Lin, Wen-Yang; Li, He-Yi; Du, Jhih-Wei; Feng, Wen-Yu; Lo, Chiao-Feng; Soo, Von-Wun
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.
Hwang, Youhyeon; Oh, Min; Jang, Giup; Lee, Taekeon; Park, Chihyun; Ahn, Jaegyoon; Yoon, Youngmi
Adverse drug reactions (ADRs) are one of the major concerns threatening public health and have resulted in failures in drug development. Thus, predicting ADRs and discovering the mechanisms underlying ADRs have become important tasks in pharmacovigilance. Identification of potential ADRs by computational approaches in the early stages would be advantageous in drug development. Here we propose a computational method that elucidates the action mechanisms of ADRs and predicts potential ADRs by utilizing ADR genes, drug features, and protein-protein interaction (PPI) networks. If some ADRs share similar features, there is a high possibility that they may appear together in a drug and share analogous mechanisms. Proceeding from this assumption, we clustered ADRs according to interactions of ADR genes in the PPI networks and the frequency of co-occurrence of ADRs in drugs. ADR clusters were verified based on a side effect database and literature data regarding whether ADRs have relevance to other ADRs in the same cluster. Gene networks shared by ADRs in each cluster were constructed by cumulating the shortest paths between drug target genes and ADR genes in the PPI network. We developed a classification model to predict potential ADRs using these gene networks shared by ADRs and calculated cross-validation AUC (area under the curve) values for each ADR cluster. In addition, in order to demonstrate correlations between gene networks shared by ADRs and ADRs in a cluster, we applied the Wilcoxon rank sum statistical test to the literature data and results of a Google query search. We attained statistically meaningful p-values (<0.05) for every ADR cluster. The results suggest that our approach provides insights into discovering the action mechanisms of ADRs and is a novel attempt to predict ADRs in a biological aspect.
Singh, Anshi; Bhatt, Parloop
Despite comprehensive and stringent phases of clinical trials and surveillance efforts, unexpected and serious adverse drug reactions (ADRs) repeatedly occur after the drug is marketed. ADR reporting is an important aspect of an efficient and effective pharmacovigilance program. Although Medwatch, Yellow Card, CDSCO form, etc. are the protocol forms of ADR collection and reports, a number of countries design and use their respective ADR forms. This review compares similarities and dissimilarities of 13 ADR forms of countries representing their geographical location. This study extracted 73 data elements mentioned in 13 different ADR forms. Only 13 elements were common. An ADR form of Malaysia and Canada covers the highest number of data 43, while Brazil falls to the opposite end with a number of 17 data elements in lieu with the Generic ADR Form. The result of this review highlights 58 data elements of the proposed generic ADR form which ensures that requisite reporting information essential for correct causality assessment of ADRs are included. The proposed “Generic ADR form” could be adopted worldwide mandatorily for reporting any/all ADRs associated with marketed drugs. PMID:23129957
Ghattaoraya, Gurpreet S; Dundar, Yenal; González-Galarza, Faviel F; Maia, Maria Helena Thomaz; Santos, Eduardo José Melo; da Silva, Andréa Luciana Soares; McCabe, Antony; Middleton, Derek; Alfirevic, Ana; Dickson, Rumona; Jones, Andrew R
Human leukocyte antigens (HLA) are an important family of genes involved in the immune system. Their primary function is to allow the host immune system to be able to distinguish between self and non-self peptides-e.g. derived from invading pathogens. However, these genes have also been implicated in immune-mediated adverse drug reactions (ADRs), presenting a problem to patients, clinicians and pharmaceutical companies. We have previously developed the Allele Frequency Net Database (AFND) that captures the allelic and haplotype frequencies for these HLA genes across many healthy populations from around the world. Here, we report the development and release of the HLA-ADR database that captures data from publications where HLA alleles and haplotypes have been associated with ADRs (e.g. Stevens-Johnson Syndrome/toxic epidermal necrolysis and drug-induced liver injury). HLA-ADR was created by using data obtained through systematic review of the literature and semi-automated literature mining. The database also draws on data already present in AFND allowing users to compare and analyze allele frequencies in both ADR patients and healthy populations. The HLA-ADR database provides clinicians and researchers with a centralized resource from which to investigate immune-mediated ADRs.Database URL: http://www.allelefrequencies.net/hla-adr/.
Faich, G A; Castle, W; Bankowski, Z
A method for standardized postapproval adverse drug reaction (ADR) reporting has been developed and implemented by seven multinational pharmaceutical manufacturers and six regulatory authorities. This is based on a set of uniform definitions, procedures and a single reporting form, and has been demonstrated to be useful and effective. When regulators and manufacturers develop requirements and systems for ADR reporting they should consider adapting this method.
Royer, R J; Benichou, C
Under the auspices of the Council for International Organizations of Medical Sciences, a working group composed of representatives of seven multinational pharmaceutical manufacturers and six regulatory authorities developed and implemented a standardized method for reporting post-approval adverse drug reactions (ADR). The method is based on a set of uniform definitions and procedures and a single reporting form, and has been demonstrated to be feasible and effective. Regulators and manufacturers, in establishing requirements and systems for reporting of adverse drug reactions, should consider adopting this method.
Kharkar, Mala; Bowalekar, Suresh
Objective: The objective was to assess knowledge, attitude and perceptions/practices (KAP) of medical practitioners (MPs) in India towards Adverse Drug Reaction (ADR) reporting. Materials and Methods: A questionnaire was designed for assessment of KAP of medical practitioners in India toward ADR reporting. This questionnaire was administered to 2-3 medical practitioners from each zone prior to administering final questionnaire which was approved by Disha Independent Ethics Committee, Mumbai. 1200 medical practitioners (about 300 from each zone) from India were selected randomly. Results: 1000 medical practitioners out of 1200 (90%), selected at random were approached. A total of 870 provided responses to the questionnaire, giving a response rate of 73% of 1200 selected randomly. A total of 47.5% respondents reported that they were aware of Government ADR centers. A total of 59.2% reported that they are familiar with the procedure of reporting ADRs to Government centers. However, only 18.5% of MPs have reported the observed ADRs to Government ADR centers. As against this relatively large number of MPs (87.9%) have reported ADRs observed during their routine practice to medical representatives of pharmaceutical company and NGOs (non-Govt. Organizations). A total of 80.5% of respondents agreed that safety plays an important role and 96% reported that ADR centers are useful. However, only 55.6% of respondents have reported that there is a need for ADR centers. Conclusion: The study reveals that practitioners are aware of ADR reporting; their perception toward ADR reporting is right but it is not reflected when it comes to the act of reporting of ADRs. In our sample of 870 respondents only 18.5 % reported ADRs to some organizations. Only 5% of respondents recorded the details of ADR and reported to the manufacturer and 1% of respondents to government health ministry. Thus, medical practitioners in India appear to have a good knowledge about ADR reporting, the right
Souvignet, Julien; Declerck, Gunnar; Asfari, Hadyl; Jaulent, Marie-Christine; Bousquet, Cédric
Efficient searching and coding in databases that use terminological resources requires that they support efficient data retrieval. The Medical Dictionary for Regulatory Activities (MedDRA) is a reference terminology for several countries and organizations to code adverse drug reactions (ADRs) for pharmacovigilance. Ontologies that are available in the medical domain provide several advantages such as reasoning to improve data retrieval. The field of pharmacovigilance does not yet benefit from a fully operational ontology to formally represent the MedDRA terms. Our objective was to build a semantic resource based on formal description logic to improve MedDRA term retrieval and aid the generation of on-demand custom groupings by appropriately and efficiently selecting terms: OntoADR. The method consists of the following steps: (1) mapping between MedDRA terms and SNOMED-CT, (2) generation of semantic definitions using semi-automatic methods, (3) storage of the resource and (4) manual curation by pharmacovigilance experts. We built a semantic resource for ADRs enabling a new type of semantics-based term search. OntoADR adds new search capabilities relative to previous approaches, overcoming the usual limitations of computation using lightweight description logic, such as the intractability of unions or negation queries, bringing it closer to user needs. Our automated approach for defining MedDRA terms enabled the association of at least one defining relationship with 67% of preferred terms. The curation work performed on our sample showed an error level of 14% for this automated approach. We tested OntoADR in practice, which allowed us to build custom groupings for several medical topics of interest. The methods we describe in this article could be adapted and extended to other terminologies which do not benefit from a formal semantic representation, thus enabling better data retrieval performance. Our custom groupings of MedDRA terms were used while performing signal
Petrovic, Mirko; Tangiisuran, Balamurugan; Rajkumar, Chakravarthi; van der Cammen, Tischa; Onder, Graziano
Adverse drug reactions (ADRs) in older people are often preventable, indicating that screening and prevention programs aimed at reducing their rate are needed in this population. The aim of this study was to externally validate the GerontoNet ADR risk score and to assess its validity in specific subpopulations of older inpatients. Data from the prospective CRIteria to assess appropriate Medication use among Elderly complex patients (CRIME) cohort were used. Dose-dependent and predictable ADRs were classified as type A, probable or definite ADRs were defined according to the Naranjo algorithm, and diagnostic accuracy was tested using receiver operating characteristic (ROC) analyses. Sensitivity and specificity were calculated for a cut-off point of 4. The mean age of the 1075 patients was 81.4 years (standard deviation 7.4) and the median number of drugs was 10 (range 7-13). At least one ADR was observed in 70 patients (6.5%); ADRs were classified as type A in 50 patients (4.7%) and defined as probable or definite in 41 patients (3.8%). Fair diagnostic accuracy to predict both type A and probable or definite ADRs was found in subpopulations aged <70 or ≥80 years with heart failure, diabetes, or a previous ADR. Good accuracy to predict type A ADRs was found in patients with a low body mass index (BMI; >18.5 kg/m(2)) and a Mini-Mental State Examination (MMSE) score of >24/30 points, as well as in patients with osteoarthritis. The cut-off point of 4 points yielded very good sensitivity but poor specificity results in these subpopulations. This study suggests that the GerontoNet ADR risk score might represent a pragmatic approach to identifying specific subpopulations of older inpatients at increased risk of an ADR with a fair to good diagnostic accuracy.
Tabali, Manuela; Jeschke, Elke; Bockelbrink, Angelina; Witt, Claudia M; Willich, Stefan N; Ostermann, Thomas; Matthes, Harald
Background Recent studies have shown that adverse drug reactions (ADRs) are underreported. This may be particularly true of ADRs associated with complementary and alternative medicine (CAM). Data on CAM-related ADRs, however, are sparse. Objective was to evaluate the impact of an educational intervention and monitoring programme designed to improve physician reporting of ADRs in a primary care setting. Methods A prospective multicentre study with 38 primary care practitioners specialized in CAM was conducted from January 2004 through June 2007. After 21 month all physicians received an educational intervention in terms of face-to-face training to assist them in classifying and reporting ADRs. The study centre monitored the quantity and quality of ADR reports and analysed the results. To measure changes in the ADR reporting rate, the median number of ADR reports and interquartile range (IQR) were calculated before and after the educational intervention. The pre-intervention and post-intervention quality of the reports was assessed in terms of changes in the completeness of data provided for obligatory items. Interrater reliability between the physicians and the study centre was calculated using Cohen's kappa with a 95% confidence interval (CI). We used Mann Whitney U-test for testing continuous data and chi-square test was used for categorical data. The level of statistical significance was set at P < 0.05. Results A total of 404 ADRs were reported during the complete study period. An initial 148% increase (P = 0.001) in the number of ADR reports was observed after the educational intervention. Compared to baseline the postinterventional number of ADR reportings was statistically significant higher (P < 0.005) through the first 16 months after the intervention but not significant in the last 4-month period (median: 8.00 (IQR [2.75; 8.75]; P = 0.605). The completeness of the ADR reports increased from 80.3% before to 90.7% after the intervention. The completeness of
Tabali, Manuela; Jeschke, Elke; Bockelbrink, Angelina; Witt, Claudia M; Willich, Stefan N; Ostermann, Thomas; Matthes, Harald
Recent studies have shown that adverse drug reactions (ADRs) are underreported. This may be particularly true of ADRs associated with complementary and alternative medicine (CAM). Data on CAM-related ADRs, however, are sparse.Objective was to evaluate the impact of an educational intervention and monitoring programme designed to improve physician reporting of ADRs in a primary care setting. A prospective multicentre study with 38 primary care practitioners specialized in CAM was conducted from January 2004 through June 2007. After 21 month all physicians received an educational intervention in terms of face-to-face training to assist them in classifying and reporting ADRs. The study centre monitored the quantity and quality of ADR reports and analysed the results.To measure changes in the ADR reporting rate, the median number of ADR reports and interquartile range (IQR) were calculated before and after the educational intervention. The pre-intervention and post-intervention quality of the reports was assessed in terms of changes in the completeness of data provided for obligatory items. Interrater reliability between the physicians and the study centre was calculated using Cohen's kappa with a 95% confidence interval (CI). We used Mann Whitney U-test for testing continuous data and chi-square test was used for categorical data. The level of statistical significance was set at P < 0.05. A total of 404 ADRs were reported during the complete study period. An initial 148% increase (P = 0.001) in the number of ADR reports was observed after the educational intervention. Compared to baseline the postinterventional number of ADR reportings was statistically significant higher (P < 0.005) through the first 16 months after the intervention but not significant in the last 4-month period (median: 8.00 (IQR [2.75; 8.75]; P = 0.605). The completeness of the ADR reports increased from 80.3% before to 90.7% after the intervention. The completeness of the item for classifying ADRs
Liang, Zhaohui; Huang, Jimmy Xiangji; Zeng, Xing; Zhang, Gang
Genomic variations are associated with the metabolism and the occurrence of adverse reactions of many therapeutic agents. The polymorphisms on over 2000 locations of cytochrome P450 enzymes (CYP) due to many factors such as ethnicity, mutations, and inheritance attribute to the diversity of response and side effects of various drugs. The associations of the single nucleotide polymorphisms (SNPs), the internal pharmacokinetic patterns and the vulnerability of specific adverse reactions become one of the research interests of pharmacogenomics. The conventional genomewide association studies (GWAS) mainly focuses on the relation of single or multiple SNPs to a specific risk factors which are a one-to-many relation. However, there are no robust methods to establish a many-to-many network which can combine the direct and indirect associations between multiple SNPs and a serial of events (e.g. adverse reactions, metabolic patterns, prognostic factors etc.). In this paper, we present a novel deep learning model based on generative stochastic networks and hidden Markov chain to classify the observed samples with SNPs on five loci of two genes (CYP2D6 and CYP1A2) respectively to the vulnerable population of 14 types of adverse reactions. A supervised deep learning model is proposed in this study. The revised generative stochastic networks (GSN) model with transited by the hidden Markov chain is used. The data of the training set are collected from clinical observation. The training set is composed of 83 observations of blood samples with the genotypes respectively on CYP2D6*2, *10, *14 and CYP1A2*1C, *1 F. The samples are genotyped by the polymerase chain reaction (PCR) method. A hidden Markov chain is used as the transition operator to simulate the probabilistic distribution. The model can perform learning at lower cost compared to the conventional maximal likelihood method because the transition distribution is conditional on the previous state of the hidden Markov
Avillach, Paul; Dufour, Jean-Charles; Diallo, Gayo; Salvo, Francesco; Joubert, Michel; Thiessard, Frantz; Mougin, Fleur; Trifirò, Gianluca; Fourrier-Réglat, Annie; Pariente, Antoine; Fieschi, Marius
Objectives The aim of this research was to automate the search of publications concerning adverse drug reactions (ADR) by defining the queries used to search MEDLINE and by determining the required threshold for the number of extracted publications to confirm the drug/event association in the literature. Methods We defined an approach based on the medical subject headings (MeSH) ‘descriptor records’ and ‘supplementary concept records’ thesaurus, using the subheadings ‘chemically induced’ and ‘adverse effects’ with the ‘pharmacological action’ knowledge. An expert-built validation set of true positive and true negative drug/adverse event associations (n=61) was used to validate our method. Results Using a threshold of three of more extracted publications, the automated search method presented a sensitivity of 90% and a specificity of 100%. For nine different drug/event pairs selected, the recall of the automated search ranged from 24% to 64% and the precision from 93% to 48%. Conclusions This work presents a method to find previously established relationships between drugs and adverse events in the literature. Using MEDLINE, following a MeSH approach to filter the signals, is a valid option. Our contribution is available as a web service that will be integrated in the final European EU–ADR project (Exploring and Understanding Adverse Drug Reactions by integrative mining of clinical records and biomedical knowledge) automated system. PMID:23195749
What was the nature of the CPD activity, practice-related feedback and/or event and/or experience in your practice? The CPD article defined the different types of adverse drug reactions (ADRs) and explored when they can occur. It emphasised the importance of being knowledgeable about medications, considering patient safety when patients are taking medications, being alert to the possibility of ADRs, and recognising and responding to suspected ADRs.
Wooten, James M
Pharmacovigilance is the process of identifying, monitoring, and effectively reducing adverse drug reactions. Adverse drug reactions (ADRs) are an important consideration when assessing a patient's health. The proliferation of new pharmaceuticals means that the incidence of ADRs is increasing. The goal for all health care providers must be to minimize the risk of ADRs as much as possible. Steps to achieve this include understanding the pharmacology for all drugs prescribed and proactively assessing and monitoring those patients at greatest risk for developing an ADR. Groups at greatest risk for developing ADRs include the elderly, children, and pregnant patients, as well as others. Pharmacovigilance must be effectively practiced by all health care providers in order to avoid ADRs.
Wooten, James M
Pharmacovigilance is the process of identifying, monitoring, and effectively reducing adverse drug reactions. Adverse drug reactions (ADRs) are an important consideration when assessing a patient's health. The proliferation of new pharmaceuticals means that the incidence of ADRs is increasing. The goal for all health care providers must be to minimize the risk of ADRs as much as possible. Steps to achieve this include understanding the pharmacology for all drugs prescribed and proactively assessing and monitoring those patients at greatest risk for developing an ADR. Groups at greatest risk for developing ADRs include the elderly, children, and pregnant patients, as well as others. Pharmacovigilance must effectively be practiced by all health providers in order to avoid ADRs.
Gurmesa, Lense Temesgen
Background. Adverse drug reactions are global problems of major concern. Adverse drug reaction reporting helps the drug monitoring system to detect the unwanted effects of those drugs which are already in the market. Aims. To assess the knowledge, attitude, and practice of health care professionals working in Nekemte town towards adverse drug reaction reporting. Methods and Materials. A cross-sectional study design was conducted on a total of 133 health care professionals by interview to assess their knowledge, attitude, and practice using structured questionnaire. Results. Of the total respondents, only 64 (48.2%), 56 (42.1%), and 13 (9.8%) health care professionals have correctly answered the knowledge, attitude, and practice assessment questions, respectively. Lack of awareness and knowledge on what, when, and to whom to report adverse drug reactions and lack of commitments of health care professionals were identified as the major discouraging factors against adverse drug reaction reporting. Conclusion. This study has revealed that the knowledge, attitude, and practice of the health care professionals working in Nekemte town towards spontaneous adverse drug reaction reporting were low that we would like to recommend the concerned bodies to strive on the improvement of the knowledge, attitude, and practice status of health care professionals. PMID:28042569
Alsbou, Mohammed; Alzubiedi, Sameh; Alzobi, Hamed; Samhadanah, Nawal Abu; Alsaraireh, Yousef; Alrawashdeh, Omar; Aqel, Amin; Al-Salem, Khalil
Adverse drug reactions (ADRs) represent a major health care problem. To identify the most common ADRs, drugs implicated in ADRs, and to assess their causality, severity, preventability and risk factors predisposing to reported ADRs in Jordan. Al-Karak teaching hospital, southern of Jordan. Method A cross sectional observational study was carried out for 11 months from January to November 2013. Suspected ADRs were recorded in ADRs report forms and analyzed for causality, severity, and preventability. Most common ADRs, drugs involved in these ADRs, causality, severity, and preventability of suspected ADRs. A total of 64 reports were received. Some patients suffered more than one ADR. The total number of ADRs identified was 108. Forty one drugs were involved in causing these ADRs. About 2/3 of adverse reactions (73.4 %) did not cause admission to the hospital, whereas 26.6 % of the ADRs resulted in admission. Majority of the ADRs were type A (62.5 %). Most of ADRs (92.2 %) were assessed as probable. Nearly, 65.6 % of ADRs were categorized as mild. Majority of ADRs were assessed as "not preventable" (75 %). The most common classes of drugs involved in ADRs were antibiotics, analgesics, vaccines and antiepileptics. The most commonly identified ADRs were abdominal pain, skin rash, shortness of breath, fever, upper gastrointestinal bleeding and vomiting. Risk factors contributed to ADRs were age and polypharmacy. Jordanian healthcare providers should be aware of the importance of detecting and reporting ADRs, in order to prevent and reduce the incidence of ADRs. Awareness of risk factors predisposing to ADRs may help in identifying patients with higher risk and therefore reducing the risk of these ADRs and improving patient outcome.
Jacquot, Julien; Bagheri, Haleh; Montastruc, Jean-Louis
In August 2012, general practitioners of Haute- Garonne received a letter from Health insurance system, informing that prescriptions could be endorsed by "not substituable" after reporting an adverse drug reactions (ADR). Compared to an equivalent period before this letter, we observed an increase of ADRs reports for generics, mainly concerning gastrointestinal ADR and lack of efficacy.
Gallelli, Luca; Siniscalchi, Antonio; Palleria, Caterina; Mumoli, Laura; Staltari, Orietta; Squillace, Aida; Maida, Francesca; Russo, Emilio; Gratteri, Santo; De Sarro, Giovambattista
Drug treatment may be related with the development of adverse drug reactions (ADRs). Here, 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 April30, 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 this time, we analyzed 2870 clinical records and 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) 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 prescription on 11,138 (27.4%), with a mean of 6.1±0.29 drugs that was significantly higher (P<0.01) respect to patients that not experienced ADRs (mean of 3.4±0.13 drugs). About 19% of ADRs were not diagnosed and treated as new disease. In conclusion, we documented that age and gender are risk factors for the development of ADRs, that in some patients are under-diagnosed. Therefore, it is important to motivate healthcare to report the ADRs in order optimize the patient safety. Copyright© Bentham Science Publishers; For any queries, please email at email@example.com.
Lortie, F M
The surveillance of adverse drug reactions (ADRs) is an unqualified must. However, the optimal means of surveillance is still unclear. Although anecdotal reports are the backbone of an ADR surveillance system, they are not enough. The pharmaceutical industry, academics and regulatory agencies need to expand their efforts in monitoring ADRs. The author discusses the various techniques for counting and evaluating adverse reactions and suggests ways in which the system could be improved. PMID:3719483
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
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. .
Tuccori, Marco; Montagnani, Sabrina; Capogrosso-Sansone, Alice; Mantarro, Stefania; Antonioli, Luca; Fornai, Matteo; Blandizzi, Corrado
Oncology is one of the areas of medicine with the most active research being conducted on new drugs. New pharmacological entities frequently enter the clinical arena, and therefore, the safety profile of anticancer products deserves continuous monitoring. However, only very severe and (unusual) suspected adverse drug reactions (ADRs) are usually reported, since cancer patients develop ADRs very frequently and some practical selectivity must be used. Notably, a recent study was able to identify 76 serious ADRs reported in updated drug labels of oncologic drugs and 50% of them (n = 38) were potentially fatal. Of these, 49 and 58%, respectively, were not described in initial drug labels. The aims of this article are to provide an overview about spontaneous reporting of ADRs of oncologic drugs and to discuss the available methods to analyze the safety of anticancer drugs using databases of spontaneous ADR reporting.
White, Ryen W; Wang, Sheng; Pant, Apurv; Harpaz, Rave; Shukla, Pushpraj; Sun, Walter; DuMouchel, William; Horvitz, Eric
The timely and accurate identification of adverse drug reactions (ADRs) following drug approval is a persistent and serious public health challenge. Aggregated data drawn from anonymized logs of Web searchers has been shown to be a useful source of evidence for detecting ADRs. However, prior studies have been based on the analysis of established ADRs, the existence of which may already be known publically. Awareness of these ADRs can inject existing knowledge about the known ADRs into online content and online behavior, and thus raise questions about the ability of the behavioral log-based methods to detect new ADRs. In contrast to previous studies, we investigate the use of search logs for the early detection of known ADRs. We use a large set of recently labeled ADRs and negative controls to evaluate the ability of search logs to accurately detect ADRs in advance of their publication. We leverage the Internet Archive to estimate when evidence of an ADR first appeared in the public domain and adjust the index date in a backdated analysis. Our results demonstrate how search logs can be used to detect new ADRs, the central challenge in pharmacovigilance.
Wei, Xu; Xie, Yan-Ming
Adverse drug reaction (ADR) is the key contents in traditional Chinese medicine (TCM) injection safety research. However, influencing factors of ADR is not clearly, mechanism research is relatively rare, which are to be found in the literature to date. Qualified drugs and normal usage and dosage are the premise condition of ADR judgment. Age, sex, basic diseases, allergic constitution or drug allergy history are common factors. Kinds of solvent, drug concentration, storage time after liquid drug preparation, dripping speed, incompatibility of TCM injection and clinical commonly used medicine are the major ADR research factors. Adverse events mechanism should be synthetically judged by pre-clinical research, clinical manifestation, drug epidemiological trials results. In order to judge and study ADR correctly, It should be acquainted with TCM injection adverse events or ADR influencing factors,improve injection specification, and pay attention to the ADR mechanism, promote post-marketed reevaluation of safety in TCM injection.
Petrovic, Mirko; van der Cammen, Tischa; Onder, Graziano
Adverse drug reactions (ADRs) in older adults are an important healthcare problem since they are frequently a cause of hospitalization, occur commonly during admission, and are an important cause of morbidity and mortality. Older adults are particularly susceptible to ADRs because they are usually on multiple drug regimens and because age is associated with changes in pharmacokinetics and pharmacodynamics. The presentation of an ADR in older adults is often atypical, which further complicates its recognition. One potential strategy for improving recognition of ADRs is to identify those patients who are at risk of an ADR. The recently developed GerontoNet ADR Risk Score is a practical tool for identification of older patients who are at increased risk for an ADR and who may represent a target for interventions aimed at reducing ADRs. Provision of adequate education in the domain of clinical geriatric pharmacology can improve recognition of ADRs. Besides formal surveillance systems, built-in computer programs with electronic prescribing databases and clinical pharmacist involvement in patient care within multidisciplinary geriatric teams might help to minimize the occurrence of ADRs. In addition, a number of actions can be taken in hospitals to stimulate appropriate prescribing and to assure adequate communication between primary and hospital care. In older adults with complex medical problems and needs, a global evaluation obtained through a comprehensive geriatric assessment may be helpful in simplifying drug prescription and prioritizing pharmacological and healthcare needs, resulting in an improvement in quality of prescribing.
Fricke-Galindo, I; Jung-Cook, H; LLerena, A; López-López, M
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. Published by Elsevier España, S.L.U. All rights reserved.
Lövborg, Henrik; Eriksson, Linda Ring; Jönsson, Anna K; Bradley, Thomas; Hägg, Staffan
Adverse drug reactions (ADRs) are a major patient safety issue, and a substantial proportion of ADRs are, in fact, preventable. The aim of this study was to describe the proportion and pattern of preventable ADRs in spontaneously reported suspected ADRs and to study the feasibility of using data from an ADR reporting system for this purpose. All reports of ADRs, except those in which a vaccine was the suspected drug, submitted to the regional pharmacovigilance center of southeastern Sweden between 2008 and 2009 were analyzed. Causality between the suspected ADR and the medication was assessed using the World Health Organization (WHO) criteria, and preventability was assessed using Hallas criteria. During the study period, 1,290 ADRs were received and 1,255 were classified as having at least a possible causality between a reaction and a drug. Of these, 172 (14%) ADRs were considered preventable, 35 (20%) were classified as definitely preventable, and 137 (80%) as possibly preventable. Of all preventable ADRs, 96 (56%) were related to prescribing, 35 (20%) to administration, and 41 (24%) to clinical and laboratory monitoring of treatment. Warfarin, oxycodone, and ioversol were the most common drugs with preventable ADRs. This study found that a substantial part of reported ADRs are preventable. Most of these are related to drug prescription, suggesting that interventions aiming to reduce preventable ADRs should focus on this process. Moreover, systems for ADR reporting may be useful in the mission of reducing the unsafe use of drugs.
Background Reporting of adverse drug reactions (ADRs) has traditionally been the sole province of healthcare professionals. In the European Union, more countries have allowed consumers to report ADRs directly to the regulatory agencies. The aim of this study was to characterize ADRs reported by European consumer for nervous system medications. Methods ADRs reported by consumers for nervous system medications (ATC group N) from 2007 to 2011 and located in the European ADR database, EudraVigilance, were analysed. Data were categorized with respect to age and sex, category and seriousness of reported ADRs and medications. The unit of analysis was one ADR. Results We located 4766 ADRs reported for nervous system medications, and one half of these were serious including 19 deaths. Less than 5% of ADRs were reported in children. Totally, 58% of ADRs were reported for women, 42% for men. The majority of reported ADRs were of the types “nervous system disorders” (18% of total ADRs) followed by “psychiatric disorders” (18% of total ADRs) and “general disorders” (15% of total ADRs) which also were the system organ classes in which the majority of serious ADRs were found. ADR reports encompassed medicines from the therapeutic groups: antiepileptics (ATC group N03) (36% of total ADRs), parasympathomimetics (ATC group N07) (22% of total ADRs) and antidepressants ATC group N06A (9% of total ADRs). Antiepileptics were the therapeutic group with the highest share of serious ADRs (60%) followed by antidepressants (15%). Many serious ADRs were reported for pregabalin and varenicline. Conclusions The majority of ADRs from nervous system mediations reported by consumers that were identified from the EudraVigilance database were serious. The value of consumer reports in pharmacovigilance still remains unclarified. PMID:23763896
Chen, Xiaowen; Shi, Hongbo; Yang, Feng; Yang, Lei; Lv, Yingli; Wang, Shuyuan; Dai, Enyu; Sun, Dianjun; Jiang, Wei
Adverse drug reactions (ADRs) are responsible for drug failure in clinical trials and affect life quality of patients. The identification of ADRs during the early phases of drug development is an important task. Therefore, predicting potential protein targets eliciting ADRs is essential for understanding the pathogenesis of ADRs. In this study, we proposed a computational algorithm,Integrated Network for Protein-ADR relations (INPADR), to infer potential protein-ADR relations based on an integrated network. First, the integrated network was constructed by connecting the protein-protein interaction network and the ADR similarity network using known protein-ADR relations. Then, candidate protein-ADR relations were further prioritized by performing a random walk with restart on this integrated network. Leave-one-out cross validation was used to evaluate the ability of the INPADR. An AUC of 0.8486 was obtained, which was a significant improvement compared to previous methods. We also applied the INPADR to two ADRs to evaluate its accuracy. The results suggested that the INPADR is capable of finding novel protein-ADR relations. This study provides new insight to our understanding of ADRs. The predicted ADR-related proteins will provide a reference for preclinical safety pharmacology studies and facilitate the identification of ADRs during the early phases of drug development. PMID:27805066
Zhou, Zhi-Wei; Chen, Xiao-Wu; Sneed, Kevin B; Yang, Yin-Xue; Zhang, Xueji; He, Zhi-Xu; Chow, Kevin; Yang, Tianxin; Duan, Wei; Zhou, Shu-Feng
Adverse drug reactions (ADRs) are a major public health concern and cause significant patient morbidity and mortality. Pharmacogenomics is the study of how genetic polymorphisms affect an individual's response to pharmacotherapy at the level of a whole genome. This article updates our knowledge on how genetic polymorphisms of important genes alter the risk of ADR occurrence after an extensive literature search. To date, at least 244 pharmacogenes identified have been associated with ADRs of 176 clinically used drugs based on PharmGKB. At least 28 genes associated with the risk of ADRs have been listed by the Food and Drug Administration as pharmacogenomic biomarkers. With the availability of affordable and reliable testing tools, pharmacogenomics looks promising to predict, reduce, and minimize ADRs in selected populations.
Oshima, Shinji; Enjuji, Takako; Negishi, Akio; Akimoto, Hayato; Ohara, Kousuke; Okita, Mitsuyoshi; Numajiri, Sachihiko; Inoue, Naoko; Ohshima, Shigeru; Terao, Akira; Kobayashi, Daisuke
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.
Lo Russo, Lucio; Guida, Laura; Di Masi, Maria; Buccelli, Claudio; Giannatempo, Giovanni; Di Fede, Olga; Di Lorenzo, Pierpaolo; Lo Muzio, Lorenzo
Several drugs may have a number of adverse reactions (ADRs) involving the oro-facial region. The dose of the drug and the time required for the reaction to take place are relevant parameters; nonetheless, ADRs mechanisms are not always known and ADRs are not always predictable since aspects other than drug pharmacodynamics and/or pharmacokinetics, as well as various interacting variables contribute to the final outcome. All tissues and many functions of the oral cavity can be affected. In particular, salivary function is frequently involved and hypo-salivation is the main manifestation; several mucosal lesions with different morphology (ulcerations, vesiculobullous lesions, white lesions, pigmentations, swelling) are also possible. Taste, sensation and trigeminal function alterations have been reported and the recent evidence regarding the occurrence of jawbones osteonecrosis, especially in bisphosphonates treated patients, is increasing. Clinical management may be quite difficult due to the multiplicity of involved classes of drugs and substances (dental materials, foods), the variety of affected tissues and functions, the type of produced lesions and disturbances, the complexity of related pathogenetic mechanisms (if known), the difficulties in assessing causality and managing drug withdrawal and/or dose adjustment, as well as in establishing specific treatments, if any. In this paper the most common and significant oral ADRs, their related aspects and importance (including medico-legal implications) for health care providers will be discussed.
van Hunsel, Florence; de Waal, Susan; Härmark, Linda
The purpose of this study was to investigate the contribution of patient reports to signals sent by the Netherlands Pharmacovigilance Centre Lareb to the Dutch Medicines Evaluation Board and to determine if there are certain types of signals where patient report add a distinct contribution. All signals from 2010 until 2015 were included. First, we investigated how many patient reports were present in the signals and the characteristics of these reports compared to the health care professional and marketing authorization holders' reports. In addition to source, the analysis included ATC code of the drug, MedDRA® system organ class and preferred term for the adverse drug reaction (ADR), seriousness of the ADR, and 7 other factors like reports on over-the-counter medication, and how often an ADR listed in the important medical event terms list was present. Secondly, we determined the proportion of reports submitted by the individual groups to signals, in a cross-sectional manner. A total of 150 signals were included, including 1691 ADR reports. Our results show that 26.3% of all ADR reports in Dutch drug safety signals were reported by patients, and 30.5% of the patient reports in the signals contained one or more terms listed as important medical events. The proportion of reports by patients which were included the signals was 2% and 3.9% for health care professional reports and 0.2% for marketing authorization holders reports. Patients had an important contribution to signals overall, but especially for ADRs related to generic drug substitution and psychiatric ADRs. Copyright © 2017 John Wiley & Sons, Ltd.
Palaniappan, Muthiah; George, Melvin; Subramaniyan, Ganesan; Dkhar, Steven Aibor; Pillai, Ajith Ananthakrishna; Jayaraman, Balachander; Chandrasekaran, Adithan
Background Cardiovascular diseases (CVD) are one of the leading causes of non-communicable disease related deaths globally. Patients with cardiovascular diseases are often prescribed multiple drugs and have higher risk for developing more adverse drug reactions due to polypharmacy. Aim To evaluate the pattern of adverse drug reactions reported with cardiovascular drugs in an adverse drug reaction monitoring centre (AMC) of a tertiary care hospital. Settings and Design Adverse drug reactions related to cardiovascular drugs reported to an AMC of a tertiary care hospital were included in this prospective observational study. Materials and Methods All cardiovascular drugs related adverse drug reactions (ADRs) received in AMC through spontaneous reporting system and active surveillance method from January 2011 to March 2013 were analysed for demographic profile, ADR pattern, severity and causality assessment. Statistical Analysis used The study used descriptive statistics and the values were expressed in numbers and percentages. Results During the study period, a total of 463 ADRs were reported from 397 patients which included 319 males (80.4%) and 78 females (19.6%). The cardiovascular drug related reports constituted 18.1% of the total 2188 ADR reports. In this study, the most common ADRs observed were cough (17.3%), gastritis (7.5%) and fatigue (6.5%). Assessment of ADRs using WHO-causality scale revealed that 62% of ADRs were possible, 28.2% certain and 6.8% probable. As per Naranjo’s scale most of the reports were possible (68.8%) followed by probable (29.7%). According to Hartwig severity scale majority of the reports were mild (95%) followed by moderate (4.5%). A system wise classification of ADRs showed that gastrointestinal system (20.7%) related reactions were the most frequently observed adverse reactions followed by respiratory system (18.4%) related adverse effects. From the reported ADRs, the drugs most commonly associated with ADRs were found to be
Machado-Alba, Jorge Enrique; Londoño-Builes, Manuel José; Echeverri-Cataño, Luis Felipe; Ochoa-Orozco, Sergio Andrés
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.
Saheb Sharif-Askari, Fatemeh; Saheb Sharif-Askari, Narjes; Javadi, Mohammadreza; Gholami, Kheirollah
Burden of adverse drug reactions (ADRs), in home-environment and domestic settings, is unknown. To discuss the epidemiology of reported ADRs to 13-Aban drug and poison information center (DPIC) and to discuss the burden of hospitalization caused by these ADRs from commonly implicated therapeutic groups. A retrospective analysis of the yellow card schemes of suspected ADRs reported to the 13-Aban DPIC was conducted from 21 March 2013 to 21 November 2016 inclusive. Characteristics of the ADRs, such as the sex and age of the patient, the therapeutic group involved, and the medical outcome of the exposure, were examined. ADR Hospitalization (ADRH) index was calculated for each drug group by dividing the number of ADR-related hospitalizations with total number of reported ADR cases (n = 748), and then multiplying by 100. ADRs were reported for 748 patients representing 5 cases per 1000 enquiries to the 13-Aban DPIC over almost 4-years of the study period. Public were responsible for reporting every 4 out of 5 ADR cases (n = 651, 87%) and the remaining 1 out of 5 ADR cases was reported by the health care professionals (n = 97, 13%). Most of the ADRs had a medical outcome documented as having a minor effect or were minimally bothersome to the patients (n = 509, 68%), and less than 4.9% (n = 37) were documented as having a major effect or were life-threatening. Overall, 7.4% (n = 55) of ADRs were resulted in hospitalization. Antibacterials for systemic use represented the therapeutic group with the highest hospitalization index (1.7%). The study concluded that ADRs to antibiotics are common and some of them resulted in hospitalization.
Egger, Sabin S; Krähenbühl, Stephan; Schlienger, Raymond G
Dentists may be confronted with adverse drug reactions (ADRs) in their dental practice, and are--like other health professionals--obliged to report certain ADRs. The aim of this article is to sensitise dentists for this topic, to show how to proceed in case of a supposed ADR, and to emphasise the importance of spontaneous reporting of ADRs. ADRs may not always be clearly distinguished from symptoms of underlying diseases, and in cases of polypharmacy multiple drugs may be responsible for the reaction. It is therefore important to get a detailed medical history, and to establish a temporal relationship between start of a therapy and appearance of the symptom. Information from the medical literature, exclusion of other possible causes, and identification of risk factors help to confirm a causal relationship between a suspected drug and an observed reaction. In Switzerland severe and unexpected ADRs have to be reported to one of the regional Pharmacovigilance centres with the yellow ADR reporting form from Swissmedic. The spontaneous reports of ADRs help to early identify new problems of a drug therapy, and permit to take measures to minimise the risk.
Cao, D-S; Xiao, N; Li, Y-J; Zeng, W-B; Liang, Y-Z; Lu, A-P; Xu, Q-S; Chen, AF
Identifying potential adverse drug reactions (ADRs) is critically important for drug discovery and public health. Here we developed a multiple evidence fusion (MEF) method for the large-scale prediction of drug ADRs that can handle both approved drugs and novel molecules. MEF is based on the similarity reference by collaborative filtering, and integrates multiple similarity measures from various data types, taking advantage of the complementarity in the data. We used MEF to integrate drug-related and ADR-related data from multiple levels, including the network structural data formed by known drug–ADR relationships for predicting likely unknown ADRs. On cross-validation, it obtains high sensitivity and specificity, substantially outperforming existing methods that utilize single or a few data types. We validated our prediction by their overlap with drug–ADR associations that are known in databases. The proposed computational method could be used for complementary hypothesis generation and rapid analysis of potential drug–ADR interactions. PMID:26451329
Abubakar, Abdullahi Rabiu; Chedi, Bashir A Z; Mohammed, Khalid Garba; Haque, Mainul
Spontaneous reporting (SPR) and intensive monitoring are the conventional systems used for detecting, recording, and reporting adverse drug reactions (ADRs). Using spontaneous reporting a lot of successes has been made as existing ADRs were identified and new ones prevented through this methods. The aim of this appraisal was to evaluate the knowledge, attitude, and the practice of medical students with regards to ADRs reporting and to see if differences exist between the level of study and genders. The questionnaire was adopted, modified, and validated from previous studies. It comprised of 25 questions. It was administered year-IV and V medical students of Bayero University Kano, Nigeria. The data collected were coded and analyzed using the Statistical Package for the Social Sciences (SPSS) version 20, currently known as IBM SPSS Statistics. The response rate was 74%. Among the 108 participants, 80% got the definition of ADRs correct; 63% of them knew the precise functions of pharmacovigilance (PV). In addition, 82% strongly agreed that ADR reporting is health care workers responsibility; 82% also said PV should be taught in detail. Meanwhile, 99% have noticed patient experiencing ADRs; 67% said even mild ADRs should be reported. The outcome of this study showed good knowledge and attitude with respect to ADRs and PV among the medical students surveyed. Unfortunately, the practice of medical students was found to be unsatisfactory. There is a need to upgrade the students teaching the curriculum with respect to ADRs monitoring.
Davies, Emma C; Green, Christophe F; Mottram, David R; Pirmohamed, Munir
The serious nature of adverse drug reactions (ADRs) has been highlighted in a number of instances over the last forty years, the most recent of these being the occurrence of serious thrombotic events with the use of COX-2 inhibitors. ADRs are estimated to be between the 4(th) and 6(th) leading cause of death in the USA, with fatal ADRs occurring in 0.32% of patients. A recent UK study showed that 6.5% of hospital admissions were related to ADRs. ADRs can therefore be regarded as a significant public health and economic problem. There is an urgent need to develop better preventive strategies to reduce the burden of ADRs. Because ADRs can affect any bodily system, can have many different clinical presentations, and are of widely variable severity, prevention will not be easy and will have to be multifactorial in its approach. This paper reviews the epidemiology of ADRs in hospitals and evaluates the research that has been undertaken to date to prevent ADRs.
Witcher, Robert; Dzierba, Amy L.; Kim, Catherine; Smithburger, Pamela L.; Kane-Gill, Sandra L.
Background: Therapeutic hypothermia (TH) improves survival and neurologic function in comatose survivors of cardiac arrest. Many medications used to support TH have altered pharmacokinetics and pharmacodynamics during this treatment. It is unknown if or at what frequency the medications used during TH cause adverse drug reactions (ADRs). Methods: A retrospective chart review was conducted for patients admitted to an intensive care unit (ICU) after cardiac arrest and treated with TH from January 2009 to June 2012 at two urban, university-affiliated, tertiary-care medical centres. Medications commonly used during TH were screened for association with significant ADRs (grade 3 or greater per Common Terminology Criteria for Adverse Events) using three published ADR detection instruments. Results: A total of 229 patients were included, the majority being males with median age of 62 presenting with an out-of-hospital cardiac arrest in pulseless electrical activity or asystole. The most common comorbidities were hypertension, coronary artery disease, and diabetes mellitus. There were 670 possible ADRs and 69 probable ADRs identified. Of the 670 possible ADRs, propofol, fentanyl, and acetaminophen were the most common drugs associated with ADRs. Whereas fentanyl, insulin, and propofol were the most common drugs associated with a probable ADR. Patients were managed with TH for a median of 22 hours, with 38% of patients surviving to hospital discharge. Conclusions: Patients undergoing TH after cardiac arrest frequently experience possible adverse reactions associated with medications and the corresponding laboratory abnormalities are significant. There is a need for judicious use and close monitoring of drugs in the setting of TH until recommendations for dose adjustments are available to help prevent ADRs.
Smyth, Rebecca Mary Diane; Gargon, Elizabeth; Kirkham, Jamie; Cresswell, Lynne; Golder, Su; Smyth, Rosalind; Williamson, Paula
Background Adverse drug reactions in children are an important public health problem. We have undertaken a systematic review of observational studies in children in three settings: causing admission to hospital, occurring during hospital stay and occurring in the community. We were particularly interested in understanding how ADRs might be better detected, assessed and avoided. Methods and Findings We searched nineteen electronic databases using a comprehensive search strategy. In total, 102 studies were included. The primary outcome was any clinical event described as an adverse drug reaction to one or more drugs. Additional information relating to the ADR was collected: associated drug classification; clinical presentation; associated risk factors; methods used for assessing causality, severity, and avoidability. Seventy one percent (72/102) of studies assessed causality, and thirty four percent (34/102) performed a severity assessment. Only nineteen studies (19%) assessed avoidability. Incidence rates for ADRs causing hospital admission ranged from 0.4% to 10.3% of all children (pooled estimate of 2.9% (2.6%, 3.1%)) and from 0.6% to 16.8% of all children exposed to a drug during hospital stay. Anti-infectives and anti-epileptics were the most frequently reported therapeutic class associated with ADRs in children admitted to hospital (17 studies; 12 studies respectively) and children in hospital (24 studies; 14 studies respectively), while anti-infectives and non-steroidal anti-inflammatory drugs (NSAIDs) were frequently reported as associated with ADRs in outpatient children (13 studies; 6 studies respectively). Fourteen studies reported rates ranging from 7%–98% of ADRs being either definitely/possibly avoidable. Conclusions There is extensive literature which investigates ADRs in children. Although these studies provide estimates of incidence in different settings and some indication of the therapeutic classes most frequently associated with ADRs, further
Gotta, Verena; van den Anker, Johannes; Pfister, Marc
Developmental pharmacology influences the safety profile of drugs in pediatrics. Altered pharmacokinetics and/ or pharmacodynamics of drugs make pediatric patients susceptible to adverse drug reactions (ADRs), especially infants and newborns. Since the efficacy/ safety balance of most available drugs has not been formally evaluated in pediatric clinical trials, optimal dosing is rarely known in pediatrics. Suboptimal pediatric drug formulations make dose optimization even more difficult exposing pediatric patients to medication errors like overdosing and associated ADRs. We provide an overview of pediatric ADRs and discuss recent regulatory and pharmacological measures to understand and reduce risk of ADRs in pediatric patients.
Tian, Xiao-Yin; Liu, Bing; Shi, Hao; Zhao, Zi-Ran; Zhou, Xi-Ping; Zhang, Tao; Sun, Qiu-Ning; Zuo, Ya-Gang
Cutaneous adverse drug reactions (ADRs) are common. However, no prospective study assessing cutaneous ADRs is available for Chinese populations. This study aimed to assess the incidence, manifestations, causative drugs, and other factors related to cutaneous ADRs. A total of 22,866 inpatients were surveyed prospectively from January to April 2012 at the Peking Union Medical College Hospital. Only cutaneous ADRs induced by systemic drugs were considered. Fifty cases were confirmed as cutaneous ADRs, for an estimated incidence of 2.2 per 1000 during this period (95 % confidence interval 1.6-2.8). Cases of cutaneous ADRs comprised 69 % females, while 63 % of all inpatients were female (χ (2) = 0.641, P = 0.427). The department of infectious diseases was the most frequently involved department. Morbilliform exanthema (40 %) was the most frequent cutaneous ADR, followed by urticaria (23.1 %). Anti-infection drugs (36.9 %) caused most cases of cutaneous ADRs, followed by iodinated contrast media (ICM, 18.5 %) and non-steroidal anti-inflammatory drugs (NSAIDs, 18.5 %). The most frequently associated disorders were cancer (24 %), infection (22 %), cardiovascular and cerebrovascular diseases (20 %), and autoimmune diseases (18 %). In this first prospective study assessing the incidence of cutaneous ADRs in China, anti-infection drugs were the most commonly involved drugs, followed by ICM and NSAIDs. No evidence of increased cutaneous ADR incidence in AIDS or SLE patients was observed. Our findings indicate that cancer and its treatments were often related to cutaneous ADRs in China.
Zurita-Garaicoechea, Ana; Reis-Carvalho, Joana; Ripa-Aisa, Irantzu; Jiménez-Mendoza, Ana; Díaz-Balén, Almudena; Oroviogoicoechea, Cristina
The spontaneous report system, in which suspected adverse drug reaction (ADR) are reported by healthcare workers, is currently one of the primary methods to prevent and discover new and serious ADR to marketed medicinal products. The collaboration of nursing professionals with this task makes it possible to improve patient safety and to reduce ADR costs. Although a total of 781 cases of ADR cases were reported in Navarra in 2011, only 7.33% were reported by nurses. The objectives werw to determine the factors that influence nurses in reporting of ADR, and second, to devise strategies which help to increase reporting. A bibliographic search for articles that included the words: reacciones adversas medicamentosas (adverse drug reactions), notificación (reporting) and enfermería (nursing) was conducted using the PubMed and Cinhal databases. A total of 107 articles were retrieved, of which 27 were selected according to inclusion and exclusion criteria. The conclusion learned by reading and analyzing the selected articles was that the factors that affect the notification depend on the attitude of the notifier, as well as personal and professional factors. The main strategies to encourage notification are education and training, motivation, and the availability of facilitating tools. The main factors that have an influence on under-notification are the lack of knowledge and motivation among professionals. To solve the problem of under-notification, the main actions and strategies to undertake are education, motivation and persistence. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.
Finkelstein, Joseph; Chen, Qinlang; Adams, Hayden; Friedman, Carol
Academic literature provides rich and up-to-date information concerning adverse drug reactions (ADR), but it is time consuming and labor intensive for physicians to obtain information of ADRs from academic literature because they would have to generate queries, review retrieved articles and summarize the results. In this study, a method is developed to automatically detect and summarize ADRs from journal articles, rank them and present them to physicians in a user-friendly interface. The method studied ADRs for 6 drugs and returned on average 4.8 ADRs that were correct. The results demonstrated this method was feasible and effective. This method can be applied in clinical practice for assisting physicians to efficiently obtain information about ADRs associated with specific drugs. Automated summarization of ADR information from recent publications may facilitate translation of academic research into actionable information at point of care. PMID:27570654
Rosli, Rosliana; Ming, Long Chiau; Abd Aziz, Noorizan; Manan, Mohamed Mansor
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. 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. 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. ADR reports concerning vaccines and anti-infectives were the most commonly reported in children, and are mainly seen in adolescents, with most of the
Rosli, Rosliana; Abd Aziz, Noorizan; Manan, Mohamed Mansor
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
Alomar, Muaed Jamal
Objectives To discuss the effect of certain factors on the occurrence of Adverse Drug Reactions (ADRs). Data Sources A systematic review of the literature in the period between 1991 and 2012 was made based on PubMed, the Cochrane database of systematic reviews, EMBASE and IDIS. Key words used were: medication error, adverse drug reaction, iatrogenic disease factors, ambulatory care, primary health care, side effects and treatment hazards. Summary Many factors play a crucial role in the occurrence of ADRs, some of these are patient related, drug related or socially related factors. Age for instance has a very critical impact on the occurrence of ADRs, both very young and very old patients are more vulnerable to these reactions than other age groups. Alcohol intake also has a crucial impact on ADRs. Other factors are gender, race, pregnancy, breast feeding, kidney problems, liver function, drug dose and frequency and many other factors. The effect of these factors on ADRs is well documented in the medical literature. Taking these factors into consideration during medical evaluation enables medical practitioners to choose the best drug regimen. Conclusion Many factors affect the occurrence of ADRs. Some of these factors can be changed like smoking or alcohol intake others cannot be changed like age, presence of other diseases or genetic factors. Understanding the different effects of these factors on ADRs enables healthcare professionals to choose the most appropriate medication for that particular patient. It also helps the healthcare professionals to give the best advice to patients. Pharmacogenomics is the most recent science which emphasizes the genetic predisposition of ADRs. This innovative science provides a new perspective in dealing with the decision making process of drug selection. PMID:24648818
Visacri, Marília Berlofa; de Souza, Cinthia Madeira; Sato, Catarina Miyako Shibata; Granja, Silvia; de Marialva, Mécia; Mazzola, Priscila Gava; Moriel, Patricia
Objectives The aim of this study was to determine the frequency and profile of spontaneous reports of Adverse Drug Reactions (ADRs) and quality deviations in a Brazilian teaching hospital and propose a consistent classification to study quality deviations. Methods This is a descriptive and retrospective study involving the analysis of spontaneous reports of ADRs and quality deviations in 2010. ADRs were classified according to the reaction mechanism, severity, and causality. The drugs were classified according to their therapeutic classes and symptoms according to the affected organ. The quality deviations were classified according to the type of deviation and type of medicine available in the Brazilian market. Results A total of 68 forms were examined; ADRs accounted for 39.7% of the notifications, while quality deviations accounted for 60.3%. ADRs occurred more frequently in men (51.9%) and adults (63.0%). The skin (28.0%) was the most affected organ, while anti-infectives (40.7%) were the therapeutic class that caused the most ADRs. The most common ADRs were type B (74.0%), moderates (37.0%), and probables (55.6%). In relation to quality deviations, the most frequent notifications were breaks, splits and leaks (20.9%) and related to generic drugs (43.9%). Conclusion The classification system to study quality deviations was clear and consistent. This study demonstrated that practices and public policies related to more effective pharmacovigilance need to be implemented so that the number of spontaneous reports increases. PMID:25972731
Bellis, Jennifer R; Kirkham, Jamie J; Nunn, Anthony J; Pirmohamed, Munir
National Health Service (NHS) hospitals in the UK use a system of coding for patient episodes. The coding system used is the International Classification of Disease (ICD-10). There are ICD-10 codes which may be associated with adverse drug reactions (ADRs) and there is a possibility of using these codes for ADR surveillance. This study aimed to determine whether ADRs prospectively identified in children admitted to a paediatric hospital were coded appropriately using ICD-10. The electronic admission abstract for each patient with at least one ADR was reviewed. A record was made of whether the ADR(s) had been coded using ICD-10. Of 241 ADRs, 76 (31.5%) were coded using at least one ICD-10 ADR code. Of the oncology ADRs, 70/115 (61%) were coded using an ICD-10 ADR code compared with 6/126 (4.8%) non-oncology ADRs (difference in proportions 56%, 95% CI 46.2% to 65.8%; p < 0.001). The majority of ADRs detected in a prospective study at a paediatric centre would not have been identified if the study had relied on ICD-10 codes as a single means of detection. Data derived from administrative healthcare databases are not reliable for identifying ADRs by themselves, but may complement other methods of detection.
Lin, Shih-Fang; Xiao, Ke-Ting; Huang, Yu-Ting; Chiu, Chung-Cheng; Soo, Von-Wun
The purpose of this study was to integrate knowledge about drugs, drug targets, and topological methods. The goals were to build a system facilitating the study of adverse drug events, to make it easier to find possible explanations, and to group similar drug-drug interaction cases in the adverse drug reaction reports from the US Food and Drug Administration (FDA). We developed a system that analyses adverse drug reaction (ADR) cases reported by the FDA. The system contains four modules. First, we integrate drug and drug target databases that provide information related to adverse drug reactions. Second, we classify drug and drug targets according to anatomical therapeutic chemical classification (ATC) and drug target ontology (DTO). Third, we build drug target networks based on drug and drug target databases. Finally, we apply topological analysis to reveal drug interaction complexity for each ADR case reported by the FDA. We picked 1952 ADR cases from the years 2005-2006. Our dataset consisted of 1952 cases, of which 1471 cases involved ADR targets, 845 cases involved absorption, distribution, metabolism, and excretion (ADME) targets, and 507 cases involved some drugs acting on the same targets, namely, common targets (CTs). We then investigated the cases involving ADR targets, ADME targets, and CTs using the ATC system and DTO. In the cases that led to death, the average number of common targets (NCTs) was 0.879 and the average of average clustering coefficient (ACC) was 0.067. In cases that did not lead to death, the average NCTs was 0.551, and the average of ACC was 0.039. We implemented a system that can find possible explanations and cluster similar ADR cases reported by the FDA. We found that the average of ACC and the average NCTs in cases leading to death are higher than in cases not leading to death, suggesting that the interactions in cases leading to death are generally more complicated than in cases not leading to death. This indicates that our system
Fattinger, Karin; Roos, Malgorzata; Vergères, Patrice; Holenstein, Clemens; Kind, Brigitt; Masche, Urspeter; Stocker, David N; Braunschweig, Suzanne; Kullak-Ublick, Gerd A; Galeazzi, Renato L; Follath, Ferenc; Gasser, Theo; Meier, Peter J
Aims To explore drug exposure, frequency of adverse drug reactions (ADRs), types of ADRs, predisposing risk factors and ADR-related excess hospital stay in medical inpatients. Methods Structured data regarding patient characteristics, ‘events’ (symptoms, laboratory results), diagnoses (ICD10) and drug therapy were collected using a computer-supported data entry system and an interface for data retrieval from electronic patient records. ADR data were collected by ‘event monitoring’ to minimize possible bias by the drug monitor. The causality of each event was assessed in relation to disease(s) and drug therapy. Results The analysis included 4331 (100%) hospitalizations. The median observation period was 8 days. The median number of different drugs administered per patient and day was 6 and varied between 4 (Q1) and 9 (Q3) different drugs in 50% of all hospital days. In 41% of all hospitalizations at least one disease-unrelated event could be possibly attributed to drug therapy. Clinically relevant ADRs occurred in 11% of all hospitalizations. In 3.3% of all hospitalizations ADRs were the cause of hospital admission. The incidence of possibly ADR-related deaths was 1.4. Factors predisposing for clinically relevant ADRs were female gender and polypharmacy. ADR-related excess hospital stay accounted for 8.6% of hospital days. Conclusions These data demonstrate the feasibility of the developed ‘event monitoring’ system for quantitative analysis of ADRs in medical inpatients. With increasing numbers of recorded patients the pharmacoepidemiological database provides a valuable tool to study specific questions regarding drug efficacy and safety in hospitalized patients. PMID:10671911
Martínez-Mir, Inocencia; García-López, Mercedes; Palop, Vicente; Ferrer, José M; Rubio, Elena; Morales-Olivas, Francisco J
Aims There are few publications of adverse drug reactions (ADRs) among paediatric patients, though ADR incidence is usually stated to be higher during the first year of life and in male patients. We have carried out a prospective study to assess the extent, pattern and profile risk for ADRs in hospitalized patients between 1 and 24 months of age. Methods An intensive events monitoring scheme was used. A total of 512 successive admissions to two medical paediatric wards (47 beds) were analysed. The hospital records were screened daily during two periods (summer, 105 days and winter, 99 days), and adverse clinical events observed were recorded. Results A total of 282 events were detected; of these, 112 were considered to be manifestations of ADRs. The cumulative incidence was 16.6%, no differences being observed between periods. Although there were no differences between patients under and over 12 months of age, risk was found to be significantly higher among girls compared with boys (RR = 1.66, 95% CI 1.03–2.52). The gastro-intestinal system was most frequently affected. The therapeutic group most commonly implicated was anti-infective drugs and vaccines (41.5%). The ADRs were mild or moderate in over 90% of cases. A consistent relationship was noted between the number of drugs administered and the incidence of ADRs. Conclusions Hospitalized patients exhibited an ADR risk profile that included female sex and the number of drugs administered. No particular age predisposition was observed. The most commonly prescribed drugs are those most often implicated in ADRs in paediatric patients. PMID:10383547
Bansal, Dipika; Azad, Chandrika; Kaur, Manpreet; Rudroju, Neelima; Vepa, Pravallika; Guglani, Vishal
The present study investigates the pattern and predictors of treatment-emergent adverse drug reactions (ADRs) in children diagnosed with epilepsy. We conducted prospective observational study in a tertiary care teaching hospital on 277 epileptic children. Antiepileptic drug (AED)-associated ADRs, demographic and clinical characteristics, AED regimen, and so on were recorded. Causality, severity, and preventability were performed by World Health Organization-Uppsala Monitoring Center scale, Hartwig's severity scale, and Schumock and Thornton questionnaire, respectively. Of the enrolled population, 53% children had symptomatic epilepsy, and 51% were in 5- to 10-year age group. More than two-thirds of children were on monotherapy, with phenytoin (n = 176, 63.5%) being the most common AED. Three hundred fifty-three AED-related ADRs were recorded in 175 children (63.2%). Poor scholastic performance (19%) was the most common ADR, followed by gum hypertrophy (13.3%), headache (10.2%), behavioral problems (5.7%), drowsiness (5.7%), and others. Two hundred sixteen ADRs were probable, and 126 ADRs were possible. Severe ADRs were noted in 6 children. Girls (odds ratio [OR], 1.93; 95% confidence interval [95% CI], 1.07-3.45; P = 0.03), children with secondary epilepsy (OR, 3.31; 95% CI, 1.76-6.23; P ≤ 0.001), children older than 5 years (5-10 years; OR, 6.28; 95% CI, 2.79-14.12; P ≤ 0.001), and those older than 10 years (OR, 9.04; 95% CI, 3.69-22.17; P ≤ 0.001) were found to be at higher risk of experiencing ADRs. Monotherapy was the preferred treatment. Phenytoin was the most common ADR causative agent. Female sex, symptomatic epilepsy, and older age (> 5 years) were found to be associated with higher probability of ADR development.
Trubiano, Jason A; Aung, Ar Kar; Nguyen, Mary; Fehily, Sasha R; Graudins, Linda; Cleland, Heather; Padiglione, Alex; Peleg, Anton Y
The difference in clinical presentation, causality assessments, and outcomes of patients with delayed antibiotic-associated cutaneous adverse drug reactions (AA-cADR) and nonantibiotic-associated (NA)-cADR is ill defined. We examined the etiology of AA-cADR, with regard to the type of antibiotic exposure, allergy labeling, and patient outcomes, in comparison with NA-cADR. A retrospective observational inpatient cohort study of cADR was performed from January 2004 to August 2014. Patients were divided into AA-cADR and NA-cADR groups for analysis. cADR was defined as erythema multiforme, fixed drug eruption, acute generalized erythematous pustulosis, drug reaction with eosinophilia and systemic symptoms (DRESS), drug-associated linear IgA disease, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Of the 84 patients with cADR, 48% were AA-cADR. Male sex (60% vs 32%, P = .004), median length of stay (14.5 vs 11 days, P = .05), median Charlson comorbidity index (3 vs 1, P = .03), and inpatient mortality (20% vs 5%, P = .04) were higher in AA-cADR compared with NA-cADR. The median drug latency was lower in AA-cADR (6 vs 20 days, P = .001). Sulfonamide antibiotics and glycopeptides were implicated in 20% of AA-cADR. DRESS was more frequently reported in AA-cADR. After cADR diagnosis, further antibiotic therapy was administered in 64% of patients, higher in AA-cADR (75%, 30 of 40) compared with NA-cADR (55%, 24 of 44) (P = .06). Fluoroquinolones (53% vs 21%, P = .02), glycopeptides (vancomycin and teicoplanin; 70% vs 38%, P = .05), and carbapenems (33% vs 13%, P = .11) were used more commonly in AA-cADR. Antibiotics were the cause of cADR requiring hospital admission in 48% of episodes, and were associated with longer length of stay, higher age-adjusted Charlson comorbidity index, shorter drug latency, and mortality. In AA-cADR, glycopeptide and sulfonamide antibiotic exposure predominated. Copyright © 2016 American Academy of Allergy, Asthma & Immunology
Rydberg, Diana M.; Holm, Lennart; Engqvist, Ida; Fryckstedt, Jessica; Lindh, Jonatan D.; Stiller, Carl-Olav; Asker-Hagelberg, Charlotte
Purpose To identify the prevalence and preventability of adverse drug reactions (ADRs) in an emergency ward setting in a tertiary hospital in Sweden and to what extent the detected ADRs were reported to the Medical Product Agency (MPA). Methods In this prospective cross sectional observational study, 706 patients admitted to one of the Emergency Wards, at the Karolinska University Hospital in Solna, Stockholm during September 2008 –September 2009, were included. The electronic patient records were reviewed for patients’ demographic parameters, prevalence of possible ADRs and assessment of their preventability. In addition, the extent of formal and required ADR reporting to national registers was studied. Results Approximately 40 percent of the patient population had at least one possible ADR (n = 284). In the multivariable regression model, age and number of drugs were significantly associated with risk of presenting with an ADR (p<0.01 and p<0.001, respectively). Sex was not identified as a significant predictor of ADRs (p = 0.27). The most common ADRs were cardiovascular, followed by electrolyte disturbances, and hemorrhage. In 18 percent of the patient population ADRs were the reason for admission or had contributed to admission and 24% of these ADRs were assessed as preventable. The under-reporting of ADRs to the MPA was 99%. Conclusions ADRs are common in Emergency Medicine in tertiary care in Sweden, but under-reporting of ADRs is substantial. The most frequent ADRs are caused by cardiovascular drugs, and significantly associated with age and number of drugs. However, only a minority of the detected serious ADRs contributing to admission could have been avoided by increased risk awareness. PMID:27622270
Wang, Xiao-Fang; Wang, Chun; Qin, You-Wen; Yan, Shi-Ke; Gao, Yan-Rong
This study was purposed to explore the mechanisms of drug resistance of HL-60/ADR cells and to compare the reversal drug-resistance effects of antisense oligonucleotides (AS ODN) of XIAP (X-linked inhibitor of apoptosis protein) and AS ODNs of MRP (multidrug resistance-associated protein) by use alone or in combination. Reverse transcription-PCR and Western blot were applied to detect the expression of XIAP, BCL-2, MRP and MDR1 in mRNA and protein levels of HL-60 cells and HL-60/ADR cells, respectively. Fully phosphorothioated AS ODN of XIAP and MRP was delivered into HL-60/ADR cells with Lipofectamine 2000 in the form of liposome-ODN complexes alone or in combination. CCK-8 cell viability assay was used to determine the effect of AS ODN of XIAP and MRP used alone or in combination on the chemotherapy sensitivity of HL-60/ADR cells to daunorubicin (DNR). Reverse transcription-PCR and Western blot were applied to examine the changes of XIAP, MRP in mRNA and protein levels respectively. The results showed that MRP and XIAP were both significantly higher in HL-60/ADR cells than those in HL-60 cells. AS ODN of XIAP and MRP down-regulated the expression of XIAP and MRP in HL-60/ADR cells and increased the sensitivity of HL-60/ADR cells to DNR, respectively. AS ODN of XIAP + MRP did not enhance the inhibition expression of XIAP in HL-60/ADR cells but increased the sensitivity of HL-60/ADR cells to DNR significantly as compared with AS ODN of XIAP (P < 0.05). AS ODN of XIAP + MRP did not increase the concentration of DNR nor enhanced the inhibition expression of MRP in HL-60/ADR cells but increased the sensitivity of HL-60/ADR cells to DNR significantly (P < 0.05), as compared with AS ODN of MRP. It is concluded that both XIAP and MRP may be involved in the drug resistance mechanisms of HL-60/ADR cells. Drug-resistance of HL-60/ADR cells can be reversed significantly when antisense oligonucleotides of XIAP and MRP were used in combination.
Davies, Emma C.; Green, Christopher F.; Taylor, Stephen; Williamson, Paula R.; Mottram, David R.; Pirmohamed, Munir
Adverse drug reactions (ADRs) are a major cause of hospital admissions, but recent data on the incidence and clinical characteristics of ADRs which occur following hospital admission, are lacking. Patients admitted to twelve wards over a six-month period in 2005 were assessed for ADRs throughout their admission. Suspected ADRs were recorded and analysed for causality, severity and avoidability and whether they increased the length of stay. Multivariable analysis was undertaken to identify the risk factors for ADRs. The 5% significance level was used when assessing factors for inclusion in multivariable models. Out of the 3695 patient episodes assessed for ADRs, 545 (14.7%, 95% CI 13.6–15.9%) experienced one or more ADRs. Half of ADRs were definitely or possibly avoidable. The patients experiencing ADRs were more likely to be older, female, taking a larger number of medicines, and had a longer length of stay than those without ADRs. However, the only significant predictor of ADRs, from the multivariable analysis of a representative sample of patients, was the number of medicines taken by the patient with each additional medication multiplying the hazard of an ADR episode by 1.14 (95% CI 1.09, 1.20). ADRs directly increased length of stay in 147 (26.8%) patients. The drugs most frequently associated with ADRs were diuretics, opioid analgesics, and anticoagulants. In conclusion, approximately one in seven hospital in-patients experience an ADR, which is a significant cause of morbidity, increasing the length of stay of patients by an average of 0.25 days/patient admission episode. The overall burden of ADRs on hospitals is high, and effective intervention strategies are urgently needed to reduce this burden. PMID:19209224
Vural, Fisun; Ciftci, Seval; Vural, Birol
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. 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. 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. 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.
Vural, Fisun; Ciftci, Seval; Vural, Birol
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
Lavan, Amanda Hanora; Gallagher, Paul
Adverse drug reactions (ADRs) are common in older adults, with falls, orthostatic hypotension, delirium, renal failure, gastrointestinal and intracranial bleeding being amongst the most common clinical manifestations. ADR risk increases with age-related changes in pharmacokinetics and pharmacodynamics, increasing burden of comorbidity, polypharmacy, inappropriate prescribing and suboptimal monitoring of drugs. ADRs are a preventable cause of harm to patients and an unnecessary waste of healthcare resources. Several ADR risk tools exist but none has sufficient predictive value for clinical practice. Good clinical practice for detecting and predicting ADRs in vulnerable patients includes detailed documentation and regular review of prescribed and over-the-counter medications through standardized medication reconciliation. New medications should be prescribed cautiously with clear therapeutic goals and recognition of the impact a drug can have on multiple organ systems. Prescribers should regularly review medication efficacy and be vigilant for ADRs and their contributory risk factors. Deprescribing should occur at an individual level when drugs are no longer efficacious or beneficial or when safer alternatives exist. Inappropriate prescribing and unnecessary polypharmacy should be minimized. Comprehensive geriatric assessment and the use of explicit prescribing criteria can be useful in this regard. PMID:26834959
Chan, Sze Ling; Ang, Xiaohui; Sani, Levana L.; Ng, Hong Yen; Winther, Michael D.; Liu, Jian Jun; Brunham, Liam R.
Aims Adverse drug reactions (ADRs) contribute to poorer patient outcomes and additional burden to the healthcare system. However, data on the true burden, relevant types and drugs causing ADRs are lacking. The aim of this study was to determine the prevalence of ADR‐related hospitalization in the general adult population in Singapore and to investigate their characteristics. Methods We prospectively recruited 1000 adult patients with unplanned admission to a large tertiary‐care hospital. Two independent reviewers evaluated all suspected ADRs for causality, type, severity and avoidability. The prevalence of ADR‐related hospitalization was calculated based on ‘definite’ and ‘probable’ ADRs. Logistic regression was used to evaluate predictors for having an ADR at admission. Results The prevalence of all ADRs at admission was 12.4% (95% CI: 10.5–14.6%) and ADRs causing admission was 8.1% (95% CI: 6.5–10.0%). The most common ADRs were gastrointestinal‐related. The most common drug category causing ADRs were cardiovascular drugs. Patients with ADRs had a longer length of stay than those who did not (median 4 vs. 3 days, P = 1.70 × 10−3). About 30% of ADRs at admission were caused by at least one drug with a clinical annotation in the Pharmacogenomics KnowledgeBase (PharmGKB), suggesting that some of these ADRs may have been predicted by pharmacogenetic testing. Conclusions We have quantified the burden and characteristics of clinically impactful ADRs in the Singaporean general adult population. Our results will provide vital information for efforts in reducing ADRs through targeted vigilance, patient education and pharmacogenomics in Singapore. PMID:27640819
Planchamp, F; Nguyen, K-A; Vial, T; Nasri, S; Javouhey, E; Gillet, Y; Ranchin, B; Villard, F; Floret, D; Cochat, P; Gueyffier, F; Kassaï, B
The aim of this study was to systematically evaluate adverse drug reactions (ADRs) in children consulting at the pediatric emergency unit during a 6-month period. The regional pharmacovigilance center (CRPV) and the department of clinical pharmacology prospectively and systematically recorded all potential ADRs among patients younger than 18 years of age in the pediatric emergency unit reported at the daily staff meetings. All cases were then screened and validated by the CRPV. For validated cases, preventability, seriousness, and off-label use were evaluated. During the study period, from 1 March to 1 September 2005, 90 children presented potential adverse drug events. ADRs were confirmed in 43 patients, 19 females and 24 males. Thirty-four patients (79%) were under the age of 5. According to the European definition, 14 patients (33%) had serious ADRs. One anaphylactic shock after amoxicillin injection; antimalarial prophylaxis misuse leading to convulsive status epilepticus, convulsion, and coma after hepatitis B and MMR vaccines were deemed life-threatening. Three ADRs were considered avoidable. Antibiotics and vaccines were the most common possible cause of ADRs (76%). Skin reactions (n=27), fever (n=8), and gastric disorders (n=5) were the most common clinical manifestations. Because ADRs were reported by clinicians on a voluntary basis, serious ADRs were probably reported more systematically. Compared to a similar period without active monitoring, active drug monitoring of ADRs doubled the number of confirmed cases 43 vs 17, p<0.001. Close collaboration between the pharmacovigilance center, pharmacologists, and clinicians is necessary and seems feasible for improving the monitoring of ADRs in children.
Schoretsanitis, Georgios; Stegmann, Benedikt; Hiemke, Christoph; Gründer, Gerhard; Schruers, Koen R J; Walther, Sebastian; Lammertz, Sarah E; Haen, Ekkehard; Paulzen, Michael
The aim of the study was to investigate a correlation between plasma concentrations of risperidone (RIS), its active metabolite 9-hydroxyrisperidone (9-OH-RIS) and the active moiety (AM) (RIS + 9-OH-RIS), and adverse drug reactions (ADRs) in a naturalistic sample. Plasma concentrations of RIS, 9-OH-RIS, and AM in patients out of a therapeutic drug monitoring (TDM) database complaining ADRs were categorized according to the Udvalg for Kliniske Undersogelser side effect rating scales (UKU) (n = 97) and compared to patients without ADRs (n = 398). Patients in the ADR group received a significantly lower daily dosage of risperidone (trimmed mean 3.64 mg/day) than patients without ADRs (4.40 mg/day). No differences were found for active moiety plasma concentrations between the groups (p = 0.454). Differences were detected only in the case of dose-adjusted plasma concentration values (concentration-by-dose, C/D) for 9-OH-RIS, being higher in patients reporting ADRs (4.78 ng/mL/mg) than in patients without ADRs (4.3 ng/mL/mg) (p = 0.037 for Mann-Whitney U test). Note that differences for non-adjusted 9-OH-RIS plasma levels between groups failed to reach significance (p = 0.697). Our findings are consistent with previous data supporting a prominent role of 9-hydroxyrisperidone, but not of risperidone with regard to ADRs. When studying the various subgroups of reported ADRs separately, the size of these subsamples offers some plausible limitations by reducing the power of the analysis.
Aldea, A; García Sánchez-Colomer, M; Fernández Quintana, E; García Sáiz, M
This study was conducted to evaluate relevant new information about ADRs reported in the Spanish paediatric population over a 6-year period. Adverse drug reactions (ADRs) for individuals aged 0-17 years reported to the Spanish Pharmacovigilance System from 2004 to 2009 were analysed with respect to time, age and sex, category of ADR [System Organ Class (SOC)], seriousness, suspected medicines [level 2 of the Anatomical Therapeutic Chemical (ATC) Classification System] and type of reporter. In total, 4,279 ADR reports corresponding to 8,196 ADRs were analysed, approximately two ADRs per report. The rate of paediatric ADR reports in 2009 was 165 per million, of which nearly half (46 %) were for children (age group 2-11 years). Similar total numbers of ADRs were reported for boys and girls. The most frequent ADRs reported were from the following SOCs: general disorders and administration site conditions (34 %); skin and subcutaneous tissue disorders (15 %); nervous system disorders (14 %). Reports encompassed medicines from various ATC groups: vaccines and anti-infectives for systemic use (67 %); nervous system (9 %); respiratory system (9 %). On average, 37 % of ADRs were classified as serious. There were 33 fatal ADRs, and 35 % of the paediatric population associated with the ADR notifications required hospitalization or extended hospital stay. In Spain, ADR reporting rate in the paediatric population has increased since 2004. The proportion of suspected ADR reports related to vaccines was predominant, which highlights the important role played by nurses. ADR notification of congenital malformations in newborn infants highlights the need for joint action between the Spanish System of Pharmacovigilance of Medicines for Human Use (SEFV-H) and paediatricians, obstetricians and gynaecologists. The publication of safety reports by regulatory agencies is determinant for the increased number of ADR notifications.
Manohar, Hasitha Diana; Adiga, Shalini; Thomas, Joseph; Sharma, Ajitha
The aim of the study was to analyze the adverse drug reaction (ADR) profile of microtubule-damaging antineoplastic drugs (taxanes and vinca alkaloids) and to look for unexpected ADRs among the local population. Focused study on these drugs, rampantly used in oncology department for a wide variety of tumors including early and advanced malignancies, would enable better treatment care by physicians. Data on ADRs were collected from the cancer patients belonging to both gender and of all ages, on taxanes- or vinca-based cancer chemotherapy and reported in the Indian Pharmacopoeia Commission form. Causality was assessed using the WHO criteria and Naranjo's Algorithm. Preventability and severity of ADRs were also assessed. A total of 97 ADRs were reported among 488 patients on microtubule-damaging anticancer drugs admitted over a period of 1 year. The incidence rate was 19.87%. Gastrointestinal system (40.2%) was the most affected followed by bone marrow (33%) and skin (8.2%). The highest incidence of ADRs was reported among paclitaxel (54.6%), and vincristine (39.2%). Most of the reported ADRs were of milder nature and preventable. The WHO causality assessment scale indicated 71.1% possible reactions. This study showed that most ADRs are preventable with effective ADR monitoring. There is a great need to create awareness among healthcare professionals regarding the importance of the pharmacovigilance system. Judicious use of the preventive measures will lead to a reduction in the incidence of ADRs due to the drug armamentarium, thereby enabling additional economic benefit to the patient and society.
Manohar, Hasitha Diana; Adiga, Shalini; Thomas, Joseph; Sharma, Ajitha
Objectives: The aim of the study was to analyze the adverse drug reaction (ADR) profile of microtubule-damaging antineoplastic drugs (taxanes and vinca alkaloids) and to look for unexpected ADRs among the local population. Focused study on these drugs, rampantly used in oncology department for a wide variety of tumors including early and advanced malignancies, would enable better treatment care by physicians. Materials and Methods: Data on ADRs were collected from the cancer patients belonging to both gender and of all ages, on taxanes- or vinca-based cancer chemotherapy and reported in the Indian Pharmacopoeia Commission form. Causality was assessed using the WHO criteria and Naranjo's Algorithm. Preventability and severity of ADRs were also assessed. Results: A total of 97 ADRs were reported among 488 patients on microtubule-damaging anticancer drugs admitted over a period of 1 year. The incidence rate was 19.87%. Gastrointestinal system (40.2%) was the most affected followed by bone marrow (33%) and skin (8.2%). The highest incidence of ADRs was reported among paclitaxel (54.6%), and vincristine (39.2%). Most of the reported ADRs were of milder nature and preventable. The WHO causality assessment scale indicated 71.1% possible reactions. Conclusions: This study showed that most ADRs are preventable with effective ADR monitoring. There is a great need to create awareness among healthcare professionals regarding the importance of the pharmacovigilance system. Judicious use of the preventive measures will lead to a reduction in the incidence of ADRs due to the drug armamentarium, thereby enabling additional economic benefit to the patient and society. PMID:27721535
Ernst, E; Sieder, C; März, R
Our knowledge relating to adverse drug reactions (ADRs) of phytomedicines is highly fragmentary. The aim of this study was to define the prevalence of ADRs following medication with herbal or synthetic expectorants. In a multicentre, comparative post-marketing surveillance study of more than 3000 patients with acute bronchitis, about half were treated with a herbal remedy (SinupretR) and the other half with various other expectorants. In ascending order of incidence, ADRs were noted during mono-medication of SinupretR (0.8%), Ambroxol (1.0%) and acetylcysteine (4.3%). When concomitant drugs were used, this rank order was unchanged but incidence rates were markedly increased (3.4, 6.5 and 8.2%, respectively). The most frequent ADRs were gastrointestinal symptoms. It is concluded that expectorants are associated with ADRs in roughly 1-5% of cases undergoing single drug treatment and in 3-10% when more than one medication is being used. Amongst the expectorants used in this study, the herbal preparation SinupretR is associated with the lowest incidence of ADRs.
Protić, Dragana; Vujasinović-Stupar, Nada; Bukumirić, Zoran; Pavlov-Dolijanović, Slavica; Baltić, Snežana; Mutavdžin, Slavica; Marković-Denić, Ljiljana; Zdravković, Marija; Todorović, Zoran
Background Adverse drug reactions (ADRs) have a significant impact on human health and health care costs. The aims of our study were to determine the profile of rheumatology patients willing to report ADRs and to identify bias in such a reporting system. Methods Semi-intensive ADRs reporting system was used in our study. Patients willing to participate (N=261) completed the questionnaire designed for the purpose of the study at the hospital admission. They were subsequently classified into two groups according to their ability to identify whether they had experienced ADRs during the previous month. Group 1 included 214 out of 261 patients who were able to identify ADRs, and group 2 consisted of 43 out of 261 patients who were not able to identify ADRs in their recent medical history. Results Group 1 patients were more significantly aware of their diagnosis than the patients from group 2. Marginal significance was found between rheumatology patients with and without neurological comorbidities regarding their awareness of ADRs. The majority of patients reported ADRs of cytotoxic drugs. The most reported ADRs were moderate gastrointestinal discomforts. Conclusion We may draw a profile of rheumatological patients willing to report ADRs: 1) The majority of them suffer from systemic inflammatory diseases and are slightly more prone to neurological comorbidities. 2) They are predominantly aware of their diagnosis but less able to identify the drugs that may cause their ADRs. 3) They tend to report mainly moderate gastrointestinal ADRs; that is, other cohorts of patients and other types of ADRs remain mainly undetected in such a reporting, which could represent a bias. Counseling and education of patients as well as developing a network for online communication might improve patients’ reporting of potential ADRs. PMID:26893547
Skvrce, Nikica Mirosević; Bozina, Nada; Sarinić, Viola Macolić; Tomić, Sinisa
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.
Lebrun-Vignes, B; Valeyrie-Allanore, L
Cutaneous adverse drug reactions (CADR) represent a heterogeneous field including various clinical patterns without specific features suggesting drug causality. Exanthematous eruptions, urticaria and vasculitis are the most common forms of CADR. Fixed eruption is uncommon in western countries. Serious reactions (fatal outcome, sequelae) represent 2% of CADR: bullous reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis), DRESS (drug reaction with eosinophilia and systemic symptoms or drug-induced hypersensitivity syndrome) and acute generalized exanthematous pustulosis (AGEP). These forms must be quickly diagnosed to guide their management. The main risk factors are immunosuppression, autoimmunity and some HLA alleles in bullous reactions and DRESS. Most systemic drugs may induce cutaneous adverse reactions, especially antibiotics, anticonvulsivants, antineoplastic drugs, non-steroidal anti-inflammatory drugs, allopurinol and contrast media. Pathogenesis includes immediate or delayed immunologic mechanism, usually not related to dose, and pharmacologic/toxic mechanism, commonly dose-dependent or time-dependent. In case of immunologic mechanism, allergologic exploration is possible to clarify drug causality, with a variable sensitivity according to the drug and to the CADR type. It includes epicutaneous patch testing, prick test and intradermal test. However, no in vivo or in vitro test can confirm the drug causality. To determine the cause of the eruption, a logical approach based on clinical characteristics, chronologic factors and elimination of differential diagnosis is required, completed with a literature search. A reporting to pharmacovigilance network is essential in case of a serious CADR whatever the suspected drug and in any case if the involved drug is a newly marketed one or unusually related to cutaneous reactions.
Aderemi-Williams, R I; Awodele, O; Boyle, C A
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.
Vallano Ferraz, Antonio; Agustí Escasany, Antonia; Pedrós Xolvi, Consuelo; Arnau de Bolós, Josep M
Adverse drug reactions (ADRs) are an important healthcare problem. The objective of this study was to review published articles analyzing the cost of ADRs in any healthcare setting. We conducted a search of articles published on the cost of ADRs in the bibliographic databases from 1970 to 2010. We identified 28 studies and selected 16 that included cases of ADR fitting the World Health Organization's definition of these events. The information on the characteristics of the study design, the types of costs analyzed and the reported results were reviewed. The design features and populations included in the studies were heterogeneous. Only two studies explicitly defined the perspective adopted. Only five studies compared cases of ADR with matched controls without ADRs. All studies analyzed direct healthcare costs, but none analyzed indirect or intangible costs. Fourteen publications analyzed the costs of length of hospital stay. The average (SD) percentage of ADRs was 3.04% (0.2) [median 2.4%, range 0.7% to 26.1%]. The median length of hospital stay in patients with ADRs was 8.8 days (range: 0.15 to 19.2 days). Accounting systems and monetary costs varied widely. Studies on the costs of ADRs are highly heterogeneous and have evaluated direct healthcare costs in hospitals. Their results indicate that ADRs generate substantial costs. More studies using appropriate methodology are needed on the costs of ADRs. Copyright © 2011 SESPAS. Published by Elsevier España. All rights reserved.
Tan, Yuxiang; Hu, Yong; Liu, Xiaoxiao; Yin, Zhinan; Chen, Xue-Wen; Liu, Mei
Adverse drug reactions (ADRs) are a major public health concern, causing over 100,000 fatalities in the United States every year with an annual cost of $136 billion. Early detection and accurate prediction of ADRs is thus vital for drug development and patient safety. Multiple scientific disciplines, namely pharmacology, pharmacovigilance, and pharmacoinformatics, have been addressing the ADR problem from different perspectives. With the same goal of improving drug safety, this article summarizes and links the research efforts in the multiple disciplines into a single framework from comprehensive understanding of the interactions between drugs and biological system and the identification of genetic and phenotypic predispositions of patients susceptible to higher ADR risks and finally to the current state of implementation of medication-related decision support systems. We start by describing available computational resources for building drug-target interaction networks with biological annotations, which provides a fundamental knowledge for ADR prediction. Databases are classified by functions to help users in selection. Post-marketing surveillance is then introduced where data-driven approach can not only enhance the prediction accuracy of ADRs but also enables the discovery of genetic and phenotypic risk factors of ADRs. Understanding genetic risk factors for ADR requires well organized patient genetics information and analysis by pharmacogenomic approaches. Finally, current state of clinical decision support systems is presented and described how clinicians can be assisted with the integrated knowledgebase to minimize the risk of ADR. This review ends with a discussion of existing challenges in each of disciplines with potential solutions and future directions.
Hernández-Hernández, Dulce María; Vargas-Rivera, María Josefa E; Nava-Ocampo, Alejandro A; Palma-Aguirre, José Antonio; Sumano-López, Héctor
Background Adverse drug reactions (ADR's) could be expected more frequently in pregnant women. This study was performed in order to identify ADR's to tocolytic drugs in hospitalised pregnant women. Methods A prospective cohort study was performed in two General Hospitals of the Instituto Mexicano del Seguro Social (IMSS) in Mexico City. Two hundred and seven women undergoing labor, premature labor, threatened abortion or suffering any obstetric related disease were included. Drug prescription and signs and symptoms of any potential ADR were registered daily during the hospital stay. Any potential ADR to tocolytic drugs was evaluated and classified by three of the authors using the Kramer's algorithm. Results Of the 207 patients, an ADR was positively classified in 25 cases (12.1%, CI95% 8.1 to 17.5%). All ADR's were classified as minor reactions. Grouping patients with diagnosis of threatened abortion, premature labor or under labor (n= 114), 24 ADR's were related to terbutaline, accounting for a rate of 21.1 ADR's per 100 obstetric patients. Obstetric patients suffering an ADR were older than obstetric patients without any ADR. However, the former received less drugs/day × patient-1 and had a shorter hospital stay (p < 0.05) whereas the dose of terbutaline was similar between the two groups. Terbutaline inhibited uterine motility in women with and without any ADR at a similar rate, 70 and 76% respectively (x2 = 0.07; p = 0.8). Conclusion Terbutaline, used as a tocolytic drug, was related to a high frequency of minor ADRs and to a high rate of effcicacy. PMID:11934352
Davies, E A; O’Mahony, M S
The International Conference on Harmonization considers older people a ‘special population’, as they differ from younger adults in terms of comorbidity, polypharmacy, pharmacokinetics and greater vulnerability to adverse drug reactions (ADRs). Medical practice is often based on single disease guidelines derived from clinical trials that have not included frail older people or those with multiple morbidities. This presents a challenge caring for older people, as drug doses in trials may not be achievable in real world patients and risks of ADRs are underestimated in clinical trial populations. The majority of ADRs in older people are Type A, potentially avoidable and associated with commonly prescribed medications. Several ADRs are particularly associated with major adverse consequences in the elderly and their reduction is therefore a clinical priority. Falls are strongly associated with benzodiazepines, neuroleptics, antidepressants and antihypertensives. There is good evidence for medication review as part of a multifactorial intervention to reduce falls risk in community dwelling elderly. Multiple medications also contribute to delirium, another multifactorial syndrome resulting in excess mortality particularly in frail older people. Clostridium difficile associated with use of broad spectrum antibiotics mainly affects frail older people and results in prolonged hospital stay with substantial morbidity and mortality. Antipsychotics increase the risk of stroke by more than three-fold in patients with dementia. Inappropriate prescribing can be reduced by adherence to prescribing guidelines, suitable monitoring and regular medication review. Given the heterogeneity within the older population, providing individualized care is pivotal to preventing ADRs. PMID:25619317
Rosli, Rosliana; Dali, Ahmad Fauzi; Aziz, Noorizan Abd.; Ming, Long Chiau; Manan, Mohamed Mansor
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
Rosli, Rosliana; Dali, Ahmad Fauzi; Aziz, Noorizan Abd; Ming, Long Chiau; Manan, Mohamed Mansor
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 for
Nayak, Surajit; Acharjya, Basanti
In everyday clinical practice, almost all physicians come across many instances of suspected adverse cutaneous drug reactions (ACDR) in different forms. Although such cutaneous reactions are common, comprehensive information regarding their incidence, severity and ultimate health effects are often not available as many cases go unreported. It is also a fact that in the present world, almost everyday a new drug enters market; therefore, a chance of a new drug reaction manifesting somewhere in some form in any corner of world is unknown or unreported. Although many a times, presentation is too trivial and benign, the early identification of the condition and identifying the culprit drug and omit it at earliest holds the keystone in management and prevention of a more severe drug rash. Therefore, not only the dermatologists, but all practicing physicians should be familiar with these conditions to diagnose them early and to be prepared to handle them adequately. However, we all know it is most challenging and practically difficult when patient is on multiple medicines because of myriad clinical symptoms, poorly understood multiple mechanisms of drug-host interaction, relative paucity of laboratory testing that is available for any definitive and confirmatory drug-specific testing. Therefore, in practice, the diagnosis of ACDR is purely based on clinical judgment. In this discussion, we will be primarily focusing on pathomechanism and approach to reach a diagnosis, which is the vital pillar to manage any case of ACDR.
Winstanley, P A; Irvin, L E; Smith, J C; Orme, M L; Breckenridge, A M
A pharmacy-based adverse drug reaction (ADR) reporting scheme, using pharmacists, nurses and medical practitioners as initiators of reports, was set up at the end of 1984 in the Royal Liverpool Hospital in order to encourage reporting. New reports were inspected at weekly intervals by a staff pharmacist, and a clinical pharmacologist. Reports were forwarded to the Committee on Safety of Medicines if the reaction was considered to be serious by the clinicians, or the ADR team or involved 'black triangle' drugs. The total number of ADR reports was increased eightfold by the introduction of the scheme (from 14 in 1984 to 76, 102 and 94 in 1985, 1986 and 1987 respectively), and this rate of reporting has been sustained. PMID:2775609
Garon, Sarah L; Pavlos, Rebecca K; White, Katie D; Brown, Nancy J; Stone, Cosby A; Phillips, Elizabeth J
Off-target adverse drug reactions (ADRs) are associated with significant morbidity and costs to the healthcare system and their occurrence is not predictable based on the known pharmacological action of the drug's therapeutic effect. Off-target ADRs may or may not be associated with immunological memory although they can manifest with a variety of shared clinical features including maculopapular exanthema, severe cutaneous adverse reactions (SCARs), angioedema, pruritus, and bronchospasm. Discovery of specific genes associated with a particular ADR phenotype is a foundational component of clinical translation into screening programs for their prevention. In this review, genetic associations of off-target drug-induced ADRs that have a clinical phenotype suggestive of an immunologically-mediated process and their mechanisms are highlighted. A significant proportion of these reactions lack immunological memory and current data is informative for these ADRs with regard to disease pathophysiology, therapeutic targets, and biomarkers which may identify patients at greatest risk. Although many serious delayed IM-ADRs show strong HLA associations, only a small subset have successfully been implemented in screening programs. More recently, other factors such as drug metabolism have been shown to contribute to the risk of the IM-ADR. In the future, pharmacogenomic targets and an understanding of how they interact with drugs to cause ADRs will be applied to drug design and pre-clinical testing, and this will allow selection of optimal therapy to improve patient safety.
Eriksson, Robert; Aagaard, Lise; Jensen, Lars Juhl; Borisova, Liza; Hørlück, Dorte; Brunak, Søren; Hansen, Ebba Holme
Pharmaceutical product information (PI) supplied by the regulatory authorities serves as a source of information on safe and effective use of drugs. The objectives of this study were to qualitatively and quantitatively compare PIs for selected drugs marketed in both Denmark and the USA with respect to consistency and discrepancy of listed adverse drug reaction (ADR) information. We compared individual ADRs listed in PIs from Denmark and the USA with respect to type and frequency. Consistency was defined as match of ADRs and of ADR frequency or match could not be ruled out. Discrepancies were defined as ADRs listed only in one country or listed with different frequencies. We analyzed PIs for 40 separate drugs from ten therapeutic groups and assigned the 4003 identified ADRs to System Organ Classes (Medical Dictionary for Regulatory Activities [MedDRA] terminology). Less than half of listed ADRs (n = 1874; 47%) showed consistency. Discrepancies (n = 2129; 53%) were split into ADRs listed only in the USA (n = 1558; 39%), ADRs listed only in Denmark (n = 325; 8%) and ADRs listed with different frequencies (n = 246; 6%). The majority of listed ADRs were of the type "gastrointestinal disorders" and "nervous system disorders". Our results show great differences in PIs for drugs approved in both Denmark and the USA illuminating concerns about the credibility of the publicly available PIs. The results also represent an argument for further harmonization across borders to improve consistency between authority-supplied information.
Jadav, Hasmukh R.; Ghetiya, Hitesh; Prashanth, B.; Galib; Patgiri, B. J.; Prajapati, P. K.
Adverse drug reactions (ADR) are an expression that describes harm associated with the use of medications at therapeutic dose. Traditional medicines also can develop ADRs due to their improper use. Shvitrahara Varti, one of such medicines holds Bakuchi as a component and is to be used judiciously. Furanocoumarins like psoralen present in Bakuchi makes skin hypersensitive and causes phytophotodermatitis in few cases. Hence, one should be careful while using medicines that contain Bakuchi. One such case is observed, where extensive reactions with application of Shvitrahara Varti were noticed and managed with Ayurvedic treatment. PMID:24250129
De Las Salas, Roxana; Díaz-Agudelo, Daniela
The appearance of adverse drug reactions in neonates is an important issue due to the lack of drug safety data. To identify the behavior of adverse drug reactions (ADR) in hospitalized neonates at two intensive care units in Barranquilla, Colombia. We conducted a cross-sectional prospective descriptive study based on patientcentered intensive pharmacosurveillance. We followed up and monitored the appearance of ADRs for six months. We used Naranjo's algorithm to assess causality, modified Hartwig and Siegel assessment scale to establish severity and Schumock and Thornton criteria to determine ADR preventability. We detected 123 adverse drug reactions in 78 neonates of the 284 monitored. The cumulative incidence of ADRs was 27.4% (78/284); incidence density was 30.60 ADRs per 1,000 patients/day (78/2,549). The most affected organ system was the digestive (33.6%). Systemic anti-infective drugs were the most involved pharmacological group. Most of the ADRs were mild (58.5%), 83% were classified as probable, 16.2% as possible and 0.8% as definite. ADR incidence was high in newborns, and it increased in preterm infants (less than 38 weeks of age).
Montastruc, Francois; Sommet, Agnès; Bondon-Guitton, Emmanuelle; Durrieu, Geneviève; Bui, Eric; Bagheri, Haleh; Lapeyre-Mestre, Maryse; Schmitt, Laurent; Montastruc, Jean-Louis
To quantify the importance of drug-drug interactions (DDIs) in the occurrence of adverse drug reactions (ADRs) reported with serotoninergic reuptake inhibitors in a pharmacovigilance database. All spontaneous reports of ADRs registered in 2008 by the Midi-Pyrénées PharmacoVigilance Centre that contained mention of one of the serotoninergic reuptake inhibitor (SRI) antidepressants marketed in France were reviewed. DDIs were identified according to the French National Drug Formulary (Vidal) and the interaction supplement of the French independent drug bulletin La Revue Prescrire. ADRs explained by DDIs were characterised. Among the 2,101 spontaneous reports recorded, 177 involved at least one SRI antidepressant. Among the 156 ADRs with at least one theoretical DDI, 41% (95% confidence interval 34-49%) could be explained by a DDI. The most frequent antidepressant involved in DDIs was escitalopram, followed by fluoxetine and citalopram. Among the 65 ADRs related to DDIs, 37 (52.9%) were "serious", mainly bleedings, confusion and falls, hyponatremia and serotoninergic syndromes. The most frequent drug interactions occurred with psychotropics (antipsychotics, benzodiazepines, among others), followed by antithrombotic agents (antagonists of vitamin K, antiplatelets), diuretics and angiotensin II antagonists. The group with ADRs related to DDIs was older than the group with ADRs not related to DDIs. ADRs were threefold more "serious" in the case of DDIs. Around 40% of ADRs reported with SRIs were related to DDIs. Most of these occurred after association with psychotropics, antithrombotics, or diuretics, especially in the elderly.
Suyagh, Maysa; Farah, Doaa; Abu Farha, Rana
Background 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. Objectives 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. Method 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. Results 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. Conclusion 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. PMID:25972734
Puche Cañas, E; Luna Del Castillo, J D
The aim of this study was to present the results of a meta-analysis on adverse drug reactions (ADR) in spanish patients admitted to hospital and presenting to emergency department over the past 20 years. An exhaustive review was undertaken of relevant articles in the IME (Spanish Medical Index) and MEDLINE databases and published between 1985 and 2006, rigorously selecting 12 out of 30 publications after applying inclusion and exclusion criteria. Information was required on: symptomatology, prognosis, type, drugs involved, imputability and admissions for ADR; and factors associated with ADR onset, e.g., age, sex, number of drugs, previous history of ADR, method used for ADR detection, and length of study period. A random-effects model (DerSimonian and Laird) and the STATA 9.1 programme were used for the meta-analysis. The combined estimation of the percentage of Spanish patients with ADR was 13% (95% CI); with severe ADR, 12 % (95% CI) and with fatal ADR, 0.1% (95% CI). ADR diagnosis was definite in 36% (95% CI), probable in 49.6% (95% CI), and type A in 71% (95% CI) of cases. Among patients in the Emergency Department for ADR, 5.1% (95% IC) were hospitalized. No association was found with number of prescriptions or previous history. Association was established with advanced age and female sex. Digestive, skin, nervous and cardiovascular systems were those most affected by ADR. The drugs most frequently implicated included NSAIDs, digoxin, IACE, calcium antagonists, furosemide, i.v. metamizol, antidiabetics, benzodiazepines, adrenergic bronchodilators and classic antipsychotics. ADRs constitute a major medical and economic problem with aspects that have yet to be defined. Greater efforts are warranted to unify criteria for the publication of results in observational studies on ARD and to determine the role played by some factors associated with their onset, e.g., sex, previous history and comorbidities.
Süsskind, M.; Thürmann, P. A.; Lüke, C.; Jeschke, E.; Tabali, M.; Matthes, H.; Ostermann, T.
Background. Anthroposophic medicine is one of the widely used approaches of complementary and alternative medicine. However, few prospective studies have generated safety data on its use. Objectives. We aimed to assess adverse drug reactions (ADRs) caused by anthroposophical medicines (AMEDs) in the anthroposophical Community Hospital Havelhoehe, GERMANY. Study Design and Methods. Between May and November 2007, patients of six medical wards were prospectively assessed for ADRs. Suspected ADRs occurring during hospitalization were documented and classified in terms of organ manifestation (WHO SOC-code), causality (according to the Uppsala Monitoring Centre WHO criteria), and severity. Only those ADRs with a severity of grade 2 and higher according to the CTCAE classification system are described here. Results. Of the 3,813 patients hospitalized, 174 patients (4.6%) experienced 211 ADRs (CTCAE grade 2/3 n = 191, 90.5%, CTCAE grade 4/5 n = 20, 9.5%) of which 57 ADRs (27.0%) were serious. The median age of patients with ADRs (62.1% females) was 72.0 (IQR: 61.0; 80.0). Six patients (0.2%) experienced six ADRs (2.8% of ADRs) caused by eight suspected AMEDs, all of which were mild reactions (grade 2). Conclusion. Our data show that ADRs caused by AMEDs occur rarely and are limited to mild symptoms. PMID:22315630
Palaian, Subish; Ibrahim, Mohamed I.M.; Mishra, Pranaya
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
Gómez-Pavón, Javier; González García, Paloma; Francés Román, Inés; Vidán Astiz, Maite; Gutiérrez Rodríguez, José; Jiménez Díaz, Gregorio; Montero Fernández, Nuria Pilar; Alvarez Fernández, Baldomero; Jiménez Páez, José María
The elderly are one of the groups at greatest risk for adverse drugs reactions (ADR). The mean prevalence of these reactions in this population is 30%. Dementia is not an independent risk factor of ADR, but is the main condition that increases all risk factors (polypharmacy, comorbidity, inappropriate prescribing, drug-drug interactions, advanced age, and treatment adherence). The present article discusses revised and consensual recommendations for the prevention of ADR in the elderly, as well as recommendations specifically for dementia patients in relation to the management of comorbidity and cognitive, behavioral and psychological symptoms.
Piparva, Kiran G.; Buch, J. G.; Chandrani, Kalpesh V.
Background: Novel atypical antipsychotics are superior to conventional antipsychotics as they significantly reduce both positive and negative symptoms of schizophrenia and have lower risk of extrapyramidal symptoms (EPS). However, these drugs have separate set of adverse drug reactions (ADRs). Therefore, this study was carried out to assess these ADRs, which can have impact on long-term compliance and achieving successful treatment. Materials and Methods: A prospective study of analysis of ADR of atypical antipsychotic drugs was carried out in the psychiatry outpatient department. Patients of psychotic disorder (any age, either sex), who were prescribed atypical antipsychotic drugs, were included. Those who were prescribed conventional antipsychotics or combinations of antipsychotics were excluded from the study. Apart from spontaneously reported ADRs, a questionnaire related to the likely ADR was used and patients’ responses were recorded in the case record form. Results: Totally 93 ADRs were recorded from 84 prescriptions. Majority of the ADRs (82 out of 93) were seen with risperidone and olanzepine, as they were the commonly prescribed drugs. Weight gain, dizziness, sleep disturbance and appetite disturbance accounted for nearly 78% of the total events. With risperidone (at 4–6 mg/day) and olanzepine (at 10–15 mg/day), gastrointestinal and sleep disturbance were observed in the initial (within 7 days to 2–3 months after treatment) course of treatment, while EPS, fatigue, seizure, increased frequency of micturition and dizziness were observed after long-term (3–9 months) use. Conclusion: The present study adds to the existing information on the prevalence of adverse effects of atypical antipsychotic drugs. Role of active surveillance in post-marketing phase is also emphasized. PMID:22345840
Clarke, John D; Cherrington, Nathan J
Introduction Organic anion transporting polypeptide (OATP) uptake transporters are important for the disposition of many drugs and perturbed OATP activity can contribute to adverse drug reactions (ADRs). It is well documented that both genetic and environmental factors can alter OATP expression and activity. Genetic factors include single nucleotide polymorphisms (SNPs) that change OATP activity and epigenetic regulation that modify OATP expression levels. SNPs in OATPs contribute to ADRs. Environmental factors include the pharmacological context of drug--drug interactions and the physiological context of liver diseases. Liver diseases such as non-alcoholic fatty liver disease, cholestasis and hepatocellular carcinoma change the expression of multiple OATP isoforms. The role of liver diseases in the occurrence of ADRs is unknown. Areas covered This article covers the roles OATPs play in ADRs when considered in the context of genetic or environmental factors. The reader will gain a greater appreciation for the current evidence regarding the salience and importance of each factor in OATP-mediated ADRs. Expert opinion A SNP in a single OATP transporter can cause changes in drug pharmacokinetics and contribute to ADRs but, because of overlap in substrate specificities, there is potential for compensatory transport by other OATP isoforms. By contrast, the expression of multiple OATP isoforms is decreased in liver diseases, reducing compensatory transport and thereby increasing the probability of ADRs. To date, most research has focused on the genetic factors in OATP-mediated ADRs while the impact of environmental factors has largely been ignored. PMID:22280100
Mittal, Niti; Gupta, Mahesh; Singla, Mohit
Medication-related adverse events, apart from causing significant morbidity and mortality, increase the healthcare cost burden and lead to early treatment discontinuations. Knowing the fact that cutaneous adverse drug reactions (cADRs) are most frequent, this study was conducted with an aim to describe their clinical profiles and preventive strategies. All adverse drug reaction (ADR) forms filled from January 2012 to January 2013 were scrutinised and forms with cADRs analysed and assessed for causality, preventability and severity. Of 400 ADR forms, 109 included cADRs. Sixty-eight percent patients were males and mean ± SD age was 35 ± 18 years. Rash, Steven-Johnson syndrome and toxic epidermal necrolysis were the most common presentations. Most frequent culprit drugs included antibiotics and anti-inflammatory agents. Causality was probable or possible in majority. Ninety percent cases were "not preventable". Majority of the patients had mild to moderate reactions and recovered completely after medical management. Pharmacovigilance, with special attention to monitoring and reporting of cADRs must be encouraged. As major bulk of cADRs result from physician prescribed drugs, awareness on part of the physician can help in their timely detection and management, thereby restricting the associated damage.
Harpaz, Rave; Odgers, David; Gaskin, Greg; DuMouchel, William; Winnenburg, Rainer; Bodenreider, Olivier; Ripple, Anna; Szarfman, Ana; Sorbello, Alfred; Horvitz, Eric; White, Ryen W; Shah, Nigam H
Undetected adverse drug reactions (ADRs) pose a major burden on the health system. Data mining methodologies designed to identify signals of novel ADRs are of deep importance for drug safety surveillance. The development and evaluation of these methodologies requires proper reference benchmarks. While progress has recently been made in developing such benchmarks, our understanding of the performance characteristics of the data mining methodologies is limited because existing benchmarks do not support prospective performance evaluations. We address this shortcoming by providing a reference standard to support prospective performance evaluations. The reference standard was systematically curated from drug labeling revisions, such as new warnings, which were issued and communicated by the US Food and Drug Administration in 2013. The reference standard includes 62 positive test cases and 75 negative controls, and covers 44 drugs and 38 events. We provide usage guidance and empirical support for the reference standard by applying it to analyze two data sources commonly mined for drug safety surveillance.
Berreni, Aurélia; Montastruc, François; Bondon-Guitton, Emmanuelle; Rousseau, Vanessa; Abadie, Delphine; Durrieu, Geneviève; Chebane, Leila; Giroud, Jean-Paul; Bagheri, Haleh; Montastruc, Jean-Louis
Although self-medication is widely developed, there are few detailed data about its adverse drug reactions (ADRs). This study investigated the main characteristics of ADRs with self-medication recorded in the Midi-Pyrénées PharmacoVigilance between 2008 and 2014. Self-medication included first OTC drugs and second formerly prescribed drugs later used without medical advice (reuse of previously prescribed drugs). Among the 12 365 notifications recorded, 160 (1.3%) were related to SM with 186 drugs. Around three-forth of the ADRs were 'serious'. Mean age was 48.8 years with 56.3% females. The most frequent ADRs were gastrointestinal and neuropsychiatric and main drug classes involved NSAIDs, analgesics, and benzodiazepines. Phytotherapy-homeopathy accounted for 9.1% of drugs.
Pulford, Andrew; Malcolm, William
The reporting of adverse drug reactions (ADRs) by health professionals forms an important component of ongoing surveillance of post-marketing drug safety. The extension of responsibility for all health professionals to report ADRs has coincided with national immunization programmes, such as the national childhood immunization, human papillomavirus (HPV), and seasonal and H1N1 influenza programmes. The study objective was to evaluate knowledge of, and attitudes to, reporting ADRs among the professional groups most likely to see suspected reactions to vaccines. This included nursing professionals, whose views have not been included in previous studies. A survey of 91 practice nurses, health visitors, school nurses and GPs working in Ayrshire and Arran during June, July and August 2007 was undertaken. The respondents' knowledge of ADR reporting varied considerably. Although the majority of respondents recognized that it is the responsibility of health professionals to report suspected ADRs, there were lower levels of knowledge about the purpose of the Yellow Card system specifically; less than 50% of the respondents reported good knowledge about the system. The study suggests implications for practice with regard to the implementation of large-scale immunization programmes and potential solutions to under-reporting among these professional groups.
Bhushan, Bharat; Chander, Ramesh; Kajal, N C; Ranga, Vikrant; Gupta, Ajay; Bharti, Heena
The aim of the study was to elucidate the profile of adverse drug reactions (ADRs) associated with second-line anti-tubercular treatment for drug-resistant tuberculosis. ADR profile of diagnosed drug-resistant tuberculosis cases on supervised second-line anti-tubercular drug regimen under Programmatic Management of Drug-resistant Tuberculosis under Revised National Tuberculosis Control Programme, were studied over two years' period. Adverse reactions were categorised into mild, moderate and severe types with subsequent systematic data-analysis. Out of total 207 patients in the study, 81.16% reported with adverse drug reactions. Out of total 195 adverse events, 63.58%, 18.46% and 17.94% were of mild, moderate and severe types respectively. Gastrointestinal events, hepatitis, hearing impairment, arthralgia, psychosis, hypothyroidism, visual disturbances, giddiness, peripheral neuropathy, skin reactions, swelling or pain at injection site, anorexia and sleep disturbances were important amongst these. High proportion of drug and/or alcohol abuse was an important observation. The offending drug(s) had to be terminated in 12.08% of the patients. Early detection, management and pharmaco-vigilance reporting of ADRs remain key factors in the management of drug-resistant tuberculosis with remarkable relevance of the need for early diagnosis and treatment of 'drug-sensitive tuberculosis', to prevent emergence of drug-resistant tuberculosis.
Bénard-Laribière, Anne; Miremont-Salamé, Ghada; Pérault-Pochat, Marie-Christine; Noize, Pernelle; Haramburu, Françoise
To assess the incidence of hospital admissions related to adverse drug reactions (ADRs) in France and the frequency of preventable ADRs in France, a prospective study was conducted among a representative randomly selected sample of medical wards in public hospitals between December 2006 and June 2007; all patients admitted during a 2-week period were included. An ADR-related hospitalization case was defined as a hospital admission because of an ADR, and an independent committee reviewed and validated all potential cases. Preventability was assessed using the French ADR preventability scale. Data were extrapolated to the population of France. Among 2692 admissions, 97 were related to an ADR (incidence 3.6%, 95% confidence interval, CI [2.8-4.4]). Patients admitted for an ADR were significantly older than those admitted for other reasons (P < 0.001). A third (32.0%) of ADR-related hospitalizations were 'preventable', 16.5% 'potentially preventable'. Drug interactions accounted for 29.9% of ADR-related hospitalizations. The most frequent causes of ADR-related hospitalizations were vascular disorders (20.6%), mainly bleeding complications, central nervous system disorders (11.3%), gastrointestinal disorders, and general disorders (9.3%). Antithrombotic and antineoplastic agents were the most frequently involved (12.6% each), followed by diuretics and analgesics (9.0% each). Vitamin-K-antagonists (VKAs) were the most common drugs associated with admission. The estimated annual number of ADR-related hospitalizations in France was 143 915 (95% CI [112 063-175 766]). ADRs were a significant cause of hospital admission in 2006-2007, in particular those due to VKAs. As new oral anticoagulants (NOACs) have been marketed, more attention needs to be paid to ensure a safe use of antithrombotic agents.
Scicchitano, Francesca; Giofrè, Chiara; Palleria, Caterina; Mazzitello, Carmela; Ciriaco, Miriam; Gallelli, Luca; Paletta, Laura; Marrazzo, Giuseppina; De Fazio, Salvatore; Menniti, Michele; Curia, Rubens; Arena, Concetta; Chimirri, Serafina; Patanè, Marinella; Esposito, Stefania; Cilurzo, Felisa; Staltari, Orietta; Russo, Emilio; De Sarro, Giovambattista
Background: Pharmacovigilance assesses the safety profile of drugs. Its main aim is the increase of spontaneous reporting of adverse drug reactions (ADRs). The Italian Drug Agency (AIFA; Agenzia Italiana del Farmaco) is financing several projects to the aim of increasing reporting, and in Calabria a Pharmacovigilance Information Centre has been created. Materials and Methods: We analyzed the AIFA database relatively to Calabria in the year 2011 and we have analyzed ADRs using descriptive statistics. We have also collected a questionnaire-based interview in order to describe the background knowledge in the field. Results: Regarding the number of AIFA reported ADRs from Calabria, a 38% increase (138 vs. 100) in comparison to 2010 was evidenced. Hospital Doctors represent the main source of signaling (71.7 %). Ketoprofene and the combination amoxicillin/clavulanic acid represent the most frequently reported drugs causing ADRs. Our questionnaires indicated that despite the health professionals have met at least once an ADR only a small percentage of them was reported to the authorities (37%). There is a very good knowledge of the ADR concept and reporting system (90% of interviewed distinguish an ADR and knows how to report it), and there is a strong interest in participating to training courses in the field (95% are interested). Conclusions: Despite Calabria has had a positive increase in the number of reported ADRs, the total number is very low and the pharmacovigilance culture is far from being achieved in this region. PMID:23826016
Scicchitano, Francesca; Giofrè, Chiara; Palleria, Caterina; Mazzitello, Carmela; Ciriaco, Miriam; Gallelli, Luca; Paletta, Laura; Marrazzo, Giuseppina; De Fazio, Salvatore; Menniti, Michele; Curia, Rubens; Arena, Concetta; Chimirri, Serafina; Patanè, Marinella; Esposito, Stefania; Cilurzo, Felisa; Staltari, Orietta; Russo, Emilio; De Sarro, Giovambattista
Pharmacovigilance assesses the safety profile of drugs. Its main aim is the increase of spontaneous reporting of adverse drug reactions (ADRs). The Italian Drug Agency (AIFA; Agenzia Italiana del Farmaco) is financing several projects to the aim of increasing reporting, and in Calabria a Pharmacovigilance Information Centre has been created. We analyzed the AIFA database relatively to Calabria in the year 2011 and we have analyzed ADRs using descriptive statistics. We have also collected a questionnaire-based interview in order to describe the background knowledge in the field. Regarding the number of AIFA reported ADRs from Calabria, a 38% increase (138 vs. 100) in comparison to 2010 was evidenced. Hospital Doctors represent the main source of signaling (71.7 %). Ketoprofene and the combination amoxicillin/clavulanic acid represent the most frequently reported drugs causing ADRs. Our questionnaires indicated that despite the health professionals have met at least once an ADR only a small percentage of them was reported to the authorities (37%). There is a very good knowledge of the ADR concept and reporting system (90% of interviewed distinguish an ADR and knows how to report it), and there is a strong interest in participating to training courses in the field (95% are interested). Despite Calabria has had a positive increase in the number of reported ADRs, the total number is very low and the pharmacovigilance culture is far from being achieved in this region.
