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Heliyon Mar 2024Alpelisib was approved for treatment of breast cancer. We assessed the safety signals associated with alpelisib by data mining the FDA pharmacovigilance database.
BACKGROUND
Alpelisib was approved for treatment of breast cancer. We assessed the safety signals associated with alpelisib by data mining the FDA pharmacovigilance database.
METHODS
Data from the second quarter of 2019 to the fourth quarter of 2022 had been retrieved from the FAERS database. Disproportionality analysis by reporting odds ratio were used to evaluate the potential association between adverse events (AEs) and alpelisib.
RESULTS
A total of 5,980,090 reports were extracted, 18,149 of them were chosen with alpelisib as the suspected drug. After combining the same PRIMARYID, 5647 patients remained. We observed 10 system organ classes (SOCs) with a reported number >50 and associated with alpelisib as gastrointestinal disorders, general disorders and administration site conditions, metabolism and nutrition disorders, skin and subcutaneous tissue disorders, investigations and neoplasms benign, malignant and unspecified (incl cysts and polyps), immune system disorders, nervous system disorders, psychiatric disorders, eye disorders. The median time to AEs in these patients was 13 days, with an IQR (Interquartile Range) of 7-70 days. 61.12% AEs happened within the initial month of alpelisib usage.
CONCLUSION
Our study provided a more in-depth and extensive understanding of AEs that may be associated with alpelisib, which will help to reduce the risk of AEs in the clinical treatment of alpelisib. AEs with novel preferred term (PTs) were constipation, dysphagia, diabetic ketoacidosis, feeding disorder, urticaria, eye disorders and vision blurred. 61.12% of cases developed AEs within 30 days after taking alpelisib.
PubMed: 38510044
DOI: 10.1016/j.heliyon.2024.e27599 -
Journal of Atherosclerosis and... Apr 2024Past observational studies have reported on the association between antipsychotic drugs and venous thromboembolism (VTE); however, the conclusions remain controversial,...
Association of Antipsychotic Drugs with Venous Thromboembolism: Data Mining of Food and Drug Administration Adverse Event Reporting System and Mendelian Randomization Analysis.
AIMS
Past observational studies have reported on the association between antipsychotic drugs and venous thromboembolism (VTE); however, the conclusions remain controversial, and its mechanisms are yet to be fully understood. Thus, in this study, we aim to determine the associations of antipsychotic drugs with VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE), and their potential mechanisms.
METHODS
We first mined the adverse event signals of VTE, DVT, and PE caused by antipsychotic drugs in Food and Drug Administration Adverse Event Reporting System (FAERS). Next, we used two-sample Mendelian randomization (MR) method to investigate the association of antipsychotic drug target gene expression with VTE, DVT, and PE, using single-nucleotide polymorphisms as genetic instruments. We not only used the expression of all antipsychotic drug target genes as exposure to perform MR analyses but also analyzed the effect of single target gene expression on the outcomes.
RESULTS
In the FAERS, 1694 cases of VTE events were reported by 16 drugs. However, using the MR approach, no significant association was determined between the expression of all antipsychotic target genes and VTE, DVT, or PE, either in blood or brain tissue. Although the analysis of single gene expression data showed that the expression of nine genes was associated with VTE events, these targets lacked significant pharmacological action.
CONCLUSIONS
Adverse event mining results have supported the claim that antipsychotic drugs can increase the risk of VTE. However, we failed to find any genetic evidence for this causal association and potential mechanisms. Thus, vigilance is still needed for antipsychotic drug-related VTE despite the limited supporting evidence.
Topics: United States; Humans; Venous Thromboembolism; Antipsychotic Agents; Mendelian Randomization Analysis; United States Food and Drug Administration; Pulmonary Embolism; Data Mining
PubMed: 38030236
DOI: 10.5551/jat.64461 -
Frontiers in Pharmacology 2023Cholangiocarcinoma (CCA) is a highly lethal and aggressive epithelial tumor of the hepatobiliary system. A poor prognosis, propensity for relapse, low chance of cure...
