Abstract Adverse Drug Reactions Research Articles

A Qualitative Evaluation of ADR Reporting in India: Non-Regulatory Confronts and Their Possible Solutions

Adverse drug reactions (ADRs) are one of the major causes of mortality as well as morbidity. They do have a substantial influence on human health, lowering quality of life for patients, and increasing morbidity and mortality rates, while also putting a significant financial strain on health-care systems. According to a 1998 study, ADRs are the 4th leading cause of death in the United States, accounting for up to 7 percent on average of all hospitalizations. In India, a similar situation, where physicians' inability to diagnose ADRs has caused a lot of hospitalizations and fatality cases. There are many observational studies and KAP (Knowledge, Attitude, and Practices) studies performed across the country to evaluate this issue, but none has summarized the important points at one platform to give the readers, regulatory agencies, and policymakers an idea to improvise the ADR reporting process. This comprehensive review has revealed a major KAP gap in India, and has summarized the different reasons for this gap, as well as their relevant solutions. The provided solutions help to achieve the sustainable goal of ‘good health and well-being.’

Identifying Adverse Drug Reaction-Related Text from Social Media: A Multi-View Active Learning Approach with Various Document Representations

Adverse drug reactions (ADRs) are a huge public health issue. Identifying text that mentions ADRs from a large volume of social media data is important. However, we need to address two challenges for high-performing ADR-related text detection: the data imbalance problem and the requirement of simultaneously using data-driven information and handcrafted information. Therefore, we propose an approach named multi-view active learning using domain-specific and data-driven document representations (MVAL4D), endeavoring to enhance the predictive capability and alleviate the requirement of labeled data. Specifically, a new view-generation mechanism is proposed to generate multiple views by simultaneously exploiting various document representations obtained using handcrafted feature engineering and by performing deep learning methods. Moreover, different from previous active learning studies in which all instances are chosen using the same selection criterion, MVAL4D adopts different criteria (i.e., confidence and informativeness) to select potentially positive instances and potentially negative instances for manual annotation. The experimental results verify the effectiveness of MVAL4D. The proposed approach can be generalized to many other text classification tasks. Moreover, it can offer a solid foundation for the ADR mention extraction task, and improve the feasibility of monitoring drug safety using social media data.

Drug Allergies

Adverse drug reactions (ADRs) are an important public health problem. An ADR is defined by the World Health Organization as an unintended, noxious response to a drug that occurs at a dose usually tolerated by normal subjects. The classification of ADRs by Rawlins and Thompson divides ADRs into two major subtypes: (1) type A reactions, which are dose dependent and predictable, and (2) type B reactions, which are uncommon and unpredictable. The majority of ADRs are type A reactions, which include four subtypes: overdosage or toxicity, side effects, secondary effects, and interactions. Type B reactions constitute approximately 10 to 15% of all ADRs and include four subtypes: drug intolerance, idiosyncratic reactions, pseudoallergic reactions, and drug hypersensitivity reactions. This chapter reviews the epidemiology of ADRs, risk factors for drug hypersensitivity reactions, the classification of drug reactions, diagnostic tests, reactions to specific drugs, and management of the patient with drug allergy. Figures illustrate drugs as haptens and prohaptens, the Gell and Coombs system, the four basic immunologic mechanisms for drug reactions, the chemical structure of different β-lactam antibiotics, penicillin skin testing, sulfonamide metabolism and haptenation, nonsteroidal antiinflammatory drug effects, and patient management. Tables outline the classification of ADRs, drugs frequently implicated in allergic drug reactions, and reagents and concentrations recommended for prick and intradermal skin testing. This review contains 8 figures, 7 tables, and 60 references. Key Words: Adverse drug reactions, drug hypersensitivity reactions, overdosage, toxicity, Type A reactions, Type B reactions, human leukocyte antigen, pruritus, angioedema, urticarial, bronchospasm, laryngeal edema, rhinoconjunctivitis

