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Sample records for adverse reactions conclusion

  1. Adverse reactions to cosmetics.

    PubMed

    Gendler, E

    1987-06-01

    Adverse reactions to cosmetics can be irritant or allergic and are most often caused by fragrances or preservatives. Preservatives include formaldehyde, formaldehyde releasers, and parabens. Other agents that cause allergy are paraphenylenediamine in hair dyes and toluene sulfonamide formaldehyde resin in nail polishes.

  2. Adverse reactions to cosmetics.

    PubMed

    Dogra, A; Minocha, Y C; Kaur, S

    2003-01-01

    Adverse reaction to cosmetics constitute a small but significant number of cases of contact dermatitis with varied appearances. These can present as contact allergic dermatitis, photodermatitis, contact irritant dermatitis, contact urticaria, hypopigmentation, hyperpigmentation or depigmentation, hair and nail breakage. Fifty patients were included for the study to assess the role of commonly used cosmetics in causing adverse reactions. It was found that hair dyes, lipsticks and surprisingly shaving creams caused more reaction as compared to other cosmetics. Overall incidence of contact allergic dermatitis seen was 3.3% with patients own cosmetics. Patch testing was also done with the basic ingredients and showed positive results in few cases where casual link could be established. It is recommended that labeling of the cosmetics should be done to help the dermatologists and the patients to identify the causative allergen in cosmetic preparation.

  3. 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

  4. 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…

  5. Pharmacogenomics of adverse drug reactions

    PubMed Central

    2013-01-01

    Considerable progress has been made in identifying genetic risk factors for idiosyncratic adverse drug reactions in the past 30 years. These reactions can affect various tissues and organs, including liver, skin, muscle and heart, in a drug-dependent manner. Using both candidate gene and genome-wide association studies, various genes that make contributions of varying extents to each of these forms of reactions have been identified. Many of the associations identified for reactions affecting the liver and skin involve human leukocyte antigen (HLA) genes and for reactions relating to the drugs abacavir and carbamazepine, HLA genotyping is now in routine use prior to drug prescription. Other HLA associations are not sufficiently specific for translation but are still of interest in relation to underlying mechanisms for the reactions. Progress on non-HLA genes affecting adverse drug reactions has been less, but some important associations, such as those of SLCO1B1 and statin myopathy, KCNE1 and drug-induced QT prolongation and NAT2 and isoniazid-induced liver injury, are considered. Future prospects for identification of additional genetic risk factors for the various adverse drug reactions are discussed. PMID:23360680

  6. Adverse reactions to food additives.

    PubMed

    Simon, R A

    1986-01-01

    There are thousands of agents that are intentionally added to the food that we consume. These include preservatives, stabilizers, conditioners, thickeners, colorings, flavorings, sweeteners, antioxidants, etc. etc. Yet only a surprisingly small number have been associated with hypersensitivity reactions. Amongst all the additives, FD&C dyes have been most frequently associated with adverse reactions. Tartrazine is the most notorious of them all; however, critical review of the medical literature and current Scripps Clinic studies would indicate that tartrazine has been confirmed to be at best only occasionally associated with flares of urticaria or asthma. There is no convincing evidence in the literature of reactivity to the other azo or nonazo dyes. This can also be said of BHA/BHT, nitrites/nitrates and sorbates. Parabens have been shown to elicit IgE mediated hypersensitivity reactions when used as pharmaceutical preservatives; however, as with the other additives noted above, ingested parabens have only occasionally been associated with adverse reactions. MSG, the cause of the 'Chinese restaurant syndrome' has only been linked to asthma in one report. Sulfiting agents used primarily as food fresheners and to control microbial growth in fermented beverages have been established as the cause of any where from mild to severe and even fatal reactions in at least 5% of the asthmatic population. Other reactions reported to follow sulfite ingestion include anaphylaxis, gastro intestinal complaints and dermatological eruptions. The prevalence of these non asthmatic reactions is unknown. The mechanism of sulfite sensitive asthma is also unknown but most likely involves hyperreactivity to inhale SO2 in the great majority of cases; however, there are reports of IgE mediated reactions and other sulfite sensitive asthmatics have been found with low levels of sulfite oxidase; necessary to oxidize endogenous sulfite to sulfate.

  7. Adverse reactions to injectable soft tissue fillers.

    PubMed

    Requena, Luis; Requena, Celia; Christensen, Lise; Zimmermann, Ute S; Kutzner, Heinz; Cerroni, Lorenzo

    2011-01-01

    In recent years, injections with filler agents are often used for wrinkle-treatment and soft tissue augmentation by dermatologists and plastic surgeons. Unfortunately, the ideal filler has not yet been discovered and all of them may induce adverse reactions. Quickly biodegradable or resorbable agents may induce severe complications, but they will normally disappear spontaneously in a few months. Slowly biodegradable or nonresorbable fillers may give rise to severe reactions that show little or no tendency to spontaneous improvement. They may appear several years after the injection, when the patient does not remember which product was injected, and treatment is often insufficient. In this review, we discuss the most commonly used fillers, their most frequent adverse reactions as well as the characteristic histopathologic findings that allow the identification of the injected filler agent. In conclusion, histopathologic study remains as the gold standard technique to identify the responsible filler.

  8. 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

  9. Adverse reaction; patent blue turning patient blue.

    PubMed

    Joshi, Meera; Hart, Matthew; Ahmed, Farid; McPherson, Sandy

    2012-11-30

    The authors report a severe anaphylactic reaction to Patent Blue V dye used in sentinel node biopsy for lymphatic mapping during breast cancer surgery to stage the axilla. Patent Blue dye is the most widely used in the UK; however, adverse reactions have been reported with the blue dye previously. This case highlights that reactions may not always be immediately evident and to be vigilant in all patients that have undergone procedures using blue dye. If the patients are not responding appropriately particularly during an anaesthetic, one must always think of a possible adverse reaction to the dye. All surgical patients should give consent for adverse reactions to patent blue dye preoperatively. Alternative agents such as methylene blue are considered.

  10. Monitoring Adverse Drug Reactions: A Preliminary Study

    PubMed Central

    Reynolds, J. L.

    1981-01-01

    The feasibility of family physicians functioning as monitors of adverse drug reactions (ADR) was examined over one month in ten practices. This was done as a preliminary trial, before attempting to use the 200 family physicians of the National Reporting System of the College of Family Physicians of Canada to monitor ADRs on a national basis. Both of these trials were designed to examine the feasibility of family physicians acting as prospective monitors of ADRs in newly marketed drugs and to identify a drug group suitable for monitoring. This study examined the detection of ADRs, prescribing and practice profiles. No firm conclusion could be reached as to the value of family doctors monitoring ADRs. This study supports the evidence that older patients receive more drugs and are at even greater risk of an ADR. Antibiotics, cardiovascular, anti-inflammatory or antidepressant drugs are suggested as those most suitable for prospective monitoring in a family practice setting. PMID:21289786

  11. 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

  12. 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

  13. ADVERSE DRUG REACTIONS IN THE ORAL CAVITY.

    PubMed

    Boras, Vanja Vučićević; Andabak-Rogulj, Ana; Brailo, Vlaho; Šimunković, Sonja Kraljević; Gabrić, Dragana; Vrdoljak, Danko Velimir

    2015-06-01

    Every medication may lead to adverse effects, even when used in standard doses and mode of application. In the oral cavity, adverse effects may affect every part of oral mucosa and are the result of medications taken either locally or systemically. Oral adverse reactions to drugs are not typical and therefore sometimes not easy to recognize. On diagnosing adverse side effects in the oral cavity, experienced clinician will usually diagnose the condition on the basis of detailed medical history and clinical finding. However, the only objective evidence for the offending drug is 're-challenge', i.e. exposure to the drug after its discontinuation. It carries a huge risk of anaphylactic reaction; therefore it has to be performed in a controlled hospital setting. Therapy is based on immediate exclusion of the offending drug and, if lesions are present in the oral cavity, topical or systemic corticosteroid therapy is prescribed. This article gives a review of patients with oral adverse drug reactions referred to the Department of Oral Medicine in Zagreb.

  14. Adverse Drug Reactions Causing Admission to a Paediatric Hospital

    PubMed Central

    Gallagher, Ruairi M.; Mason, Jennifer R.; Bird, Kim A.; Kirkham, Jamie J.; Peak, Matthew; Williamson, Paula R.; Nunn, Anthony J.; Turner, Mark A.; Pirmohamed, Munir; Smyth, Rosalind L.

    2012-01-01

    Objective(s) To obtain reliable information about the incidence of adverse drug reactions, and identify potential areas where intervention may reduce the burden of ill-health. Design Prospective observational study. Setting A large tertiary children’s hospital providing general and specialty care in the UK. Participants All acute paediatric admissions over a one year period. Main Exposure Any medication taken in the two weeks prior to admission. Outcome Measures Occurrence of adverse drug reaction. Results 240/8345 admissions in 178/6821 patients admitted acutely to a paediatric hospital were thought to be related to an adverse drug reaction, giving an estimated incidence of 2.9% (95% CI 2.5, 3.3), with the reaction directly causing, or contributing to the cause, of admission in 97.1% of cases. No deaths were attributable to an adverse drug reaction. 22.1% (95% CI 17%, 28%) of the reactions were either definitely or possibly avoidable. Prescriptions originating in the community accounted for 44/249 (17.7%) of adverse drug reactions, the remainder originating from hospital. 120/249 (48.2%) reactions resulted from treatment for malignancies. The drugs most commonly implicated in causing admissions were cytotoxic agents, corticosteroids, non-steroidal anti-inflammatory drugs, vaccines and immunosuppressants. The most common reactions were neutropenia, immunosuppression and thrombocytopenia. Conclusions Adverse drug reactions in children are an important public health problem. Most of those serious enough to require hospital admission are due to hospital-based prescribing, of which just over a fifth may be avoidable. Strategies to reduce the burden of ill-health from adverse drug reactions causing admission are needed. PMID:23226510

  15. Glaucoma eye drops adverse skin reactions.

    PubMed

    Cantisani, Carmen; Ambrifi, Marina; Frascani, Federica; Fazia, Gilda; Paolino, Giovanni; Lisi, Roberto; Calvieri, Stefano

    2014-01-01

    The term "Glaucoma" is used to describe a number of diseases of the eye characterized by a particular form of optic nerve damage that is often associated with high intraocular pressure (IOP). The open-angle glaucoma is the most common form that is also referred to as chronic glaucoma. This is described as an optic neuropathy with multifactorial nature in which there is a loss of characteristics of the optic nerve fibers. Therapeutic options for the treatment of this disease are different, you can take advantage of eye drops, laser therapy and conventional surgery or more combined treatments. Medicated eye drops are the most common way to treat glaucoma. Although eye drops are widely used, adverse reactions are not frequently observed and described. In particular, the adverse skin reactions are not frequently described in the literature, but often seen in dermatologic clinic, we reported their skin reactions and possible alternative treatments described in literature and their patent applications. PMID:25487259

  16. 21 CFR 606.170 - Adverse reaction file.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  17. 21 CFR 606.170 - Adverse reaction file.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Adverse reaction file. 606.170 Section 606.170... Adverse reaction file. (a) Records shall be maintained of any reports of complaints of adverse reactions... thorough investigation of each reported adverse reaction shall be made. A written report of...

  18. 21 CFR 606.170 - Adverse reaction file.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Adverse reaction file. 606.170 Section 606.170... Adverse reaction file. (a) Records shall be maintained of any reports of complaints of adverse reactions... thorough investigation of each reported adverse reaction shall be made. A written report of...

  19. Idiosyncratic adverse reactions to antiepileptic drugs.

    PubMed

    Zaccara, Gaetano; Franciotta, Diego; Perucca, Emilio

    2007-07-01

    Idiosyncratic drug reactions may be defined as adverse effects that cannot be explained by the known mechanisms of action of the offending agent, do not occur at any dose in most patients, and develop mostly unpredictably in susceptible individuals only. These reactions are generally thought to account for up to 10% of all adverse drug reactions, but their frequency may be higher depending on the definition adopted. Idiosyncratic reactions are a major source of concern because they encompass most life-threatening effects of antiepileptic drugs (AEDs), as well as many other reactions requiring discontinuation of treatment. Based on the underlying mechanisms, idiosyncratic reactions can be differentiated into (1) immune-mediated hypersensitivity reactions, which may range from benign skin rashes to serious conditions such as drug-related rash with eosinophilia and systemic symptoms; (2) reactions involving unusual nonimmune-mediated individual susceptibility, often related to abnormal production or defective detoxification of reactive cytotoxic metabolites (as in valproate-induced liver toxicity); and (3) off-target pharmacology, whereby a drug interacts directly with a system other than that for which it is intended, an example being some types of AED-induced dyskinesias. Although no AED is free from the potential of inducing idiosyncratic reactions, the magnitude of risk and the most common manifestations vary from one drug to another, a consideration that impacts on treatment choices. Serious consequences of idiosyncratic reactions can be minimized by knowledge of risk factors, avoidance of specific AEDs in subpopulations at risk, cautious dose titration, and careful monitoring of clinical response.

  20. ORAL ADVERSE DRUG REACTIONS TO CARDIOVASCULAR DRUGS.

    PubMed

    Torpet, Lis Andersen; Kragelund, Camilla; Reibel, Jesper; Nauntofte, Birgitte

    2004-01-01

    A great many cardiovascular drugs (CVDs) have the potential to induce adverse reactions in the mouth. The prevalence of such reactions is not known, however, since many are asymptomatic and therefore are believed to go unreported. As more drugs are marketed and the population includes an increasing number of elderly, the number of drug prescriptions is also expected to increase. Accordingly, it can be predicted that the occurrence of adverse drug reactions (ADRs), including the oral ones (ODRs), will continue to increase. ODRs affect the oral mucous membrane, saliva production, and taste. The pathogenesis of these reactions, especially the mucosal ones, is largely unknown and appears to involve complex interactions among the drug in question, other medications, the patient's underlying disease, genetics, and life-style factors. Along this line, there is a growing interest in the association between pharmacogenetic polymorphism and ADRs. Research focusing on polymorphism of the cytochrome P450 system (CYPs) has become increasingly important and has highlighted the intra- and inter-individual responses to drug exposure. This system has recently been suggested to be an underlying candidate regarding the pathogenesis of ADRs in the oral mucous membrane. This review focuses on those CVDs reported to induce ODRs. In addition, it will provide data on specific drugs or drug classes, and outline and discuss recent research on possible mechanisms linking ADRs to drug metabolism patterns. Abbreviations used will be as follows: ACEI, ACE inhibitor; ADR, adverse drug reaction; ANA, antinuclear antigen; ARB, angiotensin II receptor blocker; BAB, beta-adrenergic blocker; CCB, calcium-channel blocker; CDR, cutaneous drug reaction; CVD, cardiovascular drug; CYP, cytochrome P450 enzyme; EM, erythema multiforme; FDE, fixed drug eruption; I, inhibitor of CYP isoform activity; HMG-CoA, hydroxymethyl-glutaryl coenzyme A; NAT, N-acetyltransferase; ODR, oral drug reaction; RDM, reactive

  1. Linezolid Induced Adverse Drug Reactions - An Update.

    PubMed

    Kishor, Kamal; Dhasmana, Neha; Kamble, Shashank Shivaji; Sahu, Roshan Kumar

    2015-01-01

    Treatment regimen recommended for resistant tuberculosis consists of various drugs and these drugs are prescribed for at least 12-15 months. Such a long duration therapy and high dose of antibiotics result in adverse drug reactions (ADRs). ADRs may lead to various complications in disease management like replacement of drugs, dose increment, therapy withdrawal, etc. Linezolid is one of those drugs, practiced as an anti-mycobacterial agent and it is an important member of drug regimen for MDR and XDR tuberculosis. Linezolid is a broad spectrum antibiotic known for its unique mechanism of inhibition of resistant pathogenic strains. However, it causes serious adverse effects like thrombocytopenia, optic neuropathy, peripheral neuropathy, lactic acidosis, etc. Literature suggests that Linezolid can cause severe ADRs which affect patient compliance and hinder in therapy to a larger extent. Recent studies confirm the possibility of ADRs to be predicted with genetic make-up of individuals. To effectively deliver the available treatment regimen and ensure patient compliance, it is important to manage ADRs more efficiently. The role of pharmacogenomics in reducing adverse drug effects has been recently explored. In the present review, we discussed about Linezolid induced adverse drug reactions, mechanisms and genetic associations. PMID:26424176

  2. 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

  3. Adverse reactions to fragrances. A clinical review.

    PubMed

    de Groot, A C; Frosch, P J

    1997-02-01

    This article reviews side-effects of fragrance materials present in cosmetics with emphasis on clinical aspects: epidemiology, types of adverse reactions, clinical picture, diagnostic procedures, and the sensitizers. Considering the ubiquitous occurrence of fragrance materials, the risk of side-effects is small. In absolute numbers, however, fragrance allergy is common, affecting approximately 1% of the general population. Although a detailed profile of patients sensitized to fragrances needs to be elucidated, common features of contact allergy are: axillary dermatitis, dermatitis of the face (including the eyelids) and neck, well-circumscribed patches in areas of "dabbing-on" perfumes (wrists, behind the ears) and (aggravation of) hand eczema. Depending on the degree of sensitivity, the severity of dermatitis may range from mild to severe with dissemination and even erythroderma. Airborne or "connubial" contact dermatitis should always be suspected. Other less frequent adverse reactions to fragrances are photocontact dermatitis, immediate contact reactions and pigmentary changes. The fragrance mix, although very useful for the detection of sensitive patients, both causes false-positive and false-negative reactions, and detects only 70% of perfume-allergic patients. Therefore, future research should be directed at increasing the sensitivity and the specificity of the mix. Relevance is said to be established in 50-65% of positive reactions, but accurate criteria are needed. Suggestions are made for large-scale investigation of several fragrances on the basis of literature data and frequency of use in cosmetics. The literature on adverse reactions to balsam of Peru (an indicator for fragrance sensitivity), essential oils (which currently appear to be used more in aromatherapy than in perfumery) and on fragrances used as flavours and spices in foods and beverages is not discussed in detail, but pertinent side-effects data are tabulated and relevant literature is

  4. 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

  5. [Adverse drug reactions in pregnant women].

    PubMed

    Lacroix, Isabelle; Cabou, Cendrine; Montastruc, Jean-Louis; Damase-Michel, Christine

    2007-01-01

    A Prospective pharmacovigilance survey of adverse drug reactions (ADRs) in pregnant women was performed in collaboration with gynaecologists and obstetricians of Midi-Pyrenees area (south west of france). The aim of the study was to evaluate the incidence of adverse drug reactions in pregnant women. The incidence of ADRs in pregnant women was low: 0.3%. Moreover, a retrospective pharmacoepidemiological study was conducted to characterize ADRs in pregnant women. Reports of ADRs collected in the Midi-Pyrenees pharmacovigilance centre from 1982 to 2002 were used: type of ADRs, drugs involved and potential risk factors were compared for pregnant women and for age-matched non pregnant women. Forty seven and 94 reports of ADRs were collected in pregnant and non-pregnant women respectively. Anaphylactic reactions were only observed in pregnant women (3 cases, p = 0.04). We observed 1 ADR related stillbirth (due to anaphylactic reaction) in pregnant women. Drugs for gynaecological and cardiovascular systems were more frequently involved in ADRs in pregnant women than in controls. ADRs mainly occurred during the third trimester of pregnancy. The incidence of ADRs is very low in pregnant women. However, one must pay attention on the risk of anaphylactic reactions in pregnant women. PMID:18206108

  6. Adverse reactions to food: allergies and intolerances.

    PubMed

    Montalto, Massimo; Santoro, Luca; D'Onofrio, Ferruccio; Curigliano, Valentina; Gallo, Antonella; Visca, Dina; Cammarota, Giovanni; Gasbarrini, Antonio; Gasbarrini, Giovanni

    2008-01-01

    All the anomalous reactions secondary to food ingestion are defined as 'adverse reactions to food'. In 1995 the European Academy of Allergology and Clinical Immunology suggested a classification on the basis of the responsible pathogenetic mechanism; according to this classification, non-toxic reactions can be divided into 'food allergies' when they recognize immunological mechanisms, and 'food intolerances' when there are no immunological implications. The diagnostic approach to adverse reactions to food is based on accurate clinical history and objective examination, and further execution of specific tests when allergy or intolerance is suspected. The therapy for food allergies is the elimination of the food to which hypersensibility has been found; this strategy can lead, especially in pediatric age, to tolerance. If elimination diets cannot be completely performed, or if it is not possible to identify the food to eliminate, some drugs (e.g. antihistaminics, steroids, etc.) can be administered. Specific allergen immunotherapy has been recently introduced. Fundamental is food allergy prevention, especially in high-risk subjects. The therapeutic approach to secondary food intolerances is based principally on primitive disease resolution; on the other hand, some specific treatments (e.g. beta-galactosidases in lactose malabsorption) are available in case of primary intolerance. PMID:18431058

  7. 21 CFR 606.170 - Adverse reaction file.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Adverse reaction file. 606.170 Section 606.170 Food... reaction file. (a) Records shall be maintained of any reports of complaints of adverse reactions regarding... investigation of each reported adverse reaction shall be made. A written report of the investigation of...

  8. Adverse reactions to the sulphite additives

    PubMed Central

    Misso, Neil LA

    2012-01-01

    Sulphites are widely used as preservative and antioxidant additives in the food and pharmaceutical industries. Exposure to sulphites has been reported to induce a range of adverse clinical effects in sensitive individuals, ranging from dermatitis, urticaria, flushing, hypotension, abdominal pain and diarrhoea to life-threatening anaphylactic and asthmatic reactions. Exposure to the sulphites arises mainly from the consumption of foods and drinks that contain these additives; however exposure may also occur through the use of pharmaceutical products, as well as in occupational settings. Most studies report a prevalence of sulphite sensitivity of 3 to 10% among asthmatic subjects who ingest these additives. However, the severity of these reactions varies, and steroid-dependent asthmatics, those with marked airway hyperresponsiveness, and children with chronic asthma, appear to be at greater risk. Although a number of potential mechanisms have been proposed, the precise mechanisms underlying sulphite sensitivity remain unclear. PMID:24834193

  9. Adverse reaction to lupine-fortified pasta.

    PubMed

    Hefle, S L; Lemanske, R F; Bush, R K

    1994-08-01

    A 5-year-old girl with peanut sensitivity experienced urticaria and angioedema after ingesting a spaghetti-like pasta fortified with sweet lupine seed flour. The pasta was extracted and used in immunologic studies in patients with peanut sensitivity to determine whether such individuals are at similar risk. Results of skin prick tests with the lupine pasta extract were positive in five of seven subjects; these patients also reported a history of adverse reactions to green peas. In direct RAST studies IgE binding from pooled sera from patients with peanut sensitivity to the lupine pasta extract was 7 times that of a nonallergic control serum, and individual serum samples demonstrated binding from 1 to 6 times that of the negative control. Direct RAST studies of lupine seed flour with serum samples from patients with peanut allergy demonstrated IgE binding 1 to 11 times that of the negative control. Immunoblotting studies of electrophoretically separated pasta extract and lupine seed flour proteins showed IgE-binding protein bands at approximately 21 kd and in the range of 35 to 55 kd molecular weight. We conclude that some peanut-sensitive patients may be at risk for adverse reactions to lupine.

  10. Adverse allergic reaction to Technetium-99m methylene diphosphonate

    SciTech Connect

    Spicer, J.A.; Preston, D.F.; Stephens, R.L.

    1985-04-01

    Adverse allergic reactions to radiopharmaceuticals are rare but have been documented in the literature. This report presents data consistent with a definite adverse reaction to the radiopharmaceutical (/sup 99m/Tc)MDP.

  11. 21 CFR 606.170 - Adverse reaction file.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Adverse reaction file. 606.170 Section 606.170... Adverse reaction file. Link to an amendment published at 77 FR 18, Jan. 3, 2012. (a) Records shall be maintained of any reports of complaints of adverse reactions regarding each unit of blood or blood...

  12. Adverse reactions triggered by dental local anesthetics: a clinical survey.

    PubMed Central

    Kaufman, E.; Goharian, S.; Katz, Y.

    2000-01-01

    One hundred and seventy-nine patients completed a questionnaire focusing on adverse reactions to dental local anesthetics as manifested by 16 signs and symptoms. Twenty-six percent of the participants reported having at least 1 adverse reaction. It was found that most of the adverse reactions occurred within the first 2 hours following the injection of local anesthetics. Pallor, palpitations, diaphoresis, and dizziness were the most common adverse reactions reported in the study. The results pointed to a significant relationship between anxiety, gender, injection technique, and procedure with a higher incidence of adverse reactions. PMID:11432179

  13. Idiosyncratic Adverse Drug Reactions: Current Concepts

    PubMed Central

    Naisbitt, Dean J.

    2013-01-01

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

  14. Idiosyncratic adverse drug reactions: current concepts.

    PubMed

    Uetrecht, Jack; Naisbitt, Dean J

    2013-04-01

    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

  15. [Cutaneous adverse reactions to tattoos and piercings].

    PubMed

    Mataix, J; Silvestre, J F

    2009-10-01

    Piercings and tattoos have become very popular in western society in recent decades, particularly among younger generations. Reports of medical complications associated with these decorative techniques have increased in parallel with the rise in their popularity. Due to their high frequency, adverse cutaneous reactions are particularly important among these potential complications. Tattoo-related complications include a number of cutaneous and systemic infections secondary to breach of the epidermal barrier, acute and delayed inflammatory reactions with different histopathological patterns, the appearance of benign and malignant tumors on tattooed areas of skin, and certain dermatoses triggered by isomorphic phenomena. Piercing-related complications are similar, though some, such as pyogenic skin infections, are much more common due to the delayed wound healing after piercing in certain sites. We must differentiate between complications that are independent of the site of piercing, and specific complications, which are closely related to the body area pierced. The rate of complications after performing piercings or tattoos depends on the experience of the artist, the hygiene techniques applied, and the postprocedural care by the customer. However, some of these complications are unpredictable and depend on factors intrinsic to the patient. In this article, we review the most common decorative techniques of body art, with particular focus on the potential cutaneous complications and their management. PMID:19775542

  16. Managing nonteratogenic adverse reactions to isotretinoin treatment for acne vulgaris.

    PubMed

    Reilly, Bridget K; Ritsema, Tamara S

    2015-07-01

    Isotretinoin is the strongest, most effective oral treatment for patients with severe acne vulgaris, with remission rates of 89% and higher. Because of its potency, isotretinoin causes many adverse reactions. This article reviews common and severe adverse reactions to isotretinoin and how providers can best manage these reactions. Because of inconclusive research on the correlation between isotretinoin and depression and irritable bowel syndrome, providers should ask patients about symptoms monthly. Prescribing micronized isotretinoin and starting at the lowest dose with gradual upward titration also can help reduce the incidence of adverse reactions.

  17. FDI report on adverse reactions to resin-based materials.

    PubMed

    Fan, P L; Meyer, D M

    2007-02-01

    Resin-based restorative materials are considered safe for the vast majority of dental patients. Although constituent chemicals such as monomers, accelerators and initiators can potentially leach out of cured resin-based materials after placement, adverse reactions to these chemicals are rare and reaction symptoms commonly subside after removal of the materials. Dentists should be aware of the rare possibility that patients could have adverse reactions to constituents of resin-based materials and be vigilant in observing any adverse reactions after restoration placement. Dentists should also be cognisant of patient complaints about adverse reactions that may result from components of resin-based materials. To minimise monomer leaching and any potential risk of dermatological reactions, resin-based materials should be adequately cured. Dental health care workers should avoid direct skin contact with uncured resin-based materials. Latex and vinyl gloves do not provide adequate barrier protection to the monomers in resin-based materials.

  18. Determinants of adverse reaction following postoperative T-tube cholangiogram.

    PubMed Central

    Dellinger, E P; Kirshenbaum, G; Weinstein, M; Steer, M

    1980-01-01

    The incidence, nature, and mechanisms of adverse reaction following postoperative T-tube cholangiogram have received little attention in the medical literature. This paper presents the experience at one hospital over a 30-month period (1975--1977) covering 139 patients who had 170 cholangiograms. Factors examined included intraoperative and postoperative cultures of bile, the use of antibiotics prior to the performance of the cholangiogram, the technique of cholangiography, the interval between operation and cholangiogram. Eleven (6.5%) cholangiograms were followed by an adverse reaction. Two of these reactions were severe, manifested by signs of septic shock. The administration of antibiotics was not associated with a reduction in adverse reactions. The cholangiographic technique of gravity infusion of dye, which effectively limits the amount of pressure generated during the study, was associated with a significant reduction in adverse reactions. No severe reactions occurred following any study performed by the gravity technique. There was no significant correlation between the age of the patient or the number of days postoperative with adverse reaction. A review of the literature suggests that the mechanism for these severe reactions is cholangiovenous reflux. The avoidance of high intraductal pressures (above 25 cm of water) during the performance of postoperative T-tube cholangiogram should significantly reduce the incidence of adverse reactions. PMID:7369805

  19. 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

  20. Precautions and Adverse Reactions during Blood Transfusion

    MedlinePlus

    ... the transfused blood after it is collected. In addition to an increase in temperature, the person has chills and sometimes headache or back pain. Sometimes the person also has symptoms of an allergic reaction such as itching or a rash. Usually, acetaminophen ...

  1. Evaluation of adverse reactions to contrast media in the hospital

    PubMed Central

    Ryu, J-H; Kim, E-Y

    2013-01-01

    Objective: To determine and analyse the characteristics of contrast media adverse reactions (CM-ARs) reported in a hospital. Methods: A retrospective review of CM-ARs from the electronic spontaneous adverse drug reaction (ADR) report system between January 2011 and August 2012 was conducted. CM-ARs were evaluated in terms of causality, severity, preventability and affected organs. Also, agreement and correlation among the tools used to evaluate CM-ARs were analysed. Results: The overall reaction rate was 1.5% (n = 286). In total, 269 CM-ARs were identified. For ADR causality, 96.7% (n = 260) and 98.5% (n = 265) were evaluated as “probable” ADR using the Naranjo probability scale and the World Health Organization–Uppsala Monitoring Centre causality categories, whereas 98.1% (n = 264) were evaluated as “certain” with Korean algorithm v. II. Of these, 91.4% (n = 246) were mild in severity and 96.7% (n = 260) were unpreventable. Most patients (n = 233, 86.7%) could be managed with observation and/or simple treatment. The most frequent reaction (n = 383, 79.5%) was dermatological. Spearman's correlation coefficient was 0.667 (p < 0.01), and the agreement was 98.1% between the Naranjo scale and the World Health Organization–Uppsala Monitoring Centre categories. No relationship was seen between CM-AR severity and gender or between in- and outpatients. Conclusion: In our study, most CM-ARs were mild and managed with simple treatment. However, as the number of patients undergoing CT procedures continues to increase, it is essential to identify and observe patients at risk for CM-ARs to prevent severe ADRs. Advances in knowledge: Continuous careful review of reporting and treatment protocols of CM-ARs is needed to prevent morbidity and mortality. PMID:24191123

  2. 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

  3. Adverse Drug Reactions in Children—A Systematic Review

    PubMed Central

    Smyth, Rebecca Mary Diane; Gargon, Elizabeth; Kirkham, Jamie; Cresswell, Lynne; Golder, Su; Smyth, Rosalind; Williamson, Paula

    2012-01-01

    Background Adverse drug reactions in children are an important public health problem. We have undertaken a systematic review of observational studies in children in three settings: causing admission to hospital, occurring during hospital stay and occurring in the community. We were particularly interested in understanding how ADRs might be better detected, assessed and avoided. Methods and Findings We searched nineteen electronic databases using a comprehensive search strategy. In total, 102 studies were included. The primary outcome was any clinical event described as an adverse drug reaction to one or more drugs. Additional information relating to the ADR was collected: associated drug classification; clinical presentation; associated risk factors; methods used for assessing causality, severity, and avoidability. Seventy one percent (72/102) of studies assessed causality, and thirty four percent (34/102) performed a severity assessment. Only nineteen studies (19%) assessed avoidability. Incidence rates for ADRs causing hospital admission ranged from 0.4% to 10.3% of all children (pooled estimate of 2.9% (2.6%, 3.1%)) and from 0.6% to 16.8% of all children exposed to a drug during hospital stay. Anti-infectives and anti-epileptics were the most frequently reported therapeutic class associated with ADRs in children admitted to hospital (17 studies; 12 studies respectively) and children in hospital (24 studies; 14 studies respectively), while anti-infectives and non-steroidal anti-inflammatory drugs (NSAIDs) were frequently reported as associated with ADRs in outpatient children (13 studies; 6 studies respectively). Fourteen studies reported rates ranging from 7%–98% of ADRs being either definitely/possibly avoidable. Conclusions There is extensive literature which investigates ADRs in children. Although these studies provide estimates of incidence in different settings and some indication of the therapeutic classes most frequently associated with ADRs, further

  4. 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

  5. Prospective observational study of adverse drug reactions to diclofenac in children

    PubMed Central

    Standing, Joseph F; Ooi, Kuan; Keady, Simon; Howard, Richard F; Savage, Imogen; Wong, Ian C K

    2009-01-01

    AIM The aim of this study was to investigate the type of common (occurring in >1% of patients) adverse reactions caused by diclofenac when given to children for acute pain. METHODS A prospective observational study was undertaken on paediatric surgical patents aged ≤12 years at Great Ormond Street and University College London Hospitals. All adverse events were recorded, and causality assessment used to judge the likelihood of them being due to diclofenac. Prospective recruitment meant not all patients were prescribed diclofenac, allowing an analysis of utilization. Causality of all serious adverse events was reviewed by an expert panel. RESULTS Children prescribed diclofenac were significantly older, and stayed in hospital for shorter periods than those who were not. Diclofenac was not avoided in asthmatic patients. Data on 380 children showed they suffer similar types of nonserious adverse reactions to adults. The incidence (95% confidence interval) of rash was 0.8% (0.016, 2.3); minor central nervous system disturbance 0.5% (0.06, 1.9); rectal irritation with suppositories 0.3% (0.009, 1.9); and diarrhoea 0.3% (0.007, 1.5). No serious adverse event was judged to be caused by diclofenac, meaning the incidence of serious adverse reactions to diclofenac in children is <0.8%. CONCLUSION Children given diclofenac for acute pain appeared to suffer similar types of adverse reactions to adults; the incidence of serious adverse reaction is <0.8%. PMID:19694745

  6. Adverse reactions to sulfa drugs: implications for malaria chemotherapy.

    PubMed

    Björkman, A; Phillips-Howard, P A

    1991-01-01

    National adverse drug reaction registers in Sweden and the United Kingdom provided data on the type, severity and frequency of reported adverse reactions attributed to sulfa drugs. Reactions to the ten principal drugs were examined in terms of their half-lives and usual indications for use. Of 8339 reactions reported between 1968 and 1988, 1272 (15%) were blood dyscrasias, 3737 (45%) were skin disorders, and 578 (7%) involved the liver. These side-effects occurred with all types of sulfa drugs investigated, although at different relative rates, and 3525 (42%) of them were classified as serious. The overall case fatality rate (CFR) was 1:15 serious reactions, and was highest in patients with white blood cell dyscrasias (1:7). Drugs with longer elimination half-lives had higher CFRs, particularly for fatalities after skin reactions. In Sweden, the estimated incidences of serious reactions were between 9 and 33 per 100,000 short-term users of sulfa drugs (two weeks), between 53 and 111 among those on malaria prophylaxis, and between 1744 and 2031 in patients on continuous therapy. For dapsone, the incidence appeared to increase with higher doses. Our results indicate that sulfa drugs with short elimination half-lives deserve to be considered for use in combination with proguanil or chlorproguanil for malaria chemotherapy and possibly prophylaxis. The smaller risk of adverse reactions associated with lower-dose dapsone suggests that it should also be evaluated as a potentially safe alternative.

  7. [Direct reporting by patients of adverse drug reactions in Spain].

    PubMed

    Esther Salgueiro, M; Jimeno, Francisco J; Aguirre, Carmelo; García, Montserrat; Ordóñez, Lucía; Manso, Gloria

    2013-01-01

    The Spanish Pharmacovigilance System for Medicinal Products for Human Use, integrated by regional centers of pharmacovigilance coordinated by the Spanish Agency for Medicines and Health Products, is responsible for developing the Program of Spontaneous Reporting of Suspected Adverse Drug Reactions in our country. Although, until now, reports were only requesting to health professionals, the current understanding of the role of patients in the clinical setting and the experience gained in other countries of our environment, have demonstrated the convenience of developing active participation systems to patients in the reporting of suspected adverse drug reactions. In addition, this is taking into account in the new European legislation on pharmacovigilance. PMID:23461502

  8. [Direct reporting by patients of adverse drug reactions in Spain].

    PubMed

    Esther Salgueiro, M; Jimeno, Francisco J; Aguirre, Carmelo; García, Montserrat; Ordóñez, Lucía; Manso, Gloria

    2013-01-01

    The Spanish Pharmacovigilance System for Medicinal Products for Human Use, integrated by regional centers of pharmacovigilance coordinated by the Spanish Agency for Medicines and Health Products, is responsible for developing the Program of Spontaneous Reporting of Suspected Adverse Drug Reactions in our country. Although, until now, reports were only requesting to health professionals, the current understanding of the role of patients in the clinical setting and the experience gained in other countries of our environment, have demonstrated the convenience of developing active participation systems to patients in the reporting of suspected adverse drug reactions. In addition, this is taking into account in the new European legislation on pharmacovigilance.

  9. [Adverse drug reactions in the elderly: What dermatologists should know].

    PubMed

    Kratzsch, D; Simon, J-C; Treudler, R

    2016-02-01

    Pharmacotherapy in the elderly represents a challenge for dermatologists in regard to comorbidities, drug interactions, and compliance. Age-associated multimorbidity often results in polypharmacy and elevates the risk of adverse drug reactions. Crucial age-related alterations in pharmacokinetics must be considered when selecting drugs, particularly decreased total body water, altered proportion between muscle mass and adipose tissue, as well as decreased renal function. The purpose of this review is to help the reader identify relevant adverse drug reactions of often prescribed systemic dermatological pharmacons in geriatric patients and makes recommendations for their adequate application. PMID:26643292

  10. Chemical research on red pigments after adverse reactions to tattoo.

    PubMed

    Tammaro, A; Toniolo, C; Giulianelli, V; Serafini, M; Persechino, S

    2016-03-01

    Currently, the incidence of tattooing is on the rise compared to the past, especially among adolescents, and it leads to the urgency of monitoring the security status of tattooing centers, as well as to inform people about the risks of tattoo practice. In our clinical experience, 20% of tattooed patients presented adverse reactions, like allergic contact dermatitis, psoriasis with Koebner's phenomena and granulomatous reactions, with the latter most prevalent and most often related to red pigment. Adverse reactions to tattoo pigments, especially the red one, are well known and described in literature. Great attention has to be focused on the pigments used, especially for the presence of new substances, often not well known. For this reason, we decided to perform a study on 12 samples of red tattoo ink, obtained by patients affected by different cutaneous reactions in the site of tattoo, to analyze their chemical composition. PMID:26934738

  11. Chemical research on red pigments after adverse reactions to tattoo.

    PubMed

    Tammaro, A; Toniolo, C; Giulianelli, V; Serafini, M; Persechino, S

    2016-03-01

    Currently, the incidence of tattooing is on the rise compared to the past, especially among adolescents, and it leads to the urgency of monitoring the security status of tattooing centers, as well as to inform people about the risks of tattoo practice. In our clinical experience, 20% of tattooed patients presented adverse reactions, like allergic contact dermatitis, psoriasis with Koebner's phenomena and granulomatous reactions, with the latter most prevalent and most often related to red pigment. Adverse reactions to tattoo pigments, especially the red one, are well known and described in literature. Great attention has to be focused on the pigments used, especially for the presence of new substances, often not well known. For this reason, we decided to perform a study on 12 samples of red tattoo ink, obtained by patients affected by different cutaneous reactions in the site of tattoo, to analyze their chemical composition.

  12. Incidence and nature of adverse reactions to antibiotics used as endocarditis prophylaxis

    PubMed Central

    Thornhill, Martin H.; Dayer, Mark J.; Prendergast, Bernard; Baddour, Larry M.; Jones, Simon; Lockhart, Peter B.

    2015-01-01

    Objectives Antibiotic prophylaxis (AP) administration prior to invasive dental procedures has been a leading focus of infective endocarditis prevention. However, there have been long-standing concerns about the risk of adverse drug reactions as a result of this practice. The objective of this study was to identify the incidence and nature of adverse reactions to amoxicillin and clindamycin prophylaxis to prevent infective endocarditis. Methods We obtained AP prescribing data for England from January 2004 to March 2014 from the NHS Business Services Authority, and adverse drug reaction data from the Medicines and Healthcare Products Regulatory Agency's Yellow Card reporting scheme for prescriptions of the standard AP protocol of a single 3 g oral dose of amoxicillin or a single 600 mg oral dose of clindamycin for those allergic to penicillin. Results The reported adverse drug reaction rate for amoxicillin AP was 0 fatal reactions/million prescriptions (in fact 0 fatal reactions for nearly 3 million prescriptions) and 22.62 non-fatal reactions/million prescriptions. For clindamycin, it was 13 fatal and 149 non-fatal reactions/million prescriptions. Most clindamycin adverse drug reactions were Clostridium difficile infections. Conclusions AP adverse drug reaction reporting rates in England were low, particularly for amoxicillin, and lower than previous estimates. This suggests that amoxicillin AP is comparatively safe for patients without a history of amoxicillin allergy. The use of clindamycin AP was, however, associated with significant rates of fatal and non-fatal adverse drug reactions associated with C. difficile infections. These were higher than expected and similar to those for other doses, durations and routes of clindamycin administration. PMID:25925595

  13. 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

  14. Cutaneous adverse reactions specific to epidermal growth factor receptor inhibitors

    PubMed Central

    Lupu, I; Voiculescu, VM; Bacalbasa, N; Prie, BE; Cojocaru, I; Giurcaneanu, C

    2015-01-01

    Classical antineoplastic therapy is encumbered by extensively studied adverse reactions, most often of systemic nature. The emergence of new generations of anticancer treatments, including epidermal growth factor receptor inhibitors, besides improving the response to treatment and the survival rate, is accompanied by the occurrence of new specific side effects, incompletely studied. These side effects are most often cutaneous (hand foot syndrome, acneiform reactions), and in some cases are extremely severe, requiring dose reduction or drug discontinuation. The prevention of the cutaneous adverse effects and their treatment require a close collaboration between the oncologist and the dermatologist. The occurrence of some of these skin adverse effects may be a favorable prognostic factor for the response to the cancer treatment and the overall survival. Abbreviations: EGFR = epidermal growth factor receptors; EGFRI = epidermal growth factor receptors inhibitors PMID:26361513

  15. [Adverse drug reactions reporting is helping "non substituable" prescription!].

    PubMed

    Jacquot, Julien; Bagheri, Haleh; Montastruc, Jean-Louis

    2014-01-01

    In August 2012, general practitioners of Haute- Garonne received a letter from Health insurance system, informing that prescriptions could be endorsed by "not substituable" after reporting an adverse drug reactions (ADR). Compared to an equivalent period before this letter, we observed an increase of ADRs reports for generics, mainly concerning gastrointestinal ADR and lack of efficacy. PMID:24927508

  16. Cutaneous adverse drug reactions caused by antituberculosis drugs.

    PubMed

    Rezakovic, Saida; Pastar, Zrinjka; Kostovic, Kresimir

    2014-01-01

    Multidrug antituberculosis regimen is associated with diverse clinical patterns of cutaneous adverse drug reactions (CADR), ranging from mild and moderate such as pruritus, maculopapular exanthems, lichenoid eruptions, fixed drug eruptions and urticaria to severe and even life threatening ones like acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). These adverse reactions to antituberculosis drugs are commonly observed adverse events. This is of particular importance for high HIV prevalence settings and developing countries where tuberculosis is common infection resulting in higher occurrence rate of these reactions. There is still significant heterogenity in definition and classification of CADR, as well as diversity in treatment modalities following adverse reactions and rechallenge management. The aim of this review is to discuss clinical presentation, occurrence of CADR caused by antituberculosis drugs, to identify risk factors for intolerance of the standard therapy as well as to draw attention to importance of multi-disciplinary approach, early detection, prompt diagnosis and in time management of antituberculosis drugs associated CADR. CADR can cause significant treatment interruption and alteration, resulting in increased risk of treatment failure, drug resistance, relapses and increased risk of complications including even lethal outcome. Finally, it can be concluded that it is of great importance to identify the best possible treatment and preventive regimens in order to enable continuity of the antituberculosis therapy to the full extent. PMID:25039910

  17. 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

  18. Dietary aspects of adverse reactions to foods in adults.

    PubMed Central

    Parker, S L; Sussman, G L; Krondl, M

    1988-01-01

    Dietary considerations play an important role in the diagnosis, treatment and management of immunologic and nonimmunologic reactions to foods. Food diaries and trial elimination diets may prove helpful in identifying the responsible foods. Elimination diets must be monitored carefully for nutritional adequacy and should be used no longer than absolutely necessary; in some instances appropriate vitamin and mineral supplementation may be necessary. Ideally the identification of foods that provoke symptoms should be confirmed by means of double-blind challenge testing. Avoidance of some problem foods is unlikely to cause nutritional problems, but the practical and nutritional implications of allergies to staple foods such as cow's milk, eggs and wheat are far greater. Nonimmunologic adverse reactions that may mimic food allergic reactions include gastrointestinal disorders, sensitivity to food additives and psychologically based adverse reactions. There may be some degree of tolerance in metabolic disorders, which makes dietary management easier. Sensitivity to food additives necessitates careful scrutiny of food labels. In psychologic adverse reactions to foods, several foods are often involved, which increases the risk of nutritional problems. PMID:3048623

  19. 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

  20. Adverse Reactions in Allogeneic Blood Donors: A Tertiary Care Experience from a Developing Country

    PubMed Central

    Sultan, Sadia; Baig, Mohammad Amjad; Irfan, Syed Mohammed; Ahmed, Syed Ijlal; Hasan, Syeda Faiza

    2016-01-01

    Objectives Fragmented blood transfusion services along with an unmotivated blood donation culture often leads to blood shortage. Donor retention is crucial to meet the increasing blood demand, and adverse donor reactions have a negative impact on donor return. The aim of this study was to estimate adverse donor reactions and identify any demographic association.   Methods We conducted a prospective study between January 2011 and December 2013. A total of 41,759 healthy donors were enrolled. Professionally trained donor attendants drew blood and all donors were observed during and following donation for possible adverse events for 20 minutes. Blood donors were asked to report if they suffered from any delayed adverse consequences.   Results Out of 41,759 blood donors, 537 (1.3%) experienced adverse reactions. The incidence was one in every 78 donations. The mean age of donors who experienced adverse events was 26.0±6.8 years, and all were male. Out of 537 donors, 429 (80%) developed vasovagal reaction (VVR), 133 (25%) had nausea, 63 (12%) fainted, 35 (6%) developed hyperventilation, 9 (2%) had delayed syncope, and 9 (2%) developed hematoma. Arterial prick, nerve injury, cardiac arrest, and seizures were not observed. Donors aged less than < 30 years and weighing < 70 kg were significantly associated with VVR, hyperventilation, and nausea (p < 0.005). Undergraduates and Urdu speaking donors also had a significant association with fainting and nausea, respectively (p < 0.05).   Conclusion The prevalence of adverse events was low at our tertiary center. A VVR was the predominant adverse reaction and was associated with age and weight. Our study highlights the importance of these parameters in the donation process. A well-trained and experienced phlebotomist and pre-evaluation counseling of blood donors could further minimize the adverse reactions. PMID:27168923

  1. Evaluation of adverse reaction reports for a newly laundry product.

    PubMed

    Weaver, J E; Herrmann, K W

    1981-05-01

    The marketing of widely used consumer products inevitably results in some reports of adverse dermatologic reactions which are tentatively attributable through medical history to the use of these products. Just as it is important for manufacturers to perform thorough premarket safety testing, it also is important for them to investigate these reported reactions to confirm the safety of the product under widespread use conditions. This report describes the results of such a follow-up investigation into 300 adverse reaction reports obtained during the first year of marketing of new laundry product. The results of diagnostic patch and prick tests, controlled reuse testing, and definitive diagnoses by physicians (mostly allergists and dermatologists) demonstrated that this product was highly unlikely to have caused the reported dermatologic conditions. Widespread distribution of free samples of the new product appeared to be largely responsible for the frequency of anecdotal association of adverse reactions to use of the product. The diagnostic follow-up program is described. PMID:7240466

  2. [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

  3. Possible significance of adverse reactions to glutamate in humans.

    PubMed

    Reif-Lehrer, L

    1976-09-01

    Of those exposed to Chinese restaurant food, our studies indicate that 25% report adverse reactions (Chinese restaurant syndrome (CRS)), presumably to the mono-sodium glutamate (MSG) content. The possible significance of the symptoms is discussed in the light of the known neuroexcitatory activity of MSG. It is suggested that CRS may result from a "benign" inborn "error" of metabolism that is deserving of further study, particularly in individuals with certain other metabolic abnormalities or who are on certain types of drug therapy.

  4. Antiepileptic Drug-Related Adverse Reactions and Factors Influencing These Reactions

    PubMed Central

    KARIMZADEH, Parvaneh; BAKRANI, Vahid

    2013-01-01

    Objective According to the basic role of drug side effects in selection of an appropriate drug, patient compliance and the quality of life in epileptic patients, and forasmuch as new drugs with unknown side effect have been introduced, necessity of this research is explained. This study was conducted to evaluate the incidence and clinical characteristics of anti epileptic drug (AED) related adverse reactions in children. Material & Methods In this descriptive study, children less than 14 years old with AED side effects referred to the Children’s Medical Center and Mofid Childeren’s Hospital (Tehran, Iran) were evaluated during 2010-2012. The informations were: sex, age, incriminating drug, type of drug side effect, incubation period, history of drug usage, and patient and family allergy history. Exclusive criterions were age more than 14 years old and reactions due to reasons other than AEDs. Results A total of 70 patients with AED reaction were enrolled in this study. They included 26 (37%) females and 44 (63%) males. The maximum rate of incidence was seen at age less than 5 years old. All the patients had cutaneous eruptions that the most common cutaneous drug eruption was maculopapular rash. The most common culprit was phenobarbital (70%) and the least common was lamotrigine (1.4%). Conclusion In this study, we found higher rates of drug rash in patients treated with aromatic AEDs and lower rates with non-aromatic AEDs. Various endogenous and environmental factors may influence the propensity to develop these reactions. PMID:24665302

  5. Adverse food reactions--an emerging issue for adults.

    PubMed

    Skypala, Isabel

    2011-12-01

    Adverse reactions to foods are classified according to the presence or absence of involvement of the immune system, which may or may not include the production of immunoglobulin E (IgE) antibodies. This review focuses on the epidemiology, diagnosis, and management of adverse food reactions, primarily in adults, and excluding celiac disease and lactose intolerance. Reported reactions to foods are often believed to be manifestations of a food allergy; however, IgE-mediated food allergy only affects 1% to 4% of adults, with seafood, tree nuts, peanuts, fruits, and vegetables being the most common triggers. Diagnosis is challenging and most commonly achieved through careful evaluation of clinical history followed by elimination and reintroduction or challenge with the suspected offending food. With acute-onset allergic reactions, estimation of food-specific IgE antibodies is frequently used to confirm or refute the diagnosis. Recent developments, such as single allergen assays, enhance the diagnosis of IgE-mediated food allergy, but the gold standard remains oral food challenge. Despite recent advances in the management of food allergy, including the promotion of oral tolerance, the mainstay of management is still the avoidance of food triggers. Dietary management can be compromised by nutritional inadequacy, accidental exposure, food labeling, and quality of life or adherence issues. It is essential that adults with confirmed food allergy receive optimal nutrition and dietetic support to enable them to manage their condition. PMID:22117664

  6. Unravelling adverse reactions to NSAIDs using systems biology.

    PubMed

    Perkins, James R; Sanak, Marek; Canto, Gabriela; Blanca, Miguel; Cornejo-García, José Antonio

    2015-03-01

    We introduce the reader to systems biology, using adverse drug reactions (ADRs), specifically hypersensitivity reactions to multiple non-steroidal anti-inflammatory drugs (NSAIDs), as a model. To disentangle the different processes that contribute to these reactions - from drug intake to the appearance of symptoms - it will be necessary to create high-throughput datasets. Just as crucial will be the use of systems biology to integrate and make sense of them. We review previous work using systems biology to study related pathologies such as asthma/allergy, and NSAID metabolism. We show examples of their application to NSAIDs-hypersensitivity using current datasets. We describe breakthroughs in high-throughput technology and speculate on their use to improve our understanding of this and other drug-induced pathologies.

  7. [Cutaneous adverse reaction to Bio-Alcamid implant].

    PubMed

    Gómez-de la Fuente, E; Alvarez-Fernández, J G; Pinedo, F; Naz, E; Gamo, R; Vicente-Martín, F J; López-Estebaranz, J L

    2007-05-01

    In the last years new and numerous materials for the correction of defects and wrinkles have been developed. One of these materials is Bio-Alcamid, a non reabsorbable gel polymer constituted by meshes of poly-alkyl-imide, without known adverse effects. We report a 34-year-old woman that had Bio-Alcamid implants for acne scars and several months after presented nodular lesions together with a painful inflammatory nodule. The nodule was drained and culture of the purulent material yielded Streptococcus viridans. A cytology and a cellular block of that material showed a granulomatous inflammatory reaction together with a foreign body. The different types of reactions to implants and their pathogenic mechanism are discussed. It is important to know these possible reactions to filler materials given their increasing use and the potential medico-legal consequences.

  8. 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

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

    PubMed

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

    2010-07-01

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

  10. Preventing adverse drug reactions in the general population.

    PubMed

    Pezalla, Edmund

    2005-10-01

    In 2000, the number of patient deaths attributable to adverse drug reactions (ADRs) was estimated to be 218,000 annually. More than 51% of approved drugs in the market today may have serious side effects not detected before marketing approval. The causes of ADRs are many, ranging from drug-drug interactions to simple patient noncompliance. Until the use of electronic medical records becomes ubiquitous, other partnerships must be undertaken to lower the incidence of ADRs. Health plans and pharmacy benefit managers must work together to take effective steps to increase ADR monitoring and reporting and to proactively avoid ADRs through pharmacy management tools. PMID:16265935

  11. An Adverse Reaction in the Pediatric Sleep Laboratory

    PubMed Central

    Reppucci, Diana; Medin, Debra; Al-Saleh, Suhail; Smith, Mary Jane; Barter, Jill; Amin, Reshma

    2016-01-01

    We present a case of a 15-month-old boy with Cornelia de Lange Syndrome (NIPBL gene mutation). On a PSG, central sleep apnea (central apnea-hypopnea index of 19/hour) and nocturnal hypoventilation (transcutaneous CO2 > 50 mmHg for 53% of the night) were found. A positive pressure initiation study was aborted because the patient developed a serious adverse reaction. The differential diagnosis included a skin fragility condition versus an allergic contact dermatitis to the interface; this could be from the povidone-iodine solution used to clean the NiPPV interface or from the plastic of the interface itself. A skin biopsy was performed which was normal. The reaction was likely secondary to an allergic contact dermatitis from the povidone-iodine solution used to clean the NiPPV interface. The patient is currently tolerating NiPPV. PMID:27445573

  12. Adverse drug reactions: a hospital pharmacy-based reporting scheme.

    PubMed

    Winstanley, P A; Irvin, L E; Smith, J C; Orme, M L; Breckenridge, A M

    1989-07-01

    A pharmacy-based adverse drug reaction (ADR) reporting scheme, using pharmacists, nurses and medical practitioners as initiators of reports, was set up at the end of 1984 in the Royal Liverpool Hospital in order to encourage reporting. New reports were inspected at weekly intervals by a staff pharmacist, and a clinical pharmacologist. Reports were forwarded to the Committee on Safety of Medicines if the reaction was considered to be serious by the clinicians, or the ADR team or involved 'black triangle' drugs. The total number of ADR reports was increased eightfold by the introduction of the scheme (from 14 in 1984 to 76, 102 and 94 in 1985, 1986 and 1987 respectively), and this rate of reporting has been sustained. PMID:2775609

  13. An Adverse Reaction in the Pediatric Sleep Laboratory.

    PubMed

    Reppucci, Diana; Medin, Debra; Al-Saleh, Suhail; Smith, Mary Jane; Barter, Jill; Amin, Reshma

    2016-01-01

    We present a case of a 15-month-old boy with Cornelia de Lange Syndrome (NIPBL gene mutation). On a PSG, central sleep apnea (central apnea-hypopnea index of 19/hour) and nocturnal hypoventilation (transcutaneous CO2 > 50 mmHg for 53% of the night) were found. A positive pressure initiation study was aborted because the patient developed a serious adverse reaction. The differential diagnosis included a skin fragility condition versus an allergic contact dermatitis to the interface; this could be from the povidone-iodine solution used to clean the NiPPV interface or from the plastic of the interface itself. A skin biopsy was performed which was normal. The reaction was likely secondary to an allergic contact dermatitis from the povidone-iodine solution used to clean the NiPPV interface. The patient is currently tolerating NiPPV. PMID:27445573

  14. 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

  15. Adverse drug reactions in an elderly outpatient population.

    PubMed

    Schneider, J K; Mion, L C; Frengley, J D

    1992-01-01

    The prevalence of adverse drug reactions (ADRs) in elderly outpatients was investigated, along with factors that might be associated with their occurrence. The medical records of elderly patients attending an interdisciplinary geriatric clinic and a general medical clinic during 1988 were audited to collect a variety of demographic and treatment data and to detect documentation of first-time ADRs. Subjects were classified as having had an ADR if a physician documented this or if a relevant symptom was noted in the record and a score of 1 or above was obtained on the Adverse Drug Reaction Probability Scale. The presence of potential drug interactions was also assessed. The sample size was 463 patients, of whom 332 attended the medical clinic and 131 attended the geriatric clinic. Potential drug interactions were identified in the records of 143 subjects (31%). There were 107 documented ADRs in 97 patients (21%). Of these patients, 86 were noted by the physicians as having had an ADR. Twelve patients were hospitalized as a direct result of an ADR. Significant risk factors for ADRs were attendance in the geriatric clinic, the use of potentially harmful drug combinations, and the use of drugs that require therapeutic monitoring. Patient age and the number of drugs had no association with ADRs. In the elderly population studied, patients with frailty arising from multiple pathologies were more likely to have ADRs than the more robust elderly, even when their therapeutic regimens were simplified. PMID:1570873

  16. Immediate Adverse Reactions to Gadolinium-Based MR Contrast Media: A Retrospective Analysis on 10,608 Examinations

    PubMed Central

    Fusco, Roberta; dell'Aprovitola, Nicoletta; Catalano, Orlando; Filice, Salvatore; Schiavone, Vincenzo; Izzo, Francesco; Cuomo, Arturo

    2016-01-01

    Background and Purpose. Contrast media (CM) for magnetic resonance imaging (MRI) may determine the development of acute adverse reactions. Objective was to retrospectively assess the frequency and severity of adverse reactions associated with gadolinium-based contrast agents (GBCAs) injection in patients who underwent MRI. Material and Methods. At our center 10608 MRI examinations with CM were performed using five different GBCAs: Gd-BOPTA (MultiHance), Gd-DTPA (Magnevist), Gd-EOBDTPA (Primovist), Gd-DOTA (Dotarem), and Gd-BTDO3A (Gadovist). Results. 32 acute adverse reactions occurred, accounting for 0.3% of all administration. Twelve reactions were associated with Gd-DOTA injection (0.11%), 9 with Gd-BOPTA injection (0.08%), 6 with Gd-BTDO3A (0.056%), 3 with Gd-EOB-DTPA (0.028%), and 2 with Gd-DTPA (0.018%). Twenty-four reactions (75.0%) were mild, four (12.5%) moderate, and four (12.5%) severe. The most severe reactions were seen associated with use of Gd-BOPTA, with 3 severe reactions in 32 total reactions. Conclusion. Acute adverse reactions are generally rare with the overall adverse reaction rate of 0.3%. The most common adverse reactions were not severe, consisting in skin rash and hives.