Cholangiocarcinoma (CCA) is a highly lethal and aggressive epithelial tumor of the hepatobiliary system. A poor prognosis, propensity for relapse, low chance of cure and survival are some of its hallmarks. Pemigatinib, the first targeted treatment for CCA in the United States, has been demonstrated to have a significant response rate and encouraging survival data in early-phase trials. The adverse events (AEs) of pemigatinib must also be determined. To understand more deeply the safety of pemigatinib in the real world through data-mining of the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Disproportionality analysis was employed in a retrospective pharmacovigilance investigation to identify the AEs linked to pemigatinib use as signals. Data were collected between 1 January 2020 to 30 June 2022. Four data-mining methods (proportional reporting odds ratio; proportional reporting ratio; Bayesian confidence propagation neural networks of information components; empirical Bayes geometric means) were used to calculate disproportionality. A total of 203 cases using pemigatinib as the prime-suspect medication were found in our search, which involved 99 preferred terms (PTs). Thirteen signals of pemigatinib-induced AEs in seven System Organ Classes were detected after confirming the four algorithms simultaneously. Nephrolithiasis was an unexpected significant AE not listed on the drug label found in our data-mining. Comparison of the differences between pemigatinib and platinum drugs in terms of 33 PTs revealed that 13 PTs also met the criteria of the four algorithms. Ten of these PTs were identical to those compared with all other drugs, in which (excluding a reduction in phosphorus in blood) other PT signal values were higher than those of all other drugs tested. However, comparison of the differences between pemigatinib and infigratinib in terms of the 33 PTs revealed no significant signals in each algorithm method. Some significant signals were detected between pemigatinib use and AEs. PTs with apparently strong signals and PTs not mentioned in the label should be taken seriously.
PubMed: 37554985
DOI: 10.3389/fphar.2023.1194545 -
Cureus Dec 2023Atrial fibrillation (AF) is a common arrhythmia associated with significant morbidity and mortality. The optimal approach to managing AF, specifically rate control... (Review)
Review
Atrial fibrillation (AF) is a common arrhythmia associated with significant morbidity and mortality. The optimal approach to managing AF, specifically rate control versus rhythm control, remains a topic of debate in clinical practice. This systematic review aims to compare the rate control and rhythm control strategies based on their clinical outcomes, quality of life, and adverse events associated with them. A comprehensive search was conducted using PubMed, Google Scholar, Science Direct, Research Gate, MEDLINE (Medical Literature Analysis and Retrieval System Online), Scopus, and Embase (Excerpta Medica dataBASE) databases. A total of 1657 research papers were identified through the search strategy, and after applying the eligibility criteria, 28 studies were selected for the analysis. The studies encompassed a range of methodologies, including randomized controlled trials, observational studies, and meta-analyses. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed for study selection, data extraction, and analysis. The outcomes of interest included all: cause mortality, stroke, bleeding events, cardiovascular hospitalizations, quality of life, and adverse effects of treatment. Data were synthesized and presented in tables, charts, and forest plots for meta-analysis where appropriate. The results indicate that both rate control and rhythm control strategies have their own merits and limitations, with the outcomes varying based on patient characteristics and comorbidities. While rhythm control strategies may lead to better symptom control and improved quality of life, rate control strategies may be associated with lower risks of adverse events and complications. This systematic review provides a comprehensive overview of the current evidence regarding rate and rhythm control strategies in AF management, offering insights for clinical decision-making and highlighting the need for individualized treatment approaches.
PubMed: 38169694
DOI: 10.7759/cureus.49869 -
Australian Critical Care : Official... Sep 2023Different types of interventions have been assessed for the prevention of adverse events. However, determining which patient-safety practice is most effective can be... (Review)
Review
BACKGROUND
Different types of interventions have been assessed for the prevention of adverse events. However, determining which patient-safety practice is most effective can be challenging when there is no systematised evidence synthesis. An overview following the best methodological standards can provide the best reliable integrative evidence.
OBJECTIVES
The objective of this study was to provide an overview of effectiveness nonpharmacological interventions aimed at preventing adverse events in the intensive care unit.
METHODS
A review of systematic reviews (SRs) was conducted according to the Cochrane Handbook and PRISMA recommendations. PubMed, CINAHL, and Cochrane Library were searched for SRs published until March 2022. Two reviewers independently assessed the study's quality, using AMSTAR-2, and extracted data on intervention characteristics and effect on prevention of adverse events.
RESULTS
Thirty-seven SRs were included, and 27 nonpharmacological interventions were identified to prevent 11 adverse events. Most of the reviews had critically low methodological quality. Among all the identified interventions, subglottic secretion drainage, semirecumbent position, and kinetic bed therapy were effective in preventing ventilator-associated pneumonia; the use of earplugs, early mobilisation, family participation, and music in reducing delirium; physical rehabilitation in improving muscle strength; use of respiratory support in preventing reintubation; the use of a computerised physician order entry system in reducing risk of medication errors; and the use of heated water humidifier was effective in reducing artificial airway occlusion.
CONCLUSIONS
Some nonpharmacological interventions reduced adverse events in the intensive care setting. These findings should be interpreted carefully due to the low methodological quality. SRs on preventing adverse events in the intensive care unit should adhere to quality assessment tools so that best evidence can be used in decision-making.