Treudler, R; Walther, F; Ahnert, P; Simon, J-C
Few data exist on adverse drug reactions (ADR) in elderly people. In this group, pharmacotherapy represents a challenge with regard to comorbidities, drug interactions and compliance. The aim of this article is to highlight the characteristics of ADR in elderly patients. In addition to a literature review we present the first data from the Leipzig Research Center for Civilization Diseases (LIFE). Between 2011 and 2015 a total of 9537 subjects aged 40-79 years were randomly included in this population-based, age and sex standardized investigation in the inhabitants of Leipzig, Germany and special emphasis was placed on allergies including questions with regard to ADR. Of the 9537 subjects, data on allergies were available from 8979 subjects. Female gender, comorbidities and the use of multiple drugs were significantly associated with an increased risk of ADR. Women also reported ADR significantly more frequently than men. Of the subjects 22% reported suffering from some form of ADR as a result of medications, while in 2.3% this reaction had occurred within the previous 12 months. Less than 15% of LIFE patients with ADR were in possession of a document giving details of the ADR. The occurrence of ADR significantly contributes to morbidity in elderly patients. For prevention of ADR knowledge of patient-related factors, underlying diseases, drug characteristics and drug interactions are necessary.
Zhichkin, P E; Athey, B D; Avigan, M I; Abernethy, D R
The growing significance of bioinformatics and systems biology in drug safety research requires a system of adverse-event classification that goes beyond a simple vocabulary. This opinion piece outlines the need for development of an ontology-based framework of describing adverse drug reactions (ADRs) and describes the potential applications for such a framework.
Hirsch, Michael J.; Meneses, Claudio N.; Pardalos, Panos M.; Ragle, Michelle; Resende, Mauricio G. C.
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.
Hirsch, Michael J.; Meneses, Claudio N.; Pardalos, Panos M.; Ragle, Michelle; Resende, Mauricio G. C.
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.
Sridhar, Sathvik Belagodu; Al-Thamer, Sura Saad Faris; Jabbar, Riadh
Background: Adverse drug reactions (ADRs) are a significant cause of morbidity and mortality, resulting in increased healthcare cost. Association of psychotropic medications with ADRs is common. Pharmacovigilance can play a vital role in alerting the healthcare providers from the possible ADRs and thus protecting the patients receiving psychotropic medications. Aim: To monitor and report the incidence and nature of ADRs in psychiatry outpatient department (OPD). Materials and Methods: A prospective observational study was carried out in the psychiatry OPD. All the patients attending psychiatry outpatient and satisfying the inclusion criteria were monitored for ADRs. The causality, severity and preventability assessment of documented ADRs was done. Chi-square test was done to identify the association between ADRs and sociodemographic, disease and treatment-related variables. Paired Student's t-test was carried out to compare the significance difference in the weight of the patients who reported weight gain to psychotropic medications. Results: The incidence rate of ADR was found to be 10.2%. A total of 112 ADRs were documented. Weight gain 18 (16.07%) followed by somnolence 8 (7.14%) was the most commonly reported ADR. Atypical antipsychotics 37 (33.0%) were the most common class of psychotropic drugs implicated in ADRs. Escitalopram 16 (14.28%) followed by quetiapine 14 (12.5%) were associated with a maximum number of ADRs. No significant association (P > 0.05) documented between demographic and treatment-related variables with number of ADRs. Conclusion: Study revealed a moderate incidence of ADRs in patients attending the psychiatry OPD. Majority of the ADRs reported during the study were mild in nature and not preventable type. PMID:27330260
Sridhar, Sathvik Belagodu; Al-Thamer, Sura Saad Faris; Jabbar, Riadh
Adverse drug reactions (ADRs) are a significant cause of morbidity and mortality, resulting in increased healthcare cost. Association of psychotropic medications with ADRs is common. Pharmacovigilance can play a vital role in alerting the healthcare providers from the possible ADRs and thus protecting the patients receiving psychotropic medications. To monitor and report the incidence and nature of ADRs in psychiatry outpatient department (OPD). A prospective observational study was carried out in the psychiatry OPD. All the patients attending psychiatry outpatient and satisfying the inclusion criteria were monitored for ADRs. The causality, severity and preventability assessment of documented ADRs was done. Chi-square test was done to identify the association between ADRs and sociodemographic, disease and treatment-related variables. Paired Student's t-test was carried out to compare the significance difference in the weight of the patients who reported weight gain to psychotropic medications. The incidence rate of ADR was found to be 10.2%. A total of 112 ADRs were documented. Weight gain 18 (16.07%) followed by somnolence 8 (7.14%) was the most commonly reported ADR. Atypical antipsychotics 37 (33.0%) were the most common class of psychotropic drugs implicated in ADRs. Escitalopram 16 (14.28%) followed by quetiapine 14 (12.5%) were associated with a maximum number of ADRs. No significant association (P > 0.05) documented between demographic and treatment-related variables with number of ADRs. Study revealed a moderate incidence of ADRs in patients attending the psychiatry OPD. Majority of the ADRs reported during the study were mild in nature and not preventable type.
Benichou, C; Castle, W
Global management of drug safety data is the best way to make the detection and validation of adverse drug reactions (ADRs) earlier. Centralization needs a previous standardization, of which terminology is a crucial component. ADR terminology must be designed so as to enable users to know exactly what is covered by each term regarding the nature of the reaction and its significance for public health. A worldwide standardized terminology for all drug reporting purposes is currently being developed by the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use. However, practical definitions of medical terms will be necessary and could be developed by specialists on drug safety in collaboration with specialists of different system organs, as has already been achieved for some of them.
Khan, David A
Adverse drug reactions (ADRs) are a relatively common cause of morbidity and mortality. Many factors can contribute to ADRs, including genetics. The degree to which genetics contributes to ADRs is not entirely clear and varies by drug, as well as the type of ADR. Pharmacogenetics and, more recently, pharmacogenomics have been applied to the field of ADRs for both predictable ADRs and hypersensitivity drug reactions. Evaluations for glucose-6-phosphate dehydrogenase and thiopurine S-methyltransferase are commonplace clinical tests to reduce hematologic problems associated with drugs, such as dapsone and azathioprine, respectively. Numerous pharmacogenetic associations have been discovered for immediate hypersensitivity reactions to β-lactams, aspirin, and nonsteroidal anti-inflammatory drugs; however, the clinical utility of testing for these genetic associations has not been established. In contrast, pharmacogenetic testing for HLA-B*1502 before carbamazepine in patients of certain Asian ethnicities and testing for HLA-B*5701 before abacavir treatment are recommended. This review will focus on pharmacogenetics and pharmacogenomics and their role in reducing ADRs, especially those caused by drug hypersensitivity reactions. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Oshikoya, Kazeem A; Awobusuyi, Jacob O
Spontaneous adverse drug reaction (ADR) reporting is the cornerstone of pharmacovigilance. ADR reporting with Yellow Cards has tremendously improved pharmacovigilance of drugs in many developed countries and its use is advocated by the World Health Organization (WHO). This study was aimed at investigating the knowledge and attitude of doctors in a teaching hospital in Lagos, Nigeria on spontaneous ADR reporting and to suggest possible ways of improving this method of reporting. A total of 120 doctors working at the Lagos State University Teaching Hospital (LASUTH), in Nigeria were evaluated with a questionnaire for their knowledge and attitudes to ADR reporting. The questionnaire sought the demographics of the doctors, their knowledge and attitudes to ADR reporting, the factors that they perceived may influence ADR reporting, and their levels of education and training on ADR reporting. Provision was also made for suggestions on the possible ways to improve ADR reporting. The response rate was 82.5%. A majority of the respondents (89, 89.9%) considered doctors as the most qualified health professionals to report ADRs. Forty (40.4%) of the respondents knew about the existence of National Pharmacovigilance Centre (NPC) in Nigeria. Thirty-two (32.3%) respondents were aware of the Yellow Card reporting scheme but only two had ever reported ADRs to the NPC. About half (48.5%) of the respondents felt that all serious ADRs could be identified after drug marketing. There was a significant difference between the proportion of respondents who felt that ADR reporting should be either compulsory or voluntary (chi2 = 38.9, P < 0.001). ADR reporting was encouraged if the reaction was serious (77, 77.8%) and unusual (70, 70.7%). Education and training was the most recognised means of improving ADR reporting. The knowledge of ADRs and how to report them are inadequate among doctors working in a teaching hospital in Lagos, Nigeria. More awareness should be created on the Yellow Card
Background Adverse drug reactions (ADRs) are recognised as a common cause of hospital admissions, and they constitute a significant economic burden for hospitals. Hospital-based ADR monitoring and reporting programmes aim to identify and quantify the risks associated with the use of drugs provided in a hospital setting. This information may be useful for identifying and minimising preventable ADRs and may enhance the ability of prescribers to manage ADRs more effectively. The main objectives of this study were to evaluate ADRs that occurred during inpatient stays at the Hospital Geral de Palmas (HGP) in Tocantins, Brazil, and to facilitate the development of a pharmacovigilance service. Methods A prospective study was conducted at HGP over a period of 8 months, from January 2009 to August 2009. This observational, cross-sectional, descriptive study was based on an analysis of medical records. Several parameters were utilised in the data evaluation, including patient demographics, drug and reaction characteristics, and reaction outcomes. The reaction severity and predisposing factors were also assessed. Results The overall incidence of ADRs in the patient population was 3.1%, and gender was not found to be a risk factor. The highest ADR rate (75.8%) was found in the adult age group 15 to 50 years, and the lowest ADR rate was found in children aged 3 to 13 years (7.4%). Because of the high frequency of ADRs in orthopaedic (25%), general medicine (22%), and oncology (16%) patients, improved control of the drugs used in these specialties is required. Additionally, the nurse team (52.7%) registered the most ADRs in medical records, most likely due to the job responsibilities of nurses. As expected, the most noticeable ADRs occurred in skin tissues, with such ADRs are more obvious to medical staff, with rashes being the most common reactions. Metamizole, tramadol, and vancomycin were responsible for 21, 11.6, and 8.4% of ADRs, respectively. The majority of ADRs had
Wahlang, Julie Birdie; Laishram, Purnima Devi; Brahma, Dhriti Kumar; Sarkar, Chayna; Lahon, Joonmoni; Nongkynrih, Banylla Shisha
Background: An adverse drug reaction (ADR) is defined by World Health Organization (WHO) as ‘Any response to a drug which is noxious, unintended and occurs at doses used in man for prophylaxis, diagnosis or therapy’. ADRs associated with cancer chemotherapy warrant analysis on their severity and preventability. The outcome would create awareness among health care providers and prevent their recurrence. We have performed a hospital-based prospective observational study designed to analyze the pattern of ADRs to chemotherapeutic agents in cancer patients of a tertiary care hospital. Methods: A total of 119 cancer patients were monitored for suspected ADRs during the course of chemotherapy from November 2014 to December 2015. Clinical events were recorded and analyzed with regard to the demographics and drug details of the patients. Results: A total of 106 ADRs were recorded from 119 cases. The ADRs commonly encountered included constipation, nausea, vomiting, alopecia and hematological changes. Cisplatin, cyclophosphamide, paclitaxel and 5-FU were used for the treatment of commonly found cancers in this region affecting the lungs, esophagus and lymphomas. Naranjo’s causality assessment showed 86.7% possible (score 4) and 13.2% probable (score 5–6). Severity of adverse reactions showed 77.4% mild, 18.9% moderate and 3.8% severe. A total of 45.3% of ADRs were preventable reactions such as nausea, vomiting and constipation. Conclusions: This study highlights the role of active monitoring as an important tool for early detection, assessment and timely management of ADRs in patients undergoing cancer chemotherapy. The observed ADRs were preventable although ADRs such as hiccough, anemia, neutropenia and alopecia were not preventable.
Chopra, Deepti; Wardhan, Neeta; Rehan, H S
This study was aimed at investigating the knowledge, attitude and practices associated with adverse drug reaction (ADR) reporting among doctors in a teaching hospital. A total of 100 doctors working in a teaching hospital were evaluated with a questionnaire for their knowledge, attitude and practices related to ADR reporting and pharmacovigilance programmes. Nearly two third (66%) of the doctors knew the definition of ADR. Only one third (38%, 40%) could correctly define pharmacovigilance and adverse drug event (ADE) respectively. Although 100% of the doctors felt the need for a National Pharmacovigilance Programme (NPP) only approximately three fourth (73%) were aware of the existing programme in India and nearly half of the them (47%) actually knew the current status of the NPP at their institute. Surprisingly only one tenth of the doctors (10%) knew what should be reported. The majority (74.4%) felt that reactions to new drug should be reported and also those reactions that are serious and unusual. Only one third (30%) knew whom to report to and less than half (30%) had actually ever reported an ADR. The knowledge of ADRs and how to report them is inadequate among doctors. More awareness should be created regarding the purpose and usefulness of ADR reporting through Continuous Medical Education, training and integration of ADR reporting into the clinical activities of the doctors.
Moore, Nicholas; Pollack, Charles; Butkerait, Paul
Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen have a long history of safe and effective use as both prescription and over-the-counter (OTC) analgesics/antipyretics. The mechanism of action of all NSAIDs is through reversible inhibition of cyclooxygenase enzymes. Adverse drug reactions (ADRs) including gastrointestinal bleeding as well as cardiovascular and renal effects have been reported with NSAID use. In many cases, ADRs may occur because of drug–drug interactions (DDIs) between the NSAID and a concomitant medication. For example, DDIs have been reported when NSAIDs are coadministered with aspirin, alcohol, some antihypertensives, antidepressants, and other commonly used medications. Because of the pharmacologic nature of these interactions, there is a continuum of risk in that the potential for an ADR is dependent on total drug exposure. Therefore, consideration of dose and duration of NSAID use, as well as the type or class of comedication administered, is important when assessing potential risk for ADRs. Safety findings from clinical studies evaluating prescription-strength NSAIDs may not be directly applicable to OTC dosing. Health care providers can be instrumental in educating patients that using OTC NSAIDs at the lowest effective dose for the shortest required duration is vital to balancing efficacy and safety. This review discusses some of the most clinically relevant DDIs reported with NSAIDs based on major sites of ADRs and classes of medication, with a focus on OTC ibuprofen, for which the most data are available. PMID:26203254
Nelson, M R; Bacanu, S-A; Mosteller, M; Li, L; Bowman, C E; Roses, A D; Lai, E H; Ehm, M G
Adverse drug reactions (ADRs) have a major impact on patients, physicians, health care providers, regulatory agencies and pharmaceutical companies. Identifying the genetic contributions to ADR risk may lead to a better understanding of the underlying mechanisms, identification of patients at risk and a decrease in the number of events. Technological advances have made the routine monitoring and investigation of the genetic basis of ADRs during clinical trials possible. We demonstrate through simulation that genome-wide genotyping, coupled with the use of clinically matched or population controls, can yield sufficient statistical power to permit the identification of strong genetic predictors of ADR risk in a prospective manner with modest numbers of ADR cases. The results of a 500,000 single nucleotide polymorphism analysis of abacavir-associated hypersensitivity reaction suggest that the known HLA-B gene region could be identified with as few as 15 cases and 200 population controls in a sequential analysis.
Jin, Huidong Warren; Chen, Jie; He, Hongxing; Williams, Graham J; Kelman, Chris; O'Keefe, Christine M
In various real-world applications, it is very useful mining unanticipated episodes where certain event patterns unexpectedly lead to outcomes, e.g., taking two medicines together sometimes causing an adverse reaction. These unanticipated episodes are usually unexpected and infrequent, which makes existing data mining techniques, mainly designed to find frequent patterns, ineffective. In this paper, we propose unexpected temporal association rules (UTARs) to describe them. To handle the unexpectedness, we introduce a new interestingness measure, residual-leverage, and develop a novel case-based exclusion technique for its calculation. Combining it with an event-oriented data preparation technique to handle the infrequency, we develop a new algorithm MUTARC to find pairwise UTARs. The MUTARC is applied to generate adverse drug reaction (ADR) signals from real-world healthcare administrative databases. It reliably shortlists not only six known ADRs, but also another ADR, flucloxacillin possibly causing hepatitis, which our algorithm designers and experiment runners have not known before the experiments. The MUTARC performs much more effectively than existing techniques. This paper clearly illustrates the great potential along the new direction of ADR signal generation from healthcare administrative databases.
Latha, S; Choon, S E
Cutaneous adverse drug reactions (cADRs) are common. There are only few studies on the incidence of cADRs in Malaysia. To determine the incidence, clinical features and risk factors of cADRs among hospitalized patients. A prospective study was conducted among medical inpatients from July to December 2014. A total of 43 cADRs were seen among 11 017 inpatients, yielding an incidence rate of 0.4%. cADR accounted for hospitalization in 26 patients. Previous history of cADR was present in 14 patients, with 50% exposed to the same drug taken previously. Potentially lifethreatening severe cutaneous adverse reactions (SCAR), namely drug reaction with eosinophilia and systemic symptoms (DRESS: 14 cases) and Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN: 6 cases) comprise almost 50% of cADRs. The commonest culprit drug group was antibiotics (37.2%), followed by anticonvulsants (18.6%). Cotrimoxazole, phenytoin and rifampicin were the main causative drugs for DRESS. Anticonvulsants were most frequently implicated in SJS/TEN (66.7%). Most cases had "probable" causality relationship with suspected drug (69.8%). The majority of cases were of moderate severity (65.1%), while 18.6% had severe reaction with 1 death recorded. Most cases were not preventable (76.7%). Older age (> 60 years) and mucosal involvement were significantly associated with a more severe reaction. The incidence of cADRs was 0.4%, with most cases classified as moderate severity and not preventable. The commonest reaction pattern was DRESS, while the main culprit drug group was antibiotics. Older age and mucosal membrane involvement predicts a severe drug reaction.
Pathak, Anuj Kumar; Kumar, Manish; Dokania, Shambhu; Mohan, Lalit; Dikshit, Harihar
Pharmacovigilance (PV) is related to detection, assessment, understanding and prevention of Adverse Drug Reactions (ADRs) which are incurred when drug is made available in the market and used in different physiological conditions. In many countries, ADRs ranks among the top ten leading cause of morbidity and mortality. There is a lack of formal culture for monitoring and reporting of ADRs in India, with ADR reporting rate being only 1% as compared to 5% in world. This type of academic detailing activity helps to create awareness of ADR reporting in the institutions. This study was planned to evaluate and analyse the incidence and patterns of ADRs in various inpatient and outpatient departments of hospital. This was an observational, retrospective and record based study conducted by analysing the spontaneous ADR forms, collected over a period of 12 months (September 2014 to August 2015) at Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India. During the period of one year, 292 ADR forms were collected from 4,34,965 patients attending OPD and inpatients of the hospital. Incidence of ADR was 0.67 per thousand patients and average of around 24 ADR collected per month. Male:Female ratio was 1.30. Adolescent (16-30 yr) was the most common age group affected. Department of Skin and VD reported the maximum number of ADRs (33.22%), followed by the Departments of Oncology (18.84%). Antibiotics were the most common drug implicated followed by anticancer drugs. ADR reporting is an ongoing and continuous process. Studies from the institute helps to identify and rectify the problems related to ADR reporting. Pitfalls can be addressed by creating awareness among physicians and the patients to achieve finally the goal of Pharmacovigilant India.
Pathak, Anuj Kumar; Dokania, Shambhu; Mohan, Lalit; Dikshit, Harihar
Introduction Pharmacovigilance (PV) is related to detection, assessment, understanding and prevention of Adverse Drug Reactions (ADRs) which are incurred when drug is made available in the market and used in different physiological conditions. In many countries, ADRs ranks among the top ten leading cause of morbidity and mortality. There is a lack of formal culture for monitoring and reporting of ADRs in India, with ADR reporting rate being only 1% as compared to 5% in world. This type of academic detailing activity helps to create awareness of ADR reporting in the institutions. Aim This study was planned to evaluate and analyse the incidence and patterns of ADRs in various inpatient and outpatient departments of hospital. Materials and Methods This was an observational, retrospective and record based study conducted by analysing the spontaneous ADR forms, collected over a period of 12 months (September 2014 to August 2015) at Indira Gandhi Institute of Medical Sciences, Patna, Bihar, India. Results During the period of one year, 292 ADR forms were collected from 4,34,965 patients attending OPD and inpatients of the hospital. Incidence of ADR was 0.67 per thousand patients and average of around 24 ADR collected per month. Male:Female ratio was 1.30. Adolescent (16-30 yr) was the most common age group affected. Department of Skin and VD reported the maximum number of ADRs (33.22%), followed by the Departments of Oncology (18.84%). Antibiotics were the most common drug implicated followed by anticancer drugs. Conclusion ADR reporting is an ongoing and continuous process. Studies from the institute helps to identify and rectify the problems related to ADR reporting. Pitfalls can be addressed by creating awareness among physicians and the patients to achieve finally the goal of Pharmacovigilant India. PMID:27656459
Pedrós, Consuelo; Formiga, Francesc; Corbella, Xavier; Arnau, Josep Maria
To assess the prevalence of urgent hospitalization due to adverse drug reactions (ADRs) in patients aged ≥ 65 years, to compare the in-hospital mortality rates between patients admitted for ADRs and those admitted for other causes, and to describe the ADRs, the used and suspected drugs, and the drug-reaction associations. A cross-sectional study was conducted by using the institutional database of the Pharmacovigilance Programme of Bellvitge University Hospital, a 750-bed tertiary care hospital, with information corresponding to a 7-year period. ADR-related admissions of patients aged ≥ 65 years prospectively identified through a systematic daily review of all admission diagnosis were reviewed. ADRs were suspected to be the main reason for urgent admission in 1976 out of 60,263 patients aged ≥ 65 years (prevalence of ADR-related hospitalization 3.3 % [95 % CI 3.1-3.4 %]). The crude in-hospital mortality rate was 10.2 % in patients with ADR-related admission and 9 % in patients admitted for other causes (p = 0.077). Most patients (86 %) were exposed to polypharmacy, and a drug-drug interaction was suspected in 49 % of cases. The most frequent drug-reaction associations were acute renal failure related to renin-angiotensin system inhibitors, gastrointestinal bleeding caused by antithrombotics and/or non-steroidal anti-inflammatories, and intracranial bleeding induced by vitamin K antagonists. One out of every 30 urgent admissions of patients aged ≥ 65 years is ADR-related. These ADRs can be as serious and life-threatening as any other acute pathology that merits urgent hospital admission. Most cases involve patients exposed to polypharmacy and result from well-known reactions of a few commonly used drugs.
Paveliu, Marian Sorin; Bengea-Luculescu, Simona; Toma, Mihai; Paveliu, Silvia Fraga
The purpose of our study was to investigate and to assess the perceptions of Romanian doctors towards adverse drug reactions (ADRs) reporting. A questionnaire with 20 items accompanied by a letter presenting the study was circulated using Internet and face to face interviews to 532 doctors in Bucharest and two neighboring regions from Romania (Muntenia and Oltenia). 204 (56.2%) of the total number of responders expressed their opinion that the daily number of ADRs observed to be under 5 309 (58%) of responders were never informed about ADRs reporting, 439 (82.52%) did not know that the Romanian College of Physicians is scoring this activity under the "Continuous medical education program". Factors that might encourage voluntary reporting of adverse reactions were identified to be: the easiness of reporting, their periodic information and the training about all adverse reactions reported by doctors and the measures taken. Factors discouraging voluntary reporting of an adverse drug reaction were: the lack of information on where, when and how to report ADRs, the uncertain causality. Currently, the pharmacovigilance activities including reporting of ADRs in Romania are more of an accidental nature, doctors are less or not at all informed about this activity. Doctors have a favorable attitude towards reporting ADRs - as the majority believes that the reporting should be either voluntary or mandatory as opposed to a small number that would expect to be paid for this activity.
PAVELIU, Marian Sorin; BENGEA-LUCULESCU, Simona; TOMA, Mihai; PAVELIU, Silvia Fraga
ABSTRACT Aim: The purpose of our study was to investigate and to assess the perceptions of Romanian doctors towards adverse drug reactions (ADRs) reporting. Method: A questionnaire with 20 items accompanied by a letter presenting the study was circulated using Internet and face to face interviews to 532 doctors in Bucharest and two neighboring regions from Romania (Muntenia and Oltenia). Results: 204 (56.2%) of the total number of responders expressed their opinion that the daily number of ADRs observed to be under 5 309 (58%) of responders were never informed about ADRs reporting, 439 (82.52%) did not know that the Romanian College of Physicians is scoring this activity under the "Continuous medical education program". Factors that might encourage voluntary reporting of adverse reactions were identified to be: the easiness of reporting, their periodic information and the training about all adverse reactions reported by doctors and the measures taken. Factors discouraging voluntary reporting of an adverse drug reaction were: the lack of information on where, when and how to report ADRs, the uncertain causality. Conclusion: Currently, the pharmacovigilance activities including reporting of ADRs in Romania are more of an accidental nature, doctors are less or not at all informed about this activity. Doctors have a favorable attitude towards reporting ADRs – as the majority believes that the reporting should be either voluntary or mandatory as opposed to a small number that would expect to be paid for this activity. PMID:24023593
Meyer, Roger E. , Ed.
This reports a conference of psychologists, psychiatrists, geneticists and others concerned with the biological and psychological effects of lysergic acid diethylamide and other hallucinogenic drugs. Clinical data are presented on adverse drug reactions. The difficulty of determining the causes of adverse reactions is discussed, as are different…
Elzagallaai, A A; Greff, Mje; Rieder, M J
Adverse drug reactions (ADRs) represent a major health problem worldwide, with high morbidity and mortality rates. ADRs are classified into Type A (augmented) and Type B (bizarre) ADRs, with the former group being more common and the latter less common but often severe and clinically more problematic due to their unpredictable nature and occurrence at any dose. Pediatric populations are especially vulnerable to ADRs due to the lack of data for this age group from the drug development process and because of the wide use of off-label and unlicensed use of drugs. Children are more prone to specific types of ADRs because of the level of maturity of body systems involved in absorption, metabolism, transportation, and elimination of drugs. This state-of-the-art review provides an overview of definitions, classifications, epidemiology, and pathophysiology of ADRs and discusses the available evidence for related risk factors and causes of ADRs in the pediatric population. © 2017 American Society for Clinical Pharmacology and Therapeutics.
Hashiguchi, Masayuki; Imai, Shungo; Uehara, Keiko; Maruyama, Junya; Shimizu, Mikiko; Mochizuki, Mayumi
We investigated factors affecting the timing of signal detection by comparing variations in reporting time of known and unknown ADRs after initial drug release in the USA. Data on adverse event reactions (AERs) submitted to U.S. FDA was used. Six ADRs associated with 6 drugs (rosuvastatin, aripiprazole, teriparatide, telithromycin, exenatide, varenicline) were investigated: Changes in the proportional reporting ratio, reporting odds ratio, and information component as indexes of signal detection were followed every 3 months after each drugs release, and the time for detection of signals was investigated. The time for the detection of signal to be detected after drug release in the USA was 2-10 months for known ADRs and 19-44 months for unknown ones. The median lag time for known and unknown ADRs was 99.0-122.5 days and 185.5-306.0 days, respectively. When the FDA released advisory information on rare but potentially serious health risks of an unknown ADR, the time lag to report from the onset of ADRs to the FDA was shorter. This study suggested that one factor affecting signal detection time is whether an ADR was known or unknown at release.
Hashiguchi, Masayuki; Imai, Shungo; Uehara, Keiko; Maruyama, Junya; Shimizu, Mikiko; Mochizuki, Mayumi
We investigated factors affecting the timing of signal detection by comparing variations in reporting time of known and unknown ADRs after initial drug release in the USA. Data on adverse event reactions (AERs) submitted to U.S. FDA was used. Six ADRs associated with 6 drugs (rosuvastatin, aripiprazole, teriparatide, telithromycin, exenatide, varenicline) were investigated: Changes in the proportional reporting ratio, reporting odds ratio, and information component as indexes of signal detection were followed every 3 months after each drugs release, and the time for detection of signals was investigated. The time for the detection of signal to be detected after drug release in the USA was 2–10 months for known ADRs and 19–44 months for unknown ones. The median lag time for known and unknown ADRs was 99.0–122.5 days and 185.5–306.0 days, respectively. When the FDA released advisory information on rare but potentially serious health risks of an unknown ADR, the time lag to report from the onset of ADRs to the FDA was shorter. This study suggested that one factor affecting signal detection time is whether an ADR was known or unknown at release. PMID:26641634
Benard, Brigitte; Bastien, Valérie; Vinet, Benjamin; Yang, Roger; Krajinovic, Maja
Although montelukast is generally well tolerated, postmarketing studies have reported serious neuropsychiatric adverse drug reactions (ADRs) leading to a United States Food and Drug Administration black box warning. The objective of this study was to determine the incidence of neuropsychiatric ADRs leading to discontinuation of montelukast in asthmatic children. We conducted a retrospective cohort study in children aged 1–17 years initiated on montelukast. In a nested cohort study, children initiated on montelukast as monotherapy or adjunct therapy to inhaled corticosteroids (ICS) were matched to those initiated on ICS monotherapy. A non-leading parental interview served to ascertain the occurrence of any ADRs with any asthma medication, and circumstances related to, and evolution of, the event. Out of the 106 participants who initiated montelukast, most were male (58%), Caucasian (62%) with a median (interquartile range) age of 5 (3–8) years. The incidence (95% CI) of drug cessation due to neuropsychiatric ADRs was 16 (10–26)%, mostly occurring within 2 weeks. Most frequent ADRs were irritability, aggressiveness and sleep disturbances. The relative risk of neuropsychiatric ADRs associated with montelukast versus ICS was 12 (2–90). In the real-life setting, asthmatic children initiated on montelukast experienced a notable risk of neuropsychiatric ADRs leading to drug cessation, that is significantly higher than that associated with ICS. PMID:28818882
Benard, Brigitte; Bastien, Valérie; Vinet, Benjamin; Yang, Roger; Krajinovic, Maja; Ducharme, Francine M
Although montelukast is generally well tolerated, postmarketing studies have reported serious neuropsychiatric adverse drug reactions (ADRs) leading to a United States Food and Drug Administration black box warning. The objective of this study was to determine the incidence of neuropsychiatric ADRs leading to discontinuation of montelukast in asthmatic children.We conducted a retrospective cohort study in children aged 1-17 years initiated on montelukast. In a nested cohort study, children initiated on montelukast as monotherapy or adjunct therapy to inhaled corticosteroids (ICS) were matched to those initiated on ICS monotherapy. A non-leading parental interview served to ascertain the occurrence of any ADRs with any asthma medication, and circumstances related to, and evolution of, the event.Out of the 106 participants who initiated montelukast, most were male (58%), Caucasian (62%) with a median (interquartile range) age of 5 (3-8) years. The incidence (95% CI) of drug cessation due to neuropsychiatric ADRs was 16 (10-26)%, mostly occurring within 2 weeks. Most frequent ADRs were irritability, aggressiveness and sleep disturbances. The relative risk of neuropsychiatric ADRs associated with montelukast versus ICS was 12 (2-90).In the real-life setting, asthmatic children initiated on montelukast experienced a notable risk of neuropsychiatric ADRs leading to drug cessation, that is significantly higher than that associated with ICS. Copyright ©ERS 2017.
Hartholt, Klaas A; van der Velde, Nathalie; Looman, Caspar W N; Panneman, Martien J M; van Beeck, Ed F; Patka, Peter; van der Cammen, Tischa J M
Epidemiologic information on time trends of Adverse Drug Reactions (ADR) and ADR-related hospitalizations is scarce. Over time, pharmacotherapy has become increasingly complex. Because of raised awareness of ADR, a decrease in ADR might be expected. The aim of this study was to determine trends in ADR-related hospitalizations in the older Dutch population. Secular trend analysis of ADR-related hospital admissions in patients ≥60 years between 1981 and 2007, using the National Hospital Discharge Registry of The Netherlands. Numbers, age-specific and age-adjusted incidence rates (per 10,000 persons) of ADR-related hospital admissions were used as outcome measures in each year of the study. Between 1981 and 2007, ADR-related hospital admissions in persons ≥60 years increased by 143%. The overall standardized incidence rate increased from 23.3 to 38.3 per 10,000 older persons. The increase was larger in males than in females. Since 1997, the increase in incidence rates of ADR-related hospitalizations flattened (percentage annual change 0.65%), compared to the period 1981-1996 (percentage annual change 2.56%). ADR-related hospital admissions in older persons have shown a rapidly increasing trend in The Netherlands over the last three decades with a temporization since 1997. Although an encouraging flattening in the increasing trend of ADR-related admissions was found around 1997, the incidence is still rising, which warrants sustained attention to this problem.
Jamal, Salma; Goyal, Sukriti; Shanker, Asheesh; Grover, Abhinav
Adverse drug reactions (ADRs) have become one of the primary reasons for the failure of drugs and a leading cause of deaths. Owing to the severe effects of ADRs, there is an urgent need for the generation of effective models which can accurately predict ADRs during early stages of drug development based on integration of various features of drugs. In the current study, we have focused on neurological ADRs and have used various properties of drugs that include biological properties (targets, transporters and enzymes), chemical properties (substructure fingerprints), phenotypic properties (side effects (SE) and therapeutic indications) and a combinations of the two and three levels of features. We employed relief-based feature selection technique to identify relevant properties and used machine learning approach to generated learned model systems which would predict neurological ADRs prior to preclinical testing. Additionally, in order to explain the efficiency and applicability of the models, we tested them to predict the ADRs for already existing anti-Alzheimer drugs and uncharacterized drugs, respectively in side effect resource (SIDER) database. The generated models were highly accurate and our results showed that the models based on chemical (accuracy 93.20%), phenotypic (accuracy 92.41%) and combination of three properties (accuracy 94.18%) were highly accurate while the models based on biological properties (accuracy 82.11%) were highly informative.
Machado-Alba, Jorge Enrique; Ruiz, Andrés Felipe; Machado-Duque, Manuel Enrique
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.
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
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.
Kiguba, Ronald; Karamagi, Charles; Bird, Sheila M
We sought to determine the prevalence at admission and incidence during hospitalization of antibiotic-associated suspected adverse drug reactions (aa-ADRs) among Ugandan inpatients; and to characterize these aa-ADRs. We conducted a prospective cohort study of 762 consented adults admitted on medical and gynecological wards of the 1790-bed Mulago National Referral Hospital. Thirty percent were known HIV-seropositive (232/762). Nineteen percent (148/762; 95% CI: 17-22%) of inpatients experienced at least one aa-ADR. At hospital admission, 6% (45/762; 95% CI: 4-8%) of patients had at least one aa-ADR; and 15% (45/300; 11-20%) of those who had received antibiotics in the 4-weeks preadmission. Twenty-four (53%) of these 45 patients had serious aa-ADRs. The incidence of aa-ADRs was 19% (117/629; 95% CI: 16-22%) of patients who received antibiotics [community-acquired: 9% (27/300; 95% CI: 6-13%); hospital-acquired: 16% (94/603; 95% CI: 13-19%)]: 39 (33%) of 117 patients had serious aa-ADRs. Of 269 aa-ADRs, 115 (43%) were community-acquired, 66 (25%) probable/definite, 171 (64%) preventable, 86 (32%) serious, and 24 (9%) rare. Ceftriaxone was the most frequently implicated for serious hospital-acquired aa-ADRs. Cotrimoxazole, isoniazid, rifampicin, ethambutol, and pyrazinamide were the most frequently linked to serious community-acquired aa-ADRs. Fatal jaundice (isoniazid), life-threatening difficulty in breathing with shortness of breath (rifampicin) and disabling itchy skin rash with numbness of lower swollen legs (ethambutol, isoniazid) were observed. Pharmaceutical quality testing of implicated antibiotics could be worthwhile. Periodic on-ward collection and analysis of antibiotic-safety-data standardized by consumption is an efficient method of tracking antibiotics with 1%-risk for serious aa-ADRs.
Khan, Kashifullah; Khan, Amer Hayat; Sulaiman, Syed Azhar; Soo, Chow Ting; Akhtar, Ali
In the current study we explored the occurrence of adverse drug reactions (ADRs) to antiretroviral therapy among human immune-deficiency virus (HIV)/AIDS patients. We concluded an observational retrospective study in all patients who were diagnosed with HIV infection and were receiving highly active antiviral therapy from Jan. 2007 to Dec. 2012 at Hospital Pulau Pinang, Malaysia. Patient socio-demographic details along with clinical features and susceptible ADRs were observed during the study period. Out of 743 patients, 571 (76.9%) were men, and 172 (23.1%) were women. Overall 314 (42.2%) patients experienced ADRs. A total of 425 ADRs were reported, with 311 (73.1%) occurring in men and 114 (26.8%) in women, with a significant statistical relationship (P value (P) = 0.02, OR = 1.21). Overall 239 (56.2%) ADRs were recorded among Chinese, 94 (22.1%) in Malay, and 71 (16.7%) in Indian patients, which had a statistically significant association with ADRs (P = 0.05, OR = 1.50). Out of a total 425 among ADRs, lipodystrophy was recorded in 151 (35.5%) followed by skin rashes in 80 (18.8%), anemia in 74 (17.4%), and peripheral neuropathy in 27 (6.3%) patients. These findings suggest a need of intensive monitoring of ADRs in HIV treatment centres across Malaysia.
Hanafi, Somayeh; Torkamandi, Hassan; Hayatshahi, Alireza; Gholami, Kheirollah; Shahmirzadi, Nikinaz Ashrafi; Javadi, Mohammad Reza
The reporting of adverse drug reactions (ADRs) by nurses in hospitals is very important. This study was aimed at investigating the impact of an educational intervention to improve ADR reporting and whether trained nurses had better knowledge, attitude, and practice toward ADR reporting. A total of 300 nurses in a tertiary care teaching hospital in Tehran, Iran were evaluated with a knowledge, attitude, and practice (KAP) questionnaire regarding ADR reporting in March 2010. After this, an educational program about ADR was provided to nurses. Then the nurses were re-evaluated by the same questionnaire. Comparisons were made of the attitude and knowledge within nurses, before and after education. Data were analyzed using SPSS software. P < 0.05 was considered as significant level. Independent-sample t-test was used to measure the intervention effect. The response rate was 61.3% (N = 184). Knowledge of nurses before the intervention was significantly less than the knowledge after the intervention (P = 0.001). Also, there was a significant effect on attitude (P = 0.002). During the follow-up period of 4 months after the intervention, 26 spontaneous reports were received. Continuous ADR educational program, training, and integration of ADRs' reporting into the activities of the nurses would likely improve ADR reporting.
Du, Wei; Lehr, Victoria Tutag; Lieh-Lai, Mary; Koo, Winston; Ward, Robert M; Rieder, Michael J; Van Den Anker, John N; Reeves, Jaxk H; Mathew, Merene; Lulic-Botica, Mirjana; Aranda, Jacob V
Critically ill newborns in neonatal intensive care units (NICUs) are at greater risk of developing adverse drug reactions (ADRs). Differentiation of ADRs from reactions associated with organ dysfunction/immaturity is difficult. Current ADR algorithm scoring was established arbitrarily without validation in infants. The study objective was to develop a valid and reliable algorithm to identify ADRs in the NICU. Algorithm development began with a 24-item questionnaire for data collection on 100 previously suspected ADRs. Five pediatric pharmacologists independently rated cases as definite, probable, possible, and unlikely ADRs. Consensus "gold standard" was reached via teleconference. Logistic regression and iterative C programs were used to derive the scoring system. For validation, 50 prospectively collected ADR cases were assessed by 3 clinicians using the new algorithm and the Naranjo algorithm. Weighted kappa and intraclass correlation coefficient (ICC) were used to compare validity and reliability of algorithms. The new algorithm consists of 13 items. Kappa and ICC of the new algorithm were 0.76 and 0.62 versus 0.31 and 0.43 for the Naranjo algorithm. The new algorithm developed using actual patient data is more valid and reliable than the Naranjo algorithm for identifying ADRs in the NICU population. Because of the relatively small and nonrandom samples, further refinement and additional testing are needed.
Vallano, A; Cereza, G; Pedròs, C; Agustí, A; Danés, I; Aguilera, C; Arnau, J M
To describe the opinions of hospital physicians concerning problems regarding the spontaneous reporting of adverse drug reactions (ADRs) and ways to solve them. A qualitative study was carried out. Fifteen focus groups were conducted among physicians working in a tertiary teaching hospital. A total of 208 physicians from different medical specialities participated. The focus group discussions were recorded by three different observers and the transcripts of each session were analysed for issues and themes emerging from the text. Four types of obstacles to spontaneous reporting were considered particularly important: (i) problems with the ADR(S) diagnosis; (ii) problems with the usual workload and lack of time; (iii) problems related to the organization and activities of the pharmacovigilance system; (iv) and problems related to potential conflicts. The potential solutions suggested for improving spontaneous reporting were to define the kind of ADR(S) which should be reported, to facilitate an easy contact and quick access to the hospital pharmacovigilance system, to facilitate information and support for reporting and feedback of pharmacovigilance activities. The perception of the different obstacles by the hospital physicians is an important factor in determining the causes of the underreporting of ADRs and addressing these obstacles could lead to an improvement in spontaneous reporting. A closer relationship between the doctors and the pharmacovigilance centre is suggested as a means of solving these problems. More information is needed to improve the spontaneous reporting of ADR(S) in specialized healthcare.
Becker, Daniel E.
The potential for interactions with current medications should always be considered when administering or prescribing any drug. Considering the staggering number of drugs patients may be taking, this task can be daunting. Fortunately, drug classes employed in dental practice are relatively few in number and therapy is generally brief in duration. While this reduces the volume of potential interactions, there are still a significant number to be considered. This article will review basic principles of drug interactions and highlight those of greatest concern in dental practice. PMID:21410363
Liu, Mei; Cai, Ruichu; Hu, Yong; Matheny, Michael E; Sun, Jingchun; Hu, Jun; Xu, Hua
Adverse drug reaction (ADR) can have dire consequences. However, our current understanding of the causes of drug-induced toxicity is still limited. Hence it is of paramount importance to determine molecular factors of adverse drug responses so that safer therapies can be designed. We propose a causality analysis model based on structure learning (CASTLE) for identifying factors that contribute significantly to ADRs from an integration of chemical and biological properties of drugs. This study aims to address two major limitations of the existing ADR prediction studies. First, ADR prediction is mostly performed by assessing the correlations between the input features and ADRs, and the identified associations may not indicate causal relations. Second, most predictive models lack biological interpretability. CASTLE was evaluated in terms of prediction accuracy on 12 organ-specific ADRs using 830 approved drugs. The prediction was carried out by first extracting causal features with structure learning and then applying them to a support vector machine (SVM) for classification. Through rigorous experimental analyses, we observed significant increases in both macro and micro F1 scores compared with the traditional SVM classifier, from 0.88 to 0.89 and 0.74 to 0.81, respectively. Most importantly, identified links between the biological factors and organ-specific drug toxicities were partially supported by evidence in Online Mendelian Inheritance in Man. The proposed CASTLE model not only performed better in prediction than the baseline SVM but also produced more interpretable results (ie, biological factors responsible for ADRs), which is critical to discovering molecular activators of ADRs.
Liu, Mei; Cai, Ruichu; Hu, Yong; Matheny, Michael E; Sun, Jingchun; Hu, Jun; Xu, Hua
Objective Adverse drug reaction (ADR) can have dire consequences. However, our current understanding of the causes of drug-induced toxicity is still limited. Hence it is of paramount importance to determine molecular factors of adverse drug responses so that safer therapies can be designed. Methods We propose a causality analysis model based on structure learning (CASTLE) for identifying factors that contribute significantly to ADRs from an integration of chemical and biological properties of drugs. This study aims to address two major limitations of the existing ADR prediction studies. First, ADR prediction is mostly performed by assessing the correlations between the input features and ADRs, and the identified associations may not indicate causal relations. Second, most predictive models lack biological interpretability. Results CASTLE was evaluated in terms of prediction accuracy on 12 organ-specific ADRs using 830 approved drugs. The prediction was carried out by first extracting causal features with structure learning and then applying them to a support vector machine (SVM) for classification. Through rigorous experimental analyses, we observed significant increases in both macro and micro F1 scores compared with the traditional SVM classifier, from 0.88 to 0.89 and 0.74 to 0.81, respectively. Most importantly, identified links between the biological factors and organ-specific drug toxicities were partially supported by evidence in Online Mendelian Inheritance in Man. Conclusions The proposed CASTLE model not only performed better in prediction than the baseline SVM but also produced more interpretable results (ie, biological factors responsible for ADRs), which is critical to discovering molecular activators of ADRs. PMID:24334612
de Figueiredo, Tácita Pires; de Souza Groia, Ronara Camila; Barroso, Soraya Coelho Costa; do Nascimento, Mariana Martins Gonzaga; Reis, Adriano Max Moreira
Background Adverse drug reactions (ADRs) occur frequently during hospital stays and are an important public health problem, particularly in the care of the older. Objectives This study aimed to determine the prevalence of ADRs among older inpatients and the factors associated with their occurrence. Setting Brazilian teaching hospital. Methods This was a cross-sectional study with older inpatients in the internal medicine ward of a teaching hospital. The dependent variable was the occurrence of an ADR during hospitalization. The independent variables were gender, age, length of hospitalization, number of health problems, medications, and potentially inappropriate medications for the older. Logistic regression was performed to analyze the association between an ADR and the independent variables. Main outcome measure Factors associated with ADR in older inpatients. Results Among the 237 inpatients investigated, 50 (21.1%) developed at least one ADR. The total number of ADRs observed was 62 and the most frequent were acute kidney injury, hypotension, and cutaneous adverse reactions A multivariate analysis demonstrated a positive and independent association between the occurrence of an ADR and the presence of heart failure [odds ratio (OR) 2.4; 95% confidence interval (CI) 1.2-4.6], and with hospitalization time exceeding 12 days (OR 2.3; 95% CI 1.2-4.4). Conclusions The study showed a high prevalence of ADRs among the older and a positive association with hospitalization time and heart failure. Understanding the factors associated with the occurrence of ADRs among older inpatients provides elements for improving the safety of care and optimization of pharmacotherapy.
Wallach, Izhar; Jaitly, Navdeep; Lilien, Ryan
Adverse drug reactions (ADR), also known as side-effects, are complex undesired physiologic phenomena observed secondary to the administration of pharmaceuticals. Several phenomena underlie the emergence of each ADR; however, a dominant factor is the drug's ability to modulate one or more biological pathways. Understanding the biological processes behind the occurrence of ADRs would lead to the development of safer and more effective drugs. At present, no method exists to discover these ADR-pathway associations. In this paper we introduce a computational framework for identifying a subset of these associations based on the assumption that drugs capable of modulating the same pathway may induce similar ADRs. Our model exploits multiple information resources. First, we utilize a publicly available dataset pairing drugs with their observed ADRs. Second, we identify putative protein targets for each drug using the protein structure database and in-silico virtual docking. Third, we label each protein target with its known involvement in one or more biological pathways. Finally, the relationships among these information sources are mined using multiple stages of logistic-regression while controlling for over-fitting and multiple-hypothesis testing. As proof-of-concept, we examined a dataset of 506 ADRs, 730 drugs, and 830 human protein targets. Our method yielded 185 ADR-pathway associations of which 45 were selected to undergo a manual literature review. We found 32 associations to be supported by the scientific literature. PMID:20808786
Alhawassi, Tariq M; Krass, Ines; Bajorek, Beata V; Pont, Lisa G
Adverse drug reactions (ADRs) are an important health issue. While prevalence and risk factors associated with ADRs in the general adult population have been well documented, much less is known about ADRs in the elderly population. The aim of this study was to review the published literature to estimate the prevalence of ADRs in the elderly in the acute care setting and identify factors associated with an increased risk of an ADR in the elderly. A systematic review of studies published between 2003 and 2013 was conducted in the Cochrane Database of Systematic Reviews, EMBASE, Google Scholar and MEDLINE. Key search terms included: “adverse drug reactions”, “adverse effects”, “elderly patients and hospital admission”, “drug therapy”, “drug adverse effects”, “drug related”, “aged”, “older patients”, “geriatric”, “hospitalization”, and “emergency admissions”. For inclusion in the review, studies had to focus on ADRs in the elderly and had to include an explicit definition of what was considered an ADR and/or an explicit assessment of causality, and a clear description of the method used for ADR identification, and had to describe factors associated with an increased risk of an ADR. Fourteen hospital-based observational studies exploring ADRs in the elderly in the acute care setting were eligible for inclusion in this review. The mean prevalence of ADRs in the elderly in the studies included in this review was 11.0% (95% confidence interval [CI]: 5.1%–16.8%). The median prevalence of ADRs leading to hospitalization was 10.0% (95% CI: 7.2%–12.8%), while the prevalence of ADRs occurring during hospitalization was 11.5% (95% CI: 0%–27.7%). There was wide variation in the overall ADR prevalence, from 5.8% to 46.3%. Female sex, increased comorbid complexity, and increased number of medications were all significantly associated with an increased risk of an ADR. Retrospective studies and those relying on identification by the
Bandekar, M S; Anwikar, S R; Kshirsagar, N A
Adverse drug reactions (ADRs) are considered as one of the leading causes of death among hospitalized patients. Thus reporting of adverse drug reactions become an important phenomenon. Spontaneous adverse drug reaction reporting form is an essential component and a major tool of the pharmacovigilance system of any country. This form is a tool to collect information of ADRs which helps in establishing the causal relationship between the suspected drug and the reaction. As different countries have different forms, our aim was to study, analyze the suspected adverse drug reaction reporting form of different countries, and assess if these forms can capture all the data regarding the adverse drug reaction. For this analysis we identified 18 points which are essential to make a good adverse drug reaction report, enabling proper causality assessment of adverse reaction to generate a safety signal. Adverse drug reaction reporting forms of 10 different countries were collected from the internet and compared for 18 points like patient information, information about dechallenge-rechallenge, adequacy of space and columns to capture necessary information required for its causality assessment, etc. Of the ADR forms that we analyzed, Malaysia was the highest scorer with 16 out of 18 points. This study reveals that there is a need to harmonize the ADR reporting forms of all the countries because there is a lot of discrepancy in data captured by the existing ADR reporting forms as the design of these forms is different for different countries. These incomplete data obtained result in inappropriate causality assessment. Copyright © 2010 John Wiley & Sons, Ltd.
Rodrigues, Maria Cristina Soares; de Oliveira, Cesar
ABSTRACT Objective: to identify and summarize studies examining both drug-drug interactions (DDI) and adverse drug reactions (ADR) in older adults polymedicated. Methods: an integrative review of studies published from January 2008 to December 2013, according to inclusion and exclusion criteria, in MEDLINE and EMBASE electronic databases were performed. Results: forty-seven full-text studies including 14,624,492 older adults (≥ 60 years) were analyzed: 24 (51.1%) concerning ADR, 14 (29.8%) DDI, and 9 studies (19.1%) investigating both DDI and ADR. We found a variety of methodological designs. The reviewed studies reinforced that polypharmacy is a multifactorial process, and predictors and inappropriate prescribing are associated with negative health outcomes, as increasing the frequency and types of ADRs and DDIs involving different drug classes, moreover, some studies show the most successful interventions to optimize prescribing. Conclusions: DDI and ADR among older adults continue to be a significant issue in the worldwide. The findings from the studies included in this integrative review, added to the previous reviews, can contribute to the improvement of advanced practices in geriatric nursing, to promote the safety of older patients in polypharmacy. However, more research is needed to elucidate gaps. PMID:27598380
Spiteri, M. A.; James, D. G.
Drugs acting on various parts of the body may also affect the eye insidiously. Increased awareness of such drug toxicity by the prescribing doctor should encourage him to consider effects on the cornea, lens, retina, optic nerve and elsewhere when checking the patient's progress. The following review concerns adverse ocular effects of systemic drug administration. PMID:6356101
Fabiano, Valentina; Mameli, Chiara; Zuccotti, Gian Vincenzo
The detection, assessment, understanding and prevention of adverse drug reactions (ADRs) are the primary aims of pharmacovigilance activities. Pediatric patients, especially all newborns and infants, are particularly at risk for experiencing drug-related adverse events. This review briefly analyzes the physiological peculiarities of pharmacodynamic and pharmacokinetic aspects of drugs in newborns, infants and toddlers and children. It also deals with specific pediatric pharmacovigilance aspects, such as the frequent use of unlicensed and/or off-label drugs in neonatal intensive care units in European countries and in Australia. This review reports on European, American and Canadian data about the incidence and type of pediatric ADRs, particularly focusing on neonates, infants and toddlers. The awareness of pediatricians about the importance of reporting ADRs should be stimulated, new reporting systems should be encouraged and pediatric pharmacovigilance activities should be improved, first, by intensifying active post-marketing surveillance methods.