  17. Immediate Adverse Reactions to Gadolinium-Based MR Contrast Media: A Retrospective Analysis on 10,608 Examinations.

    PubMed

    Granata, Vincenza; Cascella, Marco; Fusco, Roberta; dell'Aprovitola, Nicoletta; Catalano, Orlando; Filice, Salvatore; Schiavone, Vincenzo; Izzo, Francesco; Cuomo, Arturo; Petrillo, Antonella

    2016-01-01

    Background and Purpose. Contrast media (CM) for magnetic resonance imaging (MRI) may determine the development of acute adverse reactions. Objective was to retrospectively assess the frequency and severity of adverse reactions associated with gadolinium-based contrast agents (GBCAs) injection in patients who underwent MRI. Material and Methods. At our center 10608 MRI examinations with CM were performed using five different GBCAs: Gd-BOPTA (MultiHance), Gd-DTPA (Magnevist), Gd-EOBDTPA (Primovist), Gd-DOTA (Dotarem), and Gd-BTDO3A (Gadovist). Results. 32 acute adverse reactions occurred, accounting for 0.3% of all administration. Twelve reactions were associated with Gd-DOTA injection (0.11%), 9 with Gd-BOPTA injection (0.08%), 6 with Gd-BTDO3A (0.056%), 3 with Gd-EOB-DTPA (0.028%), and 2 with Gd-DTPA (0.018%). Twenty-four reactions (75.0%) were mild, four (12.5%) moderate, and four (12.5%) severe. The most severe reactions were seen associated with use of Gd-BOPTA, with 3 severe reactions in 32 total reactions. Conclusion. Acute adverse reactions are generally rare with the overall adverse reaction rate of 0.3%. The most common adverse reactions were not severe, consisting in skin rash and hives. PMID:27652261

  18. Immediate Adverse Reactions to Gadolinium-Based MR Contrast Media: A Retrospective Analysis on 10,608 Examinations

    PubMed Central

    Fusco, Roberta; dell'Aprovitola, Nicoletta; Catalano, Orlando; Filice, Salvatore; Schiavone, Vincenzo; Izzo, Francesco; Cuomo, Arturo

    2016-01-01

    Background and Purpose. Contrast media (CM) for magnetic resonance imaging (MRI) may determine the development of acute adverse reactions. Objective was to retrospectively assess the frequency and severity of adverse reactions associated with gadolinium-based contrast agents (GBCAs) injection in patients who underwent MRI. Material and Methods. At our center 10608 MRI examinations with CM were performed using five different GBCAs: Gd-BOPTA (MultiHance), Gd-DTPA (Magnevist), Gd-EOBDTPA (Primovist), Gd-DOTA (Dotarem), and Gd-BTDO3A (Gadovist). Results. 32 acute adverse reactions occurred, accounting for 0.3% of all administration. Twelve reactions were associated with Gd-DOTA injection (0.11%), 9 with Gd-BOPTA injection (0.08%), 6 with Gd-BTDO3A (0.056%), 3 with Gd-EOB-DTPA (0.028%), and 2 with Gd-DTPA (0.018%). Twenty-four reactions (75.0%) were mild, four (12.5%) moderate, and four (12.5%) severe. The most severe reactions were seen associated with use of Gd-BOPTA, with 3 severe reactions in 32 total reactions. Conclusion. Acute adverse reactions are generally rare with the overall adverse reaction rate of 0.3%. The most common adverse reactions were not severe, consisting in skin rash and hives. PMID:27652261

  19. Adverse reactions and tolerability of high-dose sublingual allergen immunotherapy

    PubMed Central

    Moral, Angel; Moreno, Victoria; Girón, Francisco; El-Qutob, David; Moure, José D; Alcántara, Manuel; Padial, Antonia; Oehling, Alberto G; Millán, Carmen; de la Torre, Fernando

    2016-01-01

    Background Sublingual allergen immunotherapy is an effective treatment against allergic respiratory disease. Many studies have shown the safety of this type of therapy, although the factors that might affect the tolerability of high-dose sublingual immunotherapy have not been well established. The aim of this study was to determine the factors that affect the tolerability of sublingual allergen immunotherapy. Patients and methods A total of 183 subjects aged ≥5 years, diagnosed with allergic rhinitis with/without mild to moderate asthma due to sensitization to grass, olive pollen, or mites, were included in this open, retrospective, multicentric, noninterventional study. Sublingual immunotherapy was administered for at least 3 months. Results The most frequent adverse reaction was oral pruritus (13.7% of the patients). Most of the reactions were local (84.7%) and immediate (93.5%) and occurred during the initiation phase (60.6%). All reactions were mild to moderate in severity. No serious adverse reactions were registered. When comparing factors with potential influence on the occurrence of adverse reactions, the results between the groups of subjects with and without adverse reactions showed no statistically significant differences in sex (P=0.6417), age (P=0.1801), years since the disease was first diagnosed (P=0.3800), treatment composition (P=0.6946), polysensitization (P=0.1730), or clinical diagnosis (P=0.3354). However, it was found that treatment duration had a statistically significant influence (3 months, >3 months: P=0.0442) and the presence of asthma was close to statistical significance (P=0.0847). Conclusion In our study, treatment duration is significantly associated with the occurrence of adverse reactions after the administration of high doses of sublingual allergen immunotherapy. PMID:27418842

  20. 40 CFR 717.12 - Significant adverse reactions that must be recorded.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Significant adverse reactions that... SIGNIFICANT ADVERSE REACTIONS TO HEALTH OR THE ENVIRONMENT General Provisions § 717.12 Significant adverse reactions that must be recorded. (a) Except as provided in paragraph (b) of this section,...

  1. 40 CFR 717.12 - Significant adverse reactions that must be recorded.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Significant adverse reactions that... SIGNIFICANT ADVERSE REACTIONS TO HEALTH OR THE ENVIRONMENT General Provisions § 717.12 Significant adverse reactions that must be recorded. (a) Except as provided in paragraph (b) of this section,...

  2. 40 CFR 717.12 - Significant adverse reactions that must be recorded.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Significant adverse reactions that... SIGNIFICANT ADVERSE REACTIONS TO HEALTH OR THE ENVIRONMENT General Provisions § 717.12 Significant adverse reactions that must be recorded. (a) Except as provided in paragraph (b) of this section,...

  3. 40 CFR 717.12 - Significant adverse reactions that must be recorded.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Significant adverse reactions that... SIGNIFICANT ADVERSE REACTIONS TO HEALTH OR THE ENVIRONMENT General Provisions § 717.12 Significant adverse reactions that must be recorded. (a) Except as provided in paragraph (b) of this section,...

  4. 40 CFR 717.12 - Significant adverse reactions that must be recorded.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Significant adverse reactions that... SIGNIFICANT ADVERSE REACTIONS TO HEALTH OR THE ENVIRONMENT General Provisions § 717.12 Significant adverse reactions that must be recorded. (a) Except as provided in paragraph (b) of this section,...

  5. ARWAR: A network approach for predicting Adverse Drug Reactions.

    PubMed

    Rahmani, Hossein; Weiss, Gerhard; Méndez-Lucio, Oscar; Bender, Andreas

    2016-01-01

    Predicting novel drug side-effects, or Adverse Drug Reactions (ADRs), plays an important role in the drug discovery process. Existing methods consider mainly the chemical and biological characteristics of each drug individually, thereby neglecting information hidden in the relationships among drugs. Complementary to the existing individual methods, in this paper, we propose a novel network approach for ADR prediction that is called Augmented Random-WAlk with Restarts (ARWAR). ARWAR, first, applies an existing method to build a network of highly related drugs. Then, it augments the original drug network by adding new nodes and new edges to the network and finally, it applies Random Walks with Restarts to predict novel ADRs. Empirical results show that the ARWAR method presented here outperforms the existing network approach by 20% with respect to average Fmeasure. Furthermore, ARWAR is capable of generating novel hypotheses about drugs with respect to novel and biologically meaningful ADR.

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

    PubMed

    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

    2014-11-11

    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.

  7. [Adverse reactions to metal orthopedic implants after knee arthroplasty].

    PubMed

    Thomsen, M; Krenn, V; Thomas, P

    2016-05-01

    Based on several clinical examples, the range of adverse or hypersensitive reactions to metal implants especially after total knee replacement are presented. In general, we found the patients to generally be women who present with pain, swelling, and local or generalized eczema. Some also present with early aseptic loosening mainly in the first 4 years after implantation. For these patients, a detailed allergy-specific history should be taken and a patch test should be performed; if necessary, blood ion levels should be evaluated to exclude cobaltism. Before revision surgery and exchange of the implant we always perform arthroscopic inspection to obtain biopsies for microbiology and histopathology. Using the Consensus Classification a good evaluation for planning revision with the different implant options is possible.

  8. 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

  9. Adverse reactions to benzodiazepine hypnotics: spontaneous reporting system.

    PubMed

    Bixler, E O; Kales, A; Brubaker, B H; Kales, J D

    1987-01-01

    The rates of reported adverse drug reactions involving the central nervous system were compared among patients taking any of three benzodiazepine hypnotics: flurazepam, temazepam, and triazolam. These rates, based upon data collected through the spontaneous reporting system of the Food and Drug Administration, were controlled for the number and size of new prescriptions for each drug. In general, triazolam had much higher overall rates than did the other two drugs. Hyperexcitability and withdrawal effects were greatest for triazolam and least for flurazepam. Amnesia was reported almost exclusively with triazolam. Rates for other cognitive as well as affective and other behavioral effects were also much greater for triazolam and about equal for the other two drugs. Finally, daytime sedation was reported slightly more for flurazepam than triazolam and least for temazepam which was also reported most frequently as lacking hypnotic effect. PMID:2892212

  10. [Interactions and adverse drug reactions: how to obtain information].

    PubMed

    Fattinger, K E

    1999-04-15

    Adverse drug reactions (ADR) are common. They may mimick many other diseases. It is therefore important to consider always ADR as possible causes for new complaints. Interactions are less common but they may also be the source of serious problems. First informations on both topics are commonly found in the Swiss Drug Compendium ("Arzneimittel-Kompendium der Schweiz") and in the accompanying "Grundlagen der Pharmakotherapie". Further information is found in several standard text books, on new substances eventually also via the internet. Rare side-effects require a Medline-search or eventually consultation of the WHO-database on ADR. Several institutions in Switzerland provide information on ADR (an index is found in an annex of the "Arzneimittel-Kompendium der Schweiz"). It is essential for drug safety monitoring that every physician communicates observation of ADR. PMID:10355337

  11. 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

  12. [Histamine intolerance - are the criteria of an adverse reaction met?].

    PubMed

    Reese, Imke

    2016-06-01

    Searching the internet for an explaination of recurring symptoms, many people come across the so-called histamine intolerance disorder. Also many practitioners like to diagnose this disorder without making sure that reproducibility, a prerequisite for an adverse reaction, is present. Consequently, presumably affected persons are often advised to follow a low-histamine diet. Depending on the source of information, these diets often avoid a huge variety of foods containing more or less histamine, which has a considerable impact on patient quality of life. While most persons benefit from such a diet in the beginning - this might be due to the change in dietary habits or the expectation of symptom improvement by dieting - in the long run the expected loss of symptoms will not happen. Underlying a diminished capacity for histamine degradation, the lack of partial or complete symptom improvement might be due to the fact that endogenous histamine release is responsible for reactions. The role of ingested histamine is discussed controversially. However, it is more than obvious that the histamine content of a certain food alone is not enough to predict its tolerance.If histamine intolerance is suspected, an individual diagnostic and therapeutic procedure is mandatory in order to minimize avoidance and to preserve a high quality of life. Ideally this is done in a close cooperation between allergologists and nutritionists/dieticians. PMID:27177895

  13. Knowledge and attitudes to reporting adverse drug reactions.

    PubMed

    Pulford, Andrew; Malcolm, William

    The reporting of adverse drug reactions (ADRs) by health professionals forms an important component of ongoing surveillance of post-marketing drug safety. The extension of responsibility for all health professionals to report ADRs has coincided with national immunization programmes, such as the national childhood immunization, human papillomavirus (HPV), and seasonal and H1N1 influenza programmes. The study objective was to evaluate knowledge of, and attitudes to, reporting ADRs among the professional groups most likely to see suspected reactions to vaccines. This included nursing professionals, whose views have not been included in previous studies. A survey of 91 practice nurses, health visitors, school nurses and GPs working in Ayrshire and Arran during June, July and August 2007 was undertaken. The respondents' knowledge of ADR reporting varied considerably. Although the majority of respondents recognized that it is the responsibility of health professionals to report suspected ADRs, there were lower levels of knowledge about the purpose of the Yellow Card system specifically; less than 50% of the respondents reported good knowledge about the system. The study suggests implications for practice with regard to the implementation of large-scale immunization programmes and potential solutions to under-reporting among these professional groups.

  14. Adverse reactions to cosmetics and methods of testing.

    PubMed

    Nigam, P K

    2009-01-01

    Untoward reactions to cosmetics, toiletries, and topical applications are the commonest single reason for hospital referrals with allergic contact dermatitis. In most cases, these are only mild or transient and most reactions being irritant rather than allergic in nature. Various adverse effects may occur in the form of acute toxicity, percutaneous absorption, skin irritation, eye irritation, skin sensitization and photosensitization, subchronic toxicity, mutagenicity/genotoxicity, and phototoxicity/photoirritation. The safety assessment of a cosmetic product clearly depends upon how it is used, since it determines the amount of substance which may be ingested, inhaled, or absorbed through the skin or mucous membranes. Concentration of ingredients used in the different products is also important. Various test procedures include in vivo animal models and in vitro models, such as open or closed patch test, in vivo skin irritation test, skin corrosivity potential tests (rat skin transcutaneous electrical resistance test, Episkin test), eye irritation tests (in vivo eye irritancy test and Draize eye irritancy test), mutagenicity/genotoxicity tests (in vitro bacterial reverse mutation test and in vitro mammalian cell chromosome aberration test), and phototoxicity/photoirritation test (3T3 neutral red uptake phototoxicity test). Finished cosmetic products are usually tested in small populations to confirm the skin and mucous membrane compatibility, and to assess their cosmetic acceptability.

  15. Adverse drug reactions associated with antiretroviral therapy in South Africa.

    PubMed

    Birbal, Sumeshni; Dheda, Mukesh; Ojewole, Elizabeth; Oosthuizen, Frasia

    2016-09-01

    South Africa has one of the highest prevalences of HIV and AIDS in the world. HIV/AIDS patients face countless challenges, one of which is the risk of adverse drug reactions (ADRs). This study aimed to describe the ADRs reported in South Africa with reference to the type of ADRs, antiretrovirals (ARVs) implicated, seriousness of the ADRs and patient demographics associated with specific ADRs. A retrospective quantitative study was carried out using ADR reports submitted to the National Department of Health (NDoH) from 1 January 2010 to 31 December 2014. A descriptive and inferential analysis was carried out to determine the strength of the relationships between different variables. A total of 2 489 reports were analysed. This study found evidence of ADRs among patients on regimens based on stavudine (n = 1 256, 50.46%), efavirenz (n = 572, 22.98%), zidovudine (n = 209, 8.40%), tenofovir (n = 203, 8.16%) and nevirapine (n = 153, 6.15%). The 10 most common ADRs reported with the use of ARVs were peripheral neuropathy (n = 472, 19%), lipodystrophy (n = 471, 18.9%), serious skin reactions (n = 266, 10.7%), gynaecomastia (n = 219, 8.8%), renal failure (n = 140, 5.6%), dizziness (n = 133, 5.3%), hyperlactatemia (n = 118, 4.7%), psychosis/hallucinations (n = 47, 1.9%), sleep disturbances (n = 44, 1.8%) and vomiting (n = 44, 1.8%). Female patients were more likely to experience peripheral neuropathy, lipodystrophy, skin rash, anaemia and hyperlactatemia, while male patients were more prone to experience gynaecomastia and peripheral neuropathy. In addition, patients aged 30-44 years reported the most ADRs. Most reactions resulted from the use of stavudine, efavirenz, zidovudine, nevirapine and tenofovir in the population groups identified in this study. PMID:27681148

  16. Methods and systems to detect adverse drug reactions in hospitals.

    PubMed

    Thürmann, P A

    2001-01-01

    Detection of adverse drug reactions (ADRs) in hospitals offers the chance to detect serious ADRs resulting in hospitalisation and ADRs occurring in hospitalised patients, i.e. patients with high comorbidity and receiving drugs that are administered only in hospitals. The most commonly applied methods involve stimulated spontaneous reporting of doctors and nurses, comprehensive collection by trained specialists and, more recently, computer-assisted approaches using routine data from hospital information systems. The different methods of ADR detection used result in different rates and types of ADRs and, consequently, in different drug classes being responsible for these ADRs. Another factor influencing the results of surveys is the interpretation of the term ADR, where some authors adhere to the strict definition of the World Health Organization and many others include intended and unintended poisoning as well as errors in prescribing and dispensing, thus referring to adverse drug events. Depending on the method used for screening of patients, a high number of possible ADRs and only few definite ADRs are found, or vice versa. These variations have to be taken into account when comparing the results of further analyses performed with these data. ADR rates and incidences in relation to the number of drugs prescribed or patients exposed have been calculated in only a few surveys and projects, and this interesting pharmacoepidemiological approach deserves further study. In addition, the pharmacoeconomic impact of ADRs, either resulting in hospitalisation or prolonging hospital stay, has been estimated using different approaches. However, a common standardised procedure for such calculations has not yet been defined. Although detection of ADRs in hospitals offers the opportunity to detect severe ADRs of newly approved drugs, these ADRs are still discovered by spontaneous reporting systems. The prospects offered by electronic hospital information systems as well as

  17. 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

  18. [Academic discussion of adverse reaction of clinical trials of new traditional Chinese medicines and relevant influencing factors].

    PubMed

    Wang, Wen-ping; Yu, Ming; Wang, Li; Jiang, Xi-ren; Li, Xiao-bin; Wang, Hua-wei; Cao, Ying; Liu, Kai; Huang, Lu-qi

    2015-01-01

    Data of clinical trial projects involved by clinical trial institutions certified by the State Food and Drug Administration from 2002 to November 2012 were collected to summarize adverse reactions in project summary/statistical reports, analyze the rate of adverse reactions of clinical trials of new traditional Chinese medicines and relevant influencing factors, and increase the awareness of the safety of new traditional Chinese medicines. A total of 73 050 cases in 209 projects of 14 specialties were collected, including 49 689 cases in the new traditional Chinese medicine group and 271 adverse reaction cases, with an incidence rate of adverse reactions at 0.55%. The adverse reaction rate in 3 months < middle long course ≤ 6 months was the highest (1.04%), whereas that in short course ≤ half a month was the lowest (0.48%). The adverse reaction was closely related with the route of administration, 1.28% for topical > 0.63% for injection > 0.50% for oral. In the administration of only the test drug, the adverse reaction rate of patches was the highest (2.68%), whereas that of aerosols and suppositories was lowest (0). In the combined administration of the test drug and the simulation agent, the adverse reaction rate of external test patch + capsule was the highest (3.38%), whereas that of capsule + oral liquid, pills + granules, tablets + oral liquid, tablets + pills, tablet + capsule was the lowest (0). In the administration of only the test drug, the adverse reaction rate was 0.47%; In the combined administration with simulation agent (drug volume increase), the adverse reaction rate was 0.74%. Different doses caused adverse reaction different rates; The adverse reaction rate of drugs with whole-course dose between 1 100-1 200 g was the highest (3.36%), that for whole-course doses of 500-600, 900-1 000, 1 400-1 500, 1 600-1 700, 1 800-1 900 g was the lowest (0). In conclusion, the adverse reaction rate of new traditional Chinese medicines was still up to 0

  19. 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.

  20. 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

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

    PubMed Central

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

    2015-01-01

    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

  2. Adverse drug reactions to herbal and synthetic expectorants.

    PubMed

    Ernst, E; Sieder, C; März, R

    1995-01-01

    Our knowledge relating to adverse drug reactions (ADRs) of phytomedicines is highly fragmentary. The aim of this study was to define the prevalence of ADRs following medication with herbal or synthetic expectorants. In a multicentre, comparative post-marketing surveillance study of more than 3000 patients with acute bronchitis, about half were treated with a herbal remedy (SinupretR) and the other half with various other expectorants. In ascending order of incidence, ADRs were noted during mono-medication of SinupretR (0.8%), Ambroxol (1.0%) and acetylcysteine (4.3%). When concomitant drugs were used, this rank order was unchanged but incidence rates were markedly increased (3.4, 6.5 and 8.2%, respectively). The most frequent ADRs were gastrointestinal symptoms. It is concluded that expectorants are associated with ADRs in roughly 1-5% of cases undergoing single drug treatment and in 3-10% when more than one medication is being used. Amongst the expectorants used in this study, the herbal preparation SinupretR is associated with the lowest incidence of ADRs.

  3. 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

  4. Pharmacovigilance on twitter? Mining tweets for adverse drug reactions.

    PubMed

    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.

  5. Pharmacovigilance on twitter? Mining tweets for adverse drug reactions.

    PubMed

    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

  6. Adverse drug reactions in older people: detection and prevention.

    PubMed

    Petrovic, Mirko; van der Cammen, Tischa; Onder, Graziano

    2012-06-01

    Adverse drug reactions (ADRs) in older adults are an important healthcare problem since they are frequently a cause of hospitalization, occur commonly during admission, and are an important cause of morbidity and mortality. Older adults are particularly susceptible to ADRs because they are usually on multiple drug regimens and because age is associated with changes in pharmacokinetics and pharmacodynamics. The presentation of an ADR in older adults is often atypical, which further complicates its recognition. One potential strategy for improving recognition of ADRs is to identify those patients who are at risk of an ADR. The recently developed GerontoNet ADR Risk Score is a practical tool for identification of older patients who are at increased risk for an ADR and who may represent a target for interventions aimed at reducing ADRs. Provision of adequate education in the domain of clinical geriatric pharmacology can improve recognition of ADRs. Besides formal surveillance systems, built-in computer programs with electronic prescribing databases and clinical pharmacist involvement in patient care within multidisciplinary geriatric teams might help to minimize the occurrence of ADRs. In addition, a number of actions can be taken in hospitals to stimulate appropriate prescribing and to assure adequate communication between primary and hospital care. In older adults with complex medical problems and needs, a global evaluation obtained through a comprehensive geriatric assessment may be helpful in simplifying drug prescription and prioritizing pharmacological and healthcare needs, resulting in an improvement in quality of prescribing. PMID:22642780

  7. 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

  8. The Severe Adverse Reaction to Vitamin K1 Injection Is Anaphylactoid Reaction but Not Anaphylaxis

    PubMed Central

    Mi, Yan-Ni; Ping, Na-Na; Xiao, Xue; Zhu, Yan-Bing; Liu, Jing; Cao, Yong-Xiao

    2014-01-01

    The severe adverse reaction to vitamin K1 injection is always remarkable and is thought to result from anaphylaxis. Paradoxically, however, some patients administered vitamin K1 injection for the first time have adverse reactions. Using beagle dogs, the present study tested the hypothesis that the response to vitamin K1 is an anaphylactoid reaction. The results showed that serious anaphylaxis-like symptoms appeared in beagle dogs after the administration of vitamin K1 injection for the first time. The plasma histamine concentration increased, and blood pressure decreased sharply. After sensitization, dogs were challenged with vitamin K1 injection and displayed the same degree of symptoms as prior to sensitization. However, when the vitamin K1 injection-sensitized dogs were challenged with a vitamin K1-fat emulsion without solubilizers such asTween-80, the abnormal reactions did not occur. Furthermore, there was no significant change in the plasma immunoglobulin E concentration after vitamin K1 challenge. Following treatment with vitamin K1 injection, the release of histamine and β-hexosaminidase by rat basophilic leukemia-2H3 cells as well as the rate of apoptosis increased. The Tween-80 group displayed results similar to those observed following vitamin K1 injection in vivo. However, the dogs in the vitamin K1-fat emulsion group did not display any abnormal behavior or significant change in plasma histamine. Additionally, degranulation and apoptosis did not occur in rat basophilic leukemia-2H3 cells. Our results indicate that the adverse reaction induced by vitamin K1 injection is an anaphylactoid reaction, not anaphylaxis. Vitamin K1 injection induces the release of inflammatory factors via a non-IgE-mediated immune pathway, for which the trigger may be the solubilizer. PMID:24594861

  9. [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

  10. Severe adverse reactions caused by omeprazole: A case report

    PubMed Central

    Yu, Meiling; Qian, Jianghua; Guo, Daohua; Li, Li; Liu, Xiaolin

    2016-01-01

    A 61-year-old female patient was admitted to hospital following development of a whole-body rash for 10 days, diarrhea for 7 days, and unconsciousness and oliguria for 1 day. The patient had developed stomach discomfort following the oral administration of non-steroidal anti-inflammatory drugs, the exact nature of which was unknown, for the treatment of arthritic pain for >1 month. The patient was then prescribed omeprazole enteric-coated tablets (20 mg twice daily) for treatment of this symptom. However, the patient developed a whole-body rash 7 days after administering omeprazole, 10 days prior to admission. This symptom was followed by severe diarrhea with nausea and vomiting after 10 days, then shock. The shock occurred after administering omeprazole for 16 days. The patient developed a whole body rash 7 days after administering omeprazole, then 3 days later (after administering omeprazole for 10 days) severe diarrhea with nausea and vomiting occurred. The shock remained until administering omeprazole on the 16th day, with severe diarrhea with nausea and vomiting occurring 6 days later. The patient's condition did not improve following treatment for allergies, low blood pressure and oliguria in the Intensive Care Unit (ICU) department at Suzhou Municipal Hospital. For further diagnosis and treatment, the patient was admitted to the ICU department of The First Affiliated Hospital of Bengbu Medical College and was given a fluid infusion, antibiotics and phlegm-reducing treatment, a plasma infusion, blood filtration, and anti-diarrheal and anti-allergy treatment. The patient's vital signs were stable, with a normal temperature and hemogram results, and improved kidney function and deflorescence. Genetic screening revealed that the patient poorly metabolized omeprazole. Therefore, severe adverse reactions (allergic shock, rash and diarrhea) experienced by the patient were caused by the accumulation of omeprazole metabolites resulting from its slow metabolism in

  11. Evaluation of outpatient adverse drug reactions leading to hospitalization.

    PubMed

    Wu, Wenchen Kenneth; Pantaleo, Nicholas

    2003-02-01

    Outpatient adverse drug reaction (ADR)related hospitalization through the emergency department of a nonprofit hospital and the contributing factors are reviewed. Patients who were hospitalized because of suspected ADRs were selected from daily admissions reports and patient medication profiles from 1997 and 1998 by the pharmacy department of a nonprofit community teaching hospital. Hospital charges for individual patients were obtained from the institution's accounting system. Suspected drugs, their therapeutic class, and the organ systems involved in the ADRs were identified. A total of 191 patients who had a complete medical history and cost information were included in the study. Of those patients, 56% were female, and 45% of the patients were 75 years of older. The average hospital charge per ADR patient was $9491. Room and board accounted for more than 50% of total charges. The average length of stay for study patients was 8.0 +/- 10.3 days. Major therapeutic classes implicated in ADRs included antidiabetic agents (27.8%), anticoagulants (15.2%), anticonvulsants (10.0%), beta-blockers (7.9%), and angiotensin-converting-enzyme inhibitors (7.9%). Organ systems most commonly involved in ADR admissions were the endocrine (30.9%) and cardiovascular (24.1%) systems. The implicationed therapeutic groups and organ systems exhibited a different pattern from those of earlier ADR studies. The elderly and the poor are most affected by ADRs. The availability of new drugs and the shift in disease treatment necessitate the continuous monitoring of new ADRs. Patients and family members should be integral components of a multidisciplinary strategy for minimizing the personal and social impact of ADRs.

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

    PubMed Central

    Gabrilovich, Evgeniy

    2013-01-01

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

  13. Thrombopoietin Receptor Agonists Are Often Ineffective in Immune Thrombocytopenia and/or Cause Adverse Reactions: Results from One Hand

    PubMed Central

    Depré, Fabian; Aboud, Nasra; Ringel, Frauke; Salama, Abdulgabar

    2016-01-01

    Background Eltrombopag and romiplostim are thrombopoietin receptor agonists (TPOs) that have been increasingly used for the treatment of immune thrombocytopenia (ITP). Based on our experience, the incidence of abortive treatment with these drugs and the occurrence of adverse reactions that lead to therapy break-off despite response are higher than has been previously suggested. Methods During the last 8 years, a total of 65 patients were treated with eltrombopag and/or romiplostim at our institute. Results 36 of a total of 58 patients responded well to eltrombopag. In 12 patients that responded, treatment with eltrombopag was discontinued due to the development of adverse reactions. Eltrombopag was replaced by romiplostim in 23 cases (14 non-responders, 9 patients with adverse reactions). Of these patients, 83% responded to romiplostim. Among all patients treated with romiplostim (n = 32), 75% initially responded; however, 8 of these patients developed adverse reactions. Romiplostim was replaced by eltrombopag in 5 cases (4 due to adverse reactions, 1 non-responsive patient), and only 3 (60%) of these patients were observed to respond to eltrombopag. Conclusion TPOs often remain ineffective in ITP or result in adverse reactions, which lead to treatment stop or to drug switch. Therefore, alternative treatment options are required.

  14. [Adverse reaction induced by licorice preparations: clinical analysis of 93 cases].

    PubMed

    Mao, Min; Li, Wei; Wang, Wei; Wang, Shu-Xia; Lu, Jin; Chang, Zhang-Fu

    2013-11-01

    Licorice is a traditional Chinese medicine commonly used in clinic. The products,what contain licorice or licorice extract, has early been involved in the field of cosmetics except for the field of pharmaceuticals and food. Consequently, the reporting on adverse reactions induced by licorice preparations are more frequent. Based on the clinical data of licorice preparations adverse reactions, we described the characteristics of the licorice-related adverse reactions, and proposed specific measures to reduce the incidence of adverse reactions, provided a reference for the rational use of licorice preparations. PMID:24494570

  15. 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

  16. 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.

  17. Prospective audit of adverse reactions occurring in 459 primary antibody-deficient patients receiving intravenous immunoglobulin

    PubMed Central

    BRENNAN, V M; SALOMÉ-BENTLEY, N J; CHAPEL, H M

    2003-01-01

    Intravenous immunoglobulin (IVIG) is used as the standard replacement therapy for patients with primary antibody deficiencies. A previous study of adverse reactions in patients self-infusing at home over 1 year showed an overall reaction rate of 0·7%. A larger prospective study is reported here, involving a greater number of immunology centres and including children and adults who received infusions from medical or nursing staff as well as those self-infusing. Four hundred and fifty-nine patients were entered into this study and 13 508 infusions were given. The study showed that no severe reactions occurred and the reaction rate was low at 0·8%. This figure could have been lower, 0·5%, if predisposing factors responsible for some reactions had been considered before infusion. In conclusion, the study shows the importance of ongoing training for patients and staff to recognize the predisposing factors to prevent avoidable reactions. Because none of these reactions were graded as severe, the present guidance to prescribe self-injectable adrenaline for patients infusing outside hospital should be reviewed. PMID:12869031

  18. Adverse Reaction to Nicotine Gum in Malay Female Smoker: A Case Report

    ERIC Educational Resources Information Center

    Noorzurani, Md Haris Robson; Bond, Alyson; Wolff, Kim

    2008-01-01

    Nicotine replacement therapies (NRT) are prescribed in smoking cessation programmes to help smokers stop smoking. The ideal dosage of NRT should control cravings and withdrawal symptoms but avoid adverse reactions. This report describes a case of adverse reaction to nicotine gum in a female Malay smoker. Assays taken 2 h after the gum, showed that…

  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 Reaction to Cetuximab, an Epidermal Growth Factor Receptor Inhibitor.

    PubMed

    Štulhofer Buzina, Daška; Martinac, Ivana; Ledić Drvar, Daniela; Čeović, Romana; Bilić, Ivan; Marinović, Branka

    2016-04-01

    Dear Editor, Inhibition of the epidermal growth factor receptor (EGFR) is a new strategy in treatment of a variety of solid tumors, such as colorectal carcinoma, non-small cell lung cancer, squamous cell carcinoma of the head and neck, and pancreatic cancer (1). Cetuximab is a chimeric human-murine monoclonal antibody against EGFR. Cutaneous side effects are the most common adverse reactions occurring during epidermal growth factor receptor inhibitors (EGFRI) therapy. Papulopustular rash (acne like rash) develop with 80-86% patients receiving cetuximab, while xerosis, eczema, fissures, teleangiectasiae, hyperpigmentations, and nail and hair changes occur less frequently (2). The mechanism underlying these skin changes has not been established and understood. It seems EGFRI alter cell growth and differentiation, leading to impaired stratum corneum and cell apoptosis (3-5). An abdominoperineal resection of the rectal adenocarcinoma (Dukes C) was performed on a 43-year-old female patient. Following surgery, adjuvant chemo-radiotherapy was applied. After two years, the patient suffered a metastatic relapse. Abdominal lymphadenopathy was detected on multi-slice computer tomography (MSCT) images, with an increased value of the carcinoembryonic antigen (CEA) tumor marker (maximal value 57 ng/mL). Hematological and biochemical tests were within normal limits, so first-line chemotherapy with oxaliplatin and a 5-fluorouracil (FOLFOX4) protocol was introduced. A wild type of the KRAS gene was confirmed in tumor tissue (diagnostic prerequisite for the introduction of EGFRI) and cetuximab (250 mg per m2 of body surface) was added to the treatment protocol. The patient responded well to the treatment with confirmed partial regression of the tumor formations. Three months after the patient started using cetuximab, an anti-EGFR monoclonal antibody, the patient presented with a papulopustular eruption in the seborrhoeic areas (Figure 1) and eczematoid reactions on the extremities

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

    PubMed Central

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

    2013-01-01

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

  2. [Advances in studies of renal adverse reactions of Leonurus heterophyllus].

    PubMed

    Yu, Jie; Wang, Jing; Zhao, Ronghua; Bao, Zhaorigetu; Cai, Shaoqing

    2010-05-01

    Motherwort (Herb of Leonurus heterophyllus) was a traditional Chinese medicine used for the treatment of various kinds of gynaecological diseases, which was considered as non-toxic medicine since ancient times. However, adverse effects such as kidney damage, uterus damage, allergy and diarrhea were frequently reported recently. This paper reviews the possible target site, toxic dosage, chemical substance and other related factors of these kidney damage caused by motherwort from both the clinic and animal experiment view.

  3. Active Hemovigilance Significantly Improves Reporting of Acute Non-infectious Adverse Reactions to Blood Transfusion.

    PubMed

    Agnihotri, Naveen; Agnihotri, Ajju

    2016-09-01

    One of the key purposes of a hemovigilance program is to improve reporting of transfusion related adverse events and subsequent data-driven improvement in blood transfusion (BT) practices. We conducted a study over 3 years to assess the impact of healthcare worker training and an active feedback programme on reporting of adverse reactions to BTs. All hospitalized patients who required a BT were included in the study. Healthcare workers involved in BT to patients were sensitized and trained in adverse reaction reporting by conducting training sessions and meetings. All the transfused patients were 'actively' monitored for any acute adverse reaction by using a uniquely coded blood issue form. A total of 18,914 blood components transfused to 5785 different patients resulted in 61 adverse reaction episodes. This incidence of 0.32 % in our study was found to be significantly higher (p < 0.005) than that reported from the same region in the past. Red blood cell units were the most frequently transfused component and thus most commonly involved in an adverse reaction (42.6 %), however apheresis platelets had the highest chance of reaction per unit transfused (0.66 %). There was no mortality associated with the BT during the study period. An active surveillance program significantly improves reporting and management of adverse reactions to BTs. PMID:27429527

  4. Assessment of Adverse Drug Reactions Based on Spontaneous Signals at Secondary Care Public Hospital.

    PubMed

    Ponnusankar, S; Tejaswini, M; Chaitanya, M

    2015-01-01

    Adverse drug reactions are considered to be among the leading causes of morbidity and mortality. Approximately 5-25% of hospital admissions are due to adverse drug reactions and 6-15% of hospitalized patients experience serious adverse drug reactions, causing significant prolongation of hospital stay. Thus this study was aimed at determining adverse drug reactions by conducting spontaneous reporting in secondary care Govt. District Head Quarters Hospital at Ooty. A prospective Spontaneous Adverse Drug Reaction reporting study was conducted over a period of 12 months from July 2012 to June 2013. The assessment, categorization, causality, severity and preventability were assessed using standard criteria. A total of 47 suspected adverse drug reactions were reported during the study period. Over all incidences was 1.29% among the study population. Antibiotics (31.91%) were the class of drug most commonly involved, while ciprofloxacin (14.89%) was the most frequently reported. Type H (Hypersensitivity) reactions (51.06%) accounted for majority of the reports and a greater share of the adverse drug reactions are probable (89.36%) based on causality assessment. Mild reactions accounted 82.97% based on modified Hartwig and Siegel severity scale. In 76.59% of the reports, the reaction was considered to be preventable based on Schumock and Thornton preventability scale. The implementation of monitoring based on spontaneous reporting will be useful for the detection and evaluation is associated with increase in morbidity and duration of hospitalization. This study also has established the vital role of clinical pharmacist in the adverse drug reaction monitoring program. PMID:26664067

  5. Metal-on-Metal Hip Arthroplasty: A Review of Adverse Reactions and Patient Management.

    PubMed

    Drummond, James; Tran, Phong; Fary, Camdon

    2015-01-01

    Recent alarming joint registry data highlighting increased revision rates has prompted further research into the area of metal-on-metal hip replacements and resurfacings. This review article examines the latest literature on the topic of adverse reactions to metal debris and summarises the most up-to-date guidelines on patient management. Adverse reactions to metal debris can cause significant damage to soft tissue and bone if not diagnosed early. Furthermore, not every patient with an adverse reaction to metal debris will be symptomatic. As such, clinicians must remain vigilant when assessing and investigating these patients in order to detect failing implants and initiate appropriate management. PMID:26132653

  6. Metal-on-Metal Hip Arthroplasty: A Review of Adverse Reactions and Patient Management

    PubMed Central

    Drummond, James; Tran, Phong; Fary, Camdon

    2015-01-01

    Recent alarming joint registry data highlighting increased revision rates has prompted further research into the area of metal-on-metal hip replacements and resurfacings. This review article examines the latest literature on the topic of adverse reactions to metal debris and summarises the most up-to-date guidelines on patient management. Adverse reactions to metal debris can cause significant damage to soft tissue and bone if not diagnosed early. Furthermore, not every patient with an adverse reaction to metal debris will be symptomatic. As such, clinicians must remain vigilant when assessing and investigating these patients in order to detect failing implants and initiate appropriate management. PMID:26132653

  7. Adverse mucocutaneous reactions related to chemotherapeutic agents: part II.

    PubMed

    Criado, Paulo Ricardo; Brandt, Hebert Roberto Clivati; Moure, Emanuella Rosyane Duarte; Pereira, Guilherme Luiz Stelko; Sanches Júnior, Jose Antonio

    2010-01-01

    Events and reactions involving chemotherapy are common in clinical oncology. Chemotherapeutic agents are widely used in therapy. Side effects range from the common to the rare and may be confused with other mucocutaneous manifestations resulting from the oncological treatment. The objective of this paper was to present data on skin reactions to chemotherapy, particularly those cases in which the dermatologist is requested to issue a report and asked to comment on the safety and viability of readministration of a specific drug. The authors describe aspects associated with these events, presenting a detailed analysis of each one of them.

  8. A prospective study of adverse drug reactions to antiepileptic drugs in children

    PubMed Central

    Anderson, Mark; Egunsola, Oluwaseun; Cherrill, Janine; Millward, Claire; Fakis, Apostolos; Choonara, Imti

    2015-01-01

    Objectives To prospectively determine the nature and rate of adverse drug reactions (ADRs) in children on antiepileptic drugs (AEDs) and to prospectively evaluate the effect of AEDs on behaviour. Setting A single centre prospective observational study. Participants Children (<18 years old) receiving one or more AEDs for epilepsy, at each clinically determined follow-up visit. Primary and secondary outcomes Primary outcome was adverse reactions of AEDs. Behavioural and cognitive functions were secondary outcomes. Results 180 children were recruited. Sodium valproate and carbamazepine were the most frequently used AEDs. A total of 114 ADRs were recorded in 56 of these children (31%). 135 children (75%) were on monotherapy. 27 of the 45 children (60%) on polytherapy had ADRs; while 29 (21%) of those on monotherapy had ADRs. The risk of ADRs was significantly lower in patients receiving monotherapy than polytherapy (RR: 0.61, 95% CI 0.47 to 0.79, p<0.0001). Behavioural problems and somnolence were the most common ADRs. 23 children had to discontinue their AED due to an ADR. Conclusions Behavioural problems and somnolence were the most common ADRs. Polytherapy significantly increases the likelihood of ADRs in children. Trail registration number EudraCT (2007-000565-37). PMID:26033949

  9. 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

  10. 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

  11. 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.

  12. Adverse reaction to metal debris in a painful hemiarthroplasty of the hip

    PubMed Central

    Palmer, Jonathan Simon; Dean, Michael William; Briant-Evans, Toby; Stranks, Geoff

    2016-01-01

    Adverse reaction to metal debris (ARMD) in total hip arthroplasty surgery is a well-known problem. We present the case of a unipolar hemiarthroplasty requiring revision within 18 months of insertion secondary to an adverse reaction to metal debris. This case demonstrates a rare cause for failure of a hemiarthroplasty following a fragility fracture. We feel that ARMD should be considered in all cases where pain and dysfunction in the presence of any hip prosthesis cannot be explained by routine investigations.

  13. Monitoring adverse reactions to food additives in the U.S. Food and Drug Administration.

    PubMed

    Tollefson, L

    1988-12-01

    Technological advances in food science have resulted in the development of numerous food additives, most of which require premarket approval by the Food and Drug Administration (FDA). Concomitant with the benefits of these additives, such as extending the shelf life of certain food commodities, is the potential for various risks. These potential risks include the possibility of the consumer experiencing an adverse reaction to the additive. In order to ascertain the character and the gravity of alleged adverse reactions to food products which it regulates, the FDA's Center for Food Safety and Applied Nutrition has developed the Adverse Reaction Monitoring System (ARMS). This postmarketing surveillance system for food additives is designed to analyze consumer reports of adverse reactions in order to alert FDA officials about any potential public health hazard associated with an approved food additive, and to delineate specific syndromes which may lead to focused clinical investigations. To date, among the products routinely monitored in the ARMS, sulfiting agents and the artificial sweetener aspartame have generated the largest volume of consumer reports describing adverse reactions. An overview of the analyses of the sulfite and aspartame adverse reaction reports is presented, along with a description of the mechanics of the postmarketing surveillance system, and a detailed discussion of its limitations.

  14. Adverse reactions of Methylphenidate in children with attention deficit-hyperactivity disorder: Report from a referral center

    PubMed Central

    Khajehpiri, Zahra; Mahmoudi-Gharaei, Javad; Faghihi, Toktam; Karimzadeh, Iman; Khalili, Hossein; Mohammadi, Mostafa

    2014-01-01

    Objective: The aim of the current study was to determine various aspects of methylphenidate adverse reactions in children with attention deficit-hyperactivity disorder (ADHD) in Iran. Methods: During the 6 months period, all children under methylphenidate treatment alone or along with other agents attending a university-affiliated psychology clinic were screened regarding all subjective and objective adverse drug reactions (ADRs) of methylphenidate. Causality and seriousness of detected ADRs were assessed by relevant World Health Organization definitions. The Schumock and Thornton questionnaire was used to determine preventability of ADRs. Findings: Seventy-one patients including 25 girls and 46 boys with ADHD under methylphenidate treatment were enrolled within the study period. All (100%) ADHD children under methylphenidate treatment developed at least one ADR. Anorexia (74.3%), irritability (57.1%), and insomnia (47.2%) were the most frequent methylphenidate-related adverse reactions. Except for one, all other detected ADRs were determined to be mild. In addition, no ADR was considered to be preventable and serious. Conclusion: Our data suggested that although methylphenidate related adverse reactions were common in children with ADHD, but they were mainly mild and nonserious. PMID:25535621

  15. The mechanisms of delayed onset type adverse reactions to oseltamivir.

    PubMed

    Hama, Rokuro

    2016-09-01

    Oseltamivir is recommended for the treatment and prophylaxis of influenza in persons at higher risk for influenza complications such as individuals with diabetes, neuropsychiatric illnesses, and respiratory, cardiac, renal, hepatic or haematological diseases. However, a recent Cochrane review reported that reduction of antibody production, renal disorders, hyperglycaemia, psychiatric disorders, and QT prolongation may be related to oseltamivir use. The underlying mechanisms are reviewed. There is decisive evidence that administration of a clinically compatible dose of oseltamivir in mice challenged by a respiratory syncytial virus (RSV) that lacks a neuraminidase gene showed symptom-relieving effects and inhibition of viral clearance. These effects were accompanied by decreased level of T cell surface sialoglycosphingolipid (ganglioside) GM1 that is regulated by the endogenous neuraminidase in response to viral challenge. Clinical and non-clinical evidence supports the view that the usual dose of oseltamivir suppresses pro-inflammatory cytokines such as interferon-gamma, interleukin-6, and tumour necrosis factor-alpha almost completely with partial suppression of viral shedding in human influenza virus infection experiment. Animal toxicity tests support the clinical evidence with regard to renal and cardiac disorders (bradycardia and QT prolongation) and do not disprove the metabolic effect. Reduction of antibody production and cytokine induction and renal, metabolic, cardiac, and prolonged psychiatric disorders after oseltamivir use may be related to inhibition of the host's endogenous neuraminidase. While the usual clinical dose of zanamivir may not have this effect, a higher dose or prolonged administration of zanamivir and other neuraminidase inhibitors may induce similar delayed reactions, including reduction of the antibody and/or cytokine production. PMID:27251370

  16. The mechanisms of delayed onset type adverse reactions to oseltamivir

    PubMed Central

    Hama, Rokuro

    2016-01-01

    Abstract Oseltamivir is recommended for the treatment and prophylaxis of influenza in persons at higher risk for influenza complications such as individuals with diabetes, neuropsychiatric illnesses, and respiratory, cardiac, renal, hepatic or haematological diseases. However, a recent Cochrane review reported that reduction of antibody production, renal disorders, hyperglycaemia, psychiatric disorders, and QT prolongation may be related to oseltamivir use. The underlying mechanisms are reviewed. There is decisive evidence that administration of a clinically compatible dose of oseltamivir in mice challenged by a respiratory syncytial virus (RSV) that lacks a neuraminidase gene showed symptom-relieving effects and inhibition of viral clearance. These effects were accompanied by decreased level of T cell surface sialoglycosphingolipid (ganglioside) GM1 that is regulated by the endogenous neuraminidase in response to viral challenge. Clinical and non-clinical evidence supports the view that the usual dose of oseltamivir suppresses pro-inflammatory cytokines such as interferon-gamma, interleukin-6, and tumour necrosis factor-alpha almost completely with partial suppression of viral shedding in human influenza virus infection experiment. Animal toxicity tests support the clinical evidence with regard to renal and cardiac disorders (bradycardia and QT prolongation) and do not disprove the metabolic effect. Reduction of antibody production and cytokine induction and renal, metabolic, cardiac, and prolonged psychiatric disorders after oseltamivir use may be related to inhibition of the host’s endogenous neuraminidase. While the usual clinical dose of zanamivir may not have this effect, a higher dose or prolonged administration of zanamivir and other neuraminidase inhibitors may induce similar delayed reactions, including reduction of the antibody and/or cytokine production. PMID:27251370

  17. Diversity and severity of adverse reactions to quinine: A systematic review.

    PubMed

    Liles, Nathan W; Page, Evaren E; Liles, Amber L; Vesely, Sara K; Raskob, Gary E; George, James N

    2016-05-01

    Quinine is a common cause of drug-induced thrombocytopenia and the most common cause of drug-induced thrombotic microangiopathy. Other quinine-induced systemic disorders have been described. To understand the complete clinical spectrum of adverse reactions to quinine we searched 11 databases for articles that provided sufficient data to allow evaluation of levels of evidence supporting a causal association with quinine. Three reviewers independently determined the levels of evidence, including both immune-mediated and toxic adverse reactions. The principal focus of this review was on acute, immune-mediated reactions. The source of quinine exposure, the involved organ systems, the severity of the adverse reactions, and patient outcomes were documented. One hundred-fourteen articles described 142 patients with definite or probable evidence for a causal association of quinine with acute, immune-mediated reactions. These reactions included chills, fever, hypotension, painful acral cyanosis, disseminated intravascular coagulation, hemolytic anemia, thrombocytopenia, neutropenia, acute kidney injury, rhabdomyolysis, liver toxicity, cardiac ischemia, respiratory failure, hypoglycemia, blindness, and toxic epidermal necrolysis. One hundred-two (72%) reactions were caused by quinine pills; 28 (20%) by quinine-containing beverages; 12 (8%) by five other types of exposures. Excluding 41 patients who had only dermatologic reactions, 92 (91%) of 101 patients had required hospitalization for severe illness; 30 required renal replacement therapy; three died. Quinine, even with only minute exposure from common beverages, can cause severe adverse reactions involving multiple organ systems. In patients with acute, multi-system disorders of unknown origin, an adverse reaction to quinine should be considered.

  18. Diversity and severity of adverse reactions to quinine: A systematic review.

    PubMed

    Liles, Nathan W; Page, Evaren E; Liles, Amber L; Vesely, Sara K; Raskob, Gary E; George, James N

    2016-05-01

    Quinine is a common cause of drug-induced thrombocytopenia and the most common cause of drug-induced thrombotic microangiopathy. Other quinine-induced systemic disorders have been described. To understand the complete clinical spectrum of adverse reactions to quinine we searched 11 databases for articles that provided sufficient data to allow evaluation of levels of evidence supporting a causal association with quinine. Three reviewers independently determined the levels of evidence, including both immune-mediated and toxic adverse reactions. The principal focus of this review was on acute, immune-mediated reactions. The source of quinine exposure, the involved organ systems, the severity of the adverse reactions, and patient outcomes were documented. One hundred-fourteen articles described 142 patients with definite or probable evidence for a causal association of quinine with acute, immune-mediated reactions. These reactions included chills, fever, hypotension, painful acral cyanosis, disseminated intravascular coagulation, hemolytic anemia, thrombocytopenia, neutropenia, acute kidney injury, rhabdomyolysis, liver toxicity, cardiac ischemia, respiratory failure, hypoglycemia, blindness, and toxic epidermal necrolysis. One hundred-two (72%) reactions were caused by quinine pills; 28 (20%) by quinine-containing beverages; 12 (8%) by five other types of exposures. Excluding 41 patients who had only dermatologic reactions, 92 (91%) of 101 patients had required hospitalization for severe illness; 30 required renal replacement therapy; three died. Quinine, even with only minute exposure from common beverages, can cause severe adverse reactions involving multiple organ systems. In patients with acute, multi-system disorders of unknown origin, an adverse reaction to quinine should be considered. PMID:26822544

  19. Adverse reactions to iodinated contrast media administered at the time of endoscopic retrograde cholangiopancreatography (ERCP).

    PubMed

    Pan, Jen-Jung; Draganov, Peter V

    2009-03-01

    Adverse reactions after intravascular administration of iodine contrast media are common and prophylactic regiments consisting of the use of steroids and low osmolality contrast media are highly effective in significantly decreasing the adverse reactions rate. The same type of contrast media are also used for opacification of the biliary tree and the pancreatic duct at the time of endoscopic retrograde cholangiopancreatography (ERCP). Systemic absorption of contrast media after ERCP routinely occurs. Although the adverse reaction rate appears to be very low the exact incidence remains unknown due to the retrospective nature of all reports. Despite the lack of formal recommendations, numerous prophylactic regiments are routinely used prior to ERCP in patients with history of prior reaction to intravascular contrast media. Moreover, the use of prophylaxis has even expanded to patients with no prior reaction to intravascular contrast media who are somehow perceived to be at increase risk (e.g. shellfish allergy). Recently, the first large scale prospective study reported exceedingly low incidence of adverse reaction to high oslmolality iodine-containing contrast media administered at the time of ERCP done without prophylactic premedication even in patients considered to be at the highest risk (prior severe reaction to intravascular contrast media administration). These data suggest that the use of prophylactic regiments prior to ERCP appears to be unnecessary.

  20. The prevention of adverse reactions to transfusions in patients with haemoglobinopathies: a proposed algorithm

    PubMed Central

    Bennardello, Francesco; Fidone, Carmelo; Spadola, Vincenzo; Cabibbo, Sergio; Travali, Simone; Garozzo, Giovanni; Antolino, Agostino; Tavolino, Giuseppe; Falla, Cadigia; Bonomo, Pietro

    2013-01-01

    Background Transfusion therapy remains the main treatment for patients with severe haemoglobinopathies, but can cause adverse reactions which may be classified as immediate or delayed. The use of targeted prevention with drugs and treatments of blood components in selected patients can contribute to reducing the development of some reactions. The aim of our study was to develop an algorithm capable of guiding behaviours to adopt in order to reduce the incidence of immediate transfusion reactions. Materials and methods Immediate transfusion reactions occurring over a 7-year period in 81 patients with transfusion-dependent haemoglobinopathies were recorded. The patients received transfusions with red cell concentrates that had been filtered prestorage. Various measures were undertaken to prevent transfusion reactions: leucoreduction, washing the red blood cells, prophylactic administration of an antihistamine (loratidine 10 mg tablet) or an antipyretic (paracetamol 500 mg tablet). Results Over the study period 20,668 red cell concentrates were transfused and 64 adverse transfusion reactions were recorded in 36 patients. The mean incidence of reactions in the 7 years of observation was 3.1‰. Over the years the incidence gradually decreased from 6.8‰ in 2004 to 0.9‰ in 2010. Discussion Preventive measures are not required for patients who have an occasional reaction, because the probability that such a type of reaction recurs is very low. In contrast, the targeted use of drugs such as loratidine or paracetamol, sometimes combined with washing and/or double filtration of red blood cells, can reduce the rate of recurrent (allergic) reactions to about 0.9‰. The system for detecting adverse reactions and training staff involved in transfusion therapy are critical points for reliable collection of data and standardisation of the detection system is recommended for those wanting to monitor the incidence of all adverse reactions, including minor ones. PMID:23736930

  1. 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

  2. Double-blind evaluation of two commercial hypoallergenic diets in cats with adverse food reactions.

    PubMed

    Leistra, M; Willemse, T

    2002-12-01

    The aim of this study was to evaluate two commercially available selected-protein-source diets as maintenance diets in cats with dermatological manifestations of adverse food reactions. Twenty cats with a confirmed adverse food reaction were tested in a double-blind manner. An adverse food reaction was diagnosed when, after recovery with a home-cooked elimination diet, the signs relapsed after a challenge with their previous dietary components, and re-disappeared on a second elimination diet period. Hereafter the cats were blind and randomly challenged with two commercial hypoallergenic diets. Relapse of the clinical signs was seen in eight cats (40%) on a lamb and rice diet and in 13 cats (65%) on a chicken and rice diet (P>0.05). Neither one of the commercial diets was as effective in controlling the skin problems as the home-cooked elimination diet. The study confirms that commercial hypoallergenic diets are adequate for maintenance.

  3. Alert systems for post-marketing surveillance of adverse drug reactions.

    PubMed

    Praus, M; Schindel, F; Fescharek, R; Schwarz, S

    1993-12-30

    When monitoring spontaneous reports of adverse reactions to registered drugs, it is important to detect any change in the number of reported adverse reactions in the course of time. Sales adjusted adverse drug reaction rates are usually compared in order to be able to take drug exposure into account. Here we review the so-called arithmetic and some statistical procedures which could form the basis for an alert system. The advantages and disadvantages of each of these methods are discussed. The importance of data requirements and the problems which arise when using an alert system are pointed out and then clarified with the help of the example of diphtheria/tetanus vaccine. PMID:8134741

  4. 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

  5. [Enlightenment of adverse reaction monitoring on safety evaluation of traditional Chinese medicines].

    PubMed

    Song, Hai-bo; Du, Xiao-xi; Ren, Jing-tian; Yang, Le; Guo, Xiao-xin; Pang, Yu

    2015-04-01

    The adverse reaction monitoring is important in warning the risks of traditional Chinese medicines at an early stage, finding potential quality problems and ensuring the safe clinical medication. In the study, efforts were made to investigate the risk signal mining techniques in line with the characteristics of traditional Chinese medicines, particularly the complexity in component, processing, compatibility, preparation and clinical medication, find early risk signals of traditional Chinese medicines and establish a traditional Chinese medicine safety evaluation system based on adverse reaction risk signals, in order to improve the target studies on traditional Chinese medicine safety, effective and timely control risks and solve the existing frequent safety issue in traditional Chinese medicines.

  6. Adverse drug reactions: 'six rights' to ensure best practice for children.

    PubMed

    Kanneh, Agnes

    2011-06-01

    In the second of a two-part article on adverse drug reactions Agnes Kanneh describes the six 'rights' of the recipient of a drug. These are: that the right person should receive the right drug, in the right dose, at the right time within the right intervals, via the right route, followed by the right (correct) documentation. The author argues that the observance of these 'rights' by children's nurses ensures the best pharmacotherapeutic practice, thus a robust practical safeguard in adverse drug reactions and threats to the good reputation of the nursing profession.

  7. Adverse reaction to metal debris in a painful hemiarthroplasty of the hip

    PubMed Central

    Palmer, Jonathan Simon; Dean, Michael William; Briant-Evans, Toby; Stranks, Geoff

    2016-01-01

    Adverse reaction to metal debris (ARMD) in total hip arthroplasty surgery is a well-known problem. We present the case of a unipolar hemiarthroplasty requiring revision within 18 months of insertion secondary to an adverse reaction to metal debris. This case demonstrates a rare cause for failure of a hemiarthroplasty following a fragility fracture. We feel that ARMD should be considered in all cases where pain and dysfunction in the presence of any hip prosthesis cannot be explained by routine investigations. PMID:27656196

  8. Adverse reaction to metal debris in a painful hemiarthroplasty of the hip.

    PubMed

    Palmer, Jonathan Simon; Dean, Michael William; Briant-Evans, Toby; Stranks, Geoff

    2016-01-01

    Adverse reaction to metal debris (ARMD) in total hip arthroplasty surgery is a well-known problem. We present the case of a unipolar hemiarthroplasty requiring revision within 18 months of insertion secondary to an adverse reaction to metal debris. This case demonstrates a rare cause for failure of a hemiarthroplasty following a fragility fracture. We feel that ARMD should be considered in all cases where pain and dysfunction in the presence of any hip prosthesis cannot be explained by routine investigations. PMID:27656196

  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. Late-onset inflammatory adverse reactions related to soft tissue filler injections.