Topics: Humans; Critical Care; Intensive Care Units; Systematic Reviews as Topic
PubMed: 36572576
DOI: 10.1016/j.aucc.2022.11.003 -
American Journal of Clinical Dermatology Mar 2024Ruxolitinib cream is the first topical Janus kinase (JAK) inhibitor approved in the United States (US) for the treatment of mild to moderate atopic dermatitis and...
BACKGROUND
Ruxolitinib cream is the first topical Janus kinase (JAK) inhibitor approved in the United States (US) for the treatment of mild to moderate atopic dermatitis and nonsegmental vitiligo. A postmarketing study with oral tofacitinib, approved for rheumatoid arthritis, triggered class warnings for JAK inhibitors, including risk of serious infections, mortality, malignancy, major adverse cardiovascular events, and thrombosis. Because ruxolitinib cream is indicated for inflammatory conditions, it is subject to the same warnings as oral JAK inhibitors in the US. Here, nearly 14,000 patient-years of postmarketing safety data from the first year following market approval of ruxolitinib cream were reviewed.
METHODS
The Incyte global safety database (21 September 2021-20 September 2022) and US FDA Adverse Event Reporting System (as of 30 September 2022) were queried for adverse event (AE) reports received for ruxolitinib cream.
RESULTS
The search identified 294 postmarketing individual case safety reports containing 589 events, including four serious AEs and no fatal AEs. AEs (i.e., any unfavorable sign, symptom, or disease) representing >2% of all events included application site pain (n = 16), atopic dermatitis (n = 15), skin irritation (n = 15), scratch (n = 14), and condition aggravated (n = 13). The four serious AEs were skin cancer (n = 2), pericarditis, and thrombocytopenia (both n = 1), none of which had sufficient information to assess possible relatedness to ruxolitinib cream. Serious AEs associated with the class warnings for JAK inhibitors were not reported.
CONCLUSIONS
Postmarketing safety data from the year following approval suggest ruxolitinib cream is generally well tolerated, without significant systemic AEs, and with a low incidence of application site reactions.
Topics: Humans; United States; Dermatitis, Atopic; Janus Kinase Inhibitors; Nitriles; Emollients; Pyrazoles; Pyrimidines
PubMed: 38243107
DOI: 10.1007/s40257-023-00840-1 -
BMC Cancer Aug 2023Rucaparib has been approved for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer. However, the...
BACKGROUND
Rucaparib has been approved for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer. However, the long-term safety of rucaparib in large sample population was unknown. The presented study aimed to evaluate rucaparib-associated adverse events (AEs) according to the real-world pharmacovigilance database.
METHODS
Disproportionality analysis was conducted to assess the association between rucaparib and its AEs. Data were collected from the international pharmacovigilance database of US FDA Adverse Event Reporting System (FAERS) between January 2017 and June 2022. The characteristics of rucaparib-related AEs, and the onset time were further analyzed.
RESULTS
A total of 9,296,694 AE reports were recorded in the FAERS during the study period, among which 7,087 reports were associated with rucaparib. About 135 rucaparib-related AE signals in 15 system organ class (SOCs) were identified. The most common AEs included anaemia, thrombocytopenia, nausea, vomiting, fatigue, blood creatinine increase, alanine aminotransferase increase, and aspartate aminotransferase increase, which were listed in the label for rucaparib. Of note, 21 new and unexpected significant AEs that off-label were also found in our study, such as preferred term (PTs) of intestinal obstruction, gastrooesophageal reflux disease, blood iron decreased, dehydration, and hypersomnia. The median onset time of rucaparib-related AEs was 12 days (interquartile range [IQR] 1-62 days), and had early failure types.
CONCLUSION
Our study demonstrated potential new AEs of rucaparib, and further studies were expected to confirm the results.
Topics: Adult; Female; United States; Humans; Pharmacovigilance; Indoles; Databases, Factual; United States Food and Drug Administration
PubMed: 37568126
DOI: 10.1186/s12885-023-11201-w -
Healthcare (Basel, Switzerland) Feb 2024The level of safety in healthcare units is mainly characterized by the occurrence of medical adverse events. The aim of the study was to present the experiences of...