Drug Allergies

Adverse drug reactions (ADRs) are an important public health problem. An ADR is defined by the World Health Organization as an unintended, noxious response to a drug that occurs at a dose usually tolerated by normal subjects. The classification of ADRs by Rawlins and Thompson divides ADRs into two major subtypes: (1) type A reactions, which are dose dependent and predictable, and (2) type B reactions, which are uncommon and unpredictable. The majority of ADRs are type A reactions, which include four subtypes: overdosage or toxicity, side effects, secondary effects, and interactions. Type B reactions constitute approximately 10 to 15% of all ADRs and include four subtypes: drug intolerance, idiosyncratic reactions, pseudoallergic reactions, and drug hypersensitivity reactions. This chapter reviews the epidemiology of ADRs, risk factors for drug hypersensitivity reactions, the classification of drug reactions, diagnostic tests, reactions to specific drugs, and management of the patient with drug allergy. Figures illustrate drugs as haptens and prohaptens, the Gell and Coombs system, the four basic immunologic mechanisms for drug reactions, the chemical structure of different β-lactam antibiotics, penicillin skin testing, sulfonamide metabolism and haptenation, nonsteroidal antiinflammatory drug effects, and patient management. Tables outline the classification of ADRs, drugs frequently implicated in allergic drug reactions, and reagents and concentrations recommended for prick and intradermal skin testing. This chapter contains 8 highly rendered figures, 3 tables, 83 references, 5 MCQs, and 1 teaching slide set.

Drug Allergies

Adverse drug reactions (ADRs) are an important public health problem. An ADR is defined by the World Health Organization as an unintended, noxious response to a drug that occurs at a dose usually tolerated by normal subjects. The classification of ADRs by Rawlins and Thompson divides ADRs into two major subtypes: (1) type A reactions, which are dose dependent and predictable, and (2) type B reactions, which are uncommon and unpredictable. The majority of ADRs are type A reactions, which include four subtypes: overdosage or toxicity, side effects, secondary effects, and interactions. Type B reactions constitute approximately 10 to 15% of all ADRs and include four subtypes: drug intolerance, idiosyncratic reactions, pseudoallergic reactions, and drug hypersensitivity reactions. This chapter reviews the epidemiology of ADRs, risk factors for drug hypersensitivity reactions, the classification of drug reactions, diagnostic tests, reactions to specific drugs, and management of the patient with drug allergy. Figures illustrate drugs as haptens and prohaptens, the Gell and Coombs system, the four basic immunologic mechanisms for drug reactions, the chemical structure of different β-lactam antibiotics, penicillin skin testing, sulfonamide metabolism and haptenation, nonsteroidal antiinflammatory drug effects, and patient management. Tables outline the classification of ADRs, drugs frequently implicated in allergic drug reactions, and reagents and concentrations recommended for prick and intradermal skin testing. This review contains 8 figures, 7 tables, and 60 references. Key Words: Adverse drug reactions, drug hypersensitivity reactions, overdosage, toxicity, Type A reactions, Type B reactions, human leukocyte antigen, pruritus, angioedema, urticarial, bronchospasm, laryngeal edema, rhinoconjunctivitis

Application of Association Rules Analysis in Mining Adverse Drug Reaction Signals

Adverse drug reactions (ADRs) are increasingly becoming a serious public health problem. Spontaneous reporting systems (SRSs) are an important way for many countries to monitor ADRs produced in the clinical use of drugs, and they are the main data source for ADR signal detection. The traditional signal detection methods are based on disproportionality analysis (DPA) and lack the application of data mining technology. In this paper, we selected the spontaneous reports from 2011 to 2018 in Jiangsu Province of China as the research data and used association rules analysis (ARA) to mine signals. We defined some important metrics of the ARA according to the two-dimensional contingency table of ADRs, such as Confidence and Lift, and constructed performance evaluation indicators such as Precision, Recall, and F1 as objective standards. We used experimental methods based on data to objectively determine the optimal thresholds of the corresponding metrics, which, in the best case, are Confidence = 0.007 and Lift = 1. We obtained the average performance of the method through 10-fold cross-validation. The experimental results showed that F1 increased from 31.43% in the MHRA method to 40.38% in the ARA method; this was a significant improvement. To reduce drug risk and provide decision making for drug safety, more data mining methods need to be introduced and applied to ADR signal detection.