    PubMed

    Alijotas-Reig, Jaume; Fernández-Figueras, Maria Teresa; Puig, Lluís

    2013-08-01

    An ever-increasing number of persons seek medical solutions to improve the appearance of their aging skin or for aesthetic and cosmetic indications in diverse pathological conditions, such as malformations, trauma, cancer, and orthopedic, urological, or ophthalmological conditions. Currently, physicians have many different types of dermal and subdermal fillers, such as non-permanent, permanent, reversible, or non-reversible materials. Despite the claims of manufacturers and different authors that fillers are non-toxic and non-immunogenic or that complications are very uncommon, unwanted side effects do occur with all compounds used. Implanted, injected, and blood-contact biomaterials trigger a wide variety of adverse reactions, including inflammation, thrombosis, and excessive fibrosis. Usually, these adverse reactions are associated with the accumulation of large numbers of mononuclear cells. The adverse reactions related to fillers comprise a broad range of manifestations, which may appear early or late and range from local to systemic. Clinicians should be aware of them since the patient often denies the antecedent of injection or is unaware of the material employed. Most of these adverse effects seem to have an immunological basis, the fillers acting more as adjuvants than as direct T-cell activators, on a background of genetic predisposition. Their treatment has not been the subject of well-designed studies; management of both acute and systemic reactions is often difficult, and requires anti-inflammatory and occasionally immunosuppressive therapy. The clinical, pathological, and therapeutic aspects of inflammatory and immune-mediated late-onset adverse reactions related to soft tissue filler injections are thoroughly reviewed herein.

  11. Oral adverse reactions due to cinnamon-flavoured chewing gums consumption.

    PubMed

    Calapai, G; Miroddi, M; Mannucci, C; Minciullo, Pl; Gangemi, S

    2014-10-01

    Cinnamon-flavoured products (toothpaste, chewing gum, food, candy and mouthwash) can cause oral adverse reactions; among these, the most common is contact stomatitis (cinnamon contact stomatitis, CCS). Signs and symptoms of contact allergic reactions affecting the oral mucosa can mimic other common oral disorders, making diagnosis difficult. As CCS may be more prevalent than believed and its clinical features can frequently determine misdiagnosis, we reviewed case reports and case series of oral adverse reactions due to cinnamon-containing chewing gums, emphasizing clinical aspects, diagnostic and management procedures. We also proposed an algorithm to perform a diagnosis of CCS as in the previous published literature the diagnostic approach was not based on a harmonized and shared evidence-based procedure. Moreover, as patients can refer to different specialists as dentists, dermatologists and allergists, a multidisciplinary approach is suggested.

  12. 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

  13. Adverse Reactions to Foods and Food Allergy: Development and Reproducibility of a Questionnaire for Clinical Diagnosis

    PubMed Central

    Lyra, Nilza R. S.; Motta, Maria E. F. A.; Rocha, Luiz A. R.; Solé, Dirceu; Peixoto, Décio M.; Rizzo, José A.; Taborda-Barata, Luis; Sarinho, Emanuel S. C.

    2013-01-01

    Objective. To develop a questionnaire as a screening tool for adverse reactions to foods in children and to assess the technical reproducibility by test-retest. Methods. Reproducibility of the questionnaire was performed by the literature review, preparing the preliminary questionnaire, peer review, pretest, and retest analysis. The study of the test-retest reproducibility was cross-sectional and descriptive. Kappa coefficient was used to study the reproducibility of the questionnaire. The sample consisted of 125 2–4 year-old children from 15 daycare centers in Recife, Brazil, and interviews with parents or caregivers were used to collect data. Results. From the total children, sixty-three were boys (50.4%), forty-six were two years old (36.8%), forty-seven were three years old (37.6%), and thirty-two were four years old (25.6%). Forty caregivers reported that their child had health problems with food. Most frequently reported offending foods were milk, peanuts, shrimp, and chocolate. Nine questions showed a good Kappa index (≥0,6). Conclusions. The questionnaire used needs to be resized and reshaped on the basis of the issues with good internal consistency and reproducibility. The use of a validated and reproducible questionnaire in the children represents an important contribution towards assessing an eventual rise in overt food allergy. PMID:24198840

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

    PubMed

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

    2016-01-01

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

  15. Blood metal ion levels are not a useful test for adverse reactions to metal debris

    PubMed Central

    Pahuta, M.; Smolders, J. M.; van Susante, J. L.; Peck, J.; Kim, P. R.

    2016-01-01

    Objectives Alarm over the reported high failure rates for metal-on-metal (MoM) hip implants as well as their potential for locally aggressive Adverse Reactions to Metal Debris (ARMDs) has prompted government agencies, internationally, to recommend the monitoring of patients with MoM hip implants. Some have advised that a blood ion level >7 µg/L indicates potential for ARMDs. We report a systematic review and meta-analysis of the performance of metal ion testing for ARMDs. Methods We searched MEDLINE and EMBASE to identify articles from which it was possible to reconstruct a 2 × 2 table. Two readers independently reviewed all articles and extracted data using explicit criteria. We computed a summary receiver operating curve using a Bayesian random-effects hierarchical model. Results Our literature search returned 575 unique articles; only six met inclusion criteria defined a priori. The discriminative capacity of ion tests was homogeneous across studies but that there was substantial cut-point heterogeneity. Our best estimate of the “true” area under curve (AUC) for metal ion testing is 0.615, with a 95% credible interval of 0.480 to 0.735, thus we can state that the probability that metal ion testing is actually clinically useful with an AUC ≥ 0.75 is 1.7%. Conclusion Metal ion levels are not useful as a screening test for identifying high risk patients because ion testing will either lead to a large burden of false positive patients, or otherwise marginally modify the pre-test probability. With the availability of more accurate non-invasive tests, we did not find any evidence for using blood ion levels to diagnose symptomatic patients. Cite this article: M. Pahuta, J. M. Smolders, J. L. van Susante, J. Peck, P. R. Kim, P. E. Beaule. Blood metal ion levels are not a useful test for adverse reactions to metal debris: a systematic review and meta-analysis. Bone Joint Res 2016;5:379–386. DOI: 10.1302/2046-3758.59.BJR-2016-0027.R1. PMID:27612918

  16. Adverse drug reaction profile of microtubule-damaging antineoplastic drugs: A focused pharmacovigilance study in India

    PubMed Central

    Manohar, Hasitha Diana; Adiga, Shalini; Thomas, Joseph; Sharma, Ajitha

    2016-01-01

    Objectives: The aim of the study was to analyze the adverse drug reaction (ADR) profile of microtubule-damaging antineoplastic drugs (taxanes and vinca alkaloids) and to look for unexpected ADRs among the local population. Focused study on these drugs, rampantly used in oncology department for a wide variety of tumors including early and advanced malignancies, would enable better treatment care by physicians. Materials and Methods: Data on ADRs were collected from the cancer patients belonging to both gender and of all ages, on taxanes- or vinca-based cancer chemotherapy and reported in the Indian Pharmacopoeia Commission form. Causality was assessed using the WHO criteria and Naranjo's Algorithm. Preventability and severity of ADRs were also assessed. Results: A total of 97 ADRs were reported among 488 patients on microtubule-damaging anticancer drugs admitted over a period of 1 year. The incidence rate was 19.87%. Gastrointestinal system (40.2%) was the most affected followed by bone marrow (33%) and skin (8.2%). The highest incidence of ADRs was reported among paclitaxel (54.6%), and vincristine (39.2%). Most of the reported ADRs were of milder nature and preventable. The WHO causality assessment scale indicated 71.1% possible reactions. Conclusions: This study showed that most ADRs are preventable with effective ADR monitoring. There is a great need to create awareness among healthcare professionals regarding the importance of the pharmacovigilance system. Judicious use of the preventive measures will lead to a reduction in the incidence of ADRs due to the drug armamentarium, thereby enabling additional economic benefit to the patient and society. PMID:27721535

  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. Adverse drug reactions as the cause of emergency department admission: focus on the elderly.

    PubMed

    Ventura, Maria Teresa; Laddaga, Rocco; Cavallera, Pierfranco; Pugliese, Piervito; Tummolo, Roberto A; Buquicchio, Rosalba; Pierucci, Paola; Passalacqua, Gianni

    2010-09-01

    The use of medications could be responsible of both side effects and adverse drug reaction (ADR). Identifying risk factors could improve the possibility of avoiding severe reactions in old people. We investigated the prevalence of unpredictable drug adverse reactions among patients admitted to the emergency departments (EDs) of three large Italian hospitals in the period 2005-2008. Clinical characteristics and demographics were carefully recorded in a dedicated database. The assessment of the drug reactions was carried out by an allergist after the first emergency evaluation. Over the considered period, 56,031 patients were admitted at the ED, 2644 (21.2%) of which for ADR. Out of those patients, 55 (2.1%) were identified as unpredictable ADRs. In 96% of the cases the clinical presentation was cutaneous and antibiotics were the most frequently responsible drugs. Patients over 65 years accounted for 37% of the reactions. In those patients the multiple drug regimens were significantly more frequent, as well as the presence of comorbidities. Smoking habit, alcohol abuse and personal and familiar history of atopy did not differ between the younger and the elderly. In the older group, antibiotics were more frequently involved, whereas in the <65 years, nonsteroidal antinflammatory drugs accounted for most reactions. Our date outline that in the elderly the comorbidities and correlated multiple regime therapy cause an increased incidence of ADRs, thus suggesting a careful management of therapeutics regimens by means of educational campaigns for patients and guidelines for doctors finalized to avoid excessive drug prescription. PMID:20095805

  19. 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

  20. 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.

  1. [Enlightenment of adverse reaction monitoring on safety evaluation of traditional Chinese medicines].

    PubMed

    Song, Hai-bo; Du, Xiao-xi; Ren, Jing-tian; Yang, Le; Guo, Xiao-xin; Pang, Yu

    2015-04-01

    The adverse reaction monitoring is important in warning the risks of traditional Chinese medicines at an early stage, finding potential quality problems and ensuring the safe clinical medication. In the study, efforts were made to investigate the risk signal mining techniques in line with the characteristics of traditional Chinese medicines, particularly the complexity in component, processing, compatibility, preparation and clinical medication, find early risk signals of traditional Chinese medicines and establish a traditional Chinese medicine safety evaluation system based on adverse reaction risk signals, in order to improve the target studies on traditional Chinese medicine safety, effective and timely control risks and solve the existing frequent safety issue in traditional Chinese medicines. PMID:26281610

  2. [Underreporting adverse drug reactions--limitations of the Dutch Hospital Data database].

    PubMed

    Dijkers, Fred W

    2013-01-01

    Data of adverse drug reaction (ADR)-related hospitalizations derived from the Dutch Hospital Data database with reasons for hospitalization have a limited value since they are incomplete. This is attributed to underreporting and misclassification. It seems that caregivers are not careful in registering ADRs. Since 2005, many instruments (rules and agreements) have been devised to promote the safety of medical therapy. It is uncertain whether these instruments will diminish the number of ADR-related hospitalizations. Having a lot of rules is no guarantee that the process will improve. In the vast majority of the rules and agreements, patients have only a modest position. Yet they can play an important role in pharmacovigilance as is shown in a study of web-based intensive monitoring of adverse drug reactions.

  3. Adverse Drug Reaction Reporting Program of the Ontario Medical Association: the first 3 years.

    PubMed Central

    Gowdey, C W; Brennan, M

    1985-01-01

    This paper describes the Adverse Drug Reaction Reporting Program developed and operated by the Committee on Drugs and Pharmaco-therapy of the Ontario Medical Association. Analyses were done to demonstrate some of the trends derived from the reports. Some of the clinical observations based on the reports, which are published quarterly and circulated to physicians and to pharmacy, nursing and hospital organizations, are also reviewed. PMID:3871167

  4. Establishing causality in pediatric adverse drug reactions: use of the Naranjo probability scale.

    PubMed

    Avner, Marina; Finkelstein, Yaron; Hackam, Dan; Koren, Gideon

    2007-01-01

    Carbamazepine hypersensitivity syndrome is a rare, life-threatening condition. Its diagnosis is critical to avoid future exposure to aromatic anticonvulsants. Pediatricians rarely use a systematic approach to establish the cause of drug reactions in the clinical setting. We describe the use of the Naranjo adverse drug reaction probability scale to establish causality in three cases of suspected anticonvulsant hypersensitivity syndrome with the aim of introducing clinicians to this effective tool. Our analysis reveals that this method is useful, but also highlights potential areas for its improvement.

  5. Magnitude of adverse drug reaction and associated factors among HIV-infected adults on antiretroviral therapy in Hiwot Fana specialized university hospital, eastern Ethiopia

    PubMed Central

    Weldegebreal, Fitsum; Mitiku, Habtamu; Teklemariam, Zelalem

    2016-01-01

    Introduction Human immunodefiecency virus infected patients did not adhere correctly to their Antiretroviral Therapy because of the drugs adverse effects. Thus, continuous evaluation of the adverse effect of Antiretroviral Therapy will help to make more effective treatment. The aim of this study was to assess the prevalence of Adverse Drug Reaction and associated factors on Antiretroviral Therapy among Human immunodefiecency virus infected Adults at Hiwot Fana Specialized University Hospital, Eastern Ethiopia. Methods A Hospital based retrospective study was conducted among 358 of adult patients clinical records on antiretroviral Therapy from April1 to June30, 2014. Results The overall prevalence of Adverse Drug Reaction among Human immunodefiecency virus infected patients on antiretroviral Therapy was 17.0%. Of reported Adverse Drug Reaction, 80.3%, 18% and 1.7% occurred in patients on Stavudine, Zidovudine and Tenofovir based regimens respectively. The common Adverse Drug Reaction were lipodystrophy (fat change) (49.2%), numbness/tingling (27.9%), peripheral neuropathy (18%) and (8.2%) anaemia (8.2%). Patients on Stavudine containing regimens were more likely to develop Adverse Drug Reaction compared to Zidovudine (AOR = 0.212, 95% CI 0.167, 0.914, p<0.001) and Tenofovir (AOR=0.451, 95% CI 0.532, 0.948, p<0.001). Conclusion The overall prevalence of Adverse Drug Reaction among Human immunodefiecency virus infected patients in this study was 17% and more common on those patients taking Stavudine based regimen. Lipodystrophy and peripheral neuropathy were significantly associated with stavudine-based regimens, while anaemia was significantly associated with zidovudine based regimens. Thus regular clinical and laboratory monitoring of patients on Antiretroviral Therapy should be strengthened. PMID:27800108

  6. Adverse reactions to sunscreen agents: epidemiology, responsible irritants and allergens, clinical characteristics, and management.

    PubMed

    Heurung, Ashley R; Raju, Srihari I; Warshaw, Erin M

    2014-01-01

    Sunscreen is a key component in the preventive measures recommended by dermatologists and public health campaigns aimed at reducing sunburn, early skin aging, and skin cancer. To maximize compliance, adverse reactions to sunscreens should be minimized. Although inactive ingredients cause many of these reactions, it is important for dermatologists to be aware of reactions to active ultraviolet filters. There are approximately 120 chemicals that can function as ultraviolet (UV) filters. This review focuses on the 36 most common filters in commercial and historical use. Of these, 16 are approved for use by the US Food and Drug Administration. The benzophenones and dibenzoylmethanes are the most commonly implicated UV filters causing allergic and photoallergic contact dermatitis (PACD) reactions; benzophenone-3 is the leading allergen and photoallergen within this class. When clinically indicated, patch and photopatch testing should be performed to common UV filters.

  7. Monitoring adverse drug reactions in children using community pharmacies: a pilot study

    PubMed Central

    Stewart, Derek; Helms, Peter; McCaig, Dorothy; Bond, Christine; McLay, James

    2005-01-01

    Aims To determine the feasibility of a community pharmacy-based parental adverse drug reaction (ADR) reporting system for children. Design Prospective study of parent-reported ADRs using a questionnaire issued to the parent or guardians of children 0–11 years of age collecting prescribed medicine for amoxicillin, and/or salbutamol, and collecting prescribed medicine for, or purchasing, paracetamol or ibuprofen suspension. Setting Seven community pharmacies in Grampian, Scotland. Results During a 4-week period 360 prescriptions or purchases for the study medications occurred. Two hundred and sixty-seven parents (85.5%) agreed to participate in the study. One hundred and six participants (40%) returned a total of 122 questionnaires. The demographics of responders and nonresponders including medication, age of child, and social status as assessed by the Depcat score were similar. There was no evidence of under-representation of any socio-economic group. Possible adverse events were detected using a symptom tick list and perceived ADRs using free text entry. Using the symptom tick list approach the most commonly reported symptoms were diarrhoea (28.9%) and tiredness (31.6%) for amoxicillin. The levels of diarrhoea and tiredness reported for ibuprofen, paracetamol and salbutamol were 15% and 20%, 7.4% and 18.5%, and 20% and 0%, respectively. Using the freehand section of the questionnaire 15 specific ADRs were reported by parents (12.3%). Eight children (21.2%) reported ADRs attributed to amoxicilin [diarrhoea (n = 4), fever (n = 1), anorexia (n = 1), hyperactivity (n = 1) and nonspecific (n = 1)], five to paracetamol [diarrhoea (n = 3), anorexia, irritability, crying and very angry (n = 1) and not stated (n = 1)], two to ibuprofen [diarrhoea (n = 1), not stated (n =)]. Only one off-label prescription was identified and this was for salbutamol syrup prescribed to a child under 2 years of age. Conclusions The prospective monitoring of paediatric ADRs, using a

  8. Development of an Adverse Drug Reaction Risk Assessment Score among Hospitalized Patients with Chronic Kidney Disease

    PubMed Central

    Saheb Sharif-Askari, Fatemeh; Syed Sulaiman, Syed Azhar; Saheb Sharif-Askari, Narjes; Al Sayed Hussain, Ali

    2014-01-01

    Background Adverse drug reactions (ADRs) represent a major burden on the healthcare system. Chronic kidney disease (CKD) patients are particularly vulnerable to ADRs because they are usually on multiple drug regimens, have multiple comorbidities, and because of alteration in their pharmacokinetics and pharmacodynamic parameters. Therefore, one step towards reducing this burden is to identify patients who are at increased risk of an ADR. Objective To develop a method of identifying CKD patients who are at increased risk for experiencing ADRs during hospitalisation. Materials and Methods Factors associated with ADRs were identified by using demographic, clinical and laboratory variables of patients with CKD stages 3 to 5 (estimated glomerular filtration rate, 10–59 ml/min/1.73 m2) who were admitted between January 1, 2012, and December 31, 2012, to the renal unit of Dubai Hospital. An ADR risk score was developed by constructing a series of logistic regression models. The overall model performance for sequential models was evaluated using Akaike Information Criterion for goodness of fit. Odd ratios of the variables retained in the best model were used to compute the risk scores. Results Of 512 patients (mean [SD] age, 60 [16] years), 62 (12.1%) experienced an ADR during their hospitalisation. An ADR risk score included age 65 years or more, female sex, conservatively managed end-stage renal disease, vascular disease, serum level of C-reactive protein more than 10 mg/L, serum level of albumin less than 3.5 g/dL, and the use of 8 medications or more during hospitalization. The C statistic, which assesses the ability of the risk score to predict ADRs, was 0.838; 95% CI, 0.784–0.892). Conclusion A score using routinely available patient data can be used to identify CKD patients who are at increased risk of ADRs. PMID:24755778

  9. 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

  10. Adverse Drug Reactions in a Tertiary Care Emergency Medicine Ward - Prevalence, Preventability and Reporting

    PubMed Central

    Rydberg, Diana M.; Holm, Lennart; Engqvist, Ida; Fryckstedt, Jessica; Lindh, Jonatan D.; Stiller, Carl-Olav; Asker-Hagelberg, Charlotte

    2016-01-01

    Purpose To identify the prevalence and preventability of adverse drug reactions (ADRs) in an emergency ward setting in a tertiary hospital in Sweden and to what extent the detected ADRs were reported to the Medical Product Agency (MPA). Methods In this prospective cross sectional observational study, 706 patients admitted to one of the Emergency Wards, at the Karolinska University Hospital in Solna, Stockholm during September 2008 –September 2009, were included. The electronic patient records were reviewed for patients’ demographic parameters, prevalence of possible ADRs and assessment of their preventability. In addition, the extent of formal and required ADR reporting to national registers was studied. Results Approximately 40 percent of the patient population had at least one possible ADR (n = 284). In the multivariable regression model, age and number of drugs were significantly associated with risk of presenting with an ADR (p<0.01 and p<0.001, respectively). Sex was not identified as a significant predictor of ADRs (p = 0.27). The most common ADRs were cardiovascular, followed by electrolyte disturbances, and hemorrhage. In 18 percent of the patient population ADRs were the reason for admission or had contributed to admission and 24% of these ADRs were assessed as preventable. The under-reporting of ADRs to the MPA was 99%. Conclusions ADRs are common in Emergency Medicine in tertiary care in Sweden, but under-reporting of ADRs is substantial. The most frequent ADRs are caused by cardiovascular drugs, and significantly associated with age and number of drugs. However, only a minority of the detected serious ADRs contributing to admission could have been avoided by increased risk awareness. PMID:27622270

  11. Pharmacovigilance program to monitor adverse reactions of recombinant streptokinase in acute myocardial infarction

    PubMed Central

    Betancourt, Blas Y; Marrero-Miragaya, María A; Jiménez-López, Giset; Valenzuela-Silva, Carmen; García-Iglesias, Elizeth; Hernández-Bernal, Francisco; Debesa-García, Francisco; González-López, Tania; Alvarez-Falcón, Leovaldo; López-Saura, Pedro A

    2005-01-01

    Background Streptokinase (SK) is an effective fibrinolytic agent for the treatment of acute myocardial infarction (AMI). The objective of the present study was to assess the adverse drug reactions (ADRs) associated with intravenous recombinant SK in patients with AMI in routine clinical practice. Methods A national, prospective and spontaneous reporting-based pharmacovigilance program was conducted in Cuba. Patient demographics, suspected ADR description, elements to define causality, and outcomes were documented and analyzed. Results A total of 1496 suspected ADRs identified in 792 patients out of the 1660 (47.7 %) prescriptions reported in the program, were received from July 1995 to July 2002. Most of the patients (71.3%) were male, 67.2% were white and mean age was 61.6 ± 13.0 years. The mean time interval between the onset of symptoms and the start of the SK infusion was 4.9 ± 3.7 h. The most frequently reported ADRs were hypotension, arrhythmias, chills, tremors, vomiting, nauseas, allergy, bleeding and fever. ADR severity was 38% mild, 38% moderate, 10% severe, and 4% very severe. Only 3 patients with hemorrhagic stroke were reported. Seventy-two patients died in-hospital mainly because of cardiac causes associated with the patient's underlying clinical condition. Mortality was 3 times more likely in patients suffering arrhythmias than in those without this event (odds ratio 3.1, 95% CI: 1.8 to 5.1). Most of the reported ADRs were classified as possibly or probably associated with the study medication. Conclusion Recombinant SK was associated with a similar post-marketing safety profile to those suggested in previous clinical trials. PMID:16262910

  12. 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

  13. Hematopoietic SCT with cryopreserved grafts: adverse reactions after transplantation and cryoprotectant removal before infusion.

    PubMed

    Shu, Z; Heimfeld, S; Gao, D

    2014-04-01

    Transplantation of hematopoietic stem cells (HSCs) has been successfully developed as a part of treatment protocols for a large number of clinical indications, and cryopreservation of both autologous and allogeneic sources of HSC grafts is increasingly being used to facilitate logistical challenges in coordinating the collection, processing, preparation, quality control testing and release of the final HSC product with delivery to the patient. Direct infusion of cryopreserved cell products into patients has been associated with the development of adverse reactions, ranging from relatively mild symptoms to much more serious, life-threatening complications, including allergic/gastrointestinal/cardiovascular/neurological complications, renal/hepatic dysfunctions, and so on. In many cases, the cryoprotective agent (CPA) used-which is typically dimethyl sulfoxide (DMSO)-is believed to be the main causal agent of these adverse reactions and thus many studies recommend depletion of DMSO before cell infusion. In this paper, we will briefly review the history of HSC cryopreservation, the side effects reported after transplantation, along with advances in strategies for reducing the adverse reactions, including methods and devices for removal of DMSO. Strategies to minimize adverse effects include medication before and after transplantation, optimizing the infusion procedure, reducing the DMSO concentration or using alternative CPAs for cryopreservation and removing DMSO before infusion. For DMSO removal, besides the traditional and widely applied method of centrifugation, new approaches have been explored in the past decade, such as filtration by spinning membrane, stepwise dilution-centrifugation using rotating syringe, diffusion-based DMSO extraction in microfluidic channels, dialysis and dilution-filtration through hollow-fiber dialyzers and some instruments (CytoMate, Sepax S-100, Cobe 2991, microfluidic channels, dilution-filtration system, etc.) as well. However

  14. Heparin-induced thrombocytopenia: a review of concepts regarding a dangerous adverse drug reaction.

    PubMed

    Junqueira, Daniela Rezende Garcia; Carvalho, Maria das Graças; Perini, Edson

    2013-01-01

    Heparin is a natural agent with antithrombotic action, commercially available for therapeutic use as unfractionated heparin and low molecular weight heparin. Heparin-induced thrombocytopenia (HIT) is a serious adverse reaction to heparin that promotes antibody-mediated platelet activation. HIT is defined as a relative reduction in platelet count of 50% (even when the platelet count at its lowest level is above>150 x 10(9)/L) occurring within five to 14 days after initiation of the therapy. Thrombocytopenia is the main feature that directs the clinical suspicion of the reaction and the increased risk of thromboembolic complications is the most important and paradoxical consequence. The diagnosis is a delicate issue, and requires a combination of clinical probability and laboratory tests for the detection of platelet activation induced by HIT antibodies. The absolute risk of HIT has been estimated between 1% and 5% under treatment with unfractionated heparin, and less than 1% with low molecular weight heparin. However, high-quality evidence about the risk of HIT from randomized clinical trials is scarce. In addition, information on the frequency of HIT in developing countries is not widely available. This review aims to provide a better understanding of the key features of this reaction and updated information on its frequency to health professionals and other interested parties. Knowledge, familiarity, and access to therapeutic options for the treatment of this adverse reaction are mandatory to minimize the associated risks, improving patient safety.

  15. Diagnosis and Treatment of Adverse Local Tissue Reactions at the Head-Neck Junction.

    PubMed

    Cooper, Herbert J

    2016-07-01

    Modular junctions in total hip arthroplasty are susceptible to mechanically assisted crevice corrosion, leading to the release of metal wear debris. Adverse local tissue reactions result from an immune-mediated biological reaction to this debris and can have a profound effect on the surrounding periarticular soft tissue envelope. Patients often present with pain or muscle weakness and demonstrate elevated serum cobalt and chromium levels. Serum inflammatory markers and synovial fluid tests help distinguish these reactions from deep infection in the majority of cases; however, the presence of amorphous material or fragmented cells can lead to difficulty in some cases. Advanced cross-sectional imaging is essential in establishing the diagnosis. Early revision surgery is generally the treatment of choice for symptomatic adverse local tissue reaction from corrosion at the modular head-neck junction. The existing stem is retained, and a new ceramic head is placed on the existing trunnion whenever possible. This strategy generally leads to short-term improvement of symptoms with reliable clinical outcomes; however, longer term results are presently lacking.

  16. [Visualization and analysis of adverse reactions of molecularly targeted anticancer agents using the self-organizing map (SOM)].

    PubMed

    Hamamoto, Tomoyuki; Serizawa, Ayaka; Ohtsuki, Kaori; Kawakami, Junko; Sato, Kenichi

    2014-01-01

    Molecularly targeted anticancer agents cause a variety of adverse reactions compared with conventional anticancer agents because of their unique mechanisms of action. Sources of drug information such as package inserts (PIs) provide primarily document-based and numerical information. Therefore it is not easy to obtain a complete picture of drugs with similar effects, or to understand differences among drugs. In this study we used the self-organizing map (SOM) technique to visualize the adverse reactions indicated on PIs of 23 molecularly targeted anticancer agents as of March 2013. In both the presence/absence version and the frequency version, SOM was divided into domains according to mechanism of action, antibody drug or low-molecular weight drug, and molecular target. The component planes of the 753 adverse reaction items in the frequency version enabled us to grasp all available information and differences among the drugs. In some component planes in the presence/absence version, an adverse reaction that had not been reported for a drug but had already been reported for its proximally positioned drug(s) as of March 2013, was found to be reported thereafter by the Drug Safety Update (DSU) or the Adverse Event Report Search System "CzeekV," which is based on FDA Adverse Event Reporting System (FAERS). Our results suggest that visualization of the adverse reactions of molecularly targeted anticancer agents by the SOM technique is useful not only to acquire all available information and differences among drugs, but also to predict the appearance of adverse reactions.

  17. [Vigilance for veterinary medicinal products: reports of adverse reactions in the year 2012].

    PubMed

    Müntener, C R; Bruckner, L; Kupper, J; Althaus, F R; Schäublin, M

    2013-11-01

    197 adverse reactions of Swissmedic-authorized veterinary medicinal products were reported during the year 2012 (2011: 167). Species and drug classes remain unchanged over the years: most of the reports related to reactions following the use of antiparasitic products (37.6 %), antiinfectives (15.7 %) or non-steroidal antiinflammatory drugs (11.7 %) in companion animals (94 dogs and 53 cats) followed by cattle/calves (29). Additionally, 45 cases transmitted by the Swiss Toxicological Information Centre in Zürich were processed. We discuss a paradoxical reaction under the potential influence of acepromazine as well as a modified protocol for treating permethrin intoxication in cats. Finally, the vaccinovigilance program received 95 declarations following the application of various vaccines, mainly to dogs or cats.

  18. [Vigilance for veterinary medicinal products: reports of adverse reactions in the year 2012].

    PubMed

    Müntener, C R; Bruckner, L; Kupper, J; Althaus, F R; Schäublin, M

    2013-11-01

    197 adverse reactions of Swissmedic-authorized veterinary medicinal products were reported during the year 2012 (2011: 167). Species and drug classes remain unchanged over the years: most of the reports related to reactions following the use of antiparasitic products (37.6 %), antiinfectives (15.7 %) or non-steroidal antiinflammatory drugs (11.7 %) in companion animals (94 dogs and 53 cats) followed by cattle/calves (29). Additionally, 45 cases transmitted by the Swiss Toxicological Information Centre in Zürich were processed. We discuss a paradoxical reaction under the potential influence of acepromazine as well as a modified protocol for treating permethrin intoxication in cats. Finally, the vaccinovigilance program received 95 declarations following the application of various vaccines, mainly to dogs or cats. PMID:24168771

  19. 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

    prepaid text loads/credits. The 3 ADRs texted were a report of vivid dreams and nightmares, a report of disturbing dreams and memory lapses, both of which were due to montelukast use, and a report of hepatitis from an isoniazid/rifampicin fixed-dose combination. Nineteen of 51 resident physicians (37%) registered in the reporting system responded to the postintervention survey. The most common reasons for not reporting ADRs were no adverse reaction identified 11/19 (58%) and restrictive reporting syntax 4/19 (21%). All doctors preferred a free form of reporting. The direct cost of the texting-based reporting system was calculated to be US $5581.40 and the indirect cost was US $9989.40. The total cost for texting-based ADR reporting system for 12 months was US $15,570.79. Conclusions Reporting of ADRs via texting could be lower compared with an existing ADR paper-based system. Problems of Internet connectivity, reporting syntax, and expiration and reliability of text loads/credits should be addressed while implementing a text-based ADR reporting system in a developing country. PMID:27227130

  20. [Nalmefene and Opioid Withdrawal Syndrome: Analysis of the Global Pharmacovigilance Database for Adverse Drug Reactions].

    PubMed

    Dahmke, Hendrike; Kupferschmidt, Hugo; Kullak-Ublick, Gerd A; Weiler, Stefan

    2015-10-14

    Nalmefene (Selincro®) is a selective opioid receptor antagonist, licensed in April 2014 in Switzerland for the reduction of alcohol consumption in adults with a high drinking risk level. 200 reports of adverse drug reactions of nalmefene have been documented worldwide in the WHO global pharmacovigilance database between 7th March 1997 to 1st March 2015. In 21 cases (10,5%) nalmefene and an opioid were administered concomitantly, causing withdrawal symptoms. Until now, the regional pharmacovigilance center in Zurich received four cases of nalmefene combined with opioids. This combination should be avoided.

  1. Is it food allergy? Differentiating the causes of adverse reactions to food.

    PubMed

    Guarderas, J C

    2001-04-01

    Foods can produce adverse symptoms in various ways, and the patient's history can help determine whether allergy or some other mechanism is responsible. The history has limitations, however, as it is primarily subjective. Therefore, diagnostic confirmation is very important. Strict avoidance of the allergenic food is the primary course of treatment. Education is imperative to ensure that patients understand food labels and recognize the different names used to designate a specific food. Prompt treatment with epinephrine when an acute reaction occurs can make a life-or-death difference. PMID:11317463

  2. Sweet Conclusion

    ERIC Educational Resources Information Center

    Shirley, Britt M.; Wooldridge, Barbara Ross; Camp, Kerri M.

    2012-01-01

    Jen Harrington is the owner and pastry chef of Sweet Conclusion, a bakery in Tampa, Florida. Most of Harrington's business comes from baking wedding cakes, but she has been attempting to attract customers to her retail bakery, where she sells cupcakes, pies, ice cream, and coffee. Nearly four years she opened Sweet Conclusion, the retail part of…

  3. [Analysis of 103 cases with adverse drug reactions induced by sanqizongzaogan injection].

    PubMed

    Chen, Yamei; Li, Yaowang; Zhu, Guanghui

    2010-01-01

    To analyze the characteristics and relative factors of adverse drug reactions (ADR) induced by sanqizongzaogan injection, in order to provide reference for the clinical use of sanqizongzaogan injection properly. The 103 reported cases of ADR induced by sanqizongzaogan injection in China over 15 years were retrospectively analyzed. The 103 ADR cases, 41.7% occurred in patients aged above 60. The most common presentation of ADR was drug eruption, followed by allergic reactions (20.4%) and allergic shock (9.7%). The occurrence of ADR is affected by many factors. We should control the drug indication strictly, check patients drug allergy history carefully before prescription, monitor ADR afterwards, promote clinical rational drug-usage. PMID:20394303

  4. [Monitoring sheet covering long-term chemotherapy to predict individual adverse reaction patterns for patients with gynecologic chemotherapy].

    PubMed

    Doi, Chiaki; Iihara, Naomi; Kawazoe, Hitoshi; Fukuoka, Noriyasu; Houchi, Hitoshi; Kurosaki, Yuji; Morita, Shushi

    2007-06-01

    Monitoring the adverse reaction patterns specific to individual patients is important to avoid subsequent reactions. Gynecologic cancer chemotherapy is often implemented repeatedly with an altered protocol during prolonged terms. The purpose of this study was to develop and assess the efficacy of a worksheet that pharmacists can use to analyze adverse reaction patterns in individual patients with gynecologic chemotherapy. The worksheet which we developed consisted of multiple sections. One section is for necessary drug information for the proper use of antineoplastic agents. Another section is for the following items recorded by the pharmacists: a) patients' basic information such as stage of disease and protocol, b) state of implementation and break of chemotherapy and supportive therapy on calendar, and c) laboratory data and symptoms. We arranged the last item below the calendar and enabled pharmacists to easily assess individual adverse reactions coupled with the treatment course. Reviews of the developed worksheet indicated that the worksheet led to the convenient detection of individual adverse reaction patterns and effective prevention of additional adverse reactions. This monitoring sheet covering long-term chemotherapy which was designed to predict individual adverse reaction patterns will improve the individualization and safety of gynecologic chemotherapy.

  5. 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

  6. 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

  7. Polypharmacy and adverse drug reactions in Japanese elderly taking antihypertensives: a retrospective database study

    PubMed Central

    Sato, Izumi; Akazawa, Manabu

    2013-01-01

    Background The concomitant use of multiple medications by elderly patients with hypertension is a relatively common and growing phenomenon in Japan. This has been attributed to several factors, including treatment guidelines recommending prescription of multiple medications and a continuing increase in the elderly population with multiple comorbidities. Objective This study was aimed at investigating the association between polypharmacy, defined as the concomitant use of five or more medications, and risk of adverse drug reaction (ADR) in elderly Japanese hypertensive patients to examine the hypothesis that risk of ADR increases with the administration of an increasing number of co-medications. Methods Using a retrospective cohort design, the data regarding all hypertensive patients aged 65 years or older were extracted from the Risk/Benefit Assessment of Drugs – Analysis and Response Council antihypertensive medication database. The data were reviewed for classification of patients into one of three groups according to drug use at the initiation of therapy – a monotherapy group composed of patients who had taken the investigated drug only, a co-medication group composed of patients who had taken the investigated drug and a maximum of three other medications, and a polypharmacy group composed of patients who had taken the investigated drug and four or more other medications – and determination of the number of ADR events experienced. Estimated rate ratios (RRs) and 95% confidence intervals (CIs) were calculated using a Poisson regression model adjusted for drug category and patient age and sex. Various sensitivity analyses were performed to confirm the robustness of the study findings. Results Of 61,661 elderly Japanese patients (men, 41.8%; 75 years or older, 35.1%) registered in the database, 2491 patients (4.0%) experienced a total of 3144 ADR events during the study period. The rate of ADR per 10,000 person-days was 2.0 for the monotherapy group, 5.1 for

  8. Recognition and reporting of suspected adverse drug reactions by surveyed healthcare professionals in Uganda: key determinants

    PubMed Central

    Kiguba, Ronald; Karamagi, Charles; Waako, Paul; Ndagije, Helen B; Bird, Sheila M

    2014-01-01

    Objective To assess extent and determinants of past-month recognition of suspected adverse drug reactions (ADR) and past-year ADR reporting among healthcare professionals (HCPs) in Uganda. Setting Geographically diverse health facilities (public, private for-profit, private not-for-profit). Participants Of 2000 questionnaires distributed, 1345 were completed: return rate of 67%. Primary and secondary outcome measures Per cent HCPs who suspected ADR in the past month; reported ADR in the past year. Results Nurses were the majority (59%, 792/1345). Only half the respondents had heard about pharmacovigilance: 39% of nurses (295/763; 95% CI 35% to 42%), 70% otherwise (383/547; 95% CI 66% to 74%). One fifth (268/1289 or 21%; 95% CI 19% to 23%) had suspected an ADR in the previous 4 weeks, 111 of them were nurses; 15% (190/1296) had reported a suspected ADR in the past year, 103 of them were nurses. Past-month ADR suspicion was more likely by non-nurses (OR=1.7, 95% CI 1.16 to 2.40) and with medical research involvement (OR=1.5, 95% CI 1.05 to 2.15) but past-month receipt of patient ADR-complaint predominated (OR=19, 95% CI 14 to 28). Past-year ADR reporting was higher by hospital staff (OR=1.9, 95% CI 1.18 to 3.10), especially in medicine (OR=2.3, 95% CI 1.08 to 4.73); but lower from private for-profit health facilities (OR=0.5, 95% CI 0.28 to 0.77) and by older staff (OR=0.6, 95% CI 0.43 to 0.91); more likely by HCPs who had ever encountered a fatal ADR (OR=2.9, 95% CI 1.94 to 4.25), knew to whom to report (OR=1.7, 95% CI 1.18 to 2.46), or suggested how to improve ADR reporting (OR=1.6, 95% CI 1.04 to 2.49). Two attitudinal factors were important: diffidence and lethargy. Conclusions One in five HCPs suspected an ADR in the past-month and one in seven reported ADR in the previous year. Empowering patients could strengthen ADR detection and reporting in Africa. PMID:25421337

  9. 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

  10. 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

  11. Pharmacogenomics of severe cutaneous adverse reactions and drug-induced liver injury.

    PubMed

    Kaniwa, Nahoko; Saito, Yoshiro

    2013-06-01

    Rare but severe adverse drug reactions (ADRs) are an important issue in drug development and in the proper usage of drugs during the post-approval phase. The ability to predict patient susceptibility to severe ADRs would prevent drug administration to high-risk patients. This would save lives and ensure the quality of life for these patients, but occurrence of idiosyncratic severe ADRs had been very difficult to predict for a long time. However, in this decade, genetic markers have been found for several ADRs, especially for severe cutaneous adverse reactions (SCARs) and drug-induced liver injury (DILI). In this review, we summarize recent progress in identifying genetic markers for SCARS and DILI, and discuss issues that remain unresolved. As for SCARs, associations of HLA-B*15:02 or HLA-A*31:01 and HLA-B*58:01 have been revealed for carbamazepine- and allopurinol-related Stevens-Johnson syndrome and toxic epidermal neclolysis, respectively. HLA-B*57:01 is strongly associated with abacavir-induced hypersensitivity syndrome. Several HLA alleles also demonstrate drug-specific associations with DILI, such as HLA-A*33:03 for ticlopidine, HLA-B*57:01 for flucloxacillin and HLA-DQA1*02:01 for lapatinib. Efforts should be continued to find other genetic markers to achieve high predictability for ADRs, with the goal being development of genetic tests for use in clinical settings.

  12. Comparison of serious adverse reactions between thalidomide and lenalidomide: analysis in the French Pharmacovigilance database.

    PubMed

    Olivier-Abbal, Pascale; Teisseyre, Anne-Charlotte; Montastruc, Jean-Louis

    2013-12-01

    Thalidomide and lenalidomide are structural analogs and immunomodulatory drugs. Lenalidomide appears to have a different safety profile than thalidomide and could be less toxic, and as far as we know, we did not found any study comparing their safety profile. The objective of our study was to review and compare serious adverse drug reactions (SADRs) of thalidomide and lenalidomide spontaneously reported to the French Pharmacovigilance database. We extracted all medically confirmed spontaneous reports of SADR for lenalidomide-based regimens and thalidomide-based regimens from the French Pharmacovigilance database. A "serious" adverse drug reaction (ADR) was defined as an ADR that is fatal or life threatening, which causes hospitalization or prolongation of hospitalization, or permanent or significant disability. The study period was between marketing of 2 drugs and January 15, 2012. A total of 392 SADRs related to thalidomide-based regimens were identified in 244 patients and 377 SADRs related to lenalidomide-based regimens in 220 patients. In spite of their structural analogy, this study highlights interesting differences between lenalidomide and thalidomide's safety profile: nervous system and vascular disorders are more frequent with thalidomide-based regimens while hematologic, skin, infectious disorders and secondary primary cancers are more frequent with lenalidomide-based regimens.

  13. Influence of dexmedetomidine on incidence of adverse reactions introduced by hemabate in postpartum hemorrhage during cesarean section

    PubMed Central

    Liu, Yang; Chen, Hong-Xia; Kang, Dao-Lin; Kuang, Xiao-Hua; Liu, Wen-Xing; Ni, Jin

    2015-01-01

    Objective: The purpose of our study was to observe the influence of dexmedetomidine on complications caused by hemabate in patients undergoing caesarean section. Methods: A total of 120 females (age range, 20-40 years) at 35-40 weeks gestation who delivered by cesarean between September, 2014 and December, 2014 were enrolled in our study. Patients were randomly allocated into three groups that received intravenously physiological saline 20 mL (placebo group), lower dose (0.5 μg kg-1) of dexmedetomidine (low-dex gruop) and higher dose (1 μg kg-1) of dexmedetomidine (high-dex group) during cesarean section, following the delivery of the infant and intramuscular hemabate injection. Results: Nausea, vomiting, chest congestion and elevated blood pressure were the most common adverse events of placebo group. Compared with placebo group, the above mentioned adverse reactions decreased significantly in both low-dex group and high-dex group (P<0.05), whereas there were no significant difference between low-dex group and high-dex group (P>0.05). As to patient satisfaction score, low-dex group and high-dex group were all higher than placebo group (P<0.05). Furthermore, there were more patients satisfied with high-dex group than low-dex group (P<0.05). Conclusion: Dexmedetomidine (0.5 μg kg-1 and 1 μg kg-1) were all effective in preventing adverse reactions introduced by hemabate and improve parturients’ satisfaction in patients undergoing cesarean delivery. And higher dose (1 μg kg-1) of dexmedetomidine is superior to lower dose (0.5 μg kg-1) in patient satisfaction. PMID:26550325

  14. Quantitative evaluation of initial symptoms as predictors to detect adverse drug reactions using Bayes' theory: expansion and evaluation of drug-adverse drug reaction-initial symptom combinations using adverse event reporting system database.

    PubMed

    Kobayashi, Daisuke; Hosaka, Shigeru; Inoue, Emiko; Ohshima, Kimie; Kutsuma, Nobuaki; Oshima, Shinji; Okuno, Yasushi

    2013-01-01

    In prescription dispensing in Japan, to avoid adverse drug reactions (ADR) pharmacists provide patients with information concerning the initial symptoms (IS) of any ADR that might be caused by the drugs they have been prescribed. However, the usefulness of such information for preventing ADR has not been quantitatively evaluated. We previously performed a trial calculation of the usefulness of rash as a predictor of drug-induced liver disorders by applying Bayes' theorem and showed that the predictive utility of IS can be quantitatively evaluated using likelihood ratios. However, for other drug-ADR-IS combinations it was difficult to obtain the information required for the calculations from Japanese data alone. In this study, using the Adverse Event Reporting System (AERS) database of the U.S. Food and Drug Administration (FDA), we evaluated 132 drug-ADR-IS combinations that were considered to be potentially clinical significant. Regarding bezafibrate-associated rhabdomyolysis and cibenzoline-associated hypoglycemia, these ADR were not detected in cases involving monotherapy. For 58 combinations, no events that were considered to be IS of the target ADR developed. Fever, nausea, and decreased appetite were the IS of many ADR, making them very useful predictors. In contrast, pruritus and rash were not very useful. Fever might be a predictor of thiamazole-induced agranulocytosis or levofloxacin- or terbinafine-induced liver disorder, tremors might be useful for predicting paroxetine-induced serotonin syndrome, and decreased appetite might be a useful indicator of terbinafine-induced liver dysfunction. PMID:24292049

  15. Effect of the UK’s revised paracetamol poisoning management guidelines on admissions, adverse reactions and costs of treatment

    PubMed Central

    Bateman, D Nicholas; Carroll, Robert; Pettie, Janice; Yamamoto, Takahiro; Elamin, Muhammad E M O; Peart, Lucy; Dow, Margaret; Coyle, Judy; Cranfield, Kristina R; Hook, Christopher; Sandilands, Euan A; Veiraiah, Aravindan; Webb, David; Gray, Alasdair; Dargan, Paul I; Wood, David M; Thomas, Simon H L; Dear, James W; Eddleston, Michael

    2014-01-01

    Aims In September 2012 the UK’s Commission on Human Medicines (CHM) recommended changes in the management of paracetamol poisoning: use of a single ‘100 mg l−1’ nomogram treatment line, ceasing risk assessment, treating all staggered/uncertain ingestions and increasing the duration of the initial acetylcysteine (NAC) infusion from 15 to 60 min. We evaluated the effect of this on presentation, admission, treatment, adverse reactions and costs of paracetamol poisoning. Methods Data were prospectively collected from adult patients presenting to three large UK hospitals from 3 September 2011 to 3 September 2013 (year before and after change). Infusion duration effect on vomiting and anaphylactoid reactions was examined in one centre. A cost analysis from an NHS perspective was performed for 90 000 patients/annum with paracetamol overdose. Results There were increases in the numbers presenting to hospital (before 1703, after 1854; increase 8.9% [95% CI 1.9, 16.2], P = 0.011); admitted (1060/1703 [62.2%] vs. 1285/1854 [69.3%]; increase 7.1% [4.0, 10.2], P < 0.001) and proportion treated (626/1703 [36.8%] vs. 926/1854 [50.0%]; increase: 13.2% [95% CI 10.0, 16.4], P < 0.001). Increasing initial NAC infusion did not change the proportion of treated patients developing adverse reactions (15 min 87/323 [26.9%], 60 min 145/514 [28.2%]; increase: 1.3% [95% CI –4.9, 7.5], P = 0.682). Across the UK the estimated cost impact is £8.3 million (6.4 million–10.2 million) annually, with a cost-per-life saved of £17.4 million (13.4 million–21.5 million). Conclusions The changes introduced by the CHM in September 2012 have increased the numbers of patients admitted to hospital and treated with acetylcysteine without reducing adverse reactions. A safety and cost-benefit review of the CHM guidance is warranted, including novel treatment protocols and biomarkers in the assessment of poisoning. PMID:24666324

  16. [Incidence rate of adverse reaction/event by Qingkailing injection: a Meta-analysis of single rate].

    PubMed

    Ai, Chun-ling; Xie, Yan-ming; Li, Ming-quan; Wang, Lian-xin; Liao, Xing

    2015-12-01

    To systematically review the incidence rate of adverse drug reaction/event by Qingkailing injection. Such databases as the PubMed, EMbase, the Cochrane library, CNKI, VIP WanFang data and CBM were searched by computer from foundation to July 30, 2015. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data and cross check data. Then, Meta-analysis was performed by using the R 3.2.0 software, subgroup sensitivity analysis was performed based on age, mode of medicine, observation time and research quality. Sixty-three studies involving 9,793 patients with Qingkailing injection were included, 367 cases of adverse reactions/events were reported in total. The incidence rate of adverse reaction in skin and mucosa group was 2% [95% CI (0.02; 0.03)]; the digestive system adverse reaction was 6% [95% CI(0.05; 0.07); the injection site adverse reaction was 4% [95% CI (0.02; 0.07)]. In the digestive system as the main types of adverse reactions/events, incidence of children and adults were 4.6% [0.021 1; 0.097 7] and 6.9% [0.053 5; 0.089 8], respectively. Adverse reactions to skin and mucous membrane damage as the main performance/event type, the observation time > 7 days and ≤ 7 days incidence of 3% [0.012 9; 0.068 3] and 1.9% [0.007 8; 0.046 1], respectively. Subgroup analysis showed that different types of adverse reactions, combination in the incidence of adverse reactions/events were higher than that of single drug, the difference was statistically significant (P < 0.05). This study suggested the influence factors of adverse reactions occur, and clinical rational drug use, such as combination, age and other fators, and the influence factors vary in different populations. Therefore, clinical doctors for children and the elderly use special care was required for a clear and open spirit injection, the implementation of individualized medication.

  17. [Incidence rate of adverse reaction/event by Qingkailing injection: a Meta-analysis of single rate].

    PubMed

    Ai, Chun-ling; Xie, Yan-ming; Li, Ming-quan; Wang, Lian-xin; Liao, Xing

    2015-12-01

    To systematically review the incidence rate of adverse drug reaction/event by Qingkailing injection. Such databases as the PubMed, EMbase, the Cochrane library, CNKI, VIP WanFang data and CBM were searched by computer from foundation to July 30, 2015. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data and cross check data. Then, Meta-analysis was performed by using the R 3.2.0 software, subgroup sensitivity analysis was performed based on age, mode of medicine, observation time and research quality. Sixty-three studies involving 9,793 patients with Qingkailing injection were included, 367 cases of adverse reactions/events were reported in total. The incidence rate of adverse reaction in skin and mucosa group was 2% [95% CI (0.02; 0.03)]; the digestive system adverse reaction was 6% [95% CI(0.05; 0.07); the injection site adverse reaction was 4% [95% CI (0.02; 0.07)]. In the digestive system as the main types of adverse reactions/events, incidence of children and adults were 4.6% [0.021 1; 0.097 7] and 6.9% [0.053 5; 0.089 8], respectively. Adverse reactions to skin and mucous membrane damage as the main performance/event type, the observation time > 7 days and ≤ 7 days incidence of 3% [0.012 9; 0.068 3] and 1.9% [0.007 8; 0.046 1], respectively. Subgroup analysis showed that different types of adverse reactions, combination in the incidence of adverse reactions/events were higher than that of single drug, the difference was statistically significant (P < 0.05). This study suggested the influence factors of adverse reactions occur, and clinical rational drug use, such as combination, age and other fators, and the influence factors vary in different populations. Therefore, clinical doctors for children and the elderly use special care was required for a clear and open spirit injection, the implementation of individualized medication. PMID:27245021

  18. 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

  19. 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

  20. Digging Up the Human Genome: Current Progress in Deciphering Adverse Drug Reactions

    PubMed Central

    Chung, Wen-Hung

    2014-01-01

    Adverse drug reactions (ADRs) are a major clinical problem. In addition to their clinical impact on human health, there is an enormous cost associated with ADRs in health care and pharmaceutical industry. Increasing studies revealed that genetic variants can determine the susceptibility of individuals to ADRs. The development of modern genomic technologies has led to a tremendous advancement of improving the drug safety and efficacy and minimizing the ADRs. This review will discuss the pharmacogenomic techniques used to unveil the determinants of ADRs and summarize the current progresses concerning the identification of biomarkers for ADRs, with a focus on genetic variants for genes encoding drug-metabolizing enzymes, drug-transporter proteins, and human leukocyte antigen (HLA). The knowledge gained from these cutting-edge findings will form the basis for better prediction and management for ADRs, ultimately making the medicine personalized. PMID:24734245

  1. [Pharmacogenetic research in the association between human leukocyte antigen and adverse drug reactions].

    PubMed

    Xiong, Yan; Zhang, Wei; Chen, Xiaoping

    2014-07-01

    With the rapid development of pharmacogenetics, more and more studies have shown evidence in the association between polymorphisms at the human leukocyte antigen (HLA) loci and severe adverse drug reactions (SADRs). Several HLA-B alleles proved to be associated with SADRs for drugs such as carbamazepine, allopurinol, lamotrigine, and flucloxacillin. The USA Food and Drug Administration (FDA) has even recommended routine screening for HLA-B allele before the use of abacavir and carbamazepine. With the completion of human genome project and the Hapmap project, several new pharmacogenetics approaches such as genome-wide association study (GWAS) have emerged. These newly developed methods will undoubtedly accelerate the identification and clinical utilization of the pharmacogenetic biomakers. In addition, the immunogenetic mechanisms by which the HLA alleles cause SADRs are explored at the cellular and molecular level. This review focuses on the recent progresses in HLA alleles and ADRs regarding both the clinical translation and modern pharmacogenetic methods. PMID:25080918

  2. Titanium Alloy Stem as a Cause for Adverse Reaction to Metal Debris after Bipolar Hemiarthroplasty

    PubMed Central

    Watanabe, Hitoshi; Kubosawa, Hitoshi

    2014-01-01

    A 68-year-old male with failure of bipolar hemiarthroplasty consistent with adverse reaction to metal debris (ARMD) who presented with a painful cystic lesion and lower extremity swelling was encountered. However, revision surgical findings showed no apparent cause of ARMD previously described in the literature, such as corrosion at the head-neck junction and articular abrasion. Therefore, it was difficult to make a definite diagnosis of failure secondary to ARMD, which consequently led to the decision to perform two-stage revision procedure, though the stem was firmly fixed. Postoperative analysis in the retrieval tissues showed that the metal debris mainly originated from the titanium alloy stem itself. Although this is a very rare case, one should be aware that even the well-fixed femoral components themselves have the potential to be the cause of ARMD. PMID:24716061

  3. Adverse drug reactions to self-medication: a study in a pharmacovigilance database.

    PubMed

    Berreni, Aurélia; Montastruc, François; Bondon-Guitton, Emmanuelle; Rousseau, Vanessa; Abadie, Delphine; Durrieu, Geneviève; Chebane, Leila; Giroud, Jean-Paul; Bagheri, Haleh; Montastruc, Jean-Louis

    2015-10-01

    Although self-medication is widely developed, there are few detailed data about its adverse drug reactions (ADRs). This study investigated the main characteristics of ADRs with self-medication recorded in the Midi-Pyrénées PharmacoVigilance between 2008 and 2014. Self-medication included first OTC drugs and second formerly prescribed drugs later used without medical advice (reuse of previously prescribed drugs). Among the 12 365 notifications recorded, 160 (1.3%) were related to SM with 186 drugs. Around three-forth of the ADRs were 'serious'. Mean age was 48.8 years with 56.3% females. The most frequent ADRs were gastrointestinal and neuropsychiatric and main drug classes involved NSAIDs, analgesics, and benzodiazepines. Phytotherapy-homeopathy accounted for 9.1% of drugs.

  4. 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

  5. Renal function, nephrogenic systemic fibrosis and other adverse reactions associated with gadolinium-based contrast media.

    PubMed

    Canga, Ana; Kislikova, Maria; Martínez-Gálvez, María; Arias, Mercedes; Fraga-Rivas, Patricia; Poyatos, Cecilio; de Francisco, Angel L M

    2014-01-01

    Nephrogenic systemic fibrosis is a fibrosing disorder that affects patients with impaired renal function and is associated with the administration of gadolinium-based contrast media used in MRI. Despite being in a group of drugs that were considered safe, report about this potentially serious adverse reaction was a turning point in the administration guidelines of these contrast media. There has been an attempt to establish safety parameters to identify patients with risk factors of renal failure. The close pharmacovigilance and strict observation of current regulations, with special attention being paid to the value of glomerular filtration, have reduced the published cases involving the use of gadolinium-based contrast media. In a meeting between radiologists and nephrologists we reviewed the most relevant aspects currently and recommendations for its prevention.

