the graph of atomic orbitals by the Monte Carlo method, using CORAL software. Three different splits into the training, calibration, and validation sets are studied. The mechanistic interpretation of these models in terms of molecular fragment with positive or negative contributions to the endpoint is discussed. The probabilistic definition for the domain of applicability is suggested. PMID:25850638

  1. Neurological Adverse Effects after Radiation Therapy for Stage II Seminoma.

    PubMed

    Ebbeskov Lauritsen, Liv; Meidahl Petersen, Peter; Daugaard, Gedske

    2012-05-01

    We report 3 cases of patients with testicular cancer and stage II seminoma who developed neurological symptoms with bilateral leg weakness about 4 to 9 months after radiation therapy (RT). They all received RT to the para-aortic lymph nodes with a total dose of 40 Gy (36 Gy + 4 Gy as a boost against the tumour bed) with a conventional fractionation of 2 Gy/day, 5 days per week. RT was applied as hockey-stick portals, also called L-fields. In 2 cases, the symptoms fully resolved. Therapeutic irradiation can cause significant injury to the peripheral nerves of the lumbosacral plexus and/or to the spinal cord. RT is believed to produce plexus injury by both direct toxic effects and secondary microinfarction of the nerves, but the exact pathophysiology of RT-induced injury is unclear. Since reported studies of radiation-induced neurological adverse effects are limited, it is difficult to estimate their frequency and outcome. The treatment of neurological symptoms due to RT is symptomatic. PMID:22949908

  2. Management of the adverse effects associated with intravenous bisphosphonates.

    PubMed

    Tanvetyanon, T; Stiff, P J

    2006-06-01

    Intravenous bisphosphonates are widely used to treat hypercalcemia and to reduce skeletal-related morbidity among cancer patients. However, serious complications, generally occurring in less than 2% of patients participated in phase III clinical trials, including acute systemic inflammatory reaction, ocular inflammation, renal failure, nephrotic syndrome, electrolyte imbalance, and osteonecrosis of the maxilla and mandible have all been increasingly reported. Yet, strategies to deal with these complications are becoming clear. Acute systemic inflammatory reaction is often self-limited and becomes less intense during subsequent treatments. For patients who develop ocular symptoms, prompt ophthalmologic evaluation is crucial to determine the safety of a subsequent bisphosphonate therapy. Patients who receive long-term pamidronate should be evaluated at intervals for early sign of nephritic syndrome as timely cessation of the agent may result in a full recovery. To reduce the risk of severe electrolyte abnormalities, particularly hypocalcemia, correcting any pre-treatment electrolyte abnormality and supplementing vitamin D and calcium may be helpful. Finally, to reduce the risk of osteonecrosis of the maxilla and mandible, obtaining a full dental evaluation before treatment and avoidance of invasive dental procedures is suggested. The three commonly used intravenous bisphosphonates (pamidronate, zoledronic acid, and ibandronate), are generally safe; ibandronate has to date been the least reported to be associated with renal side effects. As clinical indications of intravenous bisphosphonates continue to expand, prescribing clinicians should be familiar with these possible adverse effects and discuss them with patients before commencing or continuing on therapy. PMID:16547070

  3. 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

  4. Texting-Based Reporting of Adverse Drug Reactions to Ensure Patient Safety: A Feasibility Study

    PubMed Central

    Castillo-Carandang, Nina T; Juban, Noel R; Amarillo, Maria Lourdes; Tagle, Maria Pamela; Baja, Emmanuel S

    2015-01-01

    Background Paper-based adverse drug reaction (ADR) reporting has been in practice for more than 6 decades. Health professionals remain the primary source of reports, while the value of patients’ reporting is yet unclear. With the increasing popularity of using electronic gadgets in health, it is expected that the electronic transmission of reports will become the norm within a few years. Objective The aims of this study are to investigate whether short messaging service or texting can provide an alternative or supplemental method for ADR reporting given the increasing role of mobile phones in health care monitoring; to determine the usefulness of texting in addition to paper-based reporting of ADRs by resident physicians; and to describe the barriers to ADR reporting and estimate the cost for setting up and maintaining a texting-computer reporting system. Methods This was a pre-post cross-sectional study that measured the number of ADRs texted by 51 resident physicians for 12 months from the Department of Obstetrics and Gynecology and the Department of Adult Medicine of a tertiary government hospital in Manila, Philippines, with 1350-bed capacity. Reports were captured by a texting-computer reporting system. Prior to its implementation, key informant interview and focus group discussion were conducted. Baseline information and practice on the existing paper-based reporting system were culled from the records of the hospital’s Pharmacy and Therapeutics Committee. A postintervention survey questionnaire was administered at the end of 12 months. Results Only 3 ADRs were texted by 51 resident physicians in 12 months (reporting rate 3/51 or 6%). By contrast, 240 ADRs from the paper-based reporting system from 848 resident physicians of the study hospital were collected and tabulated (reporting rate 240/848 or 28.3%). Texting ADRs was not efficient because of power interruption, competition with the existing paper-based reporting system, and unforeseen expiration of