The level of safety in healthcare units is mainly characterized by the occurrence of medical adverse events. The aim of the study was to present the experiences of reporting clinical adverse events and the perceptions of nurses working in internal medicine wards, surgical wards and midwives on these issues. The cross-sectional survey was conducted from October 2022 to April 2023. The study used the Author's Survey Questionnaire and sampling by assessment was applied. The study included nurses working in internal medicine wards and surgical wards as well as midwives at nine hospitals in a large provincial city in Poland, amounting to 745 participants. A one-way analysis of variance ANOVA and a post-hoc test (Fisher's NIR) were used. The significance level () did not exceed 0.05. Nurses working in surgical wards, internal medicine wards and midwives thought that clinical adverse events should be reported, and perceived this as an important and useful activity in ensuring patient safety. The most common adverse events reported by respondents were falls F(2.742) = 52.07; = 0.001, bedsores F(2.742) = 19.62; = 0.001, patient disappearances F(2.742) = 3.98; = 0.019, and hospital-acquired infections F(2.742) = 3.88; = 0.021. The most frequently selected factors influencing the abandonment of adverse event reporting were excessively complex paperwork, no or little harm to the patient or a fear of the negative consequences. The study suggests that an important way to overcome the barriers to nurses and midwives reporting adverse events would be to create a supportive atmosphere in which they could report errors and the reasons for them honestly and without fear, and to improve the way adverse events are reported at the personal and institutional levels.
PubMed: 38391835
DOI: 10.3390/healthcare12040460 -
BMC Gastroenterology Sep 2023Validated, accepted grading tools for preprocedural complexity assessment in ERCP are lacking. We therefore created a grading system for ERCP based on the classification...
BACKGROUND
Validated, accepted grading tools for preprocedural complexity assessment in ERCP are lacking. We therefore created a grading system for ERCP based on the classification used by the American Society for Gastrointestinal Endoscopy (ASGE).
METHODS
Data on ERCP adverse events (AE) and success were collected in a multicenter, prospective uncontrolled study. Multiple logistic regressions were applied to success and AEs in accordance with the ASGE classification. Each procedure suggested by ASGE was tested against different outcomes. Results were used to create a score and were evaluated in a control cohort.
RESULTS
16,327 ERCPs were documented in 27 centers. Analysis of ASGE categorization (10,904 cases) showed that this model fails to adequately predict parameters of complexity; only for cardiopulmonary AEs and perforation was no significant variance evident. Depending on the specific clinical circumstances, probability of success of the intervention sometimes varied significantly in risk, implying a twofold score, one part for probability of success and one for risk. A split score with three levels each was designed and tested in a validation cohort (5,423 procedures). Achieving therapeutic targets / post-ERCP pancreatitis could be correctly predicted in 87.0%/95.3%.
CONCLUSIONS
Grading ERCP success and AEs have to be considered independently. Onefold grading systems appear incomplete and unable to provide an adequate classification of severity. SASE (Success and Adverse Event Score in Endoscopic Retrograde Cholangiopancreatography) was created to incorporate these findings. Showing high predictive value, this score could be a potent tool for planning ERCP and training in endoscopy.
Topics: Humans; Cholangiopancreatography, Endoscopic Retrograde; Prospective Studies; Pancreatitis; Probability; Research Design
PubMed: 37715151
DOI: 10.1186/s12876-023-02942-w -
European Annals of Allergy and Clinical... Nov 2023Kikuchi-Fujimoto Disease (KFD) or histiocytic necrotizing lymphadenitys is a rare disorder characterized by subacute necrotizing regional lymphadenopathy. It is usually...
Kikuchi-Fujimoto Disease (KFD) or histiocytic necrotizing lymphadenitys is a rare disorder characterized by subacute necrotizing regional lymphadenopathy. It is usually presented as painful cervical nodes and associated with fever, headache, night sweats, nausea, vomiting and sore throat. Etiology of KFD is still unclear, two theories have been proposed: infections and autoimmune origin. Due to recent reports of KFD related to COVID-19 vaccination, the novelty of the mechanism of these vaccines and the immunomodulated role of both matters, a literature and adverse event databases review was carried out in order to shed light on the relationship between these two matters. A search in the Spanish and the European adverse events databases (FEDRA and Eudravigilance) was performed. Search criteria were any drug and the diagnosis "Histiocytic necrotizing lymphadenitis" according to the Medical Dictionary for Medical Activities version 25.0. All adverse events registered as June 2, 2022, were included. FEDRA encompassed two KFD reports, one related to a mRNA COVID-19 vaccine. Eudravigilance included a total of 62 KFD cases, 14 of them associated to COVID-19 vaccines and eight to other vaccines. Pharmacovigilance is of utter importance in detecting adverse events caused by new vaccines. More research is needed to establish a final connection between KFD and COVD-19 vaccines, but due to the physiopathology of the condition, how vaccines stimulate the immune system and the high number of reported KFD cases with vaccines given its rare incidence, it is plausible to think that both entities are related.
Topics: Humans; COVID-19; COVID-19 Vaccines; Histiocytic Necrotizing Lymphadenitis; Pharmacovigilance; Vaccination
PubMed: 36458479
DOI: 10.23822/EurAnnACI.1764-1489.273