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

PubMed

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

2016-03-01

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

Spontaneous adverse drug reaction reporting in rural districts of Mozambique.

PubMed

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

2008-01-01

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

[Vigilance for veterinary medicinal products: Reports of adverse reactions in the year 2015].

PubMed

Müntener, C; Kupper, J; Naegeli, H; Gassner, B

2016-11-01

A total of 292 adverse reactions to veterinary medicinal products were reported during the year 2015. This represents an increase of 9% compared to the previous year (268 reports). Similar to previous years, most of the reactions reported were linked to the use of antiparasitics (55.1%), non-steroidal anti-inflammatory products (8.9%) or antiinfectives (9.3%). The affected animal species were primarily dogs (198 reports) and cats (42 reports), followed by cattle (31 reports) and horses (8 reports). Additional 42 reports were provided within the frame of consultations with Tox Info Suisse in Zürich and involved mainly the excessive intake of flavored tablets. Eight signals were identified from the reports received or the periodic safety update reports. They resulted in revisions of the product information in sections addressing contraindications, adverse reactions or withdrawal times.

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

PubMed Central

Vural, Fisun; Ciftci, Seval; Vural, Birol

2015-01-01

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

[Suspected adverse reactions after vaccination. Results from the German Health Interview and Examination Survey for Children and Adolescents. Part 2: predictors of parental reporting of suspected adverse reactions after vaccinations].

PubMed

Poethko-Müller, C; Atzpodien, K; Schmitz, R; Schlaud, M

2011-03-01

Each method to monitor vaccine safety has strengths and limitations. Therefore, vaccine safety monitoring should rely on different types of data sources. Methods commonly rely on patient-reported adverse reactions. Little is, however, known about factors that may affect the probability with which patients report adverse reactions to vaccines. From 2003-2006, the representative National Health Interview and Examination Survey for Children and Adolescents ("Kinder- und Jugendgesundheitssurvey", KiGGS) retrospectively collected information about vaccines, vaccination dates, and suspected vaccine related adverse reactions from a total of 17,641 participants (<17 years). Poorly tolerated vaccinations were more likely reported from parents living in former West Germany compared to former East Germany (OR 1.61; 95% CI 1.08-2.39), parents of children with special health care needs (OR 1.49; 95% CI 1.08-2.04), and from parents reporting reservations against vaccinations (OR 3.29; 95% CI 2.28-4.75). Parental reporting of adverse vaccine reactions appears to be associated with parental perception and assessment of possible adverse vaccine reactions, as well as with the parents' attitude towards immunization in general.

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

PubMed

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

2017-10-01

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

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

PubMed Central

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

2013-01-01

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

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

PubMed

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

2017-01-01

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

Spontaneously Reported Adverse Reactions for Herbal Medicinal Products and Natural Remedies in Sweden 2007-15: Report from the Medical Products Agency.

PubMed

Svedlund, Erika; Larsson, Maria; Hägerkvist, Robert

2017-06-01

In relation to the extensive use of herbal medicinal products in self-care, the safety information is limited and there is a need for improvement. This study describes spontaneously reported adverse reactions related to herbal medicinal products and natural remedies in Sweden. To evaluate the characteristics and frequency of adverse events recorded by the Swedish Medical Products Agency, where herbal medicinal products and natural remedies were suspected as causative agents. Adverse drug reactions reported to the Swedish Medical Product Agency during 2007-15 related to approved herbal medicinal products or natural remedies were included and analysed in the retrospective study. Reports had been assessed for causality when they were lodged and only reports that had been assessed as at least possible were included in the study. In total, 116 reports (concerning 259 adverse reactions) related to herbal medicinal products or natural remedies were found in the Swedish national pharmacovigilance database. The active ingredients most frequently suspected during the study period were black cohosh rhizome (15 reports), purple coneflower herb (14 reports) and a combination of extracts of pollen (13 reports). Adverse reactions related to skin and subcutaneous tissue were the most commonly reported reactions. No previously unknown safety problems have been discovered in the present study. This finding could be explained by a thorough pre-approval assessment of medicinal products and the fact that most herbal preparations in medicinal products have been in clinical use for many years (for traditional herbal medicinal products, the requirements are ≥30 years), i.e. adverse reactions are acknowledged and assessed before approval.

[Adverse drug reaction reporting in emergency medicine].

PubMed

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

2004-01-01

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

Adverse reactions to contrast media: an analysis of spontaneous reports in the database of the pharmacovigilance programme of India.

PubMed

Kalaiselvan, Vivekanandan; Sharma, Surbhi; Singh, Gyanendra Nath

2014-09-01

Contrast media are used widely to improve medical imaging. Like all other pharmaceuticals, these agents are not completely devoid of risk, and continuous monitoring of adverse reactions with these agents is important. Spontaneous reporting is the simplest method for understanding the safety profile of pharmaceutical products after their approval. Our objective was to identify the pattern and characteristics of adverse reactions attributed to contrast media in the Indian population reported to the National Coordination Centre for the Pharmacovigilance Programme of India (NCC-PvPI). Individual case safety reports (ICSRs) attributed to contrast media submitted spontaneously to the NCC-PvPI were extracted from the database for July 2010 to September 2013. We analysed these reports for information related to reporter's professional category, patient's age and sex, reporter's diagnosis of the reaction, seriousness of the reaction, type of contrast media exposure, system organ class (SOC) affected (as described in World Health Organization Adverse Reaction Terminology [WHO-ART]) and outcome. Of the total 59,915 ICSRs in the database, 415 (0.7%) were suspected adverse reactions to contrast media; 44 reports were serious, including three fatal cases. The most affected SOCs were skin and appendage disorders, body as a whole-general disorders, gastrointestinal system disorders and respiratory system disorders. Hypersensitivity reactions were reported in the majority of ICSRs. The contrast media with the highest number of reports were iohexol (40.7%), iomeprol (17.8%), iopamidol (12%) and diatrizoate (12%). Most of the reactions to contrast media were allergic-like, and no previously unrecognised adverse reactions were observed in the Indian population. Further data and increased awareness among healthcare professionals is required to signal and prevent the consequences of adverse reactions attributed to contrast media.

Outbreak of Adverse Reactions Associated with Contaminated Heparin

PubMed Central

Blossom, David B.; Kallen, Alexander J.; Patel, Priti R.; Elward, Alexis; Robinson, Luke; Gao, Ganpan; Langer, Robert; Perkins, Kiran M.; Jaeger, Jennifer L.; Kurkjian, Katie M.; Jones, Marilyn; Schillie, Sarah F.; Shehab, Nadine; Ketterer, Daniel; Venkataraman, Ganesh; Kishimoto, Takashi Kei; Shriver, Zachary; McMahon, Ann W.; Austen, K. Frank; Kozlowski, Steven; Srinivasan, Arjun; Turabelidze, George; Gould, Carolyn V.; Arduino, Matthew J.; Sasisekharan, Ram

2013-01-01

BACKGROUND In January 2008, the Centers for Disease Control and Prevention began a nationwide investigation of severe adverse reactions that were first detected in a single hemodialysis facility. Preliminary findings suggested that heparin was a possible cause of the reactions. METHODS Information on clinical manifestations and on exposure was collected for patients who had signs and symptoms that were consistent with an allergic-type reaction after November 1, 2007. Twenty-one dialysis facilities that reported reactions and 23 facilities that reported no reactions were included in a case–control study to identify facility-level risk factors. Unopened heparin vials from facilities that reported reactions were tested for contaminants. RESULTS A total of 152 adverse reactions associated with heparin were identified in 113 patients from 13 states from November 19, 2007, through January 31, 2008. The use of heparin manufactured by Baxter Healthcare was the factor most strongly associated with reactions (present in 100.0% of case facilities vs. 4.3% of control facilities, P<0.001). Vials of heparin manufactured by Baxter from facilities that reported reactions contained a contaminant identified as oversulfated chondroitin sulfate (OSCS). Adverse reactions to the OSCS-contaminated heparin were often characterized by hypotension, nausea, and shortness of breath occurring within 30 minutes after administration. Of 130 reactions for which information on the heparin lot was available, 128 (98.5%) occurred in a facility that had OSCS-contaminated heparin on the premises. Of 54 reactions for which the lot number of administered heparin was known, 52 (96.3%) occurred after the administration of OSCS-contaminated heparin. CONCLUSIONS Heparin contaminated with OSCS was epidemiologically linked to adverse reactions in this nationwide outbreak. The reported clinical features of many of the cases further support the conclusion that contamination of heparin with OSCS was the cause

Severe Adverse Reactions Following Ketoconazole, Fluconazole, and Environmental Exposures: A Case Report.

PubMed

Lieberman, Allan; Curtis, Luke

2018-04-18

In this case report, we describe a 66-year-old man who developed multiple adverse reactions beginning at age 56 after exposure to several azole antifungal drugs including ketoconazole and fluconazole. He also had a history of more than 40 years exposure to chemicals including pesticides, wood preservatives, fertilizers, and welding chemicals. His reactions involved dehydration (requiring several liters of intravenous fluids in less than an hour to alleviate this condition), angioedema, nausea, tinnitus, hypotension, and difficulty breathing. His acute adverse reactions were triggered by a wide range of chemicals including gasoline, diesel fuel, pesticides, chlorine, topical isopropyl alcohol, and paper mill emissions. His acute reactions were also triggered by a wide range of foods such as bananas, apples, milk, white potatoes, and processed sweets. A number of mechanisms could be responsible for his increased sensitivity to chemicals following exposure to fluconazole/ketoconazole, including inhibition of P450 and other detoxification enzymes, acetaldehyde buildup, and neurogenic sensitization.

Adverse reactions associated with acetylcysteine.

PubMed

Sandilands, E A; Bateman, D N

2009-02-01

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

Adverse drug reactions induced by valproic acid.

PubMed

Nanau, Radu M; Neuman, Manuela G

2013-10-01

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

A UK scheme for reporting serious adverse events and reactions associated with ocular tissue transplantation.

PubMed

Kaye, Stephen; Baddon, Andrew; Jones, Mark; Armitage, W John; Fehily, Deirdre; Warwick, Ruth M

2010-02-01

Reporting and investigation of serious adverse events and reactions associated with tissue and cell transplantation is a fundamental aspect of ensuring adequate levels of safety and quality and is a requirement of the European Union Directives on tissues and cells. In the UK, a system for the reporting and analysis of events and reactions associated with ocular tissue transplantation is well established. It is operated by a network of individuals and organisations, each with clearly defined roles and responsibilities, following written procedures for reporting and investigation. Analysis of reports indicates that the most important adverse reactions associated with this type of tissue transplantation are endophthalmitis (0.58%) and primary graft failure (0.3%). This system allows the analysis of all types of events and reactions by the professionals involved so that trends can be identified and services improved. Tools to evaluate the severity and imputability of individual events or reactions, such as those developed by the EUSTITE project, can be utilised to facilitate the selection of those cases meeting the criteria for reporting to the Competent Authority. This vigilance model has been shown to be effective and could be applied in other fields of tissue or cell transplantation.

21 CFR 606.170 - Adverse reaction file.

Code of Federal Regulations, 2012 CFR

2012-04-01

... maintained of any reports of complaints of adverse reactions regarding each unit of blood or blood product arising as a result of blood collection or transfusion. A thorough investigation of each reported adverse... the manufacturer or collecting facility. (b) When a complication of blood collection or transfusion is...

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

PubMed

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

2017-01-01

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

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

PubMed Central

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

2017-01-01

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

Epidemiology of adverse drug reactions to phenformin and metformin.

PubMed Central

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

1978-01-01

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

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

PubMed

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

2011-12-01

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

Tuberculin skin testing: Spectrum of adverse reactions.

PubMed

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

2015-01-01

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

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

PubMed

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

2012-01-01

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

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

PubMed

Hauben, Manfred; Aronson, Jeffrey K

2007-01-01

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

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

Adverse cutaneous reactions induced by TNF-alpha antagonist therapy.

PubMed

Borrás-Blasco, Joaquín; Navarro-Ruiz, Andrés; Borrás, Consuelo; Casterá, Elvira

2009-11-01

To review adverse cutaneous drug reactions induced by tumor necrosis factor alpha (TNF-alpha) antagonist therapy. A literature search was performed using PubMed (1996-March 2009), EMBASE, and selected MEDLINE Ovid bibliography searches. All language clinical trial data, case reports, letters, and review articles identified from the data sources were used. Since the introduction of TNF-alpha antagonist, the incidence of adverse cutaneous drug reactions has increased significantly. A wide range of different skin lesions might occur during TNF-alpha antagonist treatment. New onset or exacerbation of psoriasis has been reported in patients treated with TNF-alpha antagonists for a variety of rheumatologic conditions. TNF-alpha antagonist therapy has been associated with a lupus-like syndrome; most of these case reports occurred in patients receiving either etanercept or infliximab. Serious skin reactions such as erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported rarely with the use of TNF-alpha antagonists. As the use of TNF-alpha antagonists continues to increase, the diagnosis and management of cutaneous side effects will become an increasingly important challenge. In patients receiving TNF-alpha antagonist treatment, skin disease should be considered, and clinicians need to be aware of the adverse reactions of these drugs.

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

PubMed

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

2018-06-16

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

Biomarkers of adverse drug reactions.

PubMed

Carr, Daniel F; Pirmohamed, Munir

2018-02-01

Adverse drug reactions can be caused by a wide range of therapeutics. Adverse drug reactions affect many bodily organ systems and vary widely in severity. Milder adverse drug reactions often resolve quickly following withdrawal of the casual drug or sometimes after dose reduction. Some adverse drug reactions are severe and lead to significant organ/tissue injury which can be fatal. Adverse drug reactions also represent a financial burden to both healthcare providers and the pharmaceutical industry. Thus, a number of stakeholders would benefit from development of new, robust biomarkers for the prediction, diagnosis, and prognostication of adverse drug reactions. There has been significant recent progress in identifying predictive genomic biomarkers with the potential to be used in clinical settings to reduce the burden of adverse drug reactions. These have included biomarkers that can be used to alter drug dose (for example, Thiopurine methyltransferase (TPMT) and azathioprine dose) and drug choice. The latter have in particular included human leukocyte antigen (HLA) biomarkers which identify susceptibility to immune-mediated injuries to major organs such as skin, liver, and bone marrow from a variety of drugs. This review covers both the current state of the art with regard to genomic adverse drug reaction biomarkers. We also review circulating biomarkers that have the potential to be used for both diagnosis and prognosis, and have the added advantage of providing mechanistic information. In the future, we will not be relying on single biomarkers (genomic/non-genomic), but on multiple biomarker panels, integrated through the application of different omics technologies, which will provide information on predisposition, early diagnosis, prognosis, and mechanisms. Impact statement • Genetic and circulating biomarkers present significant opportunities to personalize patient therapy to minimize the risk of adverse drug reactions. ADRs are a significant heath issue

Self-reported adverse food reactions and anaphylaxis in the SchoolNuts study: A population-based study of adolescents.

PubMed

McWilliam, Vicki L; Koplin, Jennifer J; Field, Michael J; Sasaki, Mari; Dharmage, Shyamali C; Tang, Mimi L K; Sawyer, Susan M; Peters, Rachel L; Allen, Katrina J

2018-03-01

Adolescents are at the highest risk of death from anaphylaxis, yet few population-based studies have described the frequencies and risk factors for allergic reactions caused by accidental allergen ingestion in this group. We describe the prevalence, frequency, and associated risk factors for recent adverse food reactions in 10- to 14-year-olds in Melbourne, Australia, recruited from a stratified, random, population-based sample of schools (SchoolNuts, n = 9663; 48% response rate). Self-reported food allergy and adverse reaction details, including anaphylaxis, were identified by using a student questionnaire over the past year. Of 547 students with possible IgE-mediated food allergy, 243 (44.4%; 95% CI, 40.3% to 48.7%) reported a reaction to a food. Fifty-three (9.7%; 95% CI, 7.2% to 12.2%) students reported 93 anaphylaxis episodes. Peanut and tree nuts were the most common food triggers. Among students with current IgE-mediated food allergy, those with resolved or current asthma (adjusted odds ratio [aOR], 1.9 [95% CI, 1.1-1.3] and 1.7 [95% CI, 1.1-2.6]) and those with more than 2 food allergies (aOR, 1.9 [95% CI, 1.1-3.1]) were at greatest risk of any adverse food reaction, and those with nut allergy were most at risk of severe reactions (aOR, 2.9 [95% CI, 1.1-4.4]). Resolved or current asthma was not associated with increased risk of severe reactions (aOR, 0.8 [95% CI, 0.3-2.2] and 1.6 [95% CI, 0.7-3.7]). Adolescents with food allergy are frequently exposed to food allergens. Those with asthma and more than 2 food allergies were at the greatest risk for adverse food reactions. Those with nut allergies were most at risk of severe reactions. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. All rights reserved.

[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

Adverse reactions of α2-adrenoceptor agonists in cats reported in 2003-2013 in Finland.

PubMed

Raekallio, Marja R; Virtanen, Marika; Happonen, Irmeli; Vainio, Outi M

2017-07-01

To describe suspected adverse drug reactions in cats associated with use of α 2 -adrenoceptor agonists. Retrospective study. A total of 90 cats. Data were collected from reports on adverse reactions to veterinary medicines sent to the Finnish Medicines Agency during 2003-2013. All reports of suspected adverse reactions associated with use of α 2 -adrenoceptor agonists in cats were included. Probable pulmonary oedema was diagnosed based on post mortem or radiological examination, or presence of frothy or excess fluid from the nostrils or trachea. If only dyspnoea and crackles on auscultation were reported, possible pulmonary oedema was presumed. Pulmonary oedema was suspected in 61 cases. Of these cats, 37 were categorised as probable and 24 as possible pulmonary oedema. The first clinical signs had been noted between 1 minute and 2 days (median, 15 minutes) after α 2 -adrenoceptor agonist administration. Many cats probably had no intravenous overhydration when the first clinical signs were detected, as either they presumably had no intravenous cannula or the signs appeared before, during or immediately after cannulation. Of the 61 cats, 43 survived, 14 died and for four the outcome was not clearly stated. Pulmonary oedema is a perilous condition that may appear within minutes of an intramuscular administration of sedative or anaesthetic agent in cats. The symptoms were not caused by intravenous overhydration, at least in cats having no venous cannula when the first clinical signs were detected. Copyright © 2017 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.

Adverse Drug Reactions in Dental Practice

PubMed Central

Becker, Daniel E.

2014-01-01

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

Severe Cutaneous Adverse Drug Reactions: A Clinicoepidemiological Study

PubMed Central

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

2015-01-01

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

Adverse drug reactions in hospitalized Colombian children.

PubMed

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

2016-09-30

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

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

PubMed

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

2016-03-01

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

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

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

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

2007-11-05

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

National differences in publishing papers on adverse drug reactions

PubMed Central

Ferner, R E; Aronson, J K

2005-01-01

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

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.

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

Sex Differences in Reported Adverse Drug Reactions of Selective Serotonin Reuptake Inhibitors.

PubMed

Ekhart, Corine; van Hunsel, Florence; Scholl, Joep; de Vries, Sieta; van Puijenbroek, Eugene

2018-02-26

Several studies have investigated sex as a risk factor for the occurrence of adverse drug reactions (ADRs) and found that women are more likely to experience ADRs than men. The aim of this explorative study was to investigate whether differences exist in reported ADRs of selective serotonin reuptake inhibitors (SSRIs) for men and women in the database of the Netherlands Pharmacovigilance Centre Lareb. A ratio of reports concerning women and men, corrected for the number of users, was calculated for all the ADRs reported on SSRIs. We found that 16 ADRs were statistically significantly more reported in women than men, and four ADRS were reported more in men than women. ADRs more reported in women than men when using SSRIs were usually dose-related ADRs or commonly occurring ADRs. Differences in the pharmacokinetics of SSRIs between men and women may explain why these reports of dose-related ADRs when using SSRIs concern women more than men.

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.

The lesser of two adverse reactions.

PubMed

Chakraborti, Chayan; Egan, John

2010-01-01

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

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

Attitudes and knowledge of hospital pharmacists to adverse drug reaction reporting

PubMed Central

Green, Christopher F; Mottram, David R; Rowe, Philip H; Pirmohamed, Munir

2001-01-01

Aims To investigate the attitudes of UK hospital pharmacists towards, and their understanding, of adverse drug reaction (ADR) reporting. Methods A postal questionnaire survey of 600 randomly selected hospital pharmacists was conducted. Results The response rate was 53.7% (n = 322). A total of 217 Yellow Cards had been submitted to the CSM/MCA by 78 (25.6%) of those responding. Half of those responding felt that ADR reporting should be compulsory and over three-quarters felt it was a professional obligation. However, almost half were unclear as to what should be reported, while the time available in clinical practice and time taken to complete forms were deemed to be major deterrents to reporting. Pharmacists were not dissuaded from reporting by the need to consult a medical colleague or by the absence of a fee. Education and training had a significant influence on pharmacists' participation in the Yellow Card Scheme. Conclusions Pharmacists have a reasonable knowledge and are supportive of the Yellow Card spontaneous ADR reporting scheme. However, education and training will be important in maintaining and increasing ADR reports from pharmacists. PMID:11167664

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

PubMed

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

2010-01-01

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

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

PubMed

Chaves, Marlén

2015-01-01

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

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

PubMed

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

2017-11-15

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

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

PubMed

Ko, Richard J

2004-03-01

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

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

PubMed Central

Castleden, C M; Pickles, H

1988-01-01

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

Experiences from consumer reports on psychiatric adverse drug reactions with antidepressant medication: a qualitative study of reports to a consumer association.

PubMed

Vilhelmsson, Andreas; Svensson, Tommy; Meeuwisse, Anna; Carlsten, Anders

2012-12-23

The new European pharmacovigilance legislation has been suggested as marking the beginning of a new chapter in drug safety, making patients an important part of pharmacovigilance. In Sweden since 2008 it has been possible for consumers to report adverse drug reactions (ADRs) to the Medical Products Agency (MPA), and these reports are now understood as an increasingly valuable contribution in the monitoring of safety aspects in medicines. Already in 2002 it was possible to report experiences with medicines to the non-profit and independent organization Consumer Association for Medicines and Health (KILEN) through a web-based report form with an opportunity to describe ADR experiences in free text comments. The aim of this study was to qualitatively analyze the free text comments appended to consumer reports on antidepressant medication. All reports of suspected adverse reactions regarding antidepressant medications submitted from January 2002 to April 2009 to KILEN's Internet-based reporting system in Sweden were analyzed according to reported narrative experience(s). Content analysis was used to interpret the content of 181 reports with free text comments. Three main categories emerged from the analyzed data material: (1) Experiences of drug treatment with subcategories (a) Severe psychiatric adverse reactions, and (b) Discontinuation symptoms; (2) Lack of communication and (3) Trust and distrust. A majority of the reports to KILEN were from patients experiencing symptoms of mental disturbances (sometimes severe) affecting them in many different ways, especially during discontinuation. Several report included narratives of patients not receiving information of potential ADRs from their doctor, but also that there were no follow-ups of the treatment. Trust was highlighted as especially important and some patients reported losing confidence in their doctor when they were not believed about the suspected ADRs they experienced, making them attempt to discontinue their

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

PubMed

Awodele, Olufunsho; Ibrahim, Ali; Orhii, Paul

2016-03-16

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

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

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

PubMed Central

Lev-Ran, Shaul

2017-01-01

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

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

PubMed

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

2017-04-01

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

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

PubMed

Mølbak, Kåre; Hansen, Niels Dalum; Valentiner-Branth, Palle

2016-01-01

Since 2013 the number of suspected adverse reactions to the quadrivalent human papillomavirus (HPV) vaccine reported to the Danish Medicines Agency (DMA) has increased. Due to the resulting public concerns about vaccine safety, the coverage of HPV vaccinations in the childhood vaccination programme has declined. The aim of the present study was to determine health care-seeking prior to the first HPV vaccination among females who suspected adverse reactions to HPV vaccine. In this registry-based case-control study, we included as cases vaccinated females with reports to the DMA of suspected severe adverse reactions. We selected controls without reports of adverse reactions from the Danish vaccination registry and matched by year of vaccination, age of vaccination, and municipality, and obtained from the Danish National Patient Registry and The National Health Insurance Service Register the history of health care usage two years prior to the first vaccine. We analysed the data by logistic regression while adjusting for the matching variables. The study included 316 cases who received first HPV vaccine between 2006 and 2014. Age range of cases was 11 to 52 years, with a peak at 12 years, corresponding to the recommended age at vaccination, and another peak at 19 to 28 years, corresponding to a catch-up programme targeting young women. Compared with 163,910 controls, cases had increased care-seeking in the two years before receiving the first HPV vaccine. A multivariable model showed higher use of telephone/email consultations (OR 1.9; 95% CI 1.2-3.2), physiotherapy (OR 2.1; 95% CI 1.6-2.8) and psychologist/psychiatrist (OR 1.9; 95% CI 1.3-2.7). Cases were more likely to have a diagnosis in the ICD-10 chapters of diseases of the digestive system (OR 1.6; 95% CI 1.0-2.4), of the musculoskeletal system (OR 1.6; 95% CI 1.1-2.2), symptoms or signs not classified elsewhere (OR 1.8; 95% CI 1.3-2.5) as well as injuries (OR 1.5; 95% CI 1.2-1.9). Before receiving the first HPV

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

PubMed

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

2015-06-01

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

Identifying genomic and developmental causes of adverse drug reactions in children

PubMed Central

Becker, Mara L; Leeder, J Steven

2011-01-01

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

[Adverse reaction caused by rabies vaccine in China: a Meta-analysis].

PubMed

Zhang, X R; Wu, Z G; Zhang, W S

2017-06-10

Objective: To conduct a Meta-analysis on the rate of adverse reaction related to rabies vaccine, so as to provide reference for rabies vaccine immunization in China. Methods: We electronically searched databases including CNKI, VIP information resource integration service platform, WanFang Data, CBM, PubMed and The Cochrane Library, to collect studies on Chinese people who had received full rabies vaccination and recording all the adverse reactions, from January 2000 to July 2016. Inclusion and exclusion criteria were strictly followed. Meta-analysis for the adverse reaction rate was performed using the R software. Results: A total of 29 related papers had met the inclusion criteria, with no publication bias noticed. A total number of 11 020 cases had adverse reactions, among all the 94 222 respondents, with an incidence of adverse reactions as 1.04 % -47.78 % . The overall incidence rate of adverse reaction was 9.82 % (95 %CI : 7.58 % -12.72 % ). A combined local adverse reaction rate appeared as 12.05 % (95 % CI : 9.26 % -15.69 % ). The systemic adverse reaction rate was 9.06 % (95 %CI : 7.07 % -11.61 % ). The overall adverse reaction rate on aqueous vaccine was 32.39 % (95 %CI : 21.88 % -47.94 % ). Combined adverse reaction rate of freeze dried vaccine appeared as 8.65 % (95 %CI : 4.54 % -16.51 % ). Significant differences were seen between both groups ( P <0.05). Conclusions: The local adverse reaction rate caused by rabies vaccination was higher than the systemic adverse reaction rate. The adverse reaction rate of aqueous rabies vaccine was higher than that of freeze dried rabies vaccine. Our results suggested that the aqueous vaccine should gradually be eliminated.

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

PubMed

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

2015-06-01

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

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

PubMed

Yom-Tov, Elad; Lev-Ran, Shaul

2017-10-26

Cannabis is one of the most widely used psychoactive substances worldwide, but adverse drug reactions (ADRs) associated with its use are difficult to study because of its prohibited status in many countries. Internet search engine queries have been used to investigate ADRs in pharmaceutical drugs. In this proof-of-concept study, we tested whether these queries can be used to detect the adverse reactions of cannabis use. We analyzed anonymized queries from US-based users of Bing, a widely used search engine, made over a period of 6 months and compared the results with the prevalence of cannabis use as reported in the US National Survey on Drug Use in the Household (NSDUH) and with ADRs reported in the Food and Drug Administration's Adverse Drug Reporting System. Predicted prevalence of cannabis use was estimated from the fraction of people making queries about cannabis, marijuana, and 121 additional synonyms. Predicted ADRs were estimated from queries containing layperson descriptions to 195 ICD-10 symptoms list. Our results indicated that the predicted prevalence of cannabis use at the US census regional level reaches an R 2 of .71 NSDUH data. Queries for ADRs made by people who also searched for cannabis reveal many of the known adverse effects of cannabis (eg, cough and psychotic symptoms), as well as plausible unknown reactions (eg, pyrexia). These results indicate that search engine queries can serve as an important tool for the study of adverse reactions of illicit drugs, which are difficult to study in other settings. ©Elad Yom-Tov, Shaul Lev-Ran. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 26.10.2017.

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

PubMed

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

2016-03-03

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

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.

Adverse drug reaction reporting among health care workers at Mulago National Referral and Teaching hospital in Uganda.

PubMed

Katusiime, Barbra; Semakula, Daniel; Lubinga, Solomon J

2015-12-01

Adverse Drug Reactions (ADRs) are an important contributor to patient morbidity and hospitalisation in Uganda. Under-reporting of ADRs may increase medicine-induced morbidity and mortality among patients. This study determined the extent of ADR reporting, and associated factors, among healthcare workers in Uganda. A quantitative, cross-sectional, study was conducted. Pretested, semi-structured questionnaires were administered to 289 randomly sampled healthcare workers over a three-month period in Mulago National Referral Hospital, Uganda. The primary outcome was the proportion of healthcare workers who had ever reported an ADR. Data was double-entered in Epidata version 3.0, cleaned and exported to STATA version 10.1 for analysis. The overall response rate was 77.2% (n=223). The majority of the respondents were females (139, 62.3%). The median age of all respondents was 32.6 years (min-23; max-65). Only about 16.6% (n=37) of healthcare workers had ever reported an ADR. Very few (n= 84, 37.7%) healthcare workers knew the tools used in ADR reporting. Less than a quarter (n=41, 18.4%) of the healthcare workers knew where to report ADRs. Lack of training was reported as the major (56.5%, 126) deterrent to reporting ADRs by healthcare workers. Adverse drug reactions are under-reported in Uganda, and healthcare workers have insufficient knowledge of existing pharmacovigilance systems, including ADR reporting systems. To address these challenges, there is need to sensitize and train healthcare workers in patient-centred aspects of medicine surveillance, so as to provide appropriate care while optimising patient safety.