  5. Tolazoline reversal of xylazine in bison (Bison bison): Mitigation of adverse effects

    USGS Publications Warehouse

    Roffe, Thomas J.; Sweeney, Steven J.

    2002-01-01

    Tolazoline is a mixed alpha-1 and -2 adrenergic antagonist used to reverse the sedative, analgesic and muscle-relaxing effects of xylazine, a potent alpha adrenergic agonist. Tolazoline has been used in cattle and is superior to yohimbine, another alpha adrenergic antagonist, in this species. In white-tailed deer, tolazoline shortened recovery times and reversed xylazine-induced bradycardia, respiratory depression, and bloat following xylazine-ketamine anesthesia (Kreeger et al. 1986). We have used it for a number of years in moose without any detected adverse reactions. Caulkett et al. (2000) used tolazoline in wood bison to reverse the xylazine-induced effects of xylazine-tiletamine/zolazepam anesthesia and did not report any ill effects. However, the reported side effects of tolazoline in horses (species for which the drug was developed and is labeled) include abdominal discomfort, gastrointestinal hypermotility, diarrhea, tachycardia, ventricular dysrhythmia, hypertension and apprehensiveness.

  6. The Development of Countermeasures for Space Radiation Induced Adverse Health Effects

    NASA Astrophysics Data System (ADS)

    Kennedy, Ann

    The Development of Countermeasures for Space Radiation Induced Adverse Health Effects Ann R. Kennedy Department of Radiation Oncology, University of Pennsylvania School of Medicine, 195 John Morgan Building, 3620 Hamilton Walk, Philadelphia, PA, United States 19104-6072 The development of countermeasures for radiation induced adverse health effects is a lengthy process, particularly when the countermeasure/drug has not yet been evaluated in human trials. One example of a drug developed from the bench to the clinic is the soybean-derived Bowman-Birk inhibitor (BBI), which has been developed as a countermeasure for radiation induced cancer. It was originally identified as a compound/drug that could prevent the radiation induced carcinogenic process in an in vitro assay system in 1975. The first observation that BBI could inhibit carcinogenesis in animals was in 1985. BBI received Investigational New Drug (IND) Status with the U.S. Food and Drug Administration (FDA) in 1992 (after several years of negotiation with the FDA about the potential IND status of the drug), and human trials began at that time. Phase I, II and III human trials utilizing BBI have been performed under several INDs with the FDA, and an ongoing Phase III trial will be ending in the very near future. Thus, the drug has been in development for 35 years at this point, and it is still not a prescription drug on the market which is available for human use. A somewhat less time-consuming process is to evaluate compounds that are on the GRAS (Generally Recognized as Safe) list. These compounds would include some over-the-counter medications, such as antioxidant vitamins utilized in human trials at the levels for which Recommended Dietary Allowances (RDAs) have been established. To determine whether GRAS substances are able to have beneficial effects on radiation induced adverse health effects, it is still likely to be a lengthy process involving many years to potentially decades of human trial work. The

  7. Identification of risk factors for carbamazepine-induced serious mucocutaneous adverse reactions: A case-control study using data from spontaneous adverse drug reaction reports

    PubMed Central

    Bertulyte, Ilma; Schwan, Sofie; Hallberg, Pär

    2014-01-01

    Objectives: To identify risk factors other than genetic for severe carbamazepine-induced mucocutaneous reactions, that is, SJS, TEN, and exfoliative dermatitis (ED). Materials and Methods: We did a case-control study using data from the Swedish national database of spontaneously reported adverse drug reactions (ADRs). We selected all patients who had been reported from January 1, 1965 to March 31, 2010 as having experienced SJS (n = 78), TEN (n = 6), or ED (n = 8), and assessed as at least possibly related to carbamazepine. We also included diagnoses possibly representative of early signs of these serious conditions, that is, erythema multiforme (EM, n = 34) and scaly rash (n = 13). We compared data on demographics, drug treatment, and clinical features for these patients (cases, n = 139) with those from patients who had experienced any other type of ADR from carbamazepine during the same time period (controls, n = 887). Results: After adjustment for multiple comparisons, alcohol abuse was statistically significantly more common among cases than controls (34.5% vs 8.7%, odds ratio 5.5 [95% confidence interval 3.6-8.4], P = 3.14 × 10-14 ). The same was seen for SJS and EM individually. Conclusion: Alcohol abuse is a possible risk factor for serious carbamazepine-induced mucocutaneous reactions. PMID:24799813

