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Journal of Asthma and Allergy 2012Omalizumab is a monoclonal antibody, indicated for the treatment of severe allergic asthma. In Europe, there have been concerns about the cardiovascular safety of...
BACKGROUND
Omalizumab is a monoclonal antibody, indicated for the treatment of severe allergic asthma. In Europe, there have been concerns about the cardiovascular safety of omalizumab. The objective of this study was to analyze the association between omalizumab and arterial thrombotic events in a spontaneous adverse drug reaction reporting database in the US.
METHODS AND MATERIALS
Reports of arterial thrombotic events submitted to the US Food and Drug Administration's Adverse Event Reporting System (AERS) between 2004 and 2011 were retrieved and analyzed by the reporting odds ratio data mining algorithm. The reporting odds ratio of arterial thrombotic events for omalizumab was compared with specific asthma medications and all drugs in the AERS. Values ≥2 were considered significant safety signals. The Medical Dictionary for Regulatory Activities Preferred Terms were used to identify arterial thrombotic events (eg, stroke, myocardial infarction).
RESULTS
In total, 293,783 reports of arterial thrombotic events were retrieved (about 2% of all adverse drug reaction reports), corresponding to 2274 asthma drug-arterial thrombotic events pairs (omalizumab, 222; inhaled corticosteroids [ICS], 131; long-acting beta-agonists [LABA], 102; single-device combination ICS-LABA, 506; inhaled short-acting beta-agonists [SABA], 475; oral SABA, 6; inhaled antimuscarinics [AMC], 477; single-device combination AMC-SABA, 127; xanthines, 50; leukotriene modifiers, 174; and mast cell stabilizers, 4). Reporting odds ratio and 95% confidence interval values for omalizumab compared with other asthma drugs and all drugs in AERS were 2.75 (2.39-316) and 1.09 (0.95-1.24), respectively. Omalizumab ranked second after ICS in the risk of arterial thrombotic events, followed by AMC, AMC-SABA, and ICS-LABA.
CONCLUSION
Omalizumab is associated with higher than expected reporting of arterial thrombotic events in asthmatic patients. This hypothesis needs further testing in robust epidemiological studies.
PubMed: 22690127
DOI: 10.2147/JAA.S29811 -
Arthritis Research & Therapy 2005The objective was to improve understanding of adverse events occurring with celecoxib in the treatment of osteoarthritis and rheumatoid arthritis. Data were extracted... (Comparative Study)
Comparative Study Meta-Analysis Review
Tolerability and adverse events in clinical trials of celecoxib in osteoarthritis and rheumatoid arthritis: systematic review and meta-analysis of information from company clinical trial reports.
The objective was to improve understanding of adverse events occurring with celecoxib in the treatment of osteoarthritis and rheumatoid arthritis. Data were extracted from company clinical trial reports of randomised trials of celecoxib in osteoarthritis or rheumatoid arthritis lasting 2 weeks or more. Outcomes were discontinuations (all cause, lack of efficacy, adverse event, gastrointestinal adverse event), endoscopically detected ulcers, gastrointestinal or cardio-renal events, and major changes in haematological parameters. The main comparisons were celecoxib (all doses) versus placebo, paracetamol (acetaminophen) 4,000 mg daily, rofecoxib 25 mg daily, or nonsteroidal anti-inflammatory drugs (NSAIDs) (naproxen, diclofenac, ibuprofen, and loxoprofen). For NSAIDs, celecoxib was compared both at all doses and at licensed doses (200 to 400 mg daily). Thirty-one trials included 39,605 randomised patients. Most patients had osteoarthritis and were women of average age 60 years or above. Most trials lasted 12 weeks or more. Doses of celecoxib were 50 to 800 mg/day. Compared with placebo, celecoxib had fewer discontinuations for any cause or for lack of efficacy, fewer serious adverse events, and less nausea. It had more patients with dyspepsia, diarrhoea, oedema, more adverse events that were gastrointestinal or treatment related, and more patients experiencing an adverse event. There were no differences for hypertension, gastrointestinal tolerability, or discontinuations for adverse events. Compared with paracetamol, celecoxib had fewer discontinuations for any cause, for lack of efficacy, or diarrhoea, but no other differences. Compared with rofecoxib, celecoxib had fewer patients with abdominal pain and oedema, but no other differences. Compared with NSAIDs, celecoxib had fewer symptomatic ulcers and bleeds, endoscopically detected ulcers, and discontinuations for adverse events or gastrointestinal adverse events. Fewer patients had any, or a gastrointestinal, or a treatment-related adverse event, or vomiting, abdominal pain, dyspepsia, or reduced haemoglobin or haematocrit. Discontinuations for lack of efficacy were higher. No differences were found for all-cause discontinuations, serious adverse events, hypertension, diarrhoea, nausea, oedema, myocardial infarction, cardiac failure, or raised creatinine. Company clinical trial reports present much more information than published papers. Adverse event information is clearly presented in company clinical trial reports, which are an ideal source of information for systematic review and meta-analysis.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Celecoxib; Drug Industry; Drug Tolerance; Gastrointestinal Diseases; Humans; Osteoarthritis; Pyrazoles; Randomized Controlled Trials as Topic; Sulfonamides
PubMed: 15899051
DOI: 10.1186/ar1704 -
Indian Journal of Community Medicine :... 2022Minor adverse event following immunizations (AEFIs) are often underreported and self-treated. This study aimed to collect information regarding any and every probable...