Genetic variants associated with phenytoin-related severe cutaneous adverse reactions.

PubMed

Chung, Wen-Hung; Chang, Wan-Chun; Lee, Yun-Shien; Wu, Ying-Ying; Yang, Chih-Hsun; Ho, Hsin-Chun; Chen, Ming-Jing; Lin, Jing-Yi; Hui, Rosaline Chung-Yee; Ho, Ji-Chen; Wu, Wei-Ming; Chen, Ting-Jui; Wu, Tony; Wu, Yih-Ru; Hsih, Mo-Song; Tu, Po-Hsun; Chang, Chen-Nen; Hsu, Chien-Ning; Wu, Tsu-Lan; Choon, Siew-Eng; Hsu, Chao-Kai; Chen, Der-Yuan; Liu, Chin-San; Lin, Ching-Yuang; Kaniwa, Nahoko; Saito, Yoshiro; Takahashi, Yukitoshi; Nakamura, Ryosuke; Azukizawa, Hiroaki; Shi, Yongyong; Wang, Tzu-Hao; Chuang, Shiow-Shuh; Tsai, Shih-Feng; Chang, Chee-Jen; Chang, Yu-Sun; Hung, Shuen-Iu

2014-08-06

The antiepileptic drug phenytoin can cause cutaneous adverse reactions, ranging from maculopapular exanthema to severe cutaneous adverse reactions, which include drug reactions with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. The pharmacogenomic basis of phenytoin-related severe cutaneous adverse reactions remains unknown. To investigate the genetic factors associated with phenytoin-related severe cutaneous adverse reactions. Case-control study conducted in 2002-2014 among 105 cases with phenytoin-related severe cutaneous adverse reactions (n=61 Stevens-Johnson syndrome/toxic epidermal necrolysis and n=44 drug reactions with eosinophilia and systemic symptoms), 78 cases with maculopapular exanthema, 130 phenytoin-tolerant control participants, and 3655 population controls from Taiwan, Japan, and Malaysia. A genome-wide association study (GWAS), direct sequencing of the associated loci, and replication analysis were conducted using the samples from Taiwan. The initial GWAS included samples of 60 cases with phenytoin-related severe cutaneous adverse reactions and 412 population controls from Taiwan. The results were validated in (1) 30 cases with severe cutaneous adverse reactions and 130 phenytoin-tolerant controls from Taiwan, (2) 9 patients with Stevens-Johnson syndrome/toxic epidermal necrolysis and 2869 population controls from Japan, and (3) 6 cases and 374 population controls from Malaysia. Specific genetic factors associated with phenytoin-related severe cutaneous adverse reactions. The GWAS discovered a cluster of 16 single-nucleotide polymorphisms in CYP2C genes at 10q23.33 that reached genome-wide significance. Direct sequencing of CYP2C identified missense variant rs1057910 (CYP2C9*3) that showed significant association with phenytoin-related severe cutaneous adverse reactions (odds ratio, 12; 95% CI, 6.6-20; P=1.1 × 10(-17)). The statistically significant association between CYP2C9*3 and phenytoin

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

PubMed

Bjånes, Tormod Karlsen

2011-03-04

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

Renal failure as a suspected adverse reaction to benoxaprofen

PubMed Central

Fine, Wilfred; Tallis, R. C.; Osman, K. M.

1982-01-01

A 77-year-old woman suffering from osteoarthritis was treated with benoxaprofen. She developed diarrhoea, skin rash and renal failure. Renal failure has not been reported before as an adverse reaction to benoxaprofen. The case is discussed in the context of multisystem and immunological response to benoxaprofen. PMID:6213949

Adverse reactions to skin prick testing in children - prevalence and possible risk factors.

PubMed

Norrman, Gunilla; Fälth-Magnusson, Karin

2009-05-01

Skin prick test (SPT) is usually considered to be a safe procedure, but recently there have been occasional case reports of generalized allergic reactions. This study was performed to delineate the prevalence of, and evaluate possible risk factors for, adverse reactions to SPT in a prospective study. Altogether 5,908 patients aged < or =18 yr from 11 different pediatric settings were included. The adverse reactions were classified into two groups: (1) Generalized allergic reactions (GAR), (2) Vasovagal reactions (VVR). Adverse reactions were observed in 14 out of 5,908 children examined with SPT. Seven of the adverse reactions were GARs and required medication, yielding a 0.12% risk for GAR. Seven of 14 were VVRs, giving the same risk, 0.12%. Identified risk factors for GAR were low age (<1 yr) (RR 6.28) and active eczema (RR 16.98). For VVR, the risk factors were female sex (RR 7.32) and multiple skin pricks performed on a single patient (p < 0.05). We conclude that GARs do occur, albeit rarely, so the need for proper emergency handling should always be acknowledged. The risk factors suggested may help to identify patients who need extra attention.

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

PubMed

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

2017-01-01

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

Adverse drug reactions in children: a ten-year review of reporting to the Portuguese Pharmacovigilance System.

PubMed

Nogueira Guerra, Leonor; Herdeiro, Maria Teresa; Ribeiro-Vaz, Inês; Clérigo, Maria Inês Pinto; Rocha, Cristina; Araújo, Ana; Pêgo, Alexandra; Rebelo Gomes, Eva

2015-01-01

Adverse drug reactions (ADR) are a public health problem. They cause significant morbidity, mortality and health costs. Less is known about pediatric ADR. Our goal was to characterize a pediatric case series of ADR reported to the Portuguese Pharmacovigilance System (PPS) during the past 10 years. Retrospective analysis of ADR reports concerning patients till 17 years old received by the PPS between 2003 and 2012. We evaluated patients' demographic data and involved drugs, as well as characteristics and seriousness of reactions, stratified by age groups. We found 1742 reports (50% females) corresponding to 9.7% of the total received. The age of the patients varied from 0 to 17 years (median: 5 years, interquartile range: 10.6), with 566 cases (32%) occurring in patients younger than 2y. Among the 1195 serious cases, 31% (370) episodes led to hospitalization. In 32 cases (2%) there was a fatal outcome. Most of the ADR reported referred to general disorders and administration site conditions, followed by skin and subcutaneous tissue reactions. Vaccines were the most represented group (42%) followed by antibacterials for systemic use (17%). Pediatric ADR represents about 10% of the reports received by the PPS. Most ADR were considered serious. Major findings varied according to age groups.

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

Adverse reactions, psychological factors, and their effect on donor retention in men and women.

PubMed

Veldhuizen, Ingrid; Atsma, Femke; van Dongen, Anne; de Kort, Wim

2012-09-01

This study investigates the effect of a vasovagal reaction (VVR) or needle reaction (NR) on the risk of stopping as a blood donor, taking into account variables from the Theory of Planned Behavior (TPB). Is stopping risk solely related to the adverse reaction itself, or do the TPB variables play a role as well? Emphasis is placed on possible sex differences. TPB variables were assessed within 12,051 whole blood donors. Also, donors reported the occurrence of adverse reactions during or after their last donation. Blood bank records were used to determine whether donors stopped donating within the next 2 years. Logistic regression analyses were performed to estimate the effect of self-reported adverse reactions on stopping risk, adjusting for the TPB variables. Analyses were performed separately for both sexes. Men have a lower odds of reporting a NR or a VVR than women (odds ratio [OR] 0.34, 95% confidence interval [CI], 0.28-0.43; and OR 0.26, 95% CI 0.19-0.36, for NR and VVR, respectively). For both sexes, only a VVR was associated with stopping risk, which is higher in men (men, OR 3.95, 95% CI 2.19-7.11; women, OR 1.78, 95% CI 1.35-2.35). After adjusting for the TPB variables both ORs declined (men, OR 3.38, 95% CI 1.86-6.15; women, OR 1.58, 95% CI 1.17-2.14). Also, self-efficacy and affective attitude are negatively associated with adverse reactions. Female donors report more VVRs than male donors, but male donors have a higher stopping risk after a VVR than female donors. Coping differences and possible reporting tendencies might play a role. For donor retention purposes, prevention and coping techniques should take sex differences into account. © 2012 American Association of Blood Banks.

Safety profile and protocol prevention of adverse reactions to uroangiographic contrast media in diagnostic imaging.

PubMed

Rossi, C; Reginelli, A; D'Amora, M; Di Grezia, G; Mandato, Y; D'Andrea, A; Brunese, L; Grassi, R; Rotondi, A

2014-01-01

The purpose of the study is to examine the incidence of adverse reactions caused by non-ionic contrast media in selected patients after desensitization treatment and to evaluate the safety profile of organ iodine contrast media (i.c.m.) in a multistep prevention protocol. In a population of 2000 patients that had received a CT scan, 100 patients with moderate/high risk for adverse reactions against iodinated contrast agents followed a premedication protocol and all adverse reactions are reported and classified as mild, moderate or severe. 1.7 percent of the pre-treated patients reported a mild, immediate type reaction to iodine contrast; of these five patients with allergy 0.71 percent had received iomeprol, 0.35 percent received ioversol and 0.71 percent received iopromide. The incidence of adverse reactions was reported to be higher (4 out of 5 patients) among those that referred a history of hypersensitivity against iodinated i.c.m. Although intravenous contrast materials have greatly improved, especially in terms of their safety profile, they should not be administered if there isn't a clear or justified indication. In conclusion, even if we know that the majority of these reactions are idiosyncratic and unpredictable we propose, with the aim of improving our knowledge on this subject, a multicenter study, based on skin allergy tests (prick test, patch test, intradermal reaction) in selected patients that have had previous experiences of hypersensitivity against parenteral organ iodine contrast media.

Adverse food reactions: Pathogenesis, clinical signs, diagnosis and alternatives to elimination diets.

PubMed

Mueller, R S; Unterer, S

2018-06-01

This review summarises available information about adverse food reactions in dogs and cats. Much of the published information on the pathogenesis of adverse food reactions in these species is transferred from what is known in mice and human beings. Clinical signs affect mostly the integument and gastrointestinal system. Pruritus of the distal limbs, face, ears and ventrum is the most common cutaneous presentation in dogs, although urticaria has also been reported. In cats, all so-called 'cutaneous reaction patterns' may be due to adverse food reactions. The most common gastrointestinal signs in both species are diarrhoea and vomiting. An elimination diet over several weeks using a protein source and a carbohydrate source previously not fed is still the diagnostic tool of choice. Improvement on such a diet, deterioration on re-challenge with the old food and improvement again on the elimination diet confirms the diagnosis of adverse food reaction, whereas alternative tests of blood, serum, saliva and hair have been found to be unsatisfactory. Patch testing with food antigens has been recommended as an aid to choose the elimination diet ingredients, since it has a reasonable negative predictability and likelihood ratio, but is laborious and costly. Copyright © 2018 Elsevier Ltd. All rights reserved.

Embolia cutis medicamentosa: an unusual adverse reaction to terlipressin

PubMed Central

Gatos-Gatopoulos, Polychronis; Kostantoudakis, Stephanos; Panayiotides, Ioannis G.; Dimitriadis, George D.; Triantafyllou, Konstantinos

2017-01-01

Terlipressin is a synthetic long-acting analog of vasopressin widely used to control variceal bleeding by lowering portal venous pressure. We report an unusual adverse reaction to terlipressin in a 78-year-old patient with esophageal variceal bleeding who developed skin necrosis soon after treatment initiation. Skin biopsy revealed embolia cutis medicamentosa. PMID:29118569

[Delayed adverse reactions to blood donation: From haemovigilance data to specific studies].

PubMed

Py, J-Y; Durieux, S; Barnoux, M; Sapey, T

2016-11-01

Delayed adverse reactions to blood donation occur after the donor left donation site. Their intrinsic gravity and possible complications can be increased by the fact the donor is alone. This can also increase bad memories, leading to a donation giving up. Blood transfusion centre is only aware in case of donor feedback, hence an event underrating. We choose to compare our data upon delayed adverse donor reactions with those we could find in past studies. A first data level comes from French haemovigilance data while serious adverse reactions declaration is mandatory. But a second level can be reached using blood transfusion centre computerized data because all the donation reactions are saved whatever the gravity is. In both cases, delayed reactions are only those reported by donors. We try to make an exhaustive search of specific studies upon the real delayed reactions incidence so as to compare with our data. There were 1957 serious adverse reactions declared in our regional haemovigilance database between 2011 and 2015: 49 % occurring during donation, 40 % after it but before donor departure, and 11 % delayed events. There were 16,050 adverse reactions recorded during the first trimester of 2016 in mainland France, with 2.7 % delayed ones. Proportion of delayed events rises when gravity rises, until 27.6 % for the most serious ones. It varies between 2.2 % and 2.7 % for vasovagal reactions, haematomas, and other local reactions, and reaches 16.2 % for other general reactions. Data found in other studies with a spontaneous donor notification are of the same kind. But four studies soliciting specifically donor notification give a dramatically higher delayed reactions incidence, with an understatement greater than three out of four. Moreover, these studies found a majority of delayed reactions, which are not included in haemovigilance like fatigue or bruising. Occurrence of a delayed donor reaction is clearly underrated in standard haemovigilance. It

Neutrophilic dermatitis and immune-mediated haematological disorders in a dog: suspected adverse reaction to carprofen.

PubMed

Mellor, P J; Roulois, A J A; Day, M J; Blacklaws, B A; Knivett, S J; Herrtage, M E

2005-05-01

This report describes the clinical and pathological findings of a suspected idiosyncratic adverse drug reaction in a young dog. The patient presented with sudden onset, severe skin lesions together with episodes of collapse. Investigations revealed a neutrophilic dermatitis with vasculitis, immune-mediated haemolytic anaemia and thrombocytopenia. Similar pathology has been described in human cases of Sweet's syndrome. The chronology of events suggested an adverse drug reaction to carprofen, although two antibiotics had been prescribed within the dog's recent history. Lymphocyte transformation tests were performed and tended to exclude both antibiotics as the cause of the reaction. To the authors' knowledge, lymphocyte transformation tests have not previously been described with regard to drug hypersensitivity assessment in the veterinary literature, and this is the first peer-reviewed case report of neutrophilic dermatitis and vasculitis with immune-mediated haemolytic anaemia and thrombocytopenia occurring as a suspected adverse drug reaction to carprofen in the dog.

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

PubMed

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

2014-10-23

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

Adverse reactions and other factors that impact subsequent blood donation visits.

PubMed

Custer, Brian; Rios, Jorge A; Schlumpf, Karen; Kakaiya, Ram M; Gottschall, Jerome L; Wright, David J

2012-01-01

The importance of adverse reactions in terms of donor safety recently has received significant attention, but their role in subsequent donation behavior has not been thoroughly investigated. Six REDS-II blood centers provided data for this analysis. Summary minor and major adverse reaction categories were created. The influence of adverse reactions on donation was examined in two ways: Kaplan-Meier curves were generated to determine the cumulative pattern of first return, and adjusted odds ratios (AORs) for demographic and other factors positively and negatively associated with return were estimated using multivariable logistic regression. Donors who had major reactions had longer times to return than donors with minor or no reactions. The AOR of returning for donors with major reactions was 0.32 (95% confidence interval [CI], 0.28-0.37) and with minor reactions 0.59 (95% CI, 0.56-0.62) when compared to donors who did not have reactions. Conversely, the most important factors positively associated with return were the number of donations in the previous year and increasing age. Subsequent return, whether a major, minor, or no reaction occurred, varied by blood center. Factors that are associated with the risk of having adverse reactions were not substantial influences on the return after adverse reactions. Having an adverse reaction leads to significantly lower odds of subsequent donation irrespective of previous donation history. Factors that have been associated with a greater risk of adverse reactions were not important positive or negative predictors of return after a reaction. © 2011 American Association of Blood Banks.

Adverse reactions in a population of Sydney pet rabbits vaccinated against rabbit calicivirus.

PubMed

Tung, T; Phalen, D; Toribio, J-Alml

2015-11-01

To determine the general clinical presentation and incidence of adverse reactions to Cylap® RCD vaccinations, of a nature serious enough for veterinary attention, in a Sydney population of pet rabbits. A retrospective survey using hospital databases. Nine veterinary hospitals in Sydney participated in a database search for the number of rabbits vaccinated within a 2-year period. The hospitals involved had an identified interest in rabbit medicine and included general, specialist and teaching hospitals. Details of the rabbit, vaccination event and any possible reaction were collected and analysed. Of 933 events recorded in 705 rabbits, 17 (1.8%) adverse reactions were observed. Of the adverse events, local injection site reactions (alopecia, abrasions and scabbing) were most common. Other reactions, including systemic signs of gastrointestinal tract stasis, lethargy and forelimb lameness, were also documented. Overall, rabbits presented for vaccination were mostly male (57.7%) and desexed (71.3%), with an average age of 28.1 months (median 19.0, range 1.4-149.8 months) and an average weight at first vaccination of 2.12 kg (median 2.08 kg, range 0.18-5.6 kg). A significant association between increasing age and decreased incidence of adverse events was demonstrated (P value, 0.038). The benefits of vaccination against RCV outweigh the risks of an adverse reaction occurring. Data from this study show that adverse reactions occur infrequently, are generally mild and self-resolving, and decrease in incidence with increasing age. These results are similar to previous field research on wild rabbit colonies and reports from government and industry. © 2015 Australian Veterinary Association.

21 CFR 600.80 - Postmarketing reporting of adverse experiences.

Code of Federal Regulations, 2010 CFR

2010-04-01

... expected pharmacological action. Blood Component. As defined in § 606.3(c) of this chapter. Disability. A... this action which shall include: (A) A copy of all adverse biological product experience reports... referenced by the licensed manufacturer's patient identification number, adverse reaction term(s), and date...

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

PubMed

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

2012-01-01

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

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

PubMed Central

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

2012-01-01

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

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, significant...

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, significant...

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

Continued Statin Prescriptions After Adverse Reactions and Patient Outcomes: A Cohort Study.

PubMed

Zhang, Huabing; Plutzky, Jorge; Shubina, Maria; Turchin, Alexander

2017-08-15

Many patients discontinue statin treatment, often after having a possible adverse reaction. The risks and benefits of continued statin therapy after an adverse reaction are not known. To examine the relationship between continuation of statin therapy (any prescription within 12 months after an adverse reaction) and clinical outcomes. Retrospective cohort study. Primary care practices affiliated with 2 academic medical centers. Patients with a presumed adverse reaction to a statin between 2000 and 2011. Information on adverse reactions to statins was obtained from structured electronic medical record data or natural-language processing of narrative provider notes. The primary composite outcome was time to a cardiovascular event (myocardial infarction or stroke) or death. Most (81%) of the adverse reactions to statins were identified from the text of electronic provider notes. Among 28 266 study patients, 19 989 (70.7%) continued receiving statin prescriptions after the adverse reaction. Four years after the presumed adverse event, the cumulative incidence of the composite primary outcome was 12.2% for patients with continued statin prescriptions, compared with 13.9% for those without them (difference, 1.7% [95% CI, 0.8% to 2.7%]; P < 0.001). In a secondary analysis of 7604 patients for whom a different statin was prescribed after the adverse reaction, 2014 (26.5%) had a documented adverse reaction to the second statin, but 1696 (84.2%) of those patients continued receiving statin prescriptions. The risk for recurrent adverse reactions to statins could not be established for the entire sample. It was also not possible to determine whether patients actually took the statins. Continued statin prescriptions after an adverse reaction were associated with a lower incidence of death and cardiovascular events. Chinese National Key Program of Clinical Science, National Natural Science Foundation of China, and Young Scientific Research Fund of Peking Union Medical College

Adverse drug reactions of non-opioid and opioid analgesics reported to Croatian national authority from 2007 to 2014.

PubMed

Sunara, Petra; Krnic, Darko; Puljak, Livia

2017-11-01

Adverse drug reactions (ADRs) are commonly observed in the health services because of system weaknesses and individual errors. Analgesics are widely used and it can be expected that with the increased use one can expect increased number of ADRs of analgesics. The aim of this study was to analyze ADRs of non-opioid and opioid analgesics reported to the Croatian Agency for Medicinal Products and Medical Devices (HALMED) from 2007 to 2014. HALMED provided data on generic drug name, year of the ADR report, type of report, institution, reporting person, patient's age, sex and ADR type. In the analyzed period 796 ADRs of analgesics were reported, of which 367 (46%) were serious ADRs. Number of ADR reports was continuously increasing during the analyzed period. There were 20 analgesics that had ≥5 reports, making 597 (75%) of all ADR reports for analgesics. The most common adverse reaction reports of those 20 analgesics referred to individual drugs (n=16; 80%). Most of the ADR reports were filed by physicians (n=257; 43%), followed by pharmacists (n=252; 42%). Most side effects (n=572; 96%) were reported spontaneously through appropriate forms by patients or health professionals. ADRs were most commonly reported in women (n=352; 59%) and most of them have occurred in adults (n=354; 59%). The most common ADRs of opioid and non-opioid analgesics have been reported on the skin and mucous membranes. Most serious ADRs were result of action of opioid analgesics. Number of ADR reports in Croatia is continuously increasing and a considerable number of them refers to serious ADRs. To keep better track of medications and ADRs it is necessary to educate and encourage health professionals and patients in reporting side effects. Copyright © 2017 by Academy of Sciences and Arts of Bosnia and Herzegovina.

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

PubMed

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

2006-02-01

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

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

PubMed

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

2016-03-01

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.  . 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.  . 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).  . 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.

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

PubMed

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

2017-12-01

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

Nexavar®-related adverse reactions: Calabrian (Italy) experience for sorafenib exposition in 2012

PubMed Central

Cilurzo, Felisa; Staltari, Orietta; Patanè, Marinella; Ammendola, Michele; Garaffo, Caterina; Di Paola, Eugenio Donato

2013-01-01

Hepatocellular carcinoma (HCC) remains a major global health problem and Calabria in the south of Italy is not an exception. Sorafenib is the first and only Food and Drug Administration approved drug for the treatment of advanced HCC and it is currently under intensive monitoring by the Health Authorities in Italy Agenzia Italiana del Farmaco. This general report has been developed with the aim of briefly reviewing the data found in the reports of adverse reactions (ADRs) collected in Calabria in 2012 for sorafenib treated patients. Extrapolated data have highlighted some differences between the adverse drug reactions reported in patients younger or older than 70 years and other important differences with the current approved leaflet. Several limitations might be present in data analysis form spontaneous reporting, however, the relevance of reporting ADRs (dermatitis, asthenia, vomiting, etc.) for the early identification of drug related signals has to be underlined. PMID:24347990

HLA Association with Drug-Induced Adverse Reactions

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-01-01

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

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

Smallpox vaccination and adverse reactions. Guidance for clinicians.

PubMed

Cono, Joanne; Casey, Christine G; Bell, David M

2003-02-21

The guidance in this report is for evaluation and treatment of patients with complications from smallpox vaccination in the preoutbreak setting. Information is also included related to reporting adverse events and seeking specialized consultation and therapies for these events. The frequencies of smallpox vaccine-associated adverse events were identified in studies of the 1960s. Because of the unknown prevalence of risk factors among today's population, precise predictions of adverse reaction rates after smallpox vaccination are unavailable. The majority of adverse events are minor, but the less-frequent serious adverse reactions require immediate evaluation for diagnosis and treatment. Agents for treatment of certain vaccine-associated severe adverse reactions are vaccinia immune globulin (VIG), the first-line therapy, and cidofovir, the second-line therapy. These agents will be available under Investigational New Drug (IND) protocols from CDC and the U.S. Department of Defense (DoD). Smallpox vaccination in the preoutbreak setting is contraindicated for persons who have the following conditions or have a close contact with the following conditions: 1) a history of atopic dermatitis (commonly referred to as eczema), irrespective of disease severity or activity; 2) active acute, chronic, or exfoliative skin conditions that disrupt the epidermis; 3) pregnant women or women who desire to become pregnant in the 28 days after vaccination; and 4) persons who are immunocompromised as a result of human immunodeficiency virus or acquired immunodeficiency syndrome, autoimmune conditions, cancer, radiation treatment, immunosuppressive medications, or other immunodeficiencies. Additional contraindications that apply only to vaccination candidates but do not include their close contacts are persons with smallpox vaccine-component allergies, women who are breastfeeding, those taking topical ocular steroid medications, those with moderate-to-severe intercurrent illness, and

Suspected adverse drug reaction reports with oral anticoagulants in Portugal: a pharmacovigilance study.

PubMed

Caldeira, Daniel; Rodrigues, Raquel; Abreu, Daisy; Anes, Ana Marta; Rosa, Mário M; Ferreira, Joaquim J

2018-04-01

In this pharmacovigilance study, we aimed to determine the incidence of spontaneously reported suspected adverse drug reactions (ADRs) related to oral anticoagulants: non-vitamin K antagonist oral anticoagulants (NOACs; apixaban, dabigatran, edoxaban, rivaroxaban) and vitamin K antagonists (VKA) Research design and methods: In this retrospective observational study, we extracted all the individual case safety reports related to oral anticoagulants recorded in the Portuguese Pharmacovigilance Database (January 2010 to April 2015). The annual incidence of suspected ADRs was estimated using drug exposure data. Disproportionality of reporting ADR was addressed through reporting odds ratio (ROR) and 99% confidence intervals. We appraised 794 suspected ADR (78% related to NOACs). The annual number of ADRs increased overtime with 9 ADRs/million Defined Daily Dose (DDD) at the end of 2014. The incidence of NOACs ADRs decreased from 2012 onwards. VKA showed a disproportion in 'Investigation' (ROR 0.10, 99%CI 0.05-0.22) and 'Injury, poisoning and procedural complications' (ROR 0.36, 99%CI 0.19-0.69) ADRs compared with NOACs. NOACs had a higher significant disproportion of 'Nervous system disorders' related ADRs (ROR 3.98, 99%CI 1.50-10.53). Reporting of ADRs associated with oral anticoagulants (mainly NOACs), is increasing. Exploratory disproportion analyses showed an increase of reports of nervous system ADRs with NOACs, and INR-related ADRs with VKA.

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.

Adverse Event Reporting for Herbal Medicines: A Result of Market Forces

PubMed Central

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

2009-01-01

Herbal products are readily available over the counter in health food stores and are often perceived to be without risk. The current Canadian adverse event reporting system suffers from severe underreporting, resulting in a scarcity of safety data on herbal products. Twelve health food store personnel in the Greater Toronto Area were interviewed about their responses to herbal product–related adverse reactions. They generally fostered customer loyalty by offering generous return policies, which included collecting contact information to be sent to the manufacturers with the returned product. Thus, despite the public's lack of knowledge about the formal reporting system, adverse reaction information was directed to manufacturers whenever it resulted in a product return. The relationship between health food stores, industry and Health Canada provides a new opportunity to facilitate adverse event reporting. Additional information could be collected during the return process, and educational initiatives could be implemented to augment current post-market surveillance procedures for herbal products. PMID:20436811

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

Code of Federal Regulations, 2014 CFR

2014-07-01

... SIGNIFICANT ADVERSE REACTIONS TO HEALTH OR THE ENVIRONMENT General Provisions § 717.12 Significant adverse... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Significant adverse reactions that must be recorded. 717.12 Section 717.12 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY...

[Recording and reporting adverse reactions in clinical trials. New legal provisions according to the 12th Law Amending the German Drug Law (AMG) and the Ordinance on GCP (GCP-V)].

PubMed

Eckhardt, K; Cremer-Schaeffer, P; König, J; Paeschke, N

2005-02-01

With the 12th Law Amending the German Drug Law and the Ordinance on GCP (GCPV), new legal provisions for clinical trials came into force in August 2004. These include specific definitions and differentiated reporting obligations affecting investigators, sponsors, authorities and ethics committees concerning pharmacovigilance in clinical trials. The definitions according to section sign3 (6-8) GCP-V make clear that these provisions focus on those adverse events and adverse drug reactions, which are related to investigational medicinal products. In the GCP-V for the first time legally binding provisions for investigators are laid down defining obligations to report all serious adverse events to the sponsor. The sponsor of clinical trials plays a decisive role concerning the evaluation, documentation and reporting to the competent higher authorities, ethics committees and investigators involved in the clinical trial. In the GCP-V different time limits concerning the reporting for sponsors are laid down. The requirements concerning expedited reporting focus on suspected unexpected serious adverse reactions (SUSARs), i. e. those adverse serious reactions, which are not described in the information on the investigational medicinal product. The time limit for reporting SUSARs leading to death or life-threatening SUSARs is 7 days, while for other SUSARs the time limit is 15 days. Besides the responsibilities on expedited reporting the sponsor has to submit a line listing of all serious adverse reactions which occurred during the clinical trial and a report on the safety of the trial subjects on an annual basis or on request. On the European level the harmonisation concerning the provisions on pharmacovigilance in clinical trials according to the Directive 2001/20/EC and the Eudravigilance database should contribute to reach a faster and more effective exchange of safety information related to clinical trials between the different competent authorities of the EU member

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

PubMed

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

2007-01-01

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

Pharmacist's knowledge, practice and attitudes toward pharmacovigilance and adverse drug reactions reporting process.