  8. Shocking Results on the Adverse Effects of CO2 Exposures

    NASA Technical Reports Server (NTRS)

    James, John T.

    2012-01-01

    Carbon dioxide (CO2) is released in large quantities from humans while they live and work in spacecraft or work outside the spacecraft during extravehicular activity (EVA). Removal of this anthropogenic pollutant requires major resources, and these resources increase dramatically as the levels of CO2 set to protect human health and performance are reduced. The current Spacecraft Maximum Allowable Concentration of CO2 aboard the ISS is 0.7% or 5.3 mmHg; however, according to Chits (mission action requests), NASA and its international partners have agreed to control CO2 levels to less than 4 mmHg. In the meantime, retrospective investigations attempting to associate crew symptoms with elevated CO2 levels over the life if the International Space Station (ISS) are underway to determine if this level is sufficient to protect against health and performance decrements. Anecdotal reports suggest that crewmembers are not able to perform complex tasks as readily in spaceflight as they were able during ground-based training. While physiological effects of CO2 have been studied for many decades, it is only recently that the effects of CO2 on higher reasoning capabilities have been studied. The initial results are shocking. For example, one study published in the respected journal Environmental Health Perspectives showed obvious adverse effects of CO2 exposures on higher reasoning at 1.9 mmHg. The implications and limitations of this study are paramount in determining future CO2 SMACs for human spaceflight, both aboard the ISS and in exploration-class missions. Key Words: carbon dioxide, spacecraft, air quality, toxic effects

  9. A supervised adverse drug reaction signalling framework imitating Bradford Hill's causality considerations.

    PubMed

    Reps, Jenna Marie; Garibaldi, Jonathan M; Aickelin, Uwe; Gibson, Jack E; Hubbard, Richard B

    2015-08-01

    Big longitudinal observational medical data potentially hold a wealth of information and have been recognised as potential sources for gaining new drug safety knowledge. Unfortunately there are many complexities and underlying issues when analysing longitudinal observational data. Due to these complexities, existing methods for large-scale detection of negative side effects using observational data all tend to have issues distinguishing between association and causality. New methods that can better discriminate causal and non-causal relationships need to be developed to fully utilise the data. In this paper we propose using a set of causality considerations developed by the epidemiologist Bradford Hill as a basis for engineering features that enable the application of supervised learning for the problem of detecting negative side effects. The Bradford Hill considerations look at various perspectives of a drug and outcome relationship to determine whether it shows causal traits. We taught a classifier to find patterns within these perspectives and it learned to discriminate between association and causality. The novelty of this research is the combination of supervised learning and Bradford Hill's causality considerations to automate the Bradford Hill's causality assessment. We evaluated the framework on a drug safety gold standard known as the observational medical outcomes partnership's non-specified association reference set. The methodology obtained excellent discrimination ability with area under the curves ranging between 0.792 and 0.940 (existing method optimal: 0.73) and a mean average precision of 0.640 (existing method optimal: 0.141). The proposed features can be calculated efficiently and be readily updated, making the framework suitable for big observational data. PMID:26116429