Yu, Yun Mi; Shin, Wan Gyoon; Lee, Ju-Yeun; Choi, Soo An; Jo, Yun Hee; Youn, So Jung; Lee, Mo Se; Choi, Kwang Hoon
Purpose To evaluate the clinical manifestations and causative drugs associated with adverse drug reactions (ADRs) spontaneously reported by community pharmacists and to compare the ADRs by age. Methods ADRs reported to the Regional Pharmacovigilance Center of the Korean Pharmaceutical Association by community pharmacists from January 2013 to June 2014 were included. Causality was assessed using the WHO-Uppsala Monitoring Centre system. The patient population was classified into three age groups. We analyzed 31,398 (74.9%) ADRs from 9,705 patients, identified as having a causal relationship, from a total pool of 41,930 ADRs from 9,873 patients. Median patient age was 58.0 years; 66.9% were female. Results Gastrointestinal system (34.4%), nervous system (14.4%), and psychiatric (12.1%) disorders were the most frequent symptoms. Prevalent causative drugs were those for acid-related disorders (11.4%), anti-inflammatory products (10.5%), analgesics (7.2%), and antibacterials (7.1%). Comparisons by age revealed diarrhea and antibacterials to be most commonly associated with ADRs in children (p < 0.001), whereas dizziness was prevalent in the elderly (p < 0.001). Anaphylactic reaction was the most frequent serious event (19.7%), mainly associated with cephalosporins and non-steroidal anti-inflammatory drugs. Among 612 ADRs caused by nonprescription drugs, the leading symptoms and causative drugs were skin disorders (29.6%) and non-steroidal anti-inflammatory drugs (16.2%), respectively. Conclusions According to the community pharmacist reports, the leading clinical manifestations and causative drugs associated with ADRs in outpatients differed among age groups. PMID:26172050
Srikanth, B. Akshaya; Babu, S. Chandra; Yadav, Harlokesh Narayan; Jain, Sunil Kumar
To estimate the incidence of adverse drug reactions (ADRs) in Human immune deficiency virus (HIV) patients on highly active antiretroviral therapy (HAART). To identify the risk factors associated with ADRs in HIV patients. To analyze reported ADRs based on various parameters like causality, severity, predictability, and preventability. Retrospective case-control study. An 18-month retrospective case-control study of 208 patients newly registered in ART center, RIMS hospital, Kadapa, were intensively monitored for ADRs to HAART. Predictability was calculated based on the history of previous exposure to drug. Multivariate logistic regressions were used to identify the risk factors for ADRs. Data were analyzed using the chi-square test for estimating the correlation between ADRs and different variables. All statistical calculations were performed using EpiInfo version 3.5.3. Monitoring of 208 retrospective patients by active Pharmacovigilance identified 105 ADRs that were identified in 71 patients. Skin rash and anemia were the most commonly observed ADRs. The organ system commonly affected by ADR was skin and appendages (31.57%). The ADRs that were moderate were 90.14% of cases. The incidence of ADRs (53.52%) was higher with Zidovudine + Lamivudine + Nevirapine combination. CD4 cell count less than <250 cells/μl were 80.28%, male gender were observed to be the risk factors for ADRs. Our study finding showed that there is a need of active pharmaceutical care with intensive monitoring for ADRs in Indian HIV-positive patients who are illiterate, of male and female gender, with CD4 count ≤250 cells/mm3 with comorbid conditions. PMID:22470896
Adler, N R; Graudins, L V; Aung, A K
We read with interest Teo et al.'s recently published article examining cutaneous adverse drug reactions (cADR) referred to an inpatient liaison dermatology service.(1) The authors assessed the number and types of cADR encountered and subsequent documentation.(1) The diagnosis and management of cADR has been recognised by NICE Guidelines on Drug Allergy as a high-priority area for quality improvement.(2) We commend Teo and colleagues(1) for examining an essential, yet often overlooked, component of health service quality. We would like to further highlight the importance of risk communication, documentation and patient-centred care, aspects that are imperative for severe cADR. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Background Adverse drug reactions (ADR) are a substantial cause of hospital admissions. We conducted a nationwide study to estimate the burden of hospital admissions for ADRs in Spain during a six-year period (2001-2006) along with the associated total health cost. Methods Data were obtained from the national surveillance system for hospital data (Minimum Basic Data Set) maintained by the Ministry of Health and Consumer Affairs, and covering more than 95% of Spanish hospitals. From these admissions we selected all hospitalization that were code as drug-related (ICD-9-CM codes E), but intended forms of overdoses, errors in administration and therapeutics failure were excluded. The average number of hospitalizations per year, annual incidence of hospital admissions, average length of stay in the hospital, and case-fatality rate, were calculated. Results During the 2001-2006 periods, the total number of hospitalized patients with ADR diagnosis was 350,835 subjects, 1.69% of all acute hospital admissions in Spain. The estimated incidence of admissions due to ADR decreased during the period 2001-2006 (p < 0.05). More than five percent of patients (n = 19,734) died during an ADR-related hospitalization. The drugs most commonly associated with ADR-related hospitalization were antineoplastic and immunosuppressive drugs (n = 75,760), adrenal cortical steroids (n = 47,539), anticoagulants (n = 26,546) and antibiotics (n = 22,144). The costs generated by patients in our study increased by 19.05% between 2001 and 2006. Conclusions Approximately 1.69% of all acute hospital admissions were associated with ADRs. The rates were much higher for elderly patients. The total cost of ADR-related hospitalization to the Spanish health system is high and has increased between 2001 and 2006. ADRs are an important cause of admission, resulting in considerable use of national health system beds and a significant number of deaths. PMID:20942906
Prajapati, Kinjal; Desai, Mira; Shah, Samidh; Panchal, Jigar; Kapadia, Jigar; Dikshit, Ramkumar
Objective: The objective of this study was to analyze the various aspects of serious adverse drug reactions (serious ADRs) such as clinical presentation, causality, severity, and preventability occurring in a hospital setting. Materials and Methods: All serious ADRs reported from January 2010 to May 2015 at ADR Monitoring Centre, Department of Pharmacology, B. J. Medical College and Civil Hospital, Ahmedabad, were selected as per the World health Organization –Uppsala Monitoring Center (WHO-UMC) criteria. A retrospective analysis was carried out for clinical presentation, causality (as per the WHO-UMC scale and Naranjo's algorithm), severity (Hartwig and Siegel scale), and preventability (Schumock and Thornton criteria). Results: Out of 2977 ADRs reported, 375 were serious in nature. The most common clinical presentation involved was skin and appendageal disorders (71, 18.9%). The common causal drug group was antitubercular (129, 34.4%) followed by antiretroviral (76, 20.3%) agents. The criteria for the majority of serious ADRs were intervention to prevent permanent impairment or damage (164, 43.7%) followed by hospitalization (158, 42.1%). Majority of the serious ADRs were continuing (191, 50.9%) at the time of reporting, few recovered (101, 26.9%), and two were fatal. The majority of serious ADRs were categorized as possible (182, 48.8%) followed by probable (173, 46.1%) in nature. Conclusion: Antitubercular, antiretroviral, and antimicrobial drugs were the most common causal drug groups for serious ADRs. This calls for robust ADR monitoring system and education of patients and prescribers for identification and effective management. PMID:27843794
Cumberland, Phillippa M; Russell-Eggitt, Isabelle; Rahi, Jugnoo S
As visual impairment (VI) due to adverse drug reactions (ADR) is rare in adults and children, there is an incomplete evidence base to inform guidance for screening and for counseling patients on the potential risks of medications. We report on suspected drugs and the eye conditions found in a national study of incidence of diagnosis of visual impairment due to suspected ADR. Case ascertainment was via the British Ophthalmological Surveillance Unit (BOSU), between March 2010 and February 2012, with follow-up after 6 months. any child or adult with bilateral or unilateral visual impairment due to a suspected ADR, using distance acuity worse than Snellen 6/18 (logMAR 0.48) in the better eye (bilateral) or affected eye (unilateral). Anonymized patient information on potential cases was provided by managing ophthalmologists, comprising visual status before and after suspected ADR, ophthalmic condition attributable to the ADR, preexisting eye disease and prescribed medications at the time of the ADR. Permanency and causality of the visual impairment were confirmed by the managing clinician, after 6 months, using the WHO Uppsala Monitoring Committee criteria. Over 2 years, 36 eligible cases were reported of whom 23 had permanent VI. While most cases were due to drugs known to have adverse side-effects, some were unanticipated sporadic cases. Visual impairment due to ADRs is rare. However, with for example, increasing polypharmacy in the elderly, monitoring of ocular ADRs, although challenging, is necessary.
Böhmdorfer, Birgit; Schaffarzick, Daniel; Nagano, Marietta; Janowitz, Susanne Melitta; Schweitzer, Ekkehard
We present a multidisciplinary (anaesthesiology--clinical pharmacy--bioinformatics) analysis of pain as possible adverse drug reaction taking different manifestations of pain, indication groups, relevance to the Austrian drug market and possible mechanistic influence of drugs on development and apprehension of pain into consideration.We designed an overview that shows how transmitters that play a part in nociception and antinociception can be influenced by drugs. This allows conclusions to the dolorigene potential of therapeutics.
Vingerhoets, R W; van Marum, R J; Jansen, P A F
Elderly patients are highly susceptible for developing adverse drug reactions (ADR) that can lead to hospitalisation or death. Most of these ADR can be prevented if doctors adjust their prescriptions. Beers et al. have developed a list of drugs that should not be prescribed to elderly patients since they are known for their association with serious ADR. In The Netherlands, 20% of elderly patients receive drugs that are in the so-called Beers list. Although the Beers list has not been adjusted to the Dutch situation, avoidance of these drugs may reduce drug-related hospital admittance. Development of an improved list of drugs that should not be prescribed to elderly patients is needed that is applicable to The Netherlands.
Mudzviti, Tinashe; Sibanda, Marvelous; Gavi, Samuel; Maponga, Charles Chiedza; Morse, Gene D.
Background Cutaneous adverse drug reactions (cADRs) can cause significant morbidity and distress in patients especially in the HIV infected population on antiretroviral therapy. Adverse Drug Reaction monitoring and ascertaining causality in resource limited settings still remains a challenge. This study was carried out to evaluate causality and measure incidence of cADRs in HIV infected patients on highly active antiretroviral therapy. The study was also designed to test a 3-step approach in the monitoring and evaluation of ADRs in resource limited settings. Methodology A retrospective patient medical records review was carried out at the Parirenyatwa Family Care Centre, (Harare, Zimbabwe). Cases of cADRs were reported to the Medicines Control Authority of Zimbabwe (Drug regulating body in Zimbabwe) for assessment and causality classification. Results Two hundred and twenty-one patient records were randomly selected and reviewed to determine if any diagnosis of cADRs was made by clinicians. Causality assessment revealed 13.1% of cADRs which were due to an offending agent in the antiretroviral therapy against an initial incidence of 17.6% which had been determined by the physicians. Conclusions cADRs had an incidence of 13.1% within the population under study due to non nucleoside reverse transcriptase inhibitors (NNRTIs). Most reactions were due to the NNRTIs which contributed 72.4 % of all cADRs. A panel of experts from the drug regulatory authority can be used as an implementation based mechanism in ascertaining causality objectively in settings where resources are constrained. PMID:23277506
de Rouw, Hendrika J. A.; Jessurun, Naomi T.; Masen-Poos, Lucie J. P.; Derijks, Hieronymus J.
In this report we describe a 53-year-old woman with advanced non-small cell lung cancer, treated with pemetrexed and cisplatin combination therapy, followed by pemetrexed monotherapy. The patient developed severe muscle spasms at least twice, shortly after administration of pemetrexed monotherapy. A possible explanation for this observation is that in combination with cisplatin therapy, the patient was hyperhydrated before administration to promote renal excretion and reduce toxicity. Pemetrexed is also renally excreted, which supports the finding that toxicity did not occur when the patient was hyperhydrated. After discontinuation of pemetrexed the symptoms did not reoccur. All aspects of this case point to a possible relationship between pemetrexed and an adverse drug reaction (ADR). We conclude that muscle spasms are a rare, but possibly dose-related ADR of pemetrexed-based therapy. PMID:28203304
Chan, Kelvin; Zhang, Hongwei; Lin, Zhi-Xiu
The safe use of Chinese materia medica (CMM) and products in traditional Chinese medicine (TCM) practice conventionally relies on correct pharmacognostic identification, good agricultural and manufacturing practices based on pharmacopoeia standards and rational/correct CMM combinations with TCM-guided clinical prescribing. These experience-based principles may not absolutely ensure safety without careful toxicological investigations when compared with development of new pharmaceutical drugs. Clinically observed toxicity reports remain as guidance for gathering toxicological evidence, though essential as pharmacovigilance, but are considered as late events for ensuring safety. The overview focuses on the following factors: global development of TCM that has affected conventional healthcare; examples of key toxic substances in CMM; reported adverse drug reactions (ADRs) consequential to taking CMM and TCM products; and proposals on rational approaches to integrate the knowledge of biomedical science and the principles of TCM practice for detecting early ADRs if both TCM products and orthodox drugs are involved. It is envisaged that good control of the quality and standards of CMM and proprietary Chinese medicines can certainly reduce the incidence of ADRs in TCM practice when these medications are used. © 2015 The British Pharmacological Society.
Chan, Kelvin; Zhang, Hongwei; Lin, Zhi-Xiu
The safe use of Chinese materia medica (CMM) and products in traditional Chinese medicine (TCM) practice conventionally relies on correct pharmacognostic identification, good agricultural and manufacturing practices based on pharmacopoeia standards and rational/correct CMM combinations with TCM-guided clinical prescribing. These experience-based principles may not absolutely ensure safety without careful toxicological investigations when compared with development of new pharmaceutical drugs. Clinically observed toxicity reports remain as guidance for gathering toxicological evidence, though essential as pharmacovigilance, but are considered as late events for ensuring safety. The overview focuses on the following factors: global development of TCM that has affected conventional healthcare; examples of key toxic substances in CMM; reported adverse drug reactions (ADRs) consequential to taking CMM and TCM products; and proposals on rational approaches to integrate the knowledge of biomedical science and the principles of TCM practice for detecting early ADRs if both TCM products and orthodox drugs are involved. It is envisaged that good control of the quality and standards of CMM and proprietary Chinese medicines can certainly reduce the incidence of ADRs in TCM practice when these medications are used. PMID:25619530
Hanafi, Somayeh; Torkamandi, Hassan; Hayatshahi, Alireza; Gholami, Kheirollah; Javadi, Mohammadreza
Background: Adverse drug reactions (ADR) are ranked as some of the major causes of patient morbidity and mortality. Spontaneous reporting of ADRs has remained the cornerstone of pharmacovigilance and is important in maintaining patient safety. This study was conducted to assess the nurses’ knowledge and attitude towards pharmacovigilance, reasons for not reporting ADRs, and their pharmacovigilance practice. Materials and Methods: A questionnaire was prepared to investigate knowledge, attitude and practice (KAP) of nurses regarding ADR reporting. In November 2009, the questionnaires were given to 500 nurses of a teaching hospital in Tehran. Findings: Knowledge and practice of participants were not satisfying; however, their attitude towards pharmacovigilance was at a high level. About 91% of the nurses had never reported an ADR. Most nurses liked to report the ADRs to the physicians (87.1%) and pharmacists in hospital's ADR center (1.8%) rather than the ADR National Center. The main cause of under-reporting of the suspected ADRs was unawareness about the existence of such a national center. Among nurses who had reported ADR for at least once, the majority preferred using phone (10 out of 50) or Yellow Cards (7 out of 50). Only 1 person out of 50 preferred using internet for submitting the reports Conclusions: Since the nurses in this study had little knowledge and poor practice regarding the pharmacovigilance and spontaneous reporting system, interventions such as holding pharmacovigilance workshops in the hospitals focusing on the aims of pharmacovigilance, completing the Yellow Card and clarifying the reporting criteria are strongly recommended. PMID:23492864
Prows, Cynthia A; Zhang, Xue; Huth, Myra M; Zhang, Kejian; Saldaña, Shannon N; Daraiseh, Nancy M; Esslinger, Hope R; Freeman, Edita; Greinwald, John H; Martin, Lisa J; Sadhasivam, Senthilkumar
To prospectively determine factors associated with codeine's adverse drug reactions (ADRs) at home in a large homogenous population of children undergoing outpatient tonsillectomy. Prospective, genotype blinded, observational study with a single group and repeated ADR measures documented by parents at home. A total of 249 children 6 to 15 years of age scheduled for tonsillectomy were enrolled. The primary outcome was number of daily codeine-related ADRs. We examined the number and type of ADR by race and by days and further modeled factors potentially associated with ADR risk in a subcohort of white children. Sedation following a dose of codeine was a secondary outcome measure. Parents recorded their children's daily ADRs and sedation scores during postoperative days (POD) 0 to 3 at home. Diaries were returned for 134 children, who were given codeine. A total of 106 (79%) reported at least one ADR. The most common ADRs were nausea, lightheadedness/dizziness for white children and nausea, and vomiting for African American children. In a subcohort of white children ≤ 45 kg, increased ADR risk was associated with the presence of one or more full function CYP2D6 alleles (P < 0.001), POD (P < 0.001), and sex (P = 0.027). Increased pain intensity (P = 0.009) and PODs 0 and 1 (P = 0.001) contributed to a higher sedation risk. Neither obstructive apnea nor predicted CYP2D6 phenotype were associated with sedation risk. Our results provide evidence that multiple factors are associated with codeine-related ADRs and support the FDA recommendation to avoid codeine's routine use following tonsillectomy in children. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.
Danton, Anne Charlotte; Montastruc, François; Sommet, Agnès; Durrieu, Geneviève; Bagheri, Haleh; Bondon-Guitton, Emmanuelle; Lapeyre-Mestre, Maryse; Montastruc, Jean-Louis
Our aim was to characterize Adverse Drug Reactions (ADRs) related to drug-drug interactions (DDIs) related to involvement of cytochrome P450 (CYP450) isoenzymes in a pharmacovigilance database. ADRs recorded by Midi-Pyrénées PharmacoVigilance center (France) between 1 January and 31 August 2008 were extracted from the French PharmacoVigilance Database (FPVD). Among the 1,205 reported ADRs, 16 (1.3 %), can be explained by involvement of CYP450 isoenzymes (including 4 "serious"). All interactions involved CYP inhibitors, mainly for CYP3A4/5. The percentage of ADRs reported in the pharmacovigilance database and related to CYP450-induced DDIs appears to be relatively low (~ 1-2 %).
Mangoni, Arduino A
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.
Kiguba, Ronald; Karamagi, Charles; Waako, Paul; Ndagije, Helen B; Bird, Sheila M
Objective To assess extent and determinants of past-month recognition of suspected adverse drug reactions (ADR) and past-year ADR reporting among healthcare professionals (HCPs) in Uganda. Setting Geographically diverse health facilities (public, private for-profit, private not-for-profit). Participants Of 2000 questionnaires distributed, 1345 were completed: return rate of 67%. Primary and secondary outcome measures Per cent HCPs who suspected ADR in the past month; reported ADR in the past year. Results Nurses were the majority (59%, 792/1345). Only half the respondents had heard about pharmacovigilance: 39% of nurses (295/763; 95% CI 35% to 42%), 70% otherwise (383/547; 95% CI 66% to 74%). One fifth (268/1289 or 21%; 95% CI 19% to 23%) had suspected an ADR in the previous 4 weeks, 111 of them were nurses; 15% (190/1296) had reported a suspected ADR in the past year, 103 of them were nurses. Past-month ADR suspicion was more likely by non-nurses (OR=1.7, 95% CI 1.16 to 2.40) and with medical research involvement (OR=1.5, 95% CI 1.05 to 2.15) but past-month receipt of patient ADR-complaint predominated (OR=19, 95% CI 14 to 28). Past-year ADR reporting was higher by hospital staff (OR=1.9, 95% CI 1.18 to 3.10), especially in medicine (OR=2.3, 95% CI 1.08 to 4.73); but lower from private for-profit health facilities (OR=0.5, 95% CI 0.28 to 0.77) and by older staff (OR=0.6, 95% CI 0.43 to 0.91); more likely by HCPs who had ever encountered a fatal ADR (OR=2.9, 95% CI 1.94 to 4.25), knew to whom to report (OR=1.7, 95% CI 1.18 to 2.46), or suggested how to improve ADR reporting (OR=1.6, 95% CI 1.04 to 2.49). Two attitudinal factors were important: diffidence and lethargy. Conclusions One in five HCPs suspected an ADR in the past-month and one in seven reported ADR in the previous year. Empowering patients could strengthen ADR detection and reporting in Africa. PMID:25421337
Zeng, Zhi-Ping; Jiang, Jian-Guo
Compared with the therapeutic effects of established medicinal drugs, it is often considered that natural product-derived drugs are of a more benign nature in side-effects, which has made natural medicines become a popular form of therapy. Traditional Chinese medicine (TCM) is generally considered as being natural and harmless. TCM has been paid much more attention than before and widely used for the treatment nowadays. However, with the increasing cases of adverse drug reactions (ADRs), the ADRs induced by TCM are becoming more widely recognized. Some ADRs are sometimes even life-threatening. This article reviews literatures on ADRs induced by TCM which was published in the past 10 years. A total of 3122 cases including complete data are selected for the present analysis. From the data of the 3122 cases, statistics is carried out to the distribution of administration routes and time of the occurrence of ADRs, the prognosis of ADRs, sex and age factors, types and clinical symptoms of ADRs, and drugs involved in ADRs. In addition, occurrence and influencing factors of TCM-induced diseases are also analysed, which includes spices confusion, processing drugs improperly, toxic components, long-term medication, improper concerted application, interaction of TCM and Western medicine. It is concluded that the efficacy and toxicity of TCM, often using the compound prescription involving various plants and animals, resulted from a variety of chemical constituents, which lead to a comprehensive response in the human body. The ‘toxicity’ of TCM should be correctly recognized and reasonably utilized. PMID:20233209
Kim, Bomi; Kim, Sunwha Zara; Lee, Jin; Jung, Ae Hee; Jung, Sun-Hoi; Hahn, Hyeon-Joo; Kang, Hye Ryun
Children with complex chronic conditions (CCC) are presumed to be vulnerable to adverse drug reactions (ADRs). The clinical profiles of ADRs in CCC are not well known. Herein, we aim to describe the ADR profiles in CCC with regard to typical presentations and vulnerable groups. We accessed the ADR yearly reports at a tertiary children's hospital whose practice is mainly dedicated to CCC and descriptively analyzed their clinical profiles according to the presence of a complex chronic condition, ADR severity, and age groups. A total of 1841 cases were analyzed, among which 1258 (68.3%) were mild, 493 (26.8%) moderate, and 90 (4.9%) cases were severe. A total of 1581 (85.9%) cases of complex chronic condition were reported. The proportion of CCC in each severity group increased as the ADR becomes more severe. In CCC, ADRs were most frequently reported by nurses in the adolescent group and in cases where the symptoms involved the gastrointestinal system. The class of antineoplastic and immunomodulating drugs was the most commonly suspected of causing an ADR, followed by one of the antibiotics. When we focus on the trend across the age groups, the ratio of severe-to-total ADRs decreased with older age. Among severe cases, the ratio of off-label prescription-related cases was the highest in the infant/toddler group and decreased as the groups aged. In conclusion, ADRs of CCCs admitted to a tertiary children’s hospital have a unique profile. These groups are vulnerable to ADRs and thus they should be monitored closely, especially when they are infants or toddlers, so that severe ADRs can be identified and treated immediately. PMID:28199420
Amr, Dena; Broderick-Villa, Gregory; Haigh, Philip I; Guenther, J Michael; DiFronzo, L Andrew
Currently, 1 per cent isosulfan blue dye and technetium-99-labeled sulfur colloid (SC) are used in lymphatic mapping (LM). Several reports have suggested that the incidence of adverse drug reactions (ADRs) during LM is high. We report our experience with LM for solid neoplasms in order to determine the incidence and risk factors for development of ADRs. Seven hundred fifty-three patients (90% women, mean age 57) underwent LM with blue dye alone or in combination with SC from 1998 to 2004. The most common malignancy was breast cancer (83%). One hundred ten patients (14%) had injection of both mapping agents. Most patients (87%) underwent intraparenchymal injection of LM agent. Eight patients (1.1%) had an ADR during LM; none had prior exposure to LM. Of these, 7 had limited reactions (mostly blue hives) that quickly resolved. One patient (0.1%) developed anaphylaxis. The ADR incidence in patients with a sulfa allergy was not significantly different than that in patients without a sulfa allergy (3.4 vs 1%, P = 0.12). No risk factors for development of ADR were identified. Overall, the incidence of ADR during LM is low. Patients with sulfa allergies and prior exposure to LM did not demonstrate an increased incidence of ADR. Anaphylaxis, though rare, can occur during LM.
Boland, Mary Regina; Jacunski, Alexandra; Lorberbaum, Tal; Romano, Joseph D; Moskovitch, Robert; Tatonetti, Nicholas P
Small molecules are indispensable to modern medical therapy. However, their use may lead to unintended, negative medical outcomes commonly referred to as adverse drug reactions (ADRs). These effects vary widely in mechanism, severity, and populations affected, making ADR prediction and identification important public health concerns. Current methods rely on clinical trials and postmarket surveillance programs to find novel ADRs; however, clinical trials are limited by small sample size, whereas postmarket surveillance methods may be biased and inherently leave patients at risk until sufficient clinical evidence has been gathered. Systems pharmacology, an emerging interdisciplinary field combining network and chemical biology, provides important tools to uncover and understand ADRs and may mitigate the drawbacks of traditional methods. In particular, network analysis allows researchers to integrate heterogeneous data sources and quantify the interactions between biological and chemical entities. Recent work in this area has combined chemical, biological, and large-scale observational health data to predict ADRs in both individual patients and global populations. In this review, we explore the rapid expansion of systems pharmacology in the study of ADRs. We enumerate the existing methods and strategies and illustrate progress in the field with a model framework that incorporates crucial data elements, such as diet and comorbidities, known to modulate ADR risk. Using this framework, we highlight avenues of research that may currently be underexplored, representing opportunities for future work. © 2015 Wiley Periodicals, Inc.
Boland, Mary Regina; Jacunski, Alexandra; Lorberbaum, Tal; Romano, Joseph; Moskovitch, Robert; Tatonetti, Nicholas P.
Small molecules are indispensable to modern medical therapy. However, their use may lead to unintended, negative medical outcomes commonly referred to as adverse drug reactions (ADRs). These effects vary widely in mechanism, severity, and populations affected, making ADR prediction and identification important public health concerns. Current methods rely on clinical trials and post-market surveillance programs to find novel ADRs; however, clinical trials are limited by small sample size, while post-market surveillance methods may be biased and inherently leave patients at risk until sufficient clinical evidence has been gathered. Systems pharmacology, an emerging interdisciplinary field combining network and chemical biology, provides important tools to uncover and understand ADRs and may mitigate the drawbacks of traditional methods. In particular, network analysis allows researchers to integrate heterogeneous data sources and quantify the interactions between biological and chemical entities. Recent work in this area has combined chemical, biological, and large-scale observational health data to predict ADRs in both individual patients and global populations. In this review, we explore the rapid expansion of systems pharmacology in the study of ADRs. We enumerate the existing methods and strategies and illustrate progress in the field with a model framework that incorporates crucial data elements, such as diet and comorbidities, known to modulate ADR risk. Using this framework, we highlight avenues of research that may currently be underexplored, representing opportunities for future work. PMID:26559926
Hou, Yongfang; Li, Xinling; Wu, Guizhi; Ye, Xiaofei
It has been more than 25 years since an adverse drug reaction (ADR) monitoring agency was first established in China. In the past few years, the National ADR Monitoring System (NADRMS) has developed rapidly in the country. However, this system has not been reviewed in detail in the literature. Our aim was to demonstrate how individual case safety reports (ICSRs) are reported and evaluated and how data quality control is achieved in China. We also aimed to discuss the present status and future of NADRMS. We reviewed the relevant regulations and literature around ADR reporting in China. ADR report collection tools in China have gone through three phases, namely paper-based reporting, software-based reporting using standalone computers, and online reporting. Nowadays the online reporting system plays an important role in China and the number of ADR reports has rapidly increased. NADRMS is similar to most of the ADR reporting systems around the world, but also has its own unique characteristics such as four levels of monitoring agencies. In summary, there is still a long way to go for China to establish a high-level ADR monitoring system to ensure drug safety.
Sevene, Esperança; Mariano, Alda; Mehta, Ushma; Machai, Maria; Dodoo, Alexander; Vilardell, David; Patel, Sam; Barnes, Karen; Carné, Xavier
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
Toska, Aikaterini; Mary, Geitona; Kyriakos, Souliotis; Maria, Saridi; Costas, Demetzos
Pharmacosurveillance during the administration of antibiotics is of extreme importance in paediatric patients given their different physiology and adverse drug reaction (ADR) profile compared to the adult population. Systematic reviews show that one in ten hospitalised children will experience ADRs. Administration of antibiotics is among the leading causes of such ADRs. The aim of this study was to assess ADRs reporting related to the administration of antibiotics in hospitalized paediatric patients in Greece. A cross-sectional study was conducted over a seven month period (January to July 2012) in paediatric departments in Greece. A self-administered questionnaire was distributed to a total of 750 health professionals providing paediatric care in 3 specialized paediatric hospitals and 33 paediatric departments in general and university hospitals. Descriptive and multivariate statistical analyses were performed. Levels of significance were two-tailed and statistical significance was set at P =0.05. Overall, 576 out of 750 questionnaires were returned completed, at a response rate of 76.8%. ADRs related to antibiotics were reported by 44.8% of nurses and 23.7% of doctors as occurring often/very often during their practice. 45% of doctors reported amoxicillin/clavulanic acid as the drug with the most frequent ADRs. Overall, 63% of nurses and 32.7% of doctors stated they had never reported ADRs. Doctors used yellow cards more often than nurses (65.2% vs 33.9%). Only 48.4% of doctors and 35.9% of nurses knew that ADR reporting constitutes part of their professional duties. ADRs following antibiotic administration are common in paediatric practice in Greece; however, underreporting remains a significant problem.
Yao, Jingyun; Wei, Xing; Lu, Yanhua
Drug resistance limits leukemia treatment and chaetominine, a cytotoxic alkaloid that promotes apoptosis in a K562 human leukemia cell line via the mitochondrial pathway was studied with respect to chemoresistance in a K562/Adr human resistant leukemia cell line. Cytotoxicity assays indicated that K562/Adr resistance to adriamycin (ADR) did not occur in the presence of chaetominine and that chaetominine increased chemosensitivity of K562/Adr to ADR. Data show that chaetominine enhanced ADR-induced apoptosis and intracellular ADR accumulation in K562/Adr cells. Accordingly, chaetominine induced apoptosis by upregulating ROS, pro-apoptotic Bax and downregulating anti-apoptotic Bcl-2. RT-PCR and western-blot confirmed that chaetominine suppressed highly expressed MRP1 at mRNA and protein levels. But little obvious alternation of another drug transporter MDR1 mRNA was observed. Furthermore, inhibition of MRP1 by chaetominine relied on inhibiting Akt phosphorylation and nuclear Nrf2. In summary, chaetominine strongly reverses drug resistance by interfering with the PI3K/Akt/Nrf2 signaling, resulting in reduction of MRP1-mediated drug efflux and induction of Bax/Bcl-2-dependent apoptosis in an ADR-resistant K562/Adr leukemia cell line. - Highlights: • Chaetominine enhanced chemosensitivity of ADR against K562/Adr cells. • Chaetominine increased intracellular ADR levels via inhibiting MRP1. • Chaetominine induced apoptosis of K562/Adr cells through upregulation of ROS and modulation of Bax/Bcl-2. • Inhibition of MRP1 and Nrf2 by chaetominine treatment was correlative with blockade of PI3K/Akt signaling.
O’Connor, Karen; Pimpalkhute, Pranoti; Nikfarjam, Azadeh; Ginn, Rachel; Smith, Karen L; Gonzalez, Graciela
Recent research has shown that Twitter data analytics can have broad implications on public health research. However, its value for pharmacovigilance has been scantly studied – with health related forums and community support groups preferred for the task. We present a systematic study of tweets collected for 74 drugs to assess their value as sources of potential signals for adverse drug reactions (ADRs). We created an annotated corpus of 10,822 tweets. Each tweet was annotated for the presence or absence of ADR mentions, with the span and Unified Medical Language System (UMLS) concept ID noted for each ADR present. Using Cohen’s kappa1, we calculated the inter-annotator agreement (IAA) for the binary annotations to be 0.69. To demonstrate the utility of the corpus, we attempted a lexicon-based approach for concept extraction, with promising success (54.1% precision, 62.1% recall, and 57.8% F-measure). A subset of the corpus is freely available at: http://diego.asu.edu/downloads. PMID:25954400
Yamada, Toru; Watanabe, Yuka; Kusama, Makiko; Sugiyama, Yuichi; Ono, Shunsuke
Spontaneous reported adverse drug reactions (ADRs) are currently the main source of pharmacovigilance activities in each country. The number of ADRs reported to the authority warns of safety risks to patients, but it also reflects the efficiency and limitations of the reporting system itself. This article explored how the accumulation of safety information, status in foreign countries (e.g., US approval), drug company attributes, and regulatory actions (e.g., early post-marketing phase vigilance; EPPV) were associated with the numbers of spontaneously reported ADRs in Japan. All serious ADRs for drugs for which the active ingredients or route of administration were approved in Japan from 2000 through 2005 were collected from the national database. The numbers of serious ADRs within the first 2 and 3 years after launch were analyzed using the negative binominal distribution model. The launch lag and the presence of drugs with a similar mode of action were negatively associated with the ADR numbers, but the number of study subjects for the new drug application (NDA) showed no clear association. The number of sales representatives and the implementation of EPPV were positively associated with the ADR numbers. The accumulation of foreign post-market evidence seemed to be more important for drug safety in Japan than was the amount of pre-approval safety data. The positive impacts of sales representatives and EPPV suggested a critical role for drug companies in drug safety and also the importance of considering how best to collect information in local situations with unique regulatory requirements. Copyright © 2012 John Wiley & Sons, Ltd.
Lucca, Jisha M; Ramesh, Madhan; Parthasarathi, Gurumurthy; Raman, Rajesh
Drug interactions are known to play a significant role in the incidence of adverse drug reactions (ADRs) both in the community and in hospitals. Both the newer atypical antipsychotics and their more traditional counterparts are subject to drug - drug interactions amongst themselves, with other psychotropics, and with the agents used in the treatment of various physical ailments. The most common interactions encountered in clinical practice are pharmacodynamic in nature. It is well established that antipsychotic drugs reduce the efficacy of levodopa in parkinson's disease by blockade of dopamine receptors in the corpus striatum. The case reported here illustrates a common pharmacodynamic drug interaction of haloperidol with levodopa in a 60-year-old female patient.
Clavenna, A; Bonati, M
To assess the incidence of adverse drug reactions (ADRs) in the paediatric population and the safety alerts concerning children and adolescents issued by international drug regulatory agencies since 2001. A bibliographic search was performed in the Medline and Embase databases for prospective studies published between January 2001 and December 2007 evaluating the ADR incidence in the paediatric population. Data were analysed by a random effect model. Moreover, the websites of nine international drug regulatory agencies were searched to collect information on safety alerts concerning the paediatric population. A total of eight prospective studies were evaluated, six of which concerned the ADR incidence in hospitalised children. The overall incidence of ADRs was 10.9% (95% CI 4.8 to 17.0) in hospitalised children and 1.0% (95% CI 0.3 to 1.7) in outpatient children. The rate of hospital admission due to ADRs was 1.8% (95% CI 0.4 to 3.2). The skin and gastrointestinal system were the organs most commonly affected and antibiotics were the drugs most commonly associated with ADRs. Safety alerts in the paediatric population were retrieved for 28 drugs, five of which were for psychotropic drugs and most of which were issued by the Food and Drug Administration (20 drugs). For 12 drugs, warnings were published in the 2006-2007 period. Antidepressants were the only drugs for which alerts were issued by all the drug regulatory agencies. To ensure safe and effective medicines for children, efforts are needed at different levels (governments, drug regulatory agencies, pharmaceutical industries, health care professionals, and parents). Collaborative regulatory initiatives, such as the use of common warnings, can also contribute to a more rational use of drugs for children.
Carnovale, Carla; Gentili, Marta; Fortino, Ida; Merlino, Luca; Clementi, Emilio; Radice, Sonia; ViGer Group
To recognise and prevent ADRs (including DDIs) in the elderly through a 4-year post-marketing active pharmacovigilance programme. The programme was designed to enhance high quality spontaneous reporting of ADRs in elderly patients by sampling the Italian population and was termed 'Pharmacovigilance in Geriatry (ViGer)'. ADRs were collected for adults aged over 65 years of age treated in nursing homes, continuing care retirement communities and territorial health services in Lombardy. ADRs were evaluated using the Adverse Drug Reaction Probability Scale (Naranjo) and analysed with respect to time, sex, category of ADR, seriousness, suspected medicines, notoriety. We analysed all the potential DDIs. We detected 1073 cases reports corresponding to 2110 ADRs. Vaccines, antibacterials for systemic use and antineoplastic agents were the pharmacotherapeutic subgroups most frequently involved. 18% of ADRs reports were classified as serious. In 752 reports patients were described as in polytherapy; in 55 patients (7.3%) the reported ADR were probably preventable because of DDIs involvement. The ViGer project demonstrated that active pos-marketing pharmacovigilance programmes are a valid strategy to increase awareness on geriatrics pharmacology, reduce underreporting and provide important information on previous unknown ADRs and DDIs, resulting in a therapy optimisation in clinical practice in the geriatric setting.
Fracchiolla, Nicola S; Artuso, Silvia; Cortelezzi, Agostino; Pelizzari, Anna M; Tozzi, Paola; Bonfichi, Maurizio; Bocchio, Federica; Gargantini, Livio; De Rosa, Elisa; Vighi, Giuseppe D; Prestini, Lucia; Sammassimo, Simona; Frungillo, Niccolò; Pasquini, Maria C; Ragazzi, Alessandra; Boghi, Daniele; Pastore, Alessia; Lanzi, Eraldo; Gritti, Giuseppe; Quaresmini, Giulia; Voltolini, Simone; Gaiardoni, Roberta; Corti, Consuelo; Vilardo, Maria C; La Targia, Maria L; Berini, Giacomo; Magagnoli, Massimo; Bacci, Claudia; Consonni, Dario; Rivolta, Alma L; Muti, Giuliana
Adverse drug reactions (ADRs) reduce patients' quality of life, increase mortality and morbidity, and have a negative economic impact on healthcare systems. Nevertheless, the importance of ADR reporting is often underestimated. The project "FarmaREL" has been developed to monitor and evaluate ADRs in haematological patients and to increase pharmacovigilance culture among haematology specialists. In 13 haematology units, based in Lombardy, Italy, a dedicated specialist with the task of encouraging ADRs reporting and sensitizing healthcare professionals to pharmacovigilance has been assigned. The ADRs occurring in haematological patients were collected electronically and then analysed with multiple logistic regression. Between January 2009 and December 2011, 887 reports were collected. The number of ADRs was higher in older adults (528; 59%), in male (490; 55%), and in non-Hodgkin lymphoma patients (343; 39%). Most reactions were severe (45% required or prolonged hospitalization), but in most cases, they were fully resolved at the time of reporting. According to Schumock and Thornton criteria, a percentage of ADRs as high as 7% was found to be preventable versus 2% according to reporter opinion. Patients' haematological diagnosis, not age or gender, resulted to be the variable that most influenced ADR, in particular severity and outcome. The employment of personnel specifically dedicated to pharmacovigilance is a successful strategy to improve the number and quality of ADR reports. "FarmaREL", the first programme of active pharmacovigilance in oncohaematologic patients, significantly contributed to reach the WHO "Gold Standard" for pharmacovigilance in Lombardy, Italy. Copyright © 2017 John Wiley & Sons, Ltd.
Berhe, Derbew Fikadu; Juhlin, Kristina; Star, Kristina; Beyene, Kidanemariam G M; Dheda, Mukesh; Haaijer-Ruskamp, Flora M; Taxis, Katja; Mol, Peter G M
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.
Hoban, Claire L; Byard, Roger W; Musgrave, Ian F
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.
Varallo, Fabiana Rossi; Planeta, Cleopatra S; Herdeiro, Maria Teresa; Mastroianni, Patricia de Carvalho
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. 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. 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). 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.
Mastroianni, Patricia de Carvalho
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
Geer, M I; Koul, P A; Tanki, S A; Shah, M Y
Hospital-based adverse drug reaction (ADR) monitoring and reporting studies are conducted to identify, quantify and minimize such risks associated with the use of drugs particularly on long-term basis. Kashmir province of Indian state of Jammu and Kashmir presents a huge market for medicines that runs into millions of rupees. Yet there was no provision to monitor these drugs for their adverse effects prior to this study in any of the leading hospitals of the province. As such the present study, which was first of its kind in the valley, was undertaken to assess the frequency, preventability, category, severity, causality, extension of hospital stay and costs of drug-related adverse effects in Kashmiri patients at a Srinagar-based tertiary care hospital. A prospective, observational, cohort study on 5482 patients was undertaken over a 270day period. Adult patients admitted in Internal Medicine in-patient department (IPD), presenting to the Internal Medicine out-patient department (OPD) and those visiting the Accident and Emergency Department of the study hospital were included in the study. Patients belonging to both the sexes were screened and monitored on a daily basis for the occurrence of any ADRs. Definition of ADR given by the World Health Organization (WHO) was used and causality of suspected ADRs was determined using Naranjo's algorithm whereas severity was assessed using modified Hartwig's scale and preventability was determined using Hallas methodology. Costs of ADRs and extension in hospital stay were calculated as per Lagnaou and Nicholas methodology respectively. ADRs accounted for 6.23% of adult Kashmiri patients visiting the tertiary care hospital under study, either for referral or hospitalization, with the majority (81.57%) of these ADRs being preventable; 23.68% of patients had mild ADRs, 69.29% had ADRs of moderate severity, and 7.01% had severe ADRs. Four classes of drugs most frequently suspected in admissions due to ADRs were anti
de Boer, Alie; van Hunsel, Florence; Bast, Aalt
Food supplements and herbal products are increasingly popular amongst consumers. This leads to increased risks of interactions between prescribed drugs and these products containing bioactive ingredients. From 1991 up to 2014, 55 cases of suspected adverse drug reactions due to concomitant intake of health-enhancing products and drugs were reported to Lareb, the Netherlands Pharmacovigilance Centre. An overview of these suspected interactions is presented and their potential mechanisms of action are described. Mainly during the metabolism of xenobiotics and due to the pharmacodynamics effects interactions seem to occur, which may result in adverse drug reactions. Where legislation is seen to distinct food and medicine, legislation concerning these different bioactive products is less clear-cut. This can only be resolved by increasing the molecular knowledge on bioactive substances and their potential interactions. Thereby potential interactions can be better understood and prevented on an individual level. By considering the dietary pattern and use of bioactive substances with prescribed medication, both health professionals and consumers will be increasingly aware of interactions and these interactive adverse effects can be prevented.
Bracken, Louise E.; Nunn, Anthony J.; Kirkham, Jamie J.; Peak, Matthew; Arnott, Janine; Smyth, Rosalind L.; Pirmohamed, Munir; Turner, Mark A.
Aim To develop and test a new tool to assess the avoidability of adverse drug reactions that is suitable for use in paediatrics but which is also applicable to a variety of other settings. Methods The study involved multiple phases. Preliminary work involved using the Hallas scale and a modification of the existing Hallas scale, to assess two different sets of adverse drug reaction (ADR) case reports. Phase 1 defined, modified and refined a new tool using multidisciplinary teams. Phase 2 involved the assessment of 50 ADR case reports from a prospective study of paediatric inpatients by individual assessors. Phase 3 compared assessments with the new tool for individuals and groups in comparison to the ‘gold standard’ (the avoidability outcome set by a panel of senior investigators: an experienced clinical pharmacologist, paediatrician and pharmacist). Main Outcome Measures Inter-rater reliability (IRR), measure of disagreement and utilization of avoidability categories. Results Preliminary work—Pilot phase: results for the original Hallas cases were fair and pairwise kappa scores ranged from 0.21 to 0.36. Results for the modified Hallas cases were poor, pairwise kappa scores ranged from 0.06 to 0.16. Phase 1: on initial use of the new tool, agreement between the two multidisciplinary groups was found on 13/20 cases with a kappa score of 0.29 (95% CI -0.04 to 0.62). Phase 2: the assessment of 50 ADR case reports by six individual reviewers yielded pairwise kappa scores ranging from poor to good 0.12 to 0.75 and percentage exact agreement (%EA) ranged from 52–90%. Phase 3: Percentage exact agreement ranged from 35–70%. Overall, individuals had better agreement with the ‘gold standard’. Conclusion Avoidability assessment is feasible but needs careful attention to methods. The Liverpool ADR avoidability assessment tool showed mixed IRR. We have developed and validated a method for assessing the avoidability of ADRs that is transparent, more objective than
Mugoša, Snežana; Djordjević, Nataša; Djukanović, Nina; Protić, Dragana; Bukumirić, Zoran; Radosavljević, Ivan; Bošković, Aneta; Todorović, Zoran
The aim of the present study was to undertake a study on the prevalence of cytochrome P450 2D6 (CYP2D6) poor metabolizer alleles (*3, *4, *5, and *6) on a Montenegrin population and its impact on developing adverse drug reactions (ADRs) of β-blockers in a hospitalized cardiac patient population. A prospective study was conducted in the Cardiology Center of the Clinical Center of Montenegro and included 138 patients who had received any β-blocker in their therapy. ADRs were collected using a specially designed questionnaire, based on the symptom list and any signs that could point to eventual ADRs. Data from patients' medical charts, laboratory tests, and other available parameters were observed and combined with the data from the questionnaire. ADRs to β-blockers were observed in 15 (10.9%) patients. There was a statistically significant difference in the frequency of ADRs in relation to genetically determined enzymatic activity (P<0.001), with ADRs' occurrence significantly correlating with slower CYP2D6 metabolism. Our study showed that the adverse reactions to β-blockers could be predicted by the length of hospitalization, CYP2D6 poor metabolizer phenotype, and the concomitant use of other CYP2D6-metabolizing drugs. Therefore, in hospitalized patients with polypharmacy CYP2D6 genotyping might be useful in detecting those at risk of ADRs.
Subiela, José D; Dapena, Elida
Adverse drug reactions (ADRs) represent the first cause of change of the first-line highly active antiretroviral therapy (HAART) regimen, therefore, they constitute the main limiting factor in the long-term follow up of HIV patients in treatment. A retrospective study was carried out in a specialized center in Lara State, Venezuela, including 99 patients over 18 years of age who had change of first-line HAART regimen due to ADRs, between 2010 and 2013. The aims of this research were to describe the sociodemographic and clinical variables, frequency of ADRs related to change of HAART, duration of the first-line HAART regimen, to determine the drugs associated with ARVs and to identify the risk factors. The ADRs constituted 47.5% of all causes of change of first-line HAART regimen, the median duration was 1.08±0.28 years. The most frequent ADRs were anemia (34.3%), hypersensitivity reactions (20.2%) and gastrointestinal intolerance (13.1%). The most frequent ARV regimen type was the protease inhibitors-based regimen (59.6%), but zidovudine was the ARV most linked to ADRs (41.4%). The regression analysis showed increased risk of ADRs in singles and students in the univariate analysis and heterosexuals and homosexuals in multivariate analysis; and decreased risk in active workers. The present work shows the high prevalence of ADRs in the studied population and represents the first case-based study that describes the pharmacoepidemiology of a cohort of HIV-positive patients treated in Venezuela.
Giofrè, Chiara; Scicchitano, Francesca; Palleria, Caterina; Mazzitello, Carmela; Ciriaco, Miriam; Gallelli, Luca; Paletta, Laura; Marrazzo, Giuseppina; Leporini, Christian; Ventrice, Pasquale; Carbone, Claudia; Saullo, Francesca; Rende, Pierandrea; Menniti, Michele; Mumoli, Laura; Chimirri, Serafina; Patanè, Marinella; Esposito, Stefania; Cilurzo, Felisa; Staltari, Orietta; Russo, Emilio; De Sarro, Giovambattista
Pharmacovigilance (PV) is designed to monitor drugs continuously after their commercialization, assessing and improving their safety profile. The main objective is to increase the spontaneous reporting of adverse drug reactions (ADRs), in order to have a wide variety of information. The Italian Drug Agency (Agenzia Italiana del Farmaco [AIFA]) is financing several projects to increase reporting. In Calabria, a PV information center has been created in 2010. We obtained data using the database of the National Health Information System AIFA relatively to Italy and Calabria in the year 2012. Descriptive statistics were performed to analyze the ADRs. A total number of 461 ADRs have been reported in the year 2012 with an increase of 234% compared with 2011 (138 reports). Hospital doctors are the main source of this reporting (51.62%). Sorafenib (Nexavar(®)), the combination of amoxicillin/clavulanic acid and ketoprofen represent the drugs most frequently reported causing adverse reactions. Adverse events in female patients (61.83%) were more frequently reported, whereas the age groups "41-65" (39.07%) and "over 65" (27.9%) were the most affected. Calabria has had a positive increase in the number of ADRs reported, although it has not yet reached the gold standard set by World Health Organization (about 600 reports), the data have shown that PV culture is making inroads in this region and that PV projects stimulating and increasing PV knowledge are needed.
Giofrè, Chiara; Scicchitano, Francesca; Palleria, Caterina; Mazzitello, Carmela; Ciriaco, Miriam; Gallelli, Luca; Paletta, Laura; Marrazzo, Giuseppina; Leporini, Christian; Ventrice, Pasquale; Carbone, Claudia; Saullo, Francesca; Rende, Pierandrea; Menniti, Michele; Mumoli, Laura; Chimirri, Serafina; Patanè, Marinella; Esposito, Stefania; Cilurzo, Felisa; Staltari, Orietta; Russo, Emilio; De Sarro, Giovambattista
Introduction: Pharmacovigilance (PV) is designed to monitor drugs continuously after their commercialization, assessing and improving their safety profile. The main objective is to increase the spontaneous reporting of adverse drug reactions (ADRs), in order to have a wide variety of information. The Italian Drug Agency (Agenzia Italiana del Farmaco [AIFA]) is financing several projects to increase reporting. In Calabria, a PV information center has been created in 2010. Materials and Methods: We obtained data using the database of the National Health Information System AIFA relatively to Italy and Calabria in the year 2012. Descriptive statistics were performed to analyze the ADRs. Results: A total number of 461 ADRs have been reported in the year 2012 with an increase of 234% compared with 2011 (138 reports). Hospital doctors are the main source of this reporting (51.62%). Sorafenib (Nexavar®), the combination of amoxicillin/clavulanic acid and ketoprofen represent the drugs most frequently reported causing adverse reactions. Adverse events in female patients (61.83%) were more frequently reported, whereas the age groups “41-65” (39.07%) and “over 65” (27.9%) were the most affected. Conclusions: Calabria has had a positive increase in the number of ADRs reported, although it has not yet reached the gold standard set by World Health Organization (about 600 reports), the data have shown that PV culture is making inroads in this region and that PV projects stimulating and increasing PV knowledge are needed. PMID:24347984
Motola, Domenico; Vargiu, Antonio; Leone, Roberto; Conforti, Anita; Moretti, Ugo; Vaccheri, Alberto; Velo, Giampaolo; Montanaro, Nicola
The reporting of adverse drug reactions (ADRs) is the mainstay of post-marketing surveillance systems. Under-reporting and selective reporting are considered the main limitations of a spontaneous reporting-based pharmacovigilance system. However, excessive reporting induced by external events may also impair signal detection by increasing the noise level. The aim of this study was to examine the influence of regulatory measures and other external factors on the rate of ADR reporting in Italy, focusing on four situations occurring in the last 10 years: ACE inhibitor-induced cough; HMG-CoA reductase inhibitors ('statins') and rhabdomyolysis; nimesulide and hepatic toxicity; and cyclo-oxygenase (COX)-2 selective inhibitors ('coxibs') and increase in cardiovascular risk. The study was based on data from spontaneous reporting in six Italian regions collected from January 1995 to December 2005. We analysed a 10-year period as a reasonable time interval around the four situations of interest, highlighting the influence of regulatory measures on the rate of ADR reporting (number of reports per million inhabitants). Chi-squared tests were used to assess the statistical significance of any changes in ADR reporting. Drug sales data were also studied to examine possible changes in drug use. Sales data were expressed as daily defined dose per 1000 inhabitants per day. ACE inhibitors: a 5-fold increase in the reporting rate of ACE inhibitor-induced cough was observed in 1998 and 1999 following a restriction on reimbursement for angiotensin receptor blockers introduced in 1998 and removed at the end of 1999. Statins: after the withdrawal of cerivastatin in 2001, the ADR reporting rate increased more than 4-fold, with musculoskeletal ADRs representing about 60% of all the ADRs reported in that year, and progressively decreased in the following years. Nimesulide: an increase in hepatic ADR reporting was observed after withdrawal of the drug from the Finnish and Spanish markets in
Olivier, Pascale; Caron, Jacques; Haramburu, Françoise; Imbs, Jean-Louis; Jonville-Béra, Annie-Pierre; Lagier, Georges; Sgro, Catherine; Vial, Thierry; Montastruc, Jean-Louis; Lapeyr-Mestre, Maryse
Adverse drug reactions (ADRs) have been recognised as an important cause of hospital admission. Most of these drug-related admissions were expected ADRs and, thus, partly preventable. However, as far as we know, the assessment of the preventability of ADRs was addressed in only two studies performed in France. In contrast, several other studies have been performed, mainly in the USA, and using different methods of assessing preventability. None of these methods were clearly evaluated with regard to reproducibility, validity or relevance. The purpose of this study was to initiate the validation of a French preventability scale. Here, we propose the first two phases of validation: the content validity and reliability of the scale. A working group of pharmacovigilance experts has been specifically established for this purpose. The content validity was assessed by collecting items representative of preventability. The choice and the formulation of items and a proposal of a score (global and for each item) were adopted after the consensus of the experts. A definitive version of the ADR preventability scale was used for the assessment of reliability. During the second phase, experts independently tested the new scale from observations of ADRs (49 central nervous system haemorrhages with antivitamine K). The concordance of the experts' judgements was calculated using two statistical methods (Kappa statistic and correlation coefficient). The content validity phase was performed during several workshops where experts discussed the choice and formulation of the best items. We decided to construct a scale with a small number of items, allowing a rapid evaluation of the preventability of ADRs. On the basis of a global score, four categories of preventability of ADRs ("preventable", "potentially preventable", "unclassable", "not preventable" ADRs) were proposed. The agreement of experts regarding the global score was low, with a poor correlation coefficient value (coefficient
Ribeiro-Vaz, Inês; Silva, Ana-Marta; Costa Santos, Cristina; Cruz-Correia, Ricardo
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
Ding, Wen Yi; Lee, Chew Kek; Choon, Siew Eng
Adverse drug reactions are most commonly cutaneous in nature. Patterns of cutaneous adverse drug reactions (ADRs) and their causative drugs vary among the different populations previously studied. Our aim is to determine the clinical pattern of drug eruptions and the common drugs implicated, particularly in severe cutaneous ADRs in our population. This study was done by analyzing the database established for all adverse cutaneous drug reactions seen from January 2001 until December 2008. A total of 281 cutaneous ADRs were seen in 280 patients. The most common reaction pattern was maculopapular eruption (111 cases, 39.5%) followed by Stevens-Johnson Syndrome (SJS: 79 cases, 28.1%), drug reaction with eosinophilia and systemic symptoms (DRESS: 19 cases, 6.8%), toxic epidermal necrolysis (TEN: 16 cases, 5.7 %), urticaria/angioedema (15 cases, 5.3%) and fixed drug eruptions (15 cases, 5.3%). Antibiotics (38.8%) and anticonvulsants (23.8%) accounted for 62.6% of the 281 cutaneous ADRs seen. Allopurinol was implicated in 39 (13.9%), carbamazepine in 29 (10.3%), phenytoin in 27 (9.6%) and cotrimoxazole in 26 (9.3%) cases. Carbamazepine, allopurinol and cotrimoxazole were the three main causative drugs of SJS/TEN accounting for 24.0%, 18.8% and 12.5% respectively of the 96 cases seen whereas DRESS was mainly caused by allopurinol (10 cases, 52.6%) and phenytoin (3 cases, 15.8%). The reaction patterns and drugs causing cutaneous ADRs in our population are similar to those seen in other countries although we have a much higher proportion of severe cutaneous ADRs probably due to referral bias, different prescribing habit and a higher prevalence of HLA-B*1502 and HLA-B*5801 which are genetic markers for carbamazepine-induced SJS/TEN and allopurinol-induced SJS/TEN/DRESS respectively. The most common reaction pattern seen in our study population was maculopapular eruptions. Antibiotics, anticonvulsants and NSAIDs were the most frequently implicated drug groups. Carbamazepine
Plichta, Danuta; Doryńska, Agnieszka; Spiewak, Radosław
The research of drug consumption is focused mainly upon the elderly, while the knowledge of drug consumption patterns among young people remains insufficient. Public health students (PHS) seem of particular interest as future opinion leaders and drug policy makers. The aim of the study was to analyze opinions and patterns of drug consumption, and adverse drug reactions (ADR) in this group. 130 PHS took part in the anonymous questionnaire survey. All students admitted to using some drug at least once in their lives. While purchasing over-the-counter (OTC) drugs, 51.6% students trusted their own knowledge and experience. Women more often relied on a pharmacist's recommendation (47.2% vs 21.7% men; p = 0.045), while men were more influenced by advertising (34.8% vs 12.3% women, p = 0.008). Strict adherence to recommended dosage of OTC and prescription drugs (Rx) was declared by 41.1% and 71.9% students, respectively. Every fourth student (24.8%) admitted to having purchased a Rx drug at least once without having the prescription. Past episodes of ADR to OTC were reported by 7.8% students and to Rx by 38.4% (p < 0.001). Respectively 27.2% and 34.4% students were never, or hardly ever asked about past ADR by prescribing physicians. According to 89.2% students, drug advertising should be subject to regulation and policing, and 66.1% considered it inaccurate and unreliable. Forty-five percent of students had an OTC drug on them while responding the questionnaire, 20.0% had a prescription drug. Students of public health seem to be notorious consumers of drugs and their attitude seems not fully rational.
MARTÍNEZ-MIR, I.; GARCÍA-LÓPEZ, M.; PALOP, V.; FERRER, J. M.; ESTAÑ, L.; RUBIO, E.; MORALES-OLIVAS, F. J.