PubMed

Suyagh, Maysa; Farah, Doaa; Abu Farha, Rana

2015-04-01

Adverse drug reactions (ADRs) are a major cause of drug related morbidity and mortality. Pharmacovigilance is the science that plays an essential role in the reduction of ADRs, thus the evolution and growth of this science are critical for effective and safe clinical practice. This study is considered the first study in the region to evaluate pharmacist's knowledge, practice and attitudes toward ADRs reporting after establishing the national ADRs reporting center in Jordan. A cross sectional study was used to evaluate pharmacist knowledge and attitude toward ADRs reporting. A structured validated questionnaire was developed for this purpose and a total of 208 pharmacists were recruited to participate in this study. The majority of pharmacists have insufficient awareness and lack of knowledge about pharmacovigilance and ADRs reporting. Also the rate of reporting of ADRs was extremely poor. Several factors were found to discourage pharmacists from reporting ADRs, which include inadequate information available from the patient, unavailability of pharmacist ADRs form when needed, unawareness of the existence of the national ADRs reporting system. Also pharmacists think that ADRs are unimportant or they did not know how to report them. The results of this study suggest that pharmacists have insufficient knowledge about the concept of pharmacovigilance and spontaneous ADRs reporting. On the other hand, pharmacists had positive attitudes toward pharmacovigilance, despite their little experience with ADRs reporting. Educational programs are needed to increase pharmacist's role in the reporting process, and thus to have a positive impact on the overall patient caring process.

Adverse Reactions to Field Vaccination Against Lumpy Skin Disease in Jordan.

PubMed

Abutarbush, S M; Hananeh, W M; Ramadan, W; Al Sheyab, O M; Alnajjar, A R; Al Zoubi, I G; Knowles, N J; Bachanek-Bankowska, K; Tuppurainen, E S M

2016-04-01

Lumpy skin disease (LSD) is an emerging disease in the Middle East region and has been recently reported in Jordan. The aim of this study was to investigate the adverse reactions that were reported after vaccine administration. Geographical areas enrolled in the study were free of the disease and away from the outbreak governorate. Sixty-three dairy cattle farms, with a total of 19,539 animals, were included in the study. Of those, 56 farms reported adverse clinical signs after vaccine administration. The duration between vaccine administration and appearance of adverse clinical signs ranged from 1 to 20 days (Mean = 10.3, SD ± 3.9). Clinical signs were similar to those observed with natural cases of lumpy skin disease. These were mainly fever, decreased feed intake, decreased milk production and variable sized cutaneous nodules (a few millimetres to around 2 cm in diameter) that could be seen anywhere on the body (head, neck, trunk, perineum), udder, and/or teats. Nodules were raised and firm initially and then formed dry scabs that could be peeled off the skin. The characteristic deep 'sit fast' appearance was rarely seen and most lesions were superficial. Some cattle had swollen lymph nodes, while a few pregnant animals aborted. The percentage of affected cattle ranged from 0.3 to 25% (Mean = 8, SD ± 5.1). Fever, decreased feed intake, and decreased milk production were seen in 83.9, 85.7, and 94.6% in cattle on the affected farms, respectively. All affected cattle displayed skin nodules over their entire bodies, while 33.9 and 7.1% of the affected farms reported nodular lesions present on the udders and teats, respectively. No mortalities were reported due to vaccine adverse reactions. Duration (course) of clinical signs ranged from 3 to 20 days (Mean = 13.7, SD ± 4.1). Two types of LSD vaccines were used by the farmers in this study. The first one was a sheep pox virus (SPPV) vaccine derived from the RM65 isolate [Jovivac, manufactured by Jordan

Comparison of online reporting systems and their compatibility check with respective adverse drug reaction reporting forms.

PubMed

Maharshi, Vikas; Nagar, Pravesh

2017-01-01

Different forms and online tools are available in different countries for spontaneous reporting, one of the most widely used methods of pharmacovigilance. Capturing sufficient information and adequate compatibility of online systems with respective reporting form is highly desirable for appropriate reporting of adverse drug reactions (ADRs). This study was aimed to compare three major online reporting systems (US, UK, and WHO) of the world and also to check their compatibility with the respective ADR reporting form. A total of 89 data elements to provide relevant information were found out from above three online reporting systems. All three online systems were compared regarding magnitude of information captured by each of them and scoring was done by providing a score of "1" to each element. Compatibility of ADR reporting forms of India (Red form), US (Form 3500), and UK (Yellow card form) was assessed by comparing the information gathered by them with that can be entered into their respective online reporting systems, namely, "VigiFlow," "US online reporting," and "Yellow card online reporting." Each unmatching item was given a score of "-1". VigiFlow scored "74" points, whereas online reporting systems of the US and UK scored "56" and "49," respectively, regarding magnitude of the information gathered by them. Compatibility score was found to be "0," "-9," and "-26" in case of ADR reporting systems of US, UK, and India, respectively. Our study reveals that "VigiFlow" is capable of capturing the maximum amount of information but "Form 3500" and "Online reporting system of US" are maximally compatible to each other among ADR reporting systems of all three countries.

21 CFR 314.80 - Postmarketing reporting of adverse drug experiences.

Code of Federal Regulations, 2010 CFR

2010-04-01

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

Structured vs. Unstructured: Factors Affecting Adverse Drug Reaction Documentation in an EMR Repository

PubMed Central

Skentzos, Stephen; Shubina, Maria; Plutzky, Jorge; Turchin, Alexander

2011-01-01

Adverse reactions to medications to which the patient was known to be intolerant are common. Electronic decision support can prevent them but only if history of adverse reactions to medications is recorded in structured format. We have conducted a retrospective study of 31,531 patients with adverse reactions to statins documented in the notes, as identified with natural language processing. The software identified statin adverse reactions with sensitivity of 86.5% and precision of 91.9%. Only 9020 of these patients had an adverse reaction to a statin recorded in structured format. In multivariable analysis the strongest predictor of structured documentation was utilization of EMR functionality that integrated the medication list with the structured medication adverse reaction repository (odds ratio 48.6, p < 0.0001). Integration of information flow between EMR modules can help improve documentation and potentially prevent adverse drug events. PMID:22195188

Impact of the HLA-B(*)58:01 Allele and Renal Impairment on Allopurinol-Induced Cutaneous Adverse Reactions.

PubMed

Ng, Chau Yee; Yeh, Yu-Ting; Wang, Chuang-Wei; Hung, Shuen-Iu; Yang, Chih-Hsun; Chang, Ya-Ching; Chang, Wan-Chun; Lin, Yu-Jr; Chang, Chee-Jen; Su, Shih-Chi; Fan, Wen-Lang; Chen, Der-Yuan; Wu, Yeong-Jian Jan; Tian, Ya-Chung; Hui, Rosaline Chung-Yee; Chung, Wen-Hung

2016-07-01

Allopurinol, a common drug for treating hyperuricemia, is associated with cutaneous adverse drug reactions ranging from mild maculopapular exanthema to life-threatening severe cutaneous adverse reactions, including drug reaction with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, and toxic epidermal necrolysis. We have previously reported that HLA-B*58:01 is strongly associated with allopurinol-induced severe cutaneous adverse reactions in Han Chinese, but the associations of the HLA-B*58:01 genotype in an allopurinol-induced hypersensitivity phenotype remain unclear. To investigate the comprehensive associations of HLA-B*58:01, we enrolled 146 patients with allopurinol-induced cutaneous adverse drug reactions (severe cutaneous adverse reactions, n = 106; maculopapular exanthema, n = 40) and 285 allopurinol-tolerant control subjects. Among these allopurinol-induced cutaneous adverse drug reactions, HLA-B*58:01 was strongly associated with severe cutaneous adverse reactions (odds ratio [OR] = 44.0; 95% confidence interval = 21.5-90.3; P = 2.6 × 10(-41)), and the association was correlated with disease severity (OR = 44.0 for severe cutaneous adverse reactions, OR = 8.5 for maculopapular exanthema). The gene dosage effect of HLA-B*58:01 also influenced the development of allopurinol-induced cutaneous adverse drug reactions (OR = 15.25 for HLA-B*58:01 heterozygotes and OR = 72.45 for homozygotes). Furthermore, coexistence of HLA-B*58:01 and renal impairment increased the risk and predictive accuracy of allopurinol-induced cutaneous adverse drug reactions (heterozygous HLA-B*58:01 and normal renal function: OR = 15.25, specificity = 82%; homozygous HLA-B*58:01 and severe renal impairment: OR = 1269.45, specificity = 100%). This HLA-B*58:01 correlation study suggests that patients with coexisting HLA-B*58:01 and renal impairment (especially estimated glomerular filtration rate < 30ml/minute/1.73 m(2)) should be cautious and avoid using

iADRs: towards online adverse drug reaction analysis.

PubMed

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

2012-12-01

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

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

Spontaneous Adverse Event Reports Associated with Zolpidem in the United States 2003-2012.

PubMed

Wong, Carmen K; Marshall, Nathaniel S; Grunstein, Ronald R; Ho, Samuel S; Fois, Romano A; Hibbs, David E; Hanrahan, Jane R; Saini, Bandana

2017-02-15

Stimulated reporting occurs when patients and healthcare professionals are influenced or "stimulated" by media publicity to report specific drug-related adverse reactions, significantly biasing pharmacovigilance analyses. Among countries where the non-benzodiazepine hypnotic drug zolpidem is marketed, the United States experienced a comparable surge of media reporting during 2006-2009 linking the above drug with the development of complex neuropsychiatric sleep-related behaviors. However, the effect of this stimulated reporting in the United States Food and Drug Administration Adverse Event Reporting System has not been explored. Using disproportionality analyses, reporting odds ratios for zolpidem exposure and the following adverse events; parasomnia, movement-based parasomnia, nonmovement-based parasomnia, amnesia, hallucination, and suicidality were determined and compared to all other medications in the database, followed by specific comparison to the benzodiazepine hypnotic class, year-by-year from 2003 to 2012. Odds ratios were increased significantly during and after the period of media publicity for parasomnias, movement-based parasomnias, amnesias and hallucinations. We also observed that zolpidem adverse drug reaction (ADR) reports have higher odds for parasomnias, movement-based parasomnias, amnesias, hallucinations, and suicidality compared to all other drugs, even before the media publicity cluster. Although our results indicate that zolpidem reports have higher odds for the ADR of interest even before the media publicity cluster, negative media coverage greatly exacerbated the reporting of these adverse reactions. The effect of such reporting must be borne in mind when decisions around drugs which have been the subject of intense media publicity are made by health professionals or regulatory bodies. © 2017 American Academy of Sleep Medicine

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

Comparison of online reporting systems and their compatibility check with respective adverse drug reaction reporting forms

PubMed Central

Maharshi, Vikas; Nagar, Pravesh

2017-01-01

AIM: Different forms and online tools are available in different countries for spontaneous reporting, one of the most widely used methods of pharmacovigilance. Capturing sufficient information and adequate compatibility of online systems with respective reporting form is highly desirable for appropriate reporting of adverse drug reactions (ADRs). This study was aimed to compare three major online reporting systems (US, UK, and WHO) of the world and also to check their compatibility with the respective ADR reporting form. MATERIALS AND METHODS: A total of 89 data elements to provide relevant information were found out from above three online reporting systems. All three online systems were compared regarding magnitude of information captured by each of them and scoring was done by providing a score of “1” to each element. Compatibility of ADR reporting forms of India (Red form), US (Form 3500), and UK (Yellow card form) was assessed by comparing the information gathered by them with that can be entered into their respective online reporting systems, namely, “VigiFlow,” “US online reporting,” and “Yellow card online reporting.” Each unmatching item was given a score of “−1”. RESULTS: VigiFlow scored “74” points, whereas online reporting systems of the US and UK scored “56” and “49,” respectively, regarding magnitude of the information gathered by them. Compatibility score was found to be “0,” “−9,” and “−26” in case of ADR reporting systems of US, UK, and India, respectively. CONCLUSION: Our study reveals that “VigiFlow” is capable of capturing the maximum amount of information but “Form 3500” and “Online reporting system of US” are maximally compatible to each other among ADR reporting systems of all three countries. PMID:29515278

[Do pediatricians identify adverse drug reactions even when they do not report them?

PubMed

Morales-Ríos, Olga; Jasso-Gutiérrez, Luis; Garduño-Espinosa, Juan; Olivar-López, Víctor; Muñoz-Hernández, Onofre

Spontaneous notification depends on the ability of pediatricians to identify adverse drug reactions (ADRs) along with their habit of reporting these incidents. During the years 2008 and 2009, the frequency of reports of ADRs to the Electronic Program of Pharmacovigilance (SISFAR) in the Hospital Infantil of Mexico Federico Gomez (HIMFG) was low (0.44% and 0.20%, respectively). Because of the above, the ability of pediatricians from the Emergency Department (ED) to identify ADRs using the clinical chart review was evaluated in 2010 in this study. A descriptive, observational, cross-sectional retrospective study was conducted in the ED from March 1 to August 31. ADRs were classified and quantified as "ADRs identified by pediatricians" when there was evidence in the clinical chart that pediatricians associated a clinical sign, symptom and laboratory value with an ADR. The numbers of notifications reported in SISFAR were quantified. Descriptive analysis was done using SPSS v.18. Considering patients who were admitted to the ED, the frequency of ADRs was 21.8%. The frequency of ADRs identified by physicians in clinical charts was 86%. The pharmacist detected 14% of ADRs. The frequency of ADRs reported by physicians was 6.1%. Although identification of ADRs in the clinical charts by pediatricians was high, it is possible that some ADRs were undetected. Because underreporting was very high, it is necessary to take actions to improve the reporting process. Copyright © 2015. Publicado por Masson Doyma México S.A.

Oral antibiotic adverse reactions after penicillin skin testing: multi-year follow-up.

PubMed

Macy, E; Burchette, R J

2002-12-01

Long-term follow-up data on adverse drug reactions after oral antibiotic use in penicillin allergy history positive individuals with penicillin skin test done in advance of need are rare. Oral antibiotic associated adverse drug reactions in 83 penicillin skin test positive individuals were compared to a sex, age, and length of follow-up matched sample of 166 penicillin skin test negative individuals, all of whom had at least one post penicillin skin test oral antibiotic. The mean post penicillin skin test follow-up interval was 34.5 +/- 16.6 months. There were 1655 total oral antibiotic exposures. In penicillin skin test positive individuals, the adverse drug reaction rate was not significantly different with cephalosporin or non-beta-lactam use (P = 0.12). In penicillin skin test negative individuals the adverse drug reaction rate was significantly lower with cephalosporin vs. non-beta-lactam use (P = 0.005). Penicillin was safely used in penicillin skin test negative individuals. Overall cephalosporins caused fewer adverse drug reactions independent of penicillin skin test status (P = 0.005). Penicillin skin testing was only able to predict penicillin associated adverse drug reactions in penicillin skin test positive individuals. Excluding accidental penicillin exposure in penicillin skin test positive individuals, non-beta-lactams were associated with adverse drug reactions more often than penicillins or cephalosporins, independent of the penicillin skin test result. Cephalosporins were used as or more safely than non-beta-lactams in both penicillin skin test positive and negative individuals.

Under-reporting of adverse drug reactions: a challenge for pharmacovigilance in India.

PubMed

Tandon, Vishal R; Mahajan, Vivek; Khajuria, Vijay; Gillani, Zahid

2015-01-01

The aim was to evaluate the extent and factors responsible for underreporting (UR) of adverse drug reactions (ADRs) in India. A retrospective observational, cross-sectional prospective questionnaire-based analysis was undertaken to evaluate the extent and factors for UR of ADRs in pharmacovigilance. 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. UR is a matter of concern PvPI. Multiple interventions are needed to improve ADR reporting.

Predictive Factors of Spontaneous Reporting of Adverse Drug Reactions among Community Pharmacists.

PubMed

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

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. 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. 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). 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.

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

[Adverse reactions to mosquito bites in scholars from Monterrey, Nuevo Leon, Mexico].

PubMed

Manrique López, María Amelia; González Díaz, Sandra N; Arias Cruz, Alfredo; Sedó Mejía, Giovanni A; Canseco Villarreal, José Ignacio; Gómez Retamoza, Ernesto Antonio; Padrón López, Olga Magdalena; Cruz Moreno, Miguel Angel; Cisneros Salazar, Guillermo Daniel

2010-01-01

Allergic reactions to insect bites are a global problem, the true incidence and prevalence of morbidity from adverse reactions to mosquito bites are unknown. To describe the adverse reactions to mosquito bites in school-age children of Monterrey, Nuevo Leon. A cross-sectional descriptive study was made via a randomized application of questionnaires to children from public elementary schools in the metropolitan area of Monterrey, Nuevo Leon. A total of 11 public schools randomly selected were included in the study. One thousand questionnaires were submitted, of which 506 fulfilled the inclusion criteria; 55% were females. Seventy-six percent referred adverse reactions to mosquito bites, itching (75%) and rash (72%) being the most frequent ones, in the last 12 months. Adverse reactions to mosquito bites occur frequently. Early detection is important to establish a prompt treatment.

Review of adverse reactions to injections of Chinese materia medica.

PubMed

Bian, Zhaoxiang; Shang, Hongcai; Cheng, Chungwah; Wu, Taixiang; Li, Youping; Zhang, Boli

2010-05-01

Using Chinese Materia Medica (CM) as injections is an innovation that is proving effective in extensive clinical use in Mainland China. However, recent reports have focused on adverse reactions, ignoring the considerable successes of these preparations. In order to achieve balance in the media and in the minds of the public, we suggest the first step is to clarify the concepts of and differences between adverse drug reactions (ADR) and adverse events (AE) for all concerned-the public, medical practitioners, government officials, and lawmakers. Second, the State Food and Drug Administration should raise the requirements for Chinese Materia Medica Injection (CMI) registration and license approval and emphasize the importance of evidence-based CMI development and evidence-based CMI license approval. Thirdly, drug companies and institutions should reinforce basic research about the quality control of herbs and CMI-drug interactions. Fourth, the Government should clarify the legal responsibilities for CMI approval agencies, CMI developers, medical doctors, and patients. Fifth, the medical association and Government should enhance training for health care professionals concerning the usage of CMIs. And finally sixth, State Food and Drug Administration should monitor the content and quality of the directions for use of CMI. © 2010 Blackwell Publishing Asia Pty Ltd and Chinese Cochrane Center, West China Hospital of Sichuan University.

Adverse Drug Reactions (ADR) and Emergencies.

PubMed

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

2018-04-13

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

Public awareness and perception toward Adverse Drug Reactions reporting in Riyadh, Saudi Arabia.

PubMed

Sales, Ibrahim; Aljadhey, Hisham; Albogami, Yasser; Mahmoud, Mansour A

2017-09-01

Purpose: To assess the general public awareness and perception about Adverse Drug Reactions (ADRs) reporting and pharmacovigilance. Method: A cross-sectional study conducted on June 2012 during awareness campaign held in two malls in Riyadh city for two days. A self-administered questionnaire consisting of three parts was distributed to the attendees who accepted to participate in the study. Results: A total of 204 questionnaires were collected with a response rate of 68%. Twenty-three percent could correctly define ADRs. Only 13(15.7%) of responders were familiar with the term "Pharmacovigilance" and only 78.6% were aware about the Saudi Pharmacovigilance Center. Sixty-seventy percent indicated that their physicians or pharmacists don't actively encourage them to report ADRs that may occur when they take their medications. The majority of responders (73.2%) believed that the medical team, rather than consumers, should report ADRs. When asked why patients do not report ADRs, 19.1(48.5%) believed that patients do not know whether the ADR is from the medication or not, 18.1(46.1%) stated that the reason was because patients don't know about the Pharmacovigilance Center, 16(40.7%) think that patients don't know about the importance of ADRs reporting, and 14(36.3%) responded that patients probably don't know how to report ADRs. Conclusion: The general public in Saudi Arabia are not aware about ADRs reporting and the pharmacovigilance system. The Saudi Food and Drug Authorities (FDA) need to put more efforts to increasing public awareness about the importance of ADRs reporting process and the importance of pharmacovigilance system in promoting patient safety.

Cutaneous drug reaction case reports: from the world literature.

PubMed

2003-01-01

Skin disorders are the most common adverse reactions attributed to drugs. Any skin disorder can be imitated, induced or aggravated by drugs. To help you keep up-to-date with the very latest skin reactions occurring with both new and established drugs, this section of the journal brings you information selected from the adverse drug reaction alerting service Reactions Weekly. Reactions Weekly is the complete drug safety alerting service and summarizes information selected from over 1600 biomedical journals. This newsletter is produced by Adis International and is available in a variety of formats. Please contact your nearest Adis office for subscription details. The use of tradenames, identified by ['~'] or the use of a registered ((R)) or trade mark ( trade mark ), is for product identification purposes only and does not imply endorsement. The following case reports are selected from the very latest to be published in the world dermatology literature. Any claim of a first report has been verified by a search of AdisBase (a proprietary database of Adis International) and Medline. In addition, the World Health Organization (WHO) Adverse Drug Reactions database is also searched. This database, maintained by the Uppsala Monitoring Centre in Sweden, is the largest and most comprehensive adverse drug reaction source in the world, with information obtained from National Centers of 65 affiliate countries. Each case report is assessed for seriousness using the FDA MedWatch definition of serious (patient outcome is: death; life-threatening; hospitalization; disability; congenital anomaly; or requires intervention to prevent permanent impairment or damage).

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

PubMed

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

2015-05-01

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

Spontaneous Adverse Event Reports Associated with Zolpidem in the United States 2003–2012

PubMed Central

Wong, Carmen K.; Marshall, Nathaniel S.; Grunstein, Ronald R.; Ho, Samuel S.; Fois, Romano A.; Hibbs, David E.; Hanrahan, Jane R.; Saini, Bandana

2017-01-01

Study Objectives: Stimulated reporting occurs when patients and healthcare professionals are influenced or “stimulated” by media publicity to report specific drug-related adverse reactions, significantly biasing pharmacovigilance analyses. Among countries where the non-benzodiazepine hypnotic drug zolpidem is marketed, the United States experienced a comparable surge of media reporting during 2006–2009 linking the above drug with the development of complex neuropsychiatric sleep-related behaviors. However, the effect of this stimulated reporting in the United States Food and Drug Administration Adverse Event Reporting System has not been explored. Methods: Using disproportionality analyses, reporting odds ratios for zolpidem exposure and the following adverse events; parasomnia, movement-based parasomnia, nonmovement-based parasomnia, amnesia, hallucination, and suicidality were determined and compared to all other medications in the database, followed by specific comparison to the benzodiazepine hypnotic class, year-by-year from 2003 to 2012. Results: Odds ratios were increased significantly during and after the period of media publicity for parasomnias, movement-based parasomnias, amnesias and hallucinations. We also observed that zolpidem adverse drug reaction (ADR) reports have higher odds for parasomnias, movement-based parasomnias, amnesias, hallucinations, and suicidality compared to all other drugs, even before the media publicity cluster. Conclusions: Although our results indicate that zolpidem reports have higher odds for the ADR of interest even before the media publicity cluster, negative media coverage greatly exacerbated the reporting of these adverse reactions. The effect of such reporting must be borne in mind when decisions around drugs which have been the subject of intense media publicity are made by health professionals or regulatory bodies. Citation: Wong CK, Marshall NS, Grunstein RR, Ho SS, Fois RA, Hibbs DE, Hanrahan JR, Saini B

An unreported clindamycin adverse reaction: wrist monoarthritis.

PubMed

Alikhani, Ahmad; Salehifar, Ebrahim

2012-01-01

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

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

PubMed

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

2015-10-01

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

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

PubMed Central

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

2015-01-01

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

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

PubMed Central

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

2013-01-01

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

Adverse drug reactions and off-label drug use in paediatric outpatients

PubMed Central

Horen, Benjamin; Montastruc, Jean-Louis; Lapeyre-mestre, Maryse

2002-01-01

Aims To investigate the potential relationship between off-label drug use and increased risk of adverse drug reactions in paediatric outpatients. Methods A prospective pharmacovigilance survey of drug prescribing in office based paediatricians was carried out in Haute-Garonne County (south west of France). Results The study involved a sample of 1419 children under 16 years old. Forty-two percent of patients were exposed to at least one off-label prescription. The incidence of adverse drug reactions was 1.41% (95% CI 0.79, 2.11). Off-label drug use was significantly associated with adverse drug reactions (relative risk 3.44; 95% CI 1.26, 9.38), particularly when it was due to an indication different than that defined in the Summary Product Characteristics (relative risk 4.42; 95% CI 1.60, 12.25). Conclusions Our data suggest an increasing risk of adverse drug reactions related to off-label drug use. This risk would be acceptable if further studies prove the potential benefit of such a drug use. PMID:12492616

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

PubMed

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

2018-04-01

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

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

PubMed Central

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

2010-01-01

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

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

PubMed

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

2013-01-01

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

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

Adverse drug reaction, patent blue V dye and anaesthesia.

PubMed

Tripathy, Swagata; Nair, Priya V

2012-11-01

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

Unusual and Interesting Adverse Cutaneous Drug Reactions.

PubMed

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

2018-01-01

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

Unusual and Interesting Adverse Cutaneous Drug Reactions

PubMed Central

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

2018-01-01

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

Online reporting of adverse drug reactions: a study from a French regional pharmacovigilance center.

PubMed

Abadie, Delphine; Chebane, Leyla; Bert, Max; Durrieu, Geneviève; Montastruc, Jean-Louis

2014-01-01

In France, online reporting via a website is a new method for notifying adverse drug reactions (ADRs). The French Midi-Pyrénées Regional Pharmacovigilance Center (RPVC) set up in July, 2010 a Web-based ADR reporting tool in order to improve ADR reporting rate. To assess feasibility, use and performances of this new ADR reporting system. To evaluate the main characteristics of these online reports. In a retrospective study, we evaluated characteristics (numbers, ADR reporting and file processing times, type of reporters, suspected drugs, "seriousness" and nature of ADRs) of online notifications reported to the RPVC between July 7(th), 2010 (first online notification) and December 31(th), 2011. We performed comparisons to a random sample of "conventional" notifications, i.e. spontaneously reported to the RPVC via traditional tools (post, fax, e-mail or telephone) during the same period. The total number of online reports was 312 over the 18-month period. There was a 45% increase in numbers of reports from ambulatory healthcare professionals after the implementation of the new reporting tool. Online reports were transmitted to the French Medicine Agency on average almost one month (26 days) earlier than "conventional" ones. This difference was mainly due to a faster ADR notification process via the online form (on average, the reporting period was decreased by 19 days with the new tool). In comparison to "conventional" notifications, online reports came more often from ambulatory healthcare professionals, and involved more frequently neuropsychiatric drugs and neuropsychiatric ADRs. None difference was observed for "seriousness" of ADRs. It is feasible to deploy an online ADR reporting system used by health professionals in current practice. We underline the efficiency of this new online reporting tool for increasing ADRs reporting. Moreover, this is the first published study demonstrating that an online reporting tool can help to save time on the ADR reporting

An EAACI “European Survey on Adverse Systemic Reactions in Allergen Immunotherapy (EASSI)”: the methodology

PubMed Central

2014-01-01

At present, there is no European report on clinically relevant systemic reactions due to the regular use of allergen immunotherapy (AIT), administered either subcutaneously or sublingually (SCIT and SLIT, respectively) outside clinical trials. Using an electronic survey and a “harmonised terminology” according to MedDRA, we aimed to prospectively collect systemic adverse reactions due to AIT from real life clinical settings. Under the framework of the EAACI, a team of European specialists in AIT, pharmacovigilance, epidemiology and drugs regulation set up a web-based prospective pilot survey to be conducted in three European countries (France, Germany and Spain). A designated “national coordinator” was responsible for following ethics requirements relative to each country and to select at least 30 doctors per country. Patients were recruited the same day they received their first dose of either SCIT or SLIT. Patient inclusion criteria were: adults and children, with IgE mediated pollen, house dust mite, Alternaria, and/or animal dander respiratory allergies who will initiate AIT. A list of 31 symptoms terms were extracted from the MedDRA (Medical Dictionary for Regulatory Activities) dictionary to harmonize the reporting of all adverse systemic reactions in this survey. The SurveyMonkey® online instrument was used by participant doctors to submit information directly to a blinded central database. Three questionnaires were generated: i) the Doctor Questionnaire, ii) the Patient Questionnaire and iii) the Adverse Reaction Questionnaire. A handbook and a mistake report form were given to each doctor. In this paper, we describe the methodology followed. PMID:25075276

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

PubMed

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

2015-07-01

Herbal medicines are perceived to be safe by the general public and medical practitioners, despite abundant evidence from clinical trials and case reports that show herbal preparations can have significant adverse effects. The overall impact of adverse events to herbal medicines in Australia is currently unknown. Post marketing surveillance of medications through spontaneous adverse drug reaction (ADR) reports to the Therapeutic Goods Administration (TGA) is one way to estimate this risk. The patterns of spontaneously reported ADRs provide insight to herbal dangers, especially when compared with patterns of a mechanistically similar conventional drug. The study compared the pattern of spontaneously reported ADRs to St. John's Wort (Hypericum perforatum), a common herbal treatment for depression which contains selective serotonin reuptake inhibitors (SSRI), to fluoxetine, a commonly prescribed synthetic SSRI antidepressant. Spontaneous ADR reports sent to the TGA between 2000-2013 for St. John's Wort (n = 84) and fluoxetine (n = 447) were obtained and analysed. The demographic information, types of interaction, severity of the ADR, and the body systems affected (using the Anatomical Therapeutic Chemical classification system) were recorded for individual ADR cases. The majority of spontaneously reported ADRs for St. John's Wort and fluoxetine were concerning females aged 26-50 years (28.6%, 22.8%). The organ systems affected by ADRs to St John's Wort and fluoxetine have a similar profile, with the majority of cases affecting the central nervous system (45.2%, 61.7%). This result demonstrates that herbal preparations can result in ADRs similar to those of prescription medications. © 2015 Wiley Publishing Asia Pty Ltd.