  10. Under-reporting of adverse drug reactions: A challenge for pharmacovigilance in India

    PubMed Central

    Tandon, Vishal R.; Mahajan, Vivek; Khajuria, Vijay; Gillani, Zahid

    2015-01-01

    Aim: The aim was to evaluate the extent and factors responsible for underreporting (UR) of adverse drug reactions (ADRs) in India. Materials and Methods: A retrospective observational, cross-sectional prospective questionnaire-based analysis was undertaken to evaluate the extent and factors for UR of ADRs in pharmacovigilance. Results: At the time, this report was prepared, 90 ADR Monitoring Centers (AMC) were operational in India. Indian AMC functional rate was 56.45%. The average number of Individual Case Safety Reports reported by our center via VigiFlow per month was 48.038. In a period of the 3 years the total number of ADRs reported was 3024. The average number of reports per month was 80.08. Active surveillance versus spontaneous reporting contributed 66.13% versus 33.86% of the total ADRs (P < 0.0001). Outpatient Department (OPD) contribution was 76.05% and indoor contribution was 23.94% of total reports (P < 0.0001). Department of Medicine (33%), followed by oncology (19.27%) and chest disease (13.49%) contributed maximally. The contribution of Pharmacology ADR monitoring OPD was 16.20%. Eye, ear, nose and throat and surgery, private Medical Colleges, hospitals in periphery, sub-district and district contributed no ADRs. ADR detection rates by clinical presentation, biochemical investigation and diagnostic tools were 84.33%, 14.57%, and 1.09% respectively (P < 0.0001). Reporting by postgraduate, registrars, consultants and nurses were 72.65%, 6.58%, 16.56% and 4.19% respectively (P < 0.0001). PG students in Pharmacology contributed an average number of 5.61 ADR reports/month. The lack of knowledge and awareness about Pharmacovigilance Programme of India (PvPI), lethargy, indifference, insecurity, complacency, workload, lack of training were the common factors responsible for UR. Major academic activity, exams, thesis and synopsis submission time influenced reporting of ADRs by postgraduate students. Conclusion: UR is a matter of concern PvPI. Multiple

  11. Portable Automatic Text Classification for Adverse Drug Reaction Detection via Multi-corpus Training

    PubMed Central

    Gonzalez, Graciela

    2014-01-01

    Objective Automatic detection of Adverse Drug Reaction (ADR) mentions from text has recently received significant interest in pharmacovigilance research. Current research focuses on various sources of text-based information, including social media — where enormous amounts of user posted data is available, which have the potential for use in pharmacovigilance if collected and filtered accurately. The aims of this study are: (i) to explore natural language processing approaches for generating useful features from text, and utilizing them in optimized machine learning algorithms for automatic classification of ADR assertive text segments; (ii) to present two data sets that we prepared for the task of ADR detection from user posted internet data; and (iii) to investigate if combining training data from distinct corpora can improve automatic classification accuracies. Methods One of our three data sets contains annotated sentences from clinical reports, and the two other data sets, built in-house, consist of annotated posts from social media. Our text classification approach relies on generating a large set of features, representing semantic properties (e.g., sentiment, polarity, and topic), from short text nuggets. Importantly, using our expanded feature sets, we combine training data from different corpora in attempts to boost classification accuracies. Results Our feature-rich classification approach performs significantly better than previously published approaches with ADR class F-scores of 0.812 (previously reported best: 0.770), 0.538 and 0.678 for the three data sets. Combining training data from multiple compatible corpora further improves the ADR F-scores for the in-house data sets to 0.597 (improvement of 5.9 units) and 0.704 (improvement of 2.6 units) respectively. Conclusions Our research results indicate that using advanced NLP techniques for generating information rich features from text can significantly improve classification accuracies over existing

  12. Are primary care factors associated with hospital episodes for adverse drug reactions? A national observational study

    PubMed Central

    McKay, Ailsa J; Newson, Roger B; Soljak, Michael; Riboli, Elio; Car, Josip

    2015-01-01

    Objective Identification of primary care factors associated with hospital admissions for adverse drug reactions (ADRs). Design and setting Cross-sectional analysis of 2010–2012 data from all National Health Service hospitals and 7664 of 8358 general practices in England. Method We identified all hospital episodes with an International Classification of Diseases (ICD) 10 code indicative of an ADR, in the 2010–2012 English Hospital Episode Statistics (HES) admissions database. These episodes were linked to contemporary data describing the associated general practice, including general practitioner (GP) and patient demographics, an estimate of overall patient population morbidity, measures of primary care supply, and Quality and Outcomes Framework (QOF) quality scores. Poisson regression models were used to examine associations between primary care factors and ADR-related episode rates. Results 212 813 ADR-related HES episodes were identified. Rates of episodes were relatively high among the very young, older and female subgroups. In fully adjusted models, the following primary care factors were associated with increased likelihood of episode: higher deprivation scores (population attributable fraction (PAF)=0.084, 95% CI 0.067 to 0.100) and relatively poor glycated haemoglobin (HbA1c) control among patients with diabetes (PAF=0.372; 0.218 to 0.496). The following were associated with reduced episode likelihood: lower GP supply (PAF=−0.016; −0.026 to −0.005), a lower proportion of GPs with UK qualifications (PAF=−0.035; −0.058 to −0.012), lower total QOF achievement rates (PAF=−0.021; −0.042 to 0.000) and relatively poor blood pressure control among patients with diabetes (PAF=−0.144; −0.280 to −0.022). Conclusions Various aspects of primary care are associated with ADR-related hospital episodes, including achievement of particular QOF indicators. Further investigation with individual level data would help develop understanding of the