1A total of 512 consecutive paediatric hospital admissions of children 2 years old or less were evaluated to assess the extent and pattern of admission caused by suspected adverse drug reactions (ADRs). The proportion of suspected ADRs related to hospital admissions was 4.3%. 2The organ-systems most commonly implicated were the central nervous system (40.5%), digestive system (16.7%), and skin and appendages (14.3%). Together, they accounted for 71.5% of admissions attributed to ADRs. The most common clinical manifestations inducing admission were convulsions (4 cases), dizziness (4), vomiting (3), and tremor, fever, itching and apnoea (2 cases each). 3The four classes of drugs most frequently suspected in admissions due to ADRs were respiratory drugs (35%), anti-infective agents (25%), drugs active on the central nervous system (15%) and drugs used in dermatology (10%). The most common drugs related to ADRs were a combination of chlorpheniramine, diphenhydramine, phenylephrine, guaiphenesin and salicylic acid (4 cases), followed by fenoterol, adrenaline, paracetamol, DTP vaccine and antipolio vaccine (2 cases each). 4There were no significant differences between children older and younger than 1 year (odds ratio 0.89; 95% CI 0.37–2.17) or between the sexes as regards hospital admittance due to suspected ADRs (odds ratio 1.94; 95% CI 0.72–5.42). 5The results of this kind of study may be influenced by patterns of drug utilization. Nevertheless, the lack of specific studies of drug effects in young children makes it desirable to carry out pharmacoepidemiological studies in this age group. PMID:8877022
Luo, Heng; Chen, Jian; Shi, Leming; Mikailov, Mike; Zhu, Huang; Wang, Kejian; He, Lin; Yang, Lun
Identifying new indications for existing drugs (drug repositioning) is an efficient way of maximizing their potential. Adverse drug reaction (ADR) is one of the leading causes of death among hospitalized patients. As both new indications and ADRs are caused by unexpected chemical–protein interactions on off-targets, it is reasonable to predict these interactions by mining the chemical–protein interactome (CPI). Making such predictions has recently been facilitated by a web server named DRAR-CPI. This server has a representative collection of drug molecules and targetable human proteins built up from our work in drug repositioning and ADR. When a user submits a molecule, the server will give the positive or negative association scores between the user’s molecule and our library drugs based on their interaction profiles towards the targets. Users can thus predict the indications or ADRs of their molecule based on the association scores towards our library drugs. We have matched our predictions of drug–drug associations with those predicted via gene-expression profiles, achieving a matching rate as high as 74%. We have also successfully predicted the connections between anti-psychotics and anti-infectives, indicating the underlying relevance of anti-psychotics in the potential treatment of infections, vice versa. This server is freely available at http://cpi.bio-x.cn/drar/. PMID:21558322
Dweik, Rania Al; Yaya, Sanni; Stacey, Dawn; Kohen, Dafna
Monitoring adverse drug reactions (ADRs) through pharmacovigilance are vital to patient safety. Spontaneous ADR reporting is one method of pharmacovigilance, and in Canada all reporter types admitted to report an ADR to the Canadian Vigilance Program at Health Canada. Reports are submitted to Health Canada by post, telephone, or via the internet. The Canada Vigilance Program electronically records submitted information to detect medication safety alerts. Although previous studies have shown differences between patients and healthcare professionals (HCPs) on the types of drugs and reactions reported, relatively little is known about the importance of patient reports to pharmacovigilance activities. This article proposed a multi-method approach to evaluate the importance of patient ADR reporting on pharmacovigilance activities, by systematically review the available literature, comparing patient-versus HCPs-generated ADR reports that were submitted to the Canada Vigilance Program, and exploring patient views and experiences regarding the Canadian ADR reporting system. Guided by a risk-perception theoretical lens, the proposed multi-methods research study will involve three phases. Phase I is a systematic review of all studies that analyse the factors influence ADR reporting by patients to the pharmacovigilance schemes. Phase II is a descriptive statistical analysis of all ADR reports received by the Canada Vigilance Program database between 1 January 2000 and 31 December 2014 from patients and HCPs to compare ADRs reported by patients with those reported by HCP reports in terms of ADR seriousness, ADR classification by system organ class, and the medication involved based on the anatomical therapeutic class system. In phase III, an interpretative descriptive approach will be used to explore patient's views and experiences on ADR reporting and usability of the Canadian Vigilance ADR report. Participants will be purposefully selected to ensure diverse backgrounds and
Steele, Megan L.; Happe, Antje; Kröz, Matthias; Matthes, Harald; Schad, Friedemann
Background. In Europe, mistletoe extracts are widely used as a complementary cancer therapy. We assessed the safety of subcutaneous mistletoe as a conjunctive therapy in cancer patients within an anthroposophic medicine setting in Germany. Methods. A multicentre, observational study was performed within the Network Oncology. Suspected mistletoe adverse drug reactions (ADRs) were described by frequency, causality, severity, and seriousness. Potential risk factors, dose relationships and drug-drug interactions were investigated. Results. Of 1923 cancer patients treated with subcutaneous mistletoe extracts, 283 patients (14.7%) reported 427 expected effects (local reactions <5 cm and increased body temperature <38°C). ADRs were documented in 162 (8.4%) patients who reported a total of 264 events. ADRs were mild (50.8%), moderate (45.1%), or severe (4.2%). All were nonserious. Logistic regression analysis revealed that expected effects were more common in females, while immunoreactivity decreased with increasing age and tumour stage. No risk factors were identified for ADRs. ADR frequency increased as mistletoe dose increased, while fewer ADRs occurred during mistletoe therapy received concurrent with conventional therapies. Conclusion. The results of this study indicate that mistletoe therapy is safe. ADRs were mostly mild to moderate in intensity and appear to be dose-related and explained by the immune-stimulating, pharmacological activity of mistletoe. PMID:24672577
Steele, Megan L; Axtner, Jan; Happe, Antje; Kröz, Matthias; Matthes, Harald; Schad, Friedemann
Background. In Europe, mistletoe extracts are widely used as a complementary cancer therapy. We assessed the safety of subcutaneous mistletoe as a conjunctive therapy in cancer patients within an anthroposophic medicine setting in Germany. Methods. A multicentre, observational study was performed within the Network Oncology. Suspected mistletoe adverse drug reactions (ADRs) were described by frequency, causality, severity, and seriousness. Potential risk factors, dose relationships and drug-drug interactions were investigated. Results. Of 1923 cancer patients treated with subcutaneous mistletoe extracts, 283 patients (14.7%) reported 427 expected effects (local reactions <5 cm and increased body temperature <38°C). ADRs were documented in 162 (8.4%) patients who reported a total of 264 events. ADRs were mild (50.8%), moderate (45.1%), or severe (4.2%). All were nonserious. Logistic regression analysis revealed that expected effects were more common in females, while immunoreactivity decreased with increasing age and tumour stage. No risk factors were identified for ADRs. ADR frequency increased as mistletoe dose increased, while fewer ADRs occurred during mistletoe therapy received concurrent with conventional therapies. Conclusion. The results of this study indicate that mistletoe therapy is safe. ADRs were mostly mild to moderate in intensity and appear to be dose-related and explained by the immune-stimulating, pharmacological activity of mistletoe.
Durrieu, Geneviève; Maupiler, Mathieu; Rousseau, Vanessa; Chebane, Leila; Montastruc, François; Bondon-Guitton, Emmanuelle; Montastruc, Jean-Louis
Studies that evaluate the safety of non-prescription drugs in children remain scarce. The aim of the present study was to compare adverse drug reactions (ADRs) due to prescription versus non-prescription drugs in children. We conducted a retrospective analysis of ADR notifications for a pediatric population (aged <18 years) registered in the French PharmacoVigilance Database (FPVD) between January 1985 and December 2016 by the Midi-Pyrénées PharmacoVigilance Center (in the south of France). We compared ADR profiles according to drug prescription status using a Chi-squared test. We included 2218 notifications concerning 3687 ADRs in the study. Non-prescription drugs were involved in 506 notifications (22.8%). Patients were younger in the non-prescription drug group (6.7 ± 5.3 vs. 8.4 ± 5.7 years in the prescription drug group). No difference by sex was found. Neurological ADRs were more frequent with prescription drugs (21.0%) than with non-prescription drugs (14.2%, p = 0.0008), whereas dermatological disorders (37.2 vs. 29.1%, respectively) and general ADRs (30.8 vs. 20.1%, respectively) were more frequent with non-prescription than with prescription drugs (p = 0.0006 and p < 0.0001, respectively). The frequency of "serious" ADRs was higher with prescription drugs than with non-prescription drugs (40.9 vs. 34.2%, p = 0.007). The non-prescription drugs most frequently implicated with serious ADRs were ibuprofen (n = 37; 4.2%), tuberculosis vaccine (n = 23; 2.6%), aspirin (n = 20, 2.3%), and paracetamol (n = 17; 1.9%). ADRs from prescription drugs involved asparaginase (n = 27; 3.1%), immunoglobulins (n = 25; 2.9%), and amoxicillin (n = 23; 2.4%). Non-prescription drugs, usually considered safe, were frequently responsible for ADR notifications. The non-prescription medication most frequently involved in serious ADRs was ibuprofen.
Blumenthal, Kimberly G.; Kuhlen, James L.; Weil, Ana A.; Varughese, Christy A.; Kubiak, David W.; Banerji, Aleena; Shenoy, Erica S.
Background Ceftaroline fosamil is a cephalosporin approved for treating skin and soft tissue infections (SSTIs), including those caused by methicillin-resistant Staphylococcus aureus (MRSA) and community acquired pneumonia (CAP). Objective We aimed to study ceftaroline use and associated adverse drug reactions (ADRs), including hypersensitivity reactions (HSRs), among inpatients. Methods We performed a retrospective electronic health record review of inpatients from Massachusetts General Hospital and Brigham and Women’s Hospital who received ceftaroline between May 2012 and February 2015. ADRs diagnosed by clinical providers during the course of clinical care were subsequently verified and classified. Risk factors for ADRs were identified. Results Among 96 patients (median age 57 years, 54% female) who received a median of 28 [IQR 6, 63] ceftaroline doses, 54% were being treated for MRSA and treatment indications other than SSTI and CAP comprised 59% of care. There were 31 ADRs observed in 20 (21%) of patients; hematologic (n=15) and cutaneous (n=9) findings were most common. Observed HSRs included rash with mucosal lesions (n=1), rash with skin desquamation (n=1) and possible organ specific HSRs (n=2). Patients who suffered an ADR received more doses of ceftaroline (median 46 vs. 21, p=0.013). There was no increased risk of ceftaroline ADR among patients with prior reported beta-lactam allergy (p >0.5). Conclusions Ceftaroline is used to treat a range of infections beyond SSTI and CAP. We observed a high rate of ADRs from ceftaroline, including signs of severe HSRs. More data are needed to understand the frequency and predictors of ceftaroline ADRs and HSRs. PMID:27130709
Yadav, Sankalp; Kumar, Raj; Wani, Umar Rasool
The Adverse Drug Reaction (ADR) to a commonly prescribed anti-microbial can pose a major public health problem. The authors report a rare case of 24-year-old young lady who presented with angioedema of lips after ingestion of Ofloxacin, prescribed to her for treatment of loose motions. Fluoroquinolones are widely prescribed antibiotics for various disease conditions. The history, clinical examination and normal laboratory parameters led to the diagnosis of ofloxacin induced hypersensitivity reaction and the patient was successfully treated with corticosteroids and antihistamines. The hypersensitivity reactions to fluoroquinolones are rare with an incidence of 0.4% to 2%. The pharmacovigilance program and self-reporting of all the ADR’s by the health care workers can help in ensuring the judicious use of the drug, drug safety and thus decrease the associated morbidity and mortality. PMID:28050397
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
Amin, Mohammad Nurul; Khan, Tahir Mehmood; Dewan, Syed Masudur Rahman; Islam, Mohammad Safiqul; Moghal, Mizanur Rahman
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
Shin, Yoo Seob; Lee, Yong-Won; Choi, Young Hwa; Park, Byungjoo; Jee, Young Koo; Choi, Sung-Kyu; Kim, Eung-Gyu; Park, Jung-Won; Hong, Chein-Soo
Patterns of prescriptions are markedly influenced by regional disease entities, medical education, culture, economic status, and available pharmaceutical companies. Features of adverse drug reactions (ADRs) may vary in different countries. In this study, we analyzed the causative drugs and clinical manifestations of spontaneously reported ADRs in Korea. Six Korean Regional Pharmacovigilance Centers collected 1418 cases of spontaneously reported adverse drug events (ADEs) by doctors, pharmacists, and nurses, and the clinical features and causative drugs were evaluated. The data were collected from general hospitals (76.5%), primary clinics, and pharmacies (23.5%). Based upon the World Health Organization (WHO)-Uppsala Monitoring Center criteria (certain-13.7%, probable-46.1%, possible-32.1%), 91.9% of the collected events were suspected to be ADRs and 15.8% of patients experienced serious ADRs. The most prevalent causative drugs were antibiotics (31.6%), followed by contrast dyes (14.0%), non-steroidal anti-inflammatory drugs (NSAIDs) (11.1%), anti-psychotics (5.4%), anti-convulsants (5.2%), cardiovascular agents (4.8%), anti-neoplastics (4.6%), and opiates and non-opiate pain killers (3.5%). Among the antibiotics, cephalosporins (8.1%) were the most common, followed by anti-tuberculosis agents (5.7%), quinolones (4.0%), vancomycin (3.1%), and penicillin (2.8%). The most common side effect was skin manifestations, which were seen in 42% of the patients, followed by neurologic manifestations (14%), gastrointestinal involvements (12.9%), generalized reactions (9.4%), and respiratory involvements (4.5%). Antibiotics, contrast dyes, and NSAIDs were the most common causative drugs for ADRs, which reflects the prescription pattern and the prevalence of diseases in Korea. These data may be useful in establishing a Korean pharmacovigilance system. 2009 John Wiley & Sons, Ltd.
Patel, Tejas K; Bhabhor, Prakash H; Desai, Nimisha; Shah, Saurabh; Patel, Parvati B; Vatsala, Ela; Panigrahi, Sanjibani
The epidemiological data are limited for the spontaneous adverse drug reaction (ADR) reporting system in psychiatry and its comparison with intensive monitoring studies in terms of causative drugs, seriousness, preventability and drug interactions. This spontaneous ADR reporting study was carried out over a period of three years in the psychiatry department. We adopted WHO definition for an ADR, Naranjo's algorithm for causality, WHO-ADR terminology for the labeling of involved organ-system, International conference on harmonisation (ICH) E2A guidelines for seriousness, modified Schumock and Thornton's criteria for preventability and Medscape drug interaction checker for drug interactions. Two subgroup analyses were performed to find out the risk factors for the serious and preventable reactions. A total of 97 ADRs from 67 patients were included for analysis. The incidence of 'overall' and 'serious ADRs were 0.69% (95% CI: 0.54%, 0.88%) and 0.18% (95% CI: 0.12-0.29%), respectively. The females experienced more ADRs than males. The most commonly reported ADR, incriminated pharmacology group and drug, were extrapyramidal movement disorders (22.68%), atypical antipsychotics (35.62%) and escitalopram (13.91%), respectively. One out of five and one out three reactions were considered as 'serious' and 'preventable', respectively. The drug interactions contributed in 34.02% reactions. The factors significantly associated with 'serious' reactions were typical antipsychotics [OR: 5.47 (1.68, 17.87)], central and peripheral nervous system disorders [OR: 24.00 (5.12, 112.5)] and extrapyramidal reactions [OR: 14.03 (4.43, 44.43)]. The polypharmacy [OR: 5.85 (1.90, 18.03)] was significantly associated with 'preventable' reactions. The spontaneous reporting system is efficient to detect serious reactions and preventable reactions.
Walji, Rishma; Boon, Heather; Barnes, Joanne; Welsh, Sandy; Austin, Zubin; Baker, G Ross
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.
Kiguba, Ronald; Karamagi, Charles; Bird, Sheila M
Objectives To determine the incidence and risk factors of hospital-acquired suspected adverse drug reactions (ADRs) among Ugandan inpatients. We also constructed risk scores to predict and qualitatively assess for peculiarities between low-risk and high-risk ADR patients. Methods Prospective cohort of consented adults admitted on medical and gynaecological wards of the 1790-bed Mulago National Referral Hospital. Hospital-acquired suspected ADRs were dichotomised as possible (possible/probable/definite) or not and probable (probable/definite) or not, using the Naranjo scale. Risk scores were generated from coefficients of ADR risk-factor logistic regression models. Results The incidence of possible hospital-acquired suspected ADRs was 25% (194/762, 95% CI: 22% to 29%): 44% (85/194) experienced serious possible ADRs. The risk of probable ADRs was 11% (87/762, 95% CI 9% to 14%): 46% (40/87) had serious probable ADRs. Antibacterials-only (51/194), uterotonics-only (21/194), cardiovascular drugs-only (16/194), antimalarials-only (12/194) and analgesics-only (10/194) were the most frequently implicated. Treatment with six or more conventional medicines during hospitalisation (OR=2.31, 95% CI 1.29 to 4.15) and self-reported herbal medicine use during the 4 weeks preadmission (OR=1.96, 95% CI 1.22 to 3.13) were the risk factors for probable hospital-acquired ADRs. Risk factors for possible hospital-acquired ADRs were: treatment with six or more conventional medicines (OR=2.72, 95% CI 1.79 to 4.13), herbal medicine use during the 4 weeks preadmission (OR=1.68, 95% CI 1.16 to 2.43), prior 3 months hospitalisation (OR=1.57, 95% CI 1.09 to 2.26) and being on gynaecological ward (OR=2.16, 95% CI 1.36 to 3.44). More drug classes were implicated among high-risk ADR-patients, with cardiovascular drugs being the most frequently linked to possible ADRs. Conclusions The risk of hospital-acquired suspected ADRs was higher with preadmission herbal medicine use and treatment with
Pedrós, Consuelo; Vallano, Antoni; Cereza, Gloria; Mendoza-Aran, Gemma; Agustí, Antònia; Aguilera, Cristina; Danés, Immaculada; Vidal, Xavier; Arnau, Josep M
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
Seebeck, J; Wulf, F; Sachs, B
In Germany, reports on adverse drug reactions (ADRs) are centrally collected and analyzed by the Federal Institute for Drugs and Medical Devices (BfArM). During routine analysis of ADR reports related to the antiobesity drug sibutramine, we repeatedly observed descriptions of its label*-inconsistent use (*European Summary of Product Characteristics (SmPC)). In order to quantify this observation, we analyzed all sibutramine-related ADR reports received by the BfArM so far. Using the same data source, we further analyzed the effect of a Dear Doctor Letter (DDL) which was distributed in 2002 in order to reinforce the label-consistent use of sibutramine. Out of a total of 170 identified reports, 104 were considered as suitable for further analysis. Of these, applying a catalogue of 24 SmPC-derived criteria, 34% (35 reports) contained information indicative of label-inconsistent use. The individual SmPC-criteria most often violated were (% of total analyzed reports): the recommended starting dose of 10 mg/day (9%), the body mass index (BMI)-related threshold permitting drug therapy (6%), and the contraindicated "history of drug abuse" (6%). The DDL was ineffective. The observed percentage of ADR reports, indicating a label-inconsistent use of sibutramine, is considered a signal for a therapeutic risk. This signal should be addressed in a drug utilization study investigating the use of sibutramine by means of a representative patient sample.
Yang, Ming; Kiang, Melody; Shang, Wei
Adverse drug reactions (ADRs) are believed to be a leading cause of death in the world. Pharmacovigilance systems are aimed at early detection of ADRs. With the popularity of social media, Web forums and discussion boards become important sources of data for consumers to share their drug use experience, as a result may provide useful information on drugs and their adverse reactions. In this study, we propose an automated ADR related posts filtering mechanism using text classification methods. In real-life settings, ADR related messages are highly distributed in social media, while non-ADR related messages are unspecific and topically diverse. It is expensive to manually label a large amount of ADR related messages (positive examples) and non-ADR related messages (negative examples) to train classification systems. To mitigate this challenge, we examine the use of a partially supervised learning classification method to automate the process. We propose a novel pharmacovigilance system leveraging a Latent Dirichlet Allocation modeling module and a partially supervised classification approach. We select drugs with more than 500 threads of discussion, and collect all the original posts and comments of these drugs using an automatic Web spidering program as the text corpus. Various classifiers were trained by varying the number of positive examples and the number of topics. The trained classifiers were applied to 3000 posts published over 60 days. Top-ranked posts from each classifier were pooled and the resulting set of 300 posts was reviewed by a domain expert to evaluate the classifiers. Compare to the alternative approaches using supervised learning methods and three general purpose partially supervised learning methods, our approach performs significantly better in terms of precision, recall, and the F measure (the harmonic mean of precision and recall), based on a computational experiment using online discussion threads from Medhelp. Our design provides
Cornelius, Victoria R; Liu, Kun; Peacock, Janet; Sauzet, Odile
To compare consistency of adverse drug reaction (ADR) data in publicly available product information documents for brand drugs, between the USA and Europe. To assess the usefulness of information for prescribers and patients. A comparison review of product information documents for antidepressants and anticonvulsants concurrently marketed by the same pharmaceutical company in the USA and Europe. For each drug, data were extracted from the US Product Inserts and the European Summary of Product Characteristics documents between 09/2013 and 01/2015. Individuals contributing ADR information to product information documents. All ADRs reported in product information sections 5 and 6 (USA), and 4·4 and 4·8 (Europe). Twelve brand drugs--24 paired documents--were included. On average, there were 77 more ADRs reported in the USA compared with in the European product information document, with a median number of 201 ADRs (range: 65-425) and 114 (range: 56-265), respectively. More product information documents in the USA reported information on the source of evidence (10 vs 5) and risk (9 vs 5) for greater than 80% of ADRs included in the document. There was negligible information included regarding duration, severity, reversibility or recurrence of ADRs. On average, only 29% of ADR terms were reported in both paired documents. Product information documents contained a large number of ADRs, but lacked contextual data and information important to patients and prescribers, such as duration, severity and reversibility. The ADR profile was found to be inconsistently reported between the USA and Europe, for the same drug. Identifying, selecting, summarising and presenting multidimensional harm data should be underpinned by practical evidence-based guidelines. In order for prescribers to provide considered risk-benefit advice across competing drug therapies to patients, they need access to comprehensible and reliable ADR information. Published by the BMJ Publishing Group Limited
Ezeuko, Amaka Y.; Ebenebe, Uzo E.; Nnebue, Chinomnso C; Ugoji, John O.
Background: Under-reporting of adverse drug reactions (ADRs) by the prescribers is a common public health problem. Monitoring of factors that influence ADR reporting will reduce risks associated with drug use; improve patients care, safety and treatment outcome. The aim of this study was to determine the factors associated with the reporting of ADRs by health workers in Nnewi Nigeria. Methods: A cross-sectional study of 372 health workers in different health facilities in Nnewi North Local Government Area of Anambra state, selected using multistage sampling technique was done. Data collection employed pretested, self-administered structured questionnaires. Data were analyzed using Statistical Package for Social Sciences version 17. Tests of statistical significance were carried out using Chi-square tests for proportions. A P < 0.05 was considered significant. Results: Out of the 372 respondents studied, 255 (68.5%) were females, and 117 (31.5%) were males. The modal age range (37.6%) was 31–40 years. Factors related by the respondents to influence ADR reporting include: Unavailability of electronic reporting (83.6%), unavailability of reporting forms (66.4%) and ignorance (58.2%). The difference among medical practitioners who related unavailability of electronic reporting process as obstacle to ADR reporting was not significant (P = 0.18). Conclusions: The study results revealed the factors associated with the reporting of ADRs among health workers in Nnewi Nigeria. It is desirable to initiate electronic reporting process, training programs on ADR reporting and make reporting forms/guidelines available to relevant health workers. PMID:25949775
Elkalmi, Ramadan Mohamed; Hassali, Mohamed Azmi; Ibrahim, Mohamed Izham M; Jamshed, Shazia Qasim; Al-Lela, Omer Qutaiba B
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.
Andrade, Paulo Henrique Santos; Santos, Adriano da Silva; Souza, Carlos Adriano Santos; Lobo, Iza Maria Fraga; da Silva, Wellington Barros
Background: The main objective of the present systematic review is to identify potential risk factors for adverse drug reactions (ADRs) through prospective cohort studies in pediatric inpatients. Methods: The data search was done in the following electronic databases PubMed/MEDLINE; Scopus; LILACS and Web of Science from the earliest record until 31 May 2015. Two reviewers independently screened each study and one of them assessed the methodological quality according to the Newcastle–Ottawa scale for cohort studies. The data extraction was conducted according to Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) initiative for cohort studies. Results: The only risk factor observed in all studies was the increase in the number of prescription drugs. However, other factors were identified, such as the increase in the length of stay or the number of low- or high-risk drugs prescribed, use of general anesthesia and oncological diagnosis. The cumulative incidence of ADR was 16.4% (95% confidence interval: 15.6 to 17.2). The main professional responsible for ADR identification was the pharmacist and the dominant category among the ADRs were gastrointestinal disorders. In addition, analgesics, antibacterial agents and corticosteroids were the drug classes commonly associated with ADRs. The methodology used in this study was tried to homogenize the data extracted; however, this was not sufficient to correct the discrepancies so it was not possible to perform a meta-analysis. Conclusions: The increase in the number of prescription drugs was the main risk factor in this population. However, additional studies are required to identify the risk factors for ADRs in pediatric inpatients. PMID:28607669
Reyes-Morales, Hortensia; Mino-León, Dolores; Doubova, Svetlana V; Flores-Hernández, Sergio
Commercialization of rosiglitazone, an oral blood glucose-lowering drug of the thiazolidinedione class, was recently suspended in Europe and significantly restricted in the United States due to a possibly increased risk of ischemic heart disease; the drug is still being marketed in Mexico. This study was aimed to analyze the post-marketing occurrence of adverse drug reactions (ADRs) with rosiglitazone when used in combination therapy in Mexican Type 2 Diabetes patients. A prospective observational study was conducted at a primary health-care clinic in Mexico City. Eligible subjects were adult patients with Type 2 diabetes inadequately controlled with maximal doses of oral monotherapy, in which one of two combined therapeutic schemes was prescribed: rosiglitazone/glibenclamide (R/G), or rosiglitazone/metformin (R/M). Patients' blood pressure, weight, treatment adherence and occurrence of ADRs were monitored during a 6-month follow-up period. 174 patients received treatment with R/M or R/G (112 and 62 patients, respectively). At least one ADR was observed in about 75%, of patients. Prior to the end of the follow-up period, moderate ADRs leading to discontinuation of the treatment occurred in 29.5% and 14.5% of patients treated with R/M and R/G, respectively. The ADRs most frequently observed were peripheral edema and moderate weight gain. The use of rosiglitazone in combination with other oral anti-diabetic drugs was associated with a high frequency of ADRs in Mexican patients with Type 2 diabetes. Post-marketing studies are relevant to identify drug-associated risks to patients in clinical practice.
Palleria, Caterina; Leporini, Christian; Chimirri, Serafina; Marrazzo, Giuseppina; Sacchetta, Sabrina; Bruno, Lucrezia; Lista, Rosaria M.; Staltari, Orietta; Scuteri, Antonio; Scicchitano, Francesca; Russo, Emilio
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
Uribe-San-Martín, Reinaldo; Ciampi, Ethel; Uslar, Wilhelm; Villagra, Silvana; Godoy, Jaime; Mellado, Patricio
Phenytoin (PHT) is an effective and inexpensive antiepileptic drug (AED). However, its use has been limited for fear of adverse drug reactions (ADRs) and is being replaced by newer AED, increasing the costs and causing major budget problems, particularly for developing countries. The objective of this study was to determine ADR frequency, explore, and establish related risk factors. Prospective data were collected from a cohort of inpatients using PHT for the first time. Pharmacovigilance was performed during hospitalization and after one month from the discharge. Clinical variables, plasma levels, and concomitant medications were collected and their association with the occurrence of different ADRs was explored. One hundred patients were included: 59 were women, and mean age was 59±21years. Thirty-three patients presented ADR, all moderate and idiosyncratic. The most frequent were rash (17%), fever (10%), and elevated transaminases (10%). Female gender (85% vs 52%, p=0.029), younger age (mean age: 49 vs 62years, p=0.032), and higher PHT plasmatic levels after IV-PO load (mean plasmatic levels: 18.6 vs 13.9μg/mL, p=0.040) were found to be associated with rash. A higher number of concomitant medications were also found to be associated with the risk for developing any ADR. The multivariate analysis revealed an association between rash and younger age (cut-off: 35years old; relative risk (RR)=11.7; p=0.026), and higher PHT plasmatic levels (cut-off: 16μg/mL; RR=12.5; p=0.021); and increased risk of elevated transaminases with use of PHT inductors (RR=18; p=0.006). A longer hospital stay was found in patients who developed fever (mean: 43days, p<0.0001) and elevated transaminases (mean: 26days, p=0.041) compared with patients without ADR (mean: 17days). Phenytoin is a widely used AED associated with easily detectable ADR through structured pharmacovigilance. The development of ADR is associated with longer hospital stays. Recognition of local risk factors may lead
Desai, Chetna K.; Iyer, Geetha; Panchal, Jigar; Shah, Samidh; Dikshit, R. K.
Objectives: 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. Materials and Methods: 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. Results: 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%). Conclusion: 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. PMID:22145123
Ahmad, Akram; Patel, Isha; Balkrishnan, Rajesh; Mohanta, G. P.; Manna, P. K.
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
Desai, Chetna K; Iyer, Geetha; Panchal, Jigar; Shah, Samidh; Dikshit, R K
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.
Husserl, F E; Messerli, F H
Early essential hypertension is asymptomatic and should remain so throughout treatment. In view of the increasing number of available antihypertensive agents, clinicians need to become familiar with the potential side effects of these drugs. By placing more emphasis on non-pharmacological treatment (sodium restriction, weight loss, exercise) and thoroughly evaluating each case in particular, the pharmacological regimen can be optimally tailored to the patient's needs. Potential side effects should be predicted and can often be avoided; if they become clinically significant they should be rapidly recognised and corrected. These side effects can be easily remembered in most instances, as they fall into 3 broad categories: (a) those caused by an exaggerated therapeutic effect; (b) those due to a non-therapeutic pharmacological effect; and (c) those caused by a non-therapeutic, non-pharmacological effect probably representing idiosyncratic reactions. This review focuses mainly on adverse effects of the second and third kind. Each group of drugs in general shares the common side effects of the first two categories, while each individual drug has its own idiosyncratic side effects.
Smithburger, Pamela L.; Buckley, Mitchell S.; Culver, Mark A.; Sokol, Sarah; Lat, Ishaq; Handler, Steven M.; Kirisci, Levent; Kane-Gill, Sandra L.
Objective Prior research indicates off-label use is common in the intensive care unit (ICU); however the safety of off-label use has not been assessed. The study objective was to determine the incidence of adverse drug reactions (ADRs) associated with off-label use and evaluate off-label use as a risk factor for the development of ADRs in an adult ICU population. Setting Medical ICUs at three academic medical centers Patients Adult patients (age ≥ 18 years old) receiving medication therapy Interventions All administered medications were evaluated for Food and Drug Administration (FDA) approved or off-label use. Patients were assessed daily for the development of an ADR through active surveillance. Three ADR assessment instruments were used to determine the probability of an ADR resulting from drug therapy. Severity and harm of the ADR were also assessed. Cox proportional hazard regression was used to identify a set of covariates that influenced the rate of ADRs. Measurements and Main Results Overall, 1654 patient days (327 patients) and 16,391 medications were evaluated, with 43% of medications being used off-label. One hundred and sixteen ADRs were categorized dichotomously (FDA or off-label), with 56% and 44% being associated with FDA approved and off-label use, respectively. The number of ADRs for medications administered and number of harmful and severe ADRs did not differ for medications used for FDA approved or off-label use (0.74% vs 0.67%, p = 0.336; 33 vs. 31 events, p=0.567; 24 vs. 24 events, p = 0.276). Age, sex, number of high-risk medications, number of off-label medications, and severity of illness score were included in the Cox proportional hazard regression. It was found that the rate of ADRs increases by 8% for every one additional off-label medication (HR = 1.08; 95 % CI: 1.018–1.154). Conclusion While ADRs do not occur more frequently with off-label use, ADR risk increases with each additional off-label medication used. PMID:25855897
Mugoša, Snežana; Djordjević, Nataša; Djukanović, Nina; Protić, Dragana; Bukumirić, Zoran; Radosavljević, Ivan; Bošković, Aneta; Todorović, Zoran
The aim of the present study was to undertake a study on the prevalence of cytochrome P450 2D6 (CYP2D6) poor metabolizer alleles (*3, *4, *5, and *6) on a Montenegrin population and its impact on developing adverse drug reactions (ADRs) of β-blockers in a hospitalized cardiac patient population. A prospective study was conducted in the Cardiology Center of the Clinical Center of Montenegro and included 138 patients who had received any β-blocker in their therapy. ADRs were collected using a specially designed questionnaire, based on the symptom list and any signs that could point to eventual ADRs. Data from patients’ medical charts, laboratory tests, and other available parameters were observed and combined with the data from the questionnaire. ADRs to β-blockers were observed in 15 (10.9%) patients. There was a statistically significant difference in the frequency of ADRs in relation to genetically determined enzymatic activity (P<0.001), with ADRs’ occurrence significantly correlating with slower CYP2D6 metabolism. Our study showed that the adverse reactions to β-blockers could be predicted by the length of hospitalization, CYP2D6 poor metabolizer phenotype, and the concomitant use of other CYP2D6-metabolizing drugs. Therefore, in hospitalized patients with polypharmacy CYP2D6 genotyping might be useful in detecting those at risk of ADRs. PMID:27536078
Cornelius, Victoria R; Liu, Kun; Peacock, Janet; Sauzet, Odile
Objective To compare consistency of adverse drug reaction (ADR) data in publicly available product information documents for brand drugs, between the USA and Europe. To assess the usefulness of information for prescribers and patients. Design A comparison review of product information documents for antidepressants and anticonvulsants concurrently marketed by the same pharmaceutical company in the USA and Europe. Setting For each drug, data were extracted from the US Product Inserts and the European Summary of Product Characteristics documents between 09/2013 and 01/2015. Participants Individuals contributing ADR information to product information documents. Main outcomes measures All ADRs reported in product information sections 5 and 6 (USA), and 4·4 and 4·8 (Europe). Results Twelve brand drugs—24 paired documents—were included. On average, there were 77 more ADRs reported in the USA compared with in the European product information document, with a median number of 201 ADRs (range: 65–425) and 114 (range: 56–265), respectively. More product information documents in the USA reported information on the source of evidence (10 vs 5) and risk (9 vs 5) for greater than 80% of ADRs included in the document. There was negligible information included regarding duration, severity, reversibility or recurrence of ADRs. On average, only 29% of ADR terms were reported in both paired documents. Conclusions Product information documents contained a large number of ADRs, but lacked contextual data and information important to patients and prescribers, such as duration, severity and reversibility. The ADR profile was found to be inconsistently reported between the USA and Europe, for the same drug. Identifying, selecting, summarising and presenting multidimensional harm data should be underpinned by practical evidence-based guidelines. In order for prescribers to provide considered risk-benefit advice across competing drug therapies to patients, they need access to
Simon, R A
There is a long list of additives used by the pharmaceutical industry. Most of the agents used have not been implicated in hypersensitivity reactions. Among those that have, only reactions to parabens and sulfites have been well established. Parabens have been shown to be responsible for rare immunoglobulin E-mediated reactions that occur after the use of local anesthetics. Sulfites, which are present in many drugs, including agents commonly used to treat asthma, have been shown to provoke severe asthmatic attacks in sensitive individuals. Recent studies indicate that additives do not play a significant role in "hyperactivity." The role of additives in urticaria is not well established and therefore the incidence of adverse reactions in this patient population is simply not known. In double-blind, placebo-controlled studies, reactions to tartrazine or additives other than sulfites, if they occur at all, are indeed quite rare for the asthmatic population, even for the aspirin-sensitive subpopulation.
Aagaard, Lise; Soendergaard, Birthe; Stenver, Doris I; Hansen, Ebba Holme
Aims Spontaneous reports of adverse drug reactions (ADRs) are often the only documentation used to justify the recall of drugs from the market. The purpose of this study was to investigate whether it would have been possible to foresee serious ADR cases based on available information on ADRs reported in Phase II and III clinical trials before marketing. Methods We conducted a retrospective analysis of reported ADR data in Phase II/III clinical trials in the registration material for three different ADR scenarios: (i) trovafloxacin/alatrofloxacin and hepatotoxicity; (ii) tolcapone and hepatotoxicity and neuroleptic malignant syndrome; and (iii) rituximab and cytokine release syndrome. We chose the scenarios because they were of serious character and caused great damage to the patients and because of different outcomes of the scientific discussions in the regulatory agencies. Results In all three cases, the registration material contained observations of ADRs, but there had been no follow-up on these observations. ADRs were mentioned in the summary of product information (SPC) purely as information, to some extent accompanied by recommendations. The information was not converted into new knowledge and remained tacit knowledge embedded in the SPCs disseminated to health professionals/prescribers. Conclusions The registration material analysed contained information about ADRs that were reported later, meaning that it would have been possible to foresee the occurrence of the ADRs at the time of licensing. More active utilization of the information from Phase II/III clinical trials is recommended to prevent the appearance of unexpected ADRs and further emphasis in SPC warnings to doctors about possible serious ADRs. What is already known about this subject? Serious and unexpected adverse drug reactions (ADRs) have been reported shortly after marketing of a number of drugs.Review of ADR cases by the regulatory authorities has resulted in suspension of drugs or
Dubus, Jean-Christophe; Bavoux, Françoise; Boyer-Gervoise, Marie-José; Jean-Pastor, Marie-Josèphe; Chalumeau, Martin
Objective To report pediatric cases of paradoxical respiratory adverse drug reactions (ADRs) after exposure to oral mucolytic drugs (carbocysteine, acetylcysteine) that led to the withdrawal of licenses for these drugs for infants in France and then Italy. Design The study followed the recommendations of the European guidelines of pharmacovigilance for medicines used in the paediatric population. Setting Cases voluntarily reported by physicians from 1989 to 2008 were identified in the national French pharmacovigilance public database and in drug company databases. Patients The definition of paradoxical respiratory ADRs was based on the literature. Exposure to mucolytic drugs was arbitrarily defined as having received mucolytic drugs for at least 2 days (>200 mg) and at least until the day before the first signs of the suspected ADR. Results The non-exclusive paradoxical respiratory ADRs reported in 59 paediatric patients (median age 5 months, range 3 weeks to 34 months, 98% younger than 2 years old) were increased bronchorrhea or mucus vomiting (n = 27), worsening of respiratory distress during respiratory tract infection (n = 35), dyspnoea (n = 18), cough aggravation or prolongation (n = 11), and bronchospasm (n = 1). Fifty-one (86%) children required hospitalization or extended hospitalization because of the ADR; one patient died of pulmonary oedema after mucus vomiting. Conclusion Parents, physicians, pharmacists, and drug regulatory agencies should know that the benefit risk ratio of mucolytic drugs is at least null and most probably negative in infants according to available evidence. PMID:21818391
Mallet, Pauline; Mourdi, Nadjette; Dubus, Jean-Christophe; Bavoux, Françoise; Boyer-Gervoise, Marie-José; Jean-Pastor, Marie-Josèphe; Chalumeau, Martin
To report pediatric cases of paradoxical respiratory adverse drug reactions (ADRs) after exposure to oral mucolytic drugs (carbocysteine, acetylcysteine) that led to the withdrawal of licenses for these drugs for infants in France and then Italy. The study followed the recommendations of the European guidelines of pharmacovigilance for medicines used in the paediatric population. Cases voluntarily reported by physicians from 1989 to 2008 were identified in the national French pharmacovigilance public database and in drug company databases. The definition of paradoxical respiratory ADRs was based on the literature. Exposure to mucolytic drugs was arbitrarily defined as having received mucolytic drugs for at least 2 days (>200 mg) and at least until the day before the first signs of the suspected ADR. The non-exclusive paradoxical respiratory ADRs reported in 59 paediatric patients (median age 5 months, range 3 weeks to 34 months, 98% younger than 2 years old) were increased bronchorrhea or mucus vomiting (n = 27), worsening of respiratory distress during respiratory tract infection (n = 35), dyspnoea (n = 18), cough aggravation or prolongation (n = 11), and bronchospasm (n = 1). Fifty-one (86%) children required hospitalization or extended hospitalization because of the ADR; one patient died of pulmonary oedema after mucus vomiting. Parents, physicians, pharmacists, and drug regulatory agencies should know that the benefit risk ratio of mucolytic drugs is at least null and most probably negative in infants according to available evidence.
Amalia, Lia; Anggadireja, Kusnandar; Aprami, Toni M; Septiani, Vina
Adverse drug reactions (ADRs) are associated with morbidity, mortality, and can contribute to increased healthcare costs. This study was conducted to identify the occurence, types, and management of ADRs, as well as analyze the causal relationship, severity, and preventability of ADRs. The study was observational analysis with concurrent data collection from patients with Coronary Artery Disease-ST segment Elevation Myocardial Infarction (CAD-STEMI) treated in the Cardiac Intensive Care Unit (CICU) at a hospital in Bandung Indonesia, during the period of December 2013 to March 2014. The occurence of identified ADRs was assessed using the probability scale of Naranjo, while the severity by the scale of Hartwig and their preventability was evaluated using the scale of Schumock-Thornton. 49 ADRs were identified in 29 patients. Organ systems most affected by the ADRs were the cardiovascular and body electrolyte, each accounting for 20.41%. The hematology and gastrointestinal systems each contributed 18.37% to ADR occurrences. The causal relationship was mostly classified as "probable," accounting for 69.39%. With regard to severity, most ADRs were classified as "moderate" at level 3, contributing to 53.06% of the occurence. In terms of preventability, most of the ADRs fell into the "non-preventable" category (79.59%). The most widely applied ADRs management was administration of an antidote or other treatments (40.82%). Further analysis revealed that the average number of drug types and duration of hospitalization significantly affected the presence of ADRs. Taken together, most patients with CAD STEMI treated in the CICU of the studied hospital experienced non-preventable ADRs and were treated with antidote or other treatments.
Tripathi, Raakhi Kaliprasad; Jalgaonkar, Sharmila Vinayak; Sarkate, Pankaj V.; Rege, Nirmala Narayan
Objectives: 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. Materials and Methods: 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. Results: 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. Conclusion: 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. PMID:28031613
Tripathi, Raakhi Kaliprasad; Jalgaonkar, Sharmila Vinayak; Sarkate, Pankaj V; Rege, Nirmala Narayan
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.
Kiguba, Ronald; Ononge, Sam; Karamagi, Charles; Bird, Sheila M
Clinical history-taking can be employed as a standardized approach to elucidate the use of herbal medicines and their linked suspected adverse drug reactions (ADRs) among hospitalized patients. We sought to identify herbal medicines nominated by Ugandan inpatients; compare nomination rates by ward and gender; confirm the herbs' known pharmacological properties from published literature; and identify ADRs linked to pre-admission use of herbal medicines. Prospective cohort of consented adult inpatients designed to assess medication use and ADRs on one gynaecological and three medical wards of 1790-bed Mulago National Referral Hospital. Baseline and follow-up data were obtained on patients' characteristics, including pre-admission use of herbal medicines. Fourteen percent (26/191) of females in Gynaecology nominated at least one specific herbal medicine compared with 20 % (114/571) of inpatients on medical wards [20 % (69/343) of females; 20 % (45/228) of males]. Frequent nominations were Persea americana (30), Mumbwa/multiple-herb clay rods (23), Aloe barbadensis (22), Beta vulgaris (12), Vernonia amygdalina (11), Commelina africana (7), Bidens pilosa (7), Hoslundia opposita (6), Mangifera indica (4), and Dicliptera laxata (4). Four inpatients experienced 10 suspected ADRs linked to pre-admission herbal medicine use including Commelina africana (4), multiple-herb-mumbwa (1), or unspecified local-herbs (5): three ADR-cases were abortion-related and one kidney-related. The named herbal medicines and their nomination rates generally differed by specialized ward, probably guided by local folklore knowledge of their use. Clinical elicitation from inpatients can generate valuable safety data on herbal medicine use. However, larger routine studies might increase the utility of our method to assess herbal medicine use and detect herb-linked ADRs. Future studies should take testable samples of ADR-implicated herbal medicines for further analysis.
Khan, Sarfaraz Alam; Goyal, Chhaya; Chandel, Nitibhushansingh; Rafi, Mohammed
Background: Underreporting of spontaneous adverse drug reaction (ADR) is a threat to pharmacovigilance. Various factors related with the knowledge and attitudes are responsible for underreporting of ADRs. Aims: The study was aimed at investigating the knowledge and attitudes of doctors to ADR reporting. Materials and Methods: It was a questionnaire-based cross-sectional study. One hundred and eight questionnaires were administered to doctors working in a teaching hospital with an ADR monitoring center. Statistical Analysis Used: The descriptive statistics were used for responses to evaluate the knowledge and attitudes toward ADR reporting. Pearson's Chi-square test was used to observe the association of knowledge and attitude with experience and position. Results: The response rate was 62.9%. Spontaneous reporting rate was found to be 19.1%. The major factors found to be responsible for underreporting of ADR include inadequate risk perception about newly marketed drugs (77.9%), fear factor (73.5%), diffidence (67.7%), lack of clarity of information on ADR form about reporting (52.9%), lethargy (42.7%), insufficient training to identify ADRs (41.2%), lack of awareness about existence of pharmacovigilance program (30.9%) and ADR monitoring center in the institute (19.1%), and inadequate risk perception of over-the-counter (OTC) product (20.6%) and herbal medicines (13.2%). Experience and position did not influence the knowledge and attitudes of doctors. Conclusion: The deficiencies in knowledge and attitudes require urgent attention not only to improve the rate of spontaneous reporting, but also for enhanced safety of the patients and society at large. PMID:23633861
Uhara, H; Kiyohara, Y; Tsuda, A; Takata, M; Yamazaki, N
Post-approval research or monitoring is important to determine real-world safety of new products; however, evidence is scant for vemurafenib in Japanese patients. In Japan, a unique system is officially obligated to investigate post-approval safety. Here we report the first adverse drug reaction (ADR) data from vemurafenib-treated Japanese patients with metastatic melanoma. Data were collected in an early post-marketing phase vigilance (EPPV) study. ADRs were events for which a causal relationship with vemurafenib could not be ruled out or was unknown. ADR data were collected for patients treated with vemurafenib (960 mg bid) between 26 February and 25 August 2015. Among 95 patients, 46 patients had 118 ADRs (24 serious ADRs in 13 patients). The most common serious ADRs were hypersensitivity (n = 1; 3 events), arthralgia (n = 2; 2 events), pyrexia (n = 2; 2 events) and drug eruption (n = 2; 2 events). Seven patients had serious skin disorders or hypersensitivity, six of whom had prior anti-programmed cell death-1 (PD-1) antibodies 5-35 days before starting vemurafenib. ADR reports of serious skin disorders appeared to be collected more rapidly than previously reported. Cutaneous squamous cell carcinoma developed in only one patient. EPPV in Japanese vemurafenib-treated patients identified no new safety signals. The most serious skin and hypersensitivity ADRs occurred in patients with prior anti-PD-1 exposure. Cutaneous squamous cell carcinoma appeared to be rare in Japanese patients. Further research is needed to clarify whether prior treatment with anti-PD-1 agents or racial differences affect the characteristic profile of cutaneous ADRs in Japanese patients.
Tanti, A; Serracino-Inglott, A; Borg, J J
The Maltese Medicines Authority was tasked with developing a reporting form that captures high-quality case information on adverse drug reactions (ADRs) and medication errors in order to fulfil its public-health obligations set by the European Union (EU) legislation on pharmacovigilance. This paper describes the process of introducing the first combined ADR/medication error reporting form in the EU for health-care professionals, the analysis of reports generated by it and the promotion of the system. A review of existing ADR forms was carried out and recommendations from the European Medicines Agency and World Health Organization audits integrated. A new, combined ADR/medication error reporting form was developed and pilot tested based on case studies. The Authority's quality system (ISO 9001 certified) was redesigned and a promotion strategy was deployed. The process used in Malta can be useful for countries that need to develop systems relative to ADR/medication error reporting and to improve the quality of data capture within their systems.
Guo, Xiao-jing; Ye, Xiao-fei; Wang, Xing-xing; Wang, Jing; Shi, Wen-tao; Gao, Qing-bin; Zhang, Tian-yi; Xu, Jin-fang; Zhu, Tian-tian; He, Jia
The goal of this study was to clarify the reporting patterns of self-reported adverse drug reactions (ADRs) in China. A variety of sources were searched, including the official website of China FDA, the national center for ADR monitoring center, publications from PubMed, and so on. We retrieved the relevant information and made descriptive and comparative analysis from the year 2009 to 2013. The ADR reporting numbers were 638,996, 692,904, 852,799, 1,200,000 and 1,317,000 from 2009 to 2013, respectively. Healthcare professionals contributed significantly, and their proportion always exceeded 80% before 2012. The average report per million inhabitants has increased from 479 to 983 from 2009 to 2013. However, the proportion of new or serious report was always below 25%. The reports mainly concern anti-infective agents and traditional Chinese medicine (TCM), especially TCM injection. The proportion of ADR reports in geriatric patients has increased for 4 consecutive years. ADR report numbers and reporting rates in China are on the rise. However, the proportion of new or serious reports as well as the proportion of reports contributed by consumers and pharmaceutical companies are still quite low. More attention should be paid to the elderly, anti-infective agents and TCM, especially TCM injections.
Alagoz, O; Durham, D; Kasirajan, K
We evaluated the cost-effectiveness of one-time pharmacogenomic testing for preventing adverse drug reactions (ADRs) over a patient's lifetime. We developed a Markov-based Monte Carlo microsimulation model to represent the ADR events in the lifetime of each patient. The base-case considered a 40-year-old patient. We measured health outcomes in life years (LYs) and quality-adjusted LYs (QALYs) and estimated costs using 2013 US$. In the base-case, one-time genetic testing had an incremental cost-effectiveness ratio (ICER) of $43,165 (95% confidence interval (CI) is ($42,769,$43,561)) per additional LY and $53,680 per additional QALY (95% CI is ($53,182,$54,179)), hence under the base-case one-time genetic testing is cost-effective. The ICER values were most sensitive to the average probability of death due to ADR, reduction in ADR rate due to genetic testing, mean ADR rate and cost of genetic testing.
Almandil, Noor B.
Objectives To document the knowledge of, attitudes toward, and practices of adverse drug reaction (ADR) reporting and pharmacovigilance systems among healthcare professionals. Methods This descriptive cross-sectional study was conducted using a questionnaire. This study took place at King Fahd Hospital of the University (KFHU), Khobar, Kingdom of Saudi Arabia, between April 2015 and April 2016. Healthcare professionals, including physicians, pharmacists, pharmacy technicians, and nurses, were considered eligible and invited to take part in the study. A link to the online questionnaire was sent to each participant via E-mail, and a hard copy was circulated at the hospital after the objectives of the study were explained. The questionnaire comprised items regarding knowledge/awareness of pharmacovigilance and ADRs, perception/attitude towards pharmacovigilance and ADR reporting, and practices of ADR reporting. Descriptive statistics were used to analyze the data. Results A total of 400 questionnaires were distributed to the healthcare professionals and 331 participants responded, providing a response rate of 82.75%. The healthcare professionals comprised 161 physicians, 39 pharmacists, 21 pharmacist technicians, and 110 nurses. Most of the participants were female (n=198) and Saudi (61.9%). Most healthcare professionals (62.5%) were unaware of the term pharmacovigilance; the pharmacists and pharmacist technicians had the highest rate of pharmacovigilance awareness (60.5% of the pharmacists and 40% of pharmacist technicians). Conclusion There is a lack of awareness and knowledge of pharmacovigilance and ADR reporting among healthcare professionals working at KFHU. PMID:27874152
Vallano, A; Cereza, G; Pedròs, C; Agustí, A; Danés, I; Aguilera, C; Arnau, J M
Aim To describe the opinions of hospital physicians concerning problems regarding the spontaneous reporting of adverse drug reactions (ADRs) and ways to solve them. Methods A qualitative study was carried out. Fifteen focus groups were conducted among physicians working in a tertiary teaching hospital. A total of 208 physicians from different medical specialities participated. The focus group discussions were recorded by three different observers and the transcripts of each session were analysed for issues and themes emerging from the text. Results Four types of obstacles to spontaneous reporting were considered particularly important: (i) problems with the ADRs diagnosis; (ii) problems with the usual workload and lack of time; (iii) problems related to the organization and activities of the pharmacovigilance system; (iv) and problems related to potential conflicts. The potential solutions suggested for improving spontaneous reporting were to define the kind of ADRs which should be reported, to facilitate an easy contact and quick access to the hospital pharmacovigilance system, to facilitate information and support for reporting and feedback of pharmacovigilance activities. Conclusions The perception of the different obstacles by the hospital physicians is an important factor in determining the causes of the underreporting of ADRs and addressing these obstacles could lead to an improvement in spontaneous reporting. A closer relationship between the doctors and the pharmacovigilance centre is suggested as a means of solving these problems. More information is needed to improve the spontaneous reporting of ADRs in specialized healthcare. PMID:16305591
Allegaert, Karel; van den Anker, Johannes N
Drug therapy is a powerful tool to improve outcome, but there is an urgent need to improve pharmacotherapy in neonates through tailored prevention and management of adverse drug reactions (ADRs). At present, infants commonly receive off-label drugs, at dosages extrapolated from those in children or adults. Besides the lack of labelling, inappropriate formulations, (poly)pharmacy, immature organ function and multiple illnesses further raise the risk for ADRs in neonates and infants. Pharmacovigilance to improve the prevention and management of ADRs needs to be tailored to neonates and infants. We illustrate this using prevention strategies for drug prescription and administration errors (e.g. formulation, bedside manipulation, access), detection through laboratory signalling or clinical outlier data (e.g. reference laboratory values, overall high morbidity), assessment through algorithm scoring (e.g. Naranjo or population specific), as well as understanding of the developmental toxicology (e.g. covariates, developmental pharmacology) to avoid re-occurrence and for development of guidelines. Such tailored strategies need collaborative initiatives to combine the knowledge and expertise of different disciplines, but hold promise to become a very effective tool to improve pharmacotherapy and reduce ADRs in infants. PMID:24862557
Li, Chanjuan; Xia, Jielai; Deng, Jianxiong; Chen, Wenge; Wang, Suzhen; Jiang, Jing; Chen, Guanquan
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.
Wang, Kejian; Weng, Zuquan; Sun, Liya; Sun, Jiazhi; Zhou, Shu-Feng; He, Lin
Adverse drug reaction (ADR) is of great importance to both regulatory agencies and the pharmaceutical industry. Various techniques, such as quantitative structure–activity relationship (QSAR) and animal toxicology, are widely used to identify potential risks during the preclinical stage of drug development. Despite these efforts, drugs with safety liabilities can still pass through safety checkpoints and enter the market. This situation raises the concern that conventional chemical structure analysis and phenotypic screening are not sufficient to avoid all clinical adverse events. Genomic expression data following in vitro drug treatments characterize drug actions and thus have become widely used in drug repositioning. In the present study, we explored prediction of ADRs based on the drug-induced gene-expression profiles from cultured human cells in the Connectivity Map (CMap) database. The results showed that drugs inducing comparable ADRs generally lead to similar CMap expression profiles. Based on such ADR-gene expression association, we established prediction models for various ADRs, including severe myocardial and infectious events. Drugs with FDA boxed warnings of safety liability were effectively identified. We therefore suggest that drug-induced gene expression change, in combination with effective computational methods, may provide a new dimension of information to facilitate systematic drug safety evaluation. - Highlights: • Drugs causing common toxicity lead to similar in vitro gene expression changes. • We built a model to predict drug toxicity with drug-specific expression profiles. • Drugs with FDA black box warnings were effectively identified by our model. • In vitro assay can detect severe toxicity in the early stage of drug development.
Lebrun-Vignes, B; Kreft-Jais, C; Castot, A; Chosidow, O
The question of quantitative and qualitative differences between adverse drug reactions (ADRs) to tetracyclines was raised many years ago, especially for minocycline and doxycycline. To assess and compare ADRs related to tetracyclines according to sales figures in France through a national survey. ADR data were collected from the French Pharmacovigilance Database (FPD), marketing authorization holders (MAH) and the literature. Sales analyses were based on MAH data provided annually to the French Drugs Agency. Among the tetracyclines available in France, doxycycline and minocycline are the most frequently used. However, their sales decreased between 1995 and 2007, more sharply for minocycline than doxycycline. According to the FPD, based on MAH data and published reports, minocycline-associated ADRs were more serious and were reported more frequently than for the other tetracyclines. Minocycline and doxycycline ADR patterns differed: gastrointestinal disorders (especially oesophageal lesions) predominated with doxycycline, while intracranial hypertension and hepatic disorders were primarily reported with minocycline. Autoimmune disorders, drug reaction with eosinophilia and systemic symptoms (DRESS) and other hypersensitivity reactions were also more frequent with minocycline. ADRs reported with lymecycline and metacycline were essentially cutaneous and gastrointestinal disorders. In the absence of markedly better efficacy against the various indications for tetracyclines, the minocycline benefit/risk ratio was clearly lower than that of doxycycline, and possibly those of lymecycline and metacycline. In light of these findings, minocycline should no longer be considered first-line therapy for inflammatory skin disorders, especially acne. © 2012 The Authors. BJD © 2012 British Association of Dermatologists.
Bond, C A; Raehl, Cynthia L
Adverse drug reactions (ADRs) were examined in 1,960,059 hospitalized Medicare patients in 584 United States hospitals in 1998. A database was constructed from the MedPAR database and the National Clinical Pharmacy Services survey. The 584 hospitals were selected because they provided specific information on 14 clinical pharmacy services and on pharmacy staffing; they also had functional ADR reporting systems. The study population consisted of 35,193 Medicare patients who experienced an ADR (rate of 1.8%). Of the 14 clinical pharmacy services, 12 were associated with reduced ADR rates. The most significant reductions occurred in hospitals offering pharmacist-provided admission drug histories (odds ratio [OR] 1.864, 95% confidence interval [CI] 1.765-1.968), drug protocol management (OR 1.365, 95% CI 1.335-1.395), and ADR management (OR 1.360, 95% CI 1.328-1.392). Multivariate analysis, performed to further evaluate these findings, showed that nine variables were associated with ADR rate: pharmacist-provided in-service education (slope -0.469, p=0.018), drug information (slope -0.488, p=0.005), ADR management (slope -0.424, p=0.021), drug protocol management (slope -0.732, p=0.002), participation on the total parenteral nutrition team (slope 0.384, p=0.04), participation on the cardiopulmonary resuscitation team (slope -0.506, p=0.008), medical round participation (slope -0.422, p=0.037), admission drug histories (slope -0.712, p=0.008), and increased clinical pharmacist staffing (slope -4.345, p=0.009). As clinical pharmacist staffing increased from the 20th to the 100th percentile (from 0.93+/-0.77/100 to 5.16+/-4.11/100 occupied beds), ADRs decreased by 47.88%. In hospitals without pharmacist-provided ADR management, the following increases were noted: mean number of ADRs/100 admissions by 34.90% (OR 1.360, 95% CI 1.328-1.392), length of stay 13.64% (Mann-Whitney U test [U]=11047367, p=0.017), death rate 53.64% (OR 1.574, 95% CI 1.423-1.731), total Medicare
Lake, C R; Gallant, S; Masson, E; Miller, P
Phenylpropanolamine (PPA) is contained in about 106 products, over half of which are available over-the-counter (OTC). Most are cough/cold remedies; nine are OTC diet aids. More than nine million Americans were using OTC diet aids in 1981, making PPA the fifth most used drug in the United States, responsible for over $200 million in revenues. The safety of PPA remains controversial. Although most controlled studies indicate minimal pressor effects with recommended doses, adverse drug reactions (ADRs) continue to be documented. Since 1965, 142 ADRs have been reported in 85 studies, 69% of these in North America. Many such cases may go unrecognized. About two thirds of all ADRs occurred in females and in patients under 30. Of ADRs attributed to legitimately sold PPA products, 85% occurred after consumption of OTC products versus only 15% after prescription drugs. The PPA product often contained combination ingredients, or PPA was consumed along with additional drugs. An overdose of PPA was taken in about a third of the cases. After ingestion of non-overdose amounts, 82% of the ADRs were severe. The most frequent side effects involved symptoms compatible with acute hypertension, with severe headache the most common complaint. Twenty-four intracranial hemorrhages, eight seizures, and eight deaths (most due to stroke) were associated with PPA ingestion. We have summarized these data in an effort to alert clinicians to the prevalence of usage of PPA products and the potential for adverse effects. In patients who present with elevated blood pressure or signs of acute hypertension, especially hypertensive encephalopathy of undetermined origin, we recommend inquiry about recent ingestion of PPA-containing diet aids and cough/cold products and suggest having such patients remain upright rather than supine.
Castillo-Carandang, Nina T; Juban, Noel R; Amarillo, Maria Lourdes; Tagle, Maria Pamela; Baja, Emmanuel S
Background Paper-based adverse drug reaction (ADR) reporting has been in practice for more than 6 decades. Health professionals remain the primary source of reports, while the value of patients’ reporting is yet unclear. With the increasing popularity of using electronic gadgets in health, it is expected that the electronic transmission of reports will become the norm within a few years. Objective The aims of this study are to investigate whether short messaging service or texting can provide an alternative or supplemental method for ADR reporting given the increasing role of mobile phones in health care monitoring; to determine the usefulness of texting in addition to paper-based reporting of ADRs by resident physicians; and to describe the barriers to ADR reporting and estimate the cost for setting up and maintaining a texting-computer reporting system. Methods This was a pre-post cross-sectional study that measured the number of ADRs texted by 51 resident physicians for 12 months from the Department of Obstetrics and Gynecology and the Department of Adult Medicine of a tertiary government hospital in Manila, Philippines, with 1350-bed capacity. Reports were captured by a texting-computer reporting system. Prior to its implementation, key informant interview and focus group discussion were conducted. Baseline information and practice on the existing paper-based reporting system were culled from the records of the hospital’s Pharmacy and Therapeutics Committee. A postintervention survey questionnaire was administered at the end of 12 months. Results Only 3 ADRs were texted by 51 resident physicians in 12 months (reporting rate 3/51 or 6%). By contrast, 240 ADRs from the paper-based reporting system from 848 resident physicians of the study hospital were collected and tabulated (reporting rate 240/848 or 28.3%). Texting ADRs was not efficient because of power interruption, competition with the existing paper-based reporting system, and unforeseen expiration of
Digra, Kishour Kumar; Pandita, Aakash; Saini, GS; Bharti, Rajni
AIM To study the pattern of various adverse drug reactions (ADRs) occurring in children attending the Department of Pediatrics, SMGS Hospital, Jammu over 1 year. SUBJECTS AND METHODS This was a prospective study, with study population of patients attending Department of Pediatrics over a period of 1 year. A structured format was used to enroll the participants. A pilot study was conducted to test the suitability of the format and feasibility of the study. The study was carried out to review various pattern of ADRs by using the Naranjo probability scale, and severity was assessed by using the Hartwig severity scale. ADRs were classified according to the classification used by the Adverse Drug Reaction Monitoring Center, Central Drugs Standard Control Organization, New Delhi, India. RESULTS In the present study, 104 patients were found to have developed acute drug reactions. Among these, 83.6% were type B, 14.42% type A, and 1.92% were type U. Furthermore, 25.96% ADRs were due to anticonvulsants, followed by antibiotics (22.11%), antipyretics (11.53%), vaccination (8.65%), steroids (6.73%), decongestants (5.67%), snake antivenom and antiemetics (3.84%), and fluids, insulin, and antacids (1.92%). The patients’ dermatological system was involved in 67.30%, followed by the central nervous system (CNS) in 11.53% patients. Renal system was involved in 6.73% patients. Cardiac, musculoskeletal, metabolic, and other systems were involved in 4.80%, 3.84%, 2.88%, and 0.96%, respectively. According to the Hartwig severity scale of ADRs, 64.4% patients had moderate ADRs, 29.8% patients had severe ADRs, and 5.76% had mild ADRs. In the present study, 64.4% patients expressed moderate severity, whereas 29.8% expressed high severity and 5.76% expressed mild ADRs. CONCLUSION ADRs were seen in 71% of the patients between 1 and 5 years of age, 26% in the age group of 5–10 years, and 3% were more than 10 years old. Anticonvulsants (25.96%) and antibiotics (22.11%) were responsible
Stewart, Derek; Helms, Peter; McCaig, Dorothy; Bond, Christine; McLay, James
To determine the feasibility of a community pharmacy-based parental adverse drug reaction (ADR) reporting system for children. 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. Seven community pharmacies in Grampian, Scotland. 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. The prospective monitoring of paediatric ADRs, using a questionnaire issued to parents or guardians in
Seger, Donna; BARKER, Kimberly; McNAUGHTON, Candace D.
Context When an adverse event occurs in an overdose patient, it may be difficult to determine whether the event was caused by the ingested drug or by medical therapy. Naranjo and colleagues developed a probability scale, the Naranjo Adverse Drug Reaction Probability Scale (Naranjo Scale), to assess the probability that a drug administered in therapeutic doses caused an adverse event thereby classifying the event as an adverse drug reaction (ADR). Although Naranjo et al. specifically excluded the application of this scale to adverse events in overdose patients, case reports demonstrate that authors continue to apply the Naranjo Scale to events in these patients. Objective The World Health Organization defines an ADR as occurring only when drugs are administered in therapeutic doses. Yet ADRs continue to be reported in overdose patients. We sought to examine the use of the Naranjo scale in case reports of overdose patients to assess the potential consequences of that application. Methods A Medline search via PubMed without language limits, through September 2012, using the search terms “Naranjo” and “overdose” or “poisoning” yielded 146 publications. Additional searches were performed to find articles with keywords of the Naranjo Scale development, current applications and validity of application in specific populations such as critically ill and overdose patients. Results From the 146 publications, we identified 17 case reports or series of overdose patients in which the Naranjo Scale was applied to a clinical complication to support a causal relationship between an administered drug and the clinical complication and thereby classify the clinical complication as an ADR. We also identified a recent publication in which the Naranjo Scale was applied to a new treatment modality (lipid emulsion) that is currently administered to overdose patients. Conclusion Adverse events that occur in overdose patients are excluded from the definition of ADR. Yet in case
Nguyen, Thin; Larsen, Mark E; O'Dea, Bridianne; Phung, Dinh; Venkatesh, Svetha; Christensen, Helen
This work aims to estimate the degree of adverse drug reactions (ADR) for psychiatric medications from social media, including Twitter, Reddit, and LiveJournal. Advances in lightning-fast cluster computing was employed to process large scale data, consisting of 6.4 terabytes of data containing 3.8 billion records from all the media. Rates of ADR were quantified using the SIDER database of drugs and side-effects, and an estimated ADR rate was based on the prevalence of discussion in the social media corpora. Agreement between these measures for a sample of ten popular psychiatric drugs was evaluated using the Pearson correlation coefficient, r, with values between 0.08 and 0.50. Word2vec, a novel neural learning framework, was utilized to improve the coverage of variants of ADR terms in the unstructured text by identifying syntactically or semantically similar terms. Improved correlation coefficients, between 0.29 and 0.59, demonstrates the capability of advanced techniques in machine learning to aid in the discovery of meaningful patterns from medical data, and social media data, at scale. Copyright © 2017 Elsevier B.V. All rights reserved.
Aagaard, Lise; Soendergaard, Birthe; Andersen, Elin; Kampmann, Jens Peter; Hansen, Ebba Holme
Data on adverse drug reactions (ADRs) have been collected in Denmark since 1968 and the process is ongoing. This article explores knowledge created by the system, including how the collected data have been used to monitor the safety of licensed drugs. Nonaka's theory of knowledge creation was used to discriminate between tacit and explicit knowledge. A total of 56,802 ADR case reports were received from 1968 to 2005. The analysis shows a rather stable number of ADR cases from 1980, with about 2000 reports per year. The distribution of cases into serious and non-serious ADRs has been one to four throughout the period under study, but with large variations. Analysis of selected ADR cases shows that the system lacked the potential to capture available knowledge. Consequently the ADR reports have had limited value and significance in the process of creating scientific knowledge. Thus, the analysis questions the way available data can become explicit as a basis for regulatory decisions and whether all data can become knowledge, including who decides what knowledge is.
Choon, Siew-Eng; Lai, Nai-Ming
The prevalence, clinical patterns, and causative drugs of cutaneous adverse drug reactions (cADR) vary among the different populations previously studied. To determine the prevalence, the clinical patterns of drug eruptions, and the common drugs implicated, particularly in severe cADR such as Stevens-Johnson Syndrome/Toxic epidermal necrolysis (SJS/TEN) and drug rash with eosinophilia and systemic symptoms (DRESS) in our population. We analyzed the database established for all cADR seen by the department of Dermatology from January 2001 till December 2010. A total of 362 cADR were seen among 42 170 new clinic attendees, yielding an incidence rate of 0.86%. The most common reaction pattern seen was maculopapular eruption (153 cases) followed by SJS/TEN (110 cases) and DRESS (34 cases). Antibiotics was the most commonly implicated drug group (146 cases) followed by anticonvulsants (81 cases) and antigout drugs (50 cases). The most frequently implicated drug was allopurinol (50 cases). Carbamazepine, allopurinol, and cotrimoxazole were the three main causative drugs of SJS/TEN accounting for 21.8%, 20.9%, and 12.7%, respectively, of the 110 cases seen, whereas DRESS was mainly caused by allopurinol (15 cases). Mortality rates for TEN, SJS, and DRESS were 28.6%, 2.2%, and 5.9%, respectively. The low rate of cADR with a high proportion of severe reactions observed in this study was probably due to referral bias. Otherwise, the reaction patterns and drugs causing cADR in our population were similar to those seen in other countries. Carbamazepine, allopurinol, and cotrimoxazole were the three main causative drugs of SJS/TEN in our population.
Cantor, Michael N; Feldman, Henry J; Triola, Marc M
Background As medical care moves towards an outpatient focus, monitoring systems for ambulatory patients are increasingly important. Because adverse outcomes due to medications are an important problem in outpatients, the authors developed an automated monitoring system for detecting adverse drug reactions (ADRs) in ambulatory patients. Methods The authors obtained a set of approximately 110 000 ambulatory care notes from the medicine clinic at Bellevue Hospital Centre for 2003–4, and manually analysed a representative sample of 1250 notes to obtain a gold standard. To detect ADRs in the text of electronic ambulatory notes, the authors used a “trigger phrases” methodology, based on a simple grammar populated with a limited set of keywords. Results Under current functionality, this system detected 38 of 54 cases in the authors' gold standard set, of which 17 were true positives, for a sensitivity of 31%, a specificity of 98%, and a positive predictive value of 45%. Their proxy measure correlated with 70% of the ADRs in the gold standard. These values are comparable or superior to other systems described in the literature. Conclusions These results show that an automated system can detect ADRs with moderate sensitivity and high specificity, and has the potential to serve as the basis for a larger scale reporting system. PMID:17403760
Carrasco-Garrido, P; Hernández-Barrera, V; Esteban-Hernández, J; Jiménez-Trujillo, I; Álvaro-Meca, A; López de Andrés, A; de Miguel Diez, J; Rodríguez Barrios, J M; Muñoz Robles, J A; Jiménez-García, R
Objective To describe and analyse hospitalisations for adverse drug reactions (ADRs) involving anticoagulants. We also analysed the progress of the reactions over time, the factors related with ADRs. Design A retrospective, descriptive, epidemiological study. Setting This study used the Spanish National Hospital Discharge Database (Conjunto Mínimo Básico de Datos, CMBD), over a 4-year period. Participants We selected CMBD data corresponding to hospital discharges with a diagnosis of ADRs to anticoagulants (International Classification of Diseases-Ninth Revision, Clinical Modification (ICD-9-CM) code E934.2) in any diagnostic field during the study period. Main outcome measures We calculated the annual incidence of ADRs to anticoagulants according to sex and age groups. The median lengths of hospital stay and in-hospital mortality (IHM) were also estimated for each year studied. Bivariate analyses of the changes in variables according to year were based on Poisson regression. IHM was analysed using logistic regression models. The estimates were expressed as ORs and their 95% CI. Results During the study period, 50 042 patients were hospitalised because of ADRs to anticoagulants (6.38% of all ADR-related admissions). The number of cases increased from 10 415 in 2010 to 13 891 in 2013. Cumulative incidence of ADRs to anticoagulants was significantly higher for men than women and in all age groups. An adjusted multivariate analysis revealed that IHM did not change significantly over time. We observed a statistically significant association between IHM and age, with the highest risk for the ≥85 age group (OR 2.67; 95% CI 2.44 to 2.93). Conclusions The incidence of ADRs to anticoagulants in Spain increased from 2010 to 2013, and was significantly higher for men than women and in all age groups. Older patients were particularly susceptible to being hospitalised with an adverse reaction to an anticoagulant. PMID:28073793
Nanau, Radu M; Neuman, Manuela G
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.
Rottenkolber, Dominik; Schmiedl, Sven; Rottenkolber, Marietta; Thuermann, Petra A; Hasford, Joerg
Therapy for adverse drug reactions (ADRs) often results in the application of blood components. This study aims to assess the demand for blood components and the resulting economic burden (hospital perspective) in German hospitals induced by ADRs leading to admissions to departments of internal medicine. In this prospective study, ADRs leading to hospitalization were surveyed in four regional pharmacovigilance centres in Germany during the years 2000-2007. ADRs assessed as 'possible', 'likely' or 'very likely' were included. Market prices for blood components and hospitalization data were determined by desktop research. A probabilistic sensitivity analysis was performed. A total of 6099 patients were admitted to internal medicine departments because of an outpatient ADR of whom 1165 patients (19.1%; mean age, 73.0 ± 13.0 years) required treatment with blood components owing to major bleeding events. Overall consumption was 4185 erythrocyte concentrates (EC), 426 fresh frozen plasma (FFP) and 48 thrombocyte (TC) units. On the basis of statistical hospital data, we estimated a nationwide demand of approximately 132,020 EC, 13,440 FFP and 1515 TC units, resulting in total costs of €12.66 million per year for all German hospitals. Some 19.2% of all ADR cases were assessed as preventable. Theoretically, a nationwide decreased demand for blood components and a savings potential of €2.43 million per year could be achieved by preventing ADRs in Germany. Blood components are used in one-fifth (mainly gastrointestinal bleeding) of all ADRs, leading to hospitalizations in internal medicine departments. Both blood demand and hospital procurement costs can be significantly lowered by preventing ADRs.
Paul, Lindsay; Robinson, Kerin M
Allergic responses to prescription drugs are largely preventable, and incur significant cost to the community both financially and in terms of healthcare outcomes. The capacity to minimise the effects of repeated events rests predominantly with the reliability of allergy documentation in medical records and computerised physician order entry systems (CPOES) with decision support such as allergy alerts. This paper presents an overview of the nature and extent of adverse drug reactions (ADRs) in Australia and other developed countries, a discussion and evaluation of strategies which have been devised to address this issue, and a commentary on the role of coded data in informing this patient safety issue. It is not concerned with pharmacovigilance systems that monitor ADRs on a global scale. There are conflicting reports regarding the efficacy of these strategies. Although in many cases allergy alerts are effective, lack of sensitivity and contextual relevance can often induce doctors to override alerts. Human factors such as user fatigue and inadequate adverse drug event reporting, including ADRs, are commonplace. The quality of and response to allergy documentation can be enhanced by the participation of nurses and pharmacists, particularly in medication reconciliation. The International Classification of Diseases (ICD) coding of drug allergies potentially yields valuable evidence, but the quality of local and national level coded data is hampered by under-documenting and under-coding.
D'Incau, Paola; Lapeyre-Mestre, Maryse; Carvajal, Alfonso; Donati, Monia; Salado, Inés; Rodriguez, Lauriane; Sáinz, María; Escudero, Antonio; Conforti, Anita
A large number of studies have suggested that being a woman represents a potential risk factor for the development of adverse drug reactions (ADRs). The aim of this study is to further explore the differences between men and women with regard to reported ADRs, particularly those associated with psychotropic drugs. We used spontaneous reports of suspected ADRs collected by Midi-Pyrénées (France), Veneto (Italy) and Castilla y León (Spain) Regional Pharmacovigilance Centres (January 2007-December 2009). All the reports including a psychotropic medication were selected in a first step; age distribution, seriousness and type of ADRs were compared between men and women. Reports of nonpsychotropic drugs were similarly identified and treated. The absolute number of reports and the proportion, considering population, were higher in women than in men. This was observed for all reports, but was particularly higher for psychotropic drugs (592 vs. 375; P < 0.001) than for nonpsychotropics drugs (5193 vs. 4035; P < 0.001). Antidepressants were the most reported (women, 303; men, 141; P < 0.001); the reporting rates (number of reports divided by exposed patients in the same period, estimated through sales data) for these drugs, however, were not significantly different between women (0.87 cases per 10 000 treated persons per year) and men (0.81 cases per 10 000 treated persons per year). Although there was a higher number of reports of ADRs in women, ADR reporting rates might be similar as highlighted by the case of antidepressants. Antidepressant ADRs in fact were similarly reported in men and in women. Gender differences are sometimes subtle and difficult to explore. International networks, as the one established for this study, do contribute to better analyse problems associated with medications. © 2013 The Authors Fundamental and Clinical Pharmacology © 2013 Société Française de Pharmacologie et de Thérapeutique.
Lee, Suehyun; Choi, Jiyeob; Kim, Hun-Sung; Kim, Grace Juyun; Lee, Kye Hwa; Park, Chan Hee; Han, Jongsoo; Yoon, Dukyong; Park, Man Young; Park, Rae Woong; Kang, Hye-Ryun; Kim, Ju Han
We propose 2 Medical Dictionary for Regulatory Activities-enabled pharmacovigilance algorithms, MetaLAB and MetaNurse, powered by a per-year meta-analysis technique and improved subject sampling strategy. This study developed 2 novel algorithms, MetaLAB for laboratory abnormalities and MetaNurse for standard nursing statements, as significantly improved versions of our previous electronic health record (EHR)-based pharmacovigilance method, called CLEAR. Adverse drug reaction (ADR) signals from 117 laboratory abnormalities and 1357 standard nursing statements for all precautionary drugs ( n = 101) were comprehensively detected and validated against SIDER (Side Effect Resource) by MetaLAB and MetaNurse against 11 817 and 76 457 drug-ADR pairs, respectively. We demonstrate that MetaLAB (area under the curve, AUC = 0.61 ± 0.18) outperformed CLEAR (AUC = 0.55 ± 0.06) when we applied the same 470 drug-event pairs as the gold standard, as in our previous research. Receiver operating characteristic curves for 101 precautionary terms in the Medical Dictionary for Regulatory Activities Preferred Terms were obtained for MetaLAB and MetaNurse (0.69 ± 0.11; 0.62 ± 0.07), which complemented each other in terms of ADR signal coverage. Novel ADR signals discovered by MetaLAB and MetaNurse were successfully validated against spontaneous reports in the US Food and Drug Administration Adverse Event Reporting System database. The present study demonstrates the symbiosis of laboratory test results and nursing statements for ADR signal detection in terms of their system organ class coverage and performance profiles. Systematic discovery and evaluation of the wide spectrum of ADR signals using standard-based observational electronic health record data across many institutions will affect drug development and use, as well as postmarketing surveillance and regulation.
Yasnoff, William A.; Tomkins, Edward L.; Dunn, Louise M.
Adverse drug reactions (ADRs) are a major source of preventable morbidity and mortality, especially among the elderly, who use more drugs and are more sensitive to them. The insurance industry has recently addressed this problem through the implementation of drug interaction alerts to pharmacists in conjunction with immediate online claims adjudication for almost 60% of prescriptions (expected to reach 90% within 5 years). These alerts are based on stored patient drug profiles maintained by pharmacy benefit managers (PBMs) which are updated whenever prescriptions are filled. While these alerts are very helpful, the pharmacist does not prescribe, resulting in time-consuming and costly delays to contact the physician and remedy potential interactions. We have developed and demonstrated the feasibility of the PINPOINT (Pharmaceutical Information Network for prevention of interactions) system for making the drug profile and interaction information easily available to the physician before the prescription is written. We plan to test the cost-effectiveness of the system in a prospective controlled clinical trial.
Chen, Kan; Yang, Xinyan; Wu, Liqin; Yu, Meilan; Li, Xiaoyan; Li, Na; Wang, Shuanghui; Li, Gongchu
Pinelliapedatisecta agglutinin (PPA) has previously been used in labeling fractions of myeloid leukemia cells in our laboratory. We report here that a bacterial expressed recombinant PPA domain b tagged with soluble coxsackie and adenovirus receptor (sCAR-PPAb) preferentially recognized drug resistant cancer cells K562/ADR and H460/5Fu, as compared to their parental cell lines. Pretreatment of K562/ADR cells with sCAR-PPAb significantly enhanced phagocytosis of K562/ADR by macrophages in vivo. Meanwhile, in a K562/ADR xenograft model, intratumoral injection of sCAR-PPAb induced macrophage infiltration and phagocytosis. Furthermore, immunoprecipitation, mass spectrometry and Western blot identified the membrane target of PPA on K562/ADR as sarcolemmal membrane associated protein (SLMAP). An antibody against SLMAP significantly promoted the phagocytosis of K562/ADR by macrophages in vitro. These findings suggest that PPA not only could be developed into a novel agent that can detect drug resistant cancer cells and predict chemotherapy outcome, but also it has potential value in immunotherapy against drug resistant cancer cells through inducing the tumoricidal activity of macrophages. PMID:24019967
van Puijenbroek, Eugène; Diemont, Willem; van Grootheest, Kees
The primary aim of spontaneous reporting systems (SRSs) is the timely detection of unknown adverse drug reactions (ADRs), or signal detection. Generally this is carried out by a systematic manual review of every report sent to an SRS. Statistical analysis of the data sets of an SRS, or quantitative signal detection, can provide additional information concerning a possible relationship between a drug and an ADR. We describe the role of quantitative signal detection and the way it is applied at the Netherlands Pharmacovigilance Centre Lareb. Results of the statistical analysis are implemented in the traditional case-by-case analysis. In addition, for data-mining purposes, a list of associations of ADRs and suspected drugs that are disproportionally present in the database is periodically generated. Finally, quantitative signal generation can be used to study more complex relationships, such as drug-drug interactions and syndromes. The results of quantitative signal detection should be considered as an additional source of information, complementary to the traditional analysis. Techniques for the detection of drug interactions and syndromes offer a new challenge for pharmacovigilance in the near future.
Hu, Loh; Kim Emily, Ang Neo; Juh Allen, Yeoh Eng
To summarise and review the best available evidence on the poorer outcome of adverse drug reactions (ADRs) induced by oral dexamethasone in adolescents with Acute Lymphoblastic Leukaemia (ALL) than in children with ALL. Five databases for published literature were searched for the period 1990 to 2009. Additionally, the reference lists of all retrieved articles were further searched for additional references. Assessment for methodological quality was undertaken using a critical appraisal tool from JBI-SUMARI. Following the critical appraisal, data extraction was carried out using the data extraction tool from JBI-MAStaRI. Specific details about the study, design, data collection methods, participants, stage of therapy, type of adverse drug reaction, location of evidence and findings were then described and compiled into a table. Data synthesis was presented in a narrative format as the methodologically heterogeneous nature of the quantitative studies made it not appropriate to perform meta-analysis. Eleven included studies, mostly descriptive, formed the basis of this systematic review. The ADRs induced by oral dexamethasone that have a poorer outlook in adolescents with ALL than in children with ALL are: transient hyperglycemia, infectious complications, thrombosis, thromboembolism and avascular necrosis. Adolescents were observed to have higher incidence and risk to these ADRs. In some included studies, adolescence age was found to be a predictor of the ADRs. The results indicated that adolescents experience more severe ADRs induced by oral dexamethasone during ALL treatment than children. This phenomenon may be explained by the age-related variability in pharmacokinetics characteristics of dexamethasone between the adolescents and younger children as well as the impact of pubertal changes that occur in adolescents. The outcome of the ADRs however, may be inevitably affected by the presence of confounders such as co-administered drugs as well. The findings call
Harpaz, Rave; Vilar, Santiago; DuMouchel, William; Salmasian, Hojjat; Haerian, Krystl; Shah, Nigam H; Chase, Herbert S; Friedman, Carol
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
Harpaz, Rave; Vilar, Santiago; Dumouchel, William; Salmasian, Hojjat; Haerian, Krystl; Shah, Nigam H; Chase, Herbert S; Friedman, Carol
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. 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. 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. 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.
Peymani, Payam; Tabrizi, Reza; Afifi, Saba; Namazi, Soha; Heydari, Seyed Taghi; Shirazi, Mohammad Khabaz; Nouraei, Hasti; Sadeghi, Elham; Lankarani, Kamran B; Maharlouei, Najmeh
An adverse drug reaction (ADRs) is linked with the use of medications and unpredictable negative consequences. The Iranian Pharmacovigilance center (IPC) has reported that the rate of ADR is very low. Thus, this study was performed to find the reasons for this under-reporting, and investigate the level of knowledge, attitude and practice (KAP) of General Practitioners (GPs) about spontaneous reporting system in Shiraz. The present cross-sectional study was conducted on 350 general practitioners (GPs) working in Shiraz, Iran from Oct 2014 to March 2015. A semi-structured questionnaire was used which included demographic features, and evaluated KAPs of GPs regarding ADRs, Pharmacovigilance, and yellow card reporting. Statistical analysis was done by descriptive and analytical statistics (frequency, Mean±SD, Student t-test, Chi-square) using SPSS version 16. Of 350 (95.1%) GPs, 333 completed the questionnaire. The respondents aged from 26 to76 years, of whom 176 (52.9%) were males with mean age 39.6±8.8 SD years. In regard to work place, 85 (25.5%) had their own office, and 112 (33.7%), 101 (30.9%), and 35 (10.5%) worked in private hospitals, in governmental hospitals, and in more than one place, respectively. Work experience mean was 13.3±8.2SD years and median was 12 years (range 1-50 years). Although, less than half of the participants (n = 151; 45.3%) described ADR correctly, 215 (64.6%) respondents claimed that they were not familiar with physician's responsibility regarding ADR reporting. Overall, few of the participants were aware of the steps in either ADR reporting or using Yellow Card System. On the whole, 100 (30%) respondents achieved acceptable knowledge score, while the median score was 9 out of 14 and minimum and maximum being 5 and 14, respectively. The physicians in Shiraz have poor knowledge of the pharmacovigilance system; however self-education leads to a better knowledge and positive attitude regarding ADRs reporting system. National
Verma, Rajesh; Vasudevan, Biju; Pragasam, Vijendran
Severe cutaneous drug reactions are one of the commonest medical challenges presenting to an emergency room in any hospital. The manifestations range from maculopapular rash to severe systemic symptoms like renal failure and cardiovascular compromise. Toxic epidermal necrolysis, erythroderma, drug rash with eosinophilia and systemic symptoms, acute generalised exanthematous pustulosis and drug induced vasculitis are the common cutaneous drug reactions which can have severe morbidity and even mortality. Careful history taking of the lag period after drug intake and associated symptoms, along with detailed examination of the skin, mucosa and various systems, help in early diagnosis of these reactions. Early stoppage of the incriminating drug, specific therapy including corticosteroids, cyclosporine and intravenous immunoglobulin depending on the case along with supportive therapy and local measures help in salvaging most patients. An overview of these important cutaneous drug reactions along with their management is being reviewed in this article. PMID:24600147
Meyer, Charles; Behm, Nicole; Brown, Emily; Copeland, Nathanial K; Sklar, Marvin J
Adverse drug reactions (ADRs) to antibiotics complicate the management of any infection, particularly opportunistic infections in advanced HIV as some ADRs are potentiated by HIV. Trimethoprim-sulfamethoxazole (TMP-SMX) causes ADRs in 40-80% of HIV infected individuals, compared to 3-5% in the general population. The incidence and severity of ADRs among HIV infected individuals appear to increase as they progress from latent infection to AIDS. We present a single case report of a 55-year-old African American male found to have an otherwise asymptomatic acute HIV infection who developed an ADR to TMP-SMX, despite having previously tolerating the medication. The proposed mechanisms for the increased incidence of sulfa hypersensitivity reactions among HIV infected individuals focus on either (1) HIV-induced changes in the immune function driven by falling levels of CD4 cells or (2) other HIV-specific factors correlated with rising viral load. To our knowledge this is the first reported case of new sulfa hypersensitivity in primary HIV and may provide clinical evidence to support the correlation between viral load and ADRs to TMP-SMX without a severely diminished CD4 count, though further research is necessary. This case also demonstrates a rare and easily overlooked presentation of HIV that may aid in early diagnosis.
Angamo, Mulugeta Tarekegn; Chalmers, Leanne; Curtain, Colin M; Bereznicki, Luke R E
Adverse drug reactions (ADRs) are one of the leading causes of hospital admissions and morbidity in developed countries and represent a substantial burden on healthcare delivery systems. However, there is little data available from low- and middle-income countries. This review compares the prevalence and characteristics of ADR-related hospitalisations in adults in developed and developing countries, including the mortality, severity and preventability associated with these events, commonly implicated drugs and contributing factors. A literature search was conducted via PubMed, Scopus, Web of Science, Embase, ProQuest and Google Scholar to find articles published in English from 2000 to 2015. Relevant observational studies were included. The median (with interquartile range [IQR]) prevalence of ADR-related hospitalisation in developed and developing countries was 6.3 % (3.3-11.0) and 5.5 % (1.1-16.9), respectively. The median proportions of preventable ADRs in developed and developing countries were 71.7 % (62.3-80.0) and 59.6 % (51.5-79.6), respectively. Similarly, the median proportions of ADRs resulting in mortality in developed and developing countries were 1.7 % (0.7-4.8) and 1.8 % (0.8-8.0), respectively. Commonly implicated drugs in both settings were antithrombotic, non-steroidal anti-inflammatory and cardiovascular drugs. Older age, female gender, number of medications, renal impairment and heart failure were reported to be associated with an increased risk for ADR-related hospitalisation in both settings while HIV/AIDS was implicated in developing countries only. The majority of ADRs were preventable in both settings, highlighting the importance of improving medication use, particularly in vulnerable patient groups such as the elderly, patients with multiple comorbidities and, in developing countries, patients with HIV/AIDS.
Galli, Thamires B.; Reis, Wálleri C.; Andrzejevski, Vânia M.
Background: Potentially inappropriate medication (PIM) use in the elderly is associated with increased risk of adverse drug reactions (ADRs), but there is limited information regarding PIM use in the intensive care unit (ICU) setting. Objective: The aim of the study is to describe the prevalence and factors associated with the use of PIM and the occurrence of PIM-related adverse reactions in the critically ill elderly. Methods: This study enrolled all critically ill older adults (60 years or more) admitted to medical or cardiovascular ICUs between January and December 2013, in a large tertiary teaching hospital. For all patients, clinical pharmacists listed the medications given during the ICU stay and data on drugs were analyzed using 2012 Beers Criteria, to identify the prevalence of PIM. For each identified PIM the medical records were analyzed to evaluate factors associated with its use. The frequency of ADRs and, the causal relationship between PIM and the ADRs identified were also evaluated through review of medical records. Results: According to 2012 Beers Criteria, 98.2% of elderly patients used at least one PIM (n=599), of which 24.8% were newly started in the ICUs. In 29.6% of PIMs, there was a clinical circumstance that justified their prescription. The number of PIMs was associated with ICU length of stay and total number of medications. There was at least one ADR identified in 17.8% of patients; more than 40% were attributed to PIM, but there was no statistical association. Conclusions: There is a high prevalence of PIM used in acutely ill older people, but they do not seem to be the major cause of adverse drug reactions in this population. Although many PIMs had a clinical circumstance that led to their prescription during the course of ICU hospitalization, many were still present upon hospital discharge. Therefore, prescription of PIMs should be minimized to improve the safety of elderly patients. PMID:28042352
Lee, Heeyoung; Song, Seungyeon; Oh, Yun-Kyoung; Kang, WonKu; Kim, Eunyoung
To evaluate the role of gender as a risk factor for developing contrast media-associated adverse drug reactions (CM-ADRs) by comparing the incidence of CM-ADR between male and female patients according to study design, ADR type, and computed tomography (CT) examination. We systematically searched three electronic databases for eligible studies. In the studies included (n=18), we assessed effect estimates of the relative incidence of CM-ADR, analysed by experimental design, ADR type and CT examination. This was calculated by using a random effects model if clinical conditions showed heterogeneity; otherwise, a fixed effects model was used. We identified 10,776 patients administered CM. According to the designs, studies were classified into randomised controlled trials (RCTs) and observational studies. Results were as follows: risk ratio (RR)=1.07 (95% confidence interval (CI): 0.79-1.46, P=0.66) for RCTs, and RR=0.77 (95% CI: 0.58-1.04, P=0.09) for observational studies. The results of analysis according to ADR type and for undergoing CT demonstrated that the incidence of CM-ADR did not differ between males and females. We found no significant difference in the incidence of CM-ADRs between male and female patients according to study design, ADR type, or CT examination. Future studies to determine why gender has shown different roles as a risk factor between CM-ADRs and non-CM ADRs are needed. Copyright © 2017 Elsevier B.V. All rights reserved.
Shang, Ning; Xu, Hua; Rindflesch, Thomas C.; Cohen, Trevor
Pharmacovigilance involves continually monitoring drug safety after drugs are put to market. To aid this process; algorithms for the identification of strongly correlated drug/adverse drug reaction (ADR) pairs from data sources such as adverse event reporting systems or Electronic Health Records have been developed. These methods are generally statistical in nature, and do not draw upon the large volumes of knowledge embedded in the biomedical literature. In this paper, we investigate the ability of scalable Literature Based Discovery (LBD) methods to identify side effects of pharmaceutical agents. The advantage of LBD methods is that they can provide evidence from the literature to support the plausibility of a drug/ ADR association, thereby assisting human review to validate the signal, which is an essential component of pharmacovigilance. To do so, we draw upon vast repositories of knowledge that has been extracted from the biomedical literature by two Natural Language Processing tools, MetaMap and SemRep. We evaluate two LBD methods that scale comfortably to the volume of knowledge available in these repositories. Specifically, we evaluate Reflective Random Indexing (RRI), a model based on concept-level co-occurrence, and Predication-based Semantic Indexing (PSI), a model that encodes the nature of the relationship between concepts to support reasoning analogically about drug-effect relationships. An evaluation set was constructed from the Side Effect Resource 2 (SIDER2), which contains known drug/ADR relations, and models were evaluated for their ability to “rediscover” these relations. In this paper, we demonstrate that both RRI and PSI can recover known drug-adverse event associations. However, PSI performed better overall, and has the additional advantage of being able to recover the literature underlying the reasoning pathways it used to make its predictions. PMID:25046831
Lucas, L. M.; Colley, C. A.
Although physicians in practice are most likely to see patients with adverse drug reactions, they may fail to recognize an adverse effect or to attribute it to a drug effect and, when recognized, they may fail to report serious reactions to the US Food and Drug Administration (FDA). To recognize and attribute an adverse event to a drug effect, physicians should review the patient's clinical course, looking at patient risk factors, the known adverse reactions to the suspected drug, and the likelihood of a causal relationship between the drug and the adverse event-based on the temporal relationship, response to stopping or restarting the drug, and whether other factors could explain the reaction. Once an adverse drug reaction has been identified, the patient should be informed and appropriate documentation made in the patient's medical record. Serious known reactions and all reactions to newly released drugs or those not previously known to occur (even if the certainty is low) should be reported to the FDA. PMID:1536067
Bhattarai, Prashant; Vance, Dylan; Hatefi, Arash; Khaw, Ban An
Drug resistance is a common phenomenon that occurs in cancer chemotherapy. Delivery of chemotherapeutic agents as polymer pro-drug conjugates (PPDCs) pretargeted with bispecific antibodies could circumvent drug resistance in cancer cells. To demonstrate this approach to overcome drug resistance, Paclitaxel (Ptxl)-resistant SKOV3 TR human ovarian- and doxorubicin (Dox)-resistant MCF7 ADR human mammary-carcinoma cell lines were used. Pre-targeting over-expressed biotin or HER2/neu receptors on cancer cells was conducted by biotinylated anti-DTPA or anti-HER2/neu affibody - anti-DTPA Fab bispecific antibody complexes. The targeting PPDCs are either D-Dox-PGA or D-Ptxl-PGA. Cytotoxicity studies demonstrate that the pretargeted approach increases cytotoxicity of Ptxl or Dox in SKOV3 TR or MCF7 ADR resistant cell lines by 5.4 and 27 times, respectively. Epifluorescent microscopy - used to track internalization of D-Dox-PGA and Dox in MCF7 ADR cells - shows that the pretargeted delivery of D-Dox-PGA resulted in a 2- to 4-fold increase in intracellular Dox concentration relative to treatment with free Dox. The mechanism of internalization of PPDCs is consistent with endocytosis. Enhanced drug delivery and intracellular retention following pretargeted delivery of PPDCs resulted in greater tumor cell toxicity in the current in vitro studies.
Wang, Liwei; Jiang, Guoqian; Li, Dingcheng; Liu, Hongfang
Normalizing data in the Adverse Event Reporting System (AERS), an FDA database, would improve the mining capacity of AERS for drug safety signal detection. In this study, we aim to normalize AERS and build a publicly available normalized Adverse drug events (ADE) data source.he drug information in AERS is normalized to RxNorm, a standard terminology source for medication. Drug class information is then obtained from the National Drug File - Reference Terminology (NDF-RT). Adverse drug events (ADE) are aggregated through mapping with the PT (Preferred Term) and SOC (System Organ Class) codes of MedDRA. Our study yields an aggregated knowledge-enhanced AERS data mining set (AERS-DM). The AERS-DM could provide more perspectives to mine AERS database for drug safety signal detection and could be used by research community in the data mining field.
Stevenson, Jennifer M; Williams, Josceline L; Burnham, Thomas G; Prevost, A Toby; Schiff, Rebekah; Erskine, S David; Davies, J Graham
Adverse drug reaction (ADR) risk-prediction models for use in older adults have been developed, but it is not clear if they are suitable for use in clinical practice. This systematic review aimed to identify and investigate the quality of validated ADR risk-prediction models for use in older adults. Standard computerized databases, the gray literature, bibliographies, and citations were searched (2012) to identify relevant peer-reviewed studies. Studies that developed and validated an ADR prediction model for use in patients over 65 years old, using a multivariable approach in the design and analysis, were included. Data were extracted and their quality assessed by independent reviewers using a standard approach. Of the 13,423 titles identified, only 549 were associated with adverse outcomes of medicines use. Four met the inclusion criteria. All were conducted in inpatient cohorts in Western Europe. None of the models satisfied the four key stages in the creation of a quality risk prediction model; development and validation were completed, but impact and implementation were not assessed. Model performance was modest; area under the receiver operator curve ranged from 0.623 to 0.73. Study quality was difficult to assess due to poor reporting, but inappropriate methods were apparent. Further work needs to be conducted concerning the existing models to enable the development of a robust ADR risk-prediction model that is externally validated, with practical design and good performance. Only then can implementation and impact be assessed with the aim of generating a model of high enough quality to be considered for use in clinical care to prioritize older people at high risk of suffering an ADR. PMID:25278750
Al-Worafi, Yaser Mohammed; Kassab, Yaman Walid; Alseragi, Wafa Mohammed; Almutairi, Masaad Saeed; Ahmed, Ali; Ming, Long Chiau; Alkhoshaiban, Ali Saleh; Hadi, Muhammad Abdul
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
Black, Corri; Tagiyeva-Milne, Nara; Helms, Peter; Moir, Dorothy
Aims 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. Methods 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. Results 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. Conclusions 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. PMID:25819310
Zhou, W. P.; Hua, H. Y.; Sun, P. C.; Zhao, Y. X.
The purpose of the present study was to develop the Solutol HS15-based doxorubicin submicron emulsion with good stability and overcoming multi-drug resistance. In this study, we prepared doxorubicin submicron emulsion, and examined the stability after autoclaving, the in vitro cytotoxic activity, the intracellular accumulation and apoptpsis of doxorubicin submicron emulsion in MCF-7/ADR cells. The physicochemical properties of doxorubicin submicron emulsion were not significantly affected after autoclaving. The doxorubicin submicron emulsion significantly increased the intracellular accumulation of doxorubicin submicron emulsion and enhanced cytotoxic activity and apoptotic effects of doxorubicin. These results may be correlated to doxorubicin submicron emulsion inhibitory effects on efflux pumps through the progressive release of intracellular free Solutol HS15 from doxorubicin submicron emulsion. Furthermore, these in vitro results suggest that the Solutol HS15-based submicron emulsion may be a potentially useful drug delivery system to circumvent multi-drug resistance of tumor cells. PMID:26664069
Banda, Juan M.; Evans, Lee; Vanguri, Rami S.; Tatonetti, Nicholas P.; Ryan, Patrick B.; Shah, Nigam H.
Identification of adverse drug reactions (ADRs) during the post-marketing phase is one of the most important goals of drug safety surveillance. Spontaneous reporting systems (SRS) data, which are the mainstay of traditional drug safety surveillance, are used for hypothesis generation and to validate the newer approaches. The publicly available US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) data requires substantial curation before they can be used appropriately, and applying different strategies for data cleaning and normalization can have material impact on analysis results. We provide a curated and standardized version of FAERS removing duplicate case records, applying standardized vocabularies with drug names mapped to RxNorm concepts and outcomes mapped to SNOMED-CT concepts, and pre-computed summary statistics about drug-outcome relationships for general consumption. This publicly available resource, along with the source code, will accelerate drug safety research by reducing the amount of time spent performing data management on the source FAERS reports, improving the quality of the underlying data, and enabling standardized analyses using common vocabularies. PMID:27193236
Banda, Juan M; Evans, Lee; Vanguri, Rami S; Tatonetti, Nicholas P; Ryan, Patrick B; Shah, Nigam H
Identification of adverse drug reactions (ADRs) during the post-marketing phase is one of the most important goals of drug safety surveillance. Spontaneous reporting systems (SRS) data, which are the mainstay of traditional drug safety surveillance, are used for hypothesis generation and to validate the newer approaches. The publicly available US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) data requires substantial curation before they can be used appropriately, and applying different strategies for data cleaning and normalization can have material impact on analysis results. We provide a curated and standardized version of FAERS removing duplicate case records, applying standardized vocabularies with drug names mapped to RxNorm concepts and outcomes mapped to SNOMED-CT concepts, and pre-computed summary statistics about drug-outcome relationships for general consumption. This publicly available resource, along with the source code, will accelerate drug safety research by reducing the amount of time spent performing data management on the source FAERS reports, improving the quality of the underlying data, and enabling standardized analyses using common vocabularies.
LaBute, Montiago X; Zhang, Xiaohua; Lenderman, Jason; Bennion, Brian J; Wong, Sergio E; Lightstone, Felice C
Late-stage or post-market identification of adverse drug reactions (ADRs) is a significant public health issue and a source of major economic liability for drug development. Thus, reliable in silico screening of drug candidates for possible ADRs would be advantageous. In this work, we introduce a computational approach that predicts ADRs by combining the results of molecular docking and leverages known ADR information from DrugBank and SIDER. We employed a recently parallelized version of AutoDock Vina (VinaLC) to dock 906 small molecule drugs to a virtual panel of 409 DrugBank protein targets. L1-regularized logistic regression models were trained on the resulting docking scores of a 560 compound subset from the initial 906 compounds to predict 85 side effects, grouped into 10 ADR phenotype groups. Only 21% (87 out of 409) of the drug-protein binding features involve known targets of the drug subset, providing a significant probe of off-target effects. As a control, associations of this drug subset with the 555 annotated targets of these compounds, as reported in DrugBank, were used as features to train a separate group of models. The Vina off-target models and the DrugBank on-target models yielded comparable median area-under-the-receiver-operating-characteristic-curves (AUCs) during 10-fold cross-validation (0.60-0.69 and 0.61-0.74, respectively). Evidence was found in the PubMed literature to support several putative ADR-protein associations identified by our analysis. Among them, several associations between neoplasm-related ADRs and known tumor suppressor and tumor invasiveness marker proteins were found. A dual role for interstitial collagenase in both neoplasms and aneurysm formation was also identified. These associations all involve off-target proteins and could not have been found using available drug/on-target interaction data. This study illustrates a path forward to comprehensive ADR virtual screening that can potentially scale with increasing number
LaBute, Montiago X.; Zhang, Xiaohua; Lenderman, Jason; Bennion, Brian J.; Wong, Sergio E.; Lightstone, Felice C.
Late-stage or post-market identification of adverse drug reactions (ADRs) is a significant public health issue and a source of major economic liability for drug development. Thus, reliable in silico screening of drug candidates for possible ADRs would be advantageous. In this work, we introduce a computational approach that predicts ADRs by combining the results of molecular docking and leverages known ADR information from DrugBank and SIDER. We employed a recently parallelized version of AutoDock Vina (VinaLC) to dock 906 small molecule drugs to a virtual panel of 409 DrugBank protein targets. L1-regularized logistic regression models were trained on the resulting docking scores of a 560 compound subset from the initial 906 compounds to predict 85 side effects, grouped into 10 ADR phenotype groups. Only 21% (87 out of 409) of the drug-protein binding features involve known targets of the drug subset, providing a significant probe of off-target effects. As a control, associations of this drug subset with the 555 annotated targets of these compounds, as reported in DrugBank, were used as features to train a separate group of models. The Vina off-target models and the DrugBank on-target models yielded comparable median area-under-the-receiver-operating-characteristic-curves (AUCs) during 10-fold cross-validation (0.60–0.69 and 0.61–0.74, respectively). Evidence was found in the PubMed literature to support several putative ADR-protein associations identified by our analysis. Among them, several associations between neoplasm-related ADRs and known tumor suppressor and tumor invasiveness marker proteins were found. A dual role for interstitial collagenase in both neoplasms and aneurysm formation was also identified. These associations all involve off-target proteins and could not have been found using available drug/on-target interaction data. This study illustrates a path forward to comprehensive ADR virtual screening that can potentially scale with increasing
Vilhelmsson, Andreas; Svensson, Tommy; Meeuwisse, Anna; Carlsten, Anders
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.
Díaz-Agudelo, Daniela; Burgos-Flórez, Francisco Javier; Vaca, Claudia; Serrano-Meriño, Dolores Vanessa
Introduction: The occurrence of adverse drug reactions is an important issue due to the lack of drug safety data in children. Objective: To describe the Adverse Drug Reactions in inpatient children under 6 years of age in two general pediatrics wards located in Barranquilla, Colombia. Methods: 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. Results: 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). Conclusions: 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. PMID:27821893
de Las Salas, Roxana; Díaz-Agudelo, Daniela; Burgos-Flórez, Francisco Javier; Vaca, Claudia; Serrano-Meriño, Dolores Vanessa
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.
Hedna, Khedidja; Hägg, Staffan; Andersson Sundell, Karolina; Petzold, Max; Hakkarainen, Katja M
To assess refill adherence to dispensed oral long-term medications among the adult population and to investigate whether the percentages of self-reported adverse drug reactions (ADRs) and sub-therapeutic effects (STEs) differed for medications with adequate refill adherence, oversupply, and undersupply. Survey responses on self-reported ADRs and STEs were linked to the Swedish Prescribed Drug Register in a cross-sectional population-based study. Refill adherence to antihypertensive, lipid-lowering, and oral anti-diabetic medications was measured using the continuous measure of medication acquisition (CMA). The percentages of self-reported ADRs and STEs were compared between medications with adequate refill adherence (CMA 0.8-1.2), oversupply (CMA > 1.2), and undersupply (CMA < 0.8). The study included 1827 persons, and the refill adherence was measured for 3014 antihypertensive, 839 lipid lowering, and 253 oral anti-diabetic medications. Overall, 65.7% of the medications had adequate refill adherence, 21.9% oversupply, and 12.4% undersupply. The percentages of self-reported ADRs and STEs were respectively 2.6%, 2.7%, and 2.1% (p > 0.5) for ADRs and 1.1%, 1.6%, and 1.5% (p > 0.5) for STEs. Adequate refill adherence was found in two thirds of the medication therapies. ADRs and STEs were unexpectedly equally commonly reported for medications with adequate refill adherence, oversupply, and undersupply. These results suggest that a better understanding of patients' refill behaviors and their perceived medication adverse outcomes is needed and should be considered in improving medication management. The impact of individual and healthcare factors that may influence the association between refill adherence and reported medication adverse outcomes should be investigated in future studies. Copyright © 2013 John Wiley & Sons, Ltd.
Liu, Mei; McPeek Hinz, Eugenia Renne; Matheny, Michael Edwin; Denny, Joshua C; Schildcrout, Jonathan Scott; Miller, Randolph A; Xu, Hua
Objective Medication safety requires that each drug be monitored throughout its market life as early detection of adverse drug reactions (ADRs) can lead to alerts that prevent patient harm. Recently, electronic medical records (EMRs) have emerged as a valuable resource for pharmacovigilance. This study examines the use of retrospective medication orders and inpatient laboratory results documented in the EMR to identify ADRs. Methods Using 12 years of EMR data from Vanderbilt University Medical Center (VUMC), we designed a study to correlate abnormal laboratory results with specific drug administrations by comparing the outcomes of a drug-exposed group and a matched unexposed group. We assessed the relative merits of six pharmacovigilance measures used in spontaneous reporting systems (SRSs): proportional reporting ratio (PRR), reporting OR (ROR), Yule's Q (YULE), the χ2 test (CHI), Bayesian confidence propagation neural networks (BCPNN), and a gamma Poisson shrinker (GPS). Results We systematically evaluated the methods on two independently constructed reference standard datasets of drug–event pairs. The dataset of Yoon et al contained 470 drug–event pairs (10 drugs and 47 laboratory abnormalities). Using VUMC's EMR, we created another dataset of 378 drug–event pairs (nine drugs and 42 laboratory abnormalities). Evaluation on our reference standard showed that CHI, ROR, PRR, and YULE all had the same F score (62%). When the reference standard of Yoon et al was used, ROR had the best F score of 68%, with 77% precision and 61% recall. Conclusions Results suggest that EMR-derived laboratory measurements and medication orders can help to validate previously reported ADRs, and detect new ADRs. PMID:23161894
Tang, Huaxiu; Solti, Imre; Kirkendall, Eric; Zhai, Haijun; Lingren, Todd; Meller, Jaroslaw; Ni, Yizhao
The objective of this study was to determine whether the Food and Drug Administration’s Adverse Event Reporting System (FAERS) data set could serve as the basis of automated electronic health record (EHR) monitoring for the adverse drug reaction (ADR) subset of adverse drug events. We retrospectively collected EHR entries for 71 909 pediatric inpatient visits at Cincinnati Children’s Hospital Medical Center. Natural language processing (NLP) techniques were used to identify positive diseases/disorders and signs/symptoms (DDSSs) from the patients’ clinical narratives. We downloaded all FAERS reports submitted by medical providers and extracted the reported drug-DDSS pairs. For each patient, we aligned the drug-DDSS pairs extracted from their clinical notes with the corresponding drug-DDSS pairs from the FAERS data set to identify Drug-Reaction Pair Sentences (DRPSs). The DRPSs were processed by NLP techniques to identify ADR-related DRPSs. We used clinician annotated, real-world EHR data as reference standard to evaluate the proposed algorithm. During evaluation, the algorithm achieved promising performance and showed great potential in identifying ADRs accurately for pediatric patients. PMID:28634427
Marcilly, Romaric; Chazard, Emmanuel; Beuscart-Zéphir, Marie-Catherine; Hackl, Werner; Băceanu, Adrian; Kushniruk, Andre; Borycki, Elizabeth M
This paper presents the design of Adverse Drug Event-Scorecards. The scorecards described are innovative and novel, not having previously been reported in the literature. The Scorecards provide organizations (e.g. hospitals) with summary information about Adverse Drug Events (ADEs) using a Web-based platform. The data used in the Scorecards are routinely updated and report on ADEs detected through data mining processes. The development of the ADE Scorecards is ongoing and they are currently undergoing clinical testing.
The classical definition of clinical pharmacology is the study or the knowledge of the effects of drugs in humans. The activities of a clinical pharmacologist can vary from country to country, usually ranging from involvement in clinical trials, especially fundamental pharmacodynamic studies, to studies of pharmacokinetics and drug metabolism, to pharmacogenetics. Most clinical pharmacologists outside industry are in hospitals or university hospitals and research centres. In addition to research, this implies teaching of clinical pharmacology, and interacting with other medical staff: in the field of research, giving advice on clinical trials methodology and often managing a therapeutic drug monitoring centre. Some clinical pharmacologists have clinical departments with beds or consulting offices. Can there be another role for the clinical pharmacologist that would increase his or her usefulness for the medical community? Adverse drug reactions (ADRs) are remarkably complex events, related to drug effects, patient characteristics (background diseases, genetics), and drug/disease interactions. Evaluation of ADRs requires understanding of drug mechanisms and interactions, and of disease diagnostics, especially in the discussion of alternative diagnoses. This implies expertise as a pharmacologist and a clinician. In addition, because not all adverse reactions or interactions are in the Summary of Product Characteristics, and because problems arise long before they report in the literature, it is necessary for the clinical pharmacologist to have knowledge of ongoing regulatory processes, in addition to having access to the published literature. Helping clinicians cope with individual patient problems will also improve the clinical pharmacologist's integration into the healthcare process.
Adverse drug events resulting from use of drugs with sulphonamide-containing anti-malarials and artemisinin-based ingredients: findings on incidence and household costs from three districts with routine demographic surveillance systems in rural Tanzania
Background Anti-malarial regimens containing sulphonamide or artemisinin ingredients are widely used in malaria-endemic countries. However, evidence of the incidence of adverse drug reactions (ADR) to these drugs is limited, especially in Africa, and there is a complete absence of information on the economic burden such ADR place on patients. This study aimed to document ADR incidence and associated household costs in three high malaria transmission districts in rural Tanzania covered by demographic surveillance systems. Methods Active and passive surveillance methods were used to identify ADR from sulphadoxine-pyrimethamine (SP) and artemisinin (AS) use. ADR were identified by trained clinicians at health facilities (passive surveillance) and through cross-sectional household surveys (active surveillance). Potential cases were followed up at home, where a complete history and physical examination was undertaken, and household cost data collected. Patients were classified as having ‘possible’ or ‘probable’ ADR by a physician. Results A total of 95 suspected ADR were identified during a two-year period, of which 79 were traced, and 67 reported use of SP and/or AS prior to ADR onset. Thirty-four cases were classified as ‘probable’ and 33 as ‘possible’ ADRs. Most (53) cases were associated with SP monotherapy, 13 with the AS/SP combination (available in one of the two areas only), and one with AS monotherapy. Annual ADR incidence per 100,000 exposures was estimated based on ‘probable’ ADR only at 5.6 for AS/SP in combination, and 25.0 and 11.6 for SP monotherapy. Median ADR treatment costs per episode ranged from US$2.23 for those making a single provider visit to US$146.93 for patients with four visits. Seventy-three per cent of patients used out-of-pocket funds or sold part of their farm harvests to pay for treatment, and 19% borrowed money. Conclusion Both passive and active surveillance methods proved feasible methods for anti-malarial ADR
Herdeiro, Maria Teresa; Ribeiro-Vaz, Inês; Ferreira, Mónica; Polónia, Jorge; Falcão, Amílcar; Figueiras, Adolfo
Spontaneous reporting of adverse drug reactions (ADRs) is the method most widely used by pharmacovigilance systems, with the principal limitation being the physician's underreporting. This study sought to evaluate the results of workshop and telephone-interview interventions designed to improve the quantity and relevance of ADR reporting by physicians. A cluster-randomized controlled trial was conducted on 6579 physicians in northern Portugal in 2008. Following randomization, we allocated 1034 physicians to a telephone-interview intervention, 438 to a workshop intervention and the remaining 5107 to the control group. At the workshop, a real clinical case was presented and participants were then asked to report on it by completing the relevant form. In the telephone intervention, participants were asked (i) whether they had ever had any suspicion of ADRs; (ii) whether they had experienced any difficulties in reporting; (iii) whether they remembered the different methods that could be used for reporting purposes; and (iv) whether they attached importance to the individual physician's role in reporting. We followed up physicians to assess ADR reporting rates to the Northern Pharmacovigilance Centre. In terms of relevance, adverse reactions were classified as serious or unexpected. Statistical analysis was performed on an intention-to-treat basis, and generalized linear mixed models were applied using the penalized quasi-likelihood method. The physicians studied were followed up over a period of 20 months. Two hundred physicians underwent the educational intervention. Comparison with the control group showed that the workshop intervention increased the spontaneous ADR reporting rate by an average of 4-fold (relative risk [RR] 3.97; 95% CI 3.86, 4.08; p < 0.001) across the 20 months post-intervention. Telephone interviews, in contrast, proved less efficient since they led to no significant difference (p = 0.052) vis-à-vis the control group in ADR reporting (RR 1.02; 95
Agarwal, Renu; Daher, Aqil Mohammad; Mohd Ismail, Nafeeza
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
Nikfarjam, Azadeh; Gonzalez, Graciela H
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%.
Nikfarjam, Azadeh; Gonzalez, Graciela H.
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
Alecu, Iulian; Bousquet, Cedric; Mougin, Fleur; Jaulent, Marie-Christine
The WHO-ART and MedDRA terminologies used for coding adverse drug reactions (ADR) do not provide formal definitions of terms. In order to improve groupings, we propose to map ADR terms to equivalent Snomed CT concepts through UMLS Metathesaurus. We performed such mappings on WHO-ART terms and can automatically classify them using a description logic definition expressing their synonymies. Our gold standard was a set of 13 MedDRA special search categories restricted to ADR terms available in WHO-ART. The overlapping of the groupings within the new structure of WHO-ART on the manually built MedDRA search categories showed a 71% success rate. We plan to improve our method in order to retrieve associative relations between WHO-ART terms.