BACKGROUND
Minor adverse event following immunizations (AEFIs) are often underreported and self-treated. This study aimed to collect information regarding any and every probable adverse event experienced by the recipient of Covishield vaccine up to 10 days following the first and second dose of vaccine. To find the incidence of minor adverse events following Covishield vaccination; draw an association between adverse events and individuals' demographic factors and comorbidities; and report new adverse events, if any.
MATERIALS AND METHODS
A descriptive observational study was conducted among 409 participants randomly sampled from the Vaccination Centre at a Tertiary Care Hospital, Mumbai. Participants were followed up post their first and second doses to enquire about adverse events.
RESULTS
Most commonly reported adverse events included injection site pain, tenderness, chills, fatigue, fever, and myalgia. Females reported more adverse events compared to men ( < 0.05). Younger individuals (18-24) experienced adverse events more as compared to individuals above 40 years of age ( < 0.005). Reported adverse events were lesser after the second dose in comparison with the first dose. Few participants reported dysgeusia.
CONCLUSIONS
Covishield vaccination has a mild AEFI profile, most commonly: injection site pain, tenderness, chills, and fatigue. It is hoped that the findings of this study will dispel anxiety around the adverse events of vaccination and reduce any persisting vaccine hesitancy. Effective communication with the population on vaccination will enable individuals to make educated and informed decisions.
PubMed: 36742958
DOI: 10.4103/ijcm.ijcm_93_22 -
Impact of High Lipoprotein(a) Levels on Clinical Outcomes Following Peripheral Endovascular Therapy.JACC. Cardiovascular Interventions Jul 2022Elevated lipoprotein(a) (Lp[a]) levels are an independent risk factor for the development of atherosclerotic diseases, including peripheral artery disease (PAD)....
BACKGROUND
Elevated lipoprotein(a) (Lp[a]) levels are an independent risk factor for the development of atherosclerotic diseases, including peripheral artery disease (PAD). However, their prognostic impact in patients with PAD remains unknown.
OBJECTIVES
The aim of this study was to examine the prognostic impact of elevated Lp(a) levels in patients with PAD undergoing endovascular therapy (EVT).
METHODS
In total, 1,169 patients who underwent successful EVT for symptomatic PAD between September 2016 and August 2021 were included in this study. High Lp(a) levels were defined as >30 mg/dL. The associations of high Lp(a) levels with incident major adverse cardiovascular events (MACE) (all-cause death, myocardial infarction, and stroke) and major adverse limb events (MALE) (repeat revascularization for target limb and major amputation) were analyzed.
RESULTS
During a median follow-up period of 1.7 years (IQR: 0.6-3.0 years), 230 MACE (210 deaths, 15 myocardial infarctions, and 22 strokes) and 263 MALE (219 reinterventions and 36 major amputations) were observed. The cumulative incidence rate of MACE (48.1% vs 27.3%) and MALE (67.9% vs 27.2%) was significantly higher in patients with high Lp(a) levels (P < 0.001 for both). The adjusted HR were 1.93 (95% CI: 1.44-2.59; P < 0.001) for MACE and 4.15 (95% CI: 3.14-5.50; P < 0.001) for MALE. These associations were not influenced by low-density lipoprotein cholesterol levels or statin administration (P for interaction >0.05 for all).
CONCLUSIONS
Elevated Lp(a) levels were independently associated with incident MACE and MALE in patients with PAD treated with revascularization irrespective of low-density lipoprotein cholesterol level and statin administration.
Topics: Biomarkers; Cholesterol; Endovascular Procedures; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipoprotein(a); Lipoproteins, LDL; Myocardial Infarction; Peripheral Arterial Disease; Risk Factors; Stroke; Treatment Outcome
PubMed: 35863797
DOI: 10.1016/j.jcin.2022.05.050 -
JMIR Medical Informatics Jun 2014The Food and Drug Administration's (FDA) Adverse Event Reporting System (FAERS) is a repository of spontaneously-reported adverse drug events (ADEs) for FDA-approved...