  6. Perception of the risk of adverse reactions to analgesics: differences between medical students and residents

    PubMed Central

    González-Santiago, Omar; Delgado-Leal, Ismael A.; Lozano-Luévano, Gerardo E.; Reyes-Rodríguez, Misael J.; Elizondo-Solis, César V.; Nava-Obregón, Teresa A.; Palacios-Ríos, Dionicio

    2016-01-01

    Background. Medications are not exempt from adverse drug reactions (ADR) and how the physician perceives the risk of prescription drugs could influence their availability to report ADR and their prescription behavior. Methods. We assess the perception of risk and the perception of ADR associated with COX2-Inbitors, paracetamol, NSAIDs, and morphine in medical students and residents of northeast of Mexico. Results. The analgesic with the highest risk perception in both group of students was morphine, while the drug with the least risk perceived was paracetamol. Addiction and gastrointestinal bleeding were the ADR with the highest score for morphine and NSAIDs respectively. Discussion. Our findings show that medical students give higher risk scores than residents toward risk due to analgesics. Continuing training and informing physicians about ADRs is necessary since the lack of training is known to induce inadequate use of drugs. PMID:27547561

  7. Adverse reactions to gentamycin in patients with ear, nose or throat infections.

    PubMed

    Singhal, S; Sharma, S C; Singhal, K C

    1992-07-01

    Eighty four patients requiring treatment with Gentamycin were selected from Otorhinolaryngology outpatient and those admitted to the hospital. Patients suffering from hepatic or renal disorders, pregnant women and children were excluded from the study. Seventy three were administered gentamycin 40 mg BD intramuscularly for 7-10 days and in 11 the drug was applied topically as ear drops for 6-12 weeks. Adverse reactions were observed in 9 (13.3%) and 11 (100%) patients given the drug parenterally and topically respectively. In parenteral group incidence was higher in females as compared to males and profile included nausea and vomiting, headache, cough, tinnitis, albuminuria, diminition of hearing and vertigo. Whereas diminition of hearing acuity was observed in all those who had topical application as evidenced by pure tone audiometry. PMID:1473850

  8. Perception of the risk of adverse reactions to analgesics: differences between medical students and residents.

    PubMed

    Castillo-Guzman, Sandra; González-Santiago, Omar; Delgado-Leal, Ismael A; Lozano-Luévano, Gerardo E; Reyes-Rodríguez, Misael J; Elizondo-Solis, César V; Nava-Obregón, Teresa A; Palacios-Ríos, Dionicio

    2016-01-01

    Background. Medications are not exempt from adverse drug reactions (ADR) and how the physician perceives the risk of prescription drugs could influence their availability to report ADR and their prescription behavior. Methods. We assess the perception of risk and the perception of ADR associated with COX2-Inbitors, paracetamol, NSAIDs, and morphine in medical students and residents of northeast of Mexico. Results. The analgesic with the highest risk perception in both group of students was morphine, while the drug with the least risk perceived was paracetamol. Addiction and gastrointestinal bleeding were the ADR with the highest score for morphine and NSAIDs respectively. Discussion. Our findings show that medical students give higher risk scores than residents toward risk due to analgesics. Continuing training and informing physicians about ADRs is necessary since the lack of training is known to induce inadequate use of drugs. PMID:27547561

  9. [The Beers List as an aid to prevent adverse drug reactions in elderly patients].

    PubMed

    Vingerhoets, R W; van Marum, R J; Jansen, P A F

    2005-09-17

    Elderly patients are highly susceptible for developing adverse drug reactions (ADR) that can lead to hospitalisation or death. Most of these ADR can be prevented if doctors adjust their prescriptions. Beers et al. have developed a list of drugs that should not be prescribed to elderly patients since they are known for their association with serious ADR. In The Netherlands, 20% of elderly patients receive drugs that are in the so-called Beers list. Although the Beers list has not been adjusted to the Dutch situation, avoidance of these drugs may reduce drug-related hospital admittance. Development of an improved list of drugs that should not be prescribed to elderly patients is needed that is applicable to The Netherlands. PMID:16201599

  10. Ci4SeR--curation interface for semantic resources--evaluation with adverse drug reactions.

    PubMed

    Souvignet, Julien; Asfari, Hadyl; Declerck, Gunnar; Lardon, Jérémy; Trombert-Paviot, Béatrice; Jaulent, Marie-Christine; Bousquet, Cédric

    2014-01-01

    Evaluation and validation have become a crucial problem for the development of semantic resources. We developed Ci4SeR, a Graphical User Interface to optimize the curation work (not taking into account structural aspects), suitable for any type of resource with lightweight description logic. We tested it on OntoADR, an ontology of adverse drug reactions. A single curator has reviewed 326 terms (1020 axioms) in an estimated time of 120 hours (2.71 concepts and 8.5 axioms reviewed per hour) and added 1874 new axioms (15.6 axioms per hour). Compared with previous manual endeavours, the interface allows increasing the speed-rate of reviewed concepts by 68% and axiom addition by 486%. A wider use of Ci4SeR would help semantic resources curation and improve completeness of knowledge modelling.

  11. Adverse reactions to aspartame: double-blind challenge in patients from a vulnerable population.

    PubMed

    Walton, R G; Hudak, R; Green-Waite, R J

    This study was designed to ascertain whether individuals with mood disorders are particularly vulnerable to adverse effects of aspartame. Although the protocol required the recruitment of 40 patients with unipolar depression and a similar number of individuals without a psychiatric history, the project was halted by the Institutional Review Board after a total of 13 individuals had completed the study because of the severity of reactions within the group of patients with a history of depression. In a crossover design, subjects received aspartame 30 mg/kg/day or placebo for 7 days. Despite the small n, there was a significant difference between aspartame and placebo in number and severity of symptoms for patients with a history of depression, whereas for individuals without such a history there was not. We conclude that individuals with mood disorders are particularly sensitive to this artificial sweetener and its use in this population should be discouraged.

  12. 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

  13. Epidemiology of adverse drug reactions in the elderly by drug class.

    PubMed

    Beyth, R J; Shorr, R I

    1999-03-01

    As the growth of the elderly population continues, the burden on the health care system and society will also increase. Since chronic diseases such as hypertension, coronary artery disease, arthritis, stroke, cancer and diabetes mellitus are more prevalent with age, the number of people with multiple chronic diseases will also increase. These patients are likely to be treated for some or all of their conditions with drug therapies. When used appropriately, drugs may be the single most important intervention in the care of an older patient, but when used inappropriately they no longer provide therapeutic benefit, and they may even endanger the health of an older patient by causing an adverse drug reaction (ADR). Factors believed to be responsible for increased adverse reactions in elderly patients are polypharmacy (including prescription and over-the-counter medications), increased drug-drug interaction, pharmacokinetic changes, pharmacodynamic changes, the pathology of aging and compliance. The exact role that age plays in ADRs is not clear. This is in part because few older patients are included in the large randomised trials, and so much of the information used to ascertain the age-associated risks of drugs comes from observational studies. Although the interactions of aging, concurrent comorbidities and polypharmacy are known, older patients do appear to be at increased risk. Improvements in the management of drug therapies of older patients can lead to improvements in their overall health, functioning and safety, as well as providing potential benefits to society by ameliorating some of the burden of their health care. PMID:10220106

  14. 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

  15. Does an allergy to fish pre-empt an adverse protamine reaction? A case report and a literature review.

    PubMed

    Collins, C; O'Donnell, A

    2008-11-01

    The operating theatre exposes patients to myriad potential agents which could result in a life-threatening anaphylactic reaction. Anaesthetic drugs, blood products, and latex are only some of the possible allergens. Reactions are deemed to be anaphylactic when immediate sensitivity is combined with cardiovascular collapse. A patient who had a known allergy to shellfish presented for first time cardiopulmonary bypass. The perfusion team were concerned that there was a realistic possibility that an adverse reaction to protamine could occur. Anaphylactic reactions to protamine in patients allergic to fish have been reported. The anaesthetic team were informed and the necessary precautions taken. We report on the outcome for our patient and also discuss other risk factors and the types of reactions that can result when an adverse reaction to protamine occurs.

  16. Adverse reactions to immunotherapy are associated with different patterns of sensitization to grass allergens.

    PubMed

    Sastre, J; Rodríguez, F; Campo, P; Laffond, E; Marín, A; Alonso, M D

    2015-05-01

    The aim of the study was to investigate whether adverse drug reactions (ADRs) during immunotherapy with a grass extract (AVANZ® Phleum, ALK-Abelló) are related to the different patterns of sensitization of patients to grass allergens. A total of 192 patients with rhinitis and/or asthma sensitized to grass pollen received a 4-week updosing with five injections. ADRs were evaluated following EAACI guidelines. A total of 432 ADRs in 133 (69%) patients were recorded, 64% local and 31% systemic. There was a significant association between the number of grass allergens that sensitized the patients and the total number of ADRs (P = 0.004) occurred locally (P = 0.003) and systemically (P = 0.01). Sensitization to Phl p1 + Phl p5 or Phl p1 + Phl p5 + Phl p12 was significantly associated with a higher frequency of local or systemic reactions (P = 0.001, both). Different patterns of sensitization to grass allergens may potentially be considered a risk marker to the development of ADRs to immunotherapy.

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

    PubMed

    Castleden, C M; Pickles, H

    1988-10-01

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

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

    SciTech Connect

    Pan, Jian-Bo; Ji, Nan; Pan, Wen; Hong, Ru; Wang, Hao; Ji, Zhi-Liang

    2014-01-01

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

  19. Predicting adverse drug reactions in older adults; a systematic review of the risk prediction models

    PubMed Central

    Stevenson, Jennifer M; Williams, Josceline L; Burnham, Thomas G; Prevost, A Toby; Schiff, Rebekah; Erskine, S David; Davies, J Graham

    2014-01-01

    Adverse drug reaction (ADR) risk-prediction models for use in older adults have been developed, but it is not clear if they are suitable for use in clinical practice. This systematic review aimed to identify and investigate the quality of validated ADR risk-prediction models for use in older adults. Standard computerized databases, the gray literature, bibliographies, and citations were searched (2012) to identify relevant peer-reviewed studies. Studies that developed and validated an ADR prediction model for use in patients over 65 years old, using a multivariable approach in the design and analysis, were included. Data were extracted and their quality assessed by independent reviewers using a standard approach. Of the 13,423 titles identified, only 549 were associated with adverse outcomes of medicines use. Four met the inclusion criteria. All were conducted in inpatient cohorts in Western Europe. None of the models satisfied the four key stages in the creation of a quality risk prediction model; development and validation were completed, but impact and implementation were not assessed. Model performance was modest; area under the receiver operator curve ranged from 0.623 to 0.73. Study quality was difficult to assess due to poor reporting, but inappropriate methods were apparent. Further work needs to be conducted concerning the existing models to enable the development of a robust ADR risk-prediction model that is externally validated, with practical design and good performance. Only then can implementation and impact be assessed with the aim of generating a model of high enough quality to be considered for use in clinical care to prioritize older people at high risk of suffering an ADR. PMID:25278750

  20. Predicting adverse drug reactions in older adults; a systematic review of the risk prediction models.

    PubMed

    Stevenson, Jennifer M; Williams, Josceline L; Burnham, Thomas G; Prevost, A Toby; Schiff, Rebekah; Erskine, S David; Davies, J Graham

    2014-01-01

    Adverse drug reaction (ADR) risk-prediction models for use in older adults have been developed, but it is not clear if they are suitable for use in clinical practice. This systematic review aimed to identify and investigate the quality of validated ADR risk-prediction models for use in older adults. Standard computerized databases, the gray literature, bibliographies, and citations were searched (2012) to identify relevant peer-reviewed studies. Studies that developed and validated an ADR prediction model for use in patients over 65 years old, using a multivariable approach in the design and analysis, were included. Data were extracted and their quality assessed by independent reviewers using a standard approach. Of the 13,423 titles identified, only 549 were associated with adverse outcomes of medicines use. Four met the inclusion criteria. All were conducted in inpatient cohorts in Western Europe. None of the models satisfied the four key stages in the creation of a quality risk prediction model; development and validation were completed, but impact and implementation were not assessed. Model performance was modest; area under the receiver operator curve ranged from 0.623 to 0.73. Study quality was difficult to assess due to poor reporting, but inappropriate methods were apparent. Further work needs to be conducted concerning the existing models to enable the development of a robust ADR risk-prediction model that is externally validated, with practical design and good performance. Only then can implementation and impact be assessed with the aim of generating a model of high enough quality to be considered for use in clinical care to prioritize older people at high risk of suffering an ADR.

  1. Predicting adverse drug reactions in older adults; a systematic review of the risk prediction models.

    PubMed

    Stevenson, Jennifer M; Williams, Josceline L; Burnham, Thomas G; Prevost, A Toby; Schiff, Rebekah; Erskine, S David; Davies, J Graham

    2014-01-01

    Adverse drug reaction (ADR) risk-prediction models for use in older adults have been developed, but it is not clear if they are suitable for use in clinical practice. This systematic review aimed to identify and investigate the quality of validated ADR risk-prediction models for use in older adults. Standard computerized databases, the gray literature, bibliographies, and citations were searched (2012) to identify relevant peer-reviewed studies. Studies that developed and validated an ADR prediction model for use in patients over 65 years old, using a multivariable approach in the design and analysis, were included. Data were extracted and their quality assessed by independent reviewers using a standard approach. Of the 13,423 titles identified, only 549 were associated with adverse outcomes of medicines use. Four met the inclusion criteria. All were conducted in inpatient cohorts in Western Europe. None of the models satisfied the four key stages in the creation of a quality risk prediction model; development and validation were completed, but impact and implementation were not assessed. Model performance was modest; area under the receiver operator curve ranged from 0.623 to 0.73. Study quality was difficult to assess due to poor reporting, but inappropriate methods were apparent. Further work needs to be conducted concerning the existing models to enable the development of a robust ADR risk-prediction model that is externally validated, with practical design and good performance. Only then can implementation and impact be assessed with the aim of generating a model of high enough quality to be considered for use in clinical care to prioritize older people at high risk of suffering an ADR. PMID:25278750

  2. Nevirapine: Most Common Cause of Cutaneous Adverse Drug Reactions in an Outpatient Department of a Tertiary Care Hospital

    PubMed Central

    Pawar, Mayur Popat; Pore, Shraddha Milind; Pradhan, Shekhar Nana; Bhoi, Umesh Yedu; Ramanand, Sunita Jaiprakash

    2015-01-01

    Introduction Skin is the most commonly involved organ in adverse drug reactions. Most of the cutaneous adverse drug reactions (CADRs) being of mild to moderate severity are likely to be diagnosed and treated in an outpatient setting. Consequently, knowledge regarding morphological pattern, severity and drugs implicated in causation of these CADRs has important implications for healthcare personnel. Aim To determine the current clinical pattern of CADRs and to assess their causality and severity with the help of standard scales. Study design and setting A prospective, observational study was conducted in the outpatient department of skin and venereal disease in a tertiary care hospital. Materials and Methods Patients with suspected CADR after consumption of systemic drug(s) were enrolled in the study. Data regarding demographics, clinical manifestations of CADR, drug history preceding the reaction, concomitant illness, relevant laboratory investigations etc was obtained. This data was then analysed for morphological pattern, causality and severity. CADRs with causality assessment possible and above on the basis of World Health Organization-Uppsala Monitoring Centre causality assessment system were considered for analysis. Statistics Descriptive statistics were used to express results of pattern, severity and causality of CADRs. Results Ninety patients were enrolled in the study. Male to female ratio for CADRs was 1:2.33. Maculopapular rash was most commonly encountered CADR in 76.67% cases followed by urticaria (8.89%), Stevens-Johnson syndrome (4.4%) and fixed dose eruptions (3.33%). Antiretrovirals were implicated in 75.56% (68/90) of CADRs. Nevirapine was suspected in 52 out of 90 (57.77%) cases of CADRs which included 39 cases of maculopapular rash, five cases of urticaria, four cases of Stevens-Johnson syndrome, and two cases each of pustular rash and angioedema respectively. Antimicrobials, antiepileptics and Non-steroidal Anti-inflammatory Drugs (NSAIDs) were

  3. 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

  4. Detecting Potential Adverse Reactions of Sulpiride in Schizophrenic Patients by Prescription Sequence Symmetry Analysis

    PubMed Central

    Lai, Edward Chia-Cheng; Hsieh, Cheng-Yang; Kao Yang, Yea-Huei; Lin, Swu-Jane

    2014-01-01

    Purpose Previous studies have demonstrated sulpiride to be significantly more effective than haloperidol, risperidone and olanzapine in schizophrenic treatment; however, only limited information is available on the potential risks associated with sulpiride treatment. This study attempts to provide information on the potential risks of sulpiride treatment of schizophrenia, especially with regard to unexpected adverse effects. Materials and Methods Patients with schizophrenia aged 18 and older, newly prescribed with a single antipsychotic medication from the National Health Insurance Research Database of Taiwan in the period from 2003 to 2010 were included. A within-subject comparison method, prescription sequence symmetry analysis (PSSA) was employed to efficiently identify potential causal relationships while controlling for potential selection bias. Results A total of 5,750 patients, with a mean age of 39, approximately half of whom were male, constituted the study cohort. The PSSA found that sulpiride was associated with EPS (adjusted SR, 1.73; 95% CI, 1.46–2.06) and hyperprolactinemia (12.04; 1.59–91.2). In comparison, EPS caused by haloperidol has a magnitude of 1.99 when analyzed with PSSA, and hyperprolactinemia caused by amisulpride has a magnitude of 8.05, respectively. Another finding was the unexpected increase in the use of stomatological corticosteroids, emollient laxatives, dermatological preparations of corticosteroids, quinolone antibacterials, and topical products for joint and muscular pain, after initiation of sulpiride treatment. Conclusions We found sulpiride to be associated with an increased risk of EPS and hyperprolactinemia, and the potential risk could be as high as that induced by haloperidol and amisulpride, respectively. Additionally, our study provides grounds for future investigations into the associations between sulpiride and the increased use of additional drugs for managing adverse effects, including stomatological

  5. 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

  6. 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.

  7. Designing a national combined reporting form for adverse drug reactions and medication errors.

    PubMed

    Tanti, A; Serracino-Inglott, A; Borg, J J

    2015-06-09

    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.

  8. Adverse Reaction of Sodium Hypochlorite during Endodontic Treatment of Primary Teeth

    PubMed Central

    Panse, Amey Manohar; Gawali, Pritesh Namdeo

    2015-01-01

    ABSTRACT Sodium hypochlorite (NaOCl) is the most common and effective intracanal medicament used in root canal treatments, because of its low-cost and a very effective antimicrobial activity against microbiota of infected root canals. Sodium hypochlorite is an effective intracanal irrigant and is used in concentrations ranging from 0.5 to 5.25%. At these concentrations, it is highly hypertonic and strongly alkaline with pH 11 to 13. Despite its safe properties, serious complications can result from inadvertent use due to its cytotoxic features. Most of the complications are the result of accidental extrusion of the solution from the apical foramen or accessory canals or perforations into the periapical area. Although it is an effective solution for disinfection of root canal system, fewer incidence of complications are reported, especially in primary teeth. Present article highlights one of such cases of NaOCl accident and its successful management in a 4-year-old child. How to cite this article: Chaugule VB, Panse AM, Gawali PN. Adverse Reaction of Sodium Hypochlorite during Endo-dontic Treatment of Primary Teeth. Int J Clin Pediatr Dent 2015;8(2):153-156. PMID:26379387

  9. The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety

    PubMed Central

    Ekor, Martins

    2014-01-01

    The use of herbal medicinal products and supplements has increased tremendously over the past three decades with not less than 80% of people worldwide relying on them for some part of primary healthcare. Although therapies involving these agents have shown promising potential with the efficacy of a good number of herbal products clearly established, many of them remain untested and their use are either poorly monitored or not even monitored at all. The consequence of this is an inadequate knowledge of their mode of action, potential adverse reactions, contraindications, and interactions with existing orthodox pharmaceuticals and functional foods to promote both safe and rational use of these agents. Since safety continues to be a major issue with the use of herbal remedies, it becomes imperative, therefore, that relevant regulatory authorities put in place appropriate measures to protect public health by ensuring that all herbal medicines are safe and of suitable quality. This review discusses toxicity-related issues and major safety concerns arising from the use of herbal medicinal products and also highlights some important challenges associated with effective monitoring of their safety. PMID:24454289

  10. Adverse Food Reaction and Functional Gastrointestinal Disorders: Role of the Dietetic Approach.

    PubMed

    Pasqui, Francesca; Poli, Carolina; Colecchia, Antonio; Marasco, Giovanni; Festi, Davide

    2015-09-01

    Bloating, abdominal discomfort or pain, disturbed bowel habits are very common symptoms, frequently reported by the patients soon after food ingestion. These symptoms may occur in different clinical conditions, such as functional bowel disorders, food adverse reactions, gluten-related syndromes, which frequently are interrelated. Consequently, in clinical practice, it is necessary to perform a correct diagnosis in order to identify, for the single patient, the most appropriate therapeutic strategy, which may include not only specific drugs, but also, and mainly, life style changes (healthy nutritional behavior and constant physical activity). The aim of this review is to provide to the general physician, according to the available evidence, the most appropriate diagnostic work-ups for recognizing the different clinical scenarios (i.e. food allergy and intolerance, functional bowel diseases, gluten-related syndromes), to identify their clinical interrelationships and to suggest the most appropriate management. In fact, as far as food intolerances are concerned, it is well known that the number of patients who believe that their symptoms are related to food intolerance is increasing and consequently they restrict their diet, possibly causing nutritional deficiencies. Furthermore, there is an increasing use of unconventional diagnostic tests for food intolerance which lack accurate scientific evidence; the application of their results may induce misdiagnosis and unhealthy therapeutic choices. Consequently the recognition of food intolerance has to be performed on the basis of reliable tests within an agreed diagnostic workup.

  11. Developing and integrating an adverse drug reaction reporting system with the hospital information system.

    PubMed

    Kataoka, Satoshi; Ohe, Kazuhiko; Mochizuki, Mayumi; Ueda, Shiro

    2002-01-01

    We have developed an adverse drug reaction (ADR) reporting system integrating it with Hospital Information System (HIS) of the University of Tokyo Hospital. Since this system is designed with JAVA, it is portable without re-compiling to any operating systems on which JAVA virtual machines work. In this system, we implemented an automatic data filling function using XML-based (extended Markup Language) files generated by HIS. This new specification would decrease the time needed for physicians and pharmacists to fill the spontaneous ADR reports. By clicking a button, the report is sent to the text database through Simple Mail Transfer Protocol (SMTP) electronic mails. The destination of the report mail can be changed arbitrarily by administrators, which adds this system more flexibility for practical operation. Although we tried our best to use the SGML-based (Standard Generalized Markup Language) ICH M2 guideline to follow the global standard of the case report, we eventually adopted XML as the output report format. This is because we found some problems in handling two bytes characters with ICH guideline and XML has a lot of useful features. According to our pilot survey conducted at the University of Tokyo Hospital, many physicians answered that our idea, integrating ADR reporting system to HIS, would increase the ADR reporting numbers.

  12. HRQoL questionnaire evaluation in lactose intolerant patients with adverse reactions to foods.

    PubMed

    Erminia, Ridolo; Ilaria, Baiardini; Tiziana, Meschi; Silvia, Peveri; Antonio, Nouvenne; Pierpaolo, Dall'Aglio; Loris, Borghi

    2013-09-01

    The occurrence of patients with gastrointestinal symptoms attributed either to food allergy or intolerance has significantly increased. Nevertheless, an accurate and detailed case history, a systematic evaluation and the outcomes of specific allergy tests to identify the offending foods, including "in vivo" and "in vitro" allergy tests, are often negative for food allergy and may indicate a lactose intolerance, which is a recurrent condition affecting about 50% of adults. The aims of our study were the following: (1) What is the real incidence of the food hypersensitivity and the primary lactose intolerance in patients with gastrointestinal symptoms, initially referred to allergy or food intolerance? (2) Does lactose intolerance affect the quality of life and compliance to the therapy program? We investigated 262 consecutive patients, 72 men and 190 women. An accurate and detailed history and clinical examination were completed to investigate the offending foods. The evaluation in each patient included: allergy tests, lactose H2 breath test (LHBT) and the HRQoL questionnaire. Five years after the diagnosis of lactose intolerance, a questionnaire on the persistence of gastrointestinal symptoms after lactose ingestion and the diet compliance was distributed. Our results demonstrate an high prevalence of lactose intolerance, more frequent in women; in these patients, bloating and diarrhea are the most reported symptoms. We observe only a significant positive correlation between adverse drug reaction (ADR) and LHBT+ patients, but not an augmented prevalence of food allergy and a negative impact on the HRQoL questionnaire of lactose intolerance. PMID:21614464

  13. 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.

  14. 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

  15. 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

  16. Psychotropic drugs in Bulgaria-frequency and risk of adverse drug reactions.

    PubMed

    Dimitrova, Z; Doma, A; Petkova, V; Getov, I; Verkkunen, E

    2002-01-01

    The aim of the study is to determine the frequency and risk of appearance of adverse drug reactions/ADRs/during the treatment with psychotropic drugs. The first part of the study is an analysis of the use of the psychotropic drugs for one-year period of time in our country, performed by DDD methodology. An attempt is made to equalize the Bulgarian list of the psychotropic drugs with the ATC classification and to estimate the DDD/1000/day. The data for Bulgaria is compared with that of the other countries. The collected data for the psychotropic drug use is divided into 2 groups: Psycholeptics and Psychoanaleptics. It is made an attempt to explain the main differences between them. The number of the standard therapeutic courses/NT/is used for assessment of the frequency and risk of ADRs. The results from the study show that the determined frequency of appearance of ADR for the different drugs is within "rare" and "very rare' for 100,000 inhabitants, according to the WHO terminology. Only for the drug Tardyl (EGIS Pharmaceuticals, Hungary) with INN Aminobarbitalum + Glutethimidum + Promethazini hydrochloridum the frequency is above 1%. That fact makes us to recommend a limitation of the prescription and usage of this drug to the Bulgarian Ministry of Health and to the National Drug Agency. PMID:12064062

  17. The risk of adverse drug reactions in older patients: beyond drug metabolism.

    PubMed

    Onder, Graziano; Lattanzio, Fabrizia; Battaglia, Miriam; Cerullo, Francesco; Sportiello, Roberta; Bernabei, Roberto; Landi, Francesco

    2011-09-01

    Changes in pharmacokinetics and pharmacodynamics, associated with increasing age, are often considered the only culprits of increasing Adverse Drug Reactions (ADR) rate observed in older adults, but other factors may be responsible for a reduction in drug efficacy and increase the risk of iatrogenic illness in this population. The aging process is characterized by a high level of complexity, which makes the care of older adults and the use of medications a challenging task. In particular, comorbidity, geriatric syndromes, cognitive and functional deficits, limited life expectancy are typical conditions observed in older adults which may reduce the efficacy of prescribed drugs and increase the risk of iatrogenic illness. As a consequence, a comprehensive assessment and management of the health care problems, with the goal of recognizing and preventing potential drug-related problems and improve quality of prescribing is necessary to reduce the risk of ADR. Several studies have assessed the effect of a comprehensive geriatric assessment and management on drug prescribing and drug related illness, showing a substantial improvement in quality of prescription and a reduction in rate of ADR. In addition, clinical guidelines providing recommendations regarding the use of drugs in chronic disease rarely assess the level of complexity observed in older adults and therefore they should be applied with caution in this population. PMID:21495971

  18. 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

  19. Avoiding adverse drug reactions in the elderly patient: issues and strategies.

    PubMed

    French, D G

    1996-09-01

    Primary care providers are faced with numerous challenges when prescribing drugs for elderly patients. Multiple drug use, coexisting illness, and normal physiologic changes associated with aging place older persons at increased risk for adverse drug reactions (ADRs). Sample selection bias in drug clinical trials and inappropriate prescribing of contraindicated drugs contribute to the risk profile. Because multiple drug use and ADRs are relatively common in the elderly, special caution should be used when prescribing for this population. The primary care provider should have a good understanding of the factors that put the elderly at increased risk for ADR, the classes of drugs inappropriate for elderly patients, the physiologic changes of aging that may produce an altered pharmacologic response, and the issues associated with adherence to drug therapy. This article identifies factors that contribute to ADRs in the elderly and proposes strategies to reduce or avoid risk. Identifying and preventing ADRs in older Americans is a Healthy People 2000 health protection goal, perhaps more important given projected demographics over the next 20 to 30 years. PMID:8884797

  20. Adverse drug reactions to unlicensed and off-label drugs on paediatric wards: a prospective study.

    PubMed

    Turner, S; Nunn, A J; Fielding, K; Choonara, I

    1999-09-01

    To determine the incidence of adverse drug reactions (ADRs) to unlicensed and off-label drugs used in paediatric inpatients, we carried out prospective surveillance on five different paediatric wards in a regional children's hospital for 13 wk. Comparison of the use of each drug with its summary of product characteristics was made to determine whether the drug was used in an unlicensed or off-label manner. The presence of an ADR was determined using previously defined criteria. In total, 4455 courses of drugs were administered to 936 patients in 1046 admissions. In 507 (48%) of the 1046 admissions, patients received one or more unlicensed or off-label drugs. ADRs occurred in 116 (11%) of the 1046 patient admissions. ADRs were associated with 112 (3.9%) of the 2881 licensed drug prescriptions and 95 (6%) of the 1574 unlicensed or off-label drug prescriptions. Use of drugs in an off-label or unlicensed manner to treat children is widespread. ADRs are a significant problem following unlicensed or off-label drug prescriptions. PMID:10519338

  1. Adverse Drug Reactions in HIV/AIDS Patients at a Tertiary Care Hospital in Penang, Malaysia.

    PubMed

    Khan, Kashifullah; Khan, Amer Hayat; Sulaiman, Syed Azhar; Soo, Chow Ting; Akhtar, Ali

    2016-01-01

    In the current study we explored the occurrence of adverse drug reactions (ADRs) to antiretroviral therapy among human immune-deficiency virus (HIV)/AIDS patients. We concluded an observational retrospective study in all patients who were diagnosed with HIV infection and were receiving highly active antiviral therapy from Jan. 2007 to Dec. 2012 at Hospital Pulau Pinang, Malaysia. Patient socio-demographic details along with clinical features and susceptible ADRs were observed during the study period. Out of 743 patients, 571 (76.9%) were men, and 172 (23.1%) were women. Overall 314 (42.2%) patients experienced ADRs. A total of 425 ADRs were reported, with 311 (73.1%) occurring in men and 114 (26.8%) in women, with a significant statistical relationship (P value (P) = 0.02, OR = 1.21). Overall 239 (56.2%) ADRs were recorded among Chinese, 94 (22.1%) in Malay, and 71 (16.7%) in Indian patients, which had a statistically significant association with ADRs (P = 0.05, OR = 1.50). Out of a total 425 among ADRs, lipodystrophy was recorded in 151 (35.5%) followed by skin rashes in 80 (18.8%), anemia in 74 (17.4%), and peripheral neuropathy in 27 (6.3%) patients. These findings suggest a need of intensive monitoring of ADRs in HIV treatment centres across Malaysia.

  2. Spontaneous monitoring of adverse reactions to drugs by Italian dermatologists: a pilot study. Gruppo Italiano Studi Epidemiologici in Dermatologia.

    PubMed

    1991-01-01

    During 1988, the Gruppo Italiano Studi Epidemiologici in Dermatologia (GISED) coordinated a pilot study aimed at evaluating the feasibility of a system for spontaneous monitoring of adverse drug reactions in dermatological practice in Italy. Approximately 400 dermatologists were asked to collaborate, and 141 agreed to the study. Procedures similar to those well established in other surveillance programs (including the use of standard forms and standardized assessment procedure) were adopted. In a 2-month period 775 reports were collected, of which 711 were maintained after careful evaluation. The general profile of the adverse reactions reported was in accordance with the experience derived by other spontaneous surveillance programs. The main purpose of spontaneous reporting systems is the identification of new reactions, and a model analysis was proposed, in our study, with reference to skin reactions to bamifylline. The demonstration of the feasibility of a drug-monitoring program in Italy, where little tradition exists in the area, is the most important result of our study.

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

    PubMed Central

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

    2012-01-01

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

  4. 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

  5. [Diagnostic and therapeutic procedure for two popular but quite distinct adverse reactions to food - fructose malabsorption and histamine intolerance].

    PubMed

    Reese, I

    2012-04-01

    Claiming to suffer from adverse food reactions is popular. In contrast to the classical food allergy, there are some pathomechanisms which are evidently dose-dependent. Thus the procedure in diagnosis and therapy must undoubtedly differ from the practice when food allergy is suspected or proven. Nevertheless many patients suffering from dose-dependent adverse reactions to food are given strict elimination diets, which is neither necessary nor helpful and decreases their quality of life broadly. This holds especially true for fructose malabsorption and histamine intolerance. For the latter, the term adverse reaction to ingested histamine is preferred, because histamine intolerance implies that symptoms are caused entirely by an enzyme defect. Why this is not very likely to be the only reason is discussed in this article. Both adverse reactions require an individual approach especially with regard to nutrition therapy. Therefore the task of diagnosis should be to establish an individual profile of tolerated and not tolerated foods taking into account that tolerance can greatly vary by meal composition, frequency and individual triggering factors. In view of this, therapeutic recommendations should not be based on the absolute quantities of the eliciting substance to be eliminated but on a feasible transfer into daily life. Thereby food restriction can be minimized and a high quality of life will be maintained.

  6. Variants in CDA and ABCB1 are predictors of capecitabine-related adverse reactions in colorectal cancer

    PubMed Central

    García, María I.; García-Alfonso, Pilar; Robles, Luis; Grávalos, Cristina; González-Haba, Eva; Marta, Pellicer; Sanjurjo, María; López-Fernández, Luis A.

    2015-01-01

    Adverse reactions to capecitabine-based chemotherapy limit full administration of cytotoxic agents. Likewise, genetic variations associated with capecitabine-related adverse reactions are associated with controversial results and a low predictive value. Thus, more evidence on the role of these variations is needed. We evaluated the association between nine polymorphisms in MTHFR, CDA, TYMS, ABCB1, and ENOSF1 and adverse reactions, dose reductions, treatment delays, and overall toxicity in 239 colorectal cancer patients treated with capecitabine-based regimens. The ABCB1*1 haplotype was associated with a high risk of delay in administration or reduction in the dose of capecitabine, diarrhea, and overall toxicity. CDA rs2072671 A was associated with a high risk of overall toxicity. TYMS rs45445694 was associated with a high risk of delay in administration or reduction in the dose of capecitabine, HFS >1 and HFS >2. Finally, ENOSF1 rs2612091 was associated with HFS >1, but was a poorer predictor than TYMS rs45445694. A score based on ABCB1-CDA polymorphisms efficiently predicts patients at high risk of severe overall toxicity (PPV, 54%; sensitivity, 43%) in colorectal cancer patients treated with regimens containing capecitabine. Polymorphisms in ABCB1, CDA, ENOSF1,and TYMS could help to predict specific and overall severe adverse reactions to capecitabine. PMID:25691056

  7. Do Longer Intervals between Challenges Reduce the Risk of Adverse Reactions in Oral Wheat Challenges?

    PubMed Central

    Yanagida, Noriyuki; Imai, Takanori; Sato, Sakura; Ebisawa, Motohiro

    2015-01-01

    Background The use of oral food challenges (OFCs) in clinics is limited because they are complicated and associated with anaphylactic symptoms. To increase their use, it is necessary to develop novel, effective, and safe methods. However, the effectiveness of different OFCs has not been compared. Objective To investigate the effect of ingestion methods on wheat allergy symptoms and treatment during OFCs. Method Without changing the total challenge dose, we changed the administration method from a 5-installment dose titration every 15 min (15-min interval method) to 3 installments every 30 min (30-min interval method). We retrospectively reviewed and compared the results of 65 positive 15-min interval wheat challenge tests conducted between July 2005 and February 2008 and 87 positive 30-min interval tests conducted between March 2008 and December 2009. Results A history of immediate symptoms was more common for the 30-min interval method; however, no difference between methods was observed in other background parameters. Switching from the 15-min to the 30-min interval method did not increase symptoms or require treatment. The rate of cardiovascular symptoms (p = 0.032), and adrenaline use (p = 0.017) was significantly lower with the 30-min interval method. The results did not change after adjusting for the effects of immediate symptom history in multivariate analysis. Conclusion This study suggests that the 30-min interval method reduces the risk of adverse events, compared to the 15-min interval method. PMID:26624006

  8. Harmonising adverse drug reaction terminology: the role of the Council for International Organizations of Medical Sciences.

    PubMed

    Venulet, J; Bankowski, Z

    1998-09-01

    Health professionals from different countries are known to differ considerably in their use of medical terminology, including the terminology used for adverse drug reactions (ADRs) and in the exact meanings attributed to terms. To remedy this situation, the Council for International Organizations of Medical Sciences (CIOMS) has attempted to provide definitions and basic requirements for proper use of ADR terms. The work has concentrated on terms liable to be misinterpreted and those used for serious and frequently reported ADRs. For every selected term a short monograph has been prepared. It consists of a preamble, definition, basic requirements for use of the term and additional comments, if any. In cooperation with medical experts, drug regulators and the pharmaceutical industry, 13 papers have been published so far. Approximately 160 terms have been defined and work on another 50 terms continues. The full collection of monographs will eventually appear in the form of a book and CD-ROM intended to help doctors fill in case reports, and regulatory agencies and the pharmaceutical industry assess reports. Pharmaceutical companies receive numerous reports of suspected ADRs from medical practitioners and other prescribing professionals. Each company is required to transmit these reports to the drug regulatory agency of the country, or countries, in which the drug is used. Therefore, in addition to receiving the correct name of the ADR, collecting and evaluating centres, regardless of whether they are part of a regulatory agency or a pharmaceutical company, need to be provided with sufficient supporting data to be convinced that what is reported was what was actually observed, and that the ADR term used represents the observed event.

  9. IgE reactivity to hen egg white allergens in dogs with cutaneous adverse food reactions.

    PubMed

    Shimakura, Hidekatsu; Uchiyama, Jumpei; Saito, Taku; Miyaji, Kazuki; Fujimura, Masato; Masuda, Kenichi; Okamoto, Noriaki; DeBoer, Douglas J; Sakaguchi, Masahiro

    2016-09-01

    Dogs with cutaneous adverse food reactions (CAFR) often have specific IgE to food allergens. Egg white, which is majorly composed of ovomucoid, ovalbumin, ovotransferrin, and lysozyme, is a food allergen in dogs. Information of the IgE reactivity to purified egg white allergens supports accurate diagnosis and efficiency treatment in humans. However, to the best of our knowledge, there have been no studies on the IgE reactivity to purified egg white allergens in dogs. Here, we investigated the IgE reactivity to crude and purified allergens of hen egg white in dogs with CAFR. First, when we examined serum samples from 82 dogs with CAFR for specific IgE to crude egg white by ELISA, 9.8% (8/82) of the dogs with CAFR showed the IgE reactivity to crude egg white. We then used sera from the eight dogs with positive IgE reactivity to crude egg white to examine the IgE reactivity to four purified allergens, ovomucoid, ovalbumin, ovotransferrin, and lysozyme, by ELISA. We found that 75% (6/8) of the dogs showed IgE reactivity to both ovomucoid and ovalbumin, and that 37.5% (3/8) of the dogs showed IgE reactivity to ovotransferrin. None (0/8) showed IgE reactivity to lysozyme. Moreover, validating these results, the immunoblot analyses were performed using the sera of the three dogs showing the highest IgE reactivity to crude egg white. Both anti-ovomucoid and anti-ovalbumin IgE were detected in the sera of these dogs, while anti-ovotransferrin IgE was not detected. Considering these, ovomucoid and ovalbumin appears to be the major egg white allergens in dogs with CAFR. PMID:27436445

  10. [The history of adverse drug reactions, relief for these health damage and safety measures in Japan].

    PubMed

    Takahashi, Haruo

    2009-01-01

    The first remarkable adverse drug reaction (ADR) reported in Japan was anaphylactic shock caused by penicillin. Although intradermal testing for antibiotics had been exercised as prediction method of anaphylactic shock for a long time, it was discontinued in 2004 because of no evidence for prediction. The malformation of limbs, etc. caused by thalidomide was a global problem, and thalidomide was withdrawn from the market. Teratogenicity testing during new drug development has been implemented since 1963. Chinoform (clioquinol)-iron chelate was detected from green tongue and green urine in patients with subacute myelo-optic neuropathy (SMON) and identified as a causal material of SMON in 1970. Chinoform was withdrawn from the market, and a fund for relief the health damage caused by ADR was established in 1979. The co-administration of sorivudine and fluorouracil anticancer agents induced fatal agranulocytosis, and sorivudine was withdrawn from the market after being on sale for one month in 1993. The guidelines for package inserts were corrected with this opportunity, and early phase pharmacovigilance of new drugs was introduced later. Since acquired immune deficiency syndrome, and hepatitis B and C were driven by virus-infected blood products, the Ministry of Health, Labor and Welfare tightened regulations regarding biological products in 2003, and a fund for relief of health damage caused by infections driven from biological products was established in 2004. The other remarkable ADRs were quadriceps contracture induced by the repeated administration of muscular injection products and Creutzfeldt-Jakob disease caused by the transplantation of human dry cranial dura matter, etc. The significance of safety measures for drugs based on experiences related to ADRs is worthy of notice. New drugs are approved based on a benefit-risk assessment, if the expected therapeutic benefits outweigh the possible risks associated with treatment. Since unexpected, rare and serious

  11. A prospective study of adverse drug reactions as a cause of admission to a paediatric hospital

    PubMed Central

    MARTÍNEZ-MIR, I.; GARCÍA-LÓPEZ, M.; PALOP, V.; FERRER, J. M.; ESTAÑ, L.; RUBIO, E.; MORALES-OLIVAS, F. J.

    1996-01-01

    1A total of 512 consecutive paediatric hospital admissions of children 2 years old or less were evaluated to assess the extent and pattern of admission caused by suspected adverse drug reactions (ADRs). The proportion of suspected ADRs related to hospital admissions was 4.3%. 2The organ-systems most commonly implicated were the central nervous system (40.5%), digestive system (16.7%), and skin and appendages (14.3%). Together, they accounted for 71.5% of admissions attributed to ADRs. The most common clinical manifestations inducing admission were convulsions (4 cases), dizziness (4), vomiting (3), and tremor, fever, itching and apnoea (2 cases each). 3The four classes of drugs most frequently suspected in admissions due to ADRs were respiratory drugs (35%), anti-infective agents (25%), drugs active on the central nervous system (15%) and drugs used in dermatology (10%). The most common drugs related to ADRs were a combination of chlorpheniramine, diphenhydramine, phenylephrine, guaiphenesin and salicylic acid (4 cases), followed by fenoterol, adrenaline, paracetamol, DTP vaccine and antipolio vaccine (2 cases each). 4There were no significant differences between children older and younger than 1 year (odds ratio 0.89; 95% CI 0.37–2.17) or between the sexes as regards hospital admittance due to suspected ADRs (odds ratio 1.94; 95% CI 0.72–5.42). 5The results of this kind of study may be influenced by patterns of drug utilization. Nevertheless, the lack of specific studies of drug effects in young children makes it desirable to carry out pharmacoepidemiological studies in this age group. PMID:8877022

  12. 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

  13. [Bleeding gastric ulcers and acute hepatitis: 2 simultaneous adverse reactions due to nimesulide in a case].

    PubMed

    Tejos, S; Torrejón, N; Reyes, H; Meneses, M

    2000-12-01

    A 66 year-old obese woman with arthrosis, self-medicated with oral nimesulide, 200 mg daily. After 6 weeks she developed nausea, jaundice and dark urine. Two weeks later she had recurrent hematemesis and was hospitalized. Besides obesity and anemia her physical examination was unremarkable. An upper GI endoscopy revealed 3 acute gastric ulcers and a 4th one in the pyloric channel. Abdominal ultrasonogram showed a slightly enlarged liver with diffuse reduction in ecogenicity; the gallbladder and biliary tract were normal. Blood tests demonstrated a conjugated hyperbilirubinemia (maximal total value: 18.4 mg/dl), ALAT 960 U/l, ASAT 850 U/l, GGT 420 U/l, alkaline phosphatases mildly elevated, pro-time 49% and albumin 2.7 mg/dl. Serum markers for hepatitis A, B and C viruses were negative. ANA, AMA, anti-SmA, were negative. Ceruloplasmin was normal. A liver biopsy showed bridging necrosis and other signs of acute toxic liver damage. Gastric ulcers healed after conventional treatment and hepatitis subsided after 2 months leaving no signs of chronic liver damage. The diagnosis of toxic hepatitis due to nimesulide was supported by the time-course of drug usage, sex, age, absence of other causes of liver disease, a compatible liver biopsy and the improvement after drug withdrawal. Peptic ulcers or toxic hepatitis have been previously described as independent adverse reactions in patients taking nimesulide or other NSAIDs but their simultaneous occurrence in a single patient is a unique event that deserves to be reported.

  14. Drugs and adverse reactions: an economic view of a medical problem.

    PubMed

    Pedroni, G

    1984-01-01

    This monograph attempts to show how patient, physician and drug producer should assess the value and risks of a drug from the economic point of view. The value of a drug lies in its efficacy against disease and pain; the risks are the various side effects. A hypothetical example illustrates the evaluation from the point of view of an individual patient. A distinction must be made here between diseases which may prove fatal and those of a less serious nature. This means that a distinction must also be made in evaluating the risks attached to a drug and the individual attitude to side effects. For the physician, the task of recognizing an adverse drug reaction (ADR) is an extremely complex one. A 11-step flow chart for decision making is presented as a benchmark procedure. Several empirical studies on the incidence of ADRs in ambulatory and hospitalized patients are shown to use shortcuts, which are entirely justified in daily medical practice, but questionable in a scientific analysis. For various reasons the drug manufacturer too is anxious to recognize ADRs at an early stage and to avoid them whenever possible. Prolonged clinical trials, however, produce a steep rise in costs and delay the launching of the product, while the additional information obtained is not always comprehensive and exhaustive. Moreover, the mere fact of recognizing an ADR does not mean that it can be prevented. The producer is therefore forced to consider the risks and costs involved in speeding up or delaying the introduction of a product. The fact that the drug has been approved for sale does not automatically release introduction of a product. The fact that the drug has been approved for sale does not automatically release him from the obligation to carry out further intensive monitoring for the entire period that it is on the market.

  15. [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.

  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. Attitude of nurses and pharmacists on adverse drug reactions reporting in selected hospitals in Sokoto, Northwest Nigeria

    PubMed Central

    Umar, Muhammad Tukur; Bello, Shaibu Oricha; Chika, Aminu; Oche, Oche Mansur

    2016-01-01

    Objective: Objective of this study was to assess the attitude of nurses and pharmacists towards adverse drug reactions (ADRs) reporting. Methods: The questionnaire was designed based on extended “Inman seven deadly sins.” Two hundred and seventy-two respondents were selected by stratified sampling technique. The questionnaires were delivered to the respondents at their places of practice. The data generated were analyzed by Sigma XL Software Inc. Findings: There was no statistically significant relationship between demographic profiles and reporting attitude except for qualification. On extended “Inman seven deadly sins” awareness of reporting protocol and nearby center for ADRs reporting were low 27.3 and 7.5%, respectively. However, respondents’ score on components of attitude of ADRs reporting is generally encouraging. On comparative basis, no statistical significance exists between pharmacists and nurses. Conclusion: The study showed that attitude of respondents towards ADRs reporting is good. However, there is a need for targeted health education intervention among these cadres of health-care professionals, especially on aspects of awareness of reporting protocol and reporting center. PMID:27512716

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

    PubMed Central

    Rodrigues, Maria Cristina Soares; de Oliveira, Cesar

    2016-01-01

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

  19. Pharmacovigilance from social media: mining adverse drug reaction mentions using sequence labeling with word embedding cluster features

    PubMed Central

    Sarker, Abeed; O’Connor, Karen; Ginn, Rachel

    2015-01-01

    Objective Social media is becoming increasingly popular as a platform for sharing personal health-related information. This information can be utilized for public health monitoring tasks, particularly for pharmacovigilance, via the use of natural language processing (NLP) techniques. However, the language in social media is highly informal, and user-expressed medical concepts are often nontechnical, descriptive, and challenging to extract. There has been limited progress in addressing these challenges, and thus far, advanced machine learning-based NLP techniques have been underutilized. Our objective is to design a machine learning-based approach to extract mentions of adverse drug reactions (ADRs) from highly informal text in social media. Methods We introduce ADRMine, a machine learning-based concept extraction system that uses conditional random fields (CRFs). ADRMine utilizes a variety of features, including a novel feature for modeling words’ semantic similarities. The similarities are modeled by clustering words based on unsupervised, pretrained word representation vectors (embeddings) generated from unlabeled user posts in social media using a deep learning technique. Results ADRMine outperforms several strong baseline systems in the ADR extraction task by achieving an F-measure of 0.82. Feature analysis demonstrates that the proposed word cluster features significantly improve extraction performance. Conclusion It is possible to extract complex medical concepts, with relatively high performance, from informal, user-generated content. Our approach is particularly scalable, suitable for social media mining, as it relies on large volumes of unlabeled data, thus diminishing the need for large, annotated training data sets. PMID:25755127

  20. Cross-sectional study exploring barriers to adverse drug reactions reporting in community pharmacy settings in Dhaka, Bangladesh

    PubMed Central

    Amin, Mohammad Nurul; Khan, Tahir Mehmood; Dewan, Syed Masudur Rahman; Islam, Mohammad Safiqul; Moghal, Mizanur Rahman

    2016-01-01

    Objectives To assess community pharmacists'/pharmacy technicians' knowledge and perceptions about adverse drug reactions (ADRs) and barriers towards the reporting of such reactions in Dhaka, Bangladesh. Method A cross-sectional study was planned to approach potential respondents for the study. A self-administered questionnaire was delivered to community pharmacists/pharmacy technicians (N=292) practising in Dhaka, Bangladesh. Results The overall response to the survey was 69.5% (n=203). The majority of the sample was comprised of pharmacy technicians (152, 74.9%) who possessed a diploma in pharmacy, followed by pharmacists (37, 18.2%) and others (12, 5.9%). Overall, 72 (35.5%) of the respondents disclosed that they had experienced an ADR at their pharmacy, yet more than half (105, 51.7%) were not familiar with the existence of an ADR reporting body in Bangladesh. Exploring the barriers to the reporting of ADRs, it was revealed that the top four barriers to ADR reporting were ‘I do not know how to report (Relative Importance Index (RII)=0.998)’, ‘reporting forms are not available (0.996)’, ‘I am not motivated to report (0.997)’ and ‘Unavailability of professional environment to discuss about ADR (RII=0.939)’. In addition to these, a majority (141, 69.46%) were not confident about the classification of ADRs (RII=0.889) and were afraid of legal liabilities associated with reporting ADRs (RII=0.806). Moreover, a lack of knowledge about pharmacotherapy and the detection of ADRs was another major factor hindering their reporting (RII=0.731). Conclusions The Directorate of Drug Administration in Bangladesh needs to consider the results of this study to help it improve and simplify ADR reporting in Bangladeshi community pharmacy settings. PMID:27489151

  1. Drug therapy and adverse drug reactions to terbutaline in obstetric patients: a prospective cohort study in hospitalized women.

    PubMed

    Hernández-Hernández, Dulce; Vargas-Rivera, María; Nava-Ocampo, Alejandro A; Palma-Aguirre, José; Sumano-López, Héctor

    2002-04-01

    BACKGROUND: Adverse drug reactions (ADR's) could be expected more frequently in pregnant women. This study was performed in order to identify ADR's to tocolytic drugs in hospitalised pregnant women. METHODS: A prospective cohort study was performed in two General Hospitals of the Instituto Mexicano del Seguro Social (IMSS) in Mexico City. Two hundred and seven women undergoing labor, premature labor, threatened abortion or suffering any obstetric related disease were included. Drug prescription and signs and symptoms of any potential ADR were registered daily during the hospital stay. Any potential ADR to tocolytic drugs was evaluated and classified by three of the authors using the Kramer's algorithm. RESULTS: Of the 207 patients, an ADR was positively classified in 25 cases (12.1%, CI95% 8.1 to 17.5%). All ADR's were classified as minor reactions. Grouping patients with diagnosis of threatened abortion, premature labor or under labor (n= 114), 24 ADR's were related to terbutaline, accounting for a rate of 21.1 ADR's per 100 obstetric patients. Obstetric patients suffering an ADR were older than obstetric patients without any ADR. However, the former received less drugs/day x patient-1 and had a shorter hospital stay (p < 0.05) whereas the dose of terbutaline was similar between the two groups. Terbutaline inhibited uterine motility in women with and without any ADR at a similar rate, 70 and 76% respectively (x2 = 0.07; p = 0.8). CONCLUSION: Terbutaline, used as a tocolytic drug, was related to a high frequency of minor ADRs and to a high rate of effcicacy. PMID:11934352

  2. Implementation and evaluation of adverse drug reaction monitoring system in a tertiary care teaching hospital in Mumbai, India.

    PubMed

    Patidar, Dindayal; Rajput, Mithun S; Nirmal, Nilesh P; Savitri, Wenny

    2013-03-01

    Adverse drug reactions (ADR) are a significant cause of morbidity and mortality, often identified only post-marketingly. Improvement in current ADR reporting, including utility of underused or innovative methods, is crucial to improve patient safety and public health. Hospital-based monitoring is one of the methods used to collect data about drug prescriptions and adverse events. The aims of this study were to identify the most frequent ADRs recognized by the attending physicians, study their nature, and to target these ADRs in order to take future preventive measures. A prospective study was conducted over a 7-month period in an internal medicine department using stimulated spontaneous reporting for identifying ADRs. Out of the 254 admissions, 32 ADRs in 37 patients (14.56%) were validated from the total of 36 suspected ADRs in 41 patients. Female predominance was noted over males in case of ADRs. Fifty percent of total ADRs occurred due to multiple drug therapy. Dermatological ADRs were found to be the most frequent (68.75%), followed by respiratory, central nervous system and gastrointestinal ADRs. The drugs most frequently involved were antibiotics, anti-tubercular agents, antigout agents, and NSAIDs. The most commonly reported reactions were itching and rashes. Out of the 32 reported ADRs, 50% of the reactions were probable, 46.87% of the reactions were possible and 3.12% of the reactions were definite. The severity assessment done by using the Hartwig and Seigel scale indicated that the majority of ADRs were 'Mild' followed by 'Moderate' and 'Severe' reactions, respectively. Out of all, 75% of ADRs were recovered. The most potent management of ADRs was found to be drug withdrawal. Our study indicated that hospital based monitoring was a good method to detect links between drug exposure and adverse drug reactions. Adequate training regarding pharmacology and optimization of drug therapy might be helpful to reduce ADR morbidity and mortality. PMID:24170978

  3. Adverse reactions of Achilles tendon xanthomas in three hypercholesterolemic patients after treatment intensification with niacin and bile acid sequestrants.

    PubMed

    Lakey, Wanda C; Greyshock, Nicole; Guyton, John R

    2013-01-01

    Multiple cholesterol-reducing therapies have been shown to induce the regression of tendon xanthoma in patients with familial hypercholesterolemia. We present 3 cases of adverse reactions in Achilles tendon xanthomas after the addition of niacin and bile acid sequestrants to ongoing statin therapy. Reduction in tendon dimensions and marked softening of xanthomas were interpreted as cholesterol removal from heavily infiltrated tissue sites. In 2 cases, changes in the xanthomas occurred despite only minor lipoprotein improvements, raising the possibility of direct drug effects in cholesterol-infiltrated tissue. Intriguingly, recent studies have described niacin receptor-mediated effects in macrophages. In summary, although adverse reactions in Achilles tendon xanthomas appear to be infrequent, clinicians should be aware of this phenomenon in their patients after intensifying lipid treatments, especially with the use of niacin in patients with familial hypercholesterolemia. Xanthoma responses may provide clues to new pharmacologic effects in cholesterol-infiltrated tissues.

  4. Pre-Vaccination Care-Seeking in Females Reporting Severe Adverse Reactions to HPV Vaccine. A Registry Based Case-Control Study

    PubMed Central

    Hansen, Niels Dalum; Valentiner-Branth, Palle

    2016-01-01

    .2–1.9). Conclusion Before receiving the first HPV vaccination, females who suspected adverse reactions has symptoms and a health care-seeking pattern that is different from the matched population. Pre-vaccination morbidity should be taken into account in the evaluation of vaccine safety signals. PMID:27611088

  5. A positive response to an adverse reaction. Diagnosis and management of food intolerance in children.

    PubMed

    Holmes, S

    1993-04-01

    1. Food intolerance is a reproducible abnormal reaction to food or food components which is not psychologically based. 2. It is straightforward to identify immediate hypersensitivity, but delayed reactions (4-27 hours) are more difficult. 3. The main foods causing reactions are wheat, milk, chicken, eggs, fish and shellfish, but any food can cause a reaction in a sensitised individual. 4. The solution to the problem relies on identification of the causative food(s) and its total elimination from the diet.

  6. Identifying and managing an adverse food reaction in a polar bear (Ursus maritimus) by an elimination diet trial.

    PubMed

    Monson, Sara; Minter, Larry J; Krouse, Marissa; De Voe, Ryan S

    2014-06-01

    A 16-yr-old polar bear (Ursus maritimus) presented with severe diarrhea shortly following transfer to the North Carolina Zoological Park. Multiple diagnostic procedures were performed over several months and the cause of the chronic diarrhea was inconclusive. Histologically, colonic mucosal biopsies were consistent with severe chronic eosinophilic and lymphoplasmacytic colitis with no evidence of etiologic agents present. A dietary elimination trial was conducted and an adverse food reaction to the dog chow in the diet was confirmed. PMID:25000711

  7. Identifying and managing an adverse food reaction in a polar bear (Ursus maritimus) by an elimination diet trial.

    PubMed

    Monson, Sara; Minter, Larry J; Krouse, Marissa; De Voe, Ryan S

    2014-06-01

    A 16-yr-old polar bear (Ursus maritimus) presented with severe diarrhea shortly following transfer to the North Carolina Zoological Park. Multiple diagnostic procedures were performed over several months and the cause of the chronic diarrhea was inconclusive. Histologically, colonic mucosal biopsies were consistent with severe chronic eosinophilic and lymphoplasmacytic colitis with no evidence of etiologic agents present. A dietary elimination trial was conducted and an adverse food reaction to the dog chow in the diet was confirmed.

  8. A Retrospective Analysis of Reporting of Adverse Drug Reactions in a Tertiary Care Teaching Hospital: One Year Survey

    PubMed Central

    Pathak, Anuj Kumar; Dokania, Shambhu; Mohan, Lalit; Dikshit, Harihar

    2016-01-01

    Introduction Pharmacovigilance (PV) is related to detection, assessment, understanding and prevention of Adverse Drug Reactions (ADRs) which are incurred when drug is made available in the market and used in different physiological conditions. In many countries, ADRs ranks among the top ten leading cause of morbidity and mortality. There is a lack of formal culture for monitoring and reporting of ADRs in India, with ADR reporting rate being only 1% as compared to 5% in world. This type of academic detailing activity helps to create awareness of ADR reporting in the institutions. Aim This study was planned to evaluate and analyse the incidence and patterns of ADRs in various inpatient and outpatient departments of hospital. Materials and Methods This was an observational, retrospective and record based study conducted by analysing the spontaneous ADR forms, collected over a period of 12 months (September 2014 to August 2015) at Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India. Results During the period of one year, 292 ADR forms were collected from 4,34,965 patients attending OPD and inpatients of the hospital. Incidence of ADR was 0.67 per thousand patients and average of around 24 ADR collected per month. Male:Female ratio was 1.30. Adolescent (16-30 yr) was the most common age group affected. Department of Skin and VD reported the maximum number of ADRs (33.22%), followed by the Departments of Oncology (18.84%). Antibiotics were the most common drug implicated followed by anticancer drugs. Conclusion ADR reporting is an ongoing and continuous process. Studies from the institute helps to identify and rectify the problems related to ADR reporting. Pitfalls can be addressed by creating awareness among physicians and the patients to achieve finally the goal of Pharmacovigilant India. PMID:27656459

  9. [Preliminary study on general safe medication regularity of Chinese patent orthopedic medicines based on adverse reaction/event literature analysis].