Ji, Yanqing; Ying, Hao; Dews, Peter; Mansour, Ayman; Tran, John; Miller, Richard E; Massanari, R Michael
Early detection of unknown adverse drug reactions (ADRs) in postmarketing surveillance saves lives and prevents harmful consequences. We propose a novel data mining approach to signaling potential ADRs from electronic health databases. More specifically, we introduce potential causal association rules (PCARs) to represent the potential causal relationship between a drug and ICD-9 (CDC. (2010). International Classification of Diseases, Ninth Revision (ICD-9). [Online]. Available: http://www.cdc.gov/nchs/icd/icd9.html) coded signs or symptoms representing potential ADRs. Due to the infrequent nature of ADRs, the existing frequency-based data mining methods cannot effectively discover PCARs. We introduce a new interestingness measure, potential causal leverage, to quantify the degree of association of a PCAR. This measure is based on the computational, experience-based fuzzy recognition-primed decision (RPD) model that we developed previously (Y. Ji, R. M. Massanari, J. Ager, J. Yen, R. E. Miller, and H. Ying, "A fuzzy logic-based computational recognition-primed decision model," Inf. Sci., vol. 177, pp. 4338-4353, 2007) on the basis of the well-known, psychology-originated qualitative RPD model (G. A. Klein, "A recognition-primed decision making model of rapid decision making," in Decision Making in Action: Models and Methods, 1993, pp. 138-147). The potential causal leverage assesses the strength of the association of a drug-symptom pair given a collection of patient cases. To test our data mining approach, we retrieved electronic medical data for 16,206 patients treated by one or more than eight drugs of our interest at the Veterans Affairs Medical Center in Detroit between 2007 and 2009. We selected enalapril as the target drug for this ADR signal generation study. We used our algorithm to preliminarily evaluate the associations between enalapril and all the ICD-9 codes associated with it. The experimental results indicate that our approach has a potential to
Parameswaran Nair, Nibu; Chalmers, Leanne; Connolly, Michael; Bereznicki, Bonnie J.; Peterson, Gregory M.; Curtain, Colin; Castelino, Ronald L.; Bereznicki, Luke R.
Background Adverse drug reactions (ADRs) are the major cause of medication-related hospital admissions in older patients living in the community. This study aimed to develop and validate a score to predict ADR-related hospitalization in people aged ≥65 years. Methods ADR-related hospitalization and its risk factors were determined using a prospective, cross-sectional study in patients aged ≥65 years admitted to two hospitals. A predictive model was developed in the derivation cohort (n = 768) and the model was applied in the validation cohort (n = 240). ADR-related hospital admission was determined through expert consensus from comprehensive reviews of medical records and patient interviews. The causality and preventability of the ADR were assessed based on the Naranjo algorithm and modified Schumock and Thornton criteria, respectively. Results In the derivation sample (mean [±SD] age, 80.1±7.7 years), 115 (15%) patients were admitted due to a definite or probable ADR; 92.2% of these admissions were deemed preventable. The number of antihypertensives was the strongest predictor of an ADR followed by presence of dementia, renal failure, drug changes in the preceding 3 months and use of anticholinergic medications; these variables were used to derive the ADR prediction score. The predictive ability of the score, assessed from calculation of the area under the receiver operator characteristic (ROC) curve, was 0.70 (95% confidence interval (CI) 0.65–0.75). In the validation sample (mean [±SD] age, 79.6±7.6 years), 30 (12.5%) patients’ admissions were related to definite or probable ADRs; 80% of these admissions were deemed preventable. The area under the ROC curve in this sample was 0.67 (95% CI 0.56–0.78). Conclusions This study proposes a practical and simple tool to identify elderly patients who are at an increased risk of preventable ADR-related hospital admission. Further refinement and testing of this tool is necessary to implement the score in
Dobashi, Akira; Kurata, Kaori; Okazaki, Mitsuhiro; Nishizawa, Mari
Purpose Spontaneous inquiries about the development of adverse drug reactions (ADRs) to medicines can be extracted based on the questions posted by the general public on the electronic Japanese bulletin board “Yahoo! Japan Chiebukuro”. Our aim was to clarify the characteristics related to people’s descriptions of suspected ADRs and determine the reasons for submitting a spontaneous inquiry. Methods Fifty brand names of medicines used for inquiry extraction were chosen by selecting 35 pharmaceutical products, based on the generic names that had the highest sales in Japan. Questions containing both the brand name of one of these medicines and the term “Fukusayō” (ADR in Japanese) that were posted from July 2004 to June 2009 were extracted from the site. Results Among 1,419 questions extracted, 614 questions had at least one identifiable brand name of a suspected medicine, an ADR description, and the extent to which the ADR appeared to be caused by the suspected medicine(s). Among these 614 questions, 589 described in detail the symptoms/signs that the inquirers themselves or their families had experienced as ADRs. The highest number of questions was found for Paxil (525). Posts asking whether the symptoms being experienced were due to an ADR accounted for the highest number of questions. In most cases, the inquirer suspected that a single medicine led to an ADR and was seeking advice from others taking the same medicine. Conclusion Our examination of spontaneous inquiries showed that people have sufficient knowledge to adequately report potential ADRs in terms of their symptoms, suspected medicines, and the disease for which the medicine was used. However, they often did not describe the start time when the ADR appeared or when the suspected medicine was started. PMID:27114703
Dobashi, Akira; Kurata, Kaori; Okazaki, Mitsuhiro; Nishizawa, Mari
Spontaneous inquiries about the development of adverse drug reactions (ADRs) to medicines can be extracted based on the questions posted by the general public on the electronic Japanese bulletin board "Yahoo! Japan Chiebukuro". Our aim was to clarify the characteristics related to people's descriptions of suspected ADRs and determine the reasons for submitting a spontaneous inquiry. Fifty brand names of medicines used for inquiry extraction were chosen by selecting 35 pharmaceutical products, based on the generic names that had the highest sales in Japan. Questions containing both the brand name of one of these medicines and the term "Fukusayō" (ADR in Japanese) that were posted from July 2004 to June 2009 were extracted from the site. Among 1,419 questions extracted, 614 questions had at least one identifiable brand name of a suspected medicine, an ADR description, and the extent to which the ADR appeared to be caused by the suspected medicine(s). Among these 614 questions, 589 described in detail the symptoms/signs that the inquirers themselves or their families had experienced as ADRs. The highest number of questions was found for Paxil (525). Posts asking whether the symptoms being experienced were due to an ADR accounted for the highest number of questions. In most cases, the inquirer suspected that a single medicine led to an ADR and was seeking advice from others taking the same medicine. Our examination of spontaneous inquiries showed that people have sufficient knowledge to adequately report potential ADRs in terms of their symptoms, suspected medicines, and the disease for which the medicine was used. However, they often did not describe the start time when the ADR appeared or when the suspected medicine was started.
Li, X; Chen, J; Zhang, L; Liu, H; Wang, S; Chen, X; Fang, J; Wang, S; Zhang, W
To analyse the pattern and factors that influence the incidence of adverse drug reactions (ADRs) induced by non-ionic iodinated contrast media and to evaluate their safety profiles. Data from 109,255 cases who underwent enhanced CT examination from 1 January 2008 to 31 August 2013 were analysed. ADRs were classified according to the criteria issued by the American College of Radiology and the Chinese Society of Radiology. A total of 375 (0.34%) patients had ADRs, including 281 mild (0.26%); 80 moderate (0.07%); and 14 severe (0.01%) ADRs; no death was found. 302 (80.53%) of the ADRs occurred within 15 min after examination. Patients aged 40-49 years (204 cases, 0.43%; p < 0.01) or who underwent coronary CT angiography (93 cases, 0.61%; p < 0.01) were at a higher risk of ADRs. Female patients (180 cases, 0.40%; p < 0.01) or outpatients had significantly higher incidence rates of ADRs. The symptoms and signs of most of the ADRs were resolved spontaneously within 24 h after appropriate treatment without sequelae. The occurrence of ADRs is caused by the combined effects of multiple factors. The ADRs induced by non-ionic iodinated contrast media are mainly mild ones, while moderate or severe ADRs are relatively rare, suggesting that enhanced CT examination with non-ionic iodinated contrast media is highly safe, and severe adverse events will seldom occur under appropriate care. The study included 109,255 patients enrolled in various types of enhanced CT examinations, which could reflect ADR conditions and regulations in Chinese population accurately and reliably.
Li, X; Chen, J; Zhang, L; Liu, H; Wang, S; Chen, X; Fang, J; Wang, S
Objective: To analyse the pattern and factors that influence the incidence of adverse drug reactions (ADRs) induced by non-ionic iodinated contrast media and to evaluate their safety profiles. Methods: Data from 109,255 cases who underwent enhanced CT examination from 1 January 2008 to 31 August 2013 were analysed. ADRs were classified according to the criteria issued by the American College of Radiology and the Chinese Society of Radiology. Results: A total of 375 (0.34%) patients had ADRs, including 281 mild (0.26%); 80 moderate (0.07%); and 14 severe (0.01%) ADRs; no death was found. 302 (80.53%) of the ADRs occurred within 15 min after examination. Patients aged 40–49 years (204 cases, 0.43%; p < 0.01) or who underwent coronary CT angiography (93 cases, 0.61%; p < 0.01) were at a higher risk of ADRs. Female patients (180 cases, 0.40%; p < 0.01) or outpatients had significantly higher incidence rates of ADRs. The symptoms and signs of most of the ADRs were resolved spontaneously within 24 h after appropriate treatment without sequelae. Conclusion: The occurrence of ADRs is caused by the combined effects of multiple factors. The ADRs induced by non-ionic iodinated contrast media are mainly mild ones, while moderate or severe ADRs are relatively rare, suggesting that enhanced CT examination with non-ionic iodinated contrast media is highly safe, and severe adverse events will seldom occur under appropriate care. Advances in knowledge: The study included 109,255 patients enrolled in various types of enhanced CT examinations, which could reflect ADR conditions and regulations in Chinese population accurately and reliably. PMID:25582519
Sánchez-Sánchez, Betsabé; Altagracia-Martínez, Marina; Kravzov-Jinich, Jaime; Moreno-Bonett, Consuelo; Vázquez-Moreno, Everardo; Martínez-Núñez, Juan Manuel
The Mexican National Centre of Pharmacovigilance (CNFV) receives suspected adverse drug reaction (ADR) reports from the pharmaceutical industry, Federal States Centre of Pharmacovigilance (CEFV) and Healthcare Institution Centres of Pharmacovigilance (CIFV). The completeness of these suspected ADR reports is particularly important for the proper evaluation of drug safety. The aim of the study was to evaluate the completeness of the information reported in a representative sample of suspected ADR reports submitted to the CNFV during 2007 and 2008, to evaluate the completeness of the suspected ADR reports submitted to the CNFV from different sources during these 2 years and to identify the therapeutic subgroups with the highest number of suspected ADR reports during the study years. A cross-sectional period-prevalence study was conducted at the CNFV. Only reports of suspected ADRs submitted by the CEFV, pharmaceutical industry and CIFV during 2007 and 2008 were included in the present study (reports related to vaccines were excluded). The sample sizes to be used for each year were determined using the formula for population rate at 95% significance level. The samples for each year were randomly selected from the reports related to synthetic drugs submitted that year. The suspected ADR reports were classified according to the standing Mexican Official Norm (Norma Oficial Mexicana [NOM]) guidelines, which were used to divide the reports into four categories (0, 1, 2 and 3) based on their completeness. The seriousness of the suspected ADRs reported was also evaluated; a suspected ADR was classified as 'non-serious' when signs and symptoms are likely to be tolerated, 'moderate' when ADR is not life threatening and needs pharmacological treatment, 'serious' when ADR is life threatening and leads to hospitalization and 'fatal' when ADR contributes directly or indirectly to the patient's death. A total sample size of 370 and 371 suspected ADR reports from 2007 and 2008
Hannaford, P C
Five hundred patients were asked whether they were allergic to any medicines. The description given of any stated reaction was assessed to see whether an important adverse drug reaction was likely to have occurred. The patients' records were also examined for collaborative evidence. Poor documentation often made it difficult to confirm the patient's claim of drug sensitivity. A total of 89 patients may have suffered from important adverse reactions to 113 drugs. Full documentation of adverse reactions is important, but only eight patients carried any information to warn others of their sensitivities. Patients should be asked about any drug sensitivities and, if appropriate, given written confirmation of them. A quick, simple method of doing this would be to provide patients' with a plastic card, similar to a credit card, with instructions and details of the reaction written on it with an indelible pen.
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
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
Tavassoli, Neda; Lapeyre-Mestre, Maryse; Sommet, Agnès; Montastruc, Jean-Louis
AIMS Three ‘weak’ opioid analgesics in association with paracetamol are marketed in France as step 2 analgesics: dextropropoxyphene, tramadol and codeine. These combinations are involved in several adverse drug reactions (ADRs), but no data are available about their comparative reporting rate. The aim was to compare the reporting rate of ADRs between tramadol/paracetamol (TRM+P), codeine/paracetamol (COD+P) and dextropropoxyphene/paracetamol (DXP+P). METHODS All spontaneous reports submitted to the French Pharmacovigilance Database from 1 January 1987 to 31 December 2006 suspected to be induced by one of the three step 2 analgesic combinations (DXP+P, TRM+P, COD+P) were extracted. Their consumption for the same period was obtained from the French Drug Agency. The number of ADRs, serious ADRs and different organ classes of ADRs were compared according to their consumption. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each variable using DXP+P as reference. RESULTS The reporting rate of ADRs was calculated as 24.9/100 000 person-years for DXP+P, 44.5/100 000 person-years for TRM+P and 12.5/100 000 person-years for COD+P. The reporting rate (OR 0.56, 95% CI 0.50, 0.63) and ‘seriousness»’ (OR 0.65, 95% CI 0.53, 0.80) of ADRs were significantly higher with TRM+P than with DXP+P. However, hepatobiliary ADRs were significantly more frequent with the DXP+P combination (OR 2.62, 95% CI 1.59, 4.37). In contrast, the reporting rate (OR 1.99, 95% CI 1.82, 2.18) and ‘seriousness’ (OR 2.64, 95% CI 2.24, 3.11) of ADRs were significantly higher with DXP+P than with COD+P. CONCLUSIONS Among the three step 2 analgesic combinations, reporting rate and ‘seriousness’ of ADRs are the highest with TRM+P and the lowest with COD+P. Our study suggests that the safety profile of DXP+P is worst than that of COD+P. PMID:19740400
de Jong, Loek; Härmark, Linda; van Puijenbroek, Eugène
The aim of this study was to gather information about frequency, latency time, outcome and management of frequently occurring adverse drug reactions (ADRs) related to the use of metformin in daily practice. A prospective, observational cohort study was performed. A total of 2490 first-time metformin users were recruited through pharmacies in the Netherlands between February 1, 2008, and April 1, 2012. Patients were invited to complete six web-based questionnaires at 2-week, 6-week, 3-month, 6-month, 9-month and 12-month intervals after starting treatment with metformin. Information was gathered about patient characteristics, ADRs and drug use. The occurrence of at least one possible ADR related to the use of metformin was reported by 34.5 % of the patients. A higher proportion of females reported the occurrence of an ADR (39.6 %) compared to the proportion in males (30.9 %). Some patients (11.4 %) stopped using metformin within 1 year after start. More than half of the patients (50.8 %) undertook no action regarding metformin after the occurrence of ADRs. A high number of patients (77.7 %) recovered or were still recovering from ADRs despite continuation of metformin. Most ADRs occurred shortly after the beginning of the treatment, with a median latency time of 1-6 days. The study revealed some ADR-specific differences in occurrence rate, latency time, management and outcome. This study successfully obtained information about frequency, latency time, outcome and management of frequently occurring ADRs related to the use of metformin in daily practise.
Yang, Y; Chen, S; Yang, F; Zhang, L; Alterovitz, G; Zhu, H; Xuan, J; Yang, X; Luo, H; Mu, J; He, L; Luo, X; Xing, Q
Clindamycin causes cutaneous adverse drug reactions (cADRs), sometimes with the mechanisms of pathogenicity or risk factors unknown. This study aims to assess whether HLA alleles are associated with clindamycin-related cADRs in the Han Chinese population. We performed an association study of 12 subjects with clindamycin-related cADRs, 279 controls and 26 clindamycin-tolerant subjects. Subjects who received clindamycin through intravenous drip were analyzed separately. Unbiased, in silico docking was conducted. We found 6 out of 12 clindamycin-induced cADR patients carried HLA-B*51:01, and all of them received clindamycin via intravenous drip (6/9). The carrier frequency of HLA-B*51:01 is significantly higher compared with the control group (P=0.0006; OR=9.731, 95% CI: 2.927-32.353) and the clindamycin-tolerant group (OR=24.000, 95% CI: 3.247-177.405). In silico docking showed clindamycin is potentially more stable inside HLA-B*51:01 protein. Our results suggested, for the first time, that HLA-B*51:01 is a risk allele for clindamycin-related cADRs in Han Chinese, especially when clindamycin is administered via intravenous drip.The Pharmacogenomics Journal advance online publication, 16 August 2016; doi:10.1038/tpj.2016.61.
McKay, Ailsa J; Newson, Roger B; Soljak, Michael; Riboli, Elio; Car, Josip
Objective Identification of primary care factors associated with hospital admissions for adverse drug reactions (ADRs). Design and setting Cross-sectional analysis of 2010–2012 data from all National Health Service hospitals and 7664 of 8358 general practices in England. Method We identified all hospital episodes with an International Classification of Diseases (ICD) 10 code indicative of an ADR, in the 2010–2012 English Hospital Episode Statistics (HES) admissions database. These episodes were linked to contemporary data describing the associated general practice, including general practitioner (GP) and patient demographics, an estimate of overall patient population morbidity, measures of primary care supply, and Quality and Outcomes Framework (QOF) quality scores. Poisson regression models were used to examine associations between primary care factors and ADR-related episode rates. Results 212 813 ADR-related HES episodes were identified. Rates of episodes were relatively high among the very young, older and female subgroups. In fully adjusted models, the following primary care factors were associated with increased likelihood of episode: higher deprivation scores (population attributable fraction (PAF)=0.084, 95% CI 0.067 to 0.100) and relatively poor glycated haemoglobin (HbA1c) control among patients with diabetes (PAF=0.372; 0.218 to 0.496). The following were associated with reduced episode likelihood: lower GP supply (PAF=−0.016; −0.026 to −0.005), a lower proportion of GPs with UK qualifications (PAF=−0.035; −0.058 to −0.012), lower total QOF achievement rates (PAF=−0.021; −0.042 to 0.000) and relatively poor blood pressure control among patients with diabetes (PAF=−0.144; −0.280 to −0.022). Conclusions Various aspects of primary care are associated with ADR-related hospital episodes, including achievement of particular QOF indicators. Further investigation with individual level data would help develop understanding of the
McKay, Ailsa J; Newson, Roger B; Soljak, Michael; Riboli, Elio; Car, Josip; Majeed, Azeem
Identification of primary care factors associated with hospital admissions for adverse drug reactions (ADRs). Cross-sectional analysis of 2010-2012 data from all National Health Service hospitals and 7664 of 8358 general practices in England. We identified all hospital episodes with an International Classification of Diseases (ICD) 10 code indicative of an ADR, in the 2010-2012 English Hospital Episode Statistics (HES) admissions database. These episodes were linked to contemporary data describing the associated general practice, including general practitioner (GP) and patient demographics, an estimate of overall patient population morbidity, measures of primary care supply, and Quality and Outcomes Framework (QOF) quality scores. Poisson regression models were used to examine associations between primary care factors and ADR-related episode rates. 212,813 ADR-related HES episodes were identified. Rates of episodes were relatively high among the very young, older and female subgroups. In fully adjusted models, the following primary care factors were associated with increased likelihood of episode: higher deprivation scores (population attributable fraction (PAF)=0.084, 95% CI 0.067 to 0.100) and relatively poor glycated haemoglobin (HbA1c) control among patients with diabetes (PAF=0.372; 0.218 to 0.496). The following were associated with reduced episode likelihood: lower GP supply (PAF=-0.016; -0.026 to -0.005), a lower proportion of GPs with UK qualifications (PAF=-0.035; -0.058 to -0.012), lower total QOF achievement rates (PAF=-0.021; -0.042 to 0.000) and relatively poor blood pressure control among patients with diabetes (PAF=-0.144; -0.280 to -0.022). Various aspects of primary care are associated with ADR-related hospital episodes, including achievement of particular QOF indicators. Further investigation with individual level data would help develop understanding of the associations identified. Interventions in primary care could help reduce the ADR burden
Khan, Lateef M; Al-Harthi, Sameer E; Osman, Abdel-Moneim M; Sattar, Mai A Alim A; Ali, Ahmed S
Basic essence of Pharmacovigilance is prevention of ADRs and its precise diagnosis is crucially a primary step, which still remains a challenge among clinicians. This study is undertaken with the objective to scrutinize and offer a notion of commonly used as well as recently developed methods of causality assessment tools for the diagnosis of adverse drug reactions and discuss their pros and cons. Overall 49 studies were recognized for all assessment methods with five major decisive factors of causality evaluation, all the information regarding reasons allocating causality, the advantages and limitations of the appraisal methods were extracted and scrutinized. From epidemiological information a past prospect is designed and subsequent possibility merged this background information with a clue in the individual case to crop up with an approximation of causation. Expert judgment is typically based on the decisive factor on which algorithms are based, nevertheless in imprecise manner. The probabilistic methods use the similar principle; however connect probabilities to each measure. Such approaches are quite skeptical and liable to generate cloudy causation results. Causation is quite intricate to ascertain than correlation in Pharmacovigilance due to numerous inherent shortcomings in causality assessment tools. We suggest that there is a need to develop a high quality assessment tool which can meticulously establish suitable diagnostic criteria for ADRs with universal acceptance to improvise the fundamental aspect of drug safety and evade the impending ADRs with the motive to convert Pharmacovigilance into a state of art.
Sekhon, Sahil; Nedorost, Susan T
Adverse drug reactions result in a substantial number of hospital admissions and inpatient events. Diagnosis usually is made with clinical judgment and circumstantiality without diagnostic testing. Furthermore, even in situations where diagnostic testing is performed, no safe gold standard tests exist. Oral rechallenge is currently the gold standard but carries the risk of recrudescence of severe allergic symptoms. Other tests include skin prick tests, the lymphocyte transformation test, immunohistochemistry, and patch testing. This article provides a review of patch testing in cases of adverse drug reactions and presents new data on this topic.
Ahmad, Syed Rizwanuddin
The Food and Drug Administration (FDA) is responsible not only for approving drugs but also for monitoring their safety after they reach the market. The complete adverse event profile of a drug is not known at the time of approval because of the small sample size, short duration, and limited generalizability of pre-approval clinical trials. This report describes the FDA's postmarketing surveillance system, to which many clinicians submit reports of adverse drug events encountered while treating their patients. Despite its limitations, the spontaneous reporting system is an extremely valuable mechanism by which hazards with drugs that were not observed or recognized at the time of approval are identified. Physicians are strongly encouraged to submit reports of adverse outcomes with suspect drugs to the FDA, and their reports make a difference. The FDA is strengthening its postmarketing surveillance with access to new data sources that have the potential to further improve the identification, quantification, and subsequent management of drug risk. PMID:12534765
Ahmad, Syed Rizwanuddin
The Food and Drug Administration (FDA) is responsible not only for approving drugs but also for monitoring their safety after they reach the market. The complete adverse event profile of a drug is not known at the time of approval because of the small sample size, short duration, and limited generalizability of pre-approval clinical trials. This report describes the FDA's postmarketing surveillance system, to which many clinicians submit reports of adverse drug events encountered while treating their patients. Despite its limitations, the spontaneous reporting system is an extremely valuable mechanism by which hazards with drugs that were not observed or recognized at the time of approval are identified. Physicians are strongly encouraged to submit reports of adverse outcomes with suspect drugs to the FDA, and their reports make a difference. The FDA is strengthening its postmarketing surveillance with access to new data sources that have the potential to further improve the identification, quantification, and subsequent management of drug risk.
Oliveira, José Luis; Lopes, Pedro; Nunes, Tiago; Campos, David; Boyer, Scott; Ahlberg, Ernst; van Mulligen, Erik M; Kors, Jan A; Singh, Bharat; Furlong, Laura I; Sanz, Ferran; Bauer-Mehren, Anna; Carrascosa, Maria C; Mestres, Jordi; Avillach, Paul; Diallo, Gayo; Díaz Acedo, Carlos; van der Lei, Johan
Pharmacovigilance methods have advanced greatly during the last decades, making post-market drug assessment an essential drug evaluation component. These methods mainly rely on the use of spontaneous reporting systems and health information databases to collect expertise from huge amounts of real-world reports. The EU-ADR Web Platform was built to further facilitate accessing, monitoring and exploring these data, enabling an in-depth analysis of adverse drug reactions risks. The EU-ADR Web Platform exploits the wealth of data collected within a large-scale European initiative, the EU-ADR project. Millions of electronic health records, provided by national health agencies, are mined for specific drug events, which are correlated with literature, protein and pathway data, resulting in a rich drug-event dataset. Next, advanced distributed computing methods are tailored to coordinate the execution of data-mining and statistical analysis tasks. This permits obtaining a ranked drug-event list, removing spurious entries and highlighting relationships with high risk potential. The EU-ADR Web Platform is an open workspace for the integrated analysis of pharmacovigilance datasets. Using this software, researchers can access a variety of tools provided by distinct partners in a single centralized environment. Besides performing standalone drug-event assessments, they can also control the pipeline for an improved batch analysis of custom datasets. Drug-event pairs can be substantiated and statistically analysed within the platform's innovative working environment. A pioneering workspace that helps in explaining the biological path of adverse drug reactions was developed within the EU-ADR project consortium. This tool, targeted at the pharmacovigilance community, is available online at https://bioinformatics.ua.pt/euadr/. Copyright © 2012 John Wiley & Sons, Ltd.
Stewart, Derek; Helms, Peter; McCaig, Dorothy; Bond, Christine; McLay, James
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
Oehme, Ann-Kathrin; Rashed, Asia N.; Hefele, Barbara; Wong, Ian C. K.; Rascher, Wolfgang; Neubert, Antje
Background In recent years, efforts have been made to improve paediatric drug therapy. The aim of this research was to investigate any changes regarding the frequency and nature of adverse drug reactions (ADRs) in hospitalized children in one paediatric general medical ward over a 9-year period. Methodology Two prospective observational cohort studies were conducted at a large University hospital in Germany in 1999 and 2008, respectively. Children aged 0–18 years admitted to the study ward during the study periods were included. ADRs were identified using intensive chart review. Uni- and multivariable regression has been used for data analysis. Results A total of 520 patients (574 admissions) were included [1999: n = 144 (167); 2008: n = 376 (407)]. Patients received a total of 2053 drugs [median 3, interquartile range (IQR) 2–5]. 19% of patients did not receive any medication. Median length of stay was 4 days (IQR 3–7; range 1–190 days) with a significantly longer length of stay in 1999. The overall ADR incidence was 13.1% (95% CI, 9.8–16.3) varying significantly between the two study cohorts [1999: 21.9%, 95% CI, 14.7–29.0; 2008: 9.2%, 95% CI, 5.9–12.5 (p<0.001)]. Antibacterials and corticosteroids for systemic use caused most of the ADRs in both cohorts (1999; 2008). Exposure to systemic antibacterials decreased from 62.9% to 43.5% whereas exposure to analgesics and anti-inflammatory drugs increased from 17.4% to 45.2%, respectively. The use of high risk drugs decreased from 75% to 62.2%. In 1999, 45.7% and in 2008 96.2% of ADRs were identified by treating clinicians (p<0.001). Conclusions Between 1999 and 2008, the incidence of ADRs decreased significantly. Improved treatment strategies and an increased awareness of ADRs by physicians are most likely to be the cause for this positive development. Nevertheless further research on ADRs particularly in primary care and the establishment of prospective pharmacovigilance systems are still
Background and the purpose of the study Adverse drug reactions (ADRs) are important public health problem associated with morbidity, mortality and financial burden on the society. Nurses play important role in medication safety surveillance through the spontaneous voluntary reporting of ADRs. Nurses’ knowledge, attitude and practice towards ADR reporting and factors affecting reporting was assessed in the study. Methods All nurses working in a tertiary care hospital, Ajman, UAE participated in this cross-sectional survey. A self administered questionnaire of four domains (knowledge, attitude, practice, factors affecting reporting) was distributed among nurses after obtaining informed consent. The knowledge and attitude components were assigned score of one for correct response. Data was analyzed using SPSS (version 19). Mann–Whitney U test was used to compare knowledge and attitude scores between subgroups; Spearman’s correlation for any relationship between knowledge and attitude. Results Of the total participants, females constituted 92.3%; average duration of clinical experience 6.5 ± 3.3 years; mean age 28.9 ± 4.1 years. Median score for knowledge components of ADR reporting was 11(total score: 17) and for attitude components was 4(total score: 8). No difference noted in knowledge and attitude scores between gender, age group, educational qualification. A positive correlation between knowledge and attitude components was observed (r = 0.38). ADRs are important cause for morbidity and mortality was reported by (54.9%). 49.5% were aware of Pharmacovigilance centers’. Uncertainty of ADRs (49.5%); concern that the report may be wrong (46.2%) and inadequate knowledge of ADR reporting procedure were the major barriers to reporting. Training in ADR reporting as the key measure to improve reporting was suggested by (86.8%). Major conclusion The results of the study strongly point out the need for interventional program among nurses focusing on the
Rodrigues, Maria Cristina Soares; Oliveira, Cesar de
to identify and summarize studies examining both drug-drug interactions (DDI) and adverse drug reactions (ADR) in older adults polymedicated. an integrative review of studies published from January 2008 to December 2013, according to inclusion and exclusion criteria, in MEDLINE and EMBASE electronic databases were performed. forty-seven full-text studies including 14,624,492 older adults (≥ 60 years) were analyzed: 24 (51.1%) concerning ADR, 14 (29.8%) DDI, and 9 studies (19.1%) investigating both DDI and ADR. We found a variety of methodological designs. The reviewed studies reinforced that polypharmacy is a multifactorial process, and predictors and inappropriate prescribing are associated with negative health outcomes, as increasing the frequency and types of ADRs and DDIs involving different drug classes, moreover, some studies show the most successful interventions to optimize prescribing. DDI and ADR among older adults continue to be a significant issue in the worldwide. The findings from the studies included in this integrative review, added to the previous reviews, can contribute to the improvement of advanced practices in geriatric nursing, to promote the safety of older patients in polypharmacy. However, more research is needed to elucidate gaps. identificar e sintetizar estudos que examinam as interações medicamentosas (IM) e reações adversas a medicamentos (RAM) em idosos polimedicados. revisão integrativa de estudos publicados de janeiro de 2008 a dezembro de 2013, de acordo com critérios de inclusão e exclusão, nas bases de dados eletrônicas MEDLINE e EMBASE. foram analisados 47 estudos de texto completo, incluindo 14,624,492 idosos (≥ 60 anos): 24 (51,1%) sobre RAM, 14 (29,8%) sobre IM e 9 estudos (19,1%) que investigaram tanto IM como RAM. Encontramos uma variedade de desenhos metodológicos. Os estudos revisados reforçaram que a polifarmácia é um processo multifatorial, e os preditores e a prescrição inadequada estão associados a
Dimri, Deepak; Thapliyal, Swati; Thawani, Vijay
Introduction Cutaneous Adverse Drug Reactions (CADR) are the common drug induced adverse reactions which usually have wide range of manifestations and severity. Aim To describe the prevalence and clinical spectrum of CADR’s in a tertiary hospital of the Garhwal region in Uttarakhand, India. Materials and Methods All patients suspected of having CADRs reported in the various out-patient departments, and in-patients of HNB Base & Teaching Hospital, from 1st January 2012 to 31st December 2014 were retrospectively analysed. Drug history was recorded in a format specified in Indian National Pharmacovigilance Programme. Results Total 111 cases of CADRs were reported from Jan 2012 to Dec 2014. Mean age of patients was 33.34±18.7 years and maximum ADRs were reported in the age group of 20-39 years (36.9%). Female were affected more than male (W:M :: 66:45). Most of the ADRs were exanthematous eruptions (EE) type (33.3%). Medicine department reported maximum cases of CADRs (47.7%), followed by Dermatology. Most of the CADRs were reported with antimicrobial agents (69.4%). Significant associations of different types of various cutaneous reactions were observed in relation to the duration (in days) of ADRs (p = 0.038), types of outcome (p= 0.006), different departments (p= 0.014) and between different groups of medicines (p = 0.008). Conclusion CADRs have proved a significant problem in healthcare for decades. Major bulk of CADR result from physician prescribed drugs. Hence, awareness on part of the physician can help in timely detection of cutaneous reactions, thereby restricting damage from them. PMID:27437240
Mattila, Riikka; Gomez-Font, Rafael; Meurman, Jukka H.
Objectives: The main objectives are to present the different adverses effects of the immunomodulatory drugs that can impair the quality of life of the immunosupressed patients and study the impact of immunomodualtion on oral diseases. Immunomodulatory drugs have changed the treatment protocols of many diseases where immune functions play a central role, such as rheumatic diseases. Their effect on oral health has not been systematically investigated, however. Study Design: We review current data on the new immunomodulatory drugs from the oral health perspective based on open literature search of the topic. Results: These target specific drugs appear to have less drug interactions than earlier immunomodulating medicines but have nevertheless potential side effects such as activating latent infections. There are some data showing that the new immunomodulatory drugs may also have a role in the treatment of certain oral diseases such as lichen planus or ameliorating symptoms in Sjögren´s syndrome, but the results have not been overly promising. Conclusions: In general, data are sparse of the effect of these new drugs vs. oral diseases and there are no properly powered randomized controlled trials published on this topic. Key words:Immunomodulatory drugs, oral diseases, adverse effects, therapeutic action. PMID:23986016
Kekäle, Meri; Peltoniemi, Marikki; Airaksinen, Marja
Purpose To evaluate adverse drug reactions (ADRs) experienced by chronic myeloid leukemia (CML) patients during per oral tyrosine kinase inhibitor (TKI) treatment and correlation of ADR symptoms with medication adherence and perceived quality of life (QoL). Patients and methods Eighty-six adult, chronic-phase CML patients who had been on TKI treatment (79% on imatinib, 10.5% dasatinib, and 10.5% nilotinib) for at least 6 months participated in the study (mean age: 57.8 years, 52% males). The mean time from diagnosis was 5.1 years. All patients were interviewed, and patient-reported ADRs were obtained using a structured list. Adherence was assessed using Morisky’s 8-item Medication Adherence Scale (MMAS). The symptoms’ interference with patient’s daily QoL was measured by asking patients about the influence of symptom(s) on their mood, general condition, enjoyment of life, walking, relationships, and work. Results Ninety-seven percent of the patients were suffering from at least one ADR. The mean number of different symptoms was seven (range: 0–15, median 6). The most commonly perceived ADRs were muscle soreness or cramp (69/86, 80%); swelling of hands, legs, feet, or around the eyes (59/86, 69%); and fatigue (43/86, 50%). No correlation was found between adherence and ADRs, because symptoms were equally common in each MMAS adherence class. Half of the patients felt that the ADRs had a negative influence on their daily QoL. A quarter of the patients reported that ADRs affected either their mood, general condition, or enjoyment of life. The incidence of almost all ADRs was much higher among patients reporting negative influence of ADRs on their daily life compared to total study population (P=0.016). Conclusion TKI-related ADRs were common among CML patients irrespective of patient’s adherence level. Patients who reported that ADRs had a negative influence on their daily QoL perceived more ADRs than those who did not experience a negative influence. PMID
Bracchi, Robert C G; Houghton, Jane; Woods, Fiona J; Thomas, Simon; Smail, Simon A; Routledge, Philip A
The effect of a distance-learning package linked to educational credits on the rate and quality of spontaneous adverse drug reaction (ADR) reporting by general practitioners (GPs) and pharmacists in Wales was investigated. In April 2000, 477 GPs and 261 pharmacists enrolled in the 12 month programme. The number and quality of yellow card reports improved compared with those of a control region in England (Northern Region). We conclude that an educational initiative in drug safety linked to incentives may be associated with a significant but perhaps short-lived improvement in the rate and quality of ADR reporting.
Bracchi, Robert C G; Houghton, Jane; Woods, Fiona J; Thomas, Simon; Smail, Simon A; Routledge, Philip A
Aims The effect of a distance-learning package linked to educational credits on the rate and quality of spontaneous adverse drug reaction (ADR) reporting by general practitioners (GPs) and pharmacists in Wales was investigated. Methods In April 2000, 477 GPs and 261 pharmacists enrolled in the 12 month programme. Results The number and quality of yellow card reports improved compared with those of a control region in England (Northern Region). Conclusions We conclude that an educational initiative in drug safety linked to incentives may be associated with a significant but perhaps short-lived improvement in the rate and quality of ADR reporting. PMID:16042677
Graudins, Linda Velta; Ly, Jenny; Trubiano, Jason; Aung, Ar Kar
To determine the gaps in practice regarding appropriate ADR documentation and risk communication for patients diagnosed with severe cutaneous adverse drug reactions (CADR). This was a retrospective observational cohort study conducted using hospital coding and databases to identify inpatients diagnosed with CADR from January 2004 to August 2014. Hospital discharge summaries, ADR reports and pharmacy dispensing records were reviewed for ADR documentation. Patients still living in Australia and who did not opt out of being contacted were invited to be surveyed by telephone to determine their understanding of recommendations, re-exposure rates and long-term effects. Of 85 patients identified, median age was 59 (IQR 44-72) years and 47.1% were male. The most common diagnosis was TENS (49.4%). Ten patients (11.8%) died as inpatients. Of the 81 patients with a drug-related causality, 47 (58%) had appropriate documentation in all three required medical record platforms. Of the 56 eligible patients, 38 (67.9%) were surveyed; 13% had no information provided upon discharge and 26.3% patients had a mismatch in knowledge of implicated medications. No surveyed patient had a relapse of CADR, but 23.7% had a subsequent unrelated allergic reaction. Thirteen patients (34.2%) reported long-term effects. We found gaps in the accuracy of ADR documentation and communication of risk at discharge, which indicated risks to patient safety. Electronic systems are being developed to improve documentation. Written information about CADR is being provided at discharge to improve patient understanding and knowledge. © 2016 The British Pharmacological Society.
Li, Xue; Liu, Heng; Zhao, Li; Liu, Junling; Cai, Li; Liu, Lei; Zhang, Weiguo
To determine the adverse drug reaction (ADR) profile of non-ionic iodinated contrast media in populations with underlying diseases and risk factors and to provide guidance for more safe and rational use of iodinated contrast media (ICMs) in the clinic. Data from 120,822 cases who underwent enhanced CT examination in our hospital from January 2014 to March 2016 were collected. A standardized case report form was used for data collection and analysis. The incidence of ADRs was 0.4% and 0.44% in patients with and without underlying diseases, respectively (p = 0.378). Risk factor analysis revealed that patients with asthma had the highest incidence of ADRs, followed by patients with cardiac insufficiency and patients who were aged had the lowest incidence. There was a low incidence of ADRs in patients under metformin (0.36%) and β-adrenaline receptor antagonist (0.20%) medication. The incidence was the highest in patients with previous ADRs to ICMs (7.17%) and the lowest in those with a history of ICM usage but no previous reactions (0.32%). ADRs were more common in patients at high risk at a higher injection dose (≥100 ml; p < 0.01) and speed (≥5 ml s(-1); p < 0.01). The incidence of ADRs was extremely low in patients regardless of underlying diseases. Some high-risk factors have certain correlations with the occurrence of ADRs. Particular attention should be given to patients at high risk when performing enhanced CT examination. Advances in knowledge: The correlation between various risk factors and underlying diseases and ADRs was comprehensively analyzed in a large-scale population.
Low, Siew-Kee; Kiyotani, Kazuma; Mushiroda, Taisei; Daigo, Yataro; Nakamura, Yusuke; Zembutsu, Hitoshi
Cyclophosphamide (CPA)-based combination treatment has known to be effective for breast cancer, but often causes adverse drug reactions (ADRs). Hence, the identification of patients at risk for toxicity by CPA is clinically significant. In this study, a stepwise case-control association study was conducted using 403 patients with breast cancer who received the CPA combination therapy. A total of 143 genetic polymorphisms in 13 candidate genes (CYP2B6, CYP2C9, CYP2C19, CYP3A4, CYP3A5, ALDH1A1, ALDH3A1, GSTA1, GSTM1, GSTP1, GSTT1, ABCC2 and ABCC4), possibly involved in the activation, metabolism and transport of CPA, were genotyped using 184 cases who developed either > or =grade 3 leukopenia/neutropenia or > or =grade 2 gastrointestinal toxicity and 219 controls who did not show any ADRs throughout the treatment. The association study revealed that one SNP, rs9561778 in ABCC4, showed a significant association with CPA-induced ADRs (Cochran-Armitage trend's P-value=0.00031; odds ratio (OR)=2.06). Subgroup analysis also indicated that the SNP rs9561778 was significantly associated with two major ADR subgroups; gastrointestinal toxicity and leukopenia/neutropenia (Cochran-Armitage trend's P-value=0.00019 and 0.014; OR=2.31 and 1.83). Furthermore, the SNP rs9561778 showed an association with breast cancer patients who were treated with CA(F) drug regimen-induced ADR (Cochran-Armitage trend's P-value=0.00028; OR=3.13). The SNPs in ABCC4 might be applicable in predicting the risk of ADRs in patients receiving CPA combination chemotherapy.
Arnet, Isabelle; Seidling, Hanna M; Hersberger, Kurt E
Community pharmacists represent an important pillar for the identification and the reporting of adverse drug effects (ADE}. Thanks to their broad view on the pharmacotherapy, over-the-counter medication included, they contribute greatly to the improvement of drug safety. In principle, the community pharmacy will face three groups of ADE which require specific attention. This article deals with these specific ADE groups and presents some illustrative examples from daily practice. Furthermore, we suggest some solutions to identify potential relevant interactions - including herbal-drug interactions - and give tips for daily practice, along with some often overseen cutaneous ADE.
Khan, Sarfaraz Alam; Goyal, Chhaya; Tonpay, S. D.
Objective: The aim was to investigate the knowledge, attitudes, and practice of dental doctors about adverse drug reaction (ADR) reporting. Materials and Methods: In a cross-sectional study, questionnaire was administered to 95 dental doctors working in a teaching dental hospital attached to a medical college with an ADR monitoring center (AMC). Statistical Analysis Used: Descriptive statistics were used to analyze responses. The association of knowledge and attitude with respect to position of dentists was analyzed with Chi-square test. Results: The response rate and spontaneous reporting rate was found to be 61.0% and 13.7%, respectively. Important factors contributing to under reporting of ADRs include lack of awareness about AMC in the institute (81.0%) and pharmacovigilance program (72.4%), complacency (67.2%), lack of training to identify ADRs (65.5%), fear factor (63.7%), lethargy (58.6%), lack of risk perception of over the counter product related ADR (39.6%), inadequate risk perception of nonallopathic and herbal medicines (31%), indifference (27.5%) and concern that report may be wrong (27.5%). No significant difference in knowledge and attitudes of doctors with respect to position was found except for reporting of ADRs of newly marketed drugs and serious reactions to established product (P < 0.05). Conclusion: The deficiencies in knowledge and attitudes appear to be the underlying factor for under reporting by dental practitioners. It should be addressed urgently in order to increase spontaneous reporting by them. PMID:26229750
Background Spontaneous reporting of adverse drug reactions (ADRs) is an important method for pharmacovigilance, but under-reporting and poor quality of reports are major limitations. The aim of this study was to evaluate if repeated one-page ADR information letters affect (i) the reporting rate of ADRs and (ii) the quality of the ADR reports. Methods All 151 primary healthcare units in the Region Västra Götaland, Sweden, were randomly allocated (1:1) to an intervention (n = 77) or a control group (n = 74). The intervention consisted of one-page ADR information letters administered at three occasions during 2008 to all physicians and nurses in the intervention units. The number of ADR reports received from the 151 units was registered, as was the quality of the reports, which was defined as high if the ADR was to be reported according to Swedish regulations, that is, if the ADR was (i) serious, (ii) unexpected, and/or (iii) related to the use of new drugs and not labelled as common in the Summary of Product Characteristics. A questionnaire was administered to evaluate if the ADR information letter had reached the intended recipient. Results Before the intervention, no significant differences in reporting rate or number of high quality reports could be detected between the randomization groups. In 2008, 79 reports were sent from 37 intervention units and 52 reports from 30 control units (mean number of reports per unit ± standard deviation: 1.0 ± 2.5 vs. 0.7 ± 1.2, P = 0.34). The number of high quality reports was higher in intervention units than in control units (37 vs. 15 reports, 0.5 ± 0.9 vs. 0.2 ± 0.6, P = 0.048). According to the returned questionnaires (n = 1,292, response rate 57%), more persons in the intervention than in the control group had received (29% vs. 19%, P < 0.0001) and read (31% vs. 26%, P < 0.0001) an ADR information letter. Conclusions This study suggests that repeated ADR information letters to physicians and nurses do not increase
Gallagher, Ruairi M; Kirkham, Jamie J; Mason, Jennifer R; Bird, Kim A; Williamson, Paula R; Nunn, Anthony J; Turner, Mark A; Smyth, Rosalind L; Pirmohamed, Munir
To develop and test a new adverse drug reaction (ADR) causality assessment tool (CAT). A comparison between seven assessors of a new CAT, formulated by an expert focus group, compared with the Naranjo CAT in 80 cases from a prospective observational study and 37 published ADR case reports (819 causality assessments in total). Utilisation of causality categories, measure of disagreements, inter-rater reliability (IRR). The Liverpool ADR CAT, using 40 cases from an observational study, showed causality categories of 1 unlikely, 62 possible, 92 probable and 125 definite (1, 62, 92, 125) and 'moderate' IRR (kappa 0.48), compared to Naranjo (0, 100, 172, 8) with 'moderate' IRR (kappa 0.45). In a further 40 cases, the Liverpool tool (0, 66, 81, 133) showed 'good' IRR (kappa 0.6) while Naranjo (1, 90, 185, 4) remained 'moderate'. The Liverpool tool assigns the full range of causality categories and shows good IRR. Further assessment by different investigators in different settings is needed to fully assess the utility of this tool.
Jeschke, Elke; Ostermann, Thomas; Lüke, Claudia; Tabali, Manuela; Kröz, Matthias; Bockelbrink, Angelina; Witt, Claudia M; Willich, Stefan N; Matthes, Harald
The use of complementary therapies by patients has increased over the past 20 years, both in terms of self-medication and physician prescriptions. Among herbal medicines, those containing extracts of Asteraceae (Compositae), such as Echinacea spp., Arnica montana, Matricaria recutita and Calendula officinalis, are especially popular in the primary-care setting. However, there remains a gap between the growing acceptance of these remedies and the lack of data on their safety. The aim of this study was to analyse prescribing patterns and adverse drug reactions (ADRs) for Asteraceae-containing remedies in Germany. Primary-care physicians, all of whom were members of the German National Association of Anthroposophic Physicians were invited to participate in this prospective, multicentre, observational study. During the study period (September 2004 to September 2006), all prescriptions and suspected ADRs for both conventional and complementary therapies were documented using a web-based system. The study centre monitored all ADR reports and conducted a causality assessment according to Uppsala Monitoring Centre guidelines. Relative risks (RRs) and proportional reporting ratios (PRRs) were calculated. Thirty-eight physicians, 55% of whom were general practitioners and 45% were specialists, fulfilled the technical requirements and were included in the investigation. Because documenting all ADRs (i.e. serious and nonserious) was time consuming, only a subgroup consisting of seven physicians agreed to report nonserious in addition to serious ADRs. During the study period, a total of 50 115 patients were evaluated and 344 ADRs for conventional and complementary remedies were reported. Altogether, 18 830 patients (58.0% female, 60.3% children) received 42 378 Asteraceae-containing remedies. The most frequently prescribed Asteraceae was Matricaria recutita (23%), followed by Calendula officinalis (20%) and Arnica montana (20%). No serious ADRs for Asteraceae
Zhang, Lu; Lu, Jiafei; Qiu, Liyan
P-glycoprotein (P-gp) overexpression has become the most common cause of occurrence of multidrug resistance in clinical settings. We aimed to construct a micellar polymer carrier to sensitize drug-resistant tumors to doxorubicin (DOX). This A-B-C-type amphiphilic copolymer was prepared by the sequential linkage of β-cyclodextrin, hydrophobic poly(d,l-lactide), and hydrophilic poly(ethylene glycol). Upon incubation of the DOX-loaded micelles with DOX-resistant human breast carcinoma MCF-7/ADR cells, significantly enhanced cytotoxicity and apoptosis were achieved. A series of studies on the action mechanism showed that the polymer components such as β-cyclodextrin, hydrophobic poly(d,l-lactide) segment, and poly(ethylene glycol) coordinatively contributed to the improved intracellular ATP depletion and ATPase activity, increased intracellular uptake of P-gp substrates via competitive binding to P-gp, and decreased P-gp expression in MCF-7/ADR cells. More interestingly, a similar phenomenon was observed in the zebrafish xenograft model, resulting in ~64% inhibition of MCF-7/ADR tumor growth. These results implied that the polymeric micelles displayed great potentials as P-gp modulators to reverse DOX resistance in MCF-7/ADR breast carcinoma. PMID:27785023
Ahmed, Bilal; Nanji, Kashmira; Mujeeb, Rakshinda; Patel, Muhammad Junaid
Adverse drug reactions (ADRs) present a challenging and expensive public health problem. Polypharmacy is defined according to the WHO criteria as the, "concurrent use of five or more different prescription medication". Elderly are more prone to adverse reactions due to comorbid conditions, longer lists of medications and sensitivity to drug effects. The aim of the study is to estimate the incidence and strength of association of ADRs due to polypharmacy among the geriatric cohort attending outpatient clinics at a tertiary care center. A hospital based prospective cohort study was conducted at ambulatory care clinics of Aga Khan University Hospital April 2012 to March 2013. One thousand geriatrics patients (age ≥ 65 years) visiting ambulatory clinics were identified. They were divided on the basis of exposure (polypharmacy vs. no polypharmacy). We followed them from the time of their enrollment (day zero) to six weeks, checking up on them once a week. Incidence was calculated and Cox Proportional Hazard Model estimates were used. The final analysis was performed on 1000 elderly patients. The occurrence of polypharmacy was 70% and the incidence of ADRs was 10.5% among the study cohort. The majority (30%) of patients were unable to read or write. The use of herbal medicine was reported by 3.2% of the patients and homeopathic by 3%. Our Cox adjusted model shows that polypharmacy was 2.3 times more associated with ADRs, con-current complementary and alternative medicine (CAM) was 7.4 times and those who cannot read and write were 1.5 times more associated with ADRs. The incidence of ADRs due to poly pharmacy is alarmingly high. The factors associated with ADRs are modifiable. Policies are needed to design and strengthen the prescription pattern.
It is surprising to see how consumer Adverse Drug Reaction (ADR) reports have been continuously increasing for the last few years in Europe. This probably results from the influence of United States (US) market where the patients feels justified in telephoning the pharmaceutical companies directly with queries regarding their treatment. The growing number of alternative sources of information (e.g. health and popular magazines, spots on radio and TV etc.) to which a consumer is exposed has added to this growth too. The changing relationship between patients and doctors may also contribute to this phenomenon. It is then interesting to evaluate the way pharmaceutical companies currently deal with consumer ADR reports. The management of consumer ADR reporting was investigated by means of a questionnaire sent to 46 French drug safety managers and drug safety officers (DSOs) of multinational pharmaceutical companies. The analysis of the survey stressed the fact that pharmaceutical companies should be prepared to face up to an increase in the number of consumer ADR reports. It clearly appears that the consumers who telephone to register side-effects should be forwarded to a trained DSO with medical or pharmaceutical background and the communication skills acquired through specific training. This person should also be able to release adequate product information validated by his/her own company. The influence of the US market seems to be changing the way pharmaceutical companies deal with consumer ADR reports. Nowadays, these reports are entered into a drug safety database by most of the companies without previously having contacted the patient's general practitioner (GP) or specialist for medical confirmation. Lastly, the drug safety managers and DSOs consulted have divided opinions about the usefulness of call centres and e-mails as tools for ADR reporting. But both tools are globally rejected by the pharmaceutical companies as a reliable means of reporting. As stated
Bascones-Martinez, Antonio; Mattila, Riikka; Gomez-Font, Rafael; Meurman, Jukka H
The main objectives are to present the different adverse effects of the immunomodulatory drugs that can impair the quality of life of the immunosuppressed patients and study the impact of immunomodulation on oral diseases. Immunomodulatory drugs have changed the treatment protocols of many diseases where immune functions play a central role, such as rheumatic diseases. Their effect on oral health has not been systematically investigated, however. We review current data on the new immunomodulatory drugs from the oral health perspective based on open literature search of the topic. These target specific drugs appear to have less drug interactions than earlier immunomodulating medicines but have nevertheless potential side effects such as activating latent infections. There are some data showing that the new immunomodulatory drugs may also have a role in the treatment of certain oral diseases such as lichen planus or ameliorating symptoms in Sjögren's syndrome, but the results have not been overly promising. In general, data are sparse of the effect of these new drugs vs. oral diseases and there are no properly powered randomized controlled trials published on this topic.
Nguyen, Ann T; Gentry, Chris A; Furrh, Rona Z
High-dose trimethoprim-sulfamethoxazole (TMP-SMX) for the empiric treatment of community-acquired methicillin-resistant Staphylococcus aureus skin and soft tissue infections has been evaluated for efficacy, but characterization of adverse reactions is lacking. To describe adverse reactions associated with high-dose TMP-SMX therapy, a retrospective medical record review of outpatients receiving TMP-SMX was conducted. Each episode (case) of a patient receiving high-dose TMP-SMX (at least 4 double-strength tablets per day) was matched by next closest prescription number with a patient (control) receiving standard-dose TMP-SMX. 982 cases were reviewed; 491 in each arm. At least one adverse drug reaction (ADR) occurred in 9.1% of patients. There was a significant difference in the incidence for any ADR between high-dose and standard-dose groups (13.0% vs 5.09%, respectively; p<0.0001). More patients taking high-dose TMP-SMX developed hyperkalemia (3.46% vs 0.81%, p=0.0066), acute renal injury (3.67% vs 1.63%, p=0.044), and rash (1.83% vs 0.20%, p=0.021). Patients receiving high-dose TMP-SMX had significantly higher rates of electrolyte abnormality ADR (5.09% vs 1.63%, p=0.0021), gastrointestinal ADR (5.30% vs 2.24%, p=0.011), renal ADR (3.67% vs 1.63%, p=0.044), central nervous system ADR (2.65% vs 0.81%, p=0.047), and hypersensitivity (2.24% vs 0.41%, p=0.022). Concomitant receipt of an angiotensin-converting enzyme (ACE) inhibitor was a univariate variable associated with hyperkalemia, and advanced age and receipt of high-dose TMP-SMX were independent variables. ADRs such as hyperkalemia are more likely to be associated with the use of high-dose TMP-SMX in the ambulatory setting. Clinicians should use caution when initiating high-dose TMP-SMX and consider laboratory monitoring in patients of advanced age or those receiving concomitant ACE inhibitor therapy.
Leon, Leticia; Gomez, Alejandro; Vadillo, Cristina; Pato, Esperanza; Rodriguez-Rodriguez, Luis; Jover, Juan Angel; Abasolo, Lydia
Biological DMARDs are widely used in the treatment of rheumatoid arthritis (RA) but their relationship with adverse drug reaction (ADR) is important. RA is now known to increase in incidence and prevalence with age. Our objective was to assess the incidence of severe ADR in the long term, compare safety between the different bDMARDs and identify other possible risk factors for severe ADR in elderly RA patients. A 14-year retrospective longitudinal study was performed. RA patients followed in an out-patient clinic starting bDMARDs after the age of 65 were included. discontinuation due to a severe ADR related to bDMARDs (etanercept, infliximab, adalimumab, rituximab, golimumab, certolizumab, abatacept and tocilizumab). Covariables: sociodemographic, clinical and therapy. Incidence rates of discontinuation were estimated using survival techniques and comparison between bDMARDs discontinuation rates and other associated factors were run by Cox regression models. We analysed 286 courses of bDMARDs therapy in 146 elderly patients (604 patient-years). 78% were women, with a mean age at diagnosis of 66.5±7 years, and a median time to the start of the first bDMARDs of 6±4 years. The incidence of discontinuation due to severe ADR estimated was 10.2% patient-years, with a median survival of around 7 years. The most frequent cause was infections. Etanercept had the lowest risk of severe ADR compared to other bDMARDs. Our study reflects the 'real world' experience in elderly RA patients on bDMARDs, with non-selected patients for a 14-year follow-up.
Naisbitt, Dean J.
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
Topaz, Maxim; Lai, Kenneth; Dhopeshwarkar, Neil; Seger, Diane L; Sa'adon, Roee; Goss, Foster; Rozenblum, Ronen; Zhou, Li
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).