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.

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.

[Serious adverse drug reactions with tramadol reported to the French pharmacovigilance database between 2011 and 2015].

PubMed

Moulis, Florence; Rousseau, Vanessa; Abadie, Delphine; Masmoudi, Kamel; Micallef, Joëlle; Vigier, Caroline; Pierre, Sabrina; Dautriche, Anne; Montastruc, François; Montastruc, Jean-Louis

2017-12-01

Tramadol is an opioid and a serotonin reuptake inhibitor drug. It is approved for moderate to severe pain in adults. The aim of this study was to assess tramadol safety through a national pharmacovigilance study in France since dextropropoxyphen withdrawal in 2011. We described all serious adverse drug reactions (SADRs) reported with tramadol in adults in the French National PharmacoVigilance Database from August 1st, 2011 to December 31st, 2015. We identified 1512 SADRs during the study period. The most frequently reported SADRs were neurological (29.4%, including troubles of consciousness [13.2%] and seizures [6.7%]), psychiatric (22.8%, including confusions [14.6%] and hallucinations [7.3%]) and gastrointestinal (17.0%, mostly nausea and vomiting [9.6%]). Unexpected SADRs were also reported: hyponatremia, cholestatic hepatitis, serotonin syndrome. This study demonstrates new unexpected hepatic and metabolic SADRs. Tramadol alone can induce serotonin syndrome in overdose situations. Copyright © 2017 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

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

PubMed Central

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

2001-01-01

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

[Adverse drug reactions of hydroxymethylglutaryl-CoA reductase inhibitors reported to agency for medicinal products and medical devices].

PubMed

Skvrce, Nikica Mirosević; Bozina, Nada; Sarinić, Viola Macolić; Tomić, Sinisa

2010-01-01

Hydroxymethylglutaryl-CoA reductase inhibitors (statins) are drugs used in the treatment of chronic diseases and frequently in concomitant therapy with many other drugs. Therefore, the risk of adverse drug reactions (ADRs), especially those caused by interactions is high. Aim of the study was to describe and analyze ADRs caused by statins reported to Croatian Agency from March 2005 to December 2008, and to emphasize reasons of their occurrence. 136 of statin ADRs were reported. 12 % of all reported statins' ADRs were caused by interactions, which is higher than percent (5.6%) of interactions caused by all other drugs in 2005 and 2006. Proportion of serious ADRs related to administered dose and thus preventable was higher than proportion of all ADRs caused by statins (p = 0.003). Most serious ADRs could have been prevented with better understanding of interactions and by use of pharmacogenomics in identifying patients that are because of genetic predisposition more sensitive to standard doses.

Case report: anaphylactic reaction to guaifenesin.

PubMed

Ray, Manujendra; Faltay, Bela; Haller, Nairmeen Awad

2009-12-01

Adverse drug reactions lead to a significant number of hospital admissions each year and thus contribute to the overall financial burden of health care. Some of these drug reactions are allergic responses. As the overall predictability of allergic responses to drugs remains low, efforts to improve our understanding of the processes underlying these responses continue as we strive toward the ultimate goal of primary prevention. Allergic reactions range from mild pruritic to severe systemic anaphylactic responses. We report a case of a young healthy man who developed an anaphylactic reaction to an over-the-counter expectorant. A skin test showed that the patient had an immunoglobulin E-mediated allergic response to guaifenesin, one of the components of commonly available cough medications. Our review of published literature showed that this is the first report of a severe allergic response to guaifenesin.

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

PubMed

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

2018-01-01

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

Lesson of the month 2: An unusual adverse reaction associated with pramipexole.

PubMed

Tashkent, Yasmina; Aiyappan, Vinod

2018-06-01

Dopamine agonists such as pramipexole are commonly used in the treatment of restless legs syndrome (RLS) as well as Parkinson's disease. Pramipexole's common side effects are well documented; however, adverse skin reactions are less well known. In this case, a 45-year-old male farmer presented with excessive daytime tiredness and reported a history suggestive of RLS. He was initiated on pramipexole but developed a maculopapular erythematous rash in sun-exposed areas 8 days after its commencement. The skin rash resolved following pramipexole's cessation and it is thought the patient experienced a drug-induced photosensitivity reaction to pramipexole. This case highlights the potential for photosensitivity reactions to pramipexole, which is especially significant in countries like Australia where UV solar radiation is especially high. © Royal College of Physicians 2018. All rights reserved.

Adverse allergic reactions to linear ionic gadolinium-based contrast agents: experience with 194, 400 injections.

PubMed

Aran, S; Shaqdan, K W; Abujudeh, H H

2015-05-01

To report the authors' experience with the administration of four gadolinium-based contrast agents (GBCA; gadopentetate dimeglumine, gadofosveset trisodium, gadoxetate disodium and gadobenate dimeglumine) in a large study population at a single, large academic medical centre. The institutional review board approved this retrospective study in which data in the electronic incident reporting system were searched. A total of 194, 400 intravenous administrations of linear ionic GBCAs were assessed for the incidence of adverse reactions and risk factors from 1 January 2007 to 14 January 2014. The severity of reactions (mild, moderate, and severe), patient type (outpatients, inpatients, and emergency), examination type, and treatment options were also investigated. In total, 204/194400 (0.1%) patients (mean age 45.7 ± 14.9) showed adverse reactions, consisting of 6/746 (0.80%), 10/3200 (0.31%), 14/6236 (0.22%) and 174/184218 (0.09%), for gadofosveset trisodium, gadoxetate disodium, gadobenate dimeglumine, and gadopentetate dimeglumine, respectively. An overall significant difference was found between different GBCAs regarding the total number of reactions (p < 0.0001). When comparing the GBCAs together, significant differences were found between gadofosveset trisodium versus gadopentetate dimeglumine (p < 0.0001), gadofosveset trisodium versus gadobenate dimeglumine (p = 0.0051), gadoxetate disodium versus gadopentetate dimeglumine (p < 0.0001) and gadopentetate dimeglumine versus gadobenate dimeglumine (p = 0.0013). Rate of reaction was higher in females (F: 146/113187, 0.13%/M: 58/81213, 0.07%; p < 0.0001). Rate of reactions was higher in outpatient (180/158885, 0.11%), emergency (10/10413, 0.10%), and inpatients (14/25102, 0.05%), respectively (p < 0.0001). Most of the patients had mild symptoms 171/204 (83.8%). Abdomen-pelvis, liver, and thoracic examinations had highest rates of reactions (0.17 versus 0.16 versus 0.15). The overall rate of adverse reaction to GBCAs

Presence of phenylethylamine in hallucinogenic Psilocybe mushroom: possible role in adverse reactions.

PubMed

Beck, O; Helander, A; Karlson-Stiber, C; Stephansson, N

1998-01-01

The use of mushrooms containing the hallucinogenic substance psilocybin for intentional intoxication is relatively common. Occasionally, this results in adverse reactions with typical tachycardia that is not evidently caused by psilocybin. This study demonstrates the presence of phenylethylamine in the species Psilocybe semilanceata using gas chromatography-mass spectrometry and shows that the amount of this substance may vary much more than that of psilocybin. The highest amount of phenylethylamine (146 microg/g wet weight) was observed in mushrooms from a case of three young men hospitalized because of adverse reactions. Comparison of the symptoms observed in clinical cases of magic mushroom intoxication with those after intake of pure psilocybin or phenylethylamine suggests that phenylethylamine might have a role in the development of adverse reactions to Psilocybe mushroom intake.

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

PubMed

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

2018-05-09

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

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.

Pharmacy student perceptions of adverse event reporting.

PubMed

Kalari, Sirisha; Dormarunno, Matthew; Zvenigorodsky, Oleg; Mohan, Aparna

2011-09-10

To assess US pharmacy students' knowledge and perceptions of adverse event reporting. To gauge pharmacy students' impressions of adverse event reporting, a 10-question survey instrument was administered that addressed student perceptions of the reporting procedures of the Food and Drug Administration (FDA) and pharmaceutical manufacturers, as well as student understanding of the Health Insurance Portability and Accountability Act (HIPAA) and its relationship to adverse event reporting. Two hundred twenty-eight pharmacy students responded to the survey. The majority of respondents believed that the FDA is more likely than a pharmaceutical company to take action regarding an adverse event. There were misconceptions relating to the way adverse event reports are handled and the influence of HIPAA regulations on reporting. Communication between the FDA and pharmaceutical manufacturers regarding adverse event reports is not well understood by pharmacy students. Education about adverse event reporting should evolve so that by the time pharmacy students become practitioners, they are well acquainted with the relevance and importance of adverse event reporting.

Elucidation of the molecular mechanisms underlying adverse reactions associated with a kinase inhibitor using systems toxicology

PubMed Central

Amemiya, Takahiro; Honma, Masashi; Kariya, Yoshiaki; Ghosh, Samik; Kitano, Hiroaki; Kurachi, Yoshihisa; Fujita, Ken-ichi; Sasaki, Yasutsuna; Homma, Yukio; Abernethy, Darrel R; Kume, Haruki; Suzuki, Hiroshi

2015-01-01

Background/Objectives: Targeted kinase inhibitors are an important class of agents in anticancer therapeutics, but their limited tolerability hampers their clinical performance. Identification of the molecular mechanisms underlying the development of adverse reactions will be helpful in establishing a rational method for the management of clinically adverse reactions. Here, we selected sunitinib as a model and demonstrated that the molecular mechanisms underlying the adverse reactions associated with kinase inhibitors can efficiently be identified using a systems toxicological approach. Methods: First, toxicological target candidates were short-listed by comparing the human kinase occupancy profiles of sunitinib and sorafenib, and the molecular mechanisms underlying adverse reactions were predicted by sequential simulations using publicly available mathematical models. Next, to evaluate the probability of these predictions, a clinical observation study was conducted in six patients treated with sunitinib. Finally, mouse experiments were performed for detailed confirmation of the hypothesized molecular mechanisms and to evaluate the efficacy of a proposed countermeasure against adverse reactions to sunitinib. Results: In silico simulations indicated the possibility that sunitinib-mediated off-target inhibition of phosphorylase kinase leads to the generation of oxidative stress in various tissues. Clinical observations of patients and mouse experiments confirmed the validity of this prediction. The simulation further suggested that concomitant use of an antioxidant may prevent sunitinib-mediated adverse reactions, which was confirmed in mouse experiments. Conclusions: A systems toxicological approach successfully predicted the molecular mechanisms underlying clinically adverse reactions associated with sunitinib and was used to plan a rational method for the management of these adverse reactions. PMID:28725458

Treatments for Severe Cutaneous Adverse Reactions

PubMed Central

Cho, Yung-Tsu

2017-01-01

Severe cutaneous adverse reaction (SCAR) is life-threatening. It consists of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), and generalized bullous fixed drug eruptions (GBFDE). In the past years, emerging studies have provided better understandings regarding the pathogenesis of these diseases. These diseases have unique presentations and distinct pathomechanisms. Therefore, theoretically, the options of treatments might be different among various SCARs. However, due to the rarity of these diseases, sufficient evidence is still lacking to support the best choice of treatment for patients with SCAR. Herein, we will provide a concise review with an emphasis on the characteristics and treatments of each SCAR. It may serve as a guidance based on the current best of knowledge and may shed light on the directions for further investigations. PMID:29445753

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

PubMed

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

2016-07-01

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

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

... filling out form FDA 1932, ``Veterinary Adverse Drug Reaction, Lack of Effectiveness, Product Defect... Drug Reaction, Lack of Effectiveness, Product Defect Report.'' II. Significance of Guidance This level...

Do Health Professionals have Positive Perception Towards Consumer Reporting of Adverse Drug Reactions?

PubMed

Alshakka, Mohammed Ahmed; Ibrahim, Mohamed Izham Mohamed; Hassali, Mohamed Azmi Ahmad

2013-10-01

The aim of this study was to evaluate the perceptions of general practitioners (GPs) and community pharmacists (CPs) in Penang, Malaysia, towards consumer reporting of Adverse Drug Reactions (ADRs). A cross-sectional mail survey was adopted for the performance of the study. Survey questionnaires were sent to 192 CPs and 400 GPs in the state of Penang, Malaysia. Reminders were sent to all the non-respondents after 3 weeks of the initial mailing. Data which were collected from the questionnaires were analyzed by using the Statistical Package for Social Science (SPSS), version 15. The Chi-square test was used to determine as to whether there was any significant difference between expected and observed frequencies at the alpha level of 0.05. Only 104 respondents (47 CPs and 57 GPs) returned the survey, with a response rate of 18.0%- a figure which could be considered to be low. This study indicated that GPs and CPs were aware about the importance and benefits of consumer reporting. A majority of them (88.0%) thought that consumer reporting would add more benefits to the existing pharmacovigilance program. Similarly, 97% of the respondents agreed that reporting of ADRs was necessary and 87.0% respondents had seen ADRs among their patients. However, 57 of them (6.0%), had not been aware that the national program in Malaysia allowed consumers to report ADRs. A majority of them (97.0%) agreed that consumers needed more education regarding ADR reporting. Most of them (84.0%) thought that consumers could not write valid reports which were similar to reports which were made by healthcare professionals (HCPs). A majority of the respondents (68.0%) had not heard about the consumer reporting program in Malaysia and half of them did not believe that consumer reporting could overcome under-reporting, which was the main problem of the national pharmacovigilance program in Malaysia. The GPs and CPs were aware about the importance and benefits of consumer reporting. Such reporting

Do Health Professionals have Positive Perception Towards Consumer Reporting of Adverse Drug Reactions?

PubMed Central

Alshakka, Mohammed Ahmed; Ibrahim, Mohamed Izham Mohamed; Hassali, Mohamed Azmi Ahmad

2013-01-01

Aim: The aim of this study was to evaluate the perceptions of general practitioners (GPs) and community pharmacists (CPs) in Penang, Malaysia, towards consumer reporting of Adverse Drug Reactions (ADRs). Methodology: A cross-sectional mail survey was adopted for the performance of the study. Survey questionnaires were sent to 192 CPs and 400 GPs in the state of Penang, Malaysia. Reminders were sent to all the non-respondents after 3 weeks of the initial mailing. Data which were collected from the questionnaires were analyzed by using the Statistical Package for Social Science (SPSS), version 15. The Chi-square test was used to determine as to whether there was any significant difference between expected and observed frequencies at the alpha level of 0.05. Results: Only 104 respondents (47 CPs and 57 GPs) returned the survey, with a response rate of 18.0%- a figure which could be considered to be low. This study indicated that GPs and CPs were aware about the importance and benefits of consumer reporting. A majority of them (88.0%) thought that consumer reporting would add more benefits to the existing pharmacovigilance program. Similarly, 97% of the respondents agreed that reporting of ADRs was necessary and 87.0% respondents had seen ADRs among their patients. However, 57 of them (6.0%), had not been aware that the national program in Malaysia allowed consumers to report ADRs. A majority of them (97.0%) agreed that consumers needed more education regarding ADR reporting. Most of them (84.0%) thought that consumers could not write valid reports which were similar to reports which were made by healthcare professionals (HCPs). A majority of the respondents (68.0%) had not heard about the consumer reporting program in Malaysia and half of them did not believe that consumer reporting could overcome under-reporting, which was the main problem of the national pharmacovigilance program in Malaysia. Conclusion: The GPs and CPs were aware about the importance and benefits

First experiences with a tool to measure the level of clinical information present in adverse drug reaction reports.

PubMed

Oosterhuis, Ingrid; Rolfes, Leàn; Ekhart, Corine; Muller-Hansma, Annemarie; Härmark, Linda

2018-02-01

To make a proper causality assessment of an adverse drug reaction (ADR) report, a certain level of clinical information is necessary. A tool was developed to measure the level of clinical information present in ADR reports. The aim of this study was to test the validity and reliability of the clinical documentation tool (ClinDoc) in an international setting. The tool was developed by a panel of pharmacovigilance experts. It includes four domains: ADR, chronology of the ADR, suspected drug and patient characteristics. The final score categorizes reports into: excellent, well, moderately or poorly documented. In two rounds, eight pharmacovigilance assessors of different countries made a total of 224 assessments using the tool, with the expert panels judgement as a standard. Sensitivity and specificity were calculated. The tool with four outcome-categories demonstrated low sensitivity. A lack of distinctiveness was demonstrated between the categories moderate and well. Results for the second round were re-analysed using three categories. This demonstrated a better validity. This is the first tool to give insight in the level of relevant clinical information present in ADR reports. It can be used internationally to compare reports coming from different reporting methods and different types of reporters in pharmacovigilance.

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

PubMed

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

2018-05-01

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

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

PubMed

Ono, Hideki; Okamura, Maya; Fukushima, Akihiro

2018-06-20

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

Days lost due to disability of diclofenac-induced adverse drug reactions.

PubMed

Thomas, Dixon; Mathew, Molly; Raghavan, C Vijaya; Mohanta, Guru P; Reddy, Y Padmanabha

2012-01-01

Disability Adjusted Life Years (DALY) is a widely used measure to quantify the burden of diseases or illness. DALYs for a disease is calculated as the sum of the Years of Life Lost (YLL) due to premature mortality in the population and the equivalent healthy Years Lost due to Disability (YLD). The only difference from the YLD and Days Lost due to Disability (DLD) calculation is that instead of considering the duration of Adverse Drug Reaction (ADR) in years, it is calculated in days. DLD was measured for diclofenac tablets to prepare the ADR profile. The study was done on the patients (18-65 years old) attending the community pharmacy at Kasaragod district, South India, with prescription of diclofenac tablets. Patients reported ADRs on their next visit to the pharmacy or they had called to the provided phone number and reported it. Disability Weight (DW) was calculated in an analogue scale from 0-1. Zero represent complete health and 1 represent death or equivalent condition. DW was multiplied with occurrence and duration of ADRs in days. About 943 patients received diclofenac tablets in 1000 prescriptions were successfully followed up for possible, probable and definite ADRs. A total of 561 reactions reported in 2010 for diclofenac tablet in the study population. There were 34 different types of ADRs under 12 physiological systems/organs. Most common reactions were on gastrointestinal (GI) system (48%), followed by skin (14%), Central Nervous System (10%), renal (7%), and cardiovascular (7%). Abdominal pain, cramps or flatulence was the highest occurring GI ADR (107), followed by 43 rashes, 42 nausea/vomiting, 37 indigestion, 34 peptic ulcers, 31 edema etc. DLD for peptic ulcer was considerably high (0.078) per 1000 of the study population on diclofenac. The most damaging ADR were peptic ulcer with or without perforation, followed by rash 0.036 DLD and edema 0.027 DLD. There was considerable DLD by acute renal failure (0.012) Steven-Johnson syndrome (0.013) even

Bypassing adverse injection reactions to nanoparticles through shape modification and attachment to erythrocytes

NASA Astrophysics Data System (ADS)

Wibroe, Peter Popp; Anselmo, Aaron C.; Nilsson, Per H.; Sarode, Apoorva; Gupta, Vivek; Urbanics, Rudolf; Szebeni, Janos; Hunter, Alan Christy; Mitragotri, Samir; Mollnes, Tom Eirik; Moghimi, Seyed Moein

2017-07-01

Intravenously injected nanopharmaceuticals, including PEGylated nanoparticles, induce adverse cardiopulmonary reactions in sensitive human subjects, and these reactions are highly reproducible in pigs. Although the underlying mechanisms are poorly understood, roles for both the complement system and reactive macrophages have been implicated. Here, we show the dominance and importance of robust pulmonary intravascular macrophage clearance of nanoparticles in mediating adverse cardiopulmonary distress in pigs irrespective of complement activation. Specifically, we show that delaying particle recognition by macrophages within the first few minutes of injection overcomes adverse reactions in pigs using two independent approaches. First, we changed the particle geometry from a spherical shape (which triggers cardiopulmonary distress) to either rod- or disk-shape morphology. Second, we physically adhered spheres to the surface of erythrocytes. These strategies, which are distinct from commonly leveraged stealth engineering approaches such as nanoparticle surface functionalization with poly(ethylene glycol) and/or immunological modulators, prevent robust macrophage recognition, resulting in the reduction or mitigation of adverse cardiopulmonary distress associated with nanopharmaceutical administration.

Suspected adverse reactions to oral administration of a praziquantel-pyrantel combination in captive cheetahs (Acinonyx jubatus).

PubMed

Whitehouse-Tedd, Katherine M; Smith, Liesl; Budd, Jane A; Lloyd, Christopher G

2017-11-15

OBJECTIVE To characterize adverse reactions to oral administration of a combination of praziquantel and pyrantel embonate or pyrantel pamoate, with or without oxantel embonate, in captive cheetahs (Acinonyx jubatus). DESIGN Retrospective case series and case-control study. ANIMALS 16 captive cheetahs with signs of adverse reaction to oral administration of praziquantel and pyrantel, with or without oxantel embonate (affected group), and 27 cheetahs without such reactions (unaffected group), all from 3 independent facilities. PROCEDURES Medical records and postmortem findings for affected cheetahs were reviewed and compared with those of unaffected animals. Anthelmintic doses administered, age, and sex of cheetahs were compared between groups. RESULTS 3 reactions in affected cheetahs were fatal, whereas the remainder ranged from mild to severe. Postmortem examination failed to reveal any disease processes or conditions to explain the deaths. No differences in anthelmintic dose were identified between affected and unaffected cheetahs for all facilities combined, and no correlation existed between dose and reaction severity. No association with sex was detected, but affected cheetahs were significantly younger than unaffected cheetahs. This difference was not significant after controlling for facility. CONCLUSIONS AND CLINICAL RELEVANCE Cheetahs were concluded to have had an adverse reaction to the praziquantel-pyrantel combination because of temporal proximity of onset of clinical signs to dose administration, similarity of signs to those reported for toxicosis in other species for these drugs, and a lack of other disease process or environmental explanatory factors. A highly cautious approach to the use of this drug combination is recommended for cheetahs.

Characteristics, Quality and Contribution to Signal Detection of Spontaneous Reports of Adverse Drug Reactions Via the WEB-RADR Mobile Application: A Descriptive Cross-Sectional Study.

PubMed

Oosterhuis, Ingrid; Taavola, Henric; Tregunno, Philip M; Mas, Petar; Gama, Sara; Newbould, Victoria; Caster, Ola; Härmark, Linda

2018-05-14

Spontaneous reporting of suspected adverse drug reactions is key for efficient post-marketing safety surveillance. To increase usability and accessibility of reporting tools, the Web-Recognising Adverse Drug Reactions (WEB-RADR) consortium developed a smartphone application (app) based on a simplified reporting form. The objective of this study was to evaluate the characteristics, quality and contribution to signals of reports submitted via the WEB-RADR app. The app was launched in the UK, the Netherlands and Croatia between July 2015 and May 2016. Spontaneous reports submitted until September 2016 with a single reporter were included. For each country, app reports and reports received through conventional means in the same time period were compared to identify characteristic features. A random subset of reports was assessed for clinical quality and completeness. The contribution to signal detection was assessed by a descriptive analysis. Higher proportions of app reports were submitted by patients in the UK (28 vs. 18%) and Croatia (32 vs. 7%); both p < 0.01. In the Netherlands, the difference was small (60 vs. 57%; p = 0.5). The proportion of female patients and the median patient ages in app reports submitted by patients were similar to the reference. The proportion of reports of at least moderate quality was high in both samples (app: 78-85%, reference: 78-98%), for all countries. App reports contributed to detecting eight potential safety signals at the national level, four of which were eventually signalled. The WEB-RADR app offers a new route of spontaneous reporting that shows promise in attracting reports from patients and that could become an important tool in the future. Patient demographics are similar to conventional routes, report quality is sufficient despite a simplified reporting form, and app reports show potential in contributing to signal detection.

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

PubMed

Salk, Allison; Ehrenpreis, Eli D

2016-01-01

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

Reported time to onset of neurological adverse drug reactions among different age and gender groups using metoclopramide: an analysis of the global database Vigibase®.

PubMed

Svendsen, Kristian; Wood, Mollie; Olsson, Erika; Nordeng, Hedvig

2018-05-01

Despite FDA and EMA warnings of long-term use, little is known regarding the time to onset (TTO) of neurological adverse drug reactions (ADR) for metoclopramide. The aims of this study were, first, to evaluate whether neurological ADRs are more commonly reported for metoclopramide than for other medications, and second, to describe how time to onset of neurological ADRs differs by age and gender. All ADR reports with metoclopramide as the suspected/interacting drug were extracted from the WHOs Global ADR database Vigibase® between 1967 and May 2016. Cox proportional hazards models were fit using TTO of neurological ADRs as the outcome and age, gender, and type of ADR as predictors. Proportional Reporting Ratios (PRRs) for neurological ADRs were compared across age and gender. Lawyer reports were excluded in the analysis. Over 47,000 ADR reports with metoclopramide were identified. Over one third (35.6%) of the reports came from lawyers. The majority of ADRs in general and neurological ADRs in specific occurred within the first 5 days of metoclopramide use (median 1 day). TTO increased with age. Neurological ADRs were reported two to four times as frequently for metoclopramide than for other drugs, with the highest PRRs observed in children (PRR = 4.24 for girls and 4.60 for boys). Most adverse drug reactions occur within the first 5 days of treatment with metoclopramide. Patients requiring use of metoclopramide should be carefully monitored for neurological ADRs during the first days of treatment.

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

PubMed

Fujiwara, Masakazu; Kawasaki, Yohei; Yamada, Hiroshi

2016-01-01

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

Paraesthesia after local anaesthetics: an analysis of reports to the FDA Adverse Event Reporting System.

PubMed

Piccinni, Carlo; Gissi, Davide B; Gabusi, Andrea; Montebugnoli, Lucio; Poluzzi, Elisabetta

2015-07-01

This study was aimed to evaluate the possible alert signals of paraesthesia by local anaesthetics, focusing on those used in dentistry. A case/non-case study of spontaneous adverse events recorded in FAERS (FDA Adverse Event Reporting System) between 2004 and 2011 was performed. Cases were represented by the reports of reactions grouped under the term 'Paraesthesias and dysaesthesias' involving local anaesthetics (ATC: N01B*); non-cases were all other reports of the same drugs. Reporting odds ratios (ROR) with the relevant 95% confidence intervals (95CI) were calculated. Alert signal was considered when number of cases >3 and lower limit of ROR 95CI > 1. To estimate the specificity of signals for dentistry, the analysis was restricted to the specific term "Oral Paraesthesia" and to reports concerning dental practice. Overall, 528 reports of 'Paraesthesias and dysaesthesias' were retrieved, corresponding to 573 drug-reaction pairs (247 lidocaine, 99 bupivacaine, 85 articaine, 30 prilocaine, 112 others). The signal was significant only for articaine (ROR=18.38; 95CI = 13.95-24.21) and prilocaine (2.66; 1.82-3.90). The analysis of the specific term "Oral Paraesthesia" retrieved 82 reports corresponding to 90 drug-reaction pairs (37 articaine, 19 lidocaine, 14 prilocaine, 7 bupivacaine, 13 others) and confirmed the signal for articaine (58.77; 37.82-91.31) and prilocaine (8.73; 4.89-15.57). The analysis of reports concerning dental procedures retrieved a signal for articaine, both for any procedures (8.84; 2.79-27.97) and for non-surgical ones (15.79; 1.87-133.46). In conclusion, among local anaesthetics, only articaine and prilocaine generated a signal of paraesthesia, especially when used in dentistry. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Changes in risk of immediate adverse reactions to iodinated contrast media by repeated administrations in patients with hepatocellular carcinoma.

PubMed

Fujiwara, Naoto; Tateishi, Ryosuke; Akahane, Masaaki; Taguri, Masataka; Minami, Tatsuya; Mikami, Shintaro; Sato, Masaya; Uchino, Koji; Uchino, Kouji; Enooku, Kenichiro; Kondo, Yuji; Asaoka, Yoshinari; Yamashiki, Noriyo; Goto, Tadashi; Shiina, Shuichiro; Yoshida, Haruhiko; Ohtomo, Kuni; Koike, Kazuhiko

2013-01-01

To elucidate whether repeated exposures to iodinated contrast media increase the risk of adverse reaction. We retrospectively reviewed 1,861 patients with hepatocellular carcinoma who visited authors' institution, a tertiary referral center, between 2004 and 2008. We analyzed cumulative probability of adverse reactions and risk factors. We categorized all symptoms into hypersensitivity reactions, physiologic reactions, and other reactions, according to the American College of Radiology guidelines, and evaluated each category as an event. We estimated the association between hazard for adverse reactions and the number of cumulative exposures to contrast media. We also evaluated subsequent contrast media injections and adverse reactions. There were 23,684 contrast media injections in 1,729 patients. One hundred and thirty-two patients were excluded because they were given no contrast media during the study period. Adverse reactions occurred in 196 (0.83%) patients. The cumulative incidence at 10(th), 20(th), and 30(th) examination was 7.9%, 15.2%, and 24.1%, respectively. Presence of renal impairment was found to be one of risk factors for adverse reactions. The estimated hazard of overall adverse reaction gradually decreased until around 10(th) exposure and rose with subsequent exposures. The estimated hazard of hypersensitivity showed V-shaped change with cumulative number of exposures. The estimated hazard of physiologic reaction had a tendency toward decreasing and that of other reaction had a tendency toward increasing. Second adverse reaction was more severe than the initial in only one among 130 patients receiving subsequent injections. Repeated exposures to iodinated contrast media increase the risk of adverse reaction.