    PubMed

    Wang, Yu-guang; Shi, Xin-yuan; Jin, Rui; Li, Hong-yan; Kong, Xiang-wen; Qiao, Yan-jiang

    2015-03-01

    Chinese patent orthopedic medicines feature complex components, mainly including desperate and toxic herbal pieces, narrow safety window, more clinical contraindications and frequent adverse drug reaction/events (ADR/ADE). To study the general safe medication regularity of Chinese patent orthopedic medicines, define key points in the medication education and ensure rational clinical medication, the authors took 80 types of commonly used Chinese patent orthopedic medicines as the study objects, collect 237 cases from 164 ADR/ADE documents through a system retrieval strategy, make a multidimensional literature analysis to determine the common risk factors for safe and rational medication of Chinese patent orthopedic medicines and establish an ADR/ADE prevention regularity. First, in the aspect of clinical symptoms, skin allergy is the most common ADR/ADE and closely related to the toxic ingredients, particularly accumulated liver or kidney damage caused by some drugs. Second, there are three time nodes in the ADR/ADE occurrence; The ADR/ADE occurred in 30 minutes is closely related to the idiosyncrasy; the ADR/ADE occurred between several months and half a year is related to the drug-induced liver and kidney damages; The most common ADR/ADE was observed within 7 days and predictable according to the pharmacological actions; Third, toxicity is an important factor in the occurrence of ADR/ADE of Chinese patent orthopedic medicines. Fourth, emphasis shall be given to the special medication factors, such as the combination with western medicines and Chinese herbal decoctions, overdose and long-course medication and self-medical therapy. In conclusion, the general ADR/ADE prevention regularity for Chinese patent orthopedic medicines was summarized to provide supports for clinicians in safe and rational medication and give the guidance for pharmacist in medication education.

  10. Monitoring of adverse drug reactions in psychiatry outpatient department of a Secondary Care Hospital of Ras Al Khaimah, UAE

    PubMed Central

    Sridhar, Sathvik Belagodu; Al-Thamer, Sura Saad Faris; Jabbar, Riadh

    2016-01-01

    Background: Adverse drug reactions (ADRs) are a significant cause of morbidity and mortality, resulting in increased healthcare cost. Association of psychotropic medications with ADRs is common. Pharmacovigilance can play a vital role in alerting the healthcare providers from the possible ADRs and thus protecting the patients receiving psychotropic medications. Aim: To monitor and report the incidence and nature of ADRs in psychiatry outpatient department (OPD). Materials and Methods: A prospective observational study was carried out in the psychiatry OPD. All the patients attending psychiatry outpatient and satisfying the inclusion criteria were monitored for ADRs. The causality, severity and preventability assessment of documented ADRs was done. Chi-square test was done to identify the association between ADRs and sociodemographic, disease and treatment-related variables. Paired Student's t-test was carried out to compare the significance difference in the weight of the patients who reported weight gain to psychotropic medications. Results: The incidence rate of ADR was found to be 10.2%. A total of 112 ADRs were documented. Weight gain 18 (16.07%) followed by somnolence 8 (7.14%) was the most commonly reported ADR. Atypical antipsychotics 37 (33.0%) were the most common class of psychotropic drugs implicated in ADRs. Escitalopram 16 (14.28%) followed by quetiapine 14 (12.5%) were associated with a maximum number of ADRs. No significant association (P > 0.05) documented between demographic and treatment-related variables with number of ADRs. Conclusion: Study revealed a moderate incidence of ADRs in patients attending the psychiatry OPD. Majority of the ADRs reported during the study were mild in nature and not preventable type. PMID:27330260

  11. Mortality from adverse drug reactions in adult medical inpatients at four hospitals in South Africa: a cross-sectional survey

    PubMed Central

    Mouton, Johannes P; Mehta, Ushma; Parrish, Andy G; Wilson, Douglas P K; Stewart, Annemie; Njuguna, Christine W; Kramer, Nicole; Maartens, Gary; Blockman, Marc; Cohen, Karen

    2015-01-01

    Aims Fatal adverse drug reactions (ADRs) are important causes of death, but data from resource-limited settings are scarce. We determined the proportion of deaths in South African medical inpatients attributable to ADRs, and their preventability, stratified by human immunodeficiency virus (HIV) status. Methods We reviewed the folders of all patients who died over a 30 day period in the medical wards of four hospitals. We identified ADR-related deaths (deaths where an ADR was ‘possible’, ‘probable’ or ‘certain’ using WHO-UMC criteria and where the ADR contributed to death). We determined preventability according to previously published criteria. Results ADRs contributed to the death of 2.9% of medical admissions and 56 of 357 deaths (16%) were ADR-related. Tenofovir, rifampicin and co-trimoxazole were the most commonly implicated drugs. 43% of ADRs were considered preventable. The following factors were independently associated with ADR-related death: HIV-infected patients on antiretroviral therapy (adjusted odds ratio (aOR) 4.4, 95% confidence interval (CI) 1.6, 12), exposure to more than seven drugs (aOR 2.5, 95% CI 1.3, 4.8) and increasing comorbidity score (aOR 1.3, 95% CI 1.1, 1.7). Conclusions In our setting, where HIV and tuberculosis are highly prevalent, fatal in-hospital ADRs were more common than reported in high income settings. Most deaths were attributed to drugs used in managing HIV and tuberculosis. A large proportion of the ADRs were preventable, highlighting the need to strengthen systems for health care worker training and support. PMID:25475751

  12. A method for controlling complex confounding effects in the detection of adverse drug reactions using electronic health records

    PubMed Central

    Li, Ying; Salmasian, Hojjat; Vilar, Santiago; Chase, Herbert; Friedman, Carol; Wei, Ying

    2014-01-01

    Objective Electronic health records (EHRs) contain information to detect adverse drug reactions (ADRs), as they contain comprehensive clinical information. A major challenge of using comprehensive information involves confounding. We propose a novel data-driven method to identify ADR signals accurately by adjusting for confounders. Materials and methods We focused on two serious ADRs, rhabdomyolysis and pancreatitis, and used information in 264 155 unique patient records. We identified an ADR using established criteria, selected potential confounders, and then used penalized logistic regressions to estimate confounder-adjusted ADR associations. A reference standard was created to evaluate and compare the precision of the proposed method and four others. Results Precision was 83.3% for rhabdomyolysis and 60.8% for pancreatitis when using the proposed method, and we identified several drug safety signals that are interesting for further clinical review. Discussion The proposed method effectively estimated ADR associations after adjusting for confounders. A main cause of error was probably due to the nature of the dataset in that a substantial number of patients had a single visit only and, therefore, it was not possible to determine correctly the appropriate sequence of events for them. It is likely that performance will be improved with use of EHR data that contain more longitudinal records. Conclusions This data-driven method is effective in controlling for confounding, resulting in either a higher or similar precision when compared with four comparators, has the unique ability to provide insight into confounders for each specific medication–ADR pair, and can be easily adapted to other EHR systems. PMID:23907285

  13. Implant based differences in adverse local tissue reaction in failed total hip arthroplasties: a morphological and immunohistochemical study

    PubMed Central

    2014-01-01

    Background Adverse local tissue reaction (ALTR) is characterized by periprosthetic soft tissue inflammation composed of a mixed inflammatory cell infiltrate, extensive soft tissue necrosis, and vascular changes. Multiple hip implant classes have been reported to result in ALTR, and clinical differences may represent variation in the soft tissue response at the cellular and tissue levels. The purpose of this study was to describe similarities and differences in periprosthetic tissue structure, organization, and cellular composition by conventional histology and immunohistochemistry in ALTR resulting from two common total hip arthroplasty (THA) implant classes. Methods Consecutive patients presenting with ALTR from two major hip implant classes (N = 54 patients with Dual-Modular Neck implant; N = 14 patients with Metal-on-Metal implant) were identified from our prospective Osteolysis Tissue Database and Repository. Clinical characteristics including age, sex, BMI, length of implantation, and serum metal ion levels were recorded. Retrieved synovial tissue morphology was graded using light microscopy and cellular composition was assessed using immunohistochemistry. Results Length of implantation was shorter in the DMN group versus MoM THA group (21.3 [8.4] months versus 43.6 [13.8] months respectively; p < 0.005) suggesting differences in implant performance. Morphologic examination revealed a common spectrum of neo-synovial proliferation and necrosis in both groups. Macrophages were more commonly present in diffuse sheets (Grade 3) in the MoM relative to DMN group (p = 0.016). Perivascular lymphocytes with germinal centers (Grade 4) were more common in the DMN group, which trended towards significance (p = 0.066). Qualitative differences in corrosion product morphology were seen between the two groups. Immunohistochemistry showed features of a CD4 and GATA-3 rich lymphocyte reaction in both implants, with increased ratios of perivascular T

  14. Two cases of overlap severe cutaneous adverse reactions to benznidazole treatment for asymptomatic Chagas disease in a nonendemic country.

    PubMed

    González-Ramos, J; Noguera-Morel, L; Tong, H Y; Ramírez, E; Ruiz-Bravo, E; Bellón, T; Cabañas, R; Cachafeiro, L; Herranz-Pinto, P

    2016-09-01

    Chagas disease is a parasitosis endemic to South America. It is normally treated with benznidazole as first choice, which has been associated with numerous cutaneous reactions. However, very few benznidazole-associated severe cutaneous adverse reactions have been reported to date. The rise of Chagas disease in nonendemic countries represents a growing public health challenge. We report two patients who met the criteria for drug reaction with eosinophilia and systemic symptoms syndrome and Stevens-Johnson syndrome/toxic epidermal necrolysis according to the RegiSCAR scoring systems. They were thus deemed overlapping cases, with a lymphocyte transformation test positive for benznidazole. Both required intensive care unit admission and both survived. Considering the rising application of this drug for trypanosomiasis in immigrant populations, clinicians should be aware of this newly reported, potentially life-threatening risk. PMID:26851874

  15. Oral Adverse Reactions Caused by Over-the-Counter Oral Agents

    PubMed Central

    Andabak Rogulj, Ana; Vidovic Juras, Danica; Gabric, Dragana; Vrdoljak, Danko Velimir

    2015-01-01

    Over-the-counter products rarely cause unwanted reactions in the oral cavity. Oral reactions to these agents are not specific and might present with various clinical oral findings. Detailed medical history is a key to the proper diagnosis of these lesions and fortunately other diagnostic procedures are rarely needed. Lesions are usually managed with elimination of the offending agent and with topical steroids. In more severe cases systemic steroids should be applied. PMID:25883811

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

    PubMed

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

    2016-04-01

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

  17. Human heterophilic antibodies against equine immunoglobulins: assessment of their role in the early adverse reactions to antivenom administration.

    PubMed

    León, Guillermo; Segura, Alvaro; Herrera, María; Otero, Rafael; França, Francisco Oscar de Siqueira; Barbaro, Katia Cristina; Cardoso, João Luiz Costa; Wen, Fan Hui; de Medeiros, Carlos Roberto; Prado, José Carlos Lopes; Malaque, Ceila María Sant'Ana; Lomonte, Bruno; Gutiérrez, José María

    2008-11-01

    The presence of human heterophilic antibodies against horse immunoglobulins (HHA-HI) was determined by ELISA in sera from healthy volunteers and from patients who received equine antivenom for therapy of snake bite envenoming. These patients were selected from two independent clinical studies: one in Colombia in which patients received antivenom constituted by whole IgG (n=25); and the other in Brazil where an antivenom constituted by F(ab')(2) fragments was administered (n=31). Results show that healthy volunteers have antibodies, mainly of the IgG class, able to react with whole equine IgG. Additionally, patients have IgG antibodies that react both with whole equine IgG and F(ab')(2) fragments. In both clinical studies, no significant differences were observed in the HHA-HI titres between the patients who presented early adverse (anaphylactoid) reactions and those who did not develop them. In addition, no variation in titre was observed in samples collected before and after antivenom administration. These results do not support the hypothesis that the incidence of early adverse reactions to antivenom administration correlates with the titre of HHA-HI in the serum of patients. Nevertheless, participation of these antibodies as part of a multifactorial pathogenic mechanism associated with these reactions cannot be ruled out. PMID:18561967

  18. [Analysis on the common causes for traditional Chinese medicinal injection induced adverse reactions and the preventive countermeasures].

    PubMed

    Wu, Guo-lin; Zhang, Li; Yu, Guo-you

    2008-12-01

    As a new dosage form, TCM injection is commonly used in clinical practice. But the increasing events of adverse drug reactions (ADRs) could even seriously endanger patients' lives. The causes of TCM injection inducing ADRs might be the unstable quality of preparation; the irrational clinical use and operation; the sensitive physique of patient and the change of patients' primary illness, etc. For preventing the occurrence of ADRs, based on guaranteeing the stable quality of product, putting stress on accurate usages and normalized operations in clinical practice, enhancing the monitor on ADRs and the precautionary awareness in medical units are very important. PMID:19317176

  19. Propranolol-induced gingival hyperplasia with Nager syndrome: A rare adverse drug reaction.

    PubMed

    Raheel, Syed Ahamed; Kujan, Omar Bashar; Tarakji, Bassel; Umar, Dilshad; Ibrahim, Salah

    2016-01-01

    Drug reactions are a group of reactionary lesions generally show their manifestations in the oral cavity. The drug reactions may vary from local rashes to well-developed swellings in the oral cavity especially involving the gingiva. Most of the drug reactions are asymptomatic and commonly triggered from the active metabolite of a drug used for a long time. Nager syndrome is a group of acrofacial dysostosis that usually results in craniofacial and limb malformations. The craniofacial defects are very similar to the mandibulofacial dysostosis. A very early intervention is needed for the habilitation of the patient especially when it is concerned with speech and language development. This paper reports a case of a 32-year-old female with craniofacial, limb, and skeletal abnormalities along with a drug-induced gingival hyperplasia.

  20. Propranolol-induced gingival hyperplasia with Nager syndrome: A rare adverse drug reaction

    PubMed Central

    Raheel, Syed Ahamed; Kujan, Omar Bashar; Tarakji, Bassel; Umar, Dilshad; Ibrahim, Salah

    2016-01-01

    Drug reactions are a group of reactionary lesions generally show their manifestations in the oral cavity. The drug reactions may vary from local rashes to well-developed swellings in the oral cavity especially involving the gingiva. Most of the drug reactions are asymptomatic and commonly triggered from the active metabolite of a drug used for a long time. Nager syndrome is a group of acrofacial dysostosis that usually results in craniofacial and limb malformations. The craniofacial defects are very similar to the mandibulofacial dysostosis. A very early intervention is needed for the habilitation of the patient especially when it is concerned with speech and language development. This paper reports a case of a 32-year-old female with craniofacial, limb, and skeletal abnormalities along with a drug-induced gingival hyperplasia. PMID:27144155

  1. A study of different indicators of Maillard reaction with whey proteins and different carbohydrates under adverse storage conditions.

    PubMed

    Leiva, Graciela E; Naranjo, Gabriela B; Malec, Laura S

    2017-01-15

    This study examined different indicators of each stage of Maillard reaction under adverse storage conditions in a system with whey proteins and lactose or glucose. The analysis of lysine loss by the o-phthaldialdehyde method can be considered a good indicator of the early stage, showing considerable differences in reactivity when systems with mono and disaccharides were analyzed. Capillary electrophoresis proved to be a sensitive method for evaluating the extent of glycosylation of the native proteins, providing valuable information when the loss of lysine was not significant. The estimation of the Amadori compound from the determination of total 5-hydroxymethyl-2-furfuraldehyde would have correlate well with reactive lysine content if the advanced stages of the reaction had not been reached. For assessing the occurrence of the intermediate and final stages, the measurement of free 5-hydroxymethyl-2-furfuraldehyde and color, proved not to be suitable for storage conditions.

  2. A study of different indicators of Maillard reaction with whey proteins and different carbohydrates under adverse storage conditions.

    PubMed

    Leiva, Graciela E; Naranjo, Gabriela B; Malec, Laura S

    2017-01-15

    This study examined different indicators of each stage of Maillard reaction under adverse storage conditions in a system with whey proteins and lactose or glucose. The analysis of lysine loss by the o-phthaldialdehyde method can be considered a good indicator of the early stage, showing considerable differences in reactivity when systems with mono and disaccharides were analyzed. Capillary electrophoresis proved to be a sensitive method for evaluating the extent of glycosylation of the native proteins, providing valuable information when the loss of lysine was not significant. The estimation of the Amadori compound from the determination of total 5-hydroxymethyl-2-furfuraldehyde would have correlate well with reactive lysine content if the advanced stages of the reaction had not been reached. For assessing the occurrence of the intermediate and final stages, the measurement of free 5-hydroxymethyl-2-furfuraldehyde and color, proved not to be suitable for storage conditions. PMID:27542493

  3. Dystonia as acute adverse reaction to cough suppressant in a 3-year-old girl.

    PubMed

    Polizzi, A; Incorpora, G; Ruggieri, M

    2001-01-01

    Cough suppressant preparations containing mixtures of dextromethorphan or codeine with antihistamines, decongestants (sympathomimetic), expectorants and antipyretics with either sedative or anticholinergic activity have been associated with dystonic reactions in children. We report on a 3-year-old girl who presented with episodic stiffness and abnormal posturing with rigidity after arbitrary maternal administration of a mixture of methylcodeine and extract from Hedera plant. PMID:11587381

  4. 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.

  5. Effects of moderate-dose versus high-dose trimethoprim on serum creatinine and creatinine clearance and adverse reactions.

    PubMed Central

    Naderer, O; Nafziger, A N; Bertino, J S

    1997-01-01

    The effects of a 10-day course of moderate-dose (10 mg/kg/day) or high-dose (20 mg/kg/day) trimethoprim therapy on serum creatinine, measured creatinine clearance, urinary creatinine excretion, and serum folate were studied in 20 healthy volunteers. Serum creatinine concentrations increased significantly during trimethoprim therapy, began to decrease near day 10, and returned to baseline during the washout phase at both dosage levels. At the same time, measured creatinine clearance and urine creatinine changed in the opposite direction. No clinical or statistical differences were noted between changes in the moderate- versus the high-dose phases. Serum folate concentration decreases during high-dose trimethoprim therapy were statistically significant. Adverse drug reactions in the two groups were statistically different during the first study period, with the high-dose group having a 75% incidence rate and the moderate-dose group having an 11% incidence rate (P < 0.02). Serum creatinine, measured creatinine clearance, and urinary creatinine excretion demonstrated statistically, but not clinically, significant changes during trimethoprim therapy. In addition, high-dose trimethoprim caused significantly more adverse drug reactions than moderate-dose trimethoprim in normal volunteers. PMID:9371351

  6. Factors affecting the development of adverse drug reactions to β-blockers in hospitalized cardiac patient population

    PubMed Central

    Mugoša, Snežana; Djordjević, Nataša; Djukanović, Nina; Protić, Dragana; Bukumirić, Zoran; Radosavljević, Ivan; Bošković, Aneta; Todorović, Zoran

    2016-01-01

    The aim of the present study was to undertake a study on the prevalence of cytochrome P450 2D6 (CYP2D6) poor metabolizer alleles (*3, *4, *5, and *6) on a Montenegrin population and its impact on developing adverse drug reactions (ADRs) of β-blockers in a hospitalized cardiac patient population. A prospective study was conducted in the Cardiology Center of the Clinical Center of Montenegro and included 138 patients who had received any β-blocker in their therapy. ADRs were collected using a specially designed questionnaire, based on the symptom list and any signs that could point to eventual ADRs. Data from patients’ medical charts, laboratory tests, and other available parameters were observed and combined with the data from the questionnaire. ADRs to β-blockers were observed in 15 (10.9%) patients. There was a statistically significant difference in the frequency of ADRs in relation to genetically determined enzymatic activity (P<0.001), with ADRs’ occurrence significantly correlating with slower CYP2D6 metabolism. Our study showed that the adverse reactions to β-blockers could be predicted by the length of hospitalization, CYP2D6 poor metabolizer phenotype, and the concomitant use of other CYP2D6-metabolizing drugs. Therefore, in hospitalized patients with polypharmacy CYP2D6 genotyping might be useful in detecting those at risk of ADRs. PMID:27536078

  7. Adverse local tissue reactions in metal-on-polyethylene total hip arthroplasty due to trunnion corrosion: the risk of misdiagnosis.

    PubMed

    Whitehouse, M R; Endo, M; Zachara, S; Nielsen, T O; Greidanus, N V; Masri, B A; Garbuz, D S; Duncan, C P

    2015-08-01

    Adverse reaction to wear and corrosion debris is a cause for concern in total hip arthroplasty (THA). Modular junctions are a potential source of such wear products and are associated with secondary pseudotumour formation. We present a consecutive series of 17 patients treated at our unit for this complication following metal-on-highly cross-linked polyethylene (MoP) THA. We emphasise the risk of misdiagnosis as infection, and present the aggregate laboratory results and pathological findings in this series. The clinical presentation was pain, swelling or instability. Solid, cystic and mixed soft-tissue lesions were noted on imaging and confirmed intra-operatively. Corrosion at the head-neck junction was noted in all cases. No bacteria were isolated on multiple pre- and intra-operative samples yet the mean erythrocyte sedimentation rate was 49 (9 to 100) and C-reactive protein 32 (0.6 to 106) and stromal polymorphonuclear cell counts were noted in nine cases. Adverse soft-tissue reactions can occur in MoP THA owing to corrosion products released from the head-neck junction. The diagnosis should be carefully considered when investigating pain after THA. This may avoid the misdiagnosis of periprosthetic infection with an unidentified organism and mitigate the unnecessary management of these cases with complete single- or two-stage exchange.

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

    PubMed Central

    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. Neuropharmacological evaluation of movement disorders that are adverse reactions to specific foods.

    PubMed

    Gerrard, J W; Richardson, J S; Donat, J

    1994-05-01

    Three cases are reported of patients who had episodic movement disorders triggered by foods or components of the diet. In the first patient, the movement consisted of shaking the head from side to side that was triggered by milk and a number of other foods. In the second patient, the movement consisted of a repeated shrugging of the shoulders that was triggered by egg and coffee. In the third, the movement consisted of rhythmic contractions of the arms and legs that were triggered by aspartame. The first patient agreed to participate in a study in which she drank 250 ml of skim milk, an amount sufficient to trigger head shaking, after pretreatment with drugs known to alter neurotransmission across beta-adrenergic, dopaminergic, GABAergic or purinergic synapses. At the doses used, propranolol and diazepam had no effect on the milk evoked movement disorder. Levodopa (plus carbidopa) blocked the reaction to milk. Haloperidol, salbutamol and theophylline by themselves triggered a reaction similar to that evoked by milk. These observations suggest that, in susceptible individuals, foods can trigger movement disorders through an action on dopamine and other neurotransmitter pathways in the brain. A videotape of the reactions of the first two patients is available.

  10. HLA-B*58:01 for Allopurinol-Induced Cutaneous Adverse Drug Reactions: Implication for Clinical Interpretation in Thailand

    PubMed Central

    Sukasem, Chonlaphat; Jantararoungtong, Thawinee; Kuntawong, Parnrat; Puangpetch, Apichaya; Koomdee, Napatrupron; Satapornpong, Patompong; Supapsophon, Patcharin; Klaewsongkram, Jettanong; Rerkpattanapipat, Ticha

    2016-01-01

    Background: The aim of this study was to investigate the predisposition to different types of allopurinol-induced cutaneous adverse drug reactions (CADR), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN; SJS-TEN, n = 13), drug reaction with eosinophilia and systemic symptoms (DRESS, n = 10) and Maculopapular eruption (MPE; n = 7), conferred by HLA-B*58:01 in a Thai population. Methods: This case-control association study compares 30 patients with allopurinol-induced CADR, allopurinol-tolerant control patients (n = 100), and a Thai general population (n = 1095). Patients' human leukocyte antigen type B (HLA-B) alleles were genotyped by using a two-stage sequence-specific oligonucleotide probe system. Results: Of a total 30 patients with CADR due to allopurinol, 29 (96.7%) patients were found to be at least heterozygous for HLA-B*58:01, compared to only 4.0% in allopurinol-tolerant patients (p < 0.001). Odds ratio (OR) for the association of HLA-B*58:01 with allopurinol-induced CADR in this population was 696.0 (95% CI: 74.8–6475.0). The HLA-B*58:01 allele was present in all patients with allopurinol-induced SJS-TEN (OR = 579.0, 95%CI: 29.5–11362.7, p < 0.001) and DRESS (OR 430.3, 95%CI: 22.6–8958.9, p < 0.001). Additionally, OR of HLA-B*58:01 was highly significant in the allopurinol-induced MPE patients (OR 144.0, 95%CI: 13.9–1497.0, p < 0.001). Conclusion: In this study we confirmed the association between HLAB*58:01 and allopurinol-induced SJS-TEN in a Thai population. In addition, we identified an association between HLA-B*58:01 and allopurinol-induced DRESS and MPE in this population. Therefore, HLA-B*58:01 can be used as a pharmacogenetic marker for allopurinol-induced CADR including SJS-TEN, DRESS and MPE. These results suggest that screening for HLA-B*58:01 alleles in patients who will be treated with allopurinol would be clinically helpful in preventing the risk of developing CARD in a Thai patients. Summary Regardless of

  11. 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

  12. 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

  13. Social dominance orientation predicts heterosexual men's adverse reactions to romantic rejection.

    PubMed

    Kelly, Ashleigh J; Dubbs, Shelli L; Barlow, Fiona Kate

    2015-05-01

    We examined the role of social dominance orientation (SDO) as a predictor of men's reactions to romantic rejection and attitudes toward female sexuality. In Study 1 (n = 158), we found that men who scored higher in SDO were more likely to blame women for romantic rejection, and report having responded to women's past rejection with persistence and manipulation (e.g., convincing her to "give him another chance"), as well as with aggression and threats of violence. In Study 2 (n = 398), we replicated these findings, and further found that men higher in SDO were more likely to endorse rape myths (e.g., believing that sometimes a woman's barriers need to be "broken down" in order to attain sex), and to want to lower the legal age of sexual consent in women. Two mediators explained this relationship, hostile sexism and the belief that insubordinate women need to be disciplined. Practical and theoretical implications are discussed.

  14. 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.

  15. Kava for the treatment of generalized anxiety disorder RCT: analysis of adverse reactions, liver function, addiction, and sexual effects.

    PubMed

    Sarris, J; Stough, C; Teschke, R; Wahid, Z T; Bousman, C A; Murray, G; Savage, K M; Mouatt, P; Ng, C; Schweitzer, I

    2013-11-01

    Presently, little is known about a number issues concerning kava (Piper methysticum), including (i) whether kava has any withdrawal or addictive effects; (ii) if genetic polymorphisms of the cytochrome (CYP) P450 2D6 liver enzyme moderates any potential adverse effects; and (iii) if medicinal application of kava has any negative or beneficial effect on sexual function and experience. The study design was a 6-week, double-blind, randomized controlled trial (n = 75) involving chronic administration of kava (one tablet of kava twice per day; 120 mg of kavalactones per day, titrated in non-response to two tablets of kava twice per day; 240 mg of kavalactones) or placebo for participants with generalized anxiety disorder. Results showed no significant differences across groups for liver function tests, nor were there any significant adverse reactions that could be attributed to kava. No differences in withdrawal or addiction were found between groups. Interesting, kava significantly increased female's sexual drive compared to placebo (p = 0.040) on a sub-domain of the Arizona Sexual Experience Scale (ASEX), with no negative effects seen in males. Further, it was found that there was a highly significant correlation between ASEX reduction (improved sexual function and performance) and anxiety reduction in the whole sample.

  16. 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

  17. Active surveillance of visual impairment due to adverse drug reactions: findings from a national study in the United Kingdom

    PubMed Central

    Cumberland, Phillippa M; Russell-Eggitt, Isabelle; Rahi, Jugnoo S

    2015-01-01

    As visual impairment (VI) due to adverse drug reactions (ADR) is rare in adults and children, there is an incomplete evidence base to inform guidance for screening and for counseling patients on the potential risks of medications. We report on suspected drugs and the eye conditions found in a national study of incidence of diagnosis of visual impairment due to suspected ADR. Case ascertainment was via the British Ophthalmological Surveillance Unit (BOSU), between March 2010 and February 2012, with follow-up after 6 months. Case definition: any child or adult with bilateral or unilateral visual impairment due to a suspected ADR, using distance acuity worse than Snellen 6/18 (logMAR 0.48) in the better eye (bilateral) or affected eye (unilateral). Anonymized patient information on potential cases was provided by managing ophthalmologists, comprising visual status before and after suspected ADR, ophthalmic condition attributable to the ADR, preexisting eye disease and prescribed medications at the time of the ADR. Permanency and causality of the visual impairment were confirmed by the managing clinician, after 6 months, using the WHO Uppsala Monitoring Committee criteria. Over 2 years, 36 eligible cases were reported of whom 23 had permanent VI. While most cases were due to drugs known to have adverse side-effects, some were unanticipated sporadic cases. Visual impairment due to ADRs is rare. However, with for example, increasing polypharmacy in the elderly, monitoring of ocular ADRs, although challenging, is necessary. PMID:25692024

  18. The Symmetry of Adverse Local Tissue Reactions in Patients with Bilateral Simultaneous and Sequential ASR Hip Replacement.

    PubMed

    Madanat, Rami; Hussey, Daniel K; Donahue, Gabrielle S; Potter, Hollis G; Wallace, Robert; Bragdon, Charles R; Muratoglu, Orhun K; Malchau, Henrik

    2015-10-01

    The purpose of this study was to evaluate whether patients with bilateral metal-on-metal (MoM) hip replacements have symmetric adverse local tissue reactions (ALTRs) at follow-up. An MRI of both hips was performed at a mean time of six years after surgery in 43 patients. The prevalence and severity of ALTRs were found to be similar in simultaneous hips but differences were observed in sequential hips. The order and timing of sequential hip arthroplasties did not affect the severity of ALTRs. Thus, in addition to metal ion exposure from an earlier MoM implant other factors may also play a role in the progression of ALTRs. Bilateral implants should be given special consideration in risk stratification algorithms for management of patients with MoM hip arthroplasty. PMID:26055146

  19. Cobalt to Chromium Ratio is Not a Key Marker for Adverse Local Tissue Reaction (ALTR) in Metal on Metal Hips.

    PubMed

    Fehring, Thomas K; Carter, Joshua L; Fehring, Keith A; Odum, Susan M; Griffin, William L

    2015-09-01

    The diagnosis of adverse local tissue reaction (ALTR) after metal-on-metal total hip arthroplasty (MoMTHA) presents a significant challenge. No single biomarker is specific for ALTR. The purpose of this study was to determine if the ratio of cobalt to chromium ions is useful for diagnosing ALTR in MoMTHA. In 89 bearing-related revision THAs, preoperative cobalt and chromium ion levels were compared to an intraoperative soft tissue damage grading scale. The average cobalt to chromium ratio was 2.96 (0-20). There was no correlation between the tissue scale and the cobalt to chromium ratio (R=0.095; P=0.41). Many variables affecting ion production/excretion mitigate the use of the ion ratio. The cobalt to chromium ratio is not a predictive biomarker for ALTR in MoMTHA.

  20. Intravenous administration of equine-derived whole IgG antivenom does not induce early adverse reactions in non-envenomed horses and cows.

    PubMed

    Estrada, Ricardo; Herrera, María; Segura, Alvaro; Araya, Javier; Boschini, Carlos; Gutiérrez, José María; León, Guillermo

    2010-11-01

    Administration of antivenoms to treat snakebite envenomings has the potential risk of inducing early adverse reactions. The mechanisms involved in these reactions are unclear. In this study, polyspecific antivenom consisting of whole IgG purified from equine plasma by caprylic acid precipitation was administered intravenously to non-envenomed horses (n = 47) and cows (n = 20) at a dose of 0.4 mL/kg. It has been reported that, in humans, this formulation (administered at a dose of 0.4 mL/kg) induces mild noticeable early adverse reactions, such as fever, vomiting, diarrhea, urticaria, generalized rash, tachypnea or tachycardia, in about 15-20% of the patients. Unexpectedly, none of the animals receiving antivenom in our study showed any evidence of early adverse reaction. Moreover, no late adverse reactions, i.e. serum sickness, were observed during 40 days after antivenom administration. Unlike studies performed in envenomed humans, our present results were obtained in a group of non-envenomed individuals. It is concluded that, in addition to the physicochemical characteristics of the formulation, other unknown factors must determine the occurrence of adverse reactions in snakebite envenomed humans treated with equine-derived antivenoms.

  1. 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.

  2. 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

  3. Methadone adverse reaction presenting with large increase in plasma methadone binding: a case series

    PubMed Central

    2011-01-01

    Introduction The use of methadone as an analgesic is on the increase, but it is widely recognized that the goal of predictable and reproducible dosing is confounded by considerable variability in methadone pharmacokinetics, and unpredictable side effects that include sedation, respiratory depression and cardiac arrhythmias. The mechanisms underlying these unpredictable effects are frequently unclear. Here, to the best of our knowledge we present the first report of an association between accidental methadone overexposure and increased plasma protein binding, a new potential mechanism for drug interactions with methadone. Case presentation We describe here the cases of two patients who experienced markedly different responses to the same dose of methadone during co-administration of letrozole. Both patients were post-menopausal Caucasian women who were among healthy volunteers participating in a clinical trial. Under the trial protocol both patients received 6 mg of intravenous methadone before and then after taking letrozole for seven days. One woman (aged 59) experienced symptoms consistent with opiate overexposure after the second dose of methadone that were reversed by naloxone, while the other (aged 49) did not. To understand the etiology of this event, we measured methadone pharmacokinetics in both patients. In our affected patient only, a fourfold to eightfold increase in methadone plasma concentrations after letrozole treatment was observed. Detailed pharmacokinetic analysis indicated no change in metabolism or renal elimination in our patient, but the percentage of unbound methadone in the plasma decreased 3.7-fold. As a result, the volume of distribution of methadone decreased approximately fourfold. The increased plasma binding in our affected patient was consistent with observed increases in plasma protein concentrations. Conclusions The marked increase in the total plasma methadone concentration observed in our patient, and the enhanced pharmacodynamic

  4. Pattern of Adverse Drug Reactions in Children Attending the Department of Pediatrics in a Tertiary Care Center: A Prospective Observational Study

    PubMed Central

    Digra, Kishour Kumar; Pandita, Aakash; Saini, GS; Bharti, Rajni

    2015-01-01

    AIM To study the pattern of various adverse drug reactions (ADRs) occurring in children attending the Department of Pediatrics, SMGS Hospital, Jammu over 1 year. SUBJECTS AND METHODS This was a prospective study, with study population of patients attending Department of Pediatrics over a period of 1 year. A structured format was used to enroll the participants. A pilot study was conducted to test the suitability of the format and feasibility of the study. The study was carried out to review various pattern of ADRs by using the Naranjo probability scale, and severity was assessed by using the Hartwig severity scale. ADRs were classified according to the classification used by the Adverse Drug Reaction Monitoring Center, Central Drugs Standard Control Organization, New Delhi, India. RESULTS In the present study, 104 patients were found to have developed acute drug reactions. Among these, 83.6% were type B, 14.42% type A, and 1.92% were type U. Furthermore, 25.96% ADRs were due to anticonvulsants, followed by antibiotics (22.11%), antipyretics (11.53%), vaccination (8.65%), steroids (6.73%), decongestants (5.67%), snake antivenom and antiemetics (3.84%), and fluids, insulin, and antacids (1.92%). The patients’ dermatological system was involved in 67.30%, followed by the central nervous system (CNS) in 11.53% patients. Renal system was involved in 6.73% patients. Cardiac, musculoskeletal, metabolic, and other systems were involved in 4.80%, 3.84%, 2.88%, and 0.96%, respectively. According to the Hartwig severity scale of ADRs, 64.4% patients had moderate ADRs, 29.8% patients had severe ADRs, and 5.76% had mild ADRs. In the present study, 64.4% patients expressed moderate severity, whereas 29.8% expressed high severity and 5.76% expressed mild ADRs. CONCLUSION ADRs were seen in 71% of the patients between 1 and 5 years of age, 26% in the age group of 5–10 years, and 3% were more than 10 years old. Anticonvulsants (25.96%) and antibiotics (22.11%) were responsible

  5. An Adverse Drug Reaction to Trimethoprim-Sulfamethoxazole Revealing Primary HIV: A Case Report and Literature Review

    PubMed Central

    Meyer, Charles; Behm, Nicole; Brown, Emily; Copeland, Nathanial K.; Sklar, Marvin J.

    2015-01-01

    Adverse drug reactions (ADRs) to antibiotics complicate the management of any infection, particularly opportunistic infections in advanced HIV as some ADRs are potentiated by HIV. Trimethoprim-sulfamethoxazole (TMP-SMX) causes ADRs in 40–80% of HIV infected individuals, compared to 3–5% in the general population. The incidence and severity of ADRs among HIV infected individuals appear to increase as they progress from latent infection to AIDS. We present a single case report of a 55-year-old African American male found to have an otherwise asymptomatic acute HIV infection who developed an ADR to TMP-SMX, despite having previously tolerating the medication. The proposed mechanisms for the increased incidence of sulfa hypersensitivity reactions among HIV infected individuals focus on either (1) HIV-induced changes in the immune function driven by falling levels of CD4 cells or (2) other HIV-specific factors correlated with rising viral load. To our knowledge this is the first reported case of new sulfa hypersensitivity in primary HIV and may provide clinical evidence to support the correlation between viral load and ADRs to TMP-SMX without a severely diminished CD4 count, though further research is necessary. This case also demonstrates a rare and easily overlooked presentation of HIV that may aid in early diagnosis. PMID:26798528

  6. An Adverse Drug Reaction to Trimethoprim-Sulfamethoxazole Revealing Primary HIV: A Case Report and Literature Review.

    PubMed

    Meyer, Charles; Behm, Nicole; Brown, Emily; Copeland, Nathanial K; Sklar, Marvin J

    2015-01-01

    Adverse drug reactions (ADRs) to antibiotics complicate the management of any infection, particularly opportunistic infections in advanced HIV as some ADRs are potentiated by HIV. Trimethoprim-sulfamethoxazole (TMP-SMX) causes ADRs in 40-80% of HIV infected individuals, compared to 3-5% in the general population. The incidence and severity of ADRs among HIV infected individuals appear to increase as they progress from latent infection to AIDS. We present a single case report of a 55-year-old African American male found to have an otherwise asymptomatic acute HIV infection who developed an ADR to TMP-SMX, despite having previously tolerating the medication. The proposed mechanisms for the increased incidence of sulfa hypersensitivity reactions among HIV infected individuals focus on either (1) HIV-induced changes in the immune function driven by falling levels of CD4 cells or (2) other HIV-specific factors correlated with rising viral load. To our knowledge this is the first reported case of new sulfa hypersensitivity in primary HIV and may provide clinical evidence to support the correlation between viral load and ADRs to TMP-SMX without a severely diminished CD4 count, though further research is necessary. This case also demonstrates a rare and easily overlooked presentation of HIV that may aid in early diagnosis.

  7. Adverse tissue reaction to corrosion at the neck-stem junction after modular primary total hip arthroplasty.

    PubMed

    Gkagkalis, G; Mettraux, P; Omoumi, P; Mischler, S; Rüdiger, H A

    2015-02-01

    Complications related to the neck-stem junction of modular stems used for total hip arthroplasty (THA) are generating increasing concern. A 74-year-old male had increasing pain and a cutaneous reaction around the scar 1 year after THA with a modular neck-stem. Imaging revealed osteolysis of the calcar and a pseudo-tumour adjacent to the neck-stem junction. Serum cobalt levels were elevated. Revision surgery to exchange the stem and liner and to resect the pseudo-tumour was performed. Analysis of the stem by scanning electron microscopy and by energy dispersive X-ray and white light interferometry showed fretting corrosion at the neck-stem junction contrasting with minimal changes at the head-neck junction. Thus, despite dry assembly of the neck and stem on the back table at primary THA, full neck-stem contact was not achieved, and the resulting micromotion at the interface led to fretting corrosion. This case highlights the mechanism of fretting corrosion at the neck-stem interface responsible for adverse local tissue reactions. Clinical and radiological follow-up is mandatory in patients with dual-modular stems.

  8. Incidence of spontaneous notifications of adverse reactions with aceclofenac, meloxicam, and rofecoxib during the first year after marketing in the United Kingdom

    PubMed Central

    Raber, Anna; Heras, Joan; Costa, Joan; Fortea, Josep; Cobos, Albert

    2007-01-01

    The objective was to compare the incidence of adverse reactions reported with three nonsteroidal anti-inflammatory drugs with different cyclo-oxygenase (COX)-2 selectivity. All spontaneous adverse reaction notifications in the pharmacovigilance database of the World Health Organisation Collaborating Centre for International Drug Monitoring with aceclofenac, meloxicam, and rofecoxib that were recorded during the first year of marketing were included. The incidence rate (adverse reactions/106 defined daily dose) and 95% confidence interval for total adverse reactions was 8.7 (6.1–12.0) for aceclofenac, 24.8 (23.1–26.6) for meloxicam, and 52.6 (49.9–55.4) for rofecoxib. Aceclofenac had a lower incidence of gastrointestinal bleeding, abdominal pain, and arterial hypertension than meloxicam and a lower incidence of gastrointestinal bleeding, abdominal pain, liver toxicity, thromboembolic cardiovascular events, arterial hypertension, and edema than rofecoxib. The incidence of total and gastrointestinal adverse reactions was significantly lower with aceclofenac than with meloxicam or rofecoxib, thus raising doubts about the hypothetical advantage of COX-2 selective inhibitors. PMID:18360631

  9. ToxAlerts: a Web server of structural alerts for toxic chemicals and compounds with potential adverse reactions.

    PubMed

    Sushko, Iurii; Salmina, Elena; Potemkin, Vladimir A; Poda, Gennadiy; Tetko, Igor V

    2012-08-27

    The article presents a Web-based platform for collecting and storing toxicological structural alerts from literature and for virtual screening of chemical libraries to flag potentially toxic chemicals and compounds that can cause adverse side effects. An alert is uniquely identified by a SMARTS template, a toxicological endpoint, and a publication where the alert was described. Additionally, the system allows storing complementary information such as name, comments, and mechanism of action, as well as other data. Most importantly, the platform can be easily used for fast virtual screening of large chemical datasets, focused libraries, or newly designed compounds against the toxicological alerts, providing a detailed profile of the chemicals grouped by structural alerts and endpoints. Such a facility can be used for decision making regarding whether a compound should be tested experimentally, validated with available QSAR models, or eliminated from consideration altogether. The alert-based screening can also be helpful for an easier interpretation of more complex QSAR models. The system is publicly accessible and tightly integrated with the Online Chemical Modeling Environment (OCHEM, http://ochem.eu). The system is open and expandable: any registered OCHEM user can introduce new alerts, browse, edit alerts introduced by other users, and virtually screen his/her data sets against all or selected alerts. The user sets being passed through the structural alerts can be used at OCHEM for other typical tasks: exporting in a wide variety of formats, development of QSAR models, additional filtering by other criteria, etc. The database already contains almost 600 structural alerts for such endpoints as mutagenicity, carcinogenicity, skin sensitization, compounds that undergo metabolic activation, and compounds that form reactive metabolites and, thus, can cause adverse reactions. The ToxAlerts platform is accessible on the Web at http://ochem.eu/alerts, and it is constantly

  10. ToxAlerts: A Web Server of Structural Alerts for Toxic Chemicals and Compounds with Potential Adverse Reactions

    PubMed Central

    2012-01-01

    The article presents a Web-based platform for collecting and storing toxicological structural alerts from literature and for virtual screening of chemical libraries to flag potentially toxic chemicals and compounds that can cause adverse side effects. An alert is uniquely identified by a SMARTS template, a toxicological endpoint, and a publication where the alert was described. Additionally, the system allows storing complementary information such as name, comments, and mechanism of action, as well as other data. Most importantly, the platform can be easily used for fast virtual screening of large chemical datasets, focused libraries, or newly designed compounds against the toxicological alerts, providing a detailed profile of the chemicals grouped by structural alerts and endpoints. Such a facility can be used for decision making regarding whether a compound should be tested experimentally, validated with available QSAR models, or eliminated from consideration altogether. The alert-based screening can also be helpful for an easier interpretation of more complex QSAR models. The system is publicly accessible and tightly integrated with the Online Chemical Modeling Environment (OCHEM, http://ochem.eu). The system is open and expandable: any registered OCHEM user can introduce new alerts, browse, edit alerts introduced by other users, and virtually screen his/her data sets against all or selected alerts. The user sets being passed through the structural alerts can be used at OCHEM for other typical tasks: exporting in a wide variety of formats, development of QSAR models, additional filtering by other criteria, etc. The database already contains almost 600 structural alerts for such endpoints as mutagenicity, carcinogenicity, skin sensitization, compounds that undergo metabolic activation, and compounds that form reactive metabolites and, thus, can cause adverse reactions. The ToxAlerts platform is accessible on the Web at http://ochem.eu/alerts, and it is constantly

  11. 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.

  12. Development of a combined system for identification and classification of adverse drug reactions: Alerts Based on ADR Causality and Severity (ABACUS).

    PubMed

    Koh, Yvonne; Yap, Chun Wei; Li, Shu-Chuen

    2010-01-01

    Currently, adverse drug reaction (ADR) causality and severity are assessed using different systems but there is no standard method to combine the results. In this work, a combined ADR causality and severity assessment system, including an online version, was developed. Logical rules were defined to translate the score obtained from the system into three alert zones: green, amber, and red. The alert zones are useful for triaging ADR cases as they help define the seriousness of the ADR and the urgency of the responses required. This new scoring system may be useful for clinicians, investigators, and regulators seeking information on the likelihood of a drug causing an adverse reaction, and whether an adverse reaction is sufficiently dangerous for the drug to be withheld or undergo further investigation.

  13. Biochemical aspects on adverse reactions to contrast media. Changes of kininogen levels in dog plasma after intravenous injections of iohexol, iopamidol, and iothalamate.

    PubMed

    Tanaka, T; Katayama, H; Shirakata, A; Takahasi, H

    1988-09-01

    The adverse reactions to contrast media have been investigated by several authors but the exact mechanisms have not yet been established. To study whether kinin-releasing systems are involved in these adverse reactions, we determined total plasma kininogen levels at intervals up to 30 minutes after the intravenous injections of contrast media in dogs. Injections of iohexol, iopamidol, and iothalamate decreased total plasma kininogen levels. This effect increased with increasing dose of the media and suggests that they activated the kinin-releasing systems in the plasma.

  14. Allele frequency net 2015 update: new features for HLA epitopes, KIR and disease and HLA adverse drug reaction associations

    PubMed Central

    González-Galarza, Faviel F.; Takeshita, Louise Y.C.; Santos, Eduardo J.M.; Kempson, Felicity; Maia, Maria Helena Thomaz; Silva, Andrea Luciana Soares da; Silva, André Luiz Teles e; Ghattaoraya, Gurpreet S.; Alfirevic, Ana; Jones, Andrew R.; Middleton, Derek

    2015-01-01

    It has been 12 years since the Allele Frequency Net Database (AFND; http://www.allelefrequencies.net) was first launched, providing the scientific community with an online repository for the storage of immune gene frequencies in different populations across the world. There have been a significant number of improvements from the first version, making AFND a primary resource for many clinical and scientific areas including histocompatibility, immunogenetics, pharmacogenetics and anthropology studies, among many others. The most widely used part of AFND stores population frequency data (alleles, genes or haplotypes) related to human leukocyte antigens (HLA), killer-cell immunoglobulin-like receptors (KIR), major histocompatibility complex class I chain-related genes (MIC) and a number of cytokine gene polymorphisms. AFND now contains >1400 populations from more than 10 million healthy individuals. Here, we report how the main features of AFND have been updated to include a new section on ‘HLA epitope’ frequencies in populations, a new section capturing the results of studies identifying HLA associations with adverse drug reactions (ADRs) and one for the examination of infectious and autoimmune diseases associated with KIR polymorphisms—thus extending AFND to serve a new user base in these growing areas of research. New criteria on data quality have also been included. PMID:25414323

  15. A case series of 35 hip revisions for adverse reactions to metal debris following Cormet hip resurfacing.

    PubMed

    Norris, Rory J; McArthur, John; Parsons, Helen; Smith, Nicholas A; Sprowson, Andrew P; Foguet, Pedro

    2014-12-01

    The primary aim of this study was to analyse our painful metal-on-metal (MoM) hip resurfacing revisions with evidence of 'adverse reactions to metal debris' (ARMD). In our series of 35 revisions the median whole blood Cobalt levels were 58 nmols/l (range 12-1407 nmols/l), and whole blood Chromium levels were 73 nmols/l (range 2-353 nmols/l). Thirty-four of our 35 patients had abnormal imaging on Ultrasound scanning (USS). The mean histological Campbell grading of ARMD was 4, and ranged from 0-9. The mean Oxford Hip Score (OHS) increased from 19 pre-revision (range 4-46) to 33 post-revision surgery (range 23-47).We found no correlation between the preoperative metal ion levels, and the severity of the disease or the outcome.Pain following hip resurfacing may arise from a number of causes and when groin pain arises in conjunction with abnormal cross sectional imaging we have offered our patients revision surgery regardless of raised metal ions or grossly abnormal imaging, with good results.

  16. Number of drugs most frequently found to be independent risk factors for serious adverse reactions: a systematic literature review.

    PubMed

    Saedder, Eva A; Lisby, Marianne; Nielsen, Lars Peter; Bonnerup, Dorthe K; Brock, Birgitte

    2015-10-01

    In order to reduce the numbers of medication errors (MEs) that cause adverse reactions (ARs) many authors have tried to identify patient-related risk factors. However, the evidence remains controversial. The aim was to review systematically the evidence on the relationship between patient-related risk factors and the risk of serious ARs. A systematic search in Pubmed, Embase, Cochrane Systematic Reviews, Psychinfo and SweMed+ was performed. Included full text articles were hand searched for further references. Peer reviewed papers including adults from primary and secondary healthcare were included if they clearly defined seriousness of the ARs and described correlations to risk factors by statistical analysis. A total of 28 studies were identified including 85,212 patients with 3385 serious ARs, resulting in an overall frequency of serious ARs in 4% of patients. Age, gender and number of drugs were by far the most frequently investigated risk factors. The total number of drugs was the most consistent correlated risk factor found in both univariate and multivariate analyses. The number of drugs is the most frequently documented independent patient-related risk factor for serious ARs in both the general adult population as well as in the elderly. The existing evidence is however conflicting due to heterogeneity of populations and study methods. The knowledge of patient-related risk factors for experiencing ARs could be used for electronic risk stratification of patients and thereby allocation of healthcare resources to high risk patients.

  17. [Evidence of indications of influenza vaccine and its efficacy--including Guillain-Barré syndrome as an adverse reaction(?)].

    PubMed

    Watanabe, Akira

    2003-11-01

    With respect to the indications of influenza vaccine, the US CDC guidelines are the most rational. All people aged not less than 50 years old, patients with pulmonary diseases, cardiac diseases and metabolic diseases such as diabetes mellitus, residents in old-age homes, high-risk subjects such as pregnant women, medical professionals at the position liable to infect the populations with influenza, employees of institutions, persons in charge of home care, and lodgers with high-risk patients are the subjects recommended for vaccination. There are many evidences of the efficacy of influenza vaccine in the world, and recently, it has been reported that vaccination has significantly reduced hospitalization and death due to not only influenza and pneumonia but also other diseases such as cerebrovascular diseases and cardiac diseases. Since Guillain-Barré syndrome which has been considered an adverse reaction of influenza vaccine was attributable to the swine influenza vaccine (swine type virus vaccine) used in the USA in the season from 1976 to 1977 and no incidence in the syndrome has been reported with subsequent vaccines, this syndrome does not become a reason for avoidance from vaccination in the subjects other than those with a history of the syndrome.

  18. On-Chip Construction of Liver Lobule-like Microtissue and Its Application for Adverse Drug Reaction Assay.

    PubMed

    Ma, Chao; Zhao, Lei; Zhou, En-Min; Xu, Juan; Shen, Shaofei; Wang, Jinyi

    2016-02-01

    Engineering the liver in vitro is promising to provide functional replacement for patients with liver failure, or tissue models for drug metabolism and toxicity analysis. In this study, we describe a microfluidics-based biomimetic approach for the fabrication of an in vitro 3D liver lobule-like microtissue composed of a radially patterned hepatic cord-like network and an intrinsic hepatic sinusoid-like network. The hepatic enzyme assay showed that the 3D biomimetic microtissue maintained high basal CYP-1A1/2 and UGT activities, responded dynamically to enzyme induction/inhibition, and preserved great hepatic capacity of drug metabolism. Using the established biomimetic microtissue, the potential adverse drug reactions that induced liver injury were successfully analyzed via drug-drug interactions of clinical pharmaceuticals. The results showed that predosed pharmaceuticals which agitated CYP-1A1/2 and/or UGT activities would alter the toxic effect of the subsequently administrated drug. All the results validated the utility of the established biomimetic microtissue in toxicological studies in vitro. Also, we anticipate the microfluidics-based bioengineering strategy would benefit liver tissue engineering and liver physiology/pathophysiology studies, as well as in vitro assessment of drug-induced hepatotoxicity. PMID:26743823

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

    PubMed Central

    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

  20. Uvangoletin induces mitochondria-mediated apoptosis in HL-60 cells in vitro and in vivo without adverse reactions of myelosuppression, leucopenia and gastrointestinal tract disturbances.

    PubMed

    Zheng, Zhuanzhen; Qiao, Zhenhua; Gong, Rong; Wang, Yalin; Zhang, Yiqun; Ma, Yanping; Zhang, Li; Lu, Yujin; Jiang, Bo; Li, Guoxia; Dong, Chunxia; Chen, Wenliang

    2016-02-01

    This study investigated the cytotoxic effect of uvangoletin on HL-60 cells, and the effects of uvangoletin on myelosuppression, leucopenia, gastrointestinal tract disturbances and the possible cytotoxic mechanisms by using CCK-8, flow cytometry, western blot, xenograft, cyclophosphamide-induced leucopenia, copper sulfate-induced emesis and ethanol-induced gastric mucosal lesions assays. The results of CCK-8, flow cytometry and western blot assays indicated that uvangoletin showed the cytotoxic effect on HL-60 cells and induced the apoptosis of HL-60 cells by downregulating the expression levels of anti-apoptotic proteins (Survivin, Bcl-xl and Bcl-2), upregulating the expression levels of pro-apoptotic proteins (Smac, Bax, Bad, c-caspase-3 and c-caspase-9), and promoting the release of cytochrome c from mitochondria to cytoplasm. Further, the results of xenograft assay suggested that uvangoletin inhibited the HL-60-induced tumor growth without adverse effect on body weight of nude mice in vivo by regulating the expression levels of above apoptotic proteins. The results indicated that the reductions of WBCs count and thighbone marrow granulocytes percentage in cyclophosphamide-induced leucopenia assay, the incubation period and number of emesis in copper sulfate-induced emesis assay and the gastric mucosal lesions in ethanol-induced gastric mucosal lesions assay were not exacerbated or reversed by uvangoletin. In conclusion, the research preliminarily indicated that uvangoletin induced apoptosis of HL-60 cells in vitro and in vivo without adverse reactions of myelosuppression, leucopenia and gastrointestinal tract disturbances, and the pro-apoptotic mechanisms may be related to mitochondria-mediated apoptotic pathway. PMID:26717974

  1. The Role of Personal Goals in Depressive Reaction to Adverse Life Events: A Cross-Sectional Study

    PubMed Central

    Couyoumdjian, Alessandro; Ottaviani, Cristina; Trincas, Roberta; Spitoni, Grazia; Tenore, Katia; Mancini, Francesco

    2012-01-01

    Consistent with cognitive views of depression, we aimed to investigate the mediating role of personal goals in the relationship between stressful events and distinct patterns of depressive symptoms in a nonclinical sample. Participants identified a dysphoric episode that occurred in the previous year by reporting the severity of 12 depressive symptoms and their plausible cause. A goal taxonomy was used to determine how much the event interfered with the achievement of a series of personal goals. After controlling for age and current level of depression, the patterns of symptoms differed based on the triggering events. The relationship between sadness and affective losses was partially mediated by the personal goal of lovableness, and success was a partial mediator in the association between an event of failure and symptoms of worthlessness and anhedonia. Although the cross-sectional design of the study does not allow for conclusions on the direction of effects, findings suggest the importance of motivational factors in the development of specific patterns of depressive symptoms to adverse events. Assuming a continuum from low mood to clinical depression, treatment models could benefit from a precise identification of the specific stressors that initiate depressive behaviour and the personal meaning assigned to those events. PMID:23304090

  2. Adaptation and validation of an adverse drug reaction preventability score for bleeding due to vitamin K antagonists.

    PubMed

    Liabeuf, Sophie; Masmoudi, Kamel; Scailteux, Lucie-Marie; Moragny, Julien; Masson, Henri; Brnet-Dufour, Valérie; Andrejak, Michel; Gras-Champel, Valérie

    2016-09-01

    Although drug therapy is inherently associated with the risk of adverse drug reactions (ADRs), some of these events are preventable. The estimated proportion of preventable ADRs varies from one study or clinical context to another. Bleeding caused by antithrombotic agents (and particularly vitamin K antagonists, VKAs) constitutes one of the most frequent causes of ADR-related hospitalization.Hence, the objective of the present study was to adapt and validate an ADR preventability score for bleeding due to VKAs and evaluate the preventability of bleeding in 906 consecutive hospitalized, VKA-treated adult patients with a risk of major bleeding (defined as an international normalized ratio ≥5) over a 2-year period. A specific preventability scale for VKA-associated bleeding was developed by adapting a published tool.Overall, 241 of the 906 patients in the study experienced at least 1 VKA-associated bleeding event. The scale's reliability was tested by 2 different evaluators. The inter-rater reliability (evaluated by calculation of Cohen's kappa) ranged from "good" to "excellent." Lastly, the validated scale was used to assess the preventability of the VKA-associated bleeding. We estimated that bleeding was preventable or potentially preventable in 109 of the 241 affected patients (45.2%).We have developed a useful, reliable tool for evaluating the preventability of VKA-associated bleeding. Application of the scale in a prospective study revealed that a high proportion of VKA-associated bleeding events in hospitalized, at-risk adult patients were preventable or potentially preventable. PMID:27684801

  3. Parent-reported adverse food reactions in Hong Kong Chinese pre-schoolers: epidemiology, clinical spectrum and risk factors.

    PubMed

    Leung, Ting Fan; Yung, Edmund; Wong, Yun Sze; Lam, Christopher W K; Wong, Gary W K

    2009-06-01

    The epidemiology of adverse food reactions (AFRs), including the potentially life-threatening food allergy (FA), in Asia is unclear. AFR is believed to be less prevalent than in Caucasians. This study determines the prevalence, clinical features and risk factors for parent-reported AFR in Chinese pre-school children in Hong Kong. Children aged 2-7 yr living in Hong Kong were recruited through local nurseries and kindergartens to ascertain the occurrence and clinical spectrum of AFR and other atopic disorders. Subjects' parents answered a self-administered questionnaire that was modified and validated based on the International Study of Asthma and Allergy in Childhood. A total of 3827 children from 21 nurseries and kindergartens returned the study questionnaires, and information on AFR was analyzable for 3677 (96.1%) children. The prevalence rates of parent-reported AFR and parent-reported, doctor-diagnosed AFR were 8.1% and 4.6%, respectively, whereas 5.0% of pre-schoolers had doctor-diagnosed asthma. The six leading causes of AFR were shellfish (15.8%), egg (9.1%), peanut (8.1%), beef (6.4%), cow's milk (5.7%), and tree nuts (5.0%). When compared with children born and raised in Hong Kong, children born in mainland China (n = 253) had less parent-reported AFR (4.0% vs. 6.7%; p = 0.016). On logistic regression, parent-reported AFR was associated with younger age (p = 0.010), born in mainland China (p = 0.038), and AFR history in father (p = 0.001), mother (p < 0.001), siblings (p = 0.020), and paternal history of rhinitis (p = 0.044). This study shows that AFR is a common atopic disorder in Hong Kong pre-school children, and prevalence rates are comparable to the Caucasians.