Antibiotic-Related Adverse Drug Reactions in Patients Treated on the Dermatology Ward of Medical University of Gdańsk.

Adverse drug reactions (ADRs) are unexpected reactions to a medication administered in a correct way at a standard dose. Drug-induced skin reactions account for 60–70% of all ADRs. The aim of the study is to determine the prevalence of antibiotic-related dermatological ADR in patients treated in the department of Dermatology, Venerology and Allergology of the University Clinical Center in Gdańsk, Poland, in the years 2004–2021. A retrospective analysis of patients’ medical files was conducted in order to identify cases of ADR connected with the use of antibiotics, yielding 84 cases. The most common group of antibiotics were β-lactam, causing ADR in 47 patients. β-lactam antibiotics in our study included amoxicillin, alone and combined with clavulanic acid, and cephalosporins, affecting 22, 18 and 7 patients, respectively. In conclusion, β-lactam antibiotics showed the highest prevalence among antibiotic-induced skin reactions. They accounted for 15% of cases of all dermatological drug reactions and 55% of those caused by antibiotics. Especially amoxicillin, prescribed as a single drug or in combination with clavulanic acid, was commonly the culprit. Due to its wide use in the hospital and outpatient clinic, these adverse reactions have to be kept in mind by both hospital staff and general practitioners.

ADR databases for on-site clinical use: Potentials of summary of products characteristics.

Adverse drug reactions (ADRs) for all drugs in Europe are described in the legally approved Summary of Product Characteristics (SmPC). An overview of all ADRs of the patients' drug list can support healthcare staff to link patient symptoms to possible ADRs. We review the possibilities and challenges to extract ADR information from SmPCs or American Structured Product Labels and present the development of our semi-automated procedure for extraction of ADRs from the tabulated section in the SmPCs to create a database, named Bikt, which is regularly updated and used at point of care in Sweden. The existence of five major table formats for ADRs used in the SmPCs required the development of different parsing scripts. Manual checks for correctness for all content have to be performed. The quality of extraction was investigated for all SmPCs by measuring precision, recall and F1 scores and compared with other methods published. We conclude that it is possible to semi-automatically extract ADR information from SmPCs. However, clear technical and content guidelines and standards for ADR tables and terms from drug registration authorities would lead to improved extraction and usability of ADR information at point of care.

AwareDX: Using Machine Learning to Identify Drugs Posing Increased Risk of Adverse Reactions to Women

Adverse drug reactions (ADRs) are the fourth leading cause of death in the US. Although women take longer to metabolize medications and experience twice the risk of developing ADRs compared to men, these sex differences are not comprehensively understood. Real-world clinical data provides an opportunity to estimate safety effects in otherwise understudied populations, ie. women. These data, however, are subject to confounding biases and correlated covariates. We present AwareDX, a pharmacovigilance algorithm that leverages advances in machine learning to study sex risks. Our algorithm mitigates these biases and quantifies the differential risk of a drug causing an adverse event in either men or women. We present a resource of 20,817 adverse drug effects posing sex specific risks. We independently validated our algorithm against known pharmacogenetic mechanisms of genes that are sex-differentially expressed. AwareDX presents an opportunity to minimize adverse events by tailoring drug prescription and dosage to sex.

Identification of Local Adverse Drug Reactions in Xinjiang Based on Attention Mechanism and BiLSTM-CNN Hybrid Network

Adverse drug reactions (ADR) include adverse reactions which are caused by drug quality problems or improper medication. In order to solve the issues which are triggered by the lack of research on local adverse drug reactions in Xinjiang and the shortcomings of traditional models in dealing with irregular sentences, this paper proposes a method for adverse drug identification in Xinjiang. The method is combined with BiLSTM-CNN hybrid network which is based on attention mechanism. The method analyzes deeply on the network text context feature and the attention pooling mechanism. These measures can reduce the information loss while acquiring the local convolution feature. The integration of attention mechanism, the addition of weight information make it becomes more sensitive to capture the importance of features which brings improvement of the ability to express features. Finally, the experiment was carried out in the Xinjiang Adverse Drug Reaction Data Set. The accuracy rate of this model in Xinjiang local drug adverse reaction identification was 87.27%, the recall rate was 88.87%, and the F value was 87.65%. Compared with the common convolutional neural network and BiLSTM, it achieves better classification results, and has obvious advantages for irregular grammar and long sentence recognition. Experiments showed that the ATT-BiLSTM-CNN model can rapidly improve the recognition performance of local adverse drug reactions in Xinjiang.