Informativeness of patient initial reports of adverse drug reactions. Can it be improved by a pharmacovigilance centre?

PubMed

Kheloufi, F; Default, A; Rouby, F; Laugier-Castellan, D; Boyer, M; Rodrigues, B; Ponte-Astoul, J; Jean-Pastor, M J; Blin, O; Micallef, J

2017-08-01

Little is known about the informativeness of initial patient reports before they are reviewed by a pharmacovigilance centre (PVC). We aim to describe the patterns of patient adverse drug reaction (ADR) reporting in France and estimate the contribution of a review by a PVC assessor on the informativeness of these reports. A retrospective study was conducted on patient reports between July 2011 and July 2015. Informativeness of 16 key elements of information (including drug start and end date, duration of treatment, time to onset and duration of the ADR, outcome, medical history and concomitant medication) was assessed in initial reports before and after review by a pharmacovigilance assessor. Overall, 240 reports concerning 522 ADR and involving 278 drugs were reported over this 4-year period. Mean number of available key elements of information in initial reports was increased from 11/16 to 15/16 after review of reports by the PVC. Time to onset and duration of the ADR were respectively available in only 51 and 58% of the reports before review compared to 83 and 90% after review. Medical history and concomitant medication were missing in 75% of the initial reports compared to less than 30% of the reports after review. Contacting the reporter enabled an increase of informativeness of most elements of information for more than 90% of the reports. Patient reports often need to be completed on key elements of information that are required to assess reports. Both upstream education of patients and downstream intervention of a pharmacovigilance assessor to complete missing information could help to enhance the informativeness of such reports.

Cimetidine: II. Adverse reactions and patterns of use.

PubMed

Freston, J W

1982-11-01

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

Community pharmacists' attitudes, perceptions, and barriers toward adverse drug reaction reporting in Malaysia: a quantitative insight.

PubMed

Elkalmi, Ramadan Mohamed; Hassali, Mohamed Azmi; Ibrahim, Mohamed Izham M; Jamshed, Shazia Qasim; Al-Lela, Omer Qutaiba B

2014-06-01

This study was designed to explore awareness and attitudes of community pharmacists toward the national ADR reporting system activities in the northern states of Malaysia. A cross-sectional survey using a validated self-administered questionnaire was used in this study. The questionnaire was delivered to all community pharmacists (N = 470) practicing in the four northern states of Malaysia (Perlis, Kedah, Pulau Pinang and Perak) during the study period. A total of 470 survey forms were sent with one wave of reminders. Only 116 pharmacists responded to the survey (response rate of 25.2%). The total number of usable responses was 104 (24.7%). The survey findings revealed that nearly three-quarters of pharmacists (n = 75; 72.1%) were not aware of the pharmacovigilance activities run by the drug regulatory authority in Malaysia. Although more than half (n = 65, 61.5%) of the surveyed pharmacists emphasized the importance of ADR reporting, only 13 pharmacists (12.9%) claimed that they submitted ADR reports to the Malaysia Adverse Drug Reaction Advisory Committee (MADRAC) before this survey. Barriers which prevent community pharmacists from ADR reporting were identified. These included lack of knowledge on how to report (n = 36; 34.7%), the unavailability of reporting forms (n = 44; 42.6%), and ignorance of where the report should be sent to (n = 46; 44.6%). Despite the unfamiliarity and the common misconceptions, the study results show that community pharmacists in the northern states of Malaysia have a very positive attitude toward the ADR reporting system in the country. However, the study findings highlight the urgent need for special education programs to establish continuous efforts to promote ADR reporting among community pharmacists. Further studies at the national level aimed at identifying and removing barriers that prevent community pharmacists from performing ADR reporting are required.

Changes in Risk of Immediate Adverse Reactions to Iodinated Contrast Media by Repeated Administrations in Patients with Hepatocellular Carcinoma

PubMed Central

Fujiwara, Naoto; Tateishi, Ryosuke; Akahane, Masaaki; Taguri, Masataka; Minami, Tatsuya; Mikami, Shintaro; Sato, Masaya; Uchino, Kouji; Enooku, Kenichiro; Kondo, Yuji; Asaoka, Yoshinari; Yamashiki, Noriyo; Goto, Tadashi; Shiina, Shuichiro; Yoshida, Haruhiko; Ohtomo, Kuni; Koike, Kazuhiko

2013-01-01

Background To elucidate whether repeated exposures to iodinated contrast media increase the risk of adverse reaction. Materials and Methods We retrospectively reviewed 1,861 patients with hepatocellular carcinoma who visited authors’ institution, a tertiary referral center, between 2004 and 2008. We analyzed cumulative probability of adverse reactions and risk factors. We categorized all symptoms into hypersensitivity reactions, physiologic reactions, and other reactions, according to the American College of Radiology guidelines, and evaluated each category as an event. We estimated the association between hazard for adverse reactions and the number of cumulative exposures to contrast media. We also evaluated subsequent contrast media injections and adverse reactions. Results There were 23,684 contrast media injections in 1,729 patients. One hundred and thirty-two patients were excluded because they were given no contrast media during the study period. Adverse reactions occurred in 196 (0.83%) patients. The cumulative incidence at 10th, 20th, and 30th examination was 7.9%, 15.2%, and 24.1%, respectively. Presence of renal impairment was found to be one of risk factors for adverse reactions. The estimated hazard of overall adverse reaction gradually decreased until around 10th exposure and rose with subsequent exposures. The estimated hazard of hypersensitivity showed V-shaped change with cumulative number of exposures. The estimated hazard of physiologic reaction had a tendency toward decreasing and that of other reaction had a tendency toward increasing. Second adverse reaction was more severe than the initial in only one among 130 patients receiving subsequent injections. Conclusion Repeated exposures to iodinated contrast media increase the risk of adverse reaction. PMID:24098420

Prior adversities predict posttraumatic stress reactions in adolescents following the Oslo Terror events 2011

PubMed Central

Nordanger, Dag Ø.; Breivik, Kyrre; Haugland, Bente Storm; Lehmann, Stine; Mæhle, Magne; Braarud, Hanne Cecilie; Hysing, Mari

2014-01-01

Background Former studies suggest that prior exposure to adverse experiences such as violence or sexual abuse increases vulnerability to posttraumatic stress reactions in victims of subsequent trauma. However, little is known about how such a history affects responses to terror in the general adolescent population. Objective To explore the role of prior exposure to adverse experiences as risk factors for posttraumatic stress reactions to the Oslo Terror events. Method We used data from 10,220 high school students in a large cross-sectional survey of adolescents in Norway that took place seven months after the Oslo Terror events. Prior exposure assessed was: direct exposure to violence, witnessing of violence, and unwanted sexual acts. We explored how these prior adversities interact with well-established risk factors such as proximity to the events, perceived life threat during the terror events, and gender. Results All types of prior exposure as well as the other risk factors were associated with terror-related posttraumatic stress reactions. The effects of prior adversities were, although small, independent of adolescents’ proximity to the terror events. Among prior adversities, only the effect of direct exposure to violence was moderated by perceived life threat. Exposure to prior adversities increased the risk of posttraumatic stress reactions equally for both genders, but proximity to the terror events and perceived life threat increased the risk more in females. Conclusions Terror events can have a more destabilizing impact on victims of prior adversities, independent of their level of exposure. The findings may be relevant to mental health workers and others providing post-trauma health care. PMID:24872862

Prior adversities predict posttraumatic stress reactions in adolescents following the Oslo Terror events 2011.

PubMed

Nordanger, Dag Ø; Breivik, Kyrre; Haugland, Bente Storm; Lehmann, Stine; Mæhle, Magne; Braarud, Hanne Cecilie; Hysing, Mari

2014-01-01

Former studies suggest that prior exposure to adverse experiences such as violence or sexual abuse increases vulnerability to posttraumatic stress reactions in victims of subsequent trauma. However, little is known about how such a history affects responses to terror in the general adolescent population. To explore the role of prior exposure to adverse experiences as risk factors for posttraumatic stress reactions to the Oslo Terror events. We used data from 10,220 high school students in a large cross-sectional survey of adolescents in Norway that took place seven months after the Oslo Terror events. Prior exposure assessed was: direct exposure to violence, witnessing of violence, and unwanted sexual acts. We explored how these prior adversities interact with well-established risk factors such as proximity to the events, perceived life threat during the terror events, and gender. All types of prior exposure as well as the other risk factors were associated with terror-related posttraumatic stress reactions. The effects of prior adversities were, although small, independent of adolescents' proximity to the terror events. Among prior adversities, only the effect of direct exposure to violence was moderated by perceived life threat. Exposure to prior adversities increased the risk of posttraumatic stress reactions equally for both genders, but proximity to the terror events and perceived life threat increased the risk more in females. Terror events can have a more destabilizing impact on victims of prior adversities, independent of their level of exposure. The findings may be relevant to mental health workers and others providing post-trauma health care.

[Treatment of Epidermal Growth Factor Receptor Inhibitors Associated Adverse Skin Reactions by Zhiyang Pingfu Liquid: a Clinical Study].

PubMed

Wang, Hong-yan; Zou, Chao; Cui, Hui-juan; Bai, Yan-ping; Li, Yuan; Tan, Huang-ying; Wang, Wei; Ju, Hai

2015-07-01

To study the curative effect of Zhiyang Pingfu Liquid (ZPL) in treating epidermal growth factor receptor inhibitors (EGFRIs) associated adverse reactions of the skin. All 54 patients with pathologically confirmed malignant tumor had EGFRIs induced adverse reactions of the skin to various degrees. ZPL was externally applied for them all, once or twice per day, 14 days consisting of one therapeutic course. Changes of adverse skin reactions, time for symptoms relief, adverse skin reaction types suitable for ZPL were observed before and after treatment. EGFRIs associated skin adverse reactions were improved to various degrees after they used ZPL. The shortest symptoms relief time was 1 day while the longest was 12 days, with an average of 6.93 days and the median time 7 days. Compared with before treatment, itching, rash/scaling, acne/acneform eruptions were obviously improved (P < 0.05). ZPL could alleviate EGFRls associated adverse skin reactions, especially showed better effect on itching, rash/scaling, acne/acneform eruptions.

Global patterns of adverse drug reactions over a decade: analyses of spontaneous reports to VigiBase™.

PubMed

Aagaard, Lise; Strandell, Johanna; Melskens, Lars; Petersen, Paw S G; Holme Hansen, Ebba

2012-12-01

Although systems to collect information about suspected adverse drug reactions (ADRs) were established in many countries and by the WHO in the 1960s, few studies have examined reported ADRs related to national income. The aim of the study was to characterize ADRs reported to the WHO-ADR database, VigiBase™, and to relate data to national income. We analysed ADR reports submitted to VigiBase™ from 2000 to 2009 with respect to reporting rate, age and sex of patient, type, seriousness and medications. Reports were also analysed with respect to national income level, classified in accordance with the World Bank definition: low, lower-middle, upper-middle and high. We analysed 1,359,067 ADR reports including 3,013,074 ADRs. Overall, 16% of reports were serious and 60% were reported for females. High-income countries had the highest ADR reporting rates (range 3-613 reports/million inhabitants/year) and low-income countries the lowest (range 0-21). Distribution of ADRs across income groups with respect to age group, seriousness and sex was non-significant. Overall, the majority of ADRs were reported for nervous system medications, followed by cardiovascular medicines. Low-income countries reported relatively more ADRs for antiinfectives for systemic use than high-income countries, and high-income countries reported more ADRs for antineoplastic and immunomodulating agents than lower-income groups. This study showed that high-income countries had the highest ADR reporting rates and low-income countries the lowest, with large variations across countries in each group. Significant differences in ADR reporting rates were only found for ADRs of the type 'skin and subcutaneous tissue disorders' and for the therapeutic groups 'antiinfectives for systemic use' and 'antineoplastic and immunomodulation agents'. To strengthen ADR reporting rates, especially in low-income countries, more research is needed about the impact of organizational structures and economic resources of

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

PubMed

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

2006-03-01

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

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

PubMed

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

2011-01-01

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

[Adverse reactions to human papillomavirus vaccine in the Valencian Community (2007-2011)].

PubMed

Rodríguez-Galán, M A; Pérez-Vilar, S; Díez-Domingo, J; Tuells, J; Gomar-Fayos, J; Morales-Olivas, F; Pastor-Villalba, E

2014-11-01

In 2009, two cases of seizures in adolescents following quadrivalent human papillomavirus vaccine (qHPV) administration, generated important media attention, and adversely affected public trust in this vaccine. Our objectives were to describe suspected adverse reactions (SARs) reported to the Pharmacovigilance Centre in the Valencian Community (PCVC) after administration of HPV vaccine, and to compare reporting rates of syncope and seizures following this vaccine with those of other vaccines administered to girls aged 13-15 years. Descriptive study of SARs reported following this vaccine to the PCVC between 2007 and 2011. The clinical symptoms most frequently reported were dizziness, headache, and syncope. Reporting rates of syncope or loss of consciousness and seizures with qHPV vaccine were 17 and 3.2 per 100,000 doses administered, respectively, and 15 and 1.6 for syncope or loss of consciousness and syncopal seizures occurred on the day of vaccination. The reporting rates of syncope or loss of consciousness and seizures were 6.4 and 0.4, for the other vaccines. Consistent with the media attention generated, and with results from other studies, the reporting rates of syncope or loss of consciousness and seizures were higher for the HPV vaccine than for other vaccines given in adolescence. Nevertheless, the overall information obtained on SARs following the qHPV vaccine suggests a good safety profile. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Clinicians' Reports in Electronic Health Records Versus Patients' Concerns in Social Media: A Pilot Study of Adverse Drug Reactions of Aspirin and Atorvastatin.

PubMed

Topaz, Maxim; Lai, Kenneth; Dhopeshwarkar, Neil; Seger, Diane L; Sa'adon, Roee; Goss, Foster; Rozenblum, Ronen; Zhou, Li

2016-03-01

Large databases of clinician reported (e.g., allergy repositories) and patient reported (e.g., social media) adverse drug reactions (ADRs) exist; however, whether patients and clinicians report the same concerns is not clear. Our objective was to compare electronic health record data and social media data to better understand differences and similarities between clinician-reported ADRs and patients' concerns regarding aspirin and atorvastatin. This pilot study explored a large repository of electronic health record data and social media data for clinician-reported ADRs and patients concerns for two common medications: aspirin (n = 31,817 ADRs accessible in clinical data; n = 19,186 potential ADRs accessible in social media data) and atorvastatin (n = 15,047 ADRs accessible in clinical data; n = 23,408 potential ADRs accessible in social media data). We found that the most frequently reported ADRs matched the most frequent patients' concerns. However, several less frequently reported reactions were more prevalent on social media (i.e., aspirin-induced hypoglycemia was discussed only on social media). Overall, we found a relatively strong positive and statistically significant correlation between the frequency ranking of reactions and patients' concerns for atorvastatin (Pearson's r = 0.61, p < 0.001) but not for aspirin (Pearson's r = 0.1, p = 0.69). Future studies should develop further natural language methods for a more detailed data analysis (i.e., identifying causality and temporal aspects in the social media data).

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

PubMed

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

2014-09-01

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

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

PubMed

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

2014-01-01

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

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

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

PubMed

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

2014-03-01

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

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

A Decade of Gabapentinoid Misuse: An Analysis of the European Medicines Agency's 'Suspected Adverse Drug Reactions' Database.

PubMed

Chiappini, Stefania; Schifano, Fabrizio

2016-07-01

The gabapentinoids pregabalin and gabapentin are being increasingly prescribed for a range of clinical conditions. Recently, although gabapentinoids at therapeutic dosages may present with low addictive liability levels, cases of misuse and rising numbers of related fatalities have been reported. The aim of the study was to identify and assess cases of gabapentinoid misuse or dependence as reported to the European Medicines Agency's EudraVigilance database, to identify the magnitude of this problem and the characteristics of these reactions. All spontaneous reports of both gabapentin- (2004-2015) and pregabalin- (2006-2015) related misuse/abuse/dependence were retrieved. A descriptive analysis by source, sex, age, and type of report was performed. From the EudraVigilance database 7639 (6.6 % of a total of 115,616) and 4301 (4.8 % of 90,166) adverse drug reaction reports of misuse/abuse/dependence were, respectively, associated with pregabalin and gabapentin, with an overall reporting frequency increasing over time. For both molecules, subjects typically involved were female adults. A total of 27 and 86 fatalities, respectively, associated with pregabalin and gabapentin, and mostly in combination with opioids, were identified. Analysis of proportional reporting ratios for drug abuse/dependence/intentional product misuse values seem to indicate that these adverse drug reactions were more frequently reported for pregabalin (1.25, 1.39, and 1.58, respectively) compared with gabapentin. Despite data collection/methodological approach limitations, the present data seem to suggest that gabapentinoid misuse may be a cause for concern, especially in patients with a history of substance misuse. Hence, healthcare professionals should be vigilant when prescribing these molecules.

Implementation of a module to promote competency in adverse drug reaction reporting in undergraduate medical students.

PubMed

Tripathi, Raakhi Kaliprasad; Jalgaonkar, Sharmila Vinayak; Sarkate, Pankaj V; Rege, Nirmala Narayan

2016-10-01

Underreporting and poor quality of adverse drug reaction (ADR) reports pose a challenge for the Pharmacovigilance Program of India. A module to impart knowledge and skills of ADR reporting to MBBS students was developed and evaluated. The module consisted of (a) e-mailing an ADR narrative and online filling of the "suspected ADR reporting form" (SARF) and (b) a week later, practical on ADR reporting was conducted followed by online filling of SARF postpractical at 1 and 6 months. SARF was an 18-item form with a total score of 36. The module was implemented in the year 2012-2013. Feedback from students and faculty was taken using 15-item prevalidated feedback questionnaires. The module was modified based on the feedback and implemented for the subsequent batch in the year 2013-2014. The evaluation consisted of recording the number of students responding and the scores achieved. A total of 171 students in 2012-2013 batch and 179 in 2013-2014 batch participated. In the 2012-2013 batch, the number of students filling the SARF decreased from basal: 171; 1 month: 122; 6 months: 17. The average scores showed improvement from basal 16.2 (45%) to 26.4 (73%) at 1 month and to 27.3 (76%) at 6 months. For the 2013-2014 batch, the number ( n = 179) remained constant throughout and the average score progressively increased from basal 10.5 (30%) to 27.8 (77%) at 1 month and 30.3 (84%) at 6 months. This module improved the accuracy of filling SARF by students and this subsequently will led to better ADR reporting. Hence, this module can be used to inculcate better ADR reporting practices in budding physicians.

DL-ADR: a novel deep learning model for classifying genomic variants into adverse drug reactions.

PubMed

Liang, Zhaohui; Huang, Jimmy Xiangji; Zeng, Xing; Zhang, Gang

2016-08-10

chain. A least square loss (LASSO) algorithm and a k-Nearest Neighbors (kNN) algorithm are used as the baselines for comparison and to evaluate the performance of our proposed deep learning model. There are 53 adverse reactions reported during the observation. They are assigned to 14 categories. In the comparison of classification accuracy, the deep learning model shows superiority over the LASSO and kNN model with a rate over 80 %. In the comparison of reliability, the deep learning model shows the best stability among the three models. Machine learning provides a new method to explore the complex associations among genomic variations and multiple events in pharmacogenomics studies. The new deep learning algorithm is capable of classifying various SNPs to the corresponding adverse reactions. We expect that as more genomic variations are added as features and more observations are made, the deep learning model can improve its performance and can act as a black-box but reliable verifier for other GWAS studies.

What can we learn from consumer reports on psychiatric adverse drug reactions with antidepressant medication? Experiences from reports to a consumer association.

PubMed

Vilhelmsson, Andreas; Svensson, Tommy; Meeuwisse, Anna; Carlsten, Anders

2011-10-25

According to the World Health Organization (WHO) the cost of adverse drug reactions (ADRs) in the general population is high and under-reporting by health professionals is a well-recognized problem. Another way to increase ADR reporting is to let the consumers themselves report directly to the authorities. In Sweden it is mandatory for prescribers to report serious ADRs to the Medical Products Agency (MPA), but there are no such regulations for consumers. The non-profit and independent organization Consumer Association for Medicines and Health, KILEN has launched the possibility for consumers to report their perceptions and experiences from their use of medicines in order to strengthen consumer rights within the health care sector. This study aimed to analyze these consumer reports. All reports submitted from January 2002 to April 2009 to an open web site in Sweden where anyone could report their experience with the use of pharmaceuticals were analyzed with focus on common psychiatric side effects related to antidepressant usage. More than one ADR for a specific drug could be reported. In total 665 reports were made during the period. 442 reports concerned antidepressant medications and the individual antidepressant reports represented 2392 ADRs and 878 (37%) of these were psychiatric ADRs. 75% of the individual reports concerned serotonin-reuptake inhibitor (SSRI) and the rest serotonin-norepinephrine reuptake inhibitor (SNRI). Women reported more antidepressant psychiatric ADRs (71%) compared to men (24%). More potentially serious psychiatric ADRs were frequently reported to KILEN and withdrawal symptoms during discontinuation were also reported as a common issue. The present study indicates that consumer reports may contribute with important information regarding more serious psychiatric ADRs following antidepressant treatment. Consumer reporting may be considered a complement to traditional ADR reporting.

Patch testing and cross sensitivity study of adverse cutaneous drug reactions due to anticonvulsants: A preliminary report.

PubMed

Shiny, T N; Mahajan, Vikram K; Mehta, Karaninder S; Chauhan, Pushpinder S; Rawat, Ritu; Sharma, Rajni

2017-03-26

To evaluate the utility of patch test and cross-sensitivity patterns in patients with adverse cutaneous drug reactions (ACDR) from common anticonvulsants. Twenty-four (M:F = 13:11) patients aged 18-75 years with ACDR from anticonvulsants were patch tested 3-27 mo after complete recovery using carbamazepine, phenytoin, phenobarbitone, lamotrigine, and sodium valproate in 10%, 20% and 30% conc. in pet. after informed consent. Positive reactions persisting on D3 and D4 were considered significant. Clinical patterns were exanthematous drug rash with or without systemic involvement (DRESS) in 18 (75%), Stevens-Johnsons syndrome/toxic epidermal necrolysis (SJS/TEN) overlap and TEN in 2 (8.3%) patients each, SJS and lichenoid drug eruption in 1 (4.2%) patient each, respectively. The implicated drugs were phenytoin in 14 (58.3%), carbamazepine in 9 (37.5%), phenobarbitone in 2 (8.3%), and lamotrigine in 1 (4.7%) patients, respectively. Twelve (50%) patients elicited positive reactions to implicated drugs; carbamazepine in 6 (50%), phenytoin alone in 4 (33.3%), phenobarbitone alone in 1 (8.3%), and both phenytoin and phenobarbitone in 1 (8.33%) patients, respectively. Cross-reactions occurred in 11 (92%) patients. Six patients with carbamazepine positive patch test reaction showed cross sensitivity with phenobarbitone, sodium valproate and/or lamotrigine. Three (75%) patients among positive phenytoin patch test reactions had cross reactions with phenobarbitone, lamotrigine, and/or valproate. Carbamazepine remains the commonest anticonvulsant causing ACDRs and cross-reactions with other anticonvulsants are possible. Drug patch testing appears useful in DRESS for drug imputability and cross-reactions established clinically.

Patch testing and cross sensitivity study of adverse cutaneous drug reactions due to anticonvulsants: A preliminary report

PubMed Central

Shiny, T N; Mahajan, Vikram K; Mehta, Karaninder S; Chauhan, Pushpinder S; Rawat, Ritu; Sharma, Rajni

2017-01-01

AIM To evaluate the utility of patch test and cross-sensitivity patterns in patients with adverse cutaneous drug reactions (ACDR) from common anticonvulsants. METHODS Twenty-four (M:F = 13:11) patients aged 18-75 years with ACDR from anticonvulsants were patch tested 3-27 mo after complete recovery using carbamazepine, phenytoin, phenobarbitone, lamotrigine, and sodium valproate in 10%, 20% and 30% conc. in pet. after informed consent. Positive reactions persisting on D3 and D4 were considered significant. RESULTS Clinical patterns were exanthematous drug rash with or without systemic involvement (DRESS) in 18 (75%), Stevens-Johnsons syndrome/toxic epidermal necrolysis (SJS/TEN) overlap and TEN in 2 (8.3%) patients each, SJS and lichenoid drug eruption in 1 (4.2%) patient each, respectively. The implicated drugs were phenytoin in 14 (58.3%), carbamazepine in 9 (37.5%), phenobarbitone in 2 (8.3%), and lamotrigine in 1 (4.7%) patients, respectively. Twelve (50%) patients elicited positive reactions to implicated drugs; carbamazepine in 6 (50%), phenytoin alone in 4 (33.3%), phenobarbitone alone in 1 (8.3%), and both phenytoin and phenobarbitone in 1 (8.33%) patients, respectively. Cross-reactions occurred in 11 (92%) patients. Six patients with carbamazepine positive patch test reaction showed cross sensitivity with phenobarbitone, sodium valproate and/or lamotrigine. Three (75%) patients among positive phenytoin patch test reactions had cross reactions with phenobarbitone, lamotrigine, and/or valproate. CONCLUSION Carbamazepine remains the commonest anticonvulsant causing ACDRs and cross-reactions with other anticonvulsants are possible. Drug patch testing appears useful in DRESS for drug imputability and cross-reactions established clinically. PMID:28396847

Detecting Signals of Disproportionate Reporting from Singapore's Spontaneous Adverse Event Reporting System: An Application of the Sequential Probability Ratio Test.

PubMed

Chan, Cheng Leng; Rudrappa, Sowmya; Ang, Pei San; Li, Shu Chuen; Evans, Stephen J W

2017-08-01

The ability to detect safety concerns from spontaneous adverse drug reaction reports in a timely and efficient manner remains important in public health. This paper explores the behaviour of the Sequential Probability Ratio Test (SPRT) and ability to detect signals of disproportionate reporting (SDRs) in the Singapore context. We used SPRT with a combination of two hypothesised relative risks (hRRs) of 2 and 4.1 to detect signals of both common and rare adverse events in our small database. We compared SPRT with other methods in terms of number of signals detected and whether labelled adverse drug reactions were detected or the reaction terms were considered serious. The other methods used were reporting odds ratio (ROR), Bayesian Confidence Propagation Neural Network (BCPNN) and Gamma Poisson Shrinker (GPS). The SPRT produced 2187 signals in common with all methods, 268 unique signals, and 70 signals in common with at least one other method, and did not produce signals in 178 cases where two other methods detected them, and there were 403 signals unique to one of the other methods. In terms of sensitivity, ROR performed better than other methods, but the SPRT method found more new signals. The performances of the methods were similar for negative predictive value and specificity. Using a combination of hRRs for SPRT could be a useful screening tool for regulatory agencies, and more detailed investigation of the medical utility of the system is merited.

Severe cutaneous adverse reactions induced by targeted anticancer therapies and immunotherapies

PubMed Central

Chen, Chun-Bing; Wu, Ming-Ying; Ng, Chau Yee; Lu, Chun-Wei; Wu, Jennifer; Kao, Pei-Han; Yang, Chan-Keng; Peng, Meng-Ting; Huang, Chen-Yang; Chang, Wen-Cheng; Hui, Rosaline Chung-Yee; Yang, Chih-Hsun; Yang, Shun-Fa; Chung, Wen-Hung; Su, Shih-Chi

2018-01-01

With the increasing use of targeted anticancer drugs and immunotherapies, there have been a substantial number of reports concerning life-threatening severe cutaneous adverse reactions (SCARs), including Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug rash with eosinophilia and systemic symptoms, drug-induced hypersensitivity syndrome, and acute generalized exanthematous pustulosis. Although the potential risks and characteristics for targeted anticancer agent- and immunotherapy-induced SCAR were not well understood, these serious adverse reactions usually result in morbidity and sequela. As a treatment guideline for this devastating condition is still unavailable, prompt withdrawal of causative drugs is believed to be a priority of patient management. In this review, we outline distinct types of SCARs caused by targeted anticancer therapies and immunotherapies. Also, we discuss the clinical course, latency, concomitant medication, tolerability of rechallenge or alternatives, tumor response, and mortality associated with these devastating conditions. Imatinib, vemurafenib, and rituximab were the top three offending medications that most commonly caused SJS/TEN, while EGFR inhibitors were the group of drugs that most frequently induced SJS/TEN. For drug rash with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome and acute generalized exanthematous pustulosis, imatinib was also the most common offending drug. Additionally, we delineated 10 SCAR cases related to innovative immunotherapies, including PD1 and CTLA4 inhibitors. There was a wide range of latency periods: 5.5–91 days (median). Only eight of 16 reported patients with SCAR showed clinical responses. Targeted anticancer drugs and immunotherapies can lead to lethal SCAR (14 deceased patients were identified as suffering from SJS/TEN). The mortality rate of TEN was high: up to 52.4%. The information compiled herein will serve as a solid foundation to formulate

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

PubMed

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

2013-01-01

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

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

PubMed

Pande, Sushil

2018-01-01

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

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

PubMed

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

2017-12-01

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

Knowledge of Adverse Drug Reaction Reporting Among Healthcare Professionals in Bhutan: A Cross-Sectional Survey.