  4. Use of HLA-B*58:01 genotyping to prevent allopurinol induced severe cutaneous adverse reactions in Taiwan: national prospective cohort study

    PubMed Central

    Ko, Tai-Ming; Tsai, Chang-Youh; Chen, Shih-Yang; Chen, Kuo-Shu; Yu, Kuang-Hui; Chu, Chih-Sheng; Huang, Chung-Ming; Wang, Chrong-Reen; Weng, Chia-Tse; Yu, Chia-Li; Hsieh, Song-Chou; Tsai, Jer-Chia; Lai, Wen-Ter; Tsai, Wen-Chan; Yin, Guang-Dar; Ou, Tsan-Teng; Cheng, Kai-Hung; Yen, Jeng-Hsien; Liou, Teh-Ling; Lin, Tsung-Hsien; Chen, Der-Yuan; Hsiao, Pi-Jung; Weng, Meng-Yu; Chen, Yi-Ming; Chen, Chen-Hung; Liu, Ming-Fei; Yen, Hsueh-Wei; Lee, Jia-Jung; Kuo, Mei-Chuan; Wu, Chen-Ching; Hung, Shih-Yuan; Luo, Shue-Fen; Yang, Ya-Hui; Chuang, Hui-Ping; Chou, Yi-Chun; Liao, Hung-Ting; Wang, Chia-Wen; Huang, Chun-Lin; Chang, Chia-Shuo; Lee, Ming-Ta Michael; Chen, Pei; Wong, Chih-Shung; Chen, Chien-Hsiun; Wu, Jer-Yuarn; Chen, Yuan-Tsong

    2015-01-01

    Objective To evaluate the use of prospective screening for the HLA-B*58:01 allele to identify Taiwanese individuals at risk of severe cutaneous adverse reactions (SCARs) induced by allopurinol treatment. Design National prospective cohort study. Setting 15 medical centres in different regions of Taiwan, from July 2009 to August 2014. Participants 2926 people who had an indication for allopurinol treatment but had not taken allopurinol previously. Participants were excluded if they had undergone a bone marrow transplant, were not of Han Chinese descent, and had a history of allopurinol induced hypersensitivity. DNA purified from 2910 participants’ peripheral blood was used to assess the presence of HLA-B*58:01. Main outcome measures Incidence of allopurinol induced SCARs with and without screening. Results Participants who tested positive for HLA-B*58:01 (19.6%, n=571) were advised to avoid allopurinol, and were referred to an alternate drug treatment or advised to continue with their prestudy treatment. Participants who tested negative (80.4%, n=2339) were given allopurinol. Participants were interviewed once a week for two months to monitor symptoms. The historical incidence of allopurinol induced SCARs, estimated by the National Health Insurance research database of Taiwan, was used for comparison. Mild, transient rash without blisters developed in 97 (3%) participants during follow-up. None of the participants was admitted to hospital owing to adverse drug reactions. SCARs did not develop in any of the participants receiving allopurinol who screened negative for HLA-B*58:01. By contrast, seven cases of SCARs were expected, based on the estimated historical incidence of allopurinol induced SCARs nationwide (0.30% per year, 95% confidence interval 0.28% to 0.31%; P=0.0026; two side one sample binomial test). Conclusions Prospective screening of the HLA-B*58:01 allele, coupled with an alternative drug treatment for carriers, significantly decreased the incidence

  5. Evaluation of immediate adverse reactions to foods in adult patients. I. Correlation of demographic, laboratory, and prick skin test data with response to controlled oral food challenge.

    PubMed

    Atkins, F M; Steinberg, S S; Metcalfe, D D

    1985-03-01

    Forty-five adult patients, referred to here as the index population, with a history of immediate adverse reactions after food ingestion were evaluated by history, physical examination, laboratory studies, and skin testing. Fifty-six percent of these patients reported adverse reactions to only one food, whereas 84% of the patients reported up to three foods as being capable of eliciting reactions. The average age obtained by history at which adverse reactions began to occur was 19 4/5 yr. The occurrence of these reactions persisted over an average of 14 4/5 yr. Most reactions involved the gastrointestinal tract alone or in combination with the skin or respiratory tract. The most frequently involved foods were shellfish, peanuts, eggs, fish, tomatoes, and walnuts. Twenty-five of the patients participated in oral challenge with the suspected food. The food challenge was positive in 10 patients. Comparison of information obtained by history including personal or family history of any other allergic disease, age of onset of sensitivity, the length of time of suspected sensitivity in years, and the number of foods to which the sensitivity was believed to exist revealed no significant differences between food challenge-positive (FC+) and food challenge-negative (FC-) patients. However, a significant difference in the reaction patterns reported by history in the FC+ and FC- patients was noted in that FC+ patients more often described reactions in which a combination of gastrointestinal, respiratory, and dermatologic symptoms occurred. The complete blood count with differential, blood chemistries, and serum immunoglobulin levels were similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Self-Reported Prevalence of Symptomatic Adverse Reactions to Gluten and Adherence to Gluten-Free Diet in an Adult Mexican Population.

    PubMed

    Ontiveros, Noe; López-Gallardo, Jesús A; Vergara-Jiménez, Marcela J; Cabrera-Chávez, Francisco

    2015-07-21

    The prevalence of symptomatic adverse reactions to gluten and adherence to gluten-free diet in Latin American countries is unknown. These measurements are strongly linked to gluten-related disorders. This work aimed to estimate the prevalence of adverse reactions to oral gluten and the adherence to gluten-free diet in the adult Mexican population. To reach this aim, a self-administered questionnaire was designed and tested for clarity/comprehension and reproducibility. Then, a self-administered questionnaire-based cross-sectional study was conducted in the Mexican population. The estimated prevalence rates were (95% CI): 11.9% (9.9-13.5) and 7.8 (6.4-9.4) for adverse and recurrent adverse reactions to gluten respectively; adherence to gluten-free diet 3.7% (2.7-4.8), wheat allergy 0.72% (0.38-1.37); celiac disease 0.08% (0.01-0.45), and NCGS 0.97% (0.55-1.68). Estimated pooled prevalence of self-reported physician-diagnosis of gluten-related disorders was 0.88% (0.49-1.5), and 93.3% respondents reported adherence to gluten-free diet without a physician-diagnosis of gluten-related disorders. Symptom comparisons between those who reported recurrent adverse reactions to gluten and other foods showed statistically significant differences for bloating, constipation, and tiredness (p < 0.05). Gluten-related disorders may be underdiagnosed in the Mexican population and most people adhering to a gluten-free diet are doing it without proper diagnostic work-up of these disorders, and probably without medical/dietician advice.

  7. Self-Reported Prevalence of Symptomatic Adverse Reactions to Gluten and Adherence to Gluten-Free Diet in an Adult Mexican Population

    PubMed Central

    Ontiveros, Noe; López-Gallardo, Jesús A.; Vergara-Jiménez, Marcela J.; Cabrera-Chávez, Francisco

    2015-01-01

    The prevalence of symptomatic adverse reactions to gluten and adherence to gluten-free diet in Latin American countries is unknown. These measurements are strongly linked to gluten-related disorders. This work aimed to estimate the prevalence of adverse reactions to oral gluten and the adherence to gluten-free diet in the adult Mexican population. To reach this aim, a self-administered questionnaire was designed and tested for clarity/comprehension and reproducibility. Then, a self-administered questionnaire-based cross-sectional study was conducted in the Mexican population. The estimated prevalence rates were (95% CI): 11.9% (9.9–13.5) and 7.8 (6.4–9.4) for adverse and recurrent adverse reactions to gluten respectively; adherence to gluten-free diet 3.7% (2.7–4.8), wheat allergy 0.72% (0.38–1.37); celiac disease 0.08% (0.01–0.45), and NCGS 0.97% (0.55–1.68). Estimated pooled prevalence of self-reported physician-diagnosis of gluten-related disorders was 0.88% (0.49–1.5), and 93.3% respondents reported adherence to gluten-free diet without a physician-diagnosis of gluten-related disorders. Symptom comparisons between those who reported recurrent adverse reactions to gluten and other foods showed statistically significant differences for bloating, constipation, and tiredness (p < 0.05). Gluten-related disorders may be underdiagnosed in the Mexican population and most people adhering to a gluten-free diet are doing it without proper diagnostic work-up of these disorders, and probably without medical/dietician advice. PMID:26197336

  8. Self-Reported Prevalence of Symptomatic Adverse Reactions to Gluten and Adherence to Gluten-Free Diet in an Adult Mexican Population.

    PubMed

    Ontiveros, Noe; López-Gallardo, Jesús A; Vergara-Jiménez, Marcela J; Cabrera-Chávez, Francisco

    2015-07-01

    The prevalence of symptomatic adverse reactions to gluten and adherence to gluten-free diet in Latin American countries is unknown. These measurements are strongly linked to gluten-related disorders. This work aimed to estimate the prevalence of adverse reactions to oral gluten and the adherence to gluten-free diet in the adult Mexican population. To reach this aim, a self-administered questionnaire was designed and tested for clarity/comprehension and reproducibility. Then, a self-administered questionnaire-based cross-sectional study was conducted in the Mexican population. The estimated prevalence rates were (95% CI): 11.9% (9.9-13.5) and 7.8 (6.4-9.4) for adverse and recurrent adverse reactions to gluten respectively; adherence to gluten-free diet 3.7% (2.7-4.8), wheat allergy 0.72% (0.38-1.37); celiac disease 0.08% (0.01-0.45), and NCGS 0.97% (0.55-1.68). Estimated pooled prevalence of self-reported physician-diagnosis of gluten-related disorders was 0.88% (0.49-1.5), and 93.3% respondents reported adherence to gluten-free diet without a physician-diagnosis of gluten-related disorders. Symptom comparisons between those who reported recurrent adverse reactions to gluten and other foods showed statistically significant differences for bloating, constipation, and tiredness (p < 0.05). Gluten-related disorders may be underdiagnosed in the Mexican population and most people adhering to a gluten-free diet are doing it without proper diagnostic work-up of these disorders, and probably without medical/dietician advice. PMID:26197336

  9. Adverse reactions to H2-receptor antagonists in Denmark before and after transfer of cimetidine and ranitidine to over-the-counter status.

    PubMed

    Andersen, M; Schou, J S

    1991-10-01

    The H2-receptor antagonists cimetidine and ranitidine were transferred from prescription only to over-the-counter (OTC) status in Denmark on March 27, 1989. Reports to the Danish Committee on Adverse Drug Reactions, a voluntary reporting system, have been evaluated to detect possible changes in frequency and pattern of adverse drug reactions (ADRs) caused by the altered delivery status. From the introduction of cimetidine in 1977 and until March 31, 1990, the Committee received 494 reports of 612 suspected adverse reactions to anti-ulcer drugs. The H2-receptor antagonists (mainly cimetidine and ranitidine) were responsible for 548 (90%) of the ADRs. The study, which presents experience with these drugs from more than a decade and a total consumption corresponding to 65 million treatment days, confirms their excellent safety record. Serious reactions were rare, and when they occurred, reversible. During the first year with cimetidine and ranitidine available OTC no changes were seen in reporting frequency or ADR pattern which could be ascribed to OTC transfer. Only one ADR report concerning OTC cimetidine was received. This may be caused by several factors: the safety of these drugs, the fact that only very little was actually sold OTC, and a relatively low sensitivity of the voluntary reporting system. PMID:1683484

  10. [Adverse events following influenza vaccination: reaction to specific reports and the necessity of a central registration system].

    PubMed

    Swaan, C M; van der Sande, M A B; Speelman, P; Conyn-van Spaendonck, M A E; Straus, S M J M; Coutinho, R A

    2007-09-29

    The influenza vaccine is considered safe, but information on vaccine-related adverse events is limited and a nationwide overview of adverse events is lacking. In 2006, after deaths occurred in Israel and the Netherlands following influenza vaccination, the Dutch Ministry of Health, Welfare and Sport (VWS) asked the National Institute for Public Health and the Environment (RIVM) twice for a recommendation regarding the continuation of the national vaccination campaign. After 4 deaths were reported in Israel in October 2006 following administration of Vaxigrip, the Dutch vaccination campaign was suspended for one week. One month later, 4 additional deaths were reported after influenza vaccination in the Netherlands. The newly appointed outbreak management team concluded that a causal relationship between vaccination and the deaths was highly unlikely, based on data regarding the individual cases, background mortality rates and prior reports of adverse events. Further suspension of the vaccination campaign was deemed unnecessary this time. A centralised nationwide registry of adverse events has since been established to provide further insight into the incidence of adverse events following influenza vaccination. Physicians are advised to report potential adverse events following influenza vaccination to the Netherlands Pharmacovigilance Centre Lareb (www.lareb.nl). PMID:17957995

  11. Adverse Drug Reactions Causing Admission to Medical Wards: A Cross-Sectional Survey at 4 Hospitals in South Africa.

    PubMed

    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

    2016-05-01

    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 South Africa's high HIV

  12. Low Rates of Cutaneous Adverse Reactions to Alcohol-Based Hand Hygiene Solution during Prolonged Use in a Large Teaching Hospital

    PubMed Central

    Graham, M.; Nixon, R.; Burrell, L. J.; Bolger, C.; Johnson, P. D. R.; Grayson, M. L.

    2005-01-01

    We assessed cutaneous adverse reactions (CARs) to alcohol-based hand rub (ABHR) after the introduction of a hand hygiene culture change program at our institution. CARs were infrequent among exposed health care workers (HCWs) (13/2,750; 0.47%; 1 CAR per 72 years of HCW exposure) and were not influenced by the duration or intensity of ABHR use but were associated with the presence of irritant contact dermatitis. PMID:16189134

  13. Drug-induced hepatic injury in children: a case/non-case study of suspected adverse drug reactions in VigiBase

    PubMed Central

    Ferrajolo, Carmen; Capuano, Annalisa; Verhamme, Katia M C; Schuemie, Martijn; Rossi, Francesco; Stricker, Bruno H; Sturkenboom, Miriam C J M

    2010-01-01

    AIM To identify which drugs are associated with reports of suspected hepatic injury in children and adolescents. METHODS Using a worldwide pharmacovigilance database, VigiBase, we conducted a case/non-case study on suspected adverse drug reactions (ADRs) occurring in the population <18 years old. Cases were all the records with hepatic ADRs and non-cases were all the other ADR records. Records regarding topically administered drugs were excluded from both groups. The association between drug and suspected hepatic ADRs was calculated using the reporting odds ratio (ROR) as a measure of disproportionality while adjusting for gender, country, reporter and calendar year. Sub-analyses were performed within therapeutic class and by excluding vaccination-related reports to reduce confounding. RESULTS Overall, 6595 (1%) out of 624 673 ADR records in children and adolescents concerned hepatic injury. Most of the reported hepatic injuries concerned children 12–17 years of age. Drugs that were most frequently reported as suspected cause and were associated with hepatic injury comprised paracetamol, valproic acid, carbamazepine, methotrexate, minocycline, zidovudine, pemoline, ceftriaxone, bosentan, ciclosporin, atomoxetine, olanzapine, basiliximab, erythromycin and voriconazole. The association between hepatotoxicity and all these drugs, except for basiliximab, is already known. CONCLUSIONS Drug-induced hepatic injury is infrequently reported (only 1% of total) as a suspected ADR in children and adolescents. The drugs associated with reported hepatotoxicity (paracetamol, antiepileptic and anti-tuberculosis agents) are known to be hepatotoxic in adults as well, but age related changes in associations were observed. VigiBase is useful as a start to plan further drug safety studies in children. PMID:21039766

  14. Analysis of spontaneous inquiries about suspected adverse drug reactions posted by the general public on the electronic Japanese bulletin board “Yahoo! Japan Chiebukuro”

    PubMed Central

    Dobashi, Akira; Kurata, Kaori; Okazaki, Mitsuhiro; Nishizawa, Mari

    2016-01-01

    Purpose Spontaneous inquiries about the development of adverse drug reactions (ADRs) to medicines can be extracted based on the questions posted by the general public on the electronic Japanese bulletin board “Yahoo! Japan Chiebukuro”. Our aim was to clarify the characteristics related to people’s descriptions of suspected ADRs and determine the reasons for submitting a spontaneous inquiry. Methods Fifty brand names of medicines used for inquiry extraction were chosen by selecting 35 pharmaceutical products, based on the generic names that had the highest sales in Japan. Questions containing both the brand name of one of these medicines and the term “Fukusayō” (ADR in Japanese) that were posted from July 2004 to June 2009 were extracted from the site. Results Among 1,419 questions extracted, 614 questions had at least one identifiable brand name of a suspected medicine, an ADR description, and the extent to which the ADR appeared to be caused by the suspected medicine(s). Among these 614 questions, 589 described in detail the symptoms/signs that the inquirers themselves or their families had experienced as ADRs. The highest number of questions was found for Paxil (525). Posts asking whether the symptoms being experienced were due to an ADR accounted for the highest number of questions. In most cases, the inquirer suspected that a single medicine led to an ADR and was seeking advice from others taking the same medicine. Conclusion Our examination of spontaneous inquiries showed that people have sufficient knowledge to adequately report potential ADRs in terms of their symptoms, suspected medicines, and the disease for which the medicine was used. However, they often did not describe the start time when the ADR appeared or when the suspected medicine was started. PMID:27114703

  15. Adverse drug reaction labelling for atomoxetine, methylphenidate and modafinil: comparison of product information for oral formulations in Australia, Denmark and the United States.

    PubMed

    Aagaard, Lise; Hansen, Ebba Holme

    2013-07-01

    Medical product information contains information about efficacy and safety for marketed pharmaceuticals. Three studies have compared safety labelling for different therapeutic categories in different countries and detected large variations in a number of reported adverse drug reactions (ADRs). The rapid increase in use of medications for treatment of ADHD symptoms has created concern due to lack of information about effects from long-term use. The aim of this study was to compare ADR information in product information (PI)/summary of product characteristics (SPC) for oral formulations of atomoxetine, methylphenidate and modafinil marketed by the same pharmaceutical companies in Australia, Denmark and the United States. Discrepancies in listed ADRs were defined as types of ADRs (system organ class) not listed in all countries. For ADRs where discrepancies were detected, we extracted information about study design (clinical trials, spontaneous report). Discrepancies in ADR labelling for the medications were found across the three countries. A total of 75 ADR categories were listed for atomoxetine and 80% of these were listed in all three countries. For methylphenidate, totally 101 ADR categories and for modafinil 115 ADR categories were listed. For both substances approximately 60% of listed ADRs were found in all three countries. Discrepancies were primarily detected for ADRs information based on clinical trials. For methylphenidate, many ADRs labelled in Australia and Denmark were not mentioned in PIs issued in the United States. In conclusion, information about possible ADRs associated with the use of a specific product should be made available worldwide, as the prescriber information about medicines' safety profile should not depend on the country in which the medication is licensed. PMID:23914751

  16. Variation in adverse drug reactions listed in product information for antidepressants and anticonvulsants, between the USA and Europe: a comparison review of paired regulatory documents

    PubMed Central

    Cornelius, Victoria R; Liu, Kun; Peacock, Janet; Sauzet, Odile

    2016-01-01

    Objective To compare consistency of adverse drug reaction (ADR) data in publicly available product information documents for brand drugs, between the USA and Europe. To assess the usefulness of information for prescribers and patients. Design A comparison review of product information documents for antidepressants and anticonvulsants concurrently marketed by the same pharmaceutical company in the USA and Europe. Setting For each drug, data were extracted from the US Product Inserts and the European Summary of Product Characteristics documents between 09/2013 and 01/2015. Participants Individuals contributing ADR information to product information documents. Main outcomes measures All ADRs reported in product information sections 5 and 6 (USA), and 4·4 and 4·8 (Europe). Results Twelve brand drugs—24 paired documents—were included. On average, there were 77 more ADRs reported in the USA compared with in the European product information document, with a median number of 201 ADRs (range: 65–425) and 114 (range: 56–265), respectively. More product information documents in the USA reported information on the source of evidence (10 vs 5) and risk (9 vs 5) for greater than 80% of ADRs included in the document. There was negligible information included regarding duration, severity, reversibility or recurrence of ADRs. On average, only 29% of ADR terms were reported in both paired documents. Conclusions Product information documents contained a large number of ADRs, but lacked contextual data and information important to patients and prescribers, such as duration, severity and reversibility. The ADR profile was found to be inconsistently reported between the USA and Europe, for the same drug. Identifying, selecting, summarising and presenting multidimensional harm data should be underpinned by practical evidence-based guidelines. In order for prescribers to provide considered risk-benefit advice across competing drug therapies to patients, they need access to

  17. Adverse drug reaction labelling for atomoxetine, methylphenidate and modafinil: comparison of product information for oral formulations in Australia, Denmark and the United States.

    PubMed

    Aagaard, Lise; Hansen, Ebba Holme

    2013-07-01

    Medical product information contains information about efficacy and safety for marketed pharmaceuticals. Three studies have compared safety labelling for different therapeutic categories in different countries and detected large variations in a number of reported adverse drug reactions (ADRs). The rapid increase in use of medications for treatment of ADHD symptoms has created concern due to lack of information about effects from long-term use. The aim of this study was to compare ADR information in product information (PI)/summary of product characteristics (SPC) for oral formulations of atomoxetine, methylphenidate and modafinil marketed by the same pharmaceutical companies in Australia, Denmark and the United States. Discrepancies in listed ADRs were defined as types of ADRs (system organ class) not listed in all countries. For ADRs where discrepancies were detected, we extracted information about study design (clinical trials, spontaneous report). Discrepancies in ADR labelling for the medications were found across the three countries. A total of 75 ADR categories were listed for atomoxetine and 80% of these were listed in all three countries. For methylphenidate, totally 101 ADR categories and for modafinil 115 ADR categories were listed. For both substances approximately 60% of listed ADRs were found in all three countries. Discrepancies were primarily detected for ADRs information based on clinical trials. For methylphenidate, many ADRs labelled in Australia and Denmark were not mentioned in PIs issued in the United States. In conclusion, information about possible ADRs associated with the use of a specific product should be made available worldwide, as the prescriber information about medicines' safety profile should not depend on the country in which the medication is licensed.

  18. Clues to Conclusions

    ERIC Educational Resources Information Center

    Soloway, Rhoda K.

    1978-01-01

    To help students learn how to interpret, infer, and speculate on conclusions, here is a week-long learning activity on "clue finding". A mitten, a bagful of debris and a few intriguing exercises with descriptive paragraphs show students that they use clues every day to draw conclusions and that they can extend this ability to analyze what they…

  19. Beginning without a Conclusion.

    ERIC Educational Resources Information Center

    Frazier, Richard

    1988-01-01

    Describes a series of activities without conclusions to introduce scientific reasoning in a ninth grade physical science course. Uses popcorn popping to get students to think about the concepts of graphing, histograms, frequency, probability, and scientific methodology. (CW)

  20. Factors contributing to adverse soft tissue reactions due to the use of tartar control toothpastes: report of a case and literature review.

    PubMed

    DeLattre, V F

    1999-07-01

    Tetrasodium and/or tetrapotassium pyrophosphate (Ppi) is the anticalculus component of most tartar control dentifrices on the market today. While pyrophosphates alone are not responsible for hypersensitivity reactions, several modifications which may lead to adverse oral manifestations may occur when pyrophosphates are added to a dentifrice. First, tetrasodium pyrophosphate in a dentifrice forms a slightly alkaline solution upon oral use which could irritate oral membranes. Second, increased concentrations of flavoring agents, known to be sensitizers, are needed to mask the strong bitter taste of pyrophosphates. Third, increased concentrations of detergents, capable of producing hypersensitivity reactions, are necessary to allow the pyrophosphates to become soluble in the dentifrice. Fourth, a pre-existing condition of reduced salivary flow may augment hypersensitivity to tartar control toothpastes. While pyrophosphates have been approved as additives in dentifrices, these compounds along with the increased concentrations of flavorings and detergents and their higher intraoral alkalinity are strongly implicated as the causative factor in certain hypersensitivity reactions.

  1. [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

  2. Clinical Pharmacology, Uses, and Adverse Reactions of Iodinated Contrast Agents: A Primer for the Non-radiologist

    PubMed Central

    Pasternak, Jeffrey J.; Williamson, Eric E.

    2012-01-01

    Iodinated contrast agents have been in use since the 1950s to facilitate radiographic imaging modalities. Physicians in almost all specialties will either administer these agents or care for patients who have received these drugs. Different iodinated contrast agents vary greatly in their properties, uses, and toxic effects. Therefore, clinicians should be at least superficially familiar with the clinical pharmacology, administration, risks, and adverse effects associated with iodinated contrast agents. This primer offers the non-radiologist physician the opportunity to gain insight into the use of this class of drugs. PMID:22469351

  3. [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.

  4. Attachment of nymphal Rhipicephalus sanguineus (Acari: Ixodidae) to a human in an urban area followed by severe adverse reaction shortly before drop-off.

    PubMed

    Uspensky, Igor

    2009-03-01

    A case of attachment and complete engorgement of a Rhipicephalus sanguineus (Latreille, 1806) nymph on a woman with severe pain shortly before nymphal drop-off is described. The pain continued for about 2 weeks after tick removal. Apparently, this is the first documented case of human adverse reaction developed at the very last stage of engorgement of nymphal R. sanguineus. The infestation most likely took place inside the enclosed household garden in the southern area of Jerusalem where the woman took care of the plants. The importance of immature R. sanguineus ticks in attacking humans is discussed. PMID:19391333

  5. A comparison of patterns of spontaneous adverse drug reaction reporting with St. John's Wort and fluoxetine during the period 2000-2013.

    PubMed

    Hoban, Claire L; Byard, Roger W; Musgrave, Ian F

    2015-07-01

    Herbal medicines are perceived to be safe by the general public and medical practitioners, despite abundant evidence from clinical trials and case reports that show herbal preparations can have significant adverse effects. The overall impact of adverse events to herbal medicines in Australia is currently unknown. Post marketing surveillance of medications through spontaneous adverse drug reaction (ADR) reports to the Therapeutic Goods Administration (TGA) is one way to estimate this risk. The patterns of spontaneously reported ADRs provide insight to herbal dangers, especially when compared with patterns of a mechanistically similar conventional drug. The study compared the pattern of spontaneously reported ADRs to St. John's Wort (Hypericum perforatum), a common herbal treatment for depression which contains selective serotonin reuptake inhibitors (SSRI), to fluoxetine, a commonly prescribed synthetic SSRI antidepressant. Spontaneous ADR reports sent to the TGA between 2000-2013 for St. John's Wort (n = 84) and fluoxetine (n = 447) were obtained and analysed. The demographic information, types of interaction, severity of the ADR, and the body systems affected (using the Anatomical Therapeutic Chemical classification system) were recorded for individual ADR cases. The majority of spontaneously reported ADRs for St. John's Wort and fluoxetine were concerning females aged 26-50 years (28.6%, 22.8%). The organ systems affected by ADRs to St John's Wort and fluoxetine have a similar profile, with the majority of cases affecting the central nervous system (45.2%, 61.7%). This result demonstrates that herbal preparations can result in ADRs similar to those of prescription medications.

  6. Association between Thiopurine S-Methyltransferase Polymorphisms and Azathioprine-Induced Adverse Drug Reactions in Patients with Autoimmune Diseases: A Meta-Analysis

    PubMed Central

    Liu, Yue-Ping; Xu, Han-Qing; Li, Ming; Yang, Xiang; Yu, Shu; Fu, Wei-Ling; Huang, Qing

    2015-01-01

    Purpose Azathioprine (AZA) is widely used as an immunosuppressive drug in autoimmune diseases, but its use is limited by significant adverse drug reactions (ADRs). Thiopurine S-methyltransferase (TPMT) is an important enzyme involved in AZA metabolism. Several clinical guidelines recommend determining TPMT genotype or phenotype before initiating AZA therapy. Although several studies have investigated the association between TPMT polymorphisms and AZA-induced ADRs, the results are inconsistent. The purpose of this study is to evaluate whether there is an association between TPMT polymorphisms and AZA-induced ADRs using meta-analysis. Methods We explored PubMed, Web of Science and Embase for articles on TPMT polymorphisms and AZA-induced ADRs. Studies that compared TPMT polymorphisms with-ADRs and without-ADRs in patients with autoimmune diseases were included. Relevant outcome data from all the included articles were extracted and the pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated using Revman 5.3 software. Results Eleven published studies, with a total of 651 patients with autoimmune diseases, investigated associations between TPMT polymorphisms and AZA-induced ADRs, were included in this meta-analysis. Our meta-analysis demonstrated that TPMT polymorphisms were significantly associated with AZA-induced overall ADRs, bone marrow toxicity and gastric intolerance; pooled ORs were 3.12 (1.48–6.56), 3.76 (1.97–7.17) and 6.43 (2.04–20.25), respectively. TPMT polymorphisms were not associated with the development of hepatotoxicity; the corresponding pooled OR was 2.86 (95%CI: 0.32–25.86). However, the association in GI subset could be driven by one single study. After this study was excluded, the OR was 2.11 (95%CI: 0.36–12.42); namely, the association became negative. Conclusions Our meta-analysis demonstrated an association of TPMT polymorphisms with overall AZA-induced ADRs, bone marrow toxicity and gastric

  7. Incidence, characteristics and risk factors of adverse drug reactions in hospitalized children – a prospective observational cohort study of 6,601 admissions

    PubMed Central

    2013-01-01

    Background Adverse drug reactions (ADRs) are an important cause of harm in children. Current data are incomplete due to methodological differences between studies: only half of all studies provide drug data, incidence rates vary (0.6% to 16.8%) and very few studies provide data on causality, severity and risk factors of pediatric ADRs. We aimed to determine the incidence of ADRs in hospitalized children, to characterize these ADRs in terms of type, drug etiology, causality and severity and to identify risk factors. Methods We undertook a year-long, prospective observational cohort study of admissions to a single UK pediatric medical and surgical secondary and tertiary referral center (Alder Hey, Liverpool, UK). Children between 0 and 16 years 11 months old and admitted for more than 48 hours were included. Observed outcomes were occurrence of ADR and time to first ADR for the risk factor analysis. Results A total of 5,118 children (6,601 admissions) were included, 17.7% of whom experienced at least one ADR. Opiate analgesics and drugs used in general anesthesia (GA) accounted for more than 50% of all drugs implicated in ADRs. Of these ADRs, 0.9% caused permanent harm or required admission to a higher level of care. Children who underwent GA were at more than six times the risk of developing an ADR than children without a GA (hazard ratio (HR) 6.40; 95% confidence interval (CI) 5.30 to 7.70). Other factors increasing the risk of an ADR were increasing age (HR 1.06 for each year; 95% CI 1.04 to 1.07), increasing number of drugs (HR 1.25 for each additional drug; 95% CI 1.22 to 1.28) and oncological treatment (HR 1.90; 95% CI 1.40 to 2.60). Conclusions ADRs are common in hospitalized children and children who had undergone a GA had more than six times the risk of developing an ADR. GA agents and opiate analgesics are a significant cause of ADRs and have been underrepresented in previous studies. This is a concern in view of the increasing number of pediatric short

  8. Economic consequences of the adverse reactions related with antipsychotics: an economic model comparing tolerability of ziprasidone, olanzapine, risperidone, and haloperidol in Spain.

    PubMed

    Bobes, Julio; Cañas, Fernando; Rejas, Javier; Mackell, Joan

    2004-12-01

    Frequency of adverse reactions (ARs) related with antipsychotics usage is high. Along with clinical implications, economic impact might be important. The purpose of this study was to model the economic consequences of ARs related with ziprasidone, olanzapine, risperidone, and haloperidol in Spain, by means of a cost-effectiveness model developed using a Markov modeling approach. The model simulated treatment of a cohort of 1000 schizophrenics for 12 months, initiating treatment with one of four antipsychotic drugs; haloperidol, risperidone, olanzapine and ziprasidone. Conditional probabilities of developing any of four adverse events were calculated. Treatment was modified (decrease dose, switch medication) according to incidence of ARs and physician judgments, obtained from a local cross-sectional study and clinical trials previously published. The analysis was conducted in year 2002 from a third party payer perspective. Results are shown as annual cost per month with psychotic symptoms controlled and included univariate sensitivity analysis. The therapeutic strategy starting with ziprasidone showed the lower costs and the greater number of months with symptoms controlled in most scenarios evaluated versus the other options considered, although the differences were weak: 9.6, 9.3, 9.5 and 9.5 controlled months per patient in base scenario, with annual cost per patient per month with symptoms controlled of 1035 Euros, 1084 Euros, 1087 Euros and 1090 Euros for ziprasidone, haloperidol, risperidone and olanzapine, respectively. Results were robust to one-way sensitivity analysis. Despite the unlike drug prices of antipsychotics, a considerable economic impact due to adverse reactions was seen in our setting. These results should be taken into account by health decision makers and clinicians in the management of patients with schizophrenia.

  9. Conclusion

    NASA Astrophysics Data System (ADS)

    Thoma, Klaus; Hiller, Daniel; Leismann, Tobias; Drees, Birgit

    Considering the breadth of perspectives in security research among Europeans, as exemplified within this publication, one may certainly note that a tremendous development of this young discipline has occurred in a short period of time. Only three years have passed since the discipline was promoted to an individual theme within the specific programme on `Cooperation' of the European Commission FP7. Since then, a conceptual framework has been established and the first collaborative projects have been executed on different levels, all at an impressive pace. Although the future of security research will remain closely linked to the political will of EU member states, the established base will serve as a solid foundation for the further development of the discipline on a European scale.

  10. Conclusion

    NASA Technical Reports Server (NTRS)

    Arnold, Steven M.; Wong, Terry T.

    2011-01-01

    This compilation of papers in this book represents approximately half of the works discussed at the MS&T 2010 symposium entitled Tools, Models, Databases, and Simulation Tools Developed and Needed to Realize the Vision of Integrated Computational Materials Engineering at Materials Science & Technology wherein five sessions comprised of 33 presentations was organized. The goal of the symposium was two fold To provide a forum in which current state-of-the-art methods for ICME (e.g., information informatics, experimentation, and modeling) could be openly discussed and critiqued by not only materials scientist but also structural engineers/researchers, component designers, industrial leaders and government program managers. To leave the symposium and in particular the panel discussion with a clear idea of the gaps and barriers (both technical, cultural and economical) that must be addressed in order for ICME to fully succeed. The organizers felt that these goals were met, as particularly evident by the standing room only attendance during a lively panel discussion session at the end of the Symposium. However it is the firm belief of the editors of this book that this symposium was merely a start in the right direction, and that subsequent conferences/symposium (e.g., First World Congress on Integrated Computational Materials Engineering to be held July 10-14, 2011 at Seven Springs Mountain Resort in Pennsylvania) must work hard to ensure that a truly diverse, multidisciplinary, community of researchers and practitioners are present and have ample opportunity for interaction. This will ensure that a proper balance between push and pull disciplines and technologies is maintained so that this emerging focus area, Integrated Computational Materials Engineering (ICME), has the greatest potential for success and impact on "system-level" payoffs. Similarly, a pro-active approach is required to reform historical modes of operation in industry, government and the academic sectors so as to facilitate multidisciplinary collaboration and to clearly articulate the vision and scope of ICME.

  11. Conclusions

    NASA Astrophysics Data System (ADS)

    Ahonen, Pasi; Alahuhta, Petteri; Daskala, Barbara; Delaitre, Sabine; Hert, Paul De; Lindner, Ralf; Maghiros, Ioannis; Moscibroda, Anna; Schreurs, Wim; Verlinden, Michiel

    Some say that an increase in security does not necessarily mean a further encroachment on privacy - indeed, security is necessary to protect personal data and our privacy. Networks must be secure, our personal devices, reliable, dependable and trustworthy. But security is a multifaceted term, with many dimensions. We are of the view that an increase in security most likely will encroach upon our privacy in an ambient intelligence world. Surveillance cameras will continue to proliferate. We assume that, whatever the law is, whatever privacy protections government and business say they honour, our telecommunications, e-mails and Internet usage will be monitored to an increasing degree. The same will be true of our interfaces with the world of ambient intelligence.

  12. Conclusion

    NASA Astrophysics Data System (ADS)

    Ivancevic, Vladimir G.; Reid, Darryn J.

    2015-11-01

    It is often held that things should always be made simple, which presumes that either that they can always be made simple or that all the jetisoned logic doesn't matter anyway. Alledgedly, anything should be explainable so that anyone can understand it. Don't get bogged down in dreary details. It should be effortless for the reader: low-dimensional systems exhibit complex behaviour while high-dimensional systems exhibit simple behaviour (to return to our prolegomonal opening), competition is a universal solution, demand must increase as price falls, and everything under the sun neatly fits a power law. Or so the story goes...

  13. A comparison of patterns of spontaneous adverse drug reaction reporting with St. John's Wort and fluoxetine during the period 2000-2013.

    PubMed

    Hoban, Claire L; Byard, Roger W; Musgrave, Ian F

    2015-07-01

    Herbal medicines are perceived to be safe by the general public and medical practitioners, despite abundant evidence from clinical trials and case reports that show herbal preparations can have significant adverse effects. The overall impact of adverse events to herbal medicines in Australia is currently unknown. Post marketing surveillance of medications through spontaneous adverse drug reaction (ADR) reports to the Therapeutic Goods Administration (TGA) is one way to estimate this risk. The patterns of spontaneously reported ADRs provide insight to herbal dangers, especially when compared with patterns of a mechanistically similar conventional drug. The study compared the pattern of spontaneously reported ADRs to St. John's Wort (Hypericum perforatum), a common herbal treatment for depression which contains selective serotonin reuptake inhibitors (SSRI), to fluoxetine, a commonly prescribed synthetic SSRI antidepressant. Spontaneous ADR reports sent to the TGA between 2000-2013 for St. John's Wort (n = 84) and fluoxetine (n = 447) were obtained and analysed. The demographic information, types of interaction, severity of the ADR, and the body systems affected (using the Anatomical Therapeutic Chemical classification system) were recorded for individual ADR cases. The majority of spontaneously reported ADRs for St. John's Wort and fluoxetine were concerning females aged 26-50 years (28.6%, 22.8%). The organ systems affected by ADRs to St John's Wort and fluoxetine have a similar profile, with the majority of cases affecting the central nervous system (45.2%, 61.7%). This result demonstrates that herbal preparations can result in ADRs similar to those of prescription medications. PMID:25988866

  14. Diagnosis and Management of Adverse Local Tissue Reactions Secondary to Corrosion at the Head-Neck Junction in Patients With Metal on Polyethylene Bearings.

    PubMed

    Plummer, Darren R; Berger, Richard A; Paprosky, Wayne G; Sporer, Scott M; Jacobs, Joshua J; Della Valle, Craig J

    2016-01-01

    We reviewed 27 patients who underwent revision for an adverse local tissue reaction (ALTR) secondary to corrosion at the head-neck junction with MoP bearings. Serum cobalt and chromium levels were elevated in all cases, with a mean cobalt of 11.2 ppb and chromium of 2.2 ppb. Patients underwent modular bearing exchange, including a ceramic head with a titanium sleeve in 23 of 27 cases with only one recurrence of ALTR in one of the four patients not treated with a ceramic head. The diagnosis of ALTR secondary to corrosion is associated with cobalt levels of >1 ppb with cobalt levels elevated above chromium. Retention of a well-fixed stem and modular exchange to a ceramic head leads to resolution of symptoms and decreases in metal levels.

  15. Adverse reactions to metal debris in metal-on-polyethylene total hip arthroplasty using a titanium-molybdenum-zirconium-iron alloy stem.

    PubMed

    Kiran, Manish; Boscainos, Petros J

    2015-02-01

    We report a series of three patients who underwent uncemented total hip arthroplasty with a modular titanium-molybdenum-zirconium-iron stem and a cobalt-chrome-molybdenum head on an ultra-high molecular weight highly cross-linked polyethylene liner bearing. All three cases subsequently developed pain and adverse reaction to metal debris, leading to revision of the implants within thirty-six months. They were subsequently found to have hypersensitivity to cobalt or chromium. However where tested, blood metal ion levels were within MHRA guideline limits. Corrosion was noted at the taper-trunnion junction. It is possible, that the multi alloy head-neck combination may lead to corrosion. Hypersensitivity to metal ions may result to ARMD at lower metal ion levels. The use of ceramic heads may help avoid this risk.

  16. The Incidence, Classification, and Management of Acute Adverse Reactions to the Low-Osmolar Iodinated Contrast Media Isovue and Ultravist in Contrast-Enhanced Computed Tomography Scanning

    PubMed Central

    Zhang, Bin; Dong, Yuhao; Liang, Long; Lian, Zhouyang; Liu, Jing; Luo, Xiaoning; Chen, Wenbo; Li, Xinyu; Liang, Changhong; Zhang, Shuixing

    2016-01-01

    Abstract Some epidemiologic surveillance studies have recorded adverse drug reactions to radiocontrast agents. We aimed to investigate the incidence and management of acute adverse reactions (AARs) to Ultravist-370 and Isovue-370 in patients who underwent contrast-enhanced computed tomography (CT) scanning. Data from 137,473 patients were analyzed. They had undergone enhanced CT scanning with intravenous injection of Ultravist-370 or Isovue-370 during the period of January 1, 2006 to December 31, 2012 in our hospital. We investigated and classified AARs according to the American College of Radiology and the Chinese Society of Radiology (CSR) guidelines for iodinated contrast media. We analyzed risk factors for AARs and compared the AARs induced by Ultravist-370 and Isovue-370. Four hundred and twenty-eight (0.31%) patients experienced AARs, which included 330 (0.24%) patients with mild AARs, 82 (0.06%) patients with moderate AARs, and 16 (0.01%) patients with severe AARs (including 3 cases of cardiac arrest and one case of death). The incidence of AARs was higher with Ultravist-370 than with Isovue-370 (0.38% vs 0.24%, P < 0.001), but only for mild AARs (0.32% vs 0.16%, P < 0.001). Analyses on risk factors indicated that female patients (n = 221, 0.43%, P < 0.001), emergency patients (n = 11, 0.51%, P < 0.001), elderly patients aged 50 to 60 years (n = 135, 0.43%, P < 0.001), and patients who underwent coronary computed tomography angiography (CTA) (n = 55, 0.51%, P < 0.001) had a higher risk of AARs. Cutaneous manifestations (50.52%)—especially rash (59.74%)—were the most frequent mild AARs. Cardiovascular manifestations accounted for most moderate and severe AARs (62.91% and 48.28%, respectively). After proper management, the symptoms and signs of 96.5% of the AARs resolved within 24 hours without sequelae. Ultravist-370 and Isovue-370 are safe for patients undergoing enhanced CT scanning. The incidence of AARs is

  17. The Incidence, Classification, and Management of Acute Adverse Reactions to the Low-Osmolar Iodinated Contrast Media Isovue and Ultravist in Contrast-Enhanced Computed Tomography Scanning.

    PubMed

    Zhang, Bin; Dong, Yuhao; Liang, Long; Lian, Zhouyang; Liu, Jing; Luo, Xiaoning; Chen, Wenbo; Li, Xinyu; Liang, Changhong; Zhang, Shuixing

    2016-03-01

    Some epidemiologic surveillance studies have recorded adverse drug reactions to radiocontrast agents. We aimed to investigate the incidence and management of acute adverse reactions (AARs) to Ultravist-370 and Isovue-370 in patients who underwent contrast-enhanced computed tomography (CT) scanning.Data from 137,473 patients were analyzed. They had undergone enhanced CT scanning with intravenous injection of Ultravist-370 or Isovue-370 during the period of January 1, 2006 to December 31, 2012 in our hospital. We investigated and classified AARs according to the American College of Radiology and the Chinese Society of Radiology (CSR) guidelines for iodinated contrast media. We analyzed risk factors for AARs and compared the AARs induced by Ultravist-370 and Isovue-370.Four hundred and twenty-eight (0.31%) patients experienced AARs, which included 330 (0.24%) patients with mild AARs, 82 (0.06%) patients with moderate AARs, and 16 (0.01%) patients with severe AARs (including 3 cases of cardiac arrest and one case of death). The incidence of AARs was higher with Ultravist-370 than with Isovue-370 (0.38% vs 0.24%, P < 0.001), but only for mild AARs (0.32% vs 0.16%, P < 0.001). Analyses on risk factors indicated that female patients (n = 221, 0.43%, P < 0.001), emergency patients (n = 11, 0.51%, P < 0.001), elderly patients aged 50 to 60 years (n = 135, 0.43%, P < 0.001), and patients who underwent coronary computed tomography angiography (CTA) (n = 55, 0.51%, P < 0.001) had a higher risk of AARs. Cutaneous manifestations (50.52%)-especially rash (59.74%)-were the most frequent mild AARs. Cardiovascular manifestations accounted for most moderate and severe AARs (62.91% and 48.28%, respectively). After proper management, the symptoms and signs of 96.5% of the AARs resolved within 24 hours without sequelae.Ultravist-370 and Isovue-370 are safe for patients undergoing enhanced CT scanning. The incidence of AARs is higher with Ultravist

  18. Hypoglycaemic complications with diabetes mellitus management: the predominant adverse drug reaction presenting to the Accident and Emergency Department of The University Hospital of the West Indies.

    PubMed

    Gossell-Williams, M; Williams-Johnson, J; Francis, L

    2010-10-01

    Evaluation of adverse drug reactions (ADRs) is important to the assessment of risk factors in an aim to ensure maximum benefits of drug therapy. This study was done to assess the types of ADRs presenting to the Accident and Emergency department (A&E) of the University Hospital of the West Indies. Admissions to the A&E associated with drugs were followed on a weekly basis for 19 weeks from October 2007 to February 2008 using the patient logbook. Medical records of patients with suspected ADRs were collected and evaluated by an Emergency Medicine Consultant of A & E to confirm the occurrence of ADRs and the suspected drug. Of the 8170 admissions to A&E, 48 (0.6%) were related to ADRs, with most occurring in females and the mean age (+/- standard error) was 58.9 (+/- 3.4) years. Drug induced hypoglycaemia accounted for 28 (56.3%) cases of ADRs and included mainly patients on insulin, with or without a sulphonylurea therapy. Most of these diabetic patients also had co-morbidities and were on multi-drug therapy (18). Allergic reactions accounted for 10 (21%) of the ADR outcomes. Other drugs accounting for ADRs included cardiovascular drugs (10.4%), analgesic/anti-inflammatory medications (8.3%), drugs acting on the central nervous system (8.3%) and anti-infectives (8.3%). It is concluded that drug-induced hypoglycaemia is the major ADR presenting to the A&E of the University Hospital of the West Indies; it is a preventable ADR and therefore further investigation should evaluate possible factors attributed to the occurrences.

  19. Trimethoprim-Sulfamethoxazole–Induced Rhabdomyolysis; Gabapentin-Induced Hypoglycemia in Diabetic and Nondiabetic Patients; Purple Glove Syndrome After Oral Phenytoin Administration; Acute Dystonic Reaction After Methylphenidate Initiation; Serotonin Syndrome with Vilazodone Monotherapy; Cabozantinib-Associated Dermatologic Adverse Reactions

    PubMed Central

    Mancano, Michael A.

    2015-01-01

    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:26715798

  20. Effect of Diabetes Mellitus on Tuberculosis Treatment Outcome and Adverse Reactions in Patients Receiving Directly Observed Treatment Strategy in India: A Prospective Study

    PubMed Central

    Siddiqui, Ali Nasir; Khayyam, Khalid Umer

    2016-01-01

    Despite successful implementation of directly observed treatment, short course (DOTS) in India, the growing number of diabetes mellitus (DM) patients appears to be a cause in the increasing tuberculosis (TB) incidence, affecting their management. In this regard, a prospective study was conducted on DOTS patients in three primary health care centers in urban slum region of South Delhi, India, to evaluate the effect of DM on sputum conversion, treatment outcome, and adverse drug reactions (ADR) due to anti-TB treatment. Eligible TB patients underwent blood glucose screening at treatment initiation. Disease presentation, clinical outcome, and ADRs were compared between patients of TB with and without DM. Out of 316 patients, the prevalence of DM was found to be 15.8%, in which 19.4% and 9.6% were PTB and EPTB patients, respectively. DM patients have observed higher sputum positivity (OR 1.247 95% CI; 0.539–2.886) at the end of 2-month treatment and poor outcome (OR 1.176 95% CI; 0.310–4.457) at the completion of treatment compared with non DM patients. Presence of DM was significantly associated (OR 3.578 95% CI; 1.114–11.494, p = 0.032) with the development of ADRs. DM influences the treatment outcome of PTB patients in our setting and also on the ADR incidence. PMID:27642601

  1. Using Rich Data on Comorbidities in Case-Control Study Design with Electronic Health Record Data Improves Control of Confounding in the Detection of Adverse Drug Reactions

    PubMed Central

    Chase, Herbert

    2016-01-01

    Recent research has suggested that the case-control study design, unlike the self-controlled study design, performs poorly in controlling confounding in the detection of adverse drug reactions (ADRs) from administrative claims and electronic health record (EHR) data, resulting in biased estimates of the causal effects of drugs on health outcomes of interest (HOI) and inaccurate confidence intervals. Here we show that using rich data on comorbidities and automatic variable selection strategies for selecting confounders can better control confounding within a case-control study design and provide a more solid basis for inference regarding the causal effects of drugs on HOIs. Four HOIs are examined: acute kidney injury, acute liver injury, acute myocardial infarction and gastrointestinal ulcer hospitalization. For each of these HOIs we use a previously published reference set of positive and negative control drugs to evaluate the performance of our methods. Our methods have AUCs that are often substantially higher than the AUCs of a baseline method that only uses demographic characteristics for confounding control. Our methods also give confidence intervals for causal effect parameters that cover the expected no effect value substantially more often than this baseline method. The case-control study design, unlike the self-controlled study design, can be used in the fairly typical setting of EHR databases without longitudinal information on patients. With our variable selection method, these databases can be more effectively used for the detection of ADRs. PMID:27716785

  2. Pharmacogenomics and Global Precision Medicine in the Context of Adverse Drug Reactions: Top 10 Opportunities and Challenges for the Next Decade

    PubMed Central

    Alessandrini, Marco; Chaudhry, Mamoonah; Dodgen, Tyren M.

    2016-01-01

    Abstract In a move indicative of the enthusiastic support of precision medicine, the U.S. President Barack Obama announced the Precision Medicine Initiative in January 2015. The global precision medicine ecosystem is, thus, receiving generous support from the United States ($215 million), and numerous other governments have followed suit. In the context of precision medicine, drug treatment and prediction of its outcomes have been important for nearly six decades in the field of pharmacogenomics. The field offers an elegant solution for minimizing the effects and occurrence of adverse drug reactions (ADRs). The Clinical Pharmacogenetics Implementation Consortium (CPIC) plays an important role in this context, and it aims at specifically guiding the translation of clinically relevant and evidence-based pharmacogenomics research. In this forward-looking analysis, we make particular reference to several of the CPIC guidelines and their role in guiding the treatment of highly relevant diseases, namely cardiovascular disease, major depressive disorder, cancer, and human immunodeficiency virus, with a view to predicting and managing ADRs. In addition, we provide a list of the top 10 crosscutting opportunities and challenges facing the fields of precision medicine and pharmacogenomics, which have broad applicability independent of the drug class involved. Many of these opportunities and challenges pertain to infrastructure, study design, policy, and science culture in the early 21st century. Ultimately, rational pharmacogenomics study design and the acquisition of comprehensive phenotypic data that proportionately match the genomics data should be an imperative as we move forward toward global precision medicine. PMID:27643672

  3. Flupentixol use and adverse reactions in comparison with other common first- and second-generation antipsychotics: data from the AMSP study.

    PubMed

    Grohmann, R; Engel, R R; Möller, H-J; Rüther, E; van der Velden, J W; Stübner, S

    2014-03-01

    This study compares the first-generation antipsychotic (FGA) flupentixol to haloperidol and common second-generation antipsychotics (SGAs) as to drug utilization and severe adverse drug reactions (ADRs) in clinical treatment of schizophrenia inpatients using data from the drug safety program Arzneimittelsicherheit in der Psychiatrie (AMSP). AMSP drug utilization and reported ADR data were analyzed. Type and frequency of severe ADRs attributed to flupentixol were compared with haloperidol, clozapine, olanzapine, quetiapine, risperidone and amisulpride in a total of 56,861 schizophrenia inpatients exposed to these drugs. In spite of increasing prescription of SGAs, flupentixol was consistently used in schizophrenic inpatients (about 5 %) over time. Reporting rates of severe ADR ranged from 0.38 to 1.20 % for the individual antipsychotics (drugs imputed alone); flupentixol ranked lowest. The type of ADR differed considerably; as to severe EPMS, flupentixol (0.27 %), such as risperidone (0.28 %), held an intermediate position between haloperidol/amisulpride (0.55/0.52 %) and olanzapine/quetiapine (<0.1 %). The study is a heuristic approach, not a confirmatory test. Flupentixol has a stable place in the treatment of schizophrenia in spite of the introduction of different SGAs. Comparative ADR profiles suggest an intermediate position between FGAs and SGAs for flupentixol in clinical practice. PMID:23835526

  4. Adverse reactions to antiepileptic drugs: a follow-up study of 355 patients with chronic antiepileptic drug treatment. Collaborative Group for Epidemiology of Epilepsy.

    PubMed

    1988-01-01

    Three hundred fifty-five patients receiving chronic antiepileptic drug (AED) treatment were followed in 15 university and hospital centers for an average of 11 months to assess the effects of intensive monitoring of adverse drug reactions (ADRs) on the frequency of reports and on the overall management of epilepsy. One hundred forty-eight patients (41.6%) had one or more ADRs during the entire follow-up period. ADRs were reported by 31% of patients at admission and by 20% at last visit, with a downward trend in the number of reports. Concurrently, the number of patients who were seizure-free rose from 24.5 to 42.8%. During the observation period, the number of prescriptions fell from 640 to 568, mostly for phenobarbital (PB), phenytoin (PHT), and valproate (VPA). The outcome of the most common ADR was only partially related to drug changes. Even with the limitations of the unstandardized criteria used for ADR reporting, the present study shows that intensive monitoring of drug-related clinical events is not only a valuable tool to provide a comprehensive survey of drug toxicity in clinical practice, but is also an educational effort to improve the quality of care for patients with epilepsy. PMID:3191896

  5. Genetic Association of Curative and Adverse Reactions to Tyrosine Kinase Inhibitors in Chinese advanced Non-Small Cell Lung Cancer patients

    PubMed Central

    Ruan, Yunfeng; Jiang, Jie; Guo, Liang; Li, Yan; Huang, Hailiang; Shen, Lu; Luan, Mengqi; Li, Mo; Du, Huihui; Ma, Cheng; He, Lin; Zhang, Xiaoqing; Qin, Shengying

    2016-01-01

    Epidermal growth factor receptor (EGFR) Tyrosine kinase inhibitor (TKI) is an effective targeted therapy for advanced non-small cell lung cancer (NSCLC) but also causes adverse drug reactions (ADRs) e.g., skin rash and diarrhea. SNPs in the EGFR signal pathway, drug metabolism/ transport pathways and miRNA might contribute to the interpersonal difference in ADRs but biomarkers for therapeutic responses and ADRs to TKIs in Chinese population are yet to be fully investigated. We recruited 226 Chinese advanced NSCLC patients who received TKIs erlotinib, gefitinib and icotinib hydrochloride and systematically studied the genetic factors associated with therapeutic responses and ADRs. Rs884225 (T > C) in EGFR 3′ UTR was significantly associated with lower risk of ADRs to erlotinib (p value = 0.0010, adjusted p value = 0.042). A multivariant interaction four-SNP model (rs884225 in EGFR 3′UTR, rs7787082 in ABCB1 intron, rs38845 in MET intron and rs3803300 in AKT1 5′UTR) was associated with ADRs in general and the more specific drug induced skin injury. The SNPs associated with both therapeutic responses and ADRs indicates they might share a common genetic basis. Our study provided potential biomarkers and clues for further research of biomarkers for therapeutic responses and ADRs in Chinese NSCLC patients. PMID:26988277

  6. Effect of Diabetes Mellitus on Tuberculosis Treatment Outcome and Adverse Reactions in Patients Receiving Directly Observed Treatment Strategy in India: A Prospective Study.

    PubMed

    Siddiqui, Ali Nasir; Khayyam, Khalid Umer; Sharma, Manju

    2016-01-01

    Despite successful implementation of directly observed treatment, short course (DOTS) in India, the growing number of diabetes mellitus (DM) patients appears to be a cause in the increasing tuberculosis (TB) incidence, affecting their management. In this regard, a prospective study was conducted on DOTS patients in three primary health care centers in urban slum region of South Delhi, India, to evaluate the effect of DM on sputum conversion, treatment outcome, and adverse drug reactions (ADR) due to anti-TB treatment. Eligible TB patients underwent blood glucose screening at treatment initiation. Disease presentation, clinical outcome, and ADRs were compared between patients of TB with and without DM. Out of 316 patients, the prevalence of DM was found to be 15.8%, in which 19.4% and 9.6% were PTB and EPTB patients, respectively. DM patients have observed higher sputum positivity (OR 1.247 95% CI; 0.539-2.886) at the end of 2-month treatment and poor outcome (OR 1.176 95% CI; 0.310-4.457) at the completion of treatment compared with non DM patients. Presence of DM was significantly associated (OR 3.578 95% CI; 1.114-11.494, p = 0.032) with the development of ADRs. DM influences the treatment outcome of PTB patients in our setting and also on the ADR incidence. PMID:27642601

  7. Effect of Diabetes Mellitus on Tuberculosis Treatment Outcome and Adverse Reactions in Patients Receiving Directly Observed Treatment Strategy in India: A Prospective Study

    PubMed Central

    Siddiqui, Ali Nasir; Khayyam, Khalid Umer

    2016-01-01

    Despite successful implementation of directly observed treatment, short course (DOTS) in India, the growing number of diabetes mellitus (DM) patients appears to be a cause in the increasing tuberculosis (TB) incidence, affecting their management. In this regard, a prospective study was conducted on DOTS patients in three primary health care centers in urban slum region of South Delhi, India, to evaluate the effect of DM on sputum conversion, treatment outcome, and adverse drug reactions (ADR) due to anti-TB treatment. Eligible TB patients underwent blood glucose screening at treatment initiation. Disease presentation, clinical outcome, and ADRs were compared between patients of TB with and without DM. Out of 316 patients, the prevalence of DM was found to be 15.8%, in which 19.4% and 9.6% were PTB and EPTB patients, respectively. DM patients have observed higher sputum positivity (OR 1.247 95% CI; 0.539–2.886) at the end of 2-month treatment and poor outcome (OR 1.176 95% CI; 0.310–4.457) at the completion of treatment compared with non DM patients. Presence of DM was significantly associated (OR 3.578 95% CI; 1.114–11.494, p = 0.032) with the development of ADRs. DM influences the treatment outcome of PTB patients in our setting and also on the ADR incidence.

  8. Serious adverse drug reaction in a woman with hyperemesis gravidarum after first exposure to vitamin B complex containing vitamins B1, B6 and B12.

    PubMed

    Kuwata, Yoshimine; Tsuruoka, Shuichi; Ohkuchi, Akihide; Matsubara, Shigeki; Izumi, Akio; Suzuki, Mitsuaki

    2009-08-01

    We report the case of a pregnant woman who suffered from hypotension after first exposure to intravenous administration of a combination drug containing vitamins B1, B6 and B12 (Vitamedin; Daiichi-Sankyo, Tokyo, Japan). A 27-year-old Japanese woman received an intravenous infusion of fluid containing a vitamin B complex due to hyperemesis gravidarum. Thirty minutes after the start of infusion she was found to be in hypotension. The patient had stupor, general sweating, blood pressure of 82/50 mmHg, and low percutaneous oxygen saturation (SpO(2)) of 88%. We immediately stopped the infusion, lifted her legs and administered oxygen. Three minutes after these treatments, she quickly recovered to a good general condition. A skin prick test for vitamin B12 was positive, but tests for B1, B6, mannitol and saline were negative, indicating this adverse reaction was one of drug hypersensitivity due to the vitamin B12 in Vitamedin. Patients should be observed carefully immediately after the administration of Vitamedin.

  9. Severe Adverse Events Related to Tattooing: An Retrospective Analysis of 11 Years

    PubMed Central

    Wollina, Uwe

    2012-01-01

    Background: The incidence of tattoos has been increased markedly during the last 20 years. Aims: To analyze the patient files for severe adverse medical reactions related to tattooing. Settings: Academic Teaching Hospital in South-East Germany. Materials and Methods: Retrospective investigation from March 2001 to May 2012. Results: The incidence of severe adverse medical reactions has been estimated as 0.02%. Infectious and non-infectious severe reactions have been observed. The consequences were medical drug therapies and surgery. Conclusions: Tattooing may be associated with severe adverse medical reactions with significant morbidity. Regulations, education and at least hygienic controls are tools to increase consumer safety. PMID:23248361

  10. Adverse effects of cannabis.

    PubMed

    2011-01-01

    Cannabis, Cannabis sativa L., is used to produce a resin that contains high levels of cannabinoids, particularly delta9-tetrahydrocannabinol (THC), which are psychoactive substances. Although cannabis use is illegal in France and in many other countries, it is widely used for its relaxing or euphoric effects, especially by adolescents and young adults. What are the adverse effects of cannabis on health? During consumption? And in the long term? Does cannabis predispose users to the development of psychotic disorders? To answer these questions, we reviewed the available evidence using the standard Prescrire methodology. The long-term adverse effects of cannabis are difficult to evaluate. Since and associated substances, with or without the user's knowledge. Tobacco and alcohol consumption, and particular lifestyles and behaviours are often associated with cannabis use. Some traits predispose individuals to the use of psychoactive substances in general. The effects of cannabis are dosedependent.The most frequently report-ed adverse effects are mental slowness, impaired reaction times, and sometimes accentuation of anxiety. Serious psychological disorders have been reported with high levels of intoxication. The relationship between poor school performance and early, regular, and frequent cannabis use seems to be a vicious circle, in which each sustains the other. Many studies have focused on the long-term effects of cannabis on memory, but their results have been inconclusive. There do not * About fifteen longitudinal cohort studies that examined the influence of cannabis on depressive thoughts or suicidal ideation have yielded conflicting results and are inconclusive. Several longitudinal cohort studies have shown a statistical association between psychotic illness and self-reported cannabis use. However, the results are difficult to interpret due to methodological problems, particularly the unknown reliability of self-reported data. It has not been possible to

  11. Adverse effects of cannabis.

    PubMed

    2011-01-01

    Cannabis, Cannabis sativa L., is used to produce a resin that contains high levels of cannabinoids, particularly delta9-tetrahydrocannabinol (THC), which are psychoactive substances. Although cannabis use is illegal in France and in many other countries, it is widely used for its relaxing or euphoric effects, especially by adolescents and young adults. What are the adverse effects of cannabis on health? During consumption? And in the long term? Does cannabis predispose users to the development of psychotic disorders? To answer these questions, we reviewed the available evidence using the standard Prescrire methodology. The long-term adverse effects of cannabis are difficult to evaluate. Since and associated substances, with or without the user's knowledge. Tobacco and alcohol consumption, and particular lifestyles and behaviours are often associated with cannabis use. Some traits predispose individuals to the use of psychoactive substances in general. The effects of cannabis are dosedependent.The most frequently report-ed adverse effects are mental slowness, impaired reaction times, and sometimes accentuation of anxiety. Serious psychological disorders have been reported with high levels of intoxication. The relationship between poor school performance and early, regular, and frequent cannabis use seems to be a vicious circle, in which each sustains the other. Many studies have focused on the long-term effects of cannabis on memory, but their results have been inconclusive. There do not * About fifteen longitudinal cohort studies that examined the influence of cannabis on depressive thoughts or suicidal ideation have yielded conflicting results and are inconclusive. Several longitudinal cohort studies have shown a statistical association between psychotic illness and self-reported cannabis use. However, the results are difficult to interpret due to methodological problems, particularly the unknown reliability of self-reported data. It has not been possible to

  12. Evaluation of Proper Usage of Glucocorticosteroid Inhalers and Their Adverse Effects in Asthmatic Patients

    PubMed Central

    Hejazi, Mohammad Esmayil; Shafiifar, Afsaneh; Mashayekhi, Siminozar

    2016-01-01

    Background: The frequent use of corticosteroid inhalers (CSIs), especially at higher doses, has been accompanied by concern about both systemic and local adverse reactions. The local adverse reactions of inhaled corticosteroids (ICSs) are considered to constitute infrequent and minor problems. However, while not usually serious, these local adverse reactions are of clinical importance. This study assessed the prevalence of local adverse reactions, their clinical features, role of inhaler devices and current measures that have been suggested to prevent the problem. Materials and Methods: This study was performed in YAS clinic in Tabriz on 500 asthmatic patients. A questionnaire about the patients’ demographic information, methods of using CSIs, local care after using CSIs, using spacer devices, doses of ICSs, and adverse reactions were filled then the patients were clinically examined for local adverse reactions. Results: Only 56% patients were using CSIs properly. In general, the incidence of complications was: oropharyngeal candidiasis 25.6%, laryngeal weakness 8.8%, choking 17.6%, tooth decay 15.2%, speechlessness 36.2%, taste decrease 20.8%, tongue burning 29.8% and tongue abrasion 27.8%. Conclusion: Persistent asthma can be effectively controlled with currently available CSIs. Although not life-threatening, local adverse reactions of ICSs are clinically significant and warrant attention. Use of spacer devices and changes in CSI usage, dosage amount and frequency and rinsing and gargling are the methods that have been used to reduce the incidence of local adverse reactions. PMID:27403173

  13. Prevalence of Adverse Drug Reactions in CAD STEMI Patients Treated in the Cardiac Intensive Care Unit at the Public Hospital in Bandung, Indonesia.

    PubMed

    Amalia, Lia; Anggadireja, Kusnandar; Aprami, Toni M; Septiani, Vina

    2016-01-01

    Adverse drug reactions (ADRs) are associated with morbidity, mortality, and can contribute to increased healthcare costs. This study was conducted to identify the occurence, types, and management of ADRs, as well as analyze the causal relationship, severity, and preventability of ADRs. The study was observational analysis with concurrent data collection from patients with Coronary Artery Disease-ST segment Elevation Myocardial Infarction (CAD-STEMI) treated in the Cardiac Intensive Care Unit (CICU) at a hospital in Bandung Indonesia, during the period of December 2013 to March 2014. The occurence of identified ADRs was assessed using the probability scale of Naranjo, while the severity by the scale of Hartwig and their preventability was evaluated using the scale of Schumock-Thornton. 49 ADRs were identified in 29 patients. Organ systems most affected by the ADRs were the cardiovascular and body electrolyte, each accounting for 20.41%. The hematology and gastrointestinal systems each contributed 18.37% to ADR occurrences. The causal relationship was mostly classified as "probable," accounting for 69.39%. With regard to severity, most ADRs were classified as "moderate" at level 3, contributing to 53.06% of the occurence. In terms of preventability, most of the ADRs fell into the "non-preventable" category (79.59%). The most widely applied ADRs management was administration of an antidote or other treatments (40.82%). Further analysis revealed that the average number of drug types and duration of hospitalization significantly affected the presence of ADRs. Taken together, most patients with CAD STEMI treated in the CICU of the studied hospital experienced non-preventable ADRs and were treated with antidote or other treatments. PMID:27110507

  14. Linking drugs to obscure illnesses: lessons from pure red cell aplasia, nephrogenic systemic fibrosis, and Reye's syndrome. a report from the Southern Network on Adverse Reactions (SONAR).

    PubMed

    Bennett, Charles L; Starko, Karen M; Thomsen, Henrik S; Cowper, Shawn; Sartor, Oliver; Macdougall, Iain C; Qureshi, Zaina P; Bookstaver, P Brandon; Miller, April D; Norris, LeAnn B; Xirasagar, Sudha; Trenery, Alyssa; Lopez, Isaac; Kahn, Adam; Murday, Alanna; Luminari, Stefano; Cournoyer, Denis; Locatelli, Francesco; Ray, Paul; Mattison, Donald R

    2012-12-01

    Identification of serious adverse drug reactions (sADRS) associated with commonly used drugs can elude detection for years. Reye's syndrome (RS), nephrogenic systemic fibrosis (NSF), and pure red cell aplasia (PRCA) among chronic kidney disease (CKD) patients were recognized in 1951, 2000, and 1998, respectively. Reports associating these syndromes with aspirin, gadodiamide, and epoetin, were published 29, 6, and 4 years later, respectively. We obtained primary information from clinicians who identified causes of these sADRs and reviewed factors contributing to delayed identification of these toxicities. Overall, 3,500 aspirin-associated RS cases in the United States, 1,605 gadolinium-associated NSF cases, and 181 epoetin-associated PRCA cases were reported. Delays in FDA regulation of over-the- counter medications and administration of aspirin to children contributed to development of RS. For NSF, in 1996, the Danish Medicine Agency approved high-dose gadodiamide administration to chronic kidney disease (CKD) patients undergoing MR scans. Overall, 88 % of Danish NSF cases were from two hospitals and 97 % of United States' NSF cases were from 60 hospitals. These hospitals frequently administered high-doses of gadodiamide to CKD patients. Another factor was the decision to administer linear chelated contrast agents versus lower risk macrocyclic chelated agents. For PRCA, increased use of subcutaneous epoetin formulations to CKD patients, in part due to convenience and cost-savings considerations, and a European regulatory requirement requiring removal of albumin as a stabilizer, led to toxicity. Overall, 81, 13, and 17 years elapsed between drug introduction into practice and identification of a causal relationship for aspirin, erythropoietin, and gadodiamide, respectively. A substantial decline in new cases of these sADRs occurred within two years of identification of the offending drug. Clinicians should be vigilant for sADRs, even for frequently

  15. Extent of poly-pharmacy, occurrence and associated factors of drug-drug interaction and potential adverse drug reactions in Gondar Teaching Referral Hospital, North West Ethiopia.

    PubMed

    Admassie, Endalkachew; Melese, Tesfahun; Mequanent, Woldeselassie; Hailu, Wubshet; Srikanth, B Akshaya

    2013-10-01

    The aim of this study was to assess the extent of poly-pharmacy, occurrence, and associated factors for the occurrence of drug-drug interaction (DDI) and potential adverse drug reaction (ADR) in Gondar University Teaching Referral Hospital. Institutional-based retrospective cross-sectional study. This study was conducted on prescriptions of both in and out-patients for a period of 3 months at Gondar University Hospital. Both bivariate analysis and multivariate logistic regression were used to identify risk factors for the occurrence of DDI and possible ADRs. All the statistical calculations were performed using SPSS(®) software. A total of 12,334 prescriptions were dispensed during the study period of which, 2,180 prescriptions were containing two or more drugs per prescription. A total of 21,210 drugs were prescribed and the average number of drugs per prescription was 1.72. Occurrences of DDI of all categories (Major, Moderate, and Minor) were analyzed and DDI were detected in 711 (32.6%) prescriptions. Sex was not found to be a risk factor for the occurrence of DDI and ADR, while age and number of medications per prescription were found to be significant risk factors for the occurrence of DDI and ADR. The mean number of drugs per prescription was 1.72 and hence with regard to the WHO limit of drugs per prescription, Gondar hospital was able to maintain the limit and prescriptions containing multiple drugs supposed to be taken systemically. Numbers of drugs per prescription as well as older age were found to be predisposing factors for the occurrence of DDI and potential ADRs while sex was not a risk factor. PMID:24350048

  16. Genetic Variants of NPAT-ATM and AURKA are Associated With an Early Adverse Reaction in the Gastrointestinal Tract of Patients With Cervical Cancer Treated With Pelvic Radiation Therapy

    SciTech Connect

    Ishikawa, Atsuko; Suga, Tomo; Shoji, Yoshimi; Kato, Shingo; Ohno, Tatsuya; Ishikawa, Hitoshi; Yoshinaga, Shinji; Ohara, Kiyoshi; Ariga, Hisanori; Nomura, Kuninori; Shibamoto, Yuta; Ishikawa, Ken-Ichi; Moritake, Takashi; Michikawa, Yuichi; Iwakawa, Mayumi; Imai, Takashi

    2011-11-15

    Purpose: This study sought to associate polymorphisms in genes related to cell cycle regulation or genome maintenance with radiotherapy (RT)-induced an early adverse reaction (EAR) in patients with cervical cancer. Methods and Materials: This study enrolled 243 cervical cancer patients who were treated with pelvic RT. An early gastrointestinal reaction was graded using the National Cancer Institute Common Toxicity Criteria, version 2. Clinical factors of the enrolled patients were analyzed, and 208 patients were grouped for genetic analysis according to their EAR (Grade {<=}1, n = 150; Grade {>=}2, n = 58). Genomic DNA was genotyped, and association with the risk of EAR for 44 functional single-nucleotide polymorphisms (SNPs) of 19 candidate genes was assessed by single-locus, haplotype, and multilocus analyses. Results: Our analysis revealed two haplotypes to be associated with an increased risk of EAR. The first, comprising rs625120C, rs189037T, rs228589A, and rs183460G, is located between the 5' ends of NPAT and ATM (OR = 1.86; 95% CI, 1.21-2.87), whereas the second is located in the AURKA gene and comprises rs2273535A and rs1047972G (OR = 1.75; 95% CI, 1.10-2.78). A third haplotype, rs2273535T and rs1047972A in AURKA, was associated with a reduced EAR risk (OR = 0.42; 95% CI, 0.20-0.89). The risk of EAR was significantly higher among patients with both risk diplotypes than in those possessing the other diplotypes (OR = 3.24; 95% CI, 1.52-6.92). Conclusions: Individual radiosensitivity of intestine may be determined by haplotypes in the NPAT-ATM and AURKA genes. These variants should be explored in larger association studies in cervical cancer patients.

  17. Efficacy of intravenous hydrocortisone administered 2-4 h prior to antivenom as prophylaxis against adverse drug reactions to snake antivenom in Sri Lanka: An open labelled randomized controlled trial.

    PubMed

    Kularatne, Senanayake A M; Weerakoon, Kosala; Silva, Anjana; Maduwage, Kalana; Walathara, Chamara; Rathnayake, Ishani; Medagedara, Senal; Paranagama, Ranjith; Mendis, Suresh; Kumarasiri, P V R

    2016-09-15

    The prevention of adverse drug reactions to antivenom serum poses a formidable challenge in the management of snakebite. Hydrocortisone is being used concurrently with antivenom in order to prevent these adverse drug reactions without a proven benefit. However, all previous studies seemed to ignore the testing of effectiveness of hydrocortisone therapy during its pharmacological effects, which come hours later. On this principle, we aimed to test the effectiveness of intravenous hydrocortisone given 2 h or more prior to the commencement of antivenom therapy to reduce adverse drug reactions to antivenom. In an open-labelled randomized controlled trial, patients with a history of snakebite were randomly assigned to receive either 500 mg intravenous hydrocortisone bolus given 2 h or more prior to antivenom therapy (Group A) or at the time of antivenom therapy (Group B). The primary endpoint was the reduction of adverse drug reactions to antivenom of any grade of severity within the first 48 h. This trial has been registered with the "Sri Lanka Clinical Trials Registry", number SLCTR/2010/005. A total of 236 patients were randomized to group A or Group B. In the group A, 38 participants received hydrocortisone 2 h before administration of antivenom whilst 33 received hydrocortisone less than 2 h before administration of antivenom. In the Group B, 84 participants received hydrocortisone at the time of antivenom therapy. In Group A (n, 38), and Group B (n, 84), 15 patients (39%) and 29 patients (35%) developed reactions respectively and the difference is not significant (p = 0.598). Moreover, hydrocortisone therapy did not significantly reduce the occurrence of antievnom reactions of any grade of severity. Further, it didn't delay the occurrence of antivenom reactions in patients who received hydrocortisone either more than 2 h or less than 2 h before the antivenom as opposed to the control group (group B). Intravenous hydrocortisone shows no difference in the

  18. Reversible Ototoxicity: A Rare Adverse Reaction of Liposomal Amphotericin-B Used for the Treatment of Antimony-Resistant Visceral Leishmaniasis in an Elderly Male

    PubMed Central

    Das, PC; Kandel, Ramesh; Sikka, Kapil; Dey, AB

    2014-01-01

    Amphotericin-B, a broad spectrum antifungal agent, has been known to cause adverse effects such as nephrotoxicity and infusion-related side effects such as fever, chills, rigor, and arthralgias. However, ototoxicity as an adverse effect of Amphotericin-B has not yet been reported in medical literature. We here report a case of a reversible form of ototoxicity induced by liposomal Amphotericin-B (L-AmB). PMID:25093006

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

  1. Conclusions. [hydrogen-based energy

    NASA Technical Reports Server (NTRS)

    1975-01-01

    Conclusions are presented according to general areas of technology with some specific examples of research and technology needs identified. These conclusions provide a base for the future development of detailed program plans and identify research needs that are not being given attention or are not being supported at a sufficient level. Emphasis is placed on hydrogen production and use.

  2. Contact dermatitis as an adverse reaction to some topically used European herbal medicinal products - part 2: Echinacea purpurea-Lavandula angustifolia.

    PubMed

    Gangemi, Sebastiano; Minciullo, Paola L; Miroddi, Marco; Chinou, Ioanna; Calapai, Gioacchino; Schmidt, Richard J

    2015-04-01

    This review focuses on contact dermatitis as an adverse effect of a selection of topically used herbal medicinal products for which the European Medicines Agency has completed an evaluation up to the end of November 2013 and for which a Community herbal monograph has been produced. Part 2: Echinacea purpurea Moench-Lavandula angustifolia Mill. PMID:25600644

  3. Contact dermatitis as an adverse reaction to some topically used European herbal medicinal products - part 1: Achillea millefolium-Curcuma longa.

    PubMed

    Calapai, Gioacchino; Miroddi, Marco; Minciullo, Paola L; Caputi, Achille P; Gangemi, Sebastiano; Schmidt, Richard J

    2014-07-01

    This review focuses on contact dermatitis as an adverse effect of a selection of topically used herbal medicinal products for which the European Medicines Agency has completed an evaluation up to the end of November 2013 and for which a Community herbal monograph has been produced. Part 1: Achillea millefolium L.-Curcuma longa L.

  4. Contact dermatitis as an adverse reaction to some topically used European herbal medicinal products - part 1: Achillea millefolium-Curcuma longa.

    PubMed

    Calapai, Gioacchino; Miroddi, Marco; Minciullo, Paola L; Caputi, Achille P; Gangemi, Sebastiano; Schmidt, Richard J

    2014-07-01

    This review focuses on contact dermatitis as an adverse effect of a selection of topically used herbal medicinal products for which the European Medicines Agency has completed an evaluation up to the end of November 2013 and for which a Community herbal monograph has been produced. Part 1: Achillea millefolium L.-Curcuma longa L. PMID:24621152

  5. Conclusions and Recommendations. Chapter 37

    NASA Technical Reports Server (NTRS)

    Lamar, John E.; Hummel, Dietrich

    2009-01-01

    This chapter provides a brief wrap-up of the task group report and focuses on the overall conclusions and recommendations for future work for the CAWAPI and VFE-2 facets beyond the task group. The overall conclusion is that the Technology Readiness Level (TRL) of CFD solvers has been improved in predicting the flow-physics of vortex-dominated flows during the work of the task group, by having flight and wind-tunnel data available for comparison. Moreover, like all good scientific studies, this task group has identified flight conditions on the F-16XL airplane or wind-tunnel test conditions for a specific leading-edge radius on the 65 delta-wing model where the TRL still needs to be increased.

  6. Conclusive exclusion of quantum states

    NASA Astrophysics Data System (ADS)

    Bandyopadhyay, Somshubhro; Jain, Rahul; Oppenheim, Jonathan; Perry, Christopher

    2014-02-01

    In the task of quantum state exclusion, we consider a quantum system prepared in a state chosen from a known set. The aim is to perform a measurement on the system which can conclusively rule that a subset of the possible preparation procedures cannot have taken place. We ask what conditions the set of states must obey in order for this to be possible and how well we can complete the task when it is not. The task of quantum state discrimination forms a subclass of this set of problems. Within this paper, we formulate the general problem as a semidefinite program (SDP), enabling us to derive sufficient and necessary conditions for a measurement to be optimal. Furthermore, we obtain a necessary condition on the set of states for exclusion to be achievable with certainty, and we give a construction for a lower bound on the probability of error. This task of conclusively excluding states has gained importance in the context of the foundations of quantum mechanics due to a result from Pusey, Barrett, and Rudolph (PBR). Motivated by this, we use our SDP to derive a bound on how well a class of hidden variable models can perform at a particular task, proving an analog of Tsirelson's bound for the PBR experiment and the optimality of a measurement given by PBR in the process. We also introduce variations of conclusive exclusion, including unambiguous state exclusion, and state exclusion with worst-case error.

  7. Contact dermatitis as an adverse reaction to some topically used European herbal medicinal products - Part 3: Mentha × piperita - Solanum dulcamara.

    PubMed

    Calapai, Gioacchino; Minciullo, Paola L; Miroddi, Marco; Chinou, Ioanna; Gangemi, Sebastiano; Schmidt, Richard J

    2016-03-01

    This review focuses on contact dermatitis as an adverse effect of a selection of topically used herbal medicinal products for which the European Medicines Agency has completed an evaluation up to the end of November 2013 and for which a Community herbal monograph - now (since 2015)(†) called a European Union herbal monograph - has been produced. Part 3: Mentha × piperita L.-Solanum dulcamara L. PMID:26563681

  8. Contact dermatitis as an adverse reaction to some topically used European herbal medicinal products - Part 3: Mentha × piperita - Solanum dulcamara.

    PubMed

    Calapai, Gioacchino; Minciullo, Paola L; Miroddi, Marco; Chinou, Ioanna; Gangemi, Sebastiano; Schmidt, Richard J

    2016-03-01

    This review focuses on contact dermatitis as an adverse effect of a selection of topically used herbal medicinal products for which the European Medicines Agency has completed an evaluation up to the end of November 2013 and for which a Community herbal monograph - now (since 2015)(†) called a European Union herbal monograph - has been produced. Part 3: Mentha × piperita L.-Solanum dulcamara L.

  9. [SENTIERI Project: discussion and conclusions].

    PubMed

    Pirastu, Roberta; Ricci, Paolo; Comba, Pietro; Bianchi, Fabrizio; Biggeri, Annibale; Conti, Susanna; Fazzo, Lucia; Forastiere, Francesco; Iavarone, Ivano; Martuzzi, Marco; Musmeci, Loredana; Pasetto, Roberto; Zona, Amerigo; Crocetti, Emanuele

    2014-01-01

    showing the increase, considering latency and the length of the observation period. Of further interest are results relating to diseases of the urinary tract such as kidney failure in the NPCSs of Basso bacino del fiume Chienti, Taranto, Milazzo and Priolo. Overall, the results discussed above are consistent with the previous findings pertaining to mortality for 1995-2002. The present analysis also introduces a new element - the study of cancer incidence and hospital discharges - which can tell us a great deal about diseases with high survival rates or non lethal ones. The first is the case of thyroid cancer, which presents increases in both databases and for both genders in a number of NPCSs (Brescia-Caffaro, Laghi di Mantova, Milazzo, Sassuolo- Scandiano and Taranto). The study of cancer incidence and hospital discharges also revealed cancer excesses for melanoma, breast cancer and non Hodgkin lymphoma in Brescia-Caffaro NPCS where PCBs (Polychlorinated biphenyl) are the site's main pollutant. PCBs, according to the 2013 evaluation of the International Agency for Research on Cancer, are ascertained human carcinogens for melanoma and probable carcinogens for breast cancer and non-Hodgkin lymphoma. The results pertaining to cancer incidence in the 17 NPCSs can also be presented using rankings by area or disease analyzed by a multivariate hierarchical Bayesian model. These rankings reveal an overlapping of credibility intervals, such that it is not possible to speak of a limited number of cancer sites or of certain NPCSs as being particularly affected. Every NPCS, therefore, must be considered individually and ordering them by ranking of cancer incidence wouldn't be appropriate. Data collected concerning some of the NPCSs in the context of the SENTIERI Project is so conclusive that remediation measures can immediately be put in place. This is the case in the Biancavilla and Brescia-Caffaro NPCSs. A similar conclusion can be drawn for complex locations such as Taranto

  10. Transnational industrial power, the medical profession and the regulatory state: adverse drug reactions and the crisis over the safety of Halcion in the Netherlands and the UK.

    PubMed

    Abraham, John

    2002-11-01

    Taking the controversy over the safety of the hypnotic, Halcion, in the Netherlands and the UK, as a case study, this article examines the problems for public health associated with responses to warnings about drug hazards by regulatory agencies, governmental expert advisers, the pharmaceutical industry and the medical profession. It is argued that regulators and the medical profession rely too heavily on manufacturers to investigate warnings from doctors' spontaneous reporting of adverse effects of drug products on the market. It is demonstrated that a pharmaceutical firm's commitment to search effectively for evidence against the safety of its own product in order to confirm doctors' warnings can have severe limitations. Deficiencies in the socio-institutional responses to post-market 'early warning systems' about drug hazards imply that the regulatory policies of 'early licensing' and minimal pre-market checks for new drugs are misconceived and threaten public health. To improve public protection from drug injury, the regulators should abandon their conviction that compelling evidence of drug hazards are required to confirm doctors' warning signals prior to regulatory intervention. Instead, they should adopt a policy of measured regulatory intervention as an immediate response to warning signals, while investigators, independent of the manufacturers, assess the significance of the signal.

  11. 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

  12. Activation/modulation of adaptive immunity emerges simultaneously after 17DD yellow fever first-time vaccination: is this the key to prevent severe adverse reactions following immunization?

    PubMed Central

    Martins, M Â; Silva, M L; Marciano, A P V; Peruhype-Magalhães, V; Eloi-Santos, S M; Ribeiro, J G L; Correa-Oliveira, R; Homma, A; Kroon, E G; Teixeira-Carvalho, A; Martins-Filho, O A

    2007-01-01

    Over past decades the 17DD yellow fever vaccine has proved to be effective in controlling yellow fever and promises to be a vaccine vector for other diseases, but the cellular and molecular mechanisms by which it elicits such broad-based immunity are still unclear. In this study we describe a detailed phenotypic investigation of major and minor peripheral blood lymphocyte subpopulations aimed at characterizing the kinetics of the adaptive immune response following primary 17DD vaccination. Our major finding is a decreased frequency of circulating CD19+ cells at day 7 followed by emerging activation/modulation phenotypic features (CD19+interleukin(IL)10R+/CD19+CD32+) at day 15. Increased frequency of CD4+human leucocyte antigen D-related(HLA-DR+) at day 7 and CD8+HLA-DR+ at day 30 suggest distinct kinetics of T cell activation, with CD4+ T cells being activated early and CD8+ T cells representing a later event following 17DD vaccination. Up-regulation of modulatory features on CD4+ and CD8+ cells at day 15 seems to be the key event leading to lower frequency of CD38+ T cells at day 30. Taken together, our findings demonstrate the co-existence of phenotypic features associated with activation events and modulatory pathways. Positive correlations between CD4+HLA-DR+ cells and CD4+CD25high regulatory T cells and the association between the type 0 chemokine receptor CCR2 and the activation status of CD4+ and CD8+ cells further support this hypothesis. We hypothesize that this controlled microenviroment seems to be the key to prevent the development of serious adverse events, and even deaths, associated with the 17DD vaccine reported in the literature. PMID:17309541

  13. Adverse skin reactions due to pegylated interferon alpha 2b plus ribavirin combination therapy in a patient with chronic hepatitis C virus.

    PubMed

    Hashimoto, Yuki; Kanto, Hiromi; Itoh, Masatoshi

    2007-08-01

    Pegylated interferon (IFN)-alpha-2b with ribavirin has recently replaced "standard" IFN-alpha for the treatment of chronic hepatitis C. The most common side-effect of pegylated IFN-alpha-2b plus ribavirin combination therapy is localized inflammatory skin lesions at the site of injection. A 66-year-old female treated with once-weekly pegylated IFN-alpha-2b plus ribavirin for active chronic hepatitis C developed inflammatory skin lesions 2 months after starting antiviral treatment. The type of skin reactions observed were vesicle erythematous eruptions at the injection sites, and pruritic papular erythematous eruptions located on the face, neck, distal limbs, dorsa of the hands, trunk and buttocks away from the injection sites. Histological examination was performed on the pruritic papular erythematous eruption located on the left forearm, away from the injection sites. It showed epidermal spongiosis, a spongiotic microvesicle, and perivascular infiltration of the upper dermis with lymphocytes. The treatment was interrupted subsequently and the patient was rechallenged with pegylated IFN-alpha-2b plus ribavirin combination therapy, oral prednisolone with olopatadine hydrochloride and topical 0.1% diflucortolone valerate, which led to a significant improvement of skin lesions. Erythema with infiltration can occur at the injection sites of pegylated IFN-alpha-2b. However, the occurrence of vesicle erythematous eruptions away from the injection sites and autosensitization dermatitis apart from injection sites have not yet been frequently reported. PMID:17683392

  14. Assessment of an oral Mycobacterium bovis BCG vaccine and an inactivated M. bovis preparation for wild boar in terms of adverse reactions, vaccine strain survival, and uptake by nontarget species.

    PubMed

    Beltrán-Beck, Beatriz; Romero, Beatriz; Sevilla, Iker A; Barasona, Jose A; Garrido, Joseba M; González-Barrio, David; Díez-Delgado, Iratxe; Minguijón, Esmeralda; Casal, Carmen; Vicente, Joaquín; Gortázar, Christian; Aranaz, Alicia

    2014-01-01

    Wildlife vaccination is increasingly being considered as an option for tuberculosis control. We combined data from laboratory trials and an ongoing field trial to assess the risk of an oral Mycobacterium bovis BCG vaccine and a prototype heat-inactivated Mycobacterium bovis preparation for Eurasian wild boar (Sus scrofa). We studied adverse reactions, BCG survival, BCG excretion, and bait uptake by nontarget species. No adverse reactions were observed after administration of BCG (n = 27) or inactivated M. bovis (n = 21). BCG was not found at necropsy (175 to 300 days postvaccination [n = 27]). No BCG excretion was detected in fecal samples (n = 162) or in urine or nasal, oral, or fecal swab samples at 258 days postvaccination (n = 29). In the field, we found no evidence of loss of BCG viability in baits collected after 36 h (temperature range, 11°C to 41°C). Camera trapping showed that wild boar (39%) and birds (56%) were the most frequent visitors to bait stations (selective feeders). Wild boar activity patterns were nocturnal, while diurnal activities were recorded for all bird species. We found large proportions of chewed capsules (29%) (likely ingestion of the vaccine) and lost baits (39%) (presumably consumed), and the proportion of chewed capsules showed a positive correlation with the presence of wild boar. Both results suggest proper bait consumption (68%). These results indicate that BCG vaccination in wild boar is safe and that, while bait consumption by other species is possible, this can be minimized by using selective cages and strict timing of bait deployment.

  15. Assessment of an Oral Mycobacterium bovis BCG Vaccine and an Inactivated M. bovis Preparation for Wild Boar in Terms of Adverse Reactions, Vaccine Strain Survival, and Uptake by Nontarget Species

    PubMed Central

    Beltrán-Beck, Beatriz; Romero, Beatriz; Sevilla, Iker A.; Barasona, Jose A.; Garrido, Joseba M.; González-Barrio, David; Díez-Delgado, Iratxe; Minguijón, Esmeralda; Casal, Carmen; Vicente, Joaquín; Gortázar, Christian

    2014-01-01

    Wildlife vaccination is increasingly being considered as an option for tuberculosis control. We combined data from laboratory trials and an ongoing field trial to assess the risk of an oral Mycobacterium bovis BCG vaccine and a prototype heat-inactivated Mycobacterium bovis preparation for Eurasian wild boar (Sus scrofa). We studied adverse reactions, BCG survival, BCG excretion, and bait uptake by nontarget species. No adverse reactions were observed after administration of BCG (n = 27) or inactivated M. bovis (n = 21). BCG was not found at necropsy (175 to 300 days postvaccination [n = 27]). No BCG excretion was detected in fecal samples (n = 162) or in urine or nasal, oral, or fecal swab samples at 258 days postvaccination (n = 29). In the field, we found no evidence of loss of BCG viability in baits collected after 36 h (temperature range, 11°C to 41°C). Camera trapping showed that wild boar (39%) and birds (56%) were the most frequent visitors to bait stations (selective feeders). Wild boar activity patterns were nocturnal, while diurnal activities were recorded for all bird species. We found large proportions of chewed capsules (29%) (likely ingestion of the vaccine) and lost baits (39%) (presumably consumed), and the proportion of chewed capsules showed a positive correlation with the presence of wild boar. Both results suggest proper bait consumption (68%). These results indicate that BCG vaccination in wild boar is safe and that, while bait consumption by other species is possible, this can be minimized by using selective cages and strict timing of bait deployment. PMID:24173022

  16. Progressive multifocal leukoencephalopathy associated with brentuximab vedotin therapy: A report of 5 cases from the Southern Network on Adverse Reactions (SONAR) project

    PubMed Central

    Carson, Kenneth R.; Newsome, Scott D.; Kim, Ellen J.; Wagner-Johnston, Nina D.; von Geldern, Gloria; Moskowitz, Craig H.; Moskowitz, Alison J.; Rook, Alain H.; Jalan, Pankaj; Loren, Alison W.; Landsburg, Daniel; Coyne, Thomas; Tsai, Donald; Raisch, Dennis W.; Norris, LeAnn B.; Bookstaver, P Brandon; Sartor, Oliver; Bennett, Charles L.

    2015-01-01

    Purpose Brentuxiumab vedotin (BV) is an anti-CD30 monoclonal antibody-drug conjugate approved in 2011 for treating anaplastic large cell and Hodgkin lymphomas. The product label indicates that three BV-treated patients developed progressive multifocal leukoencephalopathy (PML), a frequently fatal JC-virus induced central nervous system infection. Prior immunosuppressive therapy and compromised immune systems were postulated risk factors. We report 5 patients who developed BV-associated PML, including two immunocompetent patients. Patients Case information was obtained from clinicians (four patients) or a Food and Drug Administration database (one patient). Results All five patients had lymphoid malignancies. Two patients with cutaneous T-cell lymphomas had not previously received chemotherapy. PML developed after a median of three BV doses (range, 2 to 6) and within a median of 7 weeks following BV initiation (range, 3 to 34 weeks). Presenting findings included aphasia, dysarthria, confusion, hemiparesis, and gait dysfunction; JC virus in cerebrospinal fluid (two patients), or CNS biopsy (three patients); and brain MRI scans with white matter abnormalities (five patients). Four patients died a median of 8 weeks (range, 6 to 16 weeks) after PML diagnosis. The sole survivor developed immune reconstitution inflammatory syndrome. Conclusion PML can develop after a few BV doses and within weeks of BV initiation. Clinicians should be aware of this syndrome, particularly when neurologic changes develop following BV initiation. The decision to administer BV to patients with indolent cutaneous lymphomas should be based on consideration of risk-benefit profiles and of alternative options. PMID:24771533

  17. [Cutaneous adverse effects of TNFalpha antagonists].

    PubMed

    Failla, V; Sabatiello, M; Lebas, E; de Schaetzen, V; Dezfoulian, B; Nikkels, A F

    2012-01-01

    The TNFalpha antagonists, including adalimumab, etanercept and infliximab, represent a class of anti-inflammatory and immunosuppressive drugs. Although cutaneous adverse effects are uncommon, they are varied. There is no particular risk profile to develop cutaneous adverse effects. The principal acute side effects are injection site reactions and pruritus. The major long term cutaneous side effects are infectious and inflammatory conditions. Neoplastic skin diseases are exceptional. The association with other immunosuppressive agents can increase the risk of developing cutaneous adverse effects. Some adverse effects, such as lupus erythematosus, require immediate withdrawal of the biological treatment, while in other cases temporary withdrawal is sufficient. The majority of the other cutaneous adverse effects can be dealt without interrupting biologic treatment. Preclinical and clinical investigations revealed that the new biologics, aiming IL12/23, IL23 and IL17, present a similar profile of cutaneous adverse effects, although inflammatory skin reactions may be less often encountered compared to TNFalpha antagonists.

  18. Adverse local tissue reaction (ALTR) associated with corrosion products in metal-on-metal and dual modular neck total hip replacements is associated with upregulation of interferon gamma-mediated chemokine signaling.

    PubMed

    Kolatat, Kritti; Perino, Giorgio; Wilner, Gabrielle; Kaplowitz, Elianna; Ricciardi, Benjamin F; Boettner, Friedrich; Westrich, Geoffrey H; Jerabek, Seth A; Goldring, Steven R; Purdue, P Edward

    2015-10-01

    Adverse local tissue reactions (ALTR) associated with tribocorrosion following total hip arthroplasty (THA) have become a significant clinical concern in recent years. In particular, implants featuring metal-on-metal bearing surfaces and modular femoral stems have been reported to result in elevated rates of ALTR. These tribocorrosion-related tissue reactions are characterized by marked necrosis and lymphocytic infiltration, which contrasts sharply with the macrophagic and foreign body giant cell inflammation associated with polyethylene wear particle induced peri-implant osteolysis. In this study, we characterize tribocorrosion-associated ALTR at a molecular level. Gene expression profiling of peri-implant tissue around failing implants identifies upregulation of numerous inflammatory mediators in ALTR, including several interferon gamma inducible factors, most notably the chemokines MIG/CXCL9 and IP-10/CXCL10. This expression profile is distinct from that associated with polyethylene wear induced osteolysis, which is characterized by induction of markers of alternative macrophage activation, such as chitotriosidase (CHIT-1). Importantly, MIG/CXCL9 and IP-10/CXCL10 are also elevated at the protein level in the synovial fluid and, albeit more moderately, the serum, of ALTR patients, raising the possibility that these factors may serve as circulating biomarkers for the early detection of ALTR in at-risk patients. PMID:25940887

  19. Vaccine Adverse Events

    MedlinePlus

    ... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Vaccines, Blood & Biologics Home Vaccines, Blood & Biologics Safety & Availability ( ... Center for Biologics Evaluation & Research Vaccine Adverse Events Vaccine Adverse Events Share Tweet Linkedin Pin it More ...

  20. Sedating pediatric dental patients by oral ketamine with alternating bi-lateral stimulation of eye movement desensitization and minimizing adverse reaction of ketamine by acupuncture and Bi-Digital O-Ring Test.

    PubMed

    Lu, Dominic P; Wu, Ping-Shi; Lu, Winston I

    2012-01-01

    Ketamine, besides being an anesthetic agent, is also a strong analgesic that can be especially useful for painful procedures. Vivid dreams and nightmare, considered as undesirable side effects of ketamine, are rarely encountered when administrated orally, making it one of the most desirable oral sedative for children because it partially protects the pharyngeal-laryngeal reflex. Besides, if used in recommended dosage, it does not suppress the cardiopulmonary function as most other sedatives do. Ketamine's bronchodilator effect makes it a good sedative for children with asthma, allergies, and hay fever. Alternating bi-lateral stimulation (ABLS) of eye movement desensitization, applying pre-operatively before ketamine was found to reduce the post-operative violent emergence and behavioral problems. Acupressure at P 6 (Neikuan) acupoint helps to decrease nausea and vomiting episodes by ketamine. 36 patients with history of unmanageable behavior were sedated with ketamine 3mg/kg and ABLS. To prevent possible adverse reaction, Bi-Digital O-Ring Test (BDORT) were used to test all patients. ABLS significantly decreased tearful separation from parent. It took 15 to 20 minutes for ketamine to take effect, peak effect took 20 to 25 minutes. Working time ranged from 20 to 40 minutes. Post-operative recovery was more pleasant when ABLS was combined with ketamine, acupuncture/acupressure not only prevented vomiting and BDORT safeguard the patients from unpredictable untoward side effects but also promoting calmness. PMID:23156203

  1. Adverse events related to blood transfusion

    PubMed Central

    Sahu, Sandeep; Hemlata; Verma, Anupam

    2014-01-01

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

  2. Anticoagulation-associated adverse drug events

    PubMed Central

    Piazza, Gregory; Nguyen, Thanh Nha; Cios, Deborah; Labreche, Matthew; Hohlfelder, Benjamin; Fanikos, John; Fiumara, Karen; Goldhaber, Samuel Z.

    2011-01-01

    Purpose Anticoagulant drugs are among the most common medications that cause adverse drug events (ADEs) in hospitalized patients. We performed a five-year retrospective study at Brigham and Women’s Hospital to determine clinical characteristics, types, root causes, and outcomes of anticoagulant-associated adverse drug events (ADEs). Methods We reviewed all inpatient anticoagulant-associated ADEs, including adverse drug reactions (ADRs) and medication errors, reported at Brigham and Women’s Hospital through the Safety Reporting System from May 2004 to May 2009. We also collected data regarding the cost associated with hospitalizations in which ADRs occurred. Results Of 463 anticoagulant-associated ADEs, 226 were MEs (48.8%), 141 were ADRs (30.5%), and 96 (20.7%) involved both a medication error and ADR. Seventy percent of anticoagulant-associated ADEs were potentially preventable. Transcription errors (48%) were the most frequent root cause of anticoagulant-associated medication errors, while medication errors (40%) were a common root cause of anticoagulant-associated ADRs. Death within 30 days of anticoagulant-associated ADEs occurred in 11% of patients. After an anticoagulant-associated ADR, most hospitalization expenditures were attributable to nursing costs (mean $33,189 per ADR) followed by pharmacy costs (mean $7,451 per ADR). Conclusion Most anticoagulant-associated ADEs among inpatients result from medication errors and are therefore potentially preventable. We observed an elevated 30-day mortality rate among patients who suffered an anticoagulant-associated ADE and high hospitalization costs following ADRs. Further Quality Improvement efforts to reduce anticoagulant-associated medication errors are warranted to improve patient safety and decrease health care expenditures. PMID:22114827

  3. Adverse effects of anabolic steroids in athletes.

    PubMed

    Kibble, M W; Ross, M B

    1987-09-01

    The effects of anabolic steroid use on athletic performance and the adverse effects associated with the use of anabolic steroids are reviewed. Anabolic steroids increase protein synthesis in skeletal muscles and reverse catabolic processes. Because of these properties, some athletes use anabolic steroids in an attempt to improve their athletic performance. However, studies indicate that increases in muscle mass and strength during anabolic steroid administration are observed only in athletes who already are weight-trained and who continue intensive training while maintaining high-protein, high-calorie diets. Adverse effects attributed to anabolic steroid use occur frequently. Serious adverse effects include hepatic and endocrine dysfunction; cardiovascular and behavioral changes also are reported. Some of the adverse effects associated with the use of these agents are irreversible, particularly in women. The use of anabolic steroids to improve athletic performance has become prevalent. However, the reported benefits are tempered by numerous adverse reactions.

  4. Prevalence of Failure due to Adverse Reaction to Metal Debris in Modern, Medium and Large Diameter Metal-on-Metal Hip Replacements--The Effect of Novel Screening Methods: Systematic Review and Metaregression Analysis.

    PubMed

    Reito, Aleksi; Lainiala, Olli; Elo, Petra; Eskelinen, Antti

    2016-01-01

    Metal-on-metal (MoM) hip replacements were used for almost a decade before adverse reactions to metal debris (ARMD) were found to be a true clinical problem. Currently, there is a paucity of evidence regarding the usefulness of systematic screening for ARMD. We implemented a systematic review and meta-analysis to establish the prevalence of revision confirmed ARMD stratified by the use of different screening protocols in patients with MoM hip replacements. Five levels of screening were identified: no screening (level 0), targeted blood metal ion measurement and/or cross-sectional imaging (level 1), metal ion measurement without imaging (level 2), metal ion measurement with targeted imaging (level 3) and comprehensive screening (both metal ions and imaging for all; level 4). 122 studies meeting our eligibility criteria were included in analysis. These studies included 144 study arms: 100 study arms with hip resurfacings, 33 study arms with large-diameter MoM total hip replacements (THR), and 11 study arms with medium-diameter MoM THRs. For hip resurfacing, the lowest prevalence of ARMD was seen with level 0 screening (pooled prevalence 0.13%) and the highest with level 4 screening (pooled prevalace 9.49%). Pooled prevalence of ARMD with level 0 screening was 0.29% and with level 4 screening 21.3% in the large-diameter MoM THR group. In metaregression analysis of hip resurfacings, level 4 screening was superior with regard to prevalence of ARMD when compared with other levels. In the large diameter THR group level 4 screening was superior to screening 0,2 and 3. These outcomes were irrespective of follow-up time or study publication year. With hip resurfacings, routine cross-sectional imaging regardless of clinical findings is advisable. It is clear, however, that targeted metal ion measurement and/or imaging is not sufficient in the screening for ARMD in any implant concepts. However, economic aspects should be weighed when choosing the preferred screening level

  5. Association between SLCO1B1 -521T>C and -388A>G polymorphisms and risk of statin-induced adverse drug reactions: A meta-analysis.

    PubMed

    Jiang, Jiajia; Tang, Qing; Feng, Jing; Dai, Rong; Wang, Yang; Yang, Yuan; Tang, Xiaojun; Deng, Changkai; Zeng, Huan; Zhao, Yong; Zhang, Fan

    2016-01-01

    An increasing number of studies have investigated the association between SLCO1B1 -521T>C and -388A>G polymorphisms and the risk of statin-induced adverse drug reactions (ADRs), but the results have been inconsistent. This meta-analysis was performed to gain more insight into the relationship. PubMed, Embase, Cochrane Library and Web of Science were searched for relevant articles published before March 5th, 2015. The quality of included studies was evaluated by the Newcastle-Ottawa Quality scale. Pooled effect estimates (odds ratios [ORs] or hazard ratios [HRs) and corresponding 95 % confidence intervals (CIs) were calculated to assess the association in overall and subgroup analyses for various genetic models. Begg's rank correlation test and Egger's linear regression test were used to examine the publication bias. A total of nine cohort and four case-control studies involving 11, 246 statin users, of whom 2, 355 developing ADRs were included in the analysis. Combined analysis revealed a significant association between the SLCO1B1-521T>C polymorphism and increased risk for ADRs caused by various statins, but the synthesis heterogeneity was generally large (dominant model: pooled effect estimate = 1.85, 95 % CI 1.20-2.85, P = 0.005; I (2) = 80.70 %, Pheterogeneity < 0.001). Subgroup analysis by statin type showed that the ADRs risk was significantly elevated among simvastatin users (dominant model: pooled effect estimate = 3.43, 95 % CI 1.80-6.52, P = 0.001; I (2) = 59.60 %, Pheterogeneity = 0.060), but not among atorvastatin users. No significant relationship was found between the -388A>G polymorphism and ADRs caused by various statins (dominant model: pooled effect estimate = 0.94, 95 % CI 0.79-1.13, P = 0.526; I (2) = 40.10 %, Pheterogeneity = 0.196). The meta-analysis suggests that SLCO1B1 -521T>C polymorphism may be a risk factor for statin-induced ADRs, especially in simvastatin therapy. Conversely, there may be no significant

  6. Prevalence of Failure due to Adverse Reaction to Metal Debris in Modern, Medium and Large Diameter Metal-on-Metal Hip Replacements – The Effect of Novel Screening Methods: Systematic Review and Metaregression Analysis

    PubMed Central

    Reito, Aleksi; Lainiala, Olli; Elo, Petra; Eskelinen, Antti

    2016-01-01

    Metal-on-metal (MoM) hip replacements were used for almost a decade before adverse reactions to metal debris (ARMD) were found to be a true clinical problem. Currently, there is a paucity of evidence regarding the usefulness of systematic screening for ARMD. We implemented a systematic review and meta-analysis to establish the prevalence of revision confirmed ARMD stratified by the use of different screening protocols in patients with MoM hip replacements. Five levels of screening were identified: no screening (level 0), targeted blood metal ion measurement and/or cross-sectional imaging (level 1), metal ion measurement without imaging (level 2), metal ion measurement with targeted imaging (level 3) and comprehensive screening (both metal ions and imaging for all; level 4). 122 studies meeting our eligibility criteria were included in analysis. These studies included 144 study arms: 100 study arms with hip resurfacings, 33 study arms with large-diameter MoM total hip replacements (THR), and 11 study arms with medium-diameter MoM THRs. For hip resurfacing, the lowest prevalence of ARMD was seen with level 0 screening (pooled prevalence 0.13%) and the highest with level 4 screening (pooled prevalace 9.49%). Pooled prevalence of ARMD with level 0 screening was 0.29% and with level 4 screening 21.3% in the large-diameter MoM THR group. In metaregression analysis of hip resurfacings, level 4 screening was superior with regard to prevalence of ARMD when compared with other levels. In the large diameter THR group level 4 screening was superior to screening 0,2 and 3. These outcomes were irrespective of follow-up time or study publication year. With hip resurfacings, routine cross-sectional imaging regardless of clinical findings is advisable. It is clear, however, that targeted metal ion measurement and/or imaging is not sufficient in the screening for ARMD in any implant concepts. However, economic aspects should be weighed when choosing the preferred screening level

  7. Adverse effects of extra-articular corticosteroid injections: a systematic review

    PubMed Central

    2010-01-01

    Background To estimate the occurrence and type of adverse effects after application of an extra-articular (soft tissue) corticosteroid injection. Methods A systematic review of the literature was made based on a PubMed and Embase search covering the period 1956 to January 2010. Case reports were included, as were prospective and retrospective studies that reported adverse events of corticosteroid injection. All clinical trials which used extra-articular corticosteroid injections were examined. We divided the reported adverse events into major (defined as those needing intervention or not disappearing) and minor ones (transient, not requiring intervention). Results The search yielded 87 relevant studies:44 case reports, 37 prospective studies and 6 retrospective studies. The major adverse events included osteomyelitis and protothecosis; one fatal necrotizing fasciitis; cellulitis and ecchymosis; tendon ruptures; atrophy of the plantar fat was described after injecting a neuroma; and local skin effects appeared as atrophy, hypopigmentation or as skin defect. The minor adverse events effects ranged from skin rash to flushing and disturbed menstrual pattern. Increased pain or steroid flare after injection was reported in 19 studies. After extra-articular injection, the incidence of major adverse events ranged from 0-5.8% and that of minor adverse events from 0-81%. It was not feasible to pool the risk for adverse effects due to heterogeneity of study populations and difference in interventions and variance in reporting. Conclusion In this literature review it was difficult to accurately quantify the incidence of adverse effects after extra-articular corticosteroid injection. The reported adverse events were relatively mild, although one fatal reaction was reported. PMID:20836867

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

    PubMed Central

    Fujiwara, Masakazu; Kawasaki, Yohei; Yamada, Hiroshi

    2016-01-01

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

  9. Adulthood personality correlates of childhood adversity

    PubMed Central

    Carver, Charles S.; Johnson, Sheri L.; McCullough, Michael E.; Forster, Daniel E.; Joormann, Jutta

    2014-01-01

    Objective: Childhood adversity has been linked to internalizing and externalizing disorders and personality disorders in adulthood. This study extends that research by examining several personality measures as correlates of childhood adversity. Method: In a college sample self-reports were collected of childhood adversity, several scales relating to personality, and current depression symptoms as a control variable. The personality-related scales were reduced to four latent variables, which we termed anger/aggression, extrinsic focus, agreeableness, and engagement. Results: Controlling for concurrent depressive symptoms and gender, higher levels of reported childhood adversity related to lower agreeableness and to higher anger/aggression and extrinsic focus. Conclusions: Findings suggest that early adversity is linked to personality variables relevant to the building of social connection. PMID:25484874

  10. Transfusion-related adverse events at the tertiary care center in North India: An institutional hemovigilance effort

    PubMed Central

    Bhattacharya, Prasun; Marwaha, Neelam; Dhawan, Hari Krishan; Roy, Pallab; Sharma, R. R.

    2011-01-01

    Aim: This study was designed to analyze the incidence and spectrum of adverse effects of blood transfusion so as to initiate measures to minimize risks and improve overall transfusion safety in the institute. Materials and Methods: During the period from July 2002 to July 2003 all the adverse events related to transfusion of blood and blood components in various clinical specialties were recorded. They were analyzed and classified on the basis of their clinical features and laboratory tests. Attempt was also made to study the predisposing risk factors. Results: During the study period 56,503 blood and blood components were issued to 29,720 patients. A total of 105 adverse reactions due to transfusion were observed during the study period. A majority of the adverse reactions was observed in hemato-oncology patients 43% (n = 45) and in presensitized patient groups 63% (n = 66). FNHTR 41% (n = 43) and allergic reactions 34% (n = 36) were the most common of all types of adverse transfusion reactions, followed by AcHTR 8.56% (n = 9). Majority of these AcHTR were due to unmonitored storage of blood in the refrigerator of wards resulting in hemolysis due to thermal injury. Less frequently observed reactions were anaphylactoid reactions (n = 4), bacterial sepsis (n = 4), hypervolemia (n = 2), hypocalcemia (n = 2), TRALI (n = 1), DHTR (n = 1), and TAGvHD (n = 1). Conclusion: Analysis of transfusion-related adverse outcomes is essential for improving safety. Factors such as improvement of blood storage conditions outside the blood bank, improvement in cross-matching techniques, careful donor screening, adherence to good manufacturing practices while component preparation, bedside monitoring of transfusion, and documentation of adverse events will help in reducing transfusion-related morbidity and mortality. PMID:21897598

  11. 4.11 Summary and Conclusions

    NASA Astrophysics Data System (ADS)

    Noßke, D.; Mattsson, S.; Johansson, L.

    This document is part of Subvolume A 'Fundamentals and Data in Radiobiology, Radiation Biophysics, Dosimetry and Medical Radiological Protection' of Volume 7 'Medical Radiological Physics' of Landolt-Börnstein - Group VIII 'Advanced Materials and Technologies'. It contains the Section '4.11 Summary and Conclusions' of the Chapter '4 Dosimetry in Nuclear Medicine Diagnosis and Therapy'.

  12. The TOEFL and Domestic Students: Conclusively Inappropriate

    ERIC Educational Resources Information Center

    Johnson, Dixon C.

    1977-01-01

    This experiment tested college students whose first language is English with the TOEFL examination. The major conclusion was that TOEFL scores do not relate to academic aptitude or performance of domestic students and to evaluate English competency of native speakers with this test is inappropriate. (CHK)

  13. The common premise for uncommon conclusions.

    PubMed

    Coady, C A J

    2013-05-01

    Recent controversy over philosophical advocacy of infanticide (or the comically-styled euphemism 'postnatal abortion') reveals a surprisingly common premise uniting many of the opponents and supporters of the practice. This is the belief that the moral status of the early fetus or embryo with respect to a right to life is identical to that of a newly born or even very young baby. From this premise, infanticidists and strong anti-abortionists draw opposite conclusions, the former that the healthy newly born have no inherent right to life and the latter that minute embryos and the very early fetus have the same right to life as young babies. (Indeed strong anti-abortionists tend to regard this right to life as identical to that possessed by adult humans.) This paper argues that these opposed conclusions are both deeply implausible and that the implausibility resides in the common premise. The argument requires some attention to the structure of the philosophical case underpinning the supposed vice of speciesism that has been given intellectual currency by many philosophers, most notably Peter Singer, and also to the reasoning behind the strong anti-abortionist adoption of the common premise. PMID:23637428

  14. The common premise for uncommon conclusions.

    PubMed

    Coady, C A J

    2013-05-01

    Recent controversy over philosophical advocacy of infanticide (or the comically-styled euphemism 'postnatal abortion') reveals a surprisingly common premise uniting many of the opponents and supporters of the practice. This is the belief that the moral status of the early fetus or embryo with respect to a right to life is identical to that of a newly born or even very young baby. From this premise, infanticidists and strong anti-abortionists draw opposite conclusions, the former that the healthy newly born have no inherent right to life and the latter that minute embryos and the very early fetus have the same right to life as young babies. (Indeed strong anti-abortionists tend to regard this right to life as identical to that possessed by adult humans.) This paper argues that these opposed conclusions are both deeply implausible and that the implausibility resides in the common premise. The argument requires some attention to the structure of the philosophical case underpinning the supposed vice of speciesism that has been given intellectual currency by many philosophers, most notably Peter Singer, and also to the reasoning behind the strong anti-abortionist adoption of the common premise.

  15. Adverse effects of general anaesthetics.

    PubMed

    Berthoud, M C; Reilly, C S

    1992-01-01

    This review deals with the adverse reactions associated with general anaesthetic agents in current use. These reactions fall into 2 categories; those which are more common, predictable and often closely related, and those which are rare, unpredictable and carry a high mortality. Both inhalational and intravenous anaesthetic agents affect the central nervous and cardio-respiratory systems in a dose-related manner. Neuronal inhibition results in decreasing levels of consciousness and depression of the medullary vital centres which can lead to cardiorespiratory failure. Both groups of agents have some depressant effect on the myocardium and vascular smooth muscle leading to a fall in cardiac output and hypotension. Centrally-mediated respiratory depression is common to both groups and the inhalational agents have a direct effect on lung physiology. The most important idiosyncratic reactions to the volatile agents are malignant hyperpyrexia and 'halothane hepatitis'. Malignant hyperpyrexia has an incidence of 1:12,000 with a mortality of about 24%. It is triggered most often by halothane together with suxamethonium. Post halothane hepatic necrosis is rare. Evidence points to 2 distinct syndromes; direct toxicity from the products of reductive metabolism, and a more serious illness, immunologically mediated via haptens formed by liver proteins and the products of oxidative metabolism. Prolonged nitrous oxide exposure can cause bone marrow depression and life-threatening pressure effects by expansion of air-filled spaces within the body. The idiosyncratic reactions to the intravenous agents include anaphylactoid reactions (which are rare) and triggering of acute porphyria. Etomidate is immunologically 'clean', but it inhibits cortisol synthesis. PMID:1418699

  16. Underreporting of Hemorrhagic and Thrombotic Complications of Pharmaceuticals to the U.S. Food and Drug Administration: Empirical Findings for Warfarin, Clopidogrel, Ticlopidine, and Thalidomide from the Southern Network on Adverse Reactions (SONAR)

    PubMed Central

    Moore, Thomas J.; Bennett, Charles L.