BACKGROUND
The Food and Drug Administration's (FDA) Adverse Event Reporting System (FAERS) is a repository of spontaneously-reported adverse drug events (ADEs) for FDA-approved prescription drugs. FAERS reports include both structured reports and unstructured narratives. The narratives often include essential information for evaluation of the severity, causality, and description of ADEs that are not present in the structured data. The timely identification of unknown toxicities of prescription drugs is an important, unsolved problem.
OBJECTIVE
The objective of this study was to develop an annotated corpus of FAERS narratives and biomedical named entity tagger to automatically identify ADE related information in the FAERS narratives.
METHODS
We developed an annotation guideline and annotate medication information and adverse event related entities on 122 FAERS narratives comprising approximately 23,000 word tokens. A named entity tagger using supervised machine learning approaches was built for detecting medication information and adverse event entities using various categories of features.
RESULTS
The annotated corpus had an agreement of over .9 Cohen's kappa for medication and adverse event entities. The best performing tagger achieves an overall performance of 0.73 F1 score for detection of medication, adverse event and other named entities.
CONCLUSIONS
In this study, we developed an annotated corpus of FAERS narratives and machine learning based models for automatically extracting medication and adverse event information from the FAERS narratives. Our study is an important step towards enriching the FAERS data for postmarketing pharmacovigilance.
PubMed: 25600332
DOI: 10.2196/medinform.3022 -
Yakugaku Zasshi : Journal of the... 2020The Organisation for Economic Co-operation and Development (OECD) has initiated the adverse outcome pathway (AOP) Development Program in which the concept of AOP is... (Review)
Review
The Organisation for Economic Co-operation and Development (OECD) has initiated the adverse outcome pathway (AOP) Development Program in which the concept of AOP is applied to evaluate the safety of molecules such as chemicals. This program aims to assist regulatory needs and construct a knowledge base by accumulating AOP case studies. AOP consists of a molecular initiating event (MIE) as the initiating event of the pathway; key events (KEs) as the events themselves, such as cellular-molecular interactions; and adverse outcome (AO), such as signaling transduction-induced toxicity, as adverse events. KEs are extracted as important events at various levels, such as the molecular, cellular, tissue, organ, individual, and species levels; measurement of KEs and key event relationships (KERs), including mechanisms, plausibility, species differences, and empirical support information, are gathered. The development status of the AOP relating to histone deacetylase inhibition-induced testicular toxicity, currently being reviewed by the OECD, has been introduced. The AOP describing malignancies by Wnt ligand stimulation and Wnt signaling activation using gene expression network analysis-based mechanisms in molecular pathway elucidation has been suggested.
Topics: Adverse Outcome Pathways; Animals; Chemical Safety; Drug-Related Side Effects and Adverse Reactions; Gene Regulatory Networks; Humans
PubMed: 32238629
DOI: 10.1248/yakushi.19-00190-2 -
BMC Medical Research Methodology Mar 2023Drug toxicity does not affect patients equally; the toxicity may only exert in patients who possess certain attributes of susceptibility to specific drug properties...
BACKGROUND
Drug toxicity does not affect patients equally; the toxicity may only exert in patients who possess certain attributes of susceptibility to specific drug properties (i.e., drug-host interaction). This concept is crucial for personalized drug safety but remains under-studied, primarily due to methodological challenges and limited data availability. By monitoring a large volume of adverse event reports in the postmarket stage, spontaneous adverse event reporting systems provide an unparalleled resource of information for adverse events and could be utilized to explore risk disparities of specific adverse events by age, sex, and other host factors. However, well-formulated statistical methods to formally address such risk disparities are currently lacking.
METHODS
In this paper, we present a statistical framework to explore spontaneous adverse event reporting databases for drug-host interactions and detect risk disparities in adverse drug events by various host factors, adapting methods for safety signal detection. We proposed four different methods, including likelihood ratio test, normal approximation test, and two tests using subgroup ratios. We applied our proposed methods to simulated data and Food and Drug Administration (FDA) Adverse Event Reporting Systems (FAERS) and explored sex-/age-disparities in reported liver events associated with specific drug classes.
RESULTS
The simulation result demonstrates that two tests (likelihood ratio, normal approximation) can detect disparities in adverse drug events associated with host factors while controlling the family wise error rate. Application to real data on drug liver toxicity shows that the proposed method can be used to detect drugs with unusually high level of disparity regarding a host factor (sex or age) for liver toxicity or to determine whether an adverse event demonstrates a significant unbalance regarding the host factor relative to other events for the drug.
CONCLUSION
Though spontaneous adverse event reporting databases require careful data processing and inference, the sheer size of the databases with diverse data from different countries provides unique resources for exploring various questions for drug safety that are otherwise impossible to address. Our proposed methods can be used to facilitate future investigation on drug-host interactions in drug toxicity using a large number of reported adverse events.