Drug Allergies

Adverse drug reactions (ADRs) are very common, causing approximately 2% of emergency department visits. It is estimated that approximately one-half of these ADRs are preventable. Although most ADRs and allergic reactions are minor, some may be severe, and the emergency physician's first priority should be the identification of anaphylactic or life-threatening reactions. This review examines the pathophysiology, stabilization and assessment, diagnosis and treatment, and disposition and outcomes of ADRs and drug allergies. Figures show the Gell and Coombs system, the four basic immunologic mechanisms for drug reactions, drugs as haptens and prohaptens, chemical structure of different β-lactam antibiotics, and management of the patient with possible drug allergy. Tables list the types of adverse drug reactions, drugs frequently implicated in allergic reactions in the emergency department, classification of allergic reactions, pretreatment protocol for radiocontrast allergy, and important parts of a history and physical examination of a patient with a suspected or confirmed drug hypersensitivity reaction. This review contains 5 figures, 5 tables, and 128 references. Keywords: drug allergies, Adverse Drug Reactions (ADRs), Gell and Coombs system, allergic reactions, anaphylactic reactions, radiocontrast allergy, drug hypersensitivity, drug withdrawal

Drug Allergies

Adverse drug reactions (ADRs) are very common, causing approximately 2% of emergency department visits. It is estimated that approximately one-half of these ADRs are preventable. Although most ADRs and allergic reactions are minor, some may be severe, and the emergency physician's first priority should be the identification of anaphylactic or life-threatening reactions. This review examines the pathophysiology, stabilization and assessment, diagnosis and treatment, and disposition and outcomes of ADRs and drug allergies. Figures show the Gell and Coombs system, the four basic immunologic mechanisms for drug reactions, drugs as haptens and prohaptens, chemical structure of different β-lactam antibiotics, and management of the patient with possible drug allergy. Tables list the types of adverse drug reactions, drugs frequently implicated in allergic reactions in the emergency department, classification of allergic reactions, pretreatment protocol for radiocontrast allergy, and important parts of a history and physical examination of a patient with a suspected or confirmed drug hypersensitivity reaction. This review contains 5 figures, 5 tables, and 128 references. Keywords: drug allergies, Adverse Drug Reactions (ADRs), Gell and Coombs system, allergic reactions, anaphylactic reactions, radiocontrast allergy, drug hypersensitivity, drug withdrawal

Trends in the Reporting of Adverse Drug Reactions:A Global Review of Literature

Adverse drug reactions (ADRs) occurdue to the drugs that are prescribed in acute and chronic or terminal ailments. They are a bane to the healthcare society as they not only challenge the principles of prescribing individual drug candidates but also the prescribing of multiple drugs. This may hold the patient, especially geriatric and pediatric patients, at a high risk of unexpected, undesired and serious events. In the review of current literature, it was observed that it was the commonly prescribed drugs such as hematological agents, anti-hypertensive medications, anti-arrhythmic medications, neuroleptics, proton pump inhibitors and especially Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) that caused most of the ADRs in elderly patients (60 years of age and above). In most cases, the affected systems were the Cardio Vascular System (CVS), the nervous system, the Gastrointestinal (GI) system and the most common symptoms seen were nausea, vomiting, headache, stomach ache, dizziness and vertigo that led to falls. In this article, the occurrence of ADRs due to polypharmacy or Potentially Inappropriate Prescriptions (PIPs) and how they affect children belonging to the pediatric age group (i.e. 16 years and less) were investigated. In this review of literature, it was found that the main reason for ADRs were off-label prescription of drugs. The off-label prescription of drugs refers to the prescriptionofdrugsfor a different purpose other than its approved use. Off-label prescription of drugs cause major psychiatric disorders, skin eruptions, enteral problems and some severe reactions like respiratory depression, hypotension, liver failure, seizures, bradycardia, bleeding etc. with the use of drugs such as anti-tussive agents, rhinological agents and GI drugs. Ultimately, it was determined that it was not the age group that determined the occurrence of ADRs, but it was the prescription errors, polypharmacy and drug-drug interaction that caused casualties and inpatient admissions, out of which some cases proved to be fatal.