PubMed

Dorji, Choki; Tragulpiankit, Pramote; Riewpaiboon, Arthorn; Tobgay, Tashi

2016-12-01

The Bhutan National Pharmacovigilance Centre (NPC) became an official member of the WHO Programme for International Drug Monitoring in December 2014; however, the number of adverse drug reactions (ADRs) reported is very low (50 reports per 773,722 inhabitants over 10 years). Surveys of healthcare professionals (HCPs) in similar countries have indicated that adequate knowledge of both ADRs and ADR reporting is likely to increase the number of ADR reports submitted. The aim of this study was to investigate the level of knowledge of both ADRs and ADR reporting among HCPs, including traditional medicine practitioners. A cross-sectional survey was conducted, using a validated self-administered questionnaire. The questionnaires were distributed to 670 HCPs, including clinical doctors, nurses, pharmacists and traditional medicine practitioners from four referral hospitals. The survey consisted of 12 questions pertaining to ADRs and 10 questions pertaining to knowledge of ADR reporting. The collected response was then analysed descriptively and results presented as mean ± standard deviation (SD) using SPSS version 20. The overall response rate was 434 (65 %) questionnaires, with HCPs consisting of clinical doctors (94, 22 %), nurses (257, 59 %), pharmacists (52, 12 %) and traditional medicine practitioners (31, 7 %). The overall mean ± SD score with regard to the level of knowledge of ADRs was 6.52 ± 2.81 out of a maximum score of 12, among which clinical doctors scored 7.48 ± 2.95, nurses 6.15 ± 2.47, pharmacists 8.15 ± 2.49 and traditional medicine practitioners 4.13 ± 3.18. The mean ± SD score with regard to the level of knowledge of ADR reporting among HCPs was 3.94 ± 1.89 out of a maximum score of 10, among which clinical doctors scored 3.93 ± 1.81, nurses 3.75 ± 1.74, pharmacists 5.00 ± 1.81 and traditional medicine practitioners 4.00 ± 1.77. Clinical doctors and pharmacists have better knowledge of ADRs than nurses and

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

PubMed

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

2010-05-01

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

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.

Adverse reactions to orthodontic materials.

PubMed

Sifakakis, I; Eliades, T

2017-03-01

Adverse effects can arise from the clinical use of orthodontic materials, due to the release of constituent substances (ions from alloys and monomers, degradation by-products, and additives from polymers). Moreover, intraoral aging affects the biologic properties of materials. The aim of this review is to present the currently identified major adverse effects of the metallic and polymeric components found in orthodontic appliances and materials. Corrosion in metallic orthodontic attachments releases metal ions, mainly iron, chromium, and nickel. The latter has received the greatest attention because of its reported potential for an allergic response. The formation of an oxide layer may inhibit the outward movement of ions, thereby acting as an obstacle for release. Titanium alloys have superior corrosion resistance than stainless steel. The efficiency of polymerisation is considered an essential property for all polymers. A poor polymer network is susceptible to the release of biologically reactive substances, such as bisphenol-A (BPA), which is capable of inducing hormone-related effects. The close proximity of a light-curing tip to the adhesive, pumice prophylaxis after bonding, indirect irradiation and mouth rinsing during the first hour after bonding may decrease BPA release. The adverse effects of some orthodontic materials should be considered during material selection and throughout orthodontic treatment, in order to minimise possible undesirable implications. © 2017 Australian Dental Association.

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

PubMed Central

Nikfarjam, Azadeh; Gonzalez, Graciela H.

2011-01-01

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

Vertigo/dizziness as a Drugs' adverse reaction.

PubMed

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

2013-12-01

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

Vertigo/dizziness as a Drugs’ adverse reaction

PubMed Central

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

2013-01-01

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

Adverse event reporting in cancer clinical trial publications.

PubMed

Sivendran, Shanthi; Latif, Asma; McBride, Russell B; Stensland, Kristian D; Wisnivesky, Juan; Haines, Lindsay; Oh, William K; Galsky, Matthew D

2014-01-10

Reporting adverse events is a critical element of a clinical trial publication. In 2003, the Consolidated Standards of Reporting Trials (CONSORT) group generated recommendations regarding the appropriate reporting of adverse events. The degree to which these recommendations are followed in oncology publications has not been comprehensively evaluated. A review of citations from PubMed, Medline, and Embase published between Jan 1, 2009 and December 31, 2011, identified eligible randomized, controlled phase III trials in metastatic solid malignancies. Publications were assessed for 14 adverse event-reporting elements derived from the CONSORT harms extension statement; a completeness score (range, 0 to 14) was calculated by adding the number of elements reported. Linear regression analysis identified which publication characteristics associated with reporting completeness. A total of 175 publications, with data for 96,125 patients, were included in the analysis. The median completeness score was eight (range, three to 12). Most publications (96%) reported only adverse events occurring above a threshold rate or severity, 37% did not specify the criteria used to select which adverse events were reported, and 88% grouped together adverse events of varying severity. Regression analysis revealed that trials without a stated funding source and with an earlier year of publication had significantly lower completeness scores. Reporting of adverse events in oncology publications of randomized trials is suboptimal and characterized by substantial selectivity and heterogeneity. The development of oncology-specific standards for adverse event reporting should be established to ensure consistency and provide critical information required for medical decision-making.

An evaluation of knowledge, attitude and practice of Indian pharmacists towards adverse drug reaction reporting: A pilot study

PubMed Central

Ahmad, Akram; Patel, Isha; Balkrishnan, Rajesh; Mohanta, G. P.; Manna, P. K.

2013-01-01

Background: Pharmacovigilance is a useful to assure the safety of medicines and protect consumers from their harmful effects. Healthcare professionals should consider Adverse Drug Reaction (ADR) reporting as part of their professional obligation and participate in the existent pharmacovigilance programs in their countries. In India, the National PV Program was re-launched in July 2010. Objectives: This survey was conducted in order to assess the knowledge, attitude and practice of Indian pharmacists with the aim of exploring the pharmacists’ participation in ADR reporting system, identifying the reasons of under reporting and determining the steps that could be adopted to increase reporting rates. Materials and Methods: A cross-sectional survey was carried out among the pharmacists in India using a pretested questionnaire with 33 questions (10 questions on knowledge, 6 on attitude, 7 on practice, 7 on future of ADR reporting in India and 3 on benefits of reporting ADRs.). The study was conducted, over a period of 3 months from May 2012 to July 2012. Results: Out of the 600 participants to whom the survey was administered, a total of 400 were filled. The response rate of the survey was 67%. 95% responders were knowledgeable about ADRs. 90% participants had a positive attitude towards making ADRs reporting mandatory for practicing pharmacists. 87.5% participants were interested in participating in the National Pharmacovigilance program, in India. 47.5% respondents had observed ADRs in their practice, and 37% had reported it to the national pharmacovigilance center. 92% pharmacists believed reporting ADRs immensely helped in providing quality care to patients. Conclusion: The Indian pharmacists have poor knowledge, attitude, and practice (KAP) towards ADR reporting and pharmacovigilance. Pharmacists with higher qualifications such as the pharmacists with a PharmD have better KAP. With additional training on Pharmacovigilance, the Indian Pharmacists working in

Adverse drug reactions induced by cardiovascular drugs in outpatients.

PubMed

Gholami, Kheirollah; Ziaie, Shadi; Shalviri, Gloria

2008-01-01

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

Adverse events after anthrax vaccination reported to the Vaccine Adverse Event Reporting System (VAERS), 1990-2007.

PubMed

Niu, Manette T; Ball, Robert; Woo, Emily Jane; Burwen, Dale R; Knippen, Maureen; Braun, M Miles

2009-01-07

During the period March 1, 1998 to January 14, 2007, approximately 6 million doses of Anthrax vaccine adsorbed (AVA) vaccine were administered. As of January 16, 2007, 4753 reports of adverse events following receipt of AVA vaccination had been submitted to the Vaccine Adverse Event Reporting System (VAERS). Taken together, reports to VAERS did not definitively link any serious unexpected risk to this vaccine, and review of death and serious reports did not show a distinctive pattern indicative of a causal relationship to AVA vaccination. Continued monitoring of VAERS and analysis of potential associations between AVA vaccination and rare, serious events is warranted.

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

PubMed

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

2017-09-01

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

Adverse food reactions in dogs and cats.

PubMed

Gaschen, Frédéric P; Merchant, Sandra R

2011-03-01

Adverse food reactions (AFR) are a common problem that may cause cutaneous and/or gastrointestinal signs in dogs and cats. They comprise food intolerance, food intoxication, and food allergy. Response to a dietary elimination trial and recurrence of signs during dietary provocation remain the centerpiece of diagnosis and management of dogs and cats with AFR. Response to an elimination trial is frequently observed in dogs and cats with chronic idiopathic enteropathies. However, only a fraction of them relapse after a dietary challenge. These animals may have mild to enteritis and/or colitis and benefit from various additional properties of the elimination diet. Copyright © 2011 Elsevier Inc. All rights reserved.

Pharmacovigilance and adverse drug reaction reporting: a perspective of community pharmacists and pharmacy technicians in Sana'a, Yemen.

PubMed

Al-Worafi, Yaser Mohammed; Kassab, Yaman Walid; Alseragi, Wafa Mohammed; Almutairi, Masaad Saeed; Ahmed, Ali; Ming, Long Chiau; Alkhoshaiban, Ali Saleh; Hadi, Muhammad Abdul

2017-01-01

The aim of this study was to compare the knowledge, attitude and barriers of pharmacy technicians and pharmacists toward pharmacovigilance, adverse drug reactions (ADRs) and ADR reporting in community pharmacies in Yemen. This cross-sectional survey was conducted among community pharmacists and pharmacy technicians in the capital of Yemen, Sana'a. A total of 289 community pharmacies were randomly selected. The validated and pilot-tested questionnaire consisted of six sections: demographic data, knowledge about pharmacovigilance, experience with ADR reporting, attitudes toward ADR reporting, and the facilitators to improve ADR reporting. A total of 428 pharmacy technicians and pharmacists were contacted and 179 went on to complete a questionnaire (response rate: 41.8%). Of the 179 respondents, 21 (11.7%) were pharmacists and 158 (88.3%) were pharmacy technicians, of which, 176 (98.3%) were male and 3 (1.7%) were female. The mean age of the respondents was 25.87±2.63 years. There was a significant difference between the pharmacists and pharmacy technicians in terms of knowledge scores ( P <0.05). The mean knowledge scores for pharmacists was 3.33±2.852 compared to 0.15±0.666 for pharmacy technicians. With regard to attitudes toward ADR reporting, all pharmacists (100%) showed a positive attitude, while only 43% of pharmacy technicians showed a positive attitude. Pharmacists have a significantly better knowledge than pharmacy technicians with regard to pharmacovigilance. More than half of pharmacy technicians showed a negative attitude toward ADR reporting. Therefore, educational interventions and training is very important for community pharmacists and pharmacy technicians in Yemen to increase their awareness and participation in ADR reporting.

Pharmacovigilance and adverse drug reaction reporting: a perspective of community pharmacists and pharmacy technicians in Sana’a, Yemen

PubMed Central

Al-Worafi, Yaser Mohammed; Kassab, Yaman Walid; Alseragi, Wafa Mohammed; Almutairi, Masaad Saeed; Ahmed, Ali; Ming, Long Chiau; Alkhoshaiban, Ali Saleh; Hadi, Muhammad Abdul

2017-01-01

Objective The aim of this study was to compare the knowledge, attitude and barriers of pharmacy technicians and pharmacists toward pharmacovigilance, adverse drug reactions (ADRs) and ADR reporting in community pharmacies in Yemen. Methods This cross-sectional survey was conducted among community pharmacists and pharmacy technicians in the capital of Yemen, Sana’a. A total of 289 community pharmacies were randomly selected. The validated and pilot-tested questionnaire consisted of six sections: demographic data, knowledge about pharmacovigilance, experience with ADR reporting, attitudes toward ADR reporting, and the facilitators to improve ADR reporting. Results A total of 428 pharmacy technicians and pharmacists were contacted and 179 went on to complete a questionnaire (response rate: 41.8%). Of the 179 respondents, 21 (11.7%) were pharmacists and 158 (88.3%) were pharmacy technicians, of which, 176 (98.3%) were male and 3 (1.7%) were female. The mean age of the respondents was 25.87±2.63 years. There was a significant difference between the pharmacists and pharmacy technicians in terms of knowledge scores (P<0.05). The mean knowledge scores for pharmacists was 3.33±2.852 compared to 0.15±0.666 for pharmacy technicians. With regard to attitudes toward ADR reporting, all pharmacists (100%) showed a positive attitude, while only 43% of pharmacy technicians showed a positive attitude. Conclusion Pharmacists have a significantly better knowledge than pharmacy technicians with regard to pharmacovigilance. More than half of pharmacy technicians showed a negative attitude toward ADR reporting. Therefore, educational interventions and training is very important for community pharmacists and pharmacy technicians in Yemen to increase their awareness and participation in ADR reporting. PMID:28924350

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

PubMed

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

2016-02-01

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

Consistency in adult reporting of adverse childhood experiences.

PubMed

Colman, I; Kingsbury, M; Garad, Y; Zeng, Y; Naicker, K; Patten, S; Jones, P B; Wild, T C; Thompson, A H

2016-02-01

Many studies have used retrospective reports to assess the long-term consequences of early life stress. However, current individual characteristics and experiences may bias the recall of these reports. In particular, depressed mood may increase the likelihood of recall of negative experiences. The aim of the study was to assess whether specific factors are associated with consistency in the reporting of childhood adverse experiences. The sample comprised 7466 adults from Canada's National Population Health Survey who had reported on seven childhood adverse experiences in 1994/1995 and 2006/2007. Logistic regression was used to explore differences between those who consistently reported adverse experiences and those whose reports were inconsistent. Among those retrospectively reporting on childhood traumatic experiences in 1994/1995 and 2006/2007, 39% were inconsistent in their reports of these experiences. The development of depression, increasing levels of psychological distress, as well as increasing work and chronic stress were associated with an increasing likelihood of reporting a childhood adverse experience in 2006/2007 that had not been previously reported. Increases in mastery were associated with reduced likelihood of new reporting of a childhood adverse experience in 2006/2007. The development of depression and increases in chronic stress and psychological distress were also associated with reduced likelihood of 'forgetting' a previously reported event. Concurrent mental health factors may influence the reporting of traumatic childhood experiences. Studies that use retrospective reporting to estimate associations between childhood adversity and adult outcomes associated with mental health may be biased.

Preventable statin adverse reactions and therapy discontinuation. What can we learn from the spontaneous reporting system?

PubMed

Sessa, Maurizio; Rafaniello, Concetta; Scavone, Cristina; Mascolo, Annamaria; di Mauro, Gabriella; Fucile, Annamaria; Rossi, Francesco; Sportiello, Liberata; Capuano, Annalisa

2018-05-01

Statin treatment is often associated with poor adherence, which may be due to the onset of adverse drug reactions (ADRs). We investigated on potential risk factors related to preventable cases of statin-induced ADRs and to the discontinuation of statin therapy. We performed a study using the database of Italian spontaneous reporting. The target population for the preventability assessment was all patients with suspected statin-induced ADRs deriving from Campania Region (a territory of Southern Italy) between 2012 and 2017. Additionally, a local sentinel surveillance site involving General Practitioners was selected to countercheck in routine clinical practice the role of ADRs for statin discontinuation. In total, 34 of 655 (5.19%) regional cases were preventable and among detected risk factors 90.0% was related to healthcare professionals' practices and 10.0% to patient behaviour. In 81.4% (533/655) of cases, statin therapy was discontinued due to ADRs, mainly classified as not serious and associated with a positive prognosis. These results were also confirmed in the active sentinel site. Our findings suggest an inappropriate use of statins among the identified preventable cases and a potential inappropriate statin discontinuation due to ADRs. These factors may be useful for targeting interventions to improve statin adherence.

Report of Allergic Reaction After Application of Botulinum Toxin.

PubMed

Careta, Mariana Figueiroa; Delgado, Livia; Patriota, Régia

2015-07-01

Botulinum toxin is a widely used treatment with satisfactory results, and it is relatively safe in the doses used for cosmetic procedures. The authors report a case of allergic reaction to Chinese botulinum toxin serotype A (CBTX-A). Although this is a rare adverse event, it is nonetheless clinically relevant to healthcare professionals. A 44-year-old woman presented to the authors' hospital complaining of dynamic wrinkles. CBTX-A was used to treat her. Minutes after application, she developed urticarial plaques proximal to the injection site. The patient had an allergic reaction, as documented by a positive skin test, which was controlled by the administration of antihistamines and systemic corticosteroids. This report is intended to guide healthcare professionals faced with this type of adverse event regarding how to proceed without hindering the delivery and effectiveness of the treatment. When performed by a qualified health professional, this treatment brings excellent results in the vast majority of cases. 5 Risk. © 2015 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

The Quality of Clinical Information in Adverse Drug Reaction Reports by Patients and Healthcare Professionals: A Retrospective Comparative Analysis.

PubMed

Rolfes, Leàn; van Hunsel, Florence; van der Linden, Laura; Taxis, Katja; van Puijenbroek, Eugène

2017-07-01

Clinical information is needed to assess the causal relationship between a drug and an adverse drug reaction (ADR) in a reliable way. Little is known about the level of relevant clinical information about the ADRs reported by patients. The aim was to determine to what extent patients report relevant clinical information about an ADR compared with their healthcare professional. A retrospective analysis of all ADR reports on the same case, i.e., cases with a report from both the patient and the patient's healthcare professional, selected from the database of the Dutch Pharmacovigilance Center Lareb, was conducted. The extent to which relevant clinical information was reported was assessed by trained pharmacovigilance assessors, using a structured tool. The following four domains were assessed: ADR, chronology, suspected drug, and patient characteristics. For each domain, the proportion of reported information in relation to information deemed relevant was calculated. An average score of all relevant domains was determined and categorized as poorly (≤45%), moderately (from 46 to 74%) or well (≥75%) reported. Data were analyzed using a paired sample t test and Wilcoxon signed rank test. A total of 197 cases were included. In 107 cases (54.3%), patients and healthcare professionals reported a similar level of clinical information. Statistical analysis demonstrated no overall differences between the groups (p = 0.126). In a unique study of cases of ADRs reported by patients and healthcare professionals, we found that patients report clinical information at a similar level as their healthcare professional. For an optimal pharmacovigilance, both healthcare professionals and patient should be encouraged to report.

An evaluation of knowledge, attitude, and practice of adverse drug reaction reporting among prescribers at a tertiary care hospital.

PubMed

Desai, Chetna K; Iyer, Geetha; Panchal, Jigar; Shah, Samidh; Dikshit, R K

2011-10-01

Spontaneous reporting is an important tool in pharmacovigilance. However, its success depends on cooperative and motivated prescribers. Under-reporting of adverse drug reactions (ADRs) by prescribers is a common problem. The present study was undertaken to evaluate the knowledge, attitude, and practices (KAP) regarding ADR reporting among prescribers at the Civil Hospital, Ahmedabad, to get an insight into the causes of under-reporting of ADRs. A pretested KAP questionnaire comprising of 15 questions (knowledge 6, attitude 5, and practice 4) was administered to 436 prescribers. The questionnaires were assessed for their completeness (maximum score 20) and the type of responses regarding ADR reporting. Microsoft Excel worksheet (Microsoft Office 2007) and Chi-Square test were used for statistical analysis. A total of 260 (61%) prescribers completed the questionnaire (mean score of completion 18.04). The response rate of resident doctors (70.7%) was better than consultants (34.5%) (P < 0.001). ADR reporting was considered important by 97.3% of the respondents; primarily for improving patient safety (28.8%) and identifying new ADRs (24.6%). A majority of the respondents opined that they would like to report serious ADRs (56%). However, only 15% of the prescribers had reported ADRs previously. The reasons cited for this were lack of information on where (70%) and how (68%) to report and the lack of access to reporting forms (49.2%). Preferred methods for reporting were e-mail (56%) and personal communication (42%). The prescribers are aware of the ADRs and the importance of their reporting. However, under reporting and lack of knowledge about the reporting system are clearly evident. Creating awareness about ADR reporting and devising means to make it easy and convenient may aid in improving spontaneous reporting.

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

PubMed

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

2018-06-13

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

Immediate hypersensitivity reactions following monovalent 2009 pandemic influenza A (H1N1) vaccines: reports to VAERS.

PubMed

Halsey, Neal A; Griffioen, Mari; Dreskin, Stephen C; Dekker, Cornelia L; Wood, Robert; Sharma, Devindra; Jones, James F; LaRussa, Philip S; Garner, Jenny; Berger, Melvin; Proveaux, Tina; Vellozzi, Claudia; Broder, Karen; Setse, Rosanna; Pahud, Barbara; Hrncir, David; Choi, Howard; Sparks, Robert; Williams, Sarah Elizabeth; Engler, Renata J; Gidudu, Jane; Baxter, Roger; Klein, Nicola; Edwards, Kathryn; Cano, Maria; Kelso, John M

2013-12-09

Hypersensitivity disorders following vaccinations are a cause for concern. To determine the type and rate by age, gender, and vaccine received for reported hypersensitivity reactions following monovalent 2009 pandemic influenza A (H1N1) vaccines. A systematic review of reports to the Vaccine Adverse Event Reporting System (VAERS) following monovalent 2009 pandemic influenza A (H1N1) vaccines. US Civilian reports following vaccine received from October 1, 2009 through May 31, 2010. Age, gender, vaccines received, diagnoses, clinical signs, and treatment were reviewed by nurses and physicians with expertise in vaccine adverse events. A panel of experts, including seven allergists reviewed complex illnesses and those with conflicting evidence for classification of the event. Of 1984 reports, 1286 were consistent with immediate hypersensitivity disorders and 698 were attributed to anxiety reactions, syncope, or other illnesses. The female-to-male ratio was ≥4:1 for persons 20-to-59 years of age, but approximately equal for children under 10. One hundred eleven reports met Brighton Collaboration criteria for anaphylaxis; only one-half received epinephrine for initial therapy. The overall rate of reported hypersensitivity reactions was 10.7 per million vaccine doses distributed, with a 2-fold higher rate for live vaccine. Underreporting, especially of mild events, would result in an underestimate of the true rate of immediate hypersensitivity reactions. Selective reporting of events in adult females could have resulted in higher rates than reported for males. Adult females may be at higher risk of hypersensitivity reactions after influenza vaccination than men. Although the risk of hypersensitivity reactions following 2009 pandemic influenza A (H1N1) vaccines was low, all clinics administering vaccines should be familiar with treatment guidelines for these adverse events, including the use of intramuscular epinephrine early in the course of serious hypersensitivity

Immune responses in dogs with cutaneous adverse food reactions.

PubMed

Veenhof, E Z; Knol, E F; Willemse, T; Rutten, V P M G

2012-06-01

Adverse food reactions (AFR) in dogs are reactions due to apparently harmless food antigens, with an unknown aetiology, i.e. immunopathogenesis. Despite the entry of food allergens via the intestinal tract, in the majority of dogs with AFR, clinical symptoms are only associated with the skin (CAFR). In the present review, factors are presented of relevance in triggering the differentiation of naive T cells into effector T cell types and the role of these T cell types in allergy. More specifically, the allergic immune responses in intestine and skin are discussed in this article as well as the potential pathways, e.g. homing of antigen presenting cells or allergen-induced T cells to the skin, of induction of cutaneous symptoms.

Promoting spontaneous adverse drug reaction reporting in hospitals using a hyperlink to the online reporting form: an ecological study in Portugal.

PubMed

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

2012-05-01

Spontaneous adverse drug reaction (ADR) reporting has been described as an efficient method to detect drug safety signals. However, under-reporting is a major issue undermining the effectiveness of spontaneous reports. Among hospitalized patients, ADRs are a particularly serious problem because these patients are often treated with more than one drug, and these drugs are often new and aggressive. To promote spontaneous ADR reporting by healthcare professionals working in hospitals in the northern regions of Portugal, we propose the inclusion of a hyperlink to an online ADR reporting form on hospitals' electronic patient records (EPRs). The main aim of this study was to evaluate the impact of these hyperlinks on the number of spontaneous ADR reports to the Northern Pharmacovigilance Centre (UFN - Unidade de Farmacovigilância do Norte). We also assess the number of daily UFN website visits before and after the inclusion of the hyperlinks. An ecological study was performed in northern Portuguese hospitals from 2006 to 2010. The hyperlinks were included in either EPRs or on computer desktops. The median of spontaneous ADR reports (total and online) per month and the respective ranges were presented before and after the intervention in all hospitals in this study. The comparisons were performed using the Mann-Whitney U-test. Sixteen hospital centres were involved in the study (27 hospitals). Eleven centres (18 hospitals) included the hyperlinks. Considering the hospitals with hyperlink access to the EPRs, the median ADR reports per month significantly increased, from two (range 0-12) to five reports (range 1-17). The median of ADR reports per month using the online form also increased significantly, from one (range 0-5) before the intervention to four (range 1-17) after it. Moreover, serious ADRs increased 3-fold, and non-previously described ADRs increased 4.5-fold. None of these significant increases were observed in the hospitals where the hyperlink was not

A Pathway to Psychological Difficulty: Perceived Chronic Social Adversity and Its Symptomatic Reactions.

PubMed

Ding, Cody; Zhang, Jingqiu; Yang, Dong

2018-01-01

In this paper, we attempt to predict and explain psychological maladjustment or difficulty. Specifically, we discuss the concept of perceived chronic social adversity, and we expect that such perceived chronic social adversity may potentially lead to chronic stress responses. Accordingly, we propose the symptomatic reactions of perceived chronic social adversity. We put forward a set of hypotheses regarding the relationships between perceived chronic social adversity and those chronic stress responses, and we further hypothesize a mediating role of individualized negative essentialism brought by perceived chronical social adversity. Resilience and individual differences in the ability to cope with perceived adversity are discussed. Future research and prevention need to pay more attention to effects of subjective personal experiences on psychological difficulty, focusing on the importance of exploring daily social experiences in improving cognitive construction processes and developing appropriate preventions.

A Pathway to Psychological Difficulty: Perceived Chronic Social Adversity and Its Symptomatic Reactions

PubMed Central

Ding, Cody; Zhang, Jingqiu; Yang, Dong

2018-01-01

In this paper, we attempt to predict and explain psychological maladjustment or difficulty. Specifically, we discuss the concept of perceived chronic social adversity, and we expect that such perceived chronic social adversity may potentially lead to chronic stress responses. Accordingly, we propose the symptomatic reactions of perceived chronic social adversity. We put forward a set of hypotheses regarding the relationships between perceived chronic social adversity and those chronic stress responses, and we further hypothesize a mediating role of individualized negative essentialism brought by perceived chronical social adversity. Resilience and individual differences in the ability to cope with perceived adversity are discussed. Future research and prevention need to pay more attention to effects of subjective personal experiences on psychological difficulty, focusing on the importance of exploring daily social experiences in improving cognitive construction processes and developing appropriate preventions. PMID:29755394

The lack of knowledge about the voluntary reporting system of adverse drug reactions as a major cause of underreporting: direct survey among health professionals.

PubMed

Pérez García, Mariley; Figueras, Albert

2011-12-01

Underreporting suspected adverse drug reactions (ADRs) is one of the main problems that face the pharmacovigilance (PhV) systems based on yellow card schemes. To measure the knowledge level on the suspected ADR voluntary reporting system among physicians and pharmacists in Venezuela and to study its relationship with different variables. A population-based, anonymous, and self-administered questionnaire was addressed to health professionals along the national territory of Venezuela. An algorithm was developed to classify the knowledge level on the voluntary reporting system. Taken as a whole, the level of knowledge on the voluntary reporting system was "poor." Among the 515 participant physicians, 62.3% (95%CI = 58.0-66.5%) had a "poor" level of knowledge; PhV was associated with "control" of medicines use, and only 24.7% had ever reported a suspected ADR. "Medical specialty" was the only variable that showed a relationship with the knowledge level (p = 0.0041). Among the 78 participant pharmacists, 66.7% had a "poor" knowledge level (95%CI = 55.1-76.9%). The knowledge level on the voluntary reporting system among physicians and pharmacists in Venezuela is poor. These results strengthen the hypothesis that being unaware of the adverse effects of medicines and not knowing the existence of a PhV system is a major cause of underreporting. A careful study of the actual knowledge of PhV could be the basis to set up interventions specifically designed to overcome misleading concepts and to improve the reporting rate at a national level. Copyright © 2011 John Wiley & Sons, Ltd.

Language does not come "in boxes": Assessing discrepancies between adverse drug reactions spontaneous reporting and MedDRA® codes in European Portuguese.

PubMed

Inácio, Pedro; Airaksinen, Marja; Cavaco, Afonso

2015-01-01

The description of adverse drug reactions (ADRs) by health care professionals (HCPs) can be highly variable. This variation can affect the coding of a reaction with the Medical Dictionary for Regulatory Activities (MedDRA(®)), the gold standard for pharmacovigilance database entries. Ultimately, the strength of a safety signal can be compromised. The objective of this study was to assess: 1) participation of different HCPs in ADR reporting, and 2) variation of language used by HCPs when describing ADRs, and to compare it with the corresponding MedDRA(®) codes. A retrospective content analysis was performed, using the database of spontaneous reports submitted by HCPs in the region of the Southern Pharmacovigilance Unit, Portugal. Data retrieved consisted of the idiomatic description of all ADRs occurring in 2004 (first year of the Unit activity, n = 53) and in 2012 (n = 350). The agreement between the language used by HCPs and the MedDRA(®) dictionary codes was quantitatively assessed. From a total of 403 spontaneous reports received in the two years, 896 words describing ADRs were collected. HCPs presented different levels of pharmacovigilance participation and ADR idiomatic descriptions, with pharmacists providing the greatest overall contribution. The agreement between the language used in spontaneous reports and the corresponding MedDRA(®) terms varied by HCP background, with nurses presenting the poorer results than medical doctors and pharmacists when considering the dictionary as the gold standard in ADRs' language. Lexical accuracy and semantic variations exist between different HCP groups. These differences may interfere with the strength of a generated safety signal. Clinical and MedDRA(®) terminology training should be targeted to increase not only the frequency, but also the quality of spontaneous reports, in accordance with HCPs' experience and background. Copyright © 2015 Elsevier Inc. All rights reserved.