Oosterhuis, Ingrid; van Hunsel, Florence P A M; van Puijenbroek, Eugène P
In 2010, the Netherlands Pharmacovigilance Centre Lareb received more than 4000 reports from healthcare professionals (HCPs). All HCPs received individual personal feedback containing information about the reported drug-adverse drug reaction (ADR) association. It is unclear what type of information HCPs expect in this feedback letter. The aim of the study was to examine the expectations of the personal feedback of HCPs who reported an ADR to the Netherlands Pharmacovigilance Centre Lareb. A questionnaire survey was conducted among a random sample of 1200 pharmacists, general practitioners (GPs) and medical specialists who reported an ADR to the Netherlands Pharmacovigilance Centre Lareb between 1 January 2009 and 27 January 2010. Responders and non-responders were compared on the basis of profession, number of reports submitted to the pharmacovigilance since 2007 and their last report being serious or not. Questions were asked about the importance of personal feedback and the type of information reporters would like to see in their personal feedback. Both linear and logistic regression analysis were performed, with correction for possible confounding factors. The response rate to the questionnaire was 34.6% (n = 399). The type of information the respondents generally would like to see in their personal feedback is information about the time course of the ADR and information about the pharmacological mechanism. However, GPs were, in general, less interested in receiving feedback than pharmacists and medical specialists. Most of the respondents were (very) unsatisfied if they received only a confirmation letter instead of personal feedback. Personalized feedback was considered to be (very) important for reporting an ADR in the future. Most of the respondents (80.3%) stated that the personal feedback increased their knowledge. Only 0.6% of respondents had not read the personalized feedback. No differences were found between responders and non-responders, with the
Alshakka, Mohammed Ahmed; Ibrahim, Mohamed Izham Mohamed; Hassali, Mohamed Azmi Ahmad
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
Belhekar, Mahesh N; Taur, Santosh R; Munshi, Renuka P
Reliability and usefulness of various adverse drug reaction (ADR) causality assessment scales have not been fully explored. There is no universally accepted method for causality grading of ADRs. In the present study we assessed agreement between the two widely used causality assessment scales, that is, the World Health Organization-Uppsala Monitoring Center (WHO-UMC) criteria and the Naranjo algorithm. The same observer assessed all ADRs (n = 913) collected between January 2010 and December 2012 using the WHO-UMC criteria and Naranjo algorithm at a tertiary care hospital in India. We found that the most frequently assigned causality category was "possible" with both the scales. A disagreement in the causality assessment was found in 45 (4.9%) cases reflecting "poor" agreement between the two scales (Kappa statistic with 95% confidence interval = 0.143 [0.018, 0.268]). The mean time taken to assess causality of the ADR using the WHO-UMC criteria was shorter than that by the Naranjo algorithm. This study showed that there is a poor agreement between the WHO-UMC criteria and Naranjo algorithm with the former being less time-consuming.
Umar, Muhammad Tukur; Bello, Shaibu Oricha; Chika, Aminu; Oche, Oche Mansur
Objective: Objective of this study was to assess the attitude of nurses and pharmacists towards adverse drug reactions (ADRs) reporting. Methods: The questionnaire was designed based on extended “Inman seven deadly sins.” Two hundred and seventy-two respondents were selected by stratified sampling technique. The questionnaires were delivered to the respondents at their places of practice. The data generated were analyzed by Sigma XL Software Inc. Findings: There was no statistically significant relationship between demographic profiles and reporting attitude except for qualification. On extended “Inman seven deadly sins” awareness of reporting protocol and nearby center for ADRs reporting were low 27.3 and 7.5%, respectively. However, respondents’ score on components of attitude of ADRs reporting is generally encouraging. On comparative basis, no statistical significance exists between pharmacists and nurses. Conclusion: The study showed that attitude of respondents towards ADRs reporting is good. However, there is a need for targeted health education intervention among these cadres of health-care professionals, especially on aspects of awareness of reporting protocol and reporting center. PMID:27512716
Hilgers, Annika; Schaefer, Marion
Based on data of clinical trials, new agents are receiving approval to the pharmaceutical market, for which information concerning safety issues under real-life conditions is not yet available. The aim was to evaluate the tolerability of newer antiepileptic drugs (AEDs), such as topiramate, levetiracetam, zonisamide, pregabalin, extended-release oxcarbazepine, lacosamide and eslicarbazepine, under real-life conditions by means of an assessment of routine clinical data of inpatients. Over 2.75 years data of all inpatients receiving one of the newer AEDs were documented. Occurring adverse drug reactions (ADRs) were classified according to the WHO-UMC Causality Assessment concerning their likely relationship to the prescribed AEDs. For each AED, the total number of patients without and with ADRs, assessed as at least possibly related to the particular drug, was calculated and corresponding incidences compared with reference data provided in the Summary of Product Characteristics (SmPC). For statistical evaluation Spearman correlation (rs), estimated relative risk and logistic regression analysis were used. In total, the data of 562 patients were assessed, of which 90 % received up to six different AEDs. The proportion of off-label use with regard to dosage varied between 6.4 and 64.7 %. Levetiracetam and oxcarbazepine as an extended-release formulation were most commonly used, and levetiracetam showed the best tolerance. By using logistic regression, the occurrence of ADRs was significantly associated with the number of AEDs (p < 0.001) as well as the defined daily doses (p = 0.003). In total, ADRs of AEDs were documented for 318 patients (56.6 %). The most common referred to electrolyte imbalance, e.g., low sodium (n = 79, 14.1 %) and potassium (n = 25, 4.4 %) levels, the central nervous system, including dizziness (n = 61, 10.9 %), disturbed vision (n = 47, 8.4 %), fatigue (n = 40, 7.1 %), nystagmus (n = 36, 6.4 %) and ataxia (n = 29, 5
Edwards, I R
Drug safety signals will continue to come mainly from the reporting of alert clinicians and every effort should be made to enhance this and to ease the process. The use of multipurpose health databases for finding signals has much potential, if they are better planned so that the appropriate data is captured and examined routinely. Consumer reports give us information about their concerns and should not be ignored. Better information is needed on poisoning, drug misuse and on herbal remedies. The analysis of signals must be improved and speeded up, if we are even to maintain our current safety standards, given the global release of 'blockbuster products'. Benefit-risk analysis of medicines needs to be better understood in relationship to actual clinical use, both from an individual and public health perspective. Such analysis should become more logical rather than just listing the benefits and risks, and then expressing an essentially unsupported opinion. This is essential if therapies are to be compared, and their costs justified. The communication of medicines safety and benefit-risk information to clinicians, other health professionals and patients is an area where there needs to be considerable improvements. We need to be better informed about the consequences of guidance and warnings given, so that we may improve the service we offer to recipients. In the future, information technology, which provides exciting possibilities with what it offers now, will help us with all the above challenges.
Tuccori, Marco; Lapi, Francesco; Testi, Arianna; Ruggiero, Elisa; Moretti, Ugo; Vannacci, Alfredo; Bonaiuti, Roberto; Antonioli, Luca; Fornai, Matteo; Giustarini, Giulio; Scollo, Carla; Corona, Tiberio; Ferrazin, Fernanda; Sottosanti, Laura; Blandizzi, Corrado
The frequency and clinical features of drug-related taste and/or smell impairments are currently unclear. The aim of this study was to identify major drug classes associated with taste and smell alterations reported to the Italian spontaneous adverse drug reaction (ADR) reporting database. The association between drug and altered taste or smell was investigated by case/non-case methodology. The reporting odds ratio (ROR) was used as a measure of disproportionality. Cases were defined as patients with at least one ADR related to taste or smell impairments. The non-cases included all patients without any ADRs related to taste or smell alterations. According to the selection criteria, 52 166 reports were included in the analysis. Overall, 182 cases of drug-related taste and/or smell dysfunctions were identified. Statistically significant unadjusted RORs were reported for macrolides (n = 31; 7.1; 95% CI 4.8, 10.5), terbinafine (the only drug reported within the group of antimycotics belonging to the Anatomical Therapeutic Chemical class D01AE) [n = 17; 76.4; 95% CI 44.0, 132.6], fluoroquinolones (n = 15; 1.7; 95% CI 1.0, 2.8) and protein kinase inhibitors (n = 10; 4.0; 95% CI 2.1, 7.7). When RORs were adjusted for sex and age category, the disproportion remained statistically significant for all of the previously mentioned drug classes. Taste and/or smell abnormalities are common, sometimes unexpected and often persistent complaints of patients during pharmacological treatments. Physicians should be aware of the impact of these ADRs on patients' quality of life.
Sangole, Nishant V; Dadkar, Vaishali N
Angiotensin converting enzyme inhibitors (ACEIs) are known to possess different chemical structures, and change in structure of a drug can bring about change in its adverse drug reaction (ADR) profile. The study aims to observe the incidence and severity of ADRs between the di-carboxyl group containing ACEIs (d-ACEIs) versus phosphonate group containing ACEIs (p-ACEIs), in patients suffering from essential hypertension. One hundred and twenty patients with essential hypertension were randomized into four groups receiving enalapril, lisinopril, ramipril, and fosinopril. They were followed up for four months, to observe the clinical efficacy along with the associated ADRs. Mild, dry brassy cough (% incidence; 95% CI) was observed with d-ACEIs (6.6%; 0 to 15.6) versus p-ACEI (20%; 5.7 to 34.3), in which the cough observed was moderate-to-severe in intensity and two patients required treatment discontinuation (P < 0.05). No cases of hypotension were observed with the use of d-ACEIs, whereas, two patients on p-ACEI (6.6%; 0 to15.6) had hypotension (P < 0.05). Three patients (10%; 0 to 20.7) on d-ACEIs had nausea, which was not observed with p-ACEI treatment (0%) (P < 0.05). The phosphonate group in p-ACEIs may have a probable relationship with increase in the incidence and severity of ADRs such as dry brassy cough and hypotension. The di-carboxyl group in d-ACEIs may have a probable relationship with increase in the incidence of ADRs like nausea.
Sangole, Nishant V.; Dadkar, Vaishali N.
Objectives: Angiotensin converting enzyme inhibitors (ACEIs) are known to possess different chemical structures, and change in structure of a drug can bring about change in its adverse drug reaction (ADR) profile. The study aims to observe the incidence and severity of ADRs between the di-carboxyl group containing ACEIs (d-ACEIs) versus phosphonate group containing ACEIs (p-ACEIs), in patients suffering from essential hypertension. Materials and Methods: One hundred and twenty patients with essential hypertension were randomized into four groups receiving enalapril, lisinopril, ramipril, and fosinopril. They were followed up for four months, to observe the clinical efficacy along with the associated ADRs. Results: Mild, dry brassy cough (% incidence; 95% CI) was observed with d-ACEIs (6.6%; 0 to 15.6) versus p-ACEI (20%; 5.7 to 34.3), in which the cough observed was moderate-to-severe in intensity and two patients required treatment discontinuation (P < 0.05). No cases of hypotension were observed with the use of d-ACEIs, whereas, two patients on p-ACEI (6.6%; 0 to15.6) had hypotension (P < 0.05). Three patients (10%; 0 to 20.7) on d-ACEIs had nausea, which was not observed with p-ACEI treatment (0%) (P < 0.05). Conclusions: The phosphonate group in p-ACEIs may have a probable relationship with increase in the incidence and severity of ADRs such as dry brassy cough and hypotension. The di-carboxyl group in d-ACEIs may have a probable relationship with increase in the incidence of ADRs like nausea. PMID:20606833
Lin, Wen-Yang; Lan, Lin; Huang, Feng-Hsiung; Wang, Min-Hsien
Spontaneous reporting systems of adverse drug events have been widely established in many countries to collect as could as possible all adverse drug events to facilitate the detection of suspected ADR signals via some statistical or data mining methods. Unfortunately, due to privacy concern or other reasons, the reporters sometimes may omit consciously some attributes, causing many missing values existing in the reporting database. Most of research work on ADR detection or methods applied in practice simply adopted listwise deletion to eliminate all data with missing values. Very little work has noticed the possibility and examined the effect of including the missing data in the process of ADR detection. This paper represents our endeavor towards the exploration of this question. We aim at inspecting the feasibility of applying rough set theory to the ADR detection problem. Based on the concept of utilizing characteristic set based approximation to measure the strength of ADR signals, we propose twelve different rough set based measuring methods and show only six of them are feasible for the purpose. Experimental results conducted on the FARES database show that our rough-set-based approach exhibits similar capability in timeline warning of suspicious ADR signals as traditional method with missing deletion, and sometimes can yield noteworthy measures earlier than the traditional method. Copyright © 2015 Elsevier Inc. All rights reserved.
Lapi, Francesco; Tuccori, Marco; Motola, Domenico; Pugi, Alessandra; Vietri, Michele; Montanaro, Nicola; Vaccheri, Alberto; Leoni, Olivia; Cocci, Alfredo; Leone, Roberto; Conforti, Anita; Moretti, Ugo; Sessa, Emiliano; Mazzaglia, Giampiero; Mugelli, Alessandro; Mazzei, Teresita; Vannacci, Alfredo
Fluoroquinolones are widely used both in primary care and in hospital settings. Since the last comparison performed in Italy on the safety profiles of different fluoroquinolones, a new molecule, prulifloxacin, has been introduced into the market and several warnings concerning this class of drugs have been released. The aim of this study was to reassess the safety profiles of fluoroquinolones using the database of the Italian Interregional Group of Pharmacovigilance (IGP) and the administrative data of fluoroquinolone prescriptions. All adverse drug reactions (ADRs) reported in four Italian regions (Lombardy, Veneto, Emilia Romagna and Tuscany) were retrieved from the IGP database. Consumption data (defined daily dose [DDD]/1000 inhabitants/day) were used as denominators. Both single reports and all ADRs (classified by System Organ Classes and MedDRA Preferred Term [PT]) due to fluoroquinolones were considered as numerators of each analysis, comparing two periods (2005 vs 2006). All fluoroquinolones with at least ten reports per year were included in the analysis. On the basis of 272 reports (532 single ADRs or PTs), patients did not show any statistically significant differences between 2005 and 2006 in terms of sex, age and number of concurrent medications. After adjustment for drug consumption, moxifloxacin showed the highest reporting rate (84.6 reports/DDD/1000 inhabitants/day; 15.4 serious reports/DDD/1000 inhabitants/day) followed by prulifloxacin (72.2; 22.2 serious) and levofloxacin (55.3; 30.6 serious) in 2005. An increment of ADR/report rates was observed over the 2 years for all fluoroquinolones except prulifloxacin, which had the lowest ADR reporting rate in 2006 (25.0; 12.5 serious). In 2006, the rate of serious ADRs associated with prulifloxacin was lower than with ciprofloxacin, while in 2005 serious events were almost equal for both compounds (55.6 vs 47.6 serious ADRs/DDD/1000 inhabitants/day). Ciprofloxacin showed the highest proportion of
Aagaard, Lise; Hansen, Ebba Holme
Background Despite surveillance efforts, unexpected and serious adverse drug reactions (ADRs) repeatedly occur after marketing. The aim of this article is to analyse ADRs reported by available ADR signal detection approaches and to explore which information about new and unexpected ADRs these approaches have detected. Methods We selected three therapeutic cases for the review: antibiotics for systemic use, non-steroidal anti-inflammatory medicines (NSAID) and selective serotonin re-uptake inhibitors (SSRI). These groups are widely used and represent different therapeutic classes of medicines. The ADR studies were identified through literature search in Medline and Embase. The search was conducted in July 2007. For each therapeutic case, we analysed the time of publication, the strengths of the evidence of safety in the different approaches, reported ADRs and whether the studies have produced new information about ADRs compared to the information available at the time of marketing. Results 79 studies were eligible for inclusion in the analysis: 23 antibiotics studies, 35 NSAID studies, 20 SSRI studies. Studies were mainly published from the end of the 1990s and onwards. Although the drugs were launched in different decades, both analytical and observational approaches to ADR studies were similar for all three therapeutic cases: antibiotics, NSAIDs and SSRIs. The studies primarily dealt with analyses of ADRs of the type A and B and to a lesser extent C and D, cf. Rawlins' classification system. The therapeutic cases provided similar results with regard to detecting information about new ADRs despite different time periods and organs attacked. Approaches ranging higher in the evidence hierarchy provided information about risks of already known or expected ADRs, while information about new and previously unknown ADRs was only detected by case reports, the lowest ranking approach in the evidence hierarchy. Conclusion Although the medicines were launched in different
Aagaard, Lise; Hansen, Ebba Holme
Despite surveillance efforts, unexpected and serious adverse drug reactions (ADRs) repeatedly occur after marketing. The aim of this article is to analyse ADRs reported by available ADR signal detection approaches and to explore which information about new and unexpected ADRs these approaches have detected. We selected three therapeutic cases for the review: antibiotics for systemic use, non-steroidal anti-inflammatory medicines (NSAID) and selective serotonin re-uptake inhibitors (SSRI). These groups are widely used and represent different therapeutic classes of medicines. The ADR studies were identified through literature search in Medline and Embase. The search was conducted in July 2007. For each therapeutic case, we analysed the time of publication, the strengths of the evidence of safety in the different approaches, reported ADRs and whether the studies have produced new information about ADRs compared to the information available at the time of marketing. 79 studies were eligible for inclusion in the analysis: 23 antibiotics studies, 35 NSAID studies, 20 SSRI studies. Studies were mainly published from the end of the 1990s and onwards. Although the drugs were launched in different decades, both analytical and observational approaches to ADR studies were similar for all three therapeutic cases: antibiotics, NSAIDs and SSRIs. The studies primarily dealt with analyses of ADRs of the type A and B and to a lesser extent C and D, cf. Rawlins' classification system. The therapeutic cases provided similar results with regard to detecting information about new ADRs despite different time periods and organs attacked. Approaches ranging higher in the evidence hierarchy provided information about risks of already known or expected ADRs, while information about new and previously unknown ADRs was only detected by case reports, the lowest ranking approach in the evidence hierarchy. Although the medicines were launched in different decades, approaches to the ADR studies
Kovarikova, Petra; Pasakova-Vrbatova, Ivana; Vavrova, Anna; Stariat, Jan; Klimes, Jiri; Simunek, Tomas
Dexrazoxane (DEX) is the only clinically used drug effective against anthracycline-induced cardiotoxicity and extravasation injury. However, the mechanism of its cardioprotective action still remains elusive. This paucity of comprehensive data is at least partially caused by the analytical difficulties associated with selective and sensitive simultaneous determination of the parent drug and its putative active metabolite ADR-925 in the relevant biological material. The aim of this study was to develop and validate the first LC-MS/MS method for simultaneous determination of DEX and ADR-925 in the isolated rat neonatal ventricular cardiomyocytes (NVCMs) and the cell culture medium. The analysis was performed on a Synergi Polar-RP column using the gradient profile of the mobile phase composed of 2mM ammonium formate and methanol. Electrospray ionization and ion trap mass analyzer were used as ionization and detection techniques, respectively. NVCMs were precipitated with methanol and the cell culture medium samples were diluted with the same solvent prior the LC-MS/MS analysis. The method was validated within the range of 4-80pmol/10(6) NVCMs and 7-70pmol/10(6) NVCMs for DEX and ADR-925, respectively, and at the concentrations of 8-100μM for both compounds in the culture cell medium. The practical applicability of this method was confirmed by the pilot analysis of NVCMs and the corresponding cell medium samples from relevant in vitro experiment. Hence, the LC-MS/MS method developed in this study represents a modern analytical tool suitable for investigation of DEX bioactivation inside the cardiomyocytes. In addition, the basic utility of the method for the analysis of DEX and ADR-925 in plasma samples was proved in a pilot experiment. Copyright © 2013 Elsevier B.V. All rights reserved.
Objective Automatic detection of Adverse Drug Reaction (ADR) mentions from text has recently received significant interest in pharmacovigilance research. Current research focuses on various sources of text-based information, including social media — where enormous amounts of user posted data is available, which have the potential for use in pharmacovigilance if collected and filtered accurately. The aims of this study are: (i) to explore natural language processing approaches for generating useful features from text, and utilizing them in optimized machine learning algorithms for automatic classification of ADR assertive text segments; (ii) to present two data sets that we prepared for the task of ADR detection from user posted internet data; and (iii) to investigate if combining training data from distinct corpora can improve automatic classification accuracies. Methods One of our three data sets contains annotated sentences from clinical reports, and the two other data sets, built in-house, consist of annotated posts from social media. Our text classification approach relies on generating a large set of features, representing semantic properties (e.g., sentiment, polarity, and topic), from short text nuggets. Importantly, using our expanded feature sets, we combine training data from different corpora in attempts to boost classification accuracies. Results Our feature-rich classification approach performs significantly better than previously published approaches with ADR class F-scores of 0.812 (previously reported best: 0.770), 0.538 and 0.678 for the three data sets. Combining training data from multiple compatible corpora further improves the ADR F-scores for the in-house data sets to 0.597 (improvement of 5.9 units) and 0.704 (improvement of 2.6 units) respectively. Conclusions Our research results indicate that using advanced NLP techniques for generating information rich features from text can significantly improve classification accuracies over existing
Gyllensten, Hanna; Rehnberg, Clas; Jönsson, Anna K; Petzold, Max; Carlsten, Anders; Andersson Sundell, Karolina
Objectives To estimate the cost of illness (COI) of individuals with self-reported adverse drug events (ADEs) from a societal perspective and to compare these estimates with the COI for individuals without ADE. Furthermore, to estimate the direct costs resulting from two ADE categories, adverse drug reactions (ADRs) and subtherapeutic effects of medication therapy (STE). Design Cross-sectional study. Setting The adult Swedish general population. Participants The survey was distributed to a random sample of 14 000 Swedish residents aged 18 years and older, of which 7099 responded, 1377 reported at least one ADE and 943 reported an ADR or STE. Main outcome measures Societal COI, including direct and indirect costs, for individuals with at least one self-reported ADE, and the direct costs for prescription drugs and healthcare use resulting from self-reported ADRs and STEs were estimated during 30 days using a bottom-up approach. Results The economic burden for individuals with ADEs were (95% CI) 442.7 to 599.8 international dollars (Int$), of which direct costs were Int$ 279.6 to 420.0 (67.1%) and indirect costs were Int$ 143.0 to 199.8 (32.9%). The average COI was higher among those reporting ADEs compared with other respondents (COI: Int$ 442.7 to 599.8 versus Int$ 185.8 to 231.2). The COI of respondents reporting at least one ADR or STE was Int$ 468.9 to 652.9. Direct costs resulting from ADRs or STEs were Int$ 15.0 to 48.4. The reported resource use occurred both in hospitals and outside in primary care. Conclusions Self-reported ADRs and STEs cause resource use both in hospitals and in primary care. Moreover, ADEs seem to be associated with high overall COI from a societal perspective when comparing respondents with and without ADEs. There is a need to further examine this relationship and to study the indirect costs resulting from ADEs. PMID:23794552
Njuguna, Christine; Stewart, Annemie; Mouton, Johannes P.; Blockman, Marc; Maartens, Gary; Swart, Annoesjka; Chisholm, Briony; Jones, Jackie; Dheda, Mukesh; Igumbor, Ehimario U.
Introduction The National HIV & Tuberculosis Health Care Worker (HCW) Hotline provides advice on the management of suspected adverse drug reactions (ADRs). We describe suspected ADRs reported to the hotline by HCWs, concordance with advice, and patient outcomes. Methods We reviewed suspected ADRs in HIV-infected patients, patients taking antiretrovirals and patients taking anti-tuberculosis therapy reported from May 2013 to October 2014. We performed causality assessment using the World Health Organization Uppsala Monitoring Centre (WHO-UMC) criteria. We included suspected ADRs categorized as certain, probable or possible in further analysis. Results We received 772 ADR reports, of which 87/772 (11.3 %) were classified as certain, 176/772 (22.8 %) as probable, 361/772 (46.8 %) as possible, and 148/772 (19.2 %) as unlikely or unassessable. The most frequent ADRs were rash, drug-induced liver injury (DILI) and kidney injury, comprising 110/624 (17.6 %), 87/624 (13.9 %), and 77/624 (12.3 %), respectively. The ADR was severe in 27.3 % of rashes, 36.4 % of kidney injury reports and 88.5 % of DILI reports. Most frequently implicated drugs, either alone or in combination with other potentially causative drugs, were efavirenz (rashes), efavirenz and anti-tuberculosis drugs (DILI) and tenofovir (kidney injury). In 383 cases with HCW follow-up, 254 (66.3 %) improved, 9 (2.3 %) had complete resolution, 32 (8.4 %) remained unchanged, 6 (1.6 %) deteriorated, 10 (2.6 %) died and 72 (18.8 %) had unknown outcome. Advice provided was followed in 93.2 % of these cases. Of 223 ADRs with preventability data, 40 (17.9 %) were preventable. Conclusion Queries about rashes, DILIs and kidney injuries were common. Detection and management of these ADRs should be included in HCW training. In cases with follow-up, concordance with advice was high, and HCWs reported improvement in the majority. PMID:26547719
Danza, Alvaro; López, Maynés; Vola, Magdalena; Alvarez-Rocha, Alfredo
Adverse cutaneous reactions to Drugs (CDRs) are of particular interest among all adverse Drug reactions (ADR) due to their frequency, potential severity and because of the importance of an early diagnosis. Antimicrobial agents, anticonvulsants and non-steroidal anti-inflammatory Drugs are the Drugs associated to the highest risk of CDRs. To assess CDRs in hospitalized patients and identify the Drugs involved. All patients hospitalized in the Hospital de Clínicas in Montevideo, Uruguay, with suspected CDRs, detected during one year, were included in this prospective study. The imputability was established using the Karch and Lasagna algorithm modified by Naranjo. We analyzed age, gender, Drugs involved, causal disease, severity, latency and evolution. Seventeen patients, aged 17 to 85 years (15 females) with CDRs were identifed. Twelve had morbilliform exanthemas, four had reactions with eosinophilia and systemic symptoms and one had a Stevens Johnson syndrome. The Drugs involved were antimicrobials in nine cases, hypouricemic agents in four cases, anticonvulsants in three cases and aspartic insulin in one. Twelve patients had a life threatening reaction and one required admission to the intensive care unit. No deaths occurred. CDRs were more common in women and most of them were caused by antimicrobial agents.
Pan, Jian-Bo; Ji, Nan; Pan, Wen; Hong, Ru; Wang, Hao; Ji, Zhi-Liang
Drugs may induce adverse drug reactions (ADRs) when they unexpectedly bind to proteins other than their therapeutic targets. Identification of these undesired protein binding partners, called off-targets, can facilitate toxicity assessment in the early stages of drug development. In this study, a computational framework was introduced for the exploration of idiosyncratic mechanisms underlying analgesic-induced severe adverse drug reactions (SADRs). The putative analgesic-target interactions were predicted by performing reverse docking of analgesics or their active metabolites against human/mammal protein structures in a high-throughput manner. Subsequently, bioinformatics analyses were undertaken to identify ADR-associated proteins (ADRAPs) and pathways. Using the pathways and ADRAPs that this analysis identified, the mechanisms of SADRs such as cardiac disorders were explored. For instance, 53 putative ADRAPs and 24 pathways were linked with cardiac disorders, of which 10 ADRAPs were confirmed by previous experiments. Moreover, it was inferred that pathways such as base excision repair, glycolysis/glyconeogenesis, ErbB signaling, calcium signaling, and phosphatidyl inositol signaling likely play pivotal roles in drug-induced cardiac disorders. In conclusion, our framework offers an opportunity to globally understand SADRs at the molecular level, which has been difficult to realize through experiments. It also provides some valuable clues for drug repurposing. - Highlights: • A novel computational framework was developed for mechanistic study of SADRs. • Off-targets of drugs were identified in large scale and in a high-throughput manner. • SADRs like cardiac disorders were systematically explored in molecular networks. • A number of ADR-associated proteins were identified.
Wing, S S; Fantus, I G
Propylthiouracil and methimazole are frequently used in the management of hyperthyroidism. Two patients in whom adverse immunologic effects other than isolated agranulocytosis developed during treatment with propylthiouracil are described. A review of the literature revealed 53 similar cases over a 35-year period. Rash, fever, arthralgias and granulocytopenia were the most common manifestations. Vasculitis, particularly with cutaneous manifestations, occurs and may be fatal. The clinical evidence suggests that an immunologic mechanism is involved. A number of different autoantibodies were reported, but antinuclear antibodies were infrequent, and none of the cases met the criteria for a diagnosis of systemic lupus erythematosus. Thus, the reactions do not represent a true drug-induced lupus syndrome. Current hypotheses and experimental data regarding the cause of the reactions are reviewed. No specific clinical subgroup at high risk can be identified, and manifestations may occur at any dosage and at any time during therapy. Cross-reactivity between the two antithyroid drugs can be expected. Except for minor symptoms (e.g., mild arthralgias or transient rash), such reactions are an indication for withdrawal of the drug and the use of alternative methods to control the hyperthyroidism. In rare cases of severe vasculitis a short course of high-dose glucocorticoid therapy may be helpful. PMID:3539299
Iten, F; Reichling, J; Saller, R
The significantly increased sales figures many phytopharmaceuticals have achieved during the last years prove the confidence that a great part of the population has in herbal remedies. This is primarily due to the wide-spread opinion that herbal remedies are free from side-effects. The long tradition and presumed 'natural' origin are no guarantee for safety in the treatment with herbal remedies. Even if a large proportion of the undesirable events is traceable to falsifications, impurities and lacking quality controls, herbal drugs with controlled quality should not be generally classified as harmless. In the meantime it has been possible to prove the presence of active substances with toxic and cancerogenic properties in various phytopharmaceuticals. Interactions with other drugs have been documented in a number of notes, where phytopharmaceuticals could influence the blood plasma level of various drugs, presumably by activating or inhibiting the cytochrom-P450-system. At present, especially data about adverse effects during long-term administration of herbal remedies are under-represented. Particularly because of their presumed harmlessness they often are prescribed in the case of chronic diseases and then taken over a longer period of time. The frequency of undesirable effects of phytopharmaceuticals is remarkably low, even if the present lack of data about side-effects is considered.
Hoigné, R; Lawson, D H; Weber, E
Age by itself is not an important risk factor for ADRs. Age-related changes are the consequence of a number of individual factors, for example morbidity associated with polypharmacy, decline in renal or liver function in the elderly, hypoalbuminaemia, reduced body weight, etc. The relationship between gastrointestinal bleeding and non-steroidal anti-inflammatory drugs can be assessed globally in large cohort studies with access to computerized data, but complete accuracy requires access to the original patient records. The increase in the risk of GI bleeding in users of NSAIDs and aspirin was 50% above that in non-users. About a quarter of ADRs in hospitalized patients seem not to arise from purely pharmacological mechanisms. They are mainly due to allergic, anaphylactoid, or idiosyncratic reactions and to intolerance. In such non-pharmacological reactions, the time of exposure, reaction time, and even dosage may be important factors in identification of the causal drug. The use of benzodiazepines can be optimized by taking into account potency, time of action and the different syndromes encountered after withdrawal. Following long-term use problems of relapse and rebound are being increasingly recognized, in addition to organic withdrawal symptoms. In psychiatric patients extrapyramidal disorders due to neuroleptics are common. The rates of these ADRs differ markedly between various drugs, even after dosages and co-medications are taken into account. Epidemiological screening for potentially carcinogenic drugs can only be done in large cohorts of patients with pre-recorded full information sets as may be found in an HMO (Health Maintenance Organization). The findings of several such studies have been published in specialist cancer journals.(ABSTRACT TRUNCATED AT 250 WORDS)
Patadia, Vaishali K; Coloma, Preciosa; Schuemie, Martijn J; Herings, Ron; Gini, Rosa; Mazzaglia, Giampiero; Picelli, Gino; Fornari, Carla; Pedersen, Lars; van der Lei, Johan; Sturkenboom, Miriam; Trifirò, Gianluca
A prospective pharmacovigilance signal detection study, comparing the real-world healthcare data (EU-ADR) and two spontaneous reporting system (SRS) databases, US FDA's Adverse Event Reporting System and WHO's Vigibase is reported. The study compared drug safety signals found in the EU-ADR and SRS databases. The potential for signal detection in the EU-ADR system was found to be dependent on frequency of the event and utilization of drugs in the general population. The EU-ADR system may have a greater potential for detecting signals for events occurring at higher frequency in general population and those that are commonly not considered as potentially a drug-induced event. Factors influencing various differences between the datasets are discussed along with potential limitations and applications to pharmacovigilance practice.
Barnes, Joanne; Mills, Simon Y; Abbot, Neil C; Willoughby, Martin; Ernst, Edzard
Aims To determine whether adverse drug reactions (ADRs) to herbal remedies would be reported differently from similar ADRs to conventional over-the-counter (OTC) medicines by herbal-remedy users. Methods Face-to-face interviews (using a structured questionnaire) with 515 users of herbal remedies were conducted in six pharmacy stores and six healthfood stores in the UK. The questionnaire focused on the likely course of action taken by herbal-remedy users after experiencing an ADR associated with a conventional OTC medicine and a herbal remedy. Results Following a ‘serious’ suspected ADR, 156 respondents (30.3%) would consult their GP irrespective of whether the ADR was associated with the use of a herbal remedy or a conventional OTC medicine, whereas 221 respondents (42.9%) would not consult their GP for a serious ADR associated with either type of preparation. One hundred and thirty-four respondents (26.0%) would consult their GP for a serious ADR to a conventional OTC medicine, but not for a similar ADR to a herbal remedy, whereas four respondents (0.8%) would consult their GP for a serious ADR to a herbal remedy, but not for a similar ADR to a conventional OTC medicine. Similar differences were found in attitudes towards reporting ‘minor’ suspected ADRs. Conclusions Consumers of herbal remedies would act differently with regard to reporting an ADR (serious or minor) to their GP depending on whether it was associated with a herbal remedy or a conventional OTC medicine. This has implications for herbal pharmacovigilance, particularly given the increasing use of OTC herbal remedies. The finding that a high proportion of respondents would not consult their GP or pharmacist following ADRs to conventional OTC medicines is also of concern. PMID:9643624
Mudzviti, Tinashe; Maponga, Charles C.; Khoza, Star; Ma, Qing; Morse, Gene D.
Background. The main objective was to determine the impact of herbal drug use on adverse drug reactions in patients on antiretroviral therapy (ART). Methodology. Patients receiving first-line ART from the national roll-out program participated in this cross-sectional study. Participants were interviewed and a data collection sheet was used to collect information from the corresponding medical record. Results. The majority (98.2%) of participants were using at least one herbal drug together with ART. The most common herbal remedies used were Allium Sativum (72.7%), Bidens pilosa (66.0%), Eucalyptus globulus (52.3%), Moringa oleifera (44.1%), Lippia javanica (36.3%), and Peltoforum africanum (34.3%). Two indigenous herbs, Musakavakadzi (OR = 0.25; 95% CI 0.076–0.828) and Peltoforum africanum (OR = 0.495; 95% CI 0.292–0.839) reduced the occurrence of adverse drug events. Conclusions. The use of herbal drugs is high in the HIV-infected population and there is need for pharmacovigilance programs to recognize the role they play in altering ADR profiles. PMID:22506106
Charoenchokthavee, Wanaporn; Ayudhya, Duangchit Panomvana Na; Sriuranpong, Virote; Areepium, Nutthada
Tamoxifen is a pharmacological estrogen inhibitor that binds to the estrogen receptor (ER) in breast cells. However, it shows an estrogenic effect in other organs, which causes adverse drug reactions (ADRs). The sulfotransferase 1A1 (SULT1A1) enzyme encoded by the SULT1A1 gene is involved in estrogen metabolism. Previous research has suggested that the SULT1A1 copy number is linked with the plasma estradiol (E2) concentration. Here, a total of 34 premenopausal breast cancer patients, selected from the Thai Tamoxifen (TTAM) Project, were screened for their SULT1A1 copy number, plasma E2 concentration and ADRs. The mean age was 44.3±11.1 years, and they were subtyped as ER+/ progesterone receptor (PR) + (28 patients), ER+/ PR- (5 patients) and ER-/PR- (1 patient). Three patients reported ADRs, which were irregular menstruation (2 patients) and vaginal discharge (1 patient). Most (33) patients had two SULT1A1 copies, with one patient having three copies. The median plasma E2 concentration was 1,575.6 (IQR 865.4) pg/ml. Patients with ADRs had significantly higher plasma E2 concentrations than those patients without ADRs (p = 0.014). The plasma E2 concentration was numerically higher in the patient with three SULT1A1 copies, but this lacked statistical significance.
Ji, Qian; Qiu, Liyan
Chemotherapy is one of the main strategies for cancer treatment, but its effective application is seriously limited by the development of drug resistance. In this study, we designed micellar vectors for doxorubicin based on amphiphilic copolymers sequentially linking β-cyclodextrin (β-CD), polylacticacid (PLA) or polycaprolactone (PCL) block, and polyethylene glycol (PEG) block to overcome drug resistance in human acute myeloid leukemia cells (HL60/ADR) overexpressing multidrug resistance protein 1 (MRP1). The significant enhancement in cytotoxicity and inhibited HL60/ADR tumor growth in mouse was achieved. More importantly, several analyses were performed to understand the interactions between various polymers and MRP1 at the cellular level. The results showed that the polymers did not show remarkable correlation of MRP1 gene and protein expression, but could decrease intracellular ATP, mitochondrial membrane potential and glutathione levels, which was greatly dependent on the molecular structure of polymers. In conclusion, these novel micelles can be considered as a kind of promising drug delivery system for tumor therapy to reverse drug resistance related to MRP1 overexpression. Copyright © 2016 Elsevier B.V. All rights reserved.
Sammons, Helen M.; Choonara, Imti
Drug toxicity is, unfortunately, a significant problem in children both in the hospital and in the community. Drug toxicity in children is different to that seen in adults. At least one in 500 children will experience an adverse drug reaction each year. For children in hospital, the risk is far greater (one in ten). Additionally, different and sometimes unique adverse drug reactions are seen in the paediatric age groups. Some of the major cases of drug toxicity historically have occurred in neonates. It is important that we understand the mechanism of action of adverse drug reactions. Greater understanding alongside rational prescribing should hopefully reduce drug toxicity in children in the future. PMID:27417239
Herdeiro, María T; Polonia, Jorge; Gestal-Otero, Juan J; Figueiras, Adolfo
The spontaneous reporting of adverse drug reactions (ADRs) through the yellow card and made concrete by the knowledge and attitudes of doctors, has been rousing a great deal of bibliographical interest in recent years. However, there does not seem to be any actual revision in the theme on which the theoretical models that explain the process of decision in reporting are proposed. In this work an explanatory model of the factors that condition reporting is proposed and a revision of the literature on the subject has also been carried out. The proposed model is centralized in the medical professional and it considers the habit of reporting as the result of the doctor's formation and his interaction with the environment. The combination of knowledge-attitudes-practices and the theory of the satisfaction of needs seemed very adequate for ADR systematization. The results also indicate that, to improve the participation of health professionals in surveillance systems through spontaneous reporting, it might be necessary to design combined strategies that modify both intrinsic (knowledge, attitudes) and extrinsic (relationship between health professionals and their patients, the national health system and pharmaceutical companies) factors.
Bousquet, Cédric; Sadou, Éric; Souvignet, Julien; Jaulent, Marie-Christine; Declerck, Gunnar
Although MedDRA has obvious advantages over previous terminologies for coding adverse drug reactions and discovering potential signals using data mining techniques, its terminological organization constrains users to search terms according to predefined categories. Adding formal definitions to MedDRA would allow retrieval of terms according to a case definition that may correspond to novel categories that are not currently available in the terminology. To achieve semantic reasoning with MedDRA, we have associated formal definitions to MedDRA terms in an OWL file named OntoADR that is the result of our first step for providing an "ontologized" version of MedDRA. MedDRA five-levels original hierarchy was converted into a subsumption tree and formal definitions of MedDRA terms were designed using several methods: mappings to SNOMED-CT, semi-automatic definition algorithms or a fully manual way. This article presents the main steps of OntoADR conception process, its structure and content, and discusses problems and limits raised by this attempt to "ontologize" MedDRA.
Souvignet, Julien; Asfari, Hadyl; Declerck, Gunnar; Lardon, Jérémy; Trombert-Paviot, Béatrice; Jaulent, Marie-Christine; Bousquet, Cédric
Evaluation and validation have become a crucial problem for the development of semantic resources. We developed Ci4SeR, a Graphical User Interface to optimize the curation work (not taking into account structural aspects), suitable for any type of resource with lightweight description logic. We tested it on OntoADR, an ontology of adverse drug reactions. A single curator has reviewed 326 terms (1020 axioms) in an estimated time of 120 hours (2.71 concepts and 8.5 axioms reviewed per hour) and added 1874 new axioms (15.6 axioms per hour). Compared with previous manual endeavours, the interface allows increasing the speed-rate of reviewed concepts by 68% and axiom addition by 486%. A wider use of Ci4SeR would help semantic resources curation and improve completeness of knowledge modelling.
Pan, Xia; Yang, Xiaoyan; Zang, Jinglei; Zhang, Si; Huang, Nan; Guan, Xinxin; Zhang, Jianhua; Wang, Zhihui; Li, Xi; Lei, Xiaoyong
Overexpression of adenosine triphosphate-binding cassette (ABC) transport protein is emerging as a critical contributor to anticancer drug resistance. The eukaryotic translation initiation factor (eIF) 4F complex, the key modulator of mRNA translation, is regulated by the phosphoinositide 3-kinase-AKT-mammalian target of rapamycin pathway in anticancer drug-resistant tumors. The present study demonstrated the roles of ABC translation protein alterations in the acquisition of the Adriamycin (ADM)-resistant phenotype of MCF-7 human breast cells. Quantitative polymerase chain reaction and western blot analysis were applied to examine the differences in mRNA and protein levels, respectively. It was found that the expression of the ABC sub-family B member 1, ABC sub-family C member 1 and ABC sub-family G member 2 transport proteins were upregulated in MCF-7/ADR cells. An MTT assay was used to detect the cell viability, from the results MCF-7/ADR cells were less sensitive to ADM, tamoxifen (TAM) and taxol (TAX) treatment compared with MCF-7 cells. We predicted that the 3'-untranslated region of eukaryotic translation initiation factor 4-γ 1 (eIF4G) contains a potential miRNA binding site for microRNA (miR)-503 through using computational programs. These binding sites were confirmed by luciferase reporter assays. eIF4G mRNA degradation was accelerated in cells transfected with miR-503 mimics. Furthermore, it was demonstrated that eIF4G and ABC translation proteins were significantly downregulated in MCF-7/ADR cells after transfection with miR-503. It was found that miR-503 mimics could sensitize the cells to treatment with ADM, TAM and TAX. These findings demonstrated for the first time that eIF4G acted as a key factor in MCF-7/ADR cells, and may be an efficient agent for preventing and reversing multi-drug resistance in breast cancer.
Wahab, Izyan A; Pratt, Nicole L; Wiese, Michael D; Kalisch, Lisa M; Roughead, Elizabeth E
To determine the validity of sequence symmetry analysis (SSA) method to detect adverse drug reactions from an administrative claims database. Published randomised controlled trials (RCTs) of 19 medicines were identified through search databases, product information (PI) or the US Food and Drug Administration Web site. All adverse events (AEs) in the RCTs and the PI for the medicines were extracted. AEs were considered 'gold standard positive events' if they were reported as being statistically significant events in adequately powered RCTs. The remaining AEs were considered 'gold standard negative events' if the event was not listed as an AE in the PI for that medicine or any other medicine in its class. Indicators of AEs were identified by consensus from two clinical researchers. SSA was run for each medicine-indicator pair using four different time windows: 3, 6, 9 and 12 months. A total of 120 randomised placebo controlled trials were reviewed for the 19 tested medicines. A total of 165 medicine-indicator pairs (44 positive and 121 negative events) were identified and tested by SSA. At the 12-month time window, the sensitivity, specificity, positive and negative predictive values of SSA were 61% (95%CI 0.46-0.74), 93% (95%CI 0.87-0.96), 77% (95%CI 0.61-0.88) and 87% (95%CI 0.80-0.92), respectively. Using a 3-month time window, the SSA had a lower sensitivity (52%). The SSA technique was found to have moderate sensitivity and high specificity for detecting ADRs. These results suggest that SSA is a potential tool for detecting ADRs using administrative claims data that could complement existing pharmacosurveillance methods. Copyright © 2013 John Wiley & Sons, Ltd.
Issa, Amalia M
The problem of adverse drug reactions is a well-documented global public health problem. Recent withdrawals of several widely used prescription medications in the USA and other countries have raised concerns among patients, clinicians, scientists and policy makers. The increasing interest and concern regarding withdrawal of previously approved prescription medications and drug safety has prompted renewed research efforts aimed at improving surveillance of approved drugs and reducing adverse drug reactions. Pharmacogenomics research is increasingly directed at developing genomic diagnostics and tests with predictive ability for adverse drug reactions. This paper focuses on the problem of adverse drug reactions and reviews the evidence and the state of the science for the application of pharmacogenomics to adverse drug reactions.
Liabeuf, Sophie; Masmoudi, Kamel; Scailteux, Lucie-Marie; Moragny, Julien; Masson, Henri; Brnet-Dufour, Valérie; Andrejak, Michel; Gras-Champel, Valérie
Abstract Although drug therapy is inherently associated with the risk of adverse drug reactions (ADRs), some of these events are preventable. The estimated proportion of preventable ADRs varies from one study or clinical context to another. Bleeding caused by antithrombotic agents (and particularly vitamin K antagonists, VKAs) constitutes one of the most frequent causes of ADR-related hospitalization. Hence, the objective of the present study was to adapt and validate an ADR preventability score for bleeding due to VKAs and evaluate the preventability of bleeding in 906 consecutive hospitalized, VKA-treated adult patients with a risk of major bleeding (defined as an international normalized ratio ≥5) over a 2-year period. A specific preventability scale for VKA-associated bleeding was developed by adapting a published tool. Overall, 241 of the 906 patients in the study experienced at least 1 VKA-associated bleeding event. The scale's reliability was tested by 2 different evaluators. The inter-rater reliability (evaluated by calculation of Cohen's kappa) ranged from “good” to “excellent.” Lastly, the validated scale was used to assess the preventability of the VKA-associated bleeding. We estimated that bleeding was preventable or potentially preventable in 109 of the 241 affected patients (45.2%). We have developed a useful, reliable tool for evaluating the preventability of VKA-associated bleeding. Application of the scale in a prospective study revealed that a high proportion of VKA-associated bleeding events in hospitalized, at-risk adult patients were preventable or potentially preventable. PMID:27684801
Sam, Aaseer Thamby; Lian Jessica, Looi Li; Parasuraman, Subramani
To retrospectively determine the extent and types of adverse drug events (ADEs) from the patient cases sheets and identify the contributing factors of medication errors. To assess causality and severity using the World Health Organization (WHO) probability scale and Hartwig's scale, respectively. Hundred patient case sheets were randomly selected, modified version of the Institute for Healthcare Improvement (IHI) Global Trigger Tool was utilized to identify the ADEs; causality and severity were calculated utilizing the WHO probability scale and Hartwig's severity assessment scale, respectively. In total, 153 adverse events (AEs) were identified using the IHI Global Trigger Tool. Majority of the AEs are due to medication errors (46.41%) followed by 60 adverse drug reactions (ADRs), 15 therapeutic failure incidents, and 7 over-dose cases. Out of the 153 AEs, 60 are due to ADRs such as rashes, nausea, and vomiting. Therapeutic failure contributes 9.80% of the AEs, while overdose contributes to 4.58% of the total 153 AEs. Using the trigger tools, we were able to detect 45 positive triggers in 36 patient records. Among it, 19 AEs were identified in 15 patient records. The percentage of AE/100 patients is 17%. The average ADEs/1000 doses is 2.03% (calculated). The IHI Global Trigger Tool is an effective method to aid provisionally-registered pharmacists to identify ADEs quicker.
Song, Qin; Chuan, Xingxing; Chen, Binlong; He, Bing; Zhang, Hua; Dai, Wenbing; Wang, Xueqing; Zhang, Qiang
Doxorubicin (DOX) is a potent anticancer drug for the treatment of tumors, but the poor specificity and multi-drug resistance (MDR) on tumor cells have restricted its application. Here, a pH and reduction-responsive peptide-drug conjugate (PDC), pHLIP-SS-DOX, was synthesized to overcome these drawbacks. pH low insertion peptide (pHLIP) is a cell penetrating peptide (CPP) with pH-dependent transmembrane ability. And because of the unique cell membrane insertion pattern, it might reverse the MDR. The cellular uptake study showed that on both drug-sensitive MCF-7 and drug-resistant MCF-7/Adr cells, pHLIP-SS-DOX obviously facilitated the uptake of DOX at pH 6.0 and the uptake level on MCF-7/Adr cells was similar with that on MCF-7 cells, indicating that pHLIP-SS-DOX had the ability to target acidic tumor cells and reverse MDR. In vitro cytotoxicity study mediated by GSH-OEt demonstrated that the cytotoxic effect of pHLIP-SS-DOX was reduction responsive, with obvious cytotoxicity at pH 6.0; while it had poor cytotoxicity at pH 7.4, no matter with or without GSH-OEt pretreatment. This illustrated that pHLIP could deliver DOX into tumor cells with acidic microenvironment specifically and could not deliver drugs into normal cells with neutral microenvironment. In summary, pHLIP-SS-DOX is a promising strategy to target drugs to tumors and provides a possibility to overcome MDR.
Clarke, Janet B
Biologics encompass a broad range of therapeutics that include proteins and other products derived from living systems. Although the multiplicity of target organs often seen with new chemical entities is generally not seen with biologics, they can produce significant adverse reactions. Examples include IL-12 and an anti-CD28 antibody that resulted in patient deaths and/or long stays in intensive care units. Mechanisms of toxicities can be categorized as pharmacological or nonpharmacological, with most, excepting hypersensitivity reactions, associated with the interaction of the agent with its planned target. Unexpected toxicities generally arise as a result of previously unknown biology. Manufacturing quality is a significant issue relative to the toxicity of biologics. The development of recombinant technology represented the single biggest advance leading to humanized products with minimal or no contaminants in comparison to products purified from animal tissues. Nevertheless, the type of manufacturing process including choice of cell type, culture medium, and purification method can result in changes to the protein. For example, a change to the closure system for erythropoietin led to an increase in aplastic anemia as a result of changing the immunogenicity characteristics of the protein. Monoclonal antibodies represent a major class of successful biologics. Toxicities associated with these agents include those associated with the binding of the complementary determining region (CDR) with the target. First dose reactions or infusion reactions are generally thought to be mediated via the Fc region of the antibody activating cytokine release, and have been observed with several antibodies. Usually, these effects (flu-like symptoms, etc.) are transient with subsequent dosing. Although biologics can have nonpharmacologic toxicities, these are less common than with small molecule drugs.
Hammann, Felix; Drewe, Juergen
Patients, in particular elderly ones, frequently receive more than one drug at a time. With each drug added to a regime, the number of potential drug-drug interactions (DDIs) increases by a power law. Early prediction of relevant interactions by computerized tools greatly aids clinicians and can guide their prescribing choices. In this article, we discuss different types of DDIs, on which levels they can arise and what efforts have been made in the past to detect and predict them. The emphasis is on data mining technology and network analysis, but overlaps with traditional pharmacovigilance are also discussed. Finally, we discuss strategies to focus and simplify mining efforts to get meaningful results with less effort. The necessary technology for detecting adverse DDIs exists and is quite refined, although it is more often implied in lower risk scenarios (such as syntactic analysis in web searches and online libraries). Data mining for DDIs, on the other hand, still requires a great deal of human intervention, not only to validate the results but also, more importantly, to separate the relevant from the spurious. The fields of network analysis and graph theory show great promise but have not yet shown much beyond descriptive analyses.
Gallelli, Luca; Gallelli, Giuseppe; Codamo, Giuseppe; Argentieri, Angela; Michniewicz, Andzelika; Siniscalchi, Antonio; Stefanelli, Roberta; Cione, Erika; Caroleo, Maria C; Longo, Paola; De Sarro, Giovambattista
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.
Sauer, Brian; Nebeker, Jonathan; Shen, Shuying; Rupper, Randall; West, Suzanne; Shinogle, Judith A; Xu, Wu; Lohr, Kathleen N; Samore, Matthew
We present a framework for detecting possible adverse drug reactions (ADRs) using the Utah Medicaid administrative data. We examined four classes of ADRs associated with treatment of dementia by acetylcholinesterase inhibitors (AChEIs): known reactions (gastrointestinal, psychological disturbances), potential reactions (respiratory disturbance), novel reactions (hepatic, hematological disturbances), and death. Our cohort design linked drug utilization data to medical claims from Utah Medicaid recipients. We restricted the analysis to 50 years-old and older beneficiaries diagnosed with dementia-related diseases. We compared patients treated with AChEI to patients untreated with anti-dementia medication therapy. We attempted to remove confounding by establishing propensity-score-matched cohorts for each outcome investigated; we then evaluated the effects of drug treatment by conditional multivariable Cox-proportional-hazard regression. Acute and transient effects were evaluated by a crossover design using conditional logistic regression. Propensity-matched analysis of expected reactions revealed that AChEI treatment was associated with gastrointestinal episodes (Hazard Ratio [HR]: 2.02; 95%CI: 1.28-3.2), but not psychological episodes, respiratory disturbance, or death. Among the unexpected reactions, the risk of hematological episodes was higher (HR: 2.32; 95%CI: 1.47-3.6) in patients exposed to AChEI. AChEI exposure was not associated with an increase in hepatic episodes. We also noted a trend, identified in the case-crossover design, toward increase odds of experiencing acute hematological events during AChEI exposure (Odds Ratio: 3.0; 95% CI: 0.97 - 9.3). We observed an expected association between AChEIs treatment and gastrointestinal disturbances and detected a signal of possible hematological ADR after treatment with AChEIs in this pilot study. Using this analytic framework may raise awareness of potential ADEs and generate hypotheses for future investigations
Chee, Brant W; Berlin, Richard; Schatz, Bruce
Adverse drug events (ADEs) remain a large problem in the United States, being the fourth leading cause of death, despite post market drug surveillance. Much post consumer drug surveillance relies on self-reported "spontaneous" patient data. Previous work has performed datamining over the FDA's Adverse Event Reporting System (AERS) and other spontaneous reporting systems to identify drug interactions and drugs correlated with high rates of serious adverse events. However, safety problems have resulted from the lack of post marketing surveillance information about drugs, with underreporting rates of up to 98% within such systems. We explore the use of online health forums as a source of data to identify drugs for further FDA scrutiny. In this work we aggregate individuals' opinions and review of drugs similar to crowd intelligence3. We use natural language processing to group drugs discussed in similar ways and are able to successfully identify drugs withdrawn from the market based on messages discussing them before their removal.
Rolfes, Leàn; van Hunsel, Florence; Taxis, Katja; van Puijenbroek, Eugène
There is little information as to what extent adverse drug reactions (ADRs) influence patients' health-related quality of life (HR-QOL). From a pharmacovigilance perspective, capturing and making the best use of this information remains a challenge. The Netherlands Pharmacovigilance Centre Lareb received about 1800 reports after the packaging of the drug Thyrax(®) (levothyroxine; Aspen Pharma Trading Limited, Dublin, Ireland) changed from a brown glass bottle to a blister package in the Netherlands. The objective of this study was to explore the impact of ADRs on HR-QOL in patients who reported a possible ADR to Lareb in relation to the change in the packaging of the drug Thyrax(®). A secondary objective was to explore factors correlated with change in HR-QOL. Patients who reported an ADR in relation to the Thyrax(®) packaging change were included in this study. A web-based adapted version of the COOP/WONCA questionnaire was sent to explore the HR-QOL before versus during the ADR, expressed on a 5-point scale from no impact (1) to high impact (5). Multivariable linear regression analysis was used to identify factors correlated with change in HR-QOL. Overall, 1167 patients returned the questionnaire (71.2 % response rate). The difference in HR-QOL was -0.8 for physical, -1.2 for mental, -1.4 for daily activities, -1.3 for social, and -1.3 for overall health status (p < 0.001 for each domain). Age, sex, educational level of the patient, and absence from work due to an ADR were correlated with at least one domain, while severity of the ADR was found to be correlated with all domains of HR-QOL. Patients who reported possible ADRs after the Thyrax(®) packaging change experienced a significant decrease in HR-QOL. This impact was highest for the domains 'daily activities', 'overall health status', and 'mental health' and lowest for 'physical fitness'.
Coloma, Preciosa M; Schuemie, Martijn J; Trifirò, Gianluca; Gini, Rosa; Herings, Ron; Hippisley-Cox, Julia; Mazzaglia, Giampiero; Giaquinto, Carlo; Corrao, Giovanni; Pedersen, Lars; van der Lei, Johan; Sturkenboom, Miriam
In this proof-of-concept paper we describe the framework, process, and preliminary results of combining data from European electronic healthcare record (EHR) databases for large-scale monitoring of drug safety. Aggregated demographic, clinical, and prescription data from eight databases in four countries (Denmark, Italy, Netherlands, the UK) were pooled using a distributed network approach by generation of common input data followed by local aggregation through custom-built software, Jerboa(©). Comparison of incidence rates of upper gastrointestinal bleeding (UGIB) and nonsteroidal anti-inflammatory drug (NSAID) utilization patterns were used to evaluate data harmonization and quality across databases. The known association of NSAIDs and UGIB was employed to demonstrate sensitivity of the system by comparing incidence rate ratios (IRRs) of UGIB during NSAID use to UGIB during all other person-time. The study population for this analysis comprised 19,647,445 individuals corresponding to 59,929,690 person-years of follow-up. 39,967 incident cases of UGIB were identified during the study period. Crude incidence rates varied between 38.8 and 109.5/100,000 person-years, depending on country and type of database, while age-standardized rates ranged from 25.1 to 65.4/100,000 person-years. NSAID use patterns were similar for databases within the same country but heterogeneous among different countries. A statistically significant age- and gender-adjusted association between use of any NSAID and increased risk for UGIB was confirmed in all databases, IRR from 2.0 (95%CI:1.7-2.2) to 4.3 (95%CI: 4.1-4.5). Combining data from EHR databases of different countries to identify drug-adverse event associations is feasible and can set the stage for changing and enlarging the scale for drug safety monitoring. Copyright © 2010 John Wiley & Sons, Ltd.
Berger, Seth I.; Iyengar, Ravi
Systems pharmacology involves the application of systems biology approaches, combini