Stem cell models as an in vitro model for predictive toxicology.

Adverse drug reactions (ADRs) are the unintended side effects of drugs. They are categorised as either predictable or unpredictable drug-induced injury and may be exhibited after a single or prolonged exposure to one or multiple compounds. Historically, toxicology studies rely heavily on animal models to understand and characterise the toxicity of novel compounds. However, animal models are imperfect proxies for human toxicity and there have been several high-profile cases of failure of animal models to predict human toxicity e.g. fialuridine, TGN1412 which highlight the need for improved predictive models of human toxicity. As a result, stem cell-derived models are under investigation as potential models for toxicity during early stages of drug development. Stem cells retain the genotype of the individual from which they were derived, offering the opportunity to model the reproducibility of rare phenotypes in vitro. Differentiated 2D stem cell cultures have been investigated as models of hepato- and cardiotoxicity. However, insufficient maturity, particularly in the case of hepatocyte-like cells, means that their widespread use is not currently a feasible method to tackle the complex issues of off-target and often unpredictable toxicity of novel compounds. This review discusses the current state of the art for modelling clinically relevant toxicities, e.g. cardio- and hepatotoxicity, alongside the emerging need for modelling gastrointestinal toxicity and seeks to address whether stem cell technologies are a potential solution to increase the accuracy of ADR predictivity in humans.

Sentiment Ontology Analysis for Adverse Drug Effect

Adverse drug reactions (ADR) are happen more frequently based on different drugs. ADR should be monitored by Pharmacovigilance. Due to drug usage of single dose or combine dose ADR are happen. ADR can't be monitored in INDIA because of not follow the physician direction and also self-medication. Most of the Indians used drug store or online to purchase drugs. The proposed method utilised different websites and online drugs reviews with sentiment analysis and conjugate gradient method in neural network. In output, we propose the best way to monitor the ADR and drug harmfulness.

Abstract P376: The Monitoring by a Pharmacist Facilitator, of Side Effect, is Useful to Report Adverse Reactions Associated With Antihypertensive Agents in Practical Clinic in South Italy

Adverse Drug Reactions (ADRs) are a serious health related problem, which can limit the treatment options, compliance and even leads to discontinuation of therapy. Unfortunately not in all countries, the reporting reaches standard levels set by the WHO. As well, in our region (Calabria), located in south of Italy, only few reports are usually reported. For these reasons, the Italian Agency of the Drugs (AIFA) has been promoting and financing regional projects with multidisciplinary groups to increase spontaneous reporting. From first January 2018, we started a survey program finalized to report all adverse events from antihypertensive drugs observed in our Cardiovascular Prevention Clinic. We evaluated all of the 250 outpatients (≥18 years), consecutively visited in our clinic, from 1 January 2018 to 30 April 2018. All of these were in antihypertensive treatment (monotherapy or multiple drugs therapy). A total of 20 ADRs were observed. Of the 20 ADRs, 19 were non-serious events; a serious event required hospitalization (atrial-ventricular complete block). Causality assessment has been estimated with the Naranjo algorithm; the results indicated n=19 possible ADRs and n=1 probable. Incidence of ADRs was found to be higher in the age group between 45 and 54 years old (6 of 20) and males experienced more ADRs than females (35%, 7 of 20). ADRs were more frequently associated with combination therapy (65%, 13 of 20) versus monotherapy. Calcium channel-blockers were found to be the most frequently associated drugs with ADRs (n=8), followed by angiotensin receptor blockers (n=4). We compared our reports with the reports, of the same period, available for our region obtained from National Pharmacovigilance Network. During this period were reported 27 side effect reactions in all our region (5 reports in the 2017). In conclusion, in the last 4 months, regional projects, with the creation of a multidisciplinary group composed of Medical and Pharmacists Facilitator, was useful in improving and increase quality and quantity of spontaneous reports in Calabria.