Vaccine adverse events reported in post-marketing study of the Kitasato Institute from 1994 to 2004.

PubMed

Nakayama, Tetsuo; Onoda, Kazumasa

2007-01-05

General physicians, pediatricians and parents realize that serious adverse events occur with an extremely rare incidence, but have no information on the incidences of vaccine-associated adverse events. A proper understanding of vaccine adverse events would be helpful in promoting an immunization strategy. Causal association can rarely be determined in adverse events through laboratory examinations. We examined the cases reported in the post-marketing surveillance of the Kitasato Institute, categorizing them into two groups: allergic reactions and severe systemic illnesses. Anaphylactic patients with gelatin allergy after immunization with live measles, rubella and mumps monovalent vaccines have been reported since 1993, but the number of reported cases with anaphylaxis dramatically decreased after 1999 when gelatin was removed from all brands of DPT. The incidence of anaphylactic reaction was estimated to be 0.63 per million for Japanese encephalitis virus (JEV) vaccine, 0.95 for DPT and 0.68 for Influenza vaccine, but the causative component has not yet been specified. Among 67.2 million immunization practices, 6 cases with encephalitis or encephalopathy, 7 with acute disseminated encephalomyelitis (ADEM), 10 with Guillain-Barré syndrome and 12 with idiopathic thrombocytopenic purpura (ITP) were reported. The wild-type measles virus genome was detected in a patient with encephalitis and in two of four bone marrow aspirates obtained from ITP after measles vaccination. Enterovirus infection was identified in two patients after mumps vaccination (one each with encephalitis and ADEM), one patient with encephalitis after immunization with JEV vaccine, and one with aseptic meningitis after immunization with influenza vaccine. The total estimated incidence of serious neurological illness after vaccination was 0.1-0.2 per million immunization practices. We found that enterovirus or wild-type measles virus infection was coincidentally associated with vaccination in

[Recipients adverse reactions in the Ibn Sina Hospital of Rabat: State 1999-2013].

PubMed

Ouadghiri, S; Brick, C; Benseffaj, N; Atouf, O; Essakalli, M

2017-02-01

The declaration of the recipients adverse reactions (RAR) is one of the field haemovigilance activities. It provides an evaluation of transfusion side effects and thus prevents their appearance. The aim of this study is to analyze, over 14 years, the RAR supports reported in Rabat Ibn Sina hospital. All of the RAR supports sending to the blood transfusion service were analyzed. The data collected from these supports are: clinical characteristics of the patient, type of incident observed and type of labile blood products (LBP) transfused. A total of 353 RAR were declared with a mean cumulative incidence of 1.7/1000 LBP delivered. Febrile non-hemolytic transfusion reactions represent 72.8% of the RAR declared. The RAR were classified as grade 1 in 87.1% of cases and were secondary to a transfusion of the red cell concentrates in 81.9%. ABO incompatibility was found in four cases (0.02/1000 LBP delivered). The number of RAR reported by Rabat Ibn Sina hospital remains underestimated. Management and traceability RAR and rigorous investigation, under the responsibility of the corresponding haemovigilance contribute to the improvement of transfusion safety. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Toward multimodal signal detection of adverse drug reactions.

PubMed

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

2017-12-01

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

[Pharmacotherapy of hyperthyreosis--adverse drug reactions].

PubMed

Perger, Ludwig; Bürgi, Ulrich; Fattinger, Karin

2011-06-01

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

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

Key pharmacovigilance stakeholders' experiences of direct patient reporting of adverse drug reactions and their prospects of future development in the European Union.

PubMed

Inácio, P; Cavaco, A; Allan, E; Airaksinen, M

2018-02-01

In the European Union (EU), legislation allows patients to directly report adverse drug reactions (ADRs) to competent authorities. Five years after its implementation, patient reporting is not equal in all countries. This study aimed to explore key stakeholders' perceptions of patient reporting in four EU countries. Qualitative study design. Twelve representatives from national pharmacovigilance centres and/or authorities as well as national pharmaceutical industry bodies in four EU countries participated in the study. Supranational organizations were also included. Data collection was via face-semi-structured interviews. Inductive content analysis was performed thereafter, applying principles of risk management as a theoretical framework. Four themes (attitudes and beliefs, system maturation factors, regulatory improvements, and cultural shifts) emerged, conceptually interconnected. Participants from countries introducing patient reporting recently expressed a negative attitude. Participants highlighted the need for additional resources, both human and financial, to address patient reporting and associated advantages. The findings identified perceived barriers and facilitators of patient reporting. The involvement of patients, use of information, and dissemination of patient reporting are far from optimal. A better integration of the work by EU regulatory authorities is recommended. Copyright © 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

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.

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

PubMed

Stang, P E; Fox, J L

1992-02-01

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

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

PubMed

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

2017-09-01

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

Severe Cutaneous Adverse Reactions: The Pharmacogenomics from Research to Clinical Implementation

PubMed Central

Su, Shih-Chi; Hung, Shuen-Iu; Fan, Wen-Lang; Dao, Ro-Lan; Chung, Wen-Hung

2016-01-01

Severe cutaneous adverse reactions (SCARs), previously thought to be idiosyncratic or unpredictable, are a deadly form of adverse drug reactions with skin manifestations. Current pharmacogenomic studies of SCARs have made important strides, as the prevention of SCARs, to some extent, appears attainable with the identification of genetic variants for genes encoding drug-metabolizing enzymes and human leukocyte antigens (HLAs). Despite the improvement of incidence, a treatment guideline for this devastating condition is still unavailable, highlighting the inadequacy of contemporary accepted therapeutic interventions. As such, prompt withdrawal of causative drugs is believed to be a priority of patient management. In this review, we discuss recent cutting-edge findings concerning the discovery of biomarkers for SCARs and their clinical utilities in the better prediction and early diagnosis of this disease. The knowledge compiled herein provides clues for future investigations on deciphering additional genetic markers for SCARs and the design of clinical trials for the prospective identification of subjects at genetic risk for this condition, ultimately personalizing the medicine. PMID:27854302

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

PubMed

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

2018-01-01

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

Geographical variation in reporting Interstitial Lung Disease as an adverse drug reaction: findings from an European Medicines Agency analysis of reports in EudraVigilance.

PubMed

Pinheiro, Luis; Blake, Kevin; Januskiene, Justina; Yue, Qun-Ying; Arlett, Peter

2016-06-01

Clinically, interstitial lung disease (ILD) is a heterogeneous group of over 150 respiratory disorders. In the context of its signal evaluation work, the European Medicines Agency's (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) has seen geographic clustering of case reports of ILD from Japan. To explore this further, EudraVigilance (EV), the EMA's database of adverse drug reactions (ADRs), was analysed. The results have been used to inform on implications for pharmacovigilance including signal detection and evaluation activities. EV was queried for reports of respiratory ADRs coded using MedDRA for the period 1994-2014 for all medicinal products. Descriptive statistics and non-parametric (chi-square) independence tests were produced to compare reporting of ILD from Japan versus the rest of the world. As of 31 December 2014, there were 26 551 case reports of ILD in EV of which 17 526 (66%) originated in Japan. The reporting rate of ILD for Japan has been consistently higher over the period. The odds that a case report from Japan in EV refers to ILD is OR = 20.7, 95% CI 20.2, 21.3 (p < 0.001), compared to OR = 0.60, 95% CI 0.54, 0.67 (p < 0.001) for pulmonary fibrosis. A geographic imbalance between Japan and the rest of the world in reporting respiratory ADRs as ILD is confirmed. Consequently, the PRAC has developed approaches to address this in relation to signals of ILD it assesses to allow for more targeted risk minimisation including updates to the product information in the EU setting. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

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

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

PubMed

Yi Zheng; Chaowang Lan; Hui Peng; Jinyan Li

2016-08-01

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

Characterization of hypersensitivity reactions reported among Andrographis paniculata users in Thailand using Health Product Vigilance Center (HPVC) database.

PubMed

Suwankesawong, Wimon; Saokaew, Surasak; Permsuwan, Unchalee; Chaiyakunapruk, Nathorn

2014-12-24

Andrographis paniculata (andrographis) is one of the herbal products that are widely used for various indications. Hypersensitivity reactions have been reported among subjects receiving Andrographis paniculata in Thailand. Understanding of characteristics of patients, adverse events, and clinical outcomes is essential for ensuring population safety.This study aimed to describe the characteristics of hypersensitivity reactions reported in patients receiving andrographis containing products in Thailand using national pharmacovigilance database. Thai Vigibase data from February 2001 to December 2012 involving andrographis products were used. This database includes the reports submitted through the spontaneous reporting system and intensive monitoring programmes. The database contained patient characteristic, adverse events associated with andrographis products, and details on seriousness, causality, and clinical outcomes. Case reports were included for final analysis if they met the inclusion criteria; 1) reports with andrographis being the only suspected cause, 2) reports with terms consistent with the constellation of hypersensitivity reactions, and 3) reports with terms considered critical terms according to WHO criteria. Descriptive statistics were used. A total of 248 case reports of andrographis-associated adverse events were identified. Only 106 case reports specified andrographis herbal product as the only suspected drug and reported at least one term consistent with constellation of hypersensitivity reactions. Most case reports (89%) came from spontaneous reporting system with no previously documented history of drug allergy (88%). Of these, 18 case reports were classified as serious with 16 cases requiring hospitalization. For final assessment, the case reports with terms consistent with constellation of hypersensitivity reactions and critical terms were included. Thirteen case reports met such criteria including anaphylactic shock (n = 5), anaphylactic

Pharmacogenetics of adverse reactions to antiepileptic drugs.

PubMed

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

2018-04-01

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

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

PubMed

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

2007-06-01

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

Hypersensitivity Reaction Associated with Abacavir Therapy in an Indian HIV Patient - A Case Report.

PubMed

Janardhanan, Manju; Amberkar V, Mohan Babu; Vidyasagar, Sudha; Kumari K, Meena; Holla, Sadhana N

2014-09-01

The most important and unique adverse effect of abacavir (ABC) is fatal hypersensitivity reaction (HSR). The objective of this report is to describe a case of ABC induced HSR that occurred in an Indian HIV patient during treatment. Although this adverse effect is not uncommon, it is perhaps underreported or has never been reported so far in an Indian case scenario. A 44-year-old known case of HIV-1 was admitted in view of his worsening condition and very low CD4 cell counts 3 cells/μL. He was on anti-retroviral therapy since three years but not regular. On the basis of treatment failure, non-compliance and progressive low CD4 counts, the anti HIV regime was switched over to abacavir 600 mg+ atazanavir/ ritonavir 300mg/100mg Two weeks after ABC therapy he presented with maculopapular rash, headache and signs of hepatic damage (serum AST, ALP and ALT increased to 3-4 fold) suggestive of hypersensitivity reaction. As we know discontinuation of the drug is the ultimate litmus test to confirm diagnosis of drug induced adverse reaction. We did confirm ABC induced HSR by de-challenge wherein, rash disappeared within 2-3 days and LFT came back to normal within 5 days. However, no rechallenge was done. HSR was more in favour of ABC because atazanavir failed to produce any similar reaction after re-challenge.

Recent advances in the understanding of severe cutaneous adverse reactions.

PubMed

Adler, N R; Aung, A K; Ergen, E N; Trubiano, J; Goh, M S Y; Phillips, E J

2017-11-01

Severe cutaneous adverse reactions (SCARs) encompass a heterogeneous group of delayed hypersensitivity reactions, which are most frequently caused by drugs. Our understanding of several aspects of SCAR syndromes has evolved considerably over the last decade. This review explores evolving knowledge of the immunopathogenic mechanisms, pharmacogenomic associations, in vivo and ex vivo diagnostics for causality assessment, and medication cross-reactivity data related to SCAR syndromes. Given the rarity and severity of these diseases, multidisciplinary collaboration through large international, national and/or multicentre networks to collect prospective data on patients with SCAR syndromes should be prioritized. This will further enhance a systematized framework for translating epidemiological, clinical and immunopathogenetic advances into preventive efforts and improved outcomes for patients. © 2017 British Association of Dermatologists.

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

[Management of adverse drug effects].

PubMed

Schlienger, R G

2000-09-01

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

Dietary Supplement Adverse Event Report Data From the FDA Center for Food Safety and Applied Nutrition Adverse Event Reporting System (CAERS), 2004-2013.

PubMed

Timbo, Babgaleh B; Chirtel, Stuart J; Ihrie, John; Oladipo, Taiye; Velez-Suarez, Loy; Brewer, Vickery; Mozersky, Robert

2018-05-01

The Food and Drug Administration (FDA)'s Center for Food Safety and Applied Nutrition (CFSAN) oversees the safety of the nation's foods, dietary supplements, and cosmetic products. To present a descriptive analysis of the 2004-2013 dietary supplement adverse event report (AER) data from CAERS and evaluate the 2006 Dietary Supplements and Nonprescription Drug Consumer Protection Act as pertaining to dietary supplements adverse events reporting. We queried CAERS for data from the 2004-2013 AERs specifying at least 1 suspected dietary supplement product. We extracted the product name(s), the symptom(s) reported, age, sex, and serious adverse event outcomes. We examined time trends for mandatory and voluntary reporting and performed analysis using SAS v9.4 and R v3.3.0 software. Of the total AERs (n = 15 430) received from January 1, 2004, through December 31, 2013, indicating at least 1 suspected dietary supplement product, 66.9% were mandatory, 32.2% were voluntary, and 0.9% were both mandatory and voluntary. Reported serious outcomes included death, life-threatening conditions, hospitalizations, congenital anomalies/birth defects and events requiring interventions to prevent permanent impairments (5.1%). The dietary supplement adverse event reporting rate in the United States was estimated at ~2% based on CAERS data. This study characterizes CAERS dietary supplement adverse event data for the 2004-2013 period and estimates a reporting rate of 2% for dietary supplement adverse events based on CAERS data. The findings show that the 2006 Dietary Supplements and Nonprescription Drug Consumer Protection Act had a substantial impact on the reporting of adverse events.

21 CFR 1271.350 - Reporting.

Code of Federal Regulations, 2010 CFR

2010-04-01

... § 1271.350 Reporting. (a) Adverse reaction reports. (1) You must investigate any adverse reaction... report to FDA an adverse reaction involving a communicable disease if it: (i) Is fatal; (ii) Is life... reactions that are the subject of these 15-day reports and must submit followup reports within 15 calendar...

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.

[Reactions to food].

PubMed

Halvorsen, R; Eggesb M; Botten, G

1995-12-10

Adverse reactions to food occur in about 1-2% of the population, but are reported more frequently by patients. Most reactions to food are not caused by allergy. IgE-mediated food reactions are well known and of major clinical significance owing to their potentially dangerous, even life-threatening character. Adverse reactions to food can also be caused by immunological mechanisms other than IgE-mediated reactions such as, enzyme deficiencies, active pharmacological substances in food and psychological mechanisms. Double-blind provocation is the only way to diagnose a positive reaction to a food item with some certainty. Regretably no objective measures for food reactions exist.

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

PubMed

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

2012-08-01

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

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

PubMed

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

1996-12-01

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

Adverse reactions to foods.

PubMed

Ring, J; Brockow, K; Behrendt, H

2001-05-25

Allergic reactions to foods represent a prominent, actual and increasing problem in clinical medicine. Symptoms of food allergy comprise skin reactions (urticaria, angioedema, eczema) respiratory (bronchoconstriction, rhinitis), gastrointestinal (cramping, diarrhea) and cardiovascular symptoms with the maximal manifestation of anaphylactic shock. They can be elicited by minute amounts of allergens. The diagnosis of food allergy is done by history, skin test, in vitro allergy diagnosis and--if necessary--oral provocation tests, if possible placebo-controlled. Avoidance of respective allergens for the allergic patient, however, is often complicated or impossible due to deficits in declaration regulations in many countries. Increasing numbers of cases including fatalities, due to inadvertent intake of food allergens are reported. It is therefore necessary to improve declaration laws and develop methods for allergen detection in foods. Allergens can be detected by serological methods (enzyme immunoassays, in vitro basophil histamine release or in vivo skin test procedures in sensitized individuals). The problem of diagnosis of food allergy is further complicated by cross-reactivity between allergens in foods and aeroallergens (pollen, animal epithelia, latex etc.). Elicitors of pseudo-allergic reactions with similar clinical symptomatology comprise low-molecular-mass chemicals (preservatives, colorings, flavor substances etc.). For some of them (e.g. sulfites) detection assays are available. In some patients classic allergic contact eczema can be elicited systemically after oral intake of low-molecular-mass contact allergens such as nickel sulfate or flavorings such as vanillin in foods. The role of xenobiotic components in foods (e.g. pesticides) is not known at the moment. In order to improve the situation of the food allergic patient, research programs to elucidate the pathophysiology and improve allergen detection strategies have to be implemented together with

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

PubMed

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

2013-09-01

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

Evaluation of patient reporting of adverse drug reactions to the UK 'Yellow Card Scheme': literature review, descriptive and qualitative analyses, and questionnaire surveys.

PubMed

Avery, A J; Anderson, C; Bond, C M; Fortnum, H; Gifford, A; Hannaford, P C; Hazell, L; Krska, J; Lee, A J; McLernon, D J; Murphy, E; Shakir, S; Watson, M C

2011-05-01

The monitoring of adverse drug reactions (ADRs) through pharmacovigilance is vital to patient safety. Spontaneous reporting of ADRs is one method of pharmacovigilance, and in the UK this is undertaken through the Yellow Card Scheme (YCS). Yellow Card reports are submitted to the Medicines and Healthcare products Regulatory Agency (MHRA) by post, telephone or via the internet. The MHRA electronically records and reviews information submitted so that important safety issues can be detected. While previous studies have shown differences between patient and health-care professional (HCP) reports for the types of drugs and reactions reported, relatively little is known about the pharmacovigilance impact of patient reports. There have also been few studies on the views and experiences of patients/consumers on the reporting of suspected ADRs. To evaluate the pharmacovigilance impact of patient reporting of ADRs by analysing reports of suspected ADRs from the UK YCS and comparing reports from patients and HCPs. To elicit the views and experiences of patients and the public about patient reporting of ADRs. (1) Literature review and survey of international experiences of consumer reporting of ADRs; (2) descriptive analysis of Yellow Card reports; (3) signal generation analysis of Yellow Card reports; (4) qualitative analysis of Yellow Card reports; (5) questionnaire survey of patients reporting on Yellow Cards; (6) qualitative analysis of telephone interviews with patient reporters to the scheme; (7) qualitative analysis of focus groups and usability testing of the patient YCS; and (8) national omnibus telephone survey of public awareness of the YCS. Patients (n = 5180) and HCPs (n = 20,949) submitting Yellow Card reports from October 2005 to September 2007. Respondents to questionnaire survey (n = 1362). Participants at focus groups and usability testing sessions (n = 40). National omnibus telephone survey (n = 2028). The literature review included studies in English from

Knowledge of Adverse Drug Reaction Reporting and the Pharmacovigilance of Biological Medicines: A Survey of Healthcare Professionals in Ireland.

PubMed

O'Callaghan, J; Griffin, B T; Morris, J M; Bermingham, Margaret

2018-06-01

In Europe, changes to pharmacovigilance legislation, which include additional monitoring of medicines, aim to optimise adverse drug reaction (ADR) reporting systems. The legislation also makes provisions related to the traceability of biological medicines. The objective of this study was to assess (i) knowledge and general experience of ADR reporting, (ii) knowledge, behaviours, and attitudes related to the pharmacovigilance of biologicals, and (iii) awareness of additional monitoring among healthcare professionals (HCPs) in Ireland. Hospital doctors (n = 88), general practitioners (GPs) (n = 197), nurses (n = 104) and pharmacists (n = 309) completed an online questionnaire. There were differences in mean knowledge scores relating to ADR reporting and the pharmacovigilance of biologicals among the HCP groups. The majority of HCPs who use biological medicines in their practice generally record biologicals by brand name but practice behaviours relating to batch number recording differed between some professions. HCPs consider batch number recording to be valuable but also regard it as being more difficult than brand name recording. Most respondents were aware of the concept of additional monitoring but awareness rates differed between some groups. Among those who knew about additional monitoring, there was higher awareness of the inverted black triangle symbol among pharmacists (> 86.4%) compared with hospital doctors (35.1%), GPs (35.6%), and nurses (14.9%). Hospital pharmacists had more experience and knowledge of ADR reporting than other practising HCPs. This study highlights the important role hospital pharmacists play in post-marketing surveillance. There is a need to increase pharmacovigilance awareness of biological medicines and improve systems to support their batch traceability.

Adverse reactions and interactions with beta-adrenoceptor blocking drugs.

PubMed

Lewis, R V; McDevitt, D G

1986-01-01

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

An intervention to improve spontaneous adverse drug reaction reporting by hospital physicians: a time series analysis in Spain.

PubMed

Pedrós, Consuelo; Vallano, Antoni; Cereza, Gloria; Mendoza-Aran, Gemma; Agustí, Antònia; Aguilera, Cristina; Danés, Immaculada; Vidal, Xavier; Arnau, Josep M

2009-01-01

Spontaneous reporting of adverse drug reactions (ADRs) in hospitals is scarce and several obstacles to such reporting have been identified previously. To assess the effectiveness of a multifaceted intervention based on healthcare management agreements for improving spontaneous reporting of ADRs by physicians in a hospital setting. In 2003, the spontaneous reporting of ADRs was included as one of the objectives of hospital physicians at the Vall d'Hebron Hospital, Barcelona, Spain, within the context of management agreements between clinical services and hospital managers. A continuous intervention related to these management agreements, including periodic educational meetings and economic incentives, was then initiated. We carried out an ecological time series analysis and assessed the change in the total number of spontaneous reports of ADRs, and the number of serious ADRs, unexpected ADRs, and ADRs associated with new drugs between a period previous to the intervention (from 1998 to 2002) and the period during the intervention (from 2003 to 2005). A time series analysis with ARIMA (Auto-Regressive Integrated Moving Average) models was performed. The median number of reported ADRs per year increased from 40 (range 23-55) in the first period to 224 (range 98-248) in the second period. In the first period, the monthly number of reported ADRs was stable (3.47 per month; 95% CI 1.90, 5.03), but in the second period the number increased progressively (increase of 0.74 per month; 95% CI 0.62, 0.86). In the second period, the proportion of reported serious ADRs increased nearly 2-fold (63.1% vs 32.5% in the first period). The absolute number of previously unknown or poorly known ADRs increased 4-fold in the second period (54 vs 13 in the first period). There was also an increase in the absolute number of suspected pharmacological exposures to new drugs (97 vs 28) and in the number of different new drugs suspected of causing ADRs (50 vs 19). A continuous intervention

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

PubMed

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

2008-10-27

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

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

PubMed Central

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

2008-01-01

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

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

PubMed

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

2017-01-01

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

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

PubMed

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

2012-01-01

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

Apheresis platelets are more frequently associated with adverse reactions than pooled platelets both in recipients and in donors: a study from French hemovigilance data.

PubMed

Daurat, Aurélien; Roger, Claire; Gris, JeanChristophe; Daurat, Gérald; Feissel, Michel; Le Manach, Yannick; Lefrant, JeanYves; Muller, Laurent

2016-06-01

Controversy exists regarding the safety of the different types of platelet (PLT) concentrates. This study was aimed at comparing the rate of adverse reactions associated with apheresis PLT concentrates (APCs) and pooled PLT concentrates (PPCs) both in donors and in recipients. From the French national hemovigilance system, types and numbers of recipient adverse reactions were compared over a period from 2009 to 2011. Donor adverse reactions were available for 2010 and 2011. This study involved 23 of 26 French regions. Main outcomes were the rates of adverse reaction in recipients and serious adverse reaction in donors. There were 790,854 PLT transfusions during the study period (477,747 [60%] with APCs, 313,107 [40%] with PPCs). APCs were associated with more adverse reactions (6244 vs. 2469 per 1,000,000, p < 0.001) and more severe and life-threatening reactions (respectively, 241 vs. 131 per 1,000,000, p < 0.001; and 182 vs. 121 per 1,000,000, p = 0.04). Mortality rates due to an adverse transfusion reaction were similar (15 vs. 6 per 1,000,000, p = 0.5). In donors, the number of whole blood (WB) donations was 4,722,685 whereas 266,095 apheresis procedures were performed. Serious adverse reactions were more frequent for apheresis procedures than for WB donations (5445 vs. 803 per 1,000,000, p < 0.001). Our findings suggest that apheresis PLTs may be more hazardous than pooled PLTs both in recipients and in donors. This study calls for randomized trials to confirm or refute these results. © 2016 AABB.

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

PubMed

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

2008-05-01

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

Adverse reactions associated with first-line regimens in patient initiating antiretroviral therapy.

PubMed

Mendes, Jullye Campos; Bonolo, Palmira de Fátima; Ceccato, Maria das Graças Braga; Costa, Juliana de Oliveira; Reis, Adriano Max Moreira; Dos Santos, Henrique; Silveira, Micheline Rosa

2018-05-08

To evaluate the prevalence of adverse drug reactions (ADR) and associated factors during the use of Highly Active Antiretroviral Therapy (HAART) in patients initiating treatment. This is a cross-sectional analysis of a prospective study conducted in three public referral services specialized in HIV/AIDS care in Belo Horizonte, Brazil. Self-reported ADR and explanatory variables were obtained from face-to-face interview and from Information Systems. Associated factors with ADR were evaluated by logistic regression in SPSS software v.22. We included 399 patients, of which 85.5% reported at least one and 72.7% up to 5 ADRs after HAART initiation. Neurological reactions were the most frequent, with self-reported ADRs being distinct according to HAART regimen used. The global model showed higher chance of ADRs among females (OR = 3.52) and illicit drug users (OR = 2.28). Lower chance of ADRs was found for patients aged > 33 years (OR = 0.37), DTG/TDF/3TC users (OR = 0.41), and higher physical domain of quality of life (OR = 0.78). The model restricted to patients using the single-tablet regimen EFV/TDF/3TC showed lower ADRs among patients with CD4+ T lymphocyte count > 200 cells/mm 3 (OR = 0.23) and higher independence domain of quality of life (OR = 0.74). The model restricted to DTG/TDF/3TC and to other regimens showed lower ADRs with higher physical domain of quality of life (OR = 0.74 and OR = 0.55, respectively). The prevalence of self-reported ADRs to first-line antiretroviral regimens was high and patients using DTG/TDF/3TC had a smaller number of ADRs. In addition to HAART regimen, sociodemographic, clinical, and quality of life characteristics were associated with ADRs.

Immunohistopathological Findings of Severe Cutaneous Adverse Drug Reactions

PubMed Central

2017-01-01

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

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

PubMed

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

2009-07-01

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

Delayed adverse reactions to the parenteral administration of iodinated contrast media.

PubMed

Egbert, Robert E; De Cecco, Carlo N; Schoepf, U Joseph; McQuiston, Andrew D; Meinel, Felix G; Katzberg, Richard W

2014-12-01

This article presents an overview of delayed adverse reactions (DARs) to parenteral iodinated contrast media and discusses the clinical nature, risk factors, mechanisms, and potential economic implications of these DARs. DARs to contrast media are not rare but are often not recognized as being linked to contrast administration and may be falsely ascribed to other drugs. These side effects are problematic because the patient is usually without medical supervision.

Adverse Event Reporting: Harnessing Residents to Improve Patient Safety.

PubMed

Tevis, Sarah E; Schmocker, Ryan K; Wetterneck, Tosha B

2017-10-13

Reporting of adverse and near miss events are essential to identify system level targets to improve patient safety. Resident physicians historically report few events despite their role as front-line patient care providers. We sought to evaluate barriers to adverse event reporting in an effort to improve reporting. Our main outcomes were as follows: resident attitudes about event reporting and the frequency of event reporting before and after interventions to address reporting barriers. We surveyed first year residents regarding barriers to adverse event reporting and used this input to construct a fishbone diagram listing barriers to reporting. Barriers were addressed, and resident event reporting was compared before and after efforts were made to reduce obstacles to reporting. First year residents (97%) recognized the importance of submitting event reports; however, the majority (85%) had not submitted an event report in the first 6 months of residency. Only 7% of residents specified that they had not witnessed an adverse event in 6 months, whereas one third had witnessed 10 or more events. The main barriers were as follows: lack of knowledge about how to submit events (38%) and lack of time to submit reports (35%). After improving resident education around event reporting and simplifying the reporting process, resident event reporting increased 230% (68 to 154 annual reports, P = 0.025). We were able to significantly increase resident event reporting by educating residents about adverse events and near misses and addressing the primary barriers to event reporting. Moving forward, we will continue annual resident education about patient safety, focus on improving feedback to residents who submit reports, and empower senior residents to act as role models to junior residents in patient safety initiatives.

Prevention and Management of Adverse Reactions Induced by Iodinated Contrast Media.