  13. Adverse events caused by potential drug-drug interactions in an intensive care unit of a teaching hospital

    PubMed Central

    Alvim, Mariana Macedo; da Silva, Lidiane Ayres; Leite, Isabel Cristina Gonçalves; Silvério, Marcelo Silva

    2015-01-01

    Objective To evaluate the incidence of potential drug-drug interactions in an intensive care unit of a hospital, focusing on antimicrobial drugs. Methods This cross-sectional study analyzed electronic prescriptions of patients admitted to the intensive care unit of a teaching hospital between January 1 and March 31, 2014 and assessed potential drug-drug interactions associated with antimicrobial drugs. Antimicrobial drug consumption levels were expressed in daily doses per 100 patient-days. The search and classification of the interactions were based on the Micromedex® system. Results The daily prescriptions of 82 patients were analyzed, totaling 656 prescriptions. Antimicrobial drugs represented 25% of all prescription drugs, with meropenem, vancomycin and ceftriaxone being the most prescribed medications. According to the approach of daily dose per 100 patient-days, the most commonly used antimicrobial drugs were cefepime, meropenem, sulfamethoxazole + trimethoprim and ciprofloxacin. The mean number of interactions per patient was 2.6. Among the interactions, 51% were classified as contraindicated or significantly severe. Highly significant interactions (clinical value 1 and 2) were observed with a prevalence of 98%. Conclusion The current study demonstrated that antimicrobial drugs are frequently prescribed in intensive care units and present a very high number of potential drug-drug interactions, with most of them being considered highly significant. PMID:26761473

  14. The Development of Countermeasures for Space Radiation Induced Adverse Health Effects

    NASA Astrophysics Data System (ADS)

    Kennedy, Ann

    The Development of Countermeasures for Space Radiation Induced Adverse Health Effects Ann R. Kennedy Department of Radiation Oncology, University of Pennsylvania School of Medicine, 195 John Morgan Building, 3620 Hamilton Walk, Philadelphia, PA, United States 19104-6072 The development of countermeasures for radiation induced adverse health effects is a lengthy process, particularly when the countermeasure/drug has not yet been evaluated in human trials. One example of a drug developed from the bench to the clinic is the soybean-derived Bowman-Birk inhibitor (BBI), which has been developed as a countermeasure for radiation induced cancer. It was originally identified as a compound/drug that could prevent the radiation induced carcinogenic process in an in vitro assay system in 1975. The first observation that BBI could inhibit carcinogenesis in animals was in 1985. BBI received Investigational New Drug (IND) Status with the U.S. Food and Drug Administration (FDA) in 1992 (after several years of negotiation with the FDA about the potential IND status of the drug), and human trials began at that time. Phase I, II and III human trials utilizing BBI have been performed under several INDs with the FDA, and an ongoing Phase III trial will be ending in the very near future. Thus, the drug has been in development for 35 years at this point, and it is still not a prescription drug on the market which is available for human use. A somewhat less time-consuming process is to evaluate compounds that are on the GRAS (Generally Recognized as Safe) list. These compounds would include some over-the-counter medications, such as antioxidant vitamins utilized in human trials at the levels for which Recommended Dietary Allowances (RDAs) have been established. To determine whether GRAS substances are able to have beneficial effects on radiation induced adverse health effects, it is still likely to be a lengthy process involving many years to potentially decades of human trial work. The

  15. Respiratory Paradoxical Adverse Drug Reactions Associated with Acetylcysteine and Carbocysteine Systemic Use in Paediatric Patients: A National Survey

    PubMed Central

    Dubus, Jean-Christophe; Bavoux, Françoise; Boyer-Gervoise, Marie-José; Jean-Pastor, Marie-Josèphe; Chalumeau, Martin

    2011-01-01

    Objective To report pediatric cases of paradoxical respiratory adverse drug reactions (ADRs) after exposure to oral mucolytic drugs (carbocysteine, acetylcysteine) that led to the withdrawal of licenses for these drugs for infants in Fr