DILI Associated with Skin Reactions

Adverse drug reactions (ADR) frequently involve the liver and skin in the form of drug-induced liver injury or cutaneous drug eruption. Skin ADR can range from harmless rash to severe skin manifestations such as drug rash with eosinophilia and systemic symptom syndrome (DRESS syndrome), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP), all of which can be associated with severe outcome, including a 30% mortality rate in case of TEN. The association with co-occurring liver injury varies and in DRESS and SJS/TEN can contribute to substantial morbidity and mortality. Liver and skin ADR are frequent but rarely severe; however, if severe, they are not uncommonly fatal.

Adverse Drug Reactions in Palliative Care

Adverse drug reactions (ADRs) have an impact on patient morbidity and mortality. Palliative care patients constitute a vulnerable population due to the complexity of their care and treatments. This study sought to identify ADRs in palliative care, assess their severity and preventability, and identify specific medications most commonly involved. This retrospective cohort study included patients who received a consult by the hospital’s palliative care service over a 1-year period. Records were reviewed to identify ADR occurrences, causative and resulting events, and variables used to determine preventability and severity. Of the 430 patients who met inclusion criteria, 247 patients experienced an ADR (57.4%). In total, 440 ADRs were documented, with 45.7% of patients experiencing more than one. Patients with repeated hospitalizations, increased medication usage, documented drug allergies, and cancer diagnoses were more likely to experience an ADR. No associations were found between occurrences of ADR with gender or Charlson comorbidity scores. The majority of ADRs were of moderate severity (64.6%) and considered potentially preventable (81.5%). Organ systems most commonly affected by ADRs were gastrointestinal (32.7%) and neurological (15.9%). Antimicrobials, opioids, and anticoagulants were the most common causative agents. ADRs are commonly experienced in palliative care patients and are often preventable. Identification of risk factors for ADRs may prevent occurrences in the complex palliative care patient.

CD4+ T cells prevent abacavir hypersensitivity reactions in HLA-B*57:01 transgenic mice

Abstract Adverse drug reactions (ADR) are a major obstacle to drug development. Genome-wide association studies identified several human leukocyte antigens (HLA)-class I alleles as risk factors for ADR. The HLA-B*57:01 allele has been found to be associated with the development of abacavir (ABC) hypersensitivity syndrome (AHS) and with the induction of liver injury by the β-lactam antibiotic flucloxacillin. The nucleoside analog ABC, an inhibitor of the HIV reverse transcriptase, can induce severe multi-organ toxicity in >50% of HLA-B*57:01+ patients with HIV infection. In a previous study we showed that ABC induced binding to the HLA-B*57:01 of altered self-peptides containing predominantly isoleucine or leucine residues at the carboxyl terminus. Recognition of these self-peptides drives in vitro activation of cytotoxic CD8+ T cells. However, the early immune events/danger signals required to overcome the immune tolerance that otherwise suppress ADR are still unknown. In order to study HLA-linked drug hypersensitivity in vivo and to understand better drug immune tolerance, HLA-B transgenic mice were generated. Here, we show that ABC activates HLA-B*57:01 transgenic CD8+ T cells in vitro via CD8 and HLA. A systemic, but partial, early response to the drug is also observed in vivo, however, ABC fails to promote skin hypersensitivity in immunocompetent transgenic mice. Instead, depletion of CD4+ T cells breaks immune tolerance to ABC and promotes ADR in HLA-B*57:01 transgenic mice. Supported by the Intramural Research Program of the NIAID, NIH, and CDER, FDA.

A Survey on using Social Media Data Analytics for Pharmacovigilance

Adverse Drug Reactions (ADRs) are unintended effects caused by drugs prescribed for various diseases. ADR presents a significant medical problem and various government initiated ADR reporting platforms are available in many countries. Pharmacovigilance is the process of comprehending the drugs, its behaviour and preventing any such undesirable effect on consumption of the drug as prescribed. With the growing rate of discussions flowing through social media, researchers and industries have started exploring them for vital information leading to prospective insights. We explore the advantages of using the data from social media in mining and detection of events related to ADR. In this paper, we summarize the different techniques used to extract the ADR mentions in social media.