    2014-01-01

    The U.S. Food and Drug Administration's (FDA) Adverse Event Reporting System (AERS), familiarly known as “MedWatch,” is the nation's primary tool for postmarket pharmaceutical safety surveillance. This system relies on adverse events voluntarily reported by health care providers and consumers either directly to the FDA or to drug manufacturers, which are required to prepare and forward the information to the agency. Little is known about how frequently adverse events are reported. Previous estimates range from 1 to 31% depending on the event, drug, and time period. We used published incidence studies to calculate reporting rates for hemorrhage, emergency hospitalization, and venous thromboembolism (VTE) associated with four drugs. We estimated annual reporting rates of 1.07% for 33,171 emergency hospitalizations of patients older than 65 years associated with warfarin, 0.9% for 13,363 hospitalizations of clopidogrel and ticlopidine, and 1.02% for an estimated 67,200 hemorrhage cases associated with warfarin. We also estimated a 9-year reporting rate of 2.3% for VTE associated with thalidomide. The incidence of these hematologic adverse drug events is high and reporting rates are low, and near the lower boundary of the 1 to 15% range seen for other events. PMID:23086541

  17. Underreporting of hemorrhagic and thrombotic complications of pharmaceuticals to the U.S. Food and Drug Administration: empirical findings for warfarin, clopidogrel, ticlopidine, and thalidomide from the Southern Network on Adverse Reactions (SONAR).

    PubMed

    Moore, Thomas J; Bennett, Charles L

    2012-11-01

    The U.S. Food and Drug Administration's (FDA) Adverse Event Reporting System (AERS), familiarly known as "MedWatch," is the nation's primary tool for postmarket pharmaceutical safety surveillance. This system relies on adverse events voluntarily reported by health care providers and consumers either directly to the FDA or to drug manufacturers, which are required to prepare and forward the information to the agency. Little is known about how frequently adverse events are reported. Previous estimates range from 1 to 31% depending on the event, drug, and time period. We used published incidence studies to calculate reporting rates for hemorrhage, emergency hospitalization, and venous thromboembolism (VTE) associated with four drugs. We estimated annual reporting rates of 1.07% for 33,171 emergency hospitalizations of patients older than 65 years associated with warfarin, 0.9% for 13,363 hospitalizations of clopidogrel and ticlopidine, and 1.02% for an estimated 67,200 hemorrhage cases associated with warfarin. We also estimated a 9-year reporting rate of 2.3% for VTE associated with thalidomide. The incidence of these hematologic adverse drug events is high and reporting rates are low, and near the lower boundary of the 1 to 15% range seen for other events.

  18. Scientists Trace Adversity's Toll

    ERIC Educational Resources Information Center

    Sparks, Sarah D.

    2012-01-01

    The stress of a spelling bee or a challenging science project can enhance a student's focus and promote learning. But the stress of a dysfunctional or unstable home life can poison a child's cognitive ability for a lifetime, according to new research. Those studies show that stress forms the link between childhood adversity and poor academic…

  19. Epistemology applied to conclusions of expert reports.

    PubMed

    Lucena-Molina, Jose-Juan

    2016-07-01

    It is believed that to build a robust reasoning logic to make probabilistic inferences in forensic science from a merely mathematical or logistical viewpoint is not enough. Mathematical logic is the positive science of reasoning and as for that it is only interested in the positive calculus of its validity, regardless any prior ontological assumption. But without a determined ontology and epistemology which imply to define the concepts that they will use, it seems difficult that the proposed scientifically correct mathematical solution be successful as a European standard for making conclusions in forensic reports because it has to be based on judicial language. Forensic experts and Courts are not interested in the development of a positive science but in a practical science: in clarifying whether certain known facts are related to a possible crime. Therefore, not only the coherence of the demonstrative logic reasoning used (logic of propositions) is important, but also the precision of the concepts used by language and consistency among them in reasoning (logic of concepts). There is a linguistic level essential for a successful communication between the forensic practitioner and the Court which is mainly related, in our opinion, to semantics and figures of speech. The first one is involved because words used in forensic conclusions often have different meanings - it is said that they are polysemic - and the second one because there is often metonymy as well. Besides, semantic differences among languages regarding words with the same etymological root add another difficulty for a better mutual understanding. The two main European judicial systems inherit a wide and deep culture related to evidence in criminal proceedings and each of them has coined their own terminology but there are other two more abstract levels such as logical and epistemological, where we can find solid arguments by which terms used at legal level on conclusions of forensic reports could be

  20. Epistemology applied to conclusions of expert reports.

    PubMed

    Lucena-Molina, Jose-Juan

    2016-07-01

    It is believed that to build a robust reasoning logic to make probabilistic inferences in forensic science from a merely mathematical or logistical viewpoint is not enough. Mathematical logic is the positive science of reasoning and as for that it is only interested in the positive calculus of its validity, regardless any prior ontological assumption. But without a determined ontology and epistemology which imply to define the concepts that they will use, it seems difficult that the proposed scientifically correct mathematical solution be successful as a European standard for making conclusions in forensic reports because it has to be based on judicial language. Forensic experts and Courts are not interested in the development of a positive science but in a practical science: in clarifying whether certain known facts are related to a possible crime. Therefore, not only the coherence of the demonstrative logic reasoning used (logic of propositions) is important, but also the precision of the concepts used by language and consistency among them in reasoning (logic of concepts). There is a linguistic level essential for a successful communication between the forensic practitioner and the Court which is mainly related, in our opinion, to semantics and figures of speech. The first one is involved because words used in forensic conclusions often have different meanings - it is said that they are polysemic - and the second one because there is often metonymy as well. Besides, semantic differences among languages regarding words with the same etymological root add another difficulty for a better mutual understanding. The two main European judicial systems inherit a wide and deep culture related to evidence in criminal proceedings and each of them has coined their own terminology but there are other two more abstract levels such as logical and epistemological, where we can find solid arguments by which terms used at legal level on conclusions of forensic reports could be

  1. Conclusions from recent pionic--atom experiments

    SciTech Connect

    Gotta, D.; Hennebach, M.; Nekipelov, M.; Strauch, Th.; Amaro, F.; Covita, D. S.; Santos, J. M. F. dos; Veloso, J. F. C. A.; Anagnostopoulos, D. F.; Biri, S.; Gorke, H.; Gruber, A.; Hirtl, A.; Ishiwatari, T.; Marton, J.; Schmid, Ph.; Zmeskal, J.; Indelicato, P.; Jensen, Th.; Le Bigot, E.-O.

    2008-08-08

    The most recent pionic--hydrogen experiment marks the completion of a whole series of measurements, the main goal of which was to provide conclusive data on pion--nucleon interaction at threshold for comparison with calculations from Chiral perturbation theory. The precision achieved for hadronic shift and broadening of 0.2% and 2%, respectively, became possible by comprehensive studies of cascade effects in hydrogen and other light exotic atoms including results from the last years of LEAR operation. In order to obtain optimum conditions for the Bragg crystal spectrometer, the cyclotron trap II has been used to provide a suitable X--ray source. To characterize the bent crystal spectrometer, the cyclotron trap has been modified to operate as an electron--cyclotron resonance source, which produces with high intensity narrow X-ray transitions in the few keV range originating from highly charged ions.

  2. NWCC Transmission Case Study Conclusions Summary

    SciTech Connect

    Steve Wiese, Terry Allison

    2000-09-01

    OAK-B135 The NWCC Transmission Case Studies Conclusions Summary In the spring of 1999, the Utility Wind Interest Group (UWIG), with the cooperation of the National Wind Coordinating Committee (NWCC), conducted a forum on transmission issues associated with the production of energy from wind. As a result of this forum, a number of issues were identified which, if successfully resolved, could help reduce barriers to the future expansion of wind power. The NWCC, being a multi-stakeholder group, was in an ideal position to conduct follow-up activities among a cross-section of the interested parties. The follow-up activities took the form of three case studies in the areas of interest identified by forum participants: (1) Transmission policy and pricing; (2) ''Virtual wheeling'' arrangements; and, (3) Transmission system improvements. The case studies provide an interesting snapshot in time dealing with a range of issues associated with scheduled or planned regulatory and restructuring proceedings related to energy transmission. The NWCC Transmission Subcommittee and the UWIG reviewed early drafts of the case studies in November 1999. The case studies were conducted through a questionnaire and interview process with interested parties. In writing each case study, NWCC staff attempted to identify all stakeholder groups with an interest in each topic and solicit their input. While all parties do not agree on every issue presented, a serious effort has been made to present all views in an unbiased fashion. At the end of each case study, relevant conclusions are drawn and recommendations for next steps are provided where appropriate.

  3. Screening Analysis : Volume 1, Description and Conclusions.

    SciTech Connect

    Bonneville Power Administration; Corps of Engineers; Bureau of Reclamation

    1992-08-01

    The SOR consists of three analytical phases leading to a Draft EIS. The first phase Pilot Analysis, was performed for the purpose of testing the decision analysis methodology being used in the SOR. The Pilot Analysis is described later in this chapter. The second phase, Screening Analysis, examines all possible operating alternatives using a simplified analytical approach. It is described in detail in this and the next chapter. This document also presents the results of screening. The final phase, Full-Scale Analysis, will be documented in the Draft EIS and is intended to evaluate comprehensively the few, best alternatives arising from the screening analysis. The purpose of screening is to analyze a wide variety of differing ways of operating the Columbia River system to test the reaction of the system to change. The many alternatives considered reflect the range of needs and requirements of the various river users and interests in the Columbia River Basin. While some of the alternatives might be viewed as extreme, the information gained from the analysis is useful in highlighting issues and conflicts in meeting operating objectives. Screening is also intended to develop a broad technical basis for evaluation including regional experts and to begin developing an evaluation capability for each river use that will support full-scale analysis. Finally, screening provides a logical method for examining all possible options and reaching a decision on a few alternatives worthy of full-scale analysis. An organizational structure was developed and staffed to manage and execute the SOR, specifically during the screening phase and the upcoming full-scale analysis phase. The organization involves ten technical work groups, each representing a particular river use. Several other groups exist to oversee or support the efforts of the work groups.

  4. Childhood adversities and psychosis: evidence, challenges, implications

    PubMed Central

    Morgan, Craig; Gayer‐Anderson, Charlotte

    2016-01-01

    There is a substantial body of research reporting evidence of associations between various forms of childhood adversity and psychosis, across the spectrum from experiences to disorder. This has been extended, more recently, to include studies of cumulative effects, of interactions with other factors, of specific effects, and of putative biological and psychological mechanisms. In this paper we evaluate this research and highlight the remaining methodological issues and gaps that temper, but do not dismiss, conclusions about the causal role of childhood adversity. We also consider the emerging work on cumulative, synergistic, and specific effects and on mechanisms; and discuss the broader implications of this line of research for our understanding of psychosis. We conclude that the current balance of evidence is that childhood adversities – particularly exposure to multiple adversities involving hostility and threat – do, in some people, contribute to the onset of psychotic experiences and psychotic disorders. PMID:27265690

  5. Identifying Adverse Drug Events by Relational Learning.

    PubMed

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

    2012-07-01

    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

  6. The Logic of Surveillance Guidelines: An Analysis of Vaccine Adverse Event Reports from an Ontological Perspective

    PubMed Central

    Courtot, Mélanie; Brinkman, Ryan R.; Ruttenberg, Alan

    2014-01-01

    Background When increased rates of adverse events following immunization are detected, regulatory action can be taken by public health agencies. However to be interpreted reports of adverse events must be encoded in a consistent way. Regulatory agencies rely on guidelines to help determine the diagnosis of the adverse events. Manual application of these guidelines is expensive, time consuming, and open to logical errors. Representing these guidelines in a format amenable to automated processing can make this process more efficient. Methods and Findings Using the Brighton anaphylaxis case definition, we show that existing clinical guidelines used as standards in pharmacovigilance can be logically encoded using a formal representation such as the Adverse Event Reporting Ontology we developed. We validated the classification of vaccine adverse event reports using the ontology against existing rule-based systems and a manually curated subset of the Vaccine Adverse Event Reporting System. However, we encountered a number of critical issues in the formulation and application of the clinical guidelines. We report these issues and the steps being taken to address them in current surveillance systems, and in the terminological standards in use. Conclusions By standardizing and improving the reporting process, we were able to automate diagnosis confirmation. By allowing medical experts to prioritize reports such a system can accelerate the identification of adverse reactions to vaccines and the response of regulatory agencies. This approach of combining ontology and semantic technologies can be used to improve other areas of vaccine adverse event reports analysis and should inform both the design of clinical guidelines and how they are used in the future. Availability Sufficient material to reproduce our results is available, including documentation, ontology, code and datasets, at http://purl.obolibrary.org/obo/aero. PMID:24667848

  7. Vaccine adverse events.

    PubMed

    Follows, Jill

    2012-01-01

    Millions of adults are vaccinated annually against the seasonal influenza virus. An undetermined number of individuals will develop adverse events to the influenza vaccination. Those who suffer substantiated vaccine injuries, disabilities, and aggravated conditions may file a timely, no-fault and no-cost petition for financial compensation under the National Vaccine Act in the Vaccine Court. The elements of a successful vaccine injury claim are described in the context of a claim showing the seasonal influenza vaccination was the cause of Guillain-Barré syndrome.

  8. [Adverse events prevention ability].

    PubMed

    Aparo, Ugo Luigi; Aparo, Andrea

    2007-03-01

    The issue of how to address medical errors is the key to improve the health care system performances. Operational evidence collected in the last five years shows that the solution is only partially linked to future technological developments. Cultural and organisational changes are mandatory to help to manage and drastically reduce the adverse events in health care organisations. Classical management, merely based on coordination and control, is inadequate. Proactive, self-organising network based structures must be put in place and managed using adaptive, fast evolving management tools. PMID:17484160

  9. [Adverse events prevention ability].

    PubMed

    Aparo, Ugo Luigi; Aparo, Andrea

    2007-03-01

    The issue of how to address medical errors is the key to improve the health care system performances. Operational evidence collected in the last five years shows that the solution is only partially linked to future technological developments. Cultural and organisational changes are mandatory to help to manage and drastically reduce the adverse events in health care organisations. Classical management, merely based on coordination and control, is inadequate. Proactive, self-organising network based structures must be put in place and managed using adaptive, fast evolving management tools.

  10. 75 FR 29352 - Draft Guidance for Industry on Data Elements for Submission of Veterinary Adverse Event Reports...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-25

    ... Reaction, Lack of Effectiveness, Product Defect Report,'' as required by FDA regulations. DATES: Although.../ manufacturing defects on Form FDA 1932, ``Veterinary Adverse Drug Reaction, Lack of Effectiveness,...

  11. Vaccine-related adverse events in Cuban children, 1999-2008.

    PubMed

    Galindo, Belkys M; Concepción, Damarys; Galindo, Miguel A; Pérez, Antonio; Saiz, Jesús

    2012-01-01

    INTRODUCTION Cuba has implemented an effective National Immunization Program since 1962. The schedule, administered primarily to children, comprises 11 vaccines (8 domestically produced) protecting against 13 diseases. In 1999 Cuba launched a national vaccine adverse event surveillance system to monitor and assess the safety of the immunization program, its vaccination procedures and the products administered. OBJECTIVES Describe adverse events following vaccination reported in children aged <16 years in Cuba from 1999 through 2008. METHODS A retrospective descriptive study was conducted of adverse events following vaccination reported from January 1999 through December 2008. Variables used: year, number of adverse events, province, type of vaccine, type and severity of adverse events (common minor, rare, severe), vaccination program errors, number of deaths, and final results of investigations of severe events. Percentages and rates per dose administered were calculated. Adverse event rates were calculated per 100,000 doses administered and by percentages of individual effects among events reported. RESULTS A total of 45,237,532 vaccine doses were administered, and 26,159 vaccine-associated adverse events were reported (overall rate: 57.8 per 100,000 doses). The group aged 0-5 years reported the highest rate of vaccine-associated adverse events (82/100,000 doses). The DTwP vaccine exhibited the highest rate of adverse events. Common minor events were: fever (17,538), reactions at injection site (4470) and systemic side effects (2422). Rare events (by WHO definition) reported were: persistent crying (2666), hypotonic-hyporesponsive episodes (3), encephalopathy (2) and febrile seizures (112). Severe events included: anaphylaxis (2), respiratory distress (1), multiple organ failure (1), sudden death (1), vaccine-associated paralytic poliomyelitis (2), toxic shock syndrome (3), and sepsis (1). The 10 deaths and 3 cases of disability were investigated by an expert

  12. Patient stratification and identification of adverse event correlations in the space of 1190 drug related adverse events

    PubMed Central

    Roitmann, Eva; Eriksson, Robert; Brunak, Søren

    2014-01-01

    Purpose: New pharmacovigilance methods are needed as a consequence of the morbidity caused by drugs. We exploit fine-grained drug related adverse event information extracted by text mining from electronic medical records (EMRs) to stratify patients based on their adverse events and to determine adverse event co-occurrences. Methods: We analyzed the similarity of adverse event profiles of 2347 patients extracted from EMRs from a mental health center in Denmark. The patients were clustered based on their adverse event profiles and the similarities were presented as a network. The set of adverse events in each main patient cluster was evaluated. Co-occurrences of adverse events in patients (p-value < 0.01) were identified and presented as well. Results: We found that each cluster of patients typically had a most distinguishing adverse event. Examination of the co-occurrences of adverse events in patients led to the identification of potentially interesting adverse event correlations that may be further investigated as well as provide further patient stratification opportunities. Conclusions: We have demonstrated the feasibility of a novel approach in pharmacovigilance to stratify patients based on fine-grained adverse event profiles, which also makes it possible to identify adverse event correlations. Used on larger data sets, this data-driven method has the potential to reveal unknown patterns concerning adverse event occurrences. PMID:25249979

  13. Screening for adverse events.

    PubMed

    Karson, A S; Bates, D W

    1999-02-01

    Adverse events (AEs) in medical patients are common, costly, and often preventable. Development of quality improvement programs to decrease the number and impact of AEs demands effective methods for screening for AEs on a routine basis. Here we describe the impact, types, and potential causes of AEs and review various techniques for identifying AEs. We evaluate the use of generic screening criteria in detail and describe a recent study of the sensitivity and specificity of individual generic screening criteria and combinations of these criteria. In general, the most sensitive screens were the least specific and no small sub-set of screens identified a large percentage of adverse events. Combinations of screens that were limited to administrative data were the least expensive, but none were particularly sensitive, although in practice they might be effective since routine screening is currently rarely done. As computer systems increase in sophistication sensitivity will improve. We also discuss recent studies that suggest that programs that screen for and identify AEs can be useful in reducing AE rates. While tools for identifying AEs have strengths and weaknesses, they can play an important role in organizations' quality improvement portfolios. PMID:10468381

  14. Adverse effects of antihypertensive drugs.

    PubMed

    Husserl, F E; Messerli, F H

    1981-09-01

    Early essential hypertension is asymptomatic and should remain so throughout treatment. In view of the increasing number of available antihypertensive agents, clinicians need to become familiar with the potential side effects of these drugs. By placing more emphasis on non-pharmacological treatment (sodium restriction, weight loss, exercise) and thoroughly evaluating each case in particular, the pharmacological regimen can be optimally tailored to the patient's needs. Potential side effects should be predicted and can often be avoided; if they become clinically significant they should be rapidly recognised and corrected. These side effects can be easily remembered in most instances, as they fall into 3 broad categories: (a) those caused by an exaggerated therapeutic effect; (b) those due to a non-therapeutic pharmacological effect; and (c) those caused by a non-therapeutic, non-pharmacological effect probably representing idiosyncratic reactions. This review focuses mainly on adverse effects of the second and third kind. Each group of drugs in general shares the common side effects of the first two categories, while each individual drug has its own idiosyncratic side effects.

  15. Clarifying adverse drug events: a clinician's guide to terminology, documentation, and reporting.

    PubMed

    Nebeker, Jonathan R; Barach, Paul; Samore, Matthew H

    2004-05-18

    Adverse drug events cause substantial morbidity and mortality, yet they remain underappreciated and misunderstood. The terminology to describe errors and patient harm associated with medications causes much confusion. This article uses the case study of a patient with multiple adverse drug events to clarify key terms, such as adverse event, adverse drug reaction, adverse drug event, medication error, and side effect. The case discussion illustrates clinical approaches to analyzing the causal connection between a suspect drug and an adverse event. Examples and rationale for meaningful documentation of adverse drug events are provided, along with an outline of the types of events that should be reported to regulatory agencies.

  16. The Ontology of Vaccine Adverse Events (OVAE) and its usage in representing and analyzing adverse events associated with US-licensed human vaccines

    PubMed Central

    2013-01-01

    Background Licensed human vaccines can induce various adverse events (AE) in vaccinated patients. Due to the involvement of the whole immune system and complex immunological reactions after vaccination, it is difficult to identify the relations among vaccines, adverse events, and human populations in different age groups. Many known vaccine adverse events (VAEs) have been recorded in the package inserts of US-licensed commercial vaccine products. To better represent and analyze VAEs, we developed the Ontology of Vaccine Adverse Events (OVAE) as an extension of the Ontology of Adverse Events (OAE) and the Vaccine Ontology (VO). Results Like OAE and VO, OVAE is aligned with the Basic Formal Ontology (BFO). The commercial vaccines and adverse events in OVAE are imported from VO and OAE, respectively. A new population term ‘human vaccinee population’ is generated and used to define VAE occurrence. An OVAE design pattern is developed to link vaccine, adverse event, vaccinee population, age range, and VAE occurrence. OVAE has been used to represent and classify the adverse events recorded in package insert documents of commercial vaccines licensed by the USA Food and Drug Administration (FDA). OVAE currently includes over 1,300 terms, including 87 distinct types of VAEs associated with 63 human vaccines licensed in the USA. For each vaccine, occurrence rates for every VAE in different age groups have been logically represented in OVAE. SPARQL scripts were developed to query and analyze the OVAE knowledge base data. To demonstrate the usage of OVAE, the top 10 vaccines accompanying with the highest numbers of VAEs and the top 10 VAEs most frequently observed among vaccines were identified and analyzed. Asserted and inferred ontology hierarchies classify VAEs in different levels of AE groups. Different VAE occurrences in different age groups were also analyzed. Conclusions The ontology-based data representation and integration using the FDA-approved information from

  17. Adverse events after hepatitis A B combination vaccine.

    PubMed

    Woo, Emily Jane; Miller, Nancy B; Ball, Robert

    2006-03-24

    In May 2001, the U.S. Food and Drug Administration (FDA) approved Hepatitis A Inactivated and Hepatitis B Recombinant Vaccine (HEPAB) for immunization of adults. From May 2001 to September 2003, the Vaccine Adverse Event Reporting System (VAERS) received 305 reports of adverse events after HEPAB. Many events were similar to those reported after the monovalent hepatitis A and B vaccines. Non-serious events included constitutional symptoms and local reactions. Serious events included neurologic, hepatobiliary, and dermatologic conditions, and detailed medical and epidemiological review did not suggest a clear pattern of evidence supporting a causal relationship with the vaccine, except for injection site reactions and some allergic reactions.

  18. 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

  19. Adverse Effects of Common Drugs: Dietary Supplements.

    PubMed

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

    2015-09-01

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

  20. [Analysis of Spontaneously Reported Adverse Events].

    PubMed

    Nakamura, Mitsuhiro

    2016-01-01

    Observational study is necessary for the evaluation of drug effectiveness in clinical practice. In recent years, the use of spontaneous reporting systems (SRS) for adverse drug reactions has increased and they have become an important resource for regulatory science. SRS, being the largest and most well-known databases worldwide, are one of the primary tools used for postmarketing surveillance and pharmacovigilance. To analyze SRS, the US Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report Database (JADER) are reviewed. Authorized pharmacovigilance algorithms were used for signal detection, including the reporting odds ratio. An SRS is a passive reporting database and is therefore subject to numerous sources of selection bias, including overreporting, underreporting, and a lack of a denominator. Despite the inherent limitations of spontaneous reporting, SRS databases are a rich resource and data mining index that provide powerful means of identifying potential associations between drugs and their adverse effects. Our results, which are based on the evaluation of SRS databases, provide essential knowledge that could improve our understanding of clinical issues.

  1. Adverse effects of creatine supplementation: fact or fiction?

    PubMed

    Poortmans, J R; Francaux, M

    2000-09-01

    The consumption of oral creatine monohydrate has become increasingly common among professional and amateur athletes. Despite numerous publications on the ergogenic effects of this naturally occurring substance, there is little information on the possible adverse effects of this supplement. The objectives of this review are to identify the scientific facts and contrast them with reports in the news media, which have repeatedly emphasised the health risks of creatine supplementation and do not hesitate to draw broad conclusions from individual case reports. Exogenous creatine supplements are often consumed by athletes in amounts of up to 20 g/day for a few days, followed by 1 to 10 g/day for weeks, months and even years. Usually, consumers do not report any adverse effects, but body mass increases. There are few reports that creatine supplementation has protective effects in heart, muscle and neurological diseases. Gastrointestinal disturbances and muscle cramps have been reported occasionally in healthy individuals, but the effects are anecdotal. Liver and kidney dysfunction have also been suggested on the basis of small changes in markers of organ function and of occasional case reports, but well controlled studies on the adverse effects of exogenous creatine supplementation are almost nonexistent. We have investigated liver changes during medium term (4 weeks) creatine supplementation in young athletes. None showed any evidence of dysfunction on the basis of serum enzymes and urea production. Short term (5 days), medium term (9 weeks) and long term (up to 5 years) oral creatine supplementation has been studied in small cohorts of athletes whose kidney function was monitored by clearance methods and urine protein excretion rate. We did not find any adverse effects on renal function. The present review is not intended to reach conclusions on the effect of creatine supplementation on sport performance, but we believe that there is no evidence for deleterious effects

  2. Infliximab in patients with psoriasis and other inflammatory diseases: evaluation of adverse events in the treatment of 168 patients*

    PubMed Central

    Antonio, João Roberto; Sanmiguel, Jessica; Cagnon, Giovana Viotto; Augusto, Marília Silveira Faeda; de Godoy, Moacir Fernandes; Pozetti, Eurides Maria Oliveira

    2016-01-01

    Background Psoriasis is immune-mediated chronic inflammatory disease with preference for skin and joints. The skin involvement occurs by hyperproliferation and abnormal differentiation of keratinocytes. It is associated with comorbidities, mainly related to the clinical manifestations of the metabolic syndrome. Increased TNF-alpha expression (TNF-α) is related to its pathophysiology. Infliximab is an intravenous drug that acts neutralizing the biological activity of TNF-α and prevents the binding of the molecule to the target cell receptor, inhibiting cell proliferation of psoriasis and other diseases mediated by TNF-α. A lot of infusion reactions have been described in the literature. Objective To evaluate the adverse effects of intravenous treatment with infliximab, analyzing patients with psoriasis compared to those with other chronic inflammatory diseases (rheumatoid arthritis, ankylosing spondylitis, Crohn's disease and ulcerative colitis). Method Analysis of medical records and adverse events of 168 patients undergoing infliximab infusion for psoriasis and chronic inflammatory diseases treatment. Results 168 patients who have used infliximab were evaluated, 24 had psoriasis and 144 had chronic inflammatory diseases. Only 2 (8.3%) patients with psoriasis showed adverse events requiring treatment discontinuation, and just 6 (4.2%) female patients with chronic inflammatory diseases experienced adverse events. Conclusion Infliximab is a safe drug, with a low percentage of adverse events and there were more adverse events in women with chronic inflammatory diseases and in patients who received more infliximab infusions. PMID:27438197

  3. Adverse events and deterioration reported by participants in the PACE trial of therapies for chronic fatigue syndrome

    PubMed Central

    Dougall, Dominic; Johnson, Anthony; Goldsmith, Kimberley; Sharpe, Michael; Angus, Brian; Chalder, Trudie; White, Peter

    2014-01-01

    Objective Adverse events (AEs) are health related events, reported by participants in clinical trials. We describe AEs in the PACE trial of treatments for chronic fatigue syndrome (CFS) and baseline characteristics associated with them. Methods AEs were recorded on three occasions over one year in 641 participants. We compared the numbers and nature of AEs between treatment arms of specialist medical care (SMC) alone, or SMC supplemented by adaptive pacing therapy (APT), cognitive behaviour therapy (CBT) or graded exercise therapy (GET). We examined associations with baseline measures by binary logistic regression analyses, and compared the proportions of participants who deteriorated by clinically important amounts. Results Serious adverse events and reactions were infrequent. Non-serious adverse events were common; the median (quartiles) number was 4 (2, 8) per participant, with no significant differences between treatments (P = .47). A greater number of NSAEs were associated with recruitment centre, and baseline physical symptom count, body mass index, and depressive disorder. Physical function deteriorated in 39 (25%) participants after APT, 15 (9%) after CBT, 18 (11%) after GET, and 28 (18%) after SMC (P < .001), with no significant differences in worsening fatigue. Conclusions The numbers of adverse events did not differ significantly between trial treatments, but physical deterioration occurred most often after APT. The reporting of non-serious adverse events may reflect the nature of the illness rather than the effect of treatments. Differences between centres suggest that both standardisation of ascertainment methods and training are important when collecting adverse event data. PMID:24913337

  4. Coding of adverse events of suicidality in clinical study reports of duloxetine for the treatment of major depressive disorder: descriptive study

    PubMed Central

    Tendal, Britta; Hróbjartsson, Asbjørn; Lundh, Andreas; Gøtzsche, Peter C

    2014-01-01

    Objective To assess the effects of coding and coding conventions on summaries and tabulations of adverse events data on suicidality within clinical study reports. Design Systematic electronic search for adverse events of suicidality in tables, narratives, and listings of adverse events in individual patients within clinical study reports. Where possible, for each event we extracted the original term reported by the investigator, the term as coded by the medical coding dictionary, medical coding dictionary used, and the patient’s trial identification number. Using the patient’s trial identification number, we attempted to reconcile data on the same event between the different formats for presenting data on adverse events within the clinical study report. Setting 9 randomised placebo controlled trials of duloxetine for major depressive disorder submitted to the European Medicines Agency for marketing approval. Data sources Clinical study reports obtained from the EMA in 2011. Results Six trials used the medical coding dictionary COSTART (Coding Symbols for a Thesaurus of Adverse Reaction Terms) and three used MedDRA (Medical Dictionary for Regulatory Activities). Suicides were clearly identifiable in all formats of adverse event data in clinical study reports. Suicide attempts presented in tables included both definitive and provisional diagnoses. Suicidal ideation and preparatory behaviour were obscured in some tables owing to the lack of specificity of the medical coding dictionary, especially COSTART. Furthermore, we found one event of suicidal ideation described in narrative text that was absent from tables and adverse event listings of individual patients. The reason for this is unclear, but may be due to the coding conventions used. Conclusion Data on adverse events in tables in clinical study reports may not accurately represent the underlying patient data because of the medical dictionaries and coding conventions used. In clinical study reports, the

  5. Fewer adverse effects with doxycycline than with minocycline.

    PubMed

    2009-10-01

    (1) In mid-2008 the French National Pharmacovigilance Committee examined spontaneous reports of adverse effects observed during tetracycline therapy; (2) When sales figures are taken into account, reports were more frequent with minocycline than with doxycycline. The proportion of severe adverse effects was also higher with minocycline than with doxycycline; (3) Life-threatening hypersensitivity reactions and autoimmune adverse effects were more frequent with minocycline than with doxycycline; (4) In practice, minocycline has a less favourable risk-benefit balance than doxycycline, particularly in the treatment of acne.

  6. Adverse effects of equine rabies immune gobulin.

    PubMed

    Wilde, H; Chomchey, P; Prakongsri, S; Puyaratabandhu, P; Chutivongse, S

    1989-02-01

    Following a recently published prospective study of 485 recipients of equine rabies immune globulin (ERIG) manufactured by Pasteur Vaccins (Paris), this paper reports a study of 323 postexposure rabies patients receiving ERIG manufactured by the Swiss Vaccine and Serum Institute (Berna). It is concluded that there may be significant differences in adverse reaction rates, reflecting differing manufacturing or purification processes and protein content. Further studies of different ERIG products and of different lots of the same product are needed while ERIG remains an essential component of postexposure rabies treatment in developing countries.

  7. Immune reaction to propanidid.

    PubMed

    Christmas, D

    1984-05-01

    An adverse reaction to the intravenous anaesthetic agent propanidid is described in which the main features were hypotension, facial erythema, and abdominal pain. Changes in serum complement levels and differential white cell counts indicate that this was an immune reaction mediated by the classical complement pathway. The immune reaction apparently involved antibodies other than those of the IgE (reagin) class, and circumstantial evidence suggests that it was specific to propanidid rather than to the entire formulation or to Cremophor EL.

  8. Reverse Engineering Adverse Outcome Pathways

    SciTech Connect

    Perkins, Edward; Chipman, J.K.; Edwards, Stephen; Habib, Tanwir; Falciani, Francesco; Taylor, Ronald C.; Van Aggelen, Graham; Vulpe, Chris; Antczak, Philipp; Loguinov, Alexandre

    2011-01-30

    The toxicological effects of many stressors are mediated through unknown, or poorly characterized, mechanisms of action. We describe the application of reverse engineering complex interaction networks from high dimensional omics data (gene, protein, metabolic, signaling) to characterize adverse outcome pathways (AOPs) for chemicals that disrupt the hypothalamus-pituitary-gonadal endocrine axis in fathead minnows. Gene expression changes in fathead minnow ovaries in response to 7 different chemicals, over different times, doses, and in vivo versus in vitro conditions were captured in a large data set of 868 arrays. We examined potential AOPs of the antiandrogen flutamide using two mutual information theory methods, ARACNE and CLR to infer gene regulatory networks and potential adverse outcome pathways. Representative networks from these studies were used to predict a network path from stressor to adverse outcome as a candidate AOP. The relationship of individual chemicals to an adverse outcome can be determined by following perturbations through the network in response to chemical treatment leading to the nodes associated with the adverse outcome. Identification of candidate pathways allows for formation of testable hypotheses about key biologic processes, biomarkers or alternative endpoints, which could be used to monitor an adverse outcome pathway. Finally, we identify the unique challenges facing the application of this approach in ecotoxicology, and attempt to provide a road map for the utilization of these tools. Key Words: mechanism of action, toxicology, microarray, network inference

  9. Adverse effects of anabolic steroids.

    PubMed

    Hickson, R C; Ball, K L; Falduto, M T

    1989-01-01

    Anabolic steroids are used therapeutically for various disorders and as ergogenic aids by athletes to augment strength, muscular development, and to enhance performance. There is a wide range of concomitant temporary and permanent adverse effects with steroid administration. Several well-documented adverse actions of these hormones may develop rapidly within several weeks or less (i.e. altered reproductive function) or require up to several years of steroid intake (i.e. liver carcinoma). More recent studies indicate that glucose intolerance, insulin resistance, increased cardiovascular disease risk profiles, cerebral dangers, musculoskeletal injuries, prostate cancer, psychosis and schizophrenic episodes, among others, accompany anabolic steroid intake. There is, at present, no evidence to support the claim that athletes are less susceptible to adverse effects than those individuals receiving hormone treatment in a clinical setting. Based on the available information which has accumulated primarily from cross-sectional, short term longitudinal, and case studies, there is a need: (a) to develop a comprehensive battery of specific and sensitive markers of adverse effects, particularly those that would be able to detect the onset of adverse actions; and (b) to conduct controlled long term longitudinal studies in order to fully understand the extensiveness and mechanisms involved in the occurrence of adverse effects.

  10. Breakthrough reactions of iodinated and gadolinium contrast media after oral steroid premedication protocol

    PubMed Central

    2014-01-01

    Background Adverse reactions to iodinated and gadolinium contrast media are an important clinical issue. Although some guidelines have proposed oral steroid premedication protocols to prevent adverse reactions, some patients may have reactions to contrast media in spite of premedication (breakthrough reaction; BTR). The purpose of this study was to assess the frequency, type and severity of BTR when following an oral steroid premedication protocol. Methods All iodinated and gadolinium contrast-enhanced radiologic examinations between August 2011 and February 2013 for which the premedication protocol was applied in our institution were assessed for BTRs. Results The protocol was applied to a total of 252 examinations (153 patients, ages 15–87 years; 63 males, 90 females). Of these, 152 were for prior acute adverse reactions to contrast media, 85 were for a history of bronchial asthma, and 15 were for other reasons. There were 198 contrast enhanced CTs and 54 contrast enhanced MRIs. There were nine BTR (4.5%) for iodinated contrast media, and only one BTR (1.9%) for gadolinium contrast media: eight were mild and one was moderate. No patient who had a mild index reaction (IR) had a severe BTR. Conclusion Incidence of BTRs when following the premedication protocol was low. This study by no means proves the efficacy of premedication, but provides some support for following a premedication protocol to improve safety of contrast-enhanced examinations when prior adverse reactions are mild, or when there is a history of asthma. PMID:25287952

  11. 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.

  12. 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

  13. 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

  14. [Adverse reaction to cefonicid analogous to serum sickness].

    PubMed

    Ortega Calvo, M; Méndez Mora, J L; Soriano Crespo, E; Fernández Martínez, D; Torello Iserte, J; Castillo Ferrando, J R

    1995-06-01

    We report a case of a male who was treated with cephonicid because of a surgical complication. Serum-sickness like symptoms were diagnosed two weeks later. Medical references are discussed. PMID:7548647

  15. Major adverse cardiac events during endurance sports.

    PubMed

    Belonje, Anne; Nangrahary, Mary; de Swart, Hans; Umans, Victor

    2007-03-15

    Major adverse cardiac events in endurance exercise are usually due to underlying and unsuspected heart disease. The investigators present an analysis of major adverse cardiac events that occurred during 2 consecutive annual long distance races (a 36-km beach cycling race and a 21-km half marathon) over the past 5 years. All patients with events were transported to the hospital. Most of the 62,862 participants were men (77%; mean age 40 years). Of these, 4 men (3 runners, 1 cyclist; mean age 48 years) collapsed during (n = 2) or shortly after the races, rendering a prevalence of 0.006%. Two patients collapsed after developing chest pain, 1 of whom needed resuscitation at the event site, which was successful. These patients had acute myocardial infarctions and underwent primary angioplasty. The third patient was resuscitated at the site but did not have coronary disease or inducible ventricular tachycardia or ventricular fibrillation and collapsed presumably because of catecholamine-induced ventricular fibrillation. The fourth patient experienced heat stroke and had elevated creatine kinase-MB and troponins in the absence of electrocardiographic changes. In conclusion, the risk for major adverse cardiac events during endurance sports in well-trained athletes is very low.

  16. Immediate reaction to lidocaine with periorbital edema during upper blepharoplasty

    PubMed Central

    Presman, Benjamin; Vindigni, Vincenzo; Tocco-Tussardi, Ilaria

    2016-01-01

    Introduction Blepharoplasty is the fourth most commonly performed cosmetic surgery in the US, with 207,000 operations in 2014. Lidocaine is the preferred anesthetic agent for blepharoplasty. Presentation of case We describe the unusual case of acute periorbital edema following local anesthesia with lidocaine for upper blepharoplasty. At present, only two other reports of periorbital reactions to lidocaine are present in the literature. The reactions observed are significant palpebral swelling and erythema with scaling of the cheek. Fortunately the swelling, although marked, is transient in nature and resolves almost spontaneously without affecting the visual acuity. Discussion Patients reporting adverse reactions should be screened for allergy according to the standard protocols, but skin testing has only been reported to be positive in less than 10% of all cases and allergy confirmation with IgE is even more rare. Conclusion In clinical practice, we recommend that patient should be informed about the possibility of recurrence of an adverse reaction in case of re-exposure to lidocaine, even in the vast majority of cases where true allergy could not be proven. In case of further need for local anesthesia with history of an adverse event, a different agent may be chosen even from the same class (another amide) as cross-reactions in the amide group are rare. Otherwise, an anesthetic from the ester group can also be safely used. PMID:26785079

  17. 47 CFR 1.263 - Proposed findings and conclusions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 1 2013-10-01 2013-10-01 false Proposed findings and conclusions. 1.263... Proceedings Hearing and Intermediate Decision § 1.263 Proposed findings and conclusions. (a) Each party to the proceeding may file proposed findings of fact and conclusions, briefs, or memoranda of law: Provided,...

  18. 20 CFR 901.48 - Proposed findings and conclusions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Proposed findings and conclusions. 901.48... Termination of Enrollment § 901.48 Proposed findings and conclusions. Except in cases where the respondent has... proposed findings and conclusions and supporting reasons therefor....

  19. 47 CFR 1.263 - Proposed findings and conclusions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Proposed findings and conclusions. 1.263... Proceedings Hearing and Intermediate Decision § 1.263 Proposed findings and conclusions. (a) Each party to the proceeding may file proposed findings of fact and conclusions, briefs, or memoranda of law: Provided,...

  20. 10 CFR 2.712 - Proposed findings and conclusions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false Proposed findings and conclusions. 2.712 Section 2.712... Adjudications § 2.712 Proposed findings and conclusions. (a) Any party to a proceeding may, or if directed by the presiding officer shall, file proposed findings of fact and conclusions of law, briefs and...

  1. 19 CFR 111.68 - Proposed findings and conclusions.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 19 Customs Duties 1 2014-04-01 2014-04-01 false Proposed findings and conclusions. 111.68 Section... Monetary Penalty in Lieu of Suspension or Revocation § 111.68 Proposed findings and conclusions. The... record in which to submit proposed findings and conclusions and supporting reasons for the findings...

  2. 39 CFR 957.20 - Proposed findings and conclusions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Proposed findings and conclusions. 957.20 Section... RELATIVE TO DEBARMENT AND SUSPENSION FROM CONTRACTING § 957.20 Proposed findings and conclusions. (a) Each... the Judicial Officer such is not appropriate, submit proposed findings of fact, conclusions of law...

  3. 29 CFR 417.12 - Proposed findings and conclusions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 2 2010-07-01 2010-07-01 false Proposed findings and conclusions. 417.12 Section 417.12... findings and conclusions. Within 10 days following the close of hearings, interested persons may submit proposed findings and conclusions to the Administrative Law Judge, together with supporting...

  4. 39 CFR 957.20 - Proposed findings and conclusions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 39 Postal Service 1 2014-07-01 2014-07-01 false Proposed findings and conclusions. 957.20 Section... RELATIVE TO DEBARMENT AND SUSPENSION FROM CONTRACTING § 957.20 Proposed findings and conclusions. (a) Each... the Judicial Officer such is not appropriate, submit proposed findings of fact, conclusions of law...

  5. 39 CFR 3001.35 - Proposed findings and conclusions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 39 Postal Service 1 2014-07-01 2014-07-01 false Proposed findings and conclusions. 3001.35 Section... General Applicability § 3001.35 Proposed findings and conclusions. The Commission or the presiding officer may direct the filing of proposed findings and conclusions with a brief statement of the...

  6. 39 CFR 3001.35 - Proposed findings and conclusions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 39 Postal Service 1 2011-07-01 2011-07-01 false Proposed findings and conclusions. 3001.35 Section... General Applicability § 3001.35 Proposed findings and conclusions. The Commission or the presiding officer may direct the filing of proposed findings and conclusions with a brief statement of the...

  7. 39 CFR 954.18 - Proposed findings and conclusions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 39 Postal Service 1 2013-07-01 2013-07-01 false Proposed findings and conclusions. 954.18 Section... RELATIVE TO THE DENIAL, SUSPENSION, OR REVOCATION OF PERIODICALS MAIL PRIVILEGES § 954.18 Proposed findings and conclusions. (a) A party to a proceeding may submit proposed findings of fact and conclusions...

  8. 29 CFR 417.12 - Proposed findings and conclusions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 2 2012-07-01 2012-07-01 false Proposed findings and conclusions. 417.12 Section 417.12... findings and conclusions. Within 10 days following the close of hearings, interested persons may submit proposed findings and conclusions to the Administrative Law Judge, together with supporting...

  9. 47 CFR 1.263 - Proposed findings and conclusions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 1 2014-10-01 2014-10-01 false Proposed findings and conclusions. 1.263... Proceedings Hearing and Intermediate Decision § 1.263 Proposed findings and conclusions. (a) Each party to the proceeding may file proposed findings of fact and conclusions, briefs, or memoranda of law: Provided,...

  10. 39 CFR 957.20 - Proposed findings and conclusions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 39 Postal Service 1 2011-07-01 2011-07-01 false Proposed findings and conclusions. 957.20 Section... RELATIVE TO DEBARMENT AND SUSPENSION FROM CONTRACTING § 957.20 Proposed findings and conclusions. (a) Each... the Judicial Officer such is not appropriate, submit proposed findings of fact, conclusions of law...

  11. 47 CFR 1.263 - Proposed findings and conclusions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 1 2011-10-01 2011-10-01 false Proposed findings and conclusions. 1.263... Proceedings Hearing and Intermediate Decision § 1.263 Proposed findings and conclusions. (a) Each party to the proceeding may file proposed findings of fact and conclusions, briefs, or memoranda of law: Provided,...

  12. 39 CFR 954.18 - Proposed findings and conclusions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 39 Postal Service 1 2010-07-01 2010-07-01 false Proposed findings and conclusions. 954.18 Section... RELATIVE TO THE DENIAL, SUSPENSION, OR REVOCATION OF PERIODICALS MAIL PRIVILEGES § 954.18 Proposed findings and conclusions. (a) A party to a proceeding may submit proposed findings of fact and conclusions...

  13. 39 CFR 954.18 - Proposed findings and conclusions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 39 Postal Service 1 2014-07-01 2014-07-01 false Proposed findings and conclusions. 954.18 Section... RELATIVE TO THE DENIAL, SUSPENSION, OR REVOCATION OF PERIODICALS MAIL PRIVILEGES § 954.18 Proposed findings and conclusions. (a) A party to a proceeding may submit proposed findings of fact and conclusions...

  14. 19 CFR 111.68 - Proposed findings and conclusions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 1 2012-04-01 2012-04-01 false Proposed findings and conclusions. 111.68 Section... Monetary Penalty in Lieu of Suspension or Revocation § 111.68 Proposed findings and conclusions. The... record in which to submit proposed findings and conclusions and supporting reasons for the findings...

  15. 20 CFR 901.48 - Proposed findings and conclusions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 20 Employees' Benefits 4 2012-04-01 2012-04-01 false Proposed findings and conclusions. 901.48... Termination of Enrollment § 901.48 Proposed findings and conclusions. Except in cases where the respondent has... proposed findings and conclusions and supporting reasons therefor....

  16. 39 CFR 954.18 - Proposed findings and conclusions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 39 Postal Service 1 2011-07-01 2011-07-01 false Proposed findings and conclusions. 954.18 Section... RELATIVE TO THE DENIAL, SUSPENSION, OR REVOCATION OF PERIODICALS MAIL PRIVILEGES § 954.18 Proposed findings and conclusions. (a) A party to a proceeding may submit proposed findings of fact and conclusions...

  17. 39 CFR 957.20 - Proposed findings and conclusions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 39 Postal Service 1 2013-07-01 2013-07-01 false Proposed findings and conclusions. 957.20 Section... RELATIVE TO DEBARMENT AND SUSPENSION FROM CONTRACTING § 957.20 Proposed findings and conclusions. (a) Each... the Judicial Officer such is not appropriate, submit proposed findings of fact, conclusions of law...

  18. 29 CFR 417.12 - Proposed findings and conclusions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 2 2013-07-01 2013-07-01 false Proposed findings and conclusions. 417.12 Section 417.12... findings and conclusions. Within 10 days following the close of hearings, interested persons may submit proposed findings and conclusions to the Administrative Law Judge, together with supporting...

  19. 47 CFR 1.263 - Proposed findings and conclusions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 1 2012-10-01 2012-10-01 false Proposed findings and conclusions. 1.263... Proceedings Hearing and Intermediate Decision § 1.263 Proposed findings and conclusions. (a) Each party to the proceeding may file proposed findings of fact and conclusions, briefs, or memoranda of law: Provided,...

  20. 29 CFR 417.12 - Proposed findings and conclusions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 2 2014-07-01 2014-07-01 false Proposed findings and conclusions. 417.12 Section 417.12... findings and conclusions. Within 10 days following the close of hearings, interested persons may submit proposed findings and conclusions to the Administrative Law Judge, together with supporting...

  1. 29 CFR 417.12 - Proposed findings and conclusions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 2 2011-07-01 2011-07-01 false Proposed findings and conclusions. 417.12 Section 417.12... findings and conclusions. Within 10 days following the close of hearings, interested persons may submit proposed findings and conclusions to the Administrative Law Judge, together with supporting...

  2. 39 CFR 3001.35 - Proposed findings and conclusions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 39 Postal Service 1 2013-07-01 2013-07-01 false Proposed findings and conclusions. 3001.35 Section... General Applicability § 3001.35 Proposed findings and conclusions. The Commission or the presiding officer may direct the filing of proposed findings and conclusions with a brief statement of the...

  3. Urbanicity, social adversity and psychosis

    PubMed Central

    Heinz, Andreas; Deserno, Lorenz; Reininghaus, Ulrich

    2013-01-01

    In recent years, there has been increasing interest in research on geographical variation in the incidence of schizophrenia and other psychoses. In this paper, we review the evidence on variation in incidence of schizophrenia and other psychoses in terms of place, as well as the individual- and area-level factors that account for this variation. We further review findings on potential mechanisms that link adverse urban environment and psychosis. There is evidence from earlier and more recent studies that urbanicity is associated with an increased incidence of schizophrenia and non-affective psychosis. In addition, considerable variation in incidence across neighbourhoods has been observed for these disorders. Findings suggest it is unlikely that social drift alone can fully account for geographical variation in incidence. Evidence further suggests that the impact of adverse social contexts – indexed by area-level exposures such as population density, social fragmentation and deprivation – on risk of psychosis is explained (confounding) or modified (interaction) by environmental exposures at the individual level (i.e., cannabis use, social adversity, exclusion and discrimination). On a neurobiological level, several studies suggest a close link between social adversity, isolation and stress on the one hand, and monoamine dysfunction on the other, which resembles findings in schizophrenia patients. However, studies directly assessing correlations between urban stress or discrimination and neurobiological alterations in schizophrenia are lacking to date. PMID:24096775

  4. Adverse Childhood Experiences and Hallucinations

    ERIC Educational Resources Information Center

    Whitfield, C.L.; Dube, S.R.; Felitti, V.J.; Anda, R.F.

    2005-01-01

    Objective:: Little information is available about the contribution of multiple adverse childhood experiences (ACEs) to the likelihood of reporting hallucinations. We used data from the ACE study to assess this relationship. Methods:: We conducted a survey about childhood abuse and household dysfunction while growing up, with questions about health…

  5. 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

  6. 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.

  7. Contact reactions to food.

    PubMed

    Killig, Claudia; Werfel, Thomas

    2008-05-01

    Cutaneous adverse reactions to foods, spices, and food additives can occur both in occupational and nonoccupational settings in those who grow, handle, prepare, or cook food. Because spices are also utilized in cosmetics and perfumes, other exposures are encountered that can result in adverse cutaneous reactions. This article describes the reaction patterns that can occur upon contact with foods, including irritant contact dermatitis and allergic contact dermatitis. The ingestion of culprit foods by sensitized individuals can provoke a generalized eczematous rash, referred to as systemic contact dermatitis. Other contact reactions to food include contact urticaria and protein contact dermatitis provoked by high-molecular-weight food proteins often encountered in patients with atopic dermatitis. Phototoxic and photoallergic contact dermatitis are also considered.

  8. Adverse events to monoclonal antibodies used for cancer therapy

    PubMed Central

    Baldo, Brian A

    2013-01-01

    Fifteen monoclonal antibodies (mAbs) are currently registered and approved for the treatment of a range of different cancers. These mAbs are specific for a limited number of targets (9 in all). Four of these molecules are indeed directed against the B-lymphocyte antigen CD20; 3 against human epidermal growth factor receptor 2 (HER2 or ErbB2), 2 against the epidermal growth factor receptor (EGFR), and 1 each against epithelial cell adhesion molecule (EpCAM), CD30, CD52, vascular endothelial growth factor (VEGF), tumor necrosis factor (ligand) superfamily, member 11 (TNFSF11, best known as RANKL), and cytotoxic T lymphocyte-associated protein 4 (CTLA4). Collectively, the mAbs provoke a wide variety of systemic and cutaneous adverse events including the full range of true hypersensitivities: Type I immediate reactions (anaphylaxis, urticaria); Type II reactions (immune thrombocytopenia, neutopenia, hemolytic anemia); Type III responses (vasculitis, serum sickness; some pulmonary adverse events); and Type IV delayed mucocutaneous reactions as well as infusion reactions/cytokine release syndrome (IRs/CRS), tumor lysis syndrome (TLS), progressive multifocal leukoencephalopathy (PML) and cardiac events. Although the term “hypersensitivity” is widely used, no common definition has been adopted within and between disciplines and the requirement of an immunological basis for a true hypersensitivity reaction is sometimes overlooked. Consequently, some drug-induced adverse events are sometimes incorrectly described as “hypersensitivities” while others that should be described are not. PMID:24251081

  9. Psychiatric adverse effects of pediatric corticosteroid use.

    PubMed

    Drozdowicz, Linda B; Bostwick, J Michael

    2014-06-01

    Corticosteroids, highly effective drugs for myriad disease states, have considerable neuropsychiatric adverse effects that can manifest in cognitive disorders, behavioral changes, and frank psychiatric disease. Recent reviews have summarized these effects in adults, but a comprehensive review on corticosteroid effects in children has not been published since 2005. Here, we systematically review articles published since then that, we find, naturally divide into 3 main areas: (1) chronic effects of acute prenatal and neonatal exposure associated with prematurity and congenital conditions; (2) immediate behavioral effects of acute exposure via oncological protocols; and (3) acute behavioral effects of sporadic use in children and adolescents with other conditions. PsycInfo, MEDLINE, Embase, and Scopus were queried to identify articles reporting psychiatric adverse effects of corticosteroids in pediatric patients. Search terms included corticosteroids, adrenal cortex hormones, steroid psychosis, substance-induced psychoses, glucocorticoids, dexamethasone, hydrocortisone, prednisone, adverse effects, mood disorders, mental disorders, psychosis, psychotic, psychoses, side effect, chemically induced, emotions, affective symptoms, toxicity, behavior, behavioral symptoms, infant, child, adolescent, pediatric, paediatric, neonatal, children, teen, and teenager. Following guidelines for systematic reviews from the Potsdam Consultation on Meta-Analysis, we have found it difficult to draw specific conclusions that are more than general impressions owing to the quality of the available studies. We find a mixed picture with neonates exposed to dexamethasone, with some articles reporting eventual deficits in neuropsychiatric functioning and others reporting no effect. In pediatric patients with acute lymphoblastic leukemia, corticosteroid use appears to correlate with negative psychiatric and behavioral effects. In children treated with corticosteroids for noncancer conditions

  10. 37 CFR 251.52 - Proposed findings and conclusions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... COPYRIGHT ARBITRATION ROYALTY PANEL RULES AND PROCEDURES COPYRIGHT ARBITRATION ROYALTY PANEL RULES OF PROCEDURE Procedures of Copyright Arbitration Royalty Panels § 251.52 Proposed findings and conclusions....

  11. Developing a departmental culture for reporting adverse incidents.

    PubMed

    Bhatia, R; Blackshaw, G; Rogers, A; Grant, A; Kulkarni, R

    2003-01-01

    A simple, reproducible model for reporting adverse events was developed in order to promote cultural awareness and acceptance of risk management within the authors' department. A departmental proforma was created and prospective reporting of adverse events was encouraged. In the six months prior to commencing this study only four adverse incidents were reported. Following the introduction of the proforma 64 critical incidents and near-misses were reported in the one-year period. In conclusion a simple model for reporting critical incidents and near-misses has been established. This has fostered a cultural change within the department and all members of staff feel more comfortable with reporting such incidents. The process is seen as educational and an important part of continuing professional and departmental development. Protocols and changes in organisational practice have been developed to reduce and prevent the occurrence of adverse events and offer patients continuous improvement in care. PMID:12870255

  12. 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

  13. On symbolic models for Single-Conclusion Logic of Proofs

    SciTech Connect

    Krupski, Vladimir N

    2011-05-31

    In this paper we define symbolic models for Single-Conclusion Logics of Proofs. We prove the soundness and completeness of these logics with respect to the corresponding classes of symbolic models. We apply the semantic methods developed in this paper to justify the use of terms of single-conclusion logic of proofs as notation for derivations in this logic. Bibliography: 17 titles.

  14. On symbolic models for Single-Conclusion Logic of Proofs

    NASA Astrophysics Data System (ADS)

    Krupski, Vladimir N.

    2011-05-01

    In this paper we define symbolic models for Single-Conclusion Logics of Proofs. We prove the soundness and completeness of these logics with respect to the corresponding classes of symbolic models. We apply the semantic methods developed in this paper to justify the use of terms of single-conclusion logic of proofs as notation for derivations in this logic. Bibliography: 17 titles.

  15. 31 CFR 10.75 - Proposed findings and conclusions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance: Treasury 1 2011-07-01 2011-07-01 false Proposed findings and conclusions. 10... THE INTERNAL REVENUE SERVICE Rules Applicable to Disciplinary Proceedings § 10.75 Proposed findings... submit proposed findings and conclusions and their supporting reasons to the Administrative Law Judge....

  16. 31 CFR 15.737-24 - Proposed findings and conclusions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance: Treasury 1 2011-07-01 2011-07-01 false Proposed findings and conclusions. 15... EMPLOYMENT CONFLICT OF INTEREST Administrative Enforcement Proceedings § 15.737-24 Proposed findings and... afford the parties a reasonable opportunity to submit proposed findings and conclusions and...

  17. 31 CFR 10.75 - Proposed findings and conclusions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Proposed findings and conclusions. 10... THE INTERNAL REVENUE SERVICE Rules Applicable to Disciplinary Proceedings § 10.75 Proposed findings... submit proposed findings and conclusions and their supporting reasons to the Administrative Law Judge....

  18. 31 CFR 15.737-24 - Proposed findings and conclusions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance: Treasury 1 2012-07-01 2012-07-01 false Proposed findings and conclusions. 15... EMPLOYMENT CONFLICT OF INTEREST Administrative Enforcement Proceedings § 15.737-24 Proposed findings and... afford the parties a reasonable opportunity to submit proposed findings and conclusions and...

  19. 39 CFR 952.23 - Proposed findings and conclusions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 39 Postal Service 1 2013-07-01 2013-07-01 false Proposed findings and conclusions. 952.23 Section... RELATIVE TO FALSE REPRESENTATION AND LOTTERY ORDERS § 952.23 Proposed findings and conclusions. (a) Each... the discretion of the presiding officer such is not appropriate, submit proposed findings of...

  20. 39 CFR 952.23 - Proposed findings and conclusions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 39 Postal Service 1 2014-07-01 2014-07-01 false Proposed findings and conclusions. 952.23 Section... RELATIVE TO FALSE REPRESENTATION AND LOTTERY ORDERS § 952.23 Proposed findings and conclusions. (a) Each... the discretion of the presiding officer such is not appropriate, submit proposed findings of...