PubMed

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

2016-04-01

Iodinated radiocontrast media (IRCM) is widely used in current clinical practice. Although IRCM is generally safe, serious adverse drug reactions (ADRs) may still occur. IRCM-induced ADRs may be subdivided into chemotoxic and hypersensitivity reactions. Several factors have been shown to be associated with an increased risk of ADRs, including previous contrast media reactions, history of asthma and allergic disease, etc. Contrast media with lower osmolality is generally recommended for at-risk patients to prevent ADRs. Current premedication prophylaxis in at-risk patients may reduce the risk of ADRs. However, there is still a lack of consensus on the prophylactic role of premedication. Contrast-induced nephropathy (CIN) is another component of IRCM-related ADRs. Hydration remains the mainstay of CIN prophylaxis in at-risk patients. Despite several preventive measures, ADRs may still occur. Treatment strategies for potential contrast reactions are also summarised in this article. This article summarises the pathophysiology, epidemiology and risk factors of ADRs with emphasis on prevention and treatment strategies. This will allow readers to understand the rationale behind appropriate patient preparation for diagnostic imaging involving IRCM.

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

PubMed Central

2012-01-01

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

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

PubMed

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

2017-12-01

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

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

PubMed

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

2017-07-05

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

Factors associated with fatigue in acquired immunodeficiency syndrome patients with antiretroviral drug adverse reactions: a retrospective study.

PubMed

Liu, Zhibin; Yang, Jiping; Liu, Huijuan; Jin, Yantao

2013-06-01

To retrospectively study the prevalence of fatigue and factors associated with fatigue among acquired immunodeficiency syndrome (AIDS) patients with antiretroviral drug adverse reactions. Data were collected from case report forms (CRFs) for a project funded by the 11th National 5-year Special Science and Technology Program on Major Infectious Diseases. Fatigue was defined by patient self-report. The outcomes were the prevalence of fatigue and the potential risk factors of fatigue. Univariate and multivariate logistic regression analyses were conducted to identify the factors associated with fatigue. Among the 228 subjects, the prevalence of fatigue was 86.8%. In univariate analysis, the significant differences in demographic characteristics between patients with and without fatigue were: gender [OR = 2.29; 95% CI (1.05-4.98)], education level [OR = 0.40; 95% CI (0.18-0.85)], anemia [OR = 3.80; 95% CI (1.27-11.31)], time of HIV diagnosis [OR = 0.29; 95% CI (0.13-0.65)], and route of infection [OR = 0.14; 95% CI (0.06-0.32)]. Abnormal taste and rapid pulse were more commonly seen in patients with fatigue (P < 0.05), while abdominal distension and lumbar soreness were encountered less often in patients with fatigue (P < 0.05). Multivariate analysis showed that the four main factors associated with fatigue were anemia [OR = 3.50; 95% CI (1.01-12.15)], route of infection [OR = 3.40; 95% CI (1.21-9.58); P = 0.02 < 0.05], lumbar soreness [OR = 0.06; 95% CI (0.02-0.18); P = 0.000 < 0.05], and rapid pulse [OR = 10.58; 95% CI (2.16-51.75); P = 0.004 < 0.05]. This study demonstrated that fatigue is common (86.8% prevalence) in AIDS patients with antiretroviral drug adverse reactions, and that anemia, route of infection (i.e., non-commercial blood donation) and rapid pulse were risk factors, while lumbar soreness was a protective factor related to fatigue. More attention should be paid to fatigue and more efforts should be made to find ways to prevent, control and eliminate

Nodular skin reactions in eyebrow permanent makeup: two case reports and an infection by Mycobacterium haemophilum.

PubMed

Wollina, Uwe

2011-09-01

Permanent makeup is becoming more and more popular. The procedures, however, bear some medical risks. We will describe possible adverse effects of the procedure. This is a report of clinical observations. We report about two women aged 26 and 47 years, who developed nodules with some delay after permanent tattooing the eyebrows. Clinical, histologic, and laboratory investigations revealed a noninfectious granulomatous reaction not responding to topical calcineurin inhibitor but corticosteroids in the younger patient. In the other woman, an infection by Mycobacterium haemophilum could be identified. A triple combination of clarithromycin, ciprofloxacin, and rifampicin succeeded in clearance of the lesions. Adverse reactions after permanent makeup need a medical evaluation to identify health risks and initiate early treatment. © 2011 Wiley Periodicals, Inc.

Correction to: Assessment of Local Adverse Reactions to Subcutaneous Immunoglobulin (SCIG) in Clinical Trials.

PubMed

Ballow, Mark; Wasserman, Richard L; Jolles, Stephen; Chapel, Helen; Berger, Mel; Misbah, Siraj A

2018-04-27

The article Assessment of Local Adverse Reactions to Subcutaneous Immunoglobulin (SCIG) in Clinical Trials, written by Mark Ballow, Richard L. Wasserman, Stephen Jolles, Helen Chapel, Mel Berger, Siraj A. Misbah, was originally published Online First without open access.

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

PubMed

Emrani, Zahra; Shojaei, Esphandiar; Khalili, Hossein

2016-06-01

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

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

DTIC Science & Technology

2017-06-08

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

Quantifying risk: the role of absolute and relative measures in interpreting risk of adverse reactions from product labels of antipsychotic medications.

PubMed

Citrome, Leslie

2009-09-01

Pharmaceutical product labeling as approved by regulatory agencies include statements of adverse event risk. Product labels include descriptive statements such as whether events are uncommon or rare, as well as percentage occurrence for more common events. In addition tables are provided with the frequencies of the latter events for both product and placebo as observed in clinical trials. Competing products are not mentioned in a specific drug's product labeling but indirect comparisons can be made using the corresponding label information for the alternate product. Two types of tools are easily used for this purpose: absolute measures such as number needed to harm (NNH), and relative measures such as relative risk increase (RRI). The calculations for both of these types of quantitative measures are presented using as examples the oral first-line second-generation antipsychotic medications. Among three sample outcomes selected a priori, akathisia, weight gain, and discontinuation from a clinical trial because of an adverse reaction, there appears to be differences among the different antipsychotics versus placebo. Aripiprazole was associated with the highest risk for akathisia, particularly when used as adjunctive treatment of major depressive disorder (NNH 5, 95% CI 4-7; RRI 525%, 95% CI 267%-964%). Although insufficient information was available in product labeling to calculate the CI, olanzapine was associated with the highest risk for weight gain of at least 7% from baseline (NNH 6, RRI 640% for adults; NNH 4, RRI 314% for adolescents), and quetiapine for the indication of bipolar depression was associated with the highest risk of discontinuation from a clinical trial because of an adverse reaction (NNH 8, RRI 265% for 600 mg/d; NNH 15, RRI 137% for 300 mg/d). In conclusion, with certain limitations, it is possible for the clinician to extract information from medication product labeling regarding the frequency with which certain adverse reactions can be

Cutaneous reactions to proton pump inhibitors: a case-control study.

PubMed

Chularojanamontri, Leena; Jiamton, Sukhum; Manapajon, Araya; Suvanasuthi, Saroj; Kulthanan, Kanokvalai; Dhana, Naruemon; Jongjarearnprasert, Kowit

2012-10-01

Even though proton pump inhibitors (PPIs) are commonly used in clinical practice, a limited number of studies are available about cutaneous adverse reactions from PPIs, and most of these are case reports. To demonstrate the pattern of cutaneous reactions related to PPI usage and to evaluate the risk of developing PPI drug eruptions among adult patients. We reviewed the spontaneous reports of any adverse events associated with PPI use, as reported from January 2005 through May 2010 to the Adverse Drug Reaction Center at Siriraj Hospital in Thailand. Each control was sampled from 15 patients who had consecutive hospital numbers from each study case. The prevalence of cutaneous reactions to PPIs varied, ranging from three to 20 per 100,000 of the treated population. Sixty-four patients with a history of reaction to PPIs, and 65 controls were enrolled. Most cutaneous reactions were attributed to omeprazole (n=50; 78.1%), and the most frequently observed cutaneous reaction was maculopapular rash (43.8%). None of the patients experienced a cross-reaction between individual PPIs. Cutaneous adverse reactions to PPIs range from minor drug rashes to a severe, life-threatening reaction. Individuals with a history of adverse drug reaction have an increased risk of cutaneous reaction to PPIs.

Parental reporting of adverse drug reactions associated with attention-deficit hyperactivity disorder (ADHD) medications in children attending specialist paediatric clinics in the UK.

PubMed

Tobaiqy, Mansour; Stewart, Derek; Helms, Peter J; Williams, Justin; Crum, Jackie; Steer, Christopher; McLay, James

2011-03-01

The development of systems to ensure appropriate and informed use of medicines in children is a global priority. Current pharmacovigilance systems, such as the UK Yellow Card Scheme, are limited by opportunistic reporting of adverse drug reactions (ADRs), lack of a denominator and lower than expected reporting rates. To develop a pharmacovigilance system able to target specific patient populations such as children, and specific medicines of interest, using specialist medical clinics. Between January and March 2010, parents of 578 children (3-16 years of age) receiving pharmacological therapy for attention-deficit hyperactivity disorder and attending a child and adolescent clinic in the UK were sent an ADR questionnaire to elicit information on possible ADRs associated with their child's medication use. Two approaches, free text and a symptom tick list, were used to elicit possible ADRs. Two hundred and seven questionnaires were returned, of which 200 were evaluable, giving a response rate of 35.9%. 123 questionnaires reported a total of 213 free-text ADRs perceived by the parents to be due to the medications under study. Two-thirds of reported ADRs were considered to be ongoing at the time of reporting. Duration of reported ADRs ranged from 1 week to 3 years. 81 returned questionnaires reported 134 different ADRs for methylphenidate monotherapy. For methylphenidate, the most frequently reported ADRs were loss of appetite (34.3%), headache (17.9%), mood and emotional problems (14.9%), stomach upset (14.9%), sleep disturbance (10.4%), and rash and other skin problems (5.2%). 467 possible drug-related symptoms were reported using the tick-list approach. Using the tick list, the most frequently reported symptoms were mood and emotional problems (28.1% [131/467]), stomach and abdominal problems (13.3% [62/467]), insomnia (12.8% [60/467]) and lack of appetite (12.6% [59/467]). The symptom tick list identified a broader range of possible adverse effects not reported as

Mitigating adverse event reporting bias in spine surgery.

PubMed

Auerbach, Joshua D; McGowan, Kevin B; Halevi, Marci; Gerling, Michael C; Sharan, Alok D; Whang, Peter G; Maislin, Greg

2013-08-21

Recent articles in the lay press and literature have raised concerns about the ability to report honest adverse event data from industry-sponsored spine surgery studies. To address this, clinical trials may utilize an independent Clinical Events Committee (CEC) to review adverse events and readjudicate the severity and relatedness accordingly. We are aware of no prior study that has quantified either the degree to which investigator bias is present in adverse event reporting or the effect that an independent CEC has on mitigating this potential bias. The coflex Investigational Device Exemption study is a prospective randomized controlled trial comparing coflex (Paradigm Spine) stabilization with lumbar spinal fusion to treat spinal stenosis and spondylolisthesis. Investigators classified the severity of adverse events (mild, moderate, or severe) and their relationship to the surgery and device (unrelated, unlikely, possibly, probably, or definitely). An independent CEC, composed of three spine surgeons without affiliation to the study sponsor, reviewed and reclassified all adverse event reports submitted by the investigators. The CEC reclassified the level of severity, relation to the surgery, and/or relation to the device in 394 (37.3%) of 1055 reported adverse events. The proportion of adverse events that underwent reclassification was similar in the coflex and fusion groups (37.9% compared with 36.0%, p = 0.56). The CEC was 5.3 (95% confidence interval [CI], 2.6 to 10.7) times more likely to upgrade than downgrade the adverse event. The CEC was 7.3 (95% CI, 5.1 to 10.6) times more likely to upgrade than downgrade the relationship to the surgery and 11.6 (95% CI, 7.5 to 18.8) times more likely to upgrade than downgrade the relationship to the device. The status of the investigator's financial interest in the company had little effect on the reclassification of adverse events. Thirty-seven percent of adverse events were reclassified by the CEC; the large majority

Imputation of adverse drug reactions: Causality assessment in hospitals

PubMed Central

Mastroianni, Patricia de Carvalho

2017-01-01

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

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

PubMed

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

2018-05-07

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

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

PubMed

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

2015-01-01

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

A case of adverse drug reaction induced by dispensing error.

PubMed

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

2012-11-01

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

A 3-armed randomized controlled trial of nurses' continuing education meetings on adverse drug reactions.

PubMed

Sarayani, Amir; Naderi-Behdani, Fahimeh; Hadavand, Naser; Javadi, Mohammadreza; Farsad, Fariborz; Hadjibabaie, Molouk; Gholami, Kheirollah

2015-01-01

Nurses' insufficient knowledge of adverse drug reactions is reported as a barrier to spontaneous reporting. Therefore, CE meetings could be utilized to enhance nurses' competencies. In a 3-armed randomized controlled trial, 496 nurses, working in a tertiary medical center, were randomly allocated to a didactic lecture, brainstorming workshop, or the control group (delayed education). Similar instructors (2 clinical pharmacists) prepared and delivered the educational content to all 3 groups. Outcomes were declarative/procedural knowledge (primary outcome), participation rate, and satisfaction. Knowledge was evaluated using a validated researcher-made questionnaire in 3 time points: immediately before, immediately after, and 3 months after each session. Participants' satisfaction was assessed immediately after each meeting via a standard tool. Data were analyzed using appropriate parametric and nonparametric tests. Rate of participation was 37.7% for the lecture group and 47.5% for the workshop group. The workshop participants were significantly more satisfied in comparison with the lecture group (p < .05). Mean knowledge scores were similar at baseline in the 3 study groups (43-47). Immediately after the meeting, knowledge was significantly higher in the lecture group (79.1 ± 11.9 vs 73.7 ± 11.3; p = .01). At the follow-up, knowledge scores of the lecture and workshop groups were similar, while significantly higher than the control group. However, the reduction of knowledge score was significantly higher in the lecture group (-13.0 ± 15.9% vs -5.7 ± 15.1%, p = .02). Educational interventions can improve nurses' knowledge of adverse drug reactions. Short-term learning could be achieved with lecture, but the retention of knowledge will be enhanced by simple interactive techniques. © 2015 The Alliance for Continuing Education in the Health Professions, the Society for Academic Continuing Medical Education, and the Council on Continuing Medical Education

Monitoring signals for vaccine safety: the assessment of individual adverse event reports by an expert advisory committee. Advisory Committee on Causality Assessment.

PubMed Central

Collet, J. P.; MacDonald, N.; Cashman, N.; Pless, R.

2000-01-01

Monitoring vaccine safety is a complex and shared responsibility. It can be carried out in many ways, one of which is the reporting of individual cases of adverse reactions thought to be due to vaccination. The task is difficult because ascribing causality to an individual case report is fraught with challenges. A standardized evaluation instrument--known as the causality assessment form--was therefore developed for use by an expert advisory committee to facilitate the process. By following the several sections in this form, the members of the committee are taken through a series of points to establish causality. These points include the basic criteria for causation such as biological plausibility, the time elapsed between the vaccine administration and the onset of the adverse event, and whether other factors (drugs, chemicals or underlying disease) could account for the adverse symptoms. The form concludes with a consensus assessment of causality, a commentary about the assessment, and advice for further study or follow-up. This method of assessing the more serious cases of adverse reaction reported to vaccination has proven useful in evaluating ongoing safety of vaccines in Canada. Through analyses such as this, new signals can be identified and investigated further. PMID:10743282

Adverse events following quadrivalent meningococcal CRM-conjugate vaccine (Menveo®) reported to the Vaccine Adverse Event Reporting system (VAERS), 2010-2015.

PubMed

Myers, Tanya R; McNeil, Michael M; Ng, Carmen S; Li, Rongxia; Lewis, Paige W; Cano, Maria V

2017-03-27

Limited data are available describing the post-licensure safety of meningococcal vaccines, including Menveo®. We reviewed reports of adverse events (AEs) to the Vaccine Adverse Event Reporting System (VAERS) to assess safety in all age groups. VAERS is a national spontaneous vaccine safety surveillance system co-administered by the Centers for Disease Control and Prevention and the US Food and Drug Administration. We searched the VAERS database for US reports of adverse events in persons who received Menveo from 1 January 2010 through 31 December 2015. We clinically reviewed reports and available medical records for serious AEs, selected pre-specified outcomes, and vaccination during pregnancy. We used empirical Bayesian data mining to identify AEs that were disproportionately reported after receipt of Menveo. During the study period, VAERS received 2614 US reports after receipt of Menveo. Of these, 67 were classified as serious, including 1 report of death. Adolescents (aged 11-18years) accounted for 74% of reports. Most of the reported AEs were non-serious and described AEs consistent with data from pre-licensure studies. Anaphylaxis and syncope were the two most common events in the serious reports. We did not identify any new safety concerns after review of AEs that exceeded the data mining threshold, although we did observe disproportionate reporting for terms that were not associated with an adverse event (e.g., "incorrect drug dosage form administered", "wrong technique in drug usage process"). Although reports were limited, we did not find any evidence for concern regarding the use of Menveo during pregnancy. In our review of VAERS reports, findings of AEs were consistent with the data from pre-licensure studies. Vaccine providers should continue to emphasize and adhere to proper administration of the vaccine. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

The Analysis of the Adverse Reaction of Traditional Chinese Medicine Tumor Bone Marrow Suppression

NASA Astrophysics Data System (ADS)

Wei, Zhenzhen; Fang, Xiaoyan; Miao, Mingsan

2018-01-01

With the rapid increase of cancer patients, chemotherapy is the main method for the clinical treatment of cancer, but also in the treatment of the adverse reactions--bone marrow suppression is often a serious infection caused by patients after chemotherapy and the important cause of mortality. Chinese medicine has obvious advantages in the prevention and treatment of bone marrow depression after chemotherapy. According to tumor bone marrow suppression after chemotherapy of etiology and pathogenesis of traditional Chinese medicine and China national knowledge internet nearly 10 years of traditional Chinese medicine in the prevention and control of the status of clinical and laboratory research of tumor bone marrow suppression, the author analyzed and summarized its characteristics, so as to provide the basis for treating bone marrow suppression of drug research and development, and promote small adverse reactions of the development and utilization of natural medicine and its preparations.

Severe adverse drug reaction following Crotalidae Polyvalent Immune Fab (Ovine) administration for copperhead snakebite.

PubMed

Lepak, Maryjoy R; Bochenek, Samantha H; Bush, Sean P

2015-01-01

To present the case of a severe anaphylactic/anaphylactoid reaction to Crotalidae Polyvalent Immune Fab (Ovine) in a patient bitten by a copperhead snake. A 68-year-old man presented with progressive envenomation after receiving a copperhead snakebite on each hand. Crotalinae Fab antivenom was administered. While the initial and only dose was partially infusing, the patient developed an adverse drug reaction (ADR) of urticaria and hypotension, which resolved with cessation of the infusion, recurred with resumption of the infusion, and ultimately was completed with supportive care. An additional episode of hypotension, urticaria, and angioedema occurred shortly after antivenom therapy completion. Epinephrine was administered, resolving the reaction with complete patient recovery. The event received a Naranjo score of 10, indicating a definite ADR. Treating copperhead snakebites with antivenom is a matter of debate. Concern over adverse events and cost induce some physicians to manage copperhead bites without antivenom because they are generally milder in severity. As demonstrated in this case, severe ADR can occur with Crotalinae Fab antivenom, and its efficacy for copperhead envenoming needs to be better established via placebo-controlled, randomized trials. © The Author(s) 2014.

Pharmacovigilance in children: detecting adverse drug reactions in routine electronic healthcare records. A systematic review.

PubMed

Black, Corri; Tagiyeva-Milne, Nara; Helms, Peter; Moir, Dorothy

2015-10-01

A systematic review of the literature published in English over 10 years was undertaken in order to describe the use of electronic healthcare data in the identification of potential adverse drug reactions (ADRs) in children. MEDLINE and EMBASE were searched using MESH headings and text words. Titles, keywords and abstracts were checked for age <18 years, potential ADRs and electronic healthcare data. Information extracted included age, data source, pharmacovigilance method, medicines and ADRs. Studies were quality assessed. From 14 804 titles, 314 had a full text review and 71 were included in the final review. Fifty were published in North America, 10 in Scandinavia. Study size ranged from less than 1000 children to more than 10 million. Sixty per cent of studies used data from one source. Comparative observational studies were most commonly reported (66.2%) with 15% using passive surveillance. Electronic healthcare data set linkage and the quality of the data source were poorly reported. ADRs were classified using the International Classification of Disease (ICD10). Multi-system reactions were most commonly studied, followed by central nervous system and mental and behavioural disorders. Vaccines were most frequently prescribed followed by corticosteroids, general anaesthetics and antidepressants. Routine electronic healthcare records were increasingly reported to be used for pharmacovigilance in children. This growing and important health protection activity could be enhanced by consistent reporting of studies to improve the identification, interpretation and generalizability of the evidence base. © 2015 The British Pharmacological Society.

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

PubMed

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

2000-12-01

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

Suspected adverse reactions to contrast media in Campania Region (Italy): results from 14 years of post-marketing surveillance.

PubMed

Sessa, Maurizio; Rossi, Claudia; Mascolo, Annamaria; Grassi, Enrico; Fiorentino, Sonia; Scavone, Cristina; Reginelli, Alfonso; Rotondo, Antonio; Sportiello, Liberata

2015-01-01

During the last years in Italy, contrast media (CM) use increased. An increase of monitoring activities on CM-induced adverse drug reaction (ADR) is necessary, also in our regional territory. The main aim of this study was to give a preliminary evaluation of all Spontaneous Reports of ADRs (SRA) attributed to CM sent to Campania Pharmacovigilance Regional Center (CRFVC) from 01 January 2001 to 31 October 2014. For each SRA we evaluated: frequency and source, ADRs onset (time to event, seriousness and outcome), socio-demographic characteristics and risk factors of cases, the most reported CM (checking for pharmacodynamic and pharmacokinetic interactions). A total of 111 SRA were sent to CRFVC; specialist in radiology was the main source of reports. Ninety-seven SRA (87.3%) were referable to hypersensitivity reactions. Thirty-four SRA (30.6%) reported serious ADRs. The most reported CM were iopamidol, gadobenic acid and gadoteric acid. We identified two SRA induced by pharmacokinetic and/or pharmacodynamic interactions. During 14 years of post-marketing surveillance, only few SRA concerning CM-induced ADRs were sent to CRFVC probably due to underreporting. We aim to improve monitoring activity on CM-induced ADRs especially in hospitals. Most reported ADR and CM were in line with current body of literature.

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

PubMed

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

2018-03-01

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

Adverse Drug Reactions Related to Drug Administration in Hospitalized Patients.

PubMed

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

2017-01-01

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

Differences in Adverse Event Reporting Rates of Therapeutic Failure Between Two Once-daily Extended-release Methylphenidate Medications in Canada: Analysis of Spontaneous Adverse Event Reporting Databases.

PubMed

Park-Wyllie, Laura; van Stralen, Judy; Castillon, Genaro; Sherman, Stephen E; Almagor, Doron

2017-10-01

Our study evaluated adverse events of therapeutic failure (and specifically reduced duration of action) with the use of a branded product, Osmotic Release Oral System (OROS) methylphenidate, which is approved for the treatment of attention deficit/hyperactivity disorder, and a generic product (methylphenidate, methylphenidate ER-C), which was approved for marketing in Canada based on bioequivalence to OROS methylphenidate. This study was initiated following reports that some US-marketed generic methylphenidate ER products had substantially higher reporting rates of therapeutic failure than did the referenced brands. Through methodology similar to that used by the US Food and Drug Administration to investigate the issue with the US-marketed generic, reporting rates were calculated from cases of therapeutic failure identified in the Canadian Vigilance Adverse Reaction Online database for a 1-year period beginning 8 months after each product launch. Corresponding population exposure was estimated from the number of tablets dispensed. An in-depth analysis of narratives of individual case safety reports (ICSRs) with the use of the generic product was conducted in duplicate by 2 physicians to assess causality and to characterize the potential safety risk and clinical pattern of therapeutic failure. Similar secondary analyses were conducted on the US-marketed products. Reporting rates of therapeutic failure with the use of methylphenidate ER-C (generic) and OROS methylphenidate (brand name) were 411.5 and 37.5 cases per 100,000 patient-years, respectively (reporting rate ratio, 10.99; 95% CI, 5.93-22.21). In-depth analysis of narratives of 230 ICSRs of therapeutic failure with the Canadian-marketed generic determined that all ICSRs were either probably (60 [26%]) or possibly (170 [74%]) causally related to methylphenidate ER-C. Clinical symptoms suggestive of overdose were present in 31 reports of loss of efficacy (13.5%) and occurred primarily in the morning, and

Frequency of Extrapyramidal Adverse Reactions in Schizophrenic Outpatients Treated with Risperidone, Olanzapine, Quetiapine or Haloperidol : Results of the EIRE Study.

PubMed

Bobes, Julio; Rejas, J; Garcia-Garcia, M; Rico-Villademoros, F; García-Portilla, M P; Madrigal, M; Hernández, G

2002-09-01

The EIRE (Estudio de Investigaciön de Resultados en Esquizofrenia - Outcomes Research Study in Schizophrenia) study was initiated in order to assess the frequency of adverse reactions [extrapyramidal symptoms (EPS), hyperprolactinaemia, sexual dysfunction and weight gain] caused by atypical antipsychotics and haloperidol in patients with schizophrenia during routine treatment in clinical practice. This paper presents the results of the assessment of extrapyramidal adverse reactions. Outpatients diagnosed with schizophrenia according to the Diagnostic and Statistical Manual of mental disorders, 4th edition (DSM-IV), criteria and receiving a single antipsychotic (risperidone, olanzapine, quetiapine or haloperidol) for at least 4 weeks were consecutively recruited. In this cross-sectional and non-interventional study data were collected in a single visit; this included demographic and clinical characteristics, current antipsychotic and concomitant treatment, and data on several adverse effects listed in a modified version of the UKU (Udvalg for Kliniske Undersogelser - Committee on Clinical Investigations) scale. For paired comparisons of the frequency of adverse reactions between treatments the Chi-squared (χ 2 ) test was used. For estimation of the risk of a given adverse reaction with a given treatment a logistic regression method was used. 636 evaluable patients (of 669 recruited) were assessed. The frequency of EPS with haloperidol (78.3% of the cases) was higher than with risperidone (55.1%), quetiapine (39.5%) and olanzapine (35.8%) [χ 2 : p < 0.05], and the difference between risperidone and olanzapine was also statistically significant (χ 2 : p < 0.05). Very similar results were obtained in the individualised analysis of the items as regards the occurrence of akathisia, which was also more frequent in the haloperidol (36.8%) and risperidone (19.7%) groups than in the olanzapine (11.4%) and quetiapine (2.6%) groups (χ 2 : p < 0.05). Olanzapine, quetiapine

A novel approach to increase residents' involvement in reporting adverse events.

PubMed

Scott, David R; Weimer, Melissa; English, Clea; Shaker, Lynn; Ward, William; Choi, Dongseok; Cedfeldt, Andrea; Girard, Donald

2011-06-01

In the wake of the Patient Safety and Quality Improvement Act of 2005, national attention has increasingly focused on adverse-event reporting as a means of identifying systems changes to improve patient safety. However, physicians and residents have demonstrated meager involvement in this effort. In 2008-2009, the authors measured participation in adverse-event reporting by 680 residents at Oregon Health & Science University before and after implementing a quality improvement initiative, which consisted of a financial incentive and multifaceted educational campaign. The primary measure of success was an increase in the average monthly adverse-event reports submitted by residents to greater than 5% of the institution's overall report submissions. The average number of adverse events reported by residents increased from 1.6% to 9.0% of the institution's overall event reports, representing a 5.6-fold increase during the initiative (P < .001). The relative percentage of resident-submitted reports defined as "near-misses" increased from 6% to 27% during the initiative (P < .001). The novel approach of integrating a retirement benefit and educational campaign to increase residents' involvement in adverse-event reporting was successful. In addition to increasing residents' contributions to adverse-event reporting to levels higher than any documented in the current literature, there was also a remarkable increase in the relative frequency of near-miss reporting by residents.

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.

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

PubMed Central

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

1990-01-01

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

Coding of adverse events of suicidality in clinical study reports of duloxetine for the treatment of major depressive disorder: descriptive study.

PubMed

Maund, Emma; Tendal, Britta; Hróbjartsson, Asbjørn; Lundh, Andreas; Gøtzsche, Peter C

2014-06-04

To assess the effects of coding and coding conventions on summaries and tabulations of adverse events data on suicidality within clinical study reports. 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. 9 randomised placebo controlled trials of duloxetine for major depressive disorder submitted to the European Medicines Agency for marketing approval. Clinical study reports obtained from the EMA in 2011. 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. 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 listings of adverse events for individual patients and narratives

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

Flow Microscopy Imaging Is Sensitive to Characteristics of Subvisible Particles in Peginesatide Formulations Associated With Severe Adverse Reactions.

PubMed

Daniels, Austin L; Randolph, Theodore W

2018-05-01

The presence of subvisible particles in formulations of therapeutic proteins is a risk factor for adverse immune responses. Although the immunogenic potential of particulate contaminants likely depends on particle structural characteristics (e.g., composition, size, and shape), exact structure-immunogenicity relationships are unknown. Images recorded by flow imaging microscopy reflect information about particle morphology, but flow microscopy is typically used to determine only particle size distributions, neglecting information on particle morphological features that may be immunologically relevant. We recently developed computational techniques that utilize the Kullback-Leibler divergence and multidimensional scaling to compare the morphological properties of particles in sets of flow microscopy images. In the current work, we combined these techniques with expectation maximization cluster analyses and used them to compare flow imaging microscopy data sets that had been collected by the U.S. Food and Drug Administration after severe adverse drug reactions (including 7 fatalities) were observed in patients who had been administered some lots of peginesatide formulations. Flow microscopy images of particle populations found in the peginesatide lots associated with severe adverse reactions in patients were readily distinguishable from images of particles in lots where severe adverse reactions did not occur. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.