Topics: United States; Humans; Adverse Drug Reaction Reporting Systems; Drug-Related Side Effects and Adverse Reactions; Pharmaceutical Preparations; Computer Simulation; Likelihood Functions; Databases, Factual
PubMed: 36973693
DOI: 10.1186/s12874-023-01885-w -
Evidence-based Complementary and... 2019Traditional Japanese Kampo medicines have been integrated into the Japanese national health-care system. In Japan, the Ministry of Health, Labor, and Welfare's website...
OBJECTIVES
Traditional Japanese Kampo medicines have been integrated into the Japanese national health-care system. In Japan, the Ministry of Health, Labor, and Welfare's website discloses adverse drug-event data that have been obtained from medical personnel reports investigated by the Pharmaceutical and Medical Devices Agency. Using these data, we investigated adverse events associated with ethical Kampo formulations.
METHODS
Reports of adverse events associated with ethical Kampo formulations from the domestic adverse-event data were obtained from July 30, 2003, to March 31, 2018. Adverse events were then categorized, and the relationships between categories of adverse events and crude drugs were analyzed.
RESULTS
There were 4,232 reported adverse events associated with ethical Kampo formulations. The numbers of events by category were as follows: events related to liver injury, 1,193; lung injury, 1,177; pseudoaldosteronism, 889; mesenteric phlebosclerosis, 223; drug eruption, 185; and others, 565. Among events related to both liver injury and lung injury, approximately 70% were suspected to be induced by Kampo formulations containing Scutellariae Radix. The pseudoaldosteronism-related events, which are induced by Glycyrrhizae Radix, included several events related to muscle injury, heart failure, and arrhythmia. Events related to mesenteric phlebosclerosis, believed to be induced by long-term use of Kampo formulas containing Gardeniae Fructus, increased remarkably during the study period. Among the events related to drug eruption, approximately 35% were suspected to be induced by Kampo formulations containing Ephedrae Herba.
CONCLUSION
Kampo medicines may cause various adverse events. The present results provide valuable information regarding adverse events associated with Kampo medicines from the viewpoint of patient safety.
PubMed: 31118950
DOI: 10.1155/2019/1643804 -
PloS One 2022Adverse drug events are significant causes of emergency department visits. Systematic evaluation of adverse drug events leading to emergency department visits by age is... (Observational Study)
Observational Study
Adverse drug events are significant causes of emergency department visits. Systematic evaluation of adverse drug events leading to emergency department visits by age is lacking. This multicenter retrospective observational study evaluated the prevalence and features of adverse drug event-related emergency department visits across ages. We reviewed emergency department medical records obtained from three university hospitals between July 2014 and December 2014. The proportion of adverse drug events among total emergency department visits was calculated. The cause, severity, preventability, and causative drug(s) of each adverse drug event were analyzed and compared between age groups (children/adolescents [<18 years], adults [18-64 years], and the elderly [≥65 years]). Of 59,428 emergency department visits, 2,104 (3.5%) were adverse drug event-related. Adverse drug event-related emergency department visits were more likely to be female and older. Multivariate logistic regression analysis revealed that compared to non- adverse drug event-related cases, adverse drug event-related emergency department visitors were more likely to be female (60.6% vs. 53.6%, p<0.001, OR 1.285, 95% CI 1.025-1.603) and older (50.8 ± 24.6 years vs. 37.7 ± 24.4 years, p<0.001, OR 1.892, 95% CI: 1.397-2.297). Comorbidities such as diabetes, chronic kidney disease, chronic liver disease, and malignancies were also significantly associated with adverse drug event-related emergency department visits. Side effects were the most common type of adverse drug events across age groups, although main types differed substantially depending on age. Serious adverse drug events, hospitalizations, and adverse drug event-related deaths occurred more frequently in the elderly than in adults or children/adolescents. The proportion of adverse drug event-related emergency department visits that were preventable was 15.3%. Causative drugs of adverse drug events varied considerably depending on age group. Adverse drug event features differ substantially according to age group. The findings suggest that an age-specific approach should be adopted in the preventive strategies to reduce adverse drug events.
Topics: Adolescent; Adult; Aged; Child; Drug-Related Side Effects and Adverse Reactions; Emergency Service, Hospital; Female; Hospitalization; Humans; Male; Prevalence; Retrospective Studies
PubMed: 36121802
DOI: 10.1371/journal.pone.0272743 -
Journal of Chest Surgery Aug 2022Adverse events or emergency situations that are unacceptable in the context of lung transplantation may occur during the procedure. These adverse events and...
Adverse events or emergency situations that are unacceptable in the context of lung transplantation may occur during the procedure. These adverse events and circumstances are not problems that are caused by insufficient experience or can be solved by increasing surgical experience. The purpose of this review is to describe the adverse events and circumstances that occur during lung transplantation and to identify an appropriate surgical approach through an analysis of case reports in the global literature.
PubMed: 35924538
DOI: 10.5090/jcs.22.054