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Drug Discovery Today Sep 2023Adverse drug events (ADEs) are responsible for a significant number of hospital admissions and fatalities. Machine learning models have been developed to assess the... (Review)
Review
Adverse drug events (ADEs) are responsible for a significant number of hospital admissions and fatalities. Machine learning models have been developed to assess the individual patient risk of having an ADE. In this article, we have reviewed studies addressing the prediction of ADEs in observational health data with machine learning. The field of individualised ADE prediction is rapidly emerging through the increasing availability of additional data modalities (e.g., genetic data, screening data, wearables data) and advanced deep learning models such as transformers. Consequently, personalised adverse drug event predictions are becoming more feasible and tangible.
Topics: Humans; Drug-Related Side Effects and Adverse Reactions; Machine Learning
PubMed: 37467879
DOI: 10.1016/j.drudis.2023.103715 -
Current Eye Research Sep 2023The current study seeks to investigate the association between lacrimal disorders and the use of docetaxel and paclitaxel.
PURPOSE
The current study seeks to investigate the association between lacrimal disorders and the use of docetaxel and paclitaxel.
METHODS
A disproportionality analysis was conducted using the United States FDA Adverse Event Reporting System (FAERS). All adverse event reports containing the term docetaxel or paclitaxel were selected. Lacrimal adverse events were identified using the lacrimal disorders Standardized MedDRA Query (SMQ), which includes disorders that affect lacrimal gland and drainage system including blockage of nasolacrimal duct, occlusion/stenosis of punctum, lacrimal gland neoplasms, and inflammations and infections.
RESULTS
The proportionate reporting ratio (PRR) comparing lacrimal events among docetaxel to paclitaxel users was 2.47 (95% CI, 2.03-3.02). With respect to specific lacrimal events, dacryostenosis (PRR 19.54 [95% CI, 7.19-53.13]), increased lacrimation (PRR 3.2 [95% CI, 2.42-4.23]), lacrimation disorder ( = 0.02), and xeropthalmia reports ( > 0.001) were significantly more common.
CONCLUSIONS
The growing body of epidemiologic, clinical, and pathophysiologic research supports the case that docetaxel leads to adverse lacrimal events in certain patients and should be taken into consideration when oncologists consider docetaxel vs. paclitaxel.
Topics: Humans; United States; Docetaxel; Taxoids; Paclitaxel; Lacrimal Apparatus Diseases
PubMed: 37232564
DOI: 10.1080/02713683.2023.2219041 -
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 -
Journal For Nurses in Professional...Second victim phenomenon (SVP) occurs when nurses who are involved in an unanticipated adverse event become victimized and traumatized by the event. Following a needs...
Second victim phenomenon (SVP) occurs when nurses who are involved in an unanticipated adverse event become victimized and traumatized by the event. Following a needs assessment, an SVP education program was implemented, including adverse events and SVP experiences, available support, and a case study. Evaluation indicated nurses had improved knowledge and attitude and increased practice intent. Education that promotes awareness is the first step to support nurses who experience events that can precipitate SVP.
Topics: Humans; Program Evaluation; Medical Errors; Needs Assessment; Educational Status
PubMed: 37812129
DOI: 10.1097/NND.0000000000000978 -
Anticancer Research Jun 2024There have been advances in the development of immune checkpoint inhibitors for monotherapy and combination therapy with other anticancer agents in recent years. The...
BACKGROUND/AIM
There have been advances in the development of immune checkpoint inhibitors for monotherapy and combination therapy with other anticancer agents in recent years. The combination of bevacizumab, carboplatin, and paclitaxel with atezolizumab, an anti-programmed death ligand 1 antibody (ABCP therapy), has been reported to be effective for treating non-small cell lung cancer. However, reports on its adverse events are limited. In this study, a survey and disproportionality analysis based on the Japanese Adverse Drug Event Report (JADER) database was conducted to elucidate the adverse event profile of ABCP therapy.
MATERIALS AND METHODS
The reporting odds ratio (ROR) and information component were used as indicators for the disproportionality analysis. The ROR was also used to assess the changes in the reporting intensity with combination therapy, and the mutual exclusivity of the 95% confidence interval between the compared groups was considered.
RESULTS
The reported adverse events of ABCP therapy mirrored those of the individual drugs that constituted it. ABCP therapy enhanced the reporting intensity of adverse events related to leukocytes and the skin, while decreased those related to interstitial lung disease and hepatic function abnormality as immune-related adverse events caused by atezolizumab, and gastrointestinal perforation caused by bevacizumab.
CONCLUSION
Our analysis of data from the JADER database has revealed the adverse event profile of ABCP therapy. Our findings emphasize the importance of effectively managing febrile neutropenia and skin-related adverse events in ABCP therapy.
Topics: Humans; Carboplatin; Bevacizumab; Paclitaxel; Antineoplastic Combined Chemotherapy Protocols; Antibodies, Monoclonal, Humanized; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Female; Male
PubMed: 38821611
DOI: 10.21873/anticanres.17072 -
Andrology May 2024Sildenafil, a selective inhibitor of phosphodiesterase type 5 (PDE5), is widely used for the treatment of erectile dysfunction (ED). However, the safety profile of...
BACKGROUND
Sildenafil, a selective inhibitor of phosphodiesterase type 5 (PDE5), is widely used for the treatment of erectile dysfunction (ED). However, the safety profile of sildenafil, including adverse event (AEs), requires comprehensive evaluation.
METHODS
This retrospective pharmacovigilance study aimed to evaluate AEs linked to sildenafil by analyzing data sourced from the FDA Adverse Event Reporting System (FAERS) database. A case/non-case design was utilized, and various algorithms including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multiitem gamma Poisson shrinker (MGPS) were employed to measure the signals indicating the presence of sildenafil-related AEs.
RESULTS
Among 339,230 reports, 33,692 specifically mentioned sildenafil use. Most of AEs occurred in males over 60 years old. The United States accounted for the highest proportion of reported AEs. Severe outcomes, including death, disability, and life-threatening events, were reported. Significant system organ class (SOC) included "Reproductive system and breast disorders" (SOC: 10038604), "Neoplasms benign, malignant and unspecified" (SOC: 10038738), "Vascular disorders" (SOC: 10047065), and "Blood and lymphatic system disorders" (SOC: 10005329). Noteworthy preferred terms (PTs) associated with sildenafil included "Vision blurred," "Flushing," "sudden hearing loss," "Painful erection," and "Priapism." Unexpected AEs, such as "Malignant melanoma," "Pulmonary hypertension," "Malignant melanoma in situ," "Pulmonary arterial hypertension," "Metastatic malignant melanoma," "Malignant melanoma stage III," "Malignant melanoma stage II," "Acquired hemophilia," "Aortic dissection rupture," and "Intracranial artery dissection" were also identified.
CONCLUSIONS
These findings emphasize the importance of monitoring and understanding the potential risks associated with sildenafil. Further investigation is warranted to validate these associations and address previously unrecognized safety concerns.
Topics: Male; Humans; Middle Aged; Sildenafil Citrate; Melanoma; Bayes Theorem; Pharmacovigilance; Retrospective Studies
PubMed: 37724699
DOI: 10.1111/andr.13533 -
BMC Cancer Oct 2023Antibody-drug conjugates (ADCs) that target human epidermal growth factor receptor 2 (HER2) are leading a new era of targeted cancer therapy. These drugs have also been... (Meta-Analysis)
Meta-Analysis
Incidence and risk of fatal adverse events in cancer patients treated with HER2-targeted antibody-drug conjugates: a systematic review and meta-analysis of randomized controlled trials.
OBJECTIVE
Antibody-drug conjugates (ADCs) that target human epidermal growth factor receptor 2 (HER2) are leading a new era of targeted cancer therapy. These drugs have also been associated with several fatal adverse events, such as pneumonia, interstitial lung disease, and infection. We performed a meta-analysis of randomized controlled trials (RCTs) to estimate the incidence and risk of fatal adverse events in cancer patients treated with HER2-targeted ADCs.
METHODS
We performed a systematic search in Embase, PubMed, Web of Science, and Scopus databases from inception to February 1, 2022, and the last search was updated to July 1, 2023. The eligible studies for inclusion in our analysis were limited to RCTs of HER2-targeted ADCs that were approved by the US Food and Drug Administration and examined on cancer patients with available data on fatal adverse events. The protocol for this study was registered in PROSPERO (No. CRD42022331627).
RESULTS
Fifteen studies (13 RCTs) involving 7,277 patients were finally included for meta-analysis. Of these patients, 4,246 received HER2-targeted ADCs and 3,481 received the control treatment. The data were combined using Bayesian hierarchical modeling, which allowed for the estimation of the mean incidence of fatal adverse events to be 0.78% (95% CrI: 0.28-1.37%, τ = 0.006) for the patients treated with HER2-targeted ADCs. The relative risk was 0.80 (95% CrI, 0.5-1.26, τ = 0.17) compared to control patients. Among 43 reported deaths caused by HER2-targeted ADCs, the most common fatal adverse event was respiratory toxicity, including pneumonia, pneumonitis, and interstitial lung disease. On subgroup analysis, no difference in the risk of fatal adverse events was found between different HER2-targeted ADCs or cancer types.
CONCLUSION
Our findings suggest that the risk of fatal adverse events with HER2-targeted ADCs may be lower compared to standard control therapies in cancer patients, and there is no significant difference in risk observed between different HER2-targeted ADCs or cancer types. However, the most common fatal adverse event was respiratory toxicity, suggesting that cancer patients who use the above drugs should strengthen respiratory system monitoring and take preventive measures in some severe cases.
Topics: Humans; Immunoconjugates; Incidence; Randomized Controlled Trials as Topic; Neoplasms; Pneumonia; Lung Diseases, Interstitial
PubMed: 37817092
DOI: 10.1186/s12885-023-11250-1 -
JACC. CardioOncology Apr 2024Combination therapy with immune checkpoint inhibitors (ICIs) and vascular endothelial growth factor inhibitors (VEGFIs) has improved cancer outcomes and is increasingly...
BACKGROUND
Combination therapy with immune checkpoint inhibitors (ICIs) and vascular endothelial growth factor inhibitors (VEGFIs) has improved cancer outcomes and is increasingly used. These drug classes are associated with cardiovascular toxicities when used alone, but heterogeneity in trial design and reporting may limit knowledge of toxicities in patients receiving these in combination.
OBJECTIVES
The aim of this study was to assess consistency and clarity in definitions and reporting of cardiovascular eligibility criteria, baseline characteristics, and cardiovascular adverse events in ICI and VEGFI combination trials.
METHODS
A scoping review was conducted of phase 2 to 4 randomized controlled trials of ICI and VEGFI combination therapy for solid tumors. Trial cardiovascular eligibility criteria and baseline cardiovascular characteristic reporting in trial publications was assessed, and cardiovascular adverse event definitions and reporting criteria were also examined.
RESULTS
Seventeen trials (N = 10,313; published 2018-2022) were included. There were multiple cardiovascular exclusion criteria in 15 trials. No primary trial publication reported baseline cardiovascular characteristics. Thirteen trials excluded patients with prior heart failure, myocardial infarction, hypertension, or stroke. There was heterogeneity in defining cardiovascular conditions. "Grade 1 to 4" cardiovascular adverse events were reported when incidence was ≥5% to 25% in 15 trials. Incident hypertension was recorded in all trials, but other cardiovascular events were not consistently reported. No trial specifically noted the absence of cardiovascular events.
CONCLUSIONS
In ICI and VEGFI combination trials, there is heterogeneity in cardiovascular exclusion criteria, reporting of baseline characteristics, and reporting of cardiovascular adverse events. This limits an optimal understanding of the incidence and severity of events relating to these combinations. Better standardization of these elements should be pursued. (Exclusions and Representation of Patients With Kidney Disease and Cardiovascular Disease in Drug Trials of the Novel Systemic Anti-Cancer Therapies VEGF-Signalling Pathway Inhibitors Alone or in Combination With Immune Checkpoint Inhibitors; CRD42022337942).
PubMed: 38774021
DOI: 10.1016/j.jaccao.2023.12.010 -
Clinical Genitourinary Cancer Oct 2023The potential cardiovascular adverse events associated with new-generation androgen receptor pathway inhibitors (ARPI) in the treatment of prostate cancer remain...
Cardiovascular Adverse Events Associated With New-Generation Androgen Receptor Pathway Inhibitors (ARPI) for Prostate Cancer: A Disproportionality Analysis Based on the FDA Adverse Event Reporting System (FAERS).
BACKGROUND
The potential cardiovascular adverse events associated with new-generation androgen receptor pathway inhibitors (ARPI) in the treatment of prostate cancer remain unclear. We aimed to assess the pharmacovigilance (PV), reporting rate, severity, and reaction outcomes of major adverse cardiovascular events (MACE) related to new-generation ARPI for prostate cancer reported to the United States Food and Drug Administration Adverse Event Reporting System (FAERS).
METHODS
We analyzed reports of cardiovascular adverse events associated with drug therapy for prostate cancer submitted to FAERS between January 2014 and December 2022. Three primary new-generation ARPIs were identified: abiraterone acetate, enzalutamide, and apalutamide. Our primary composite endpoint was the PV of MACE caused by ARPIs in the treatment of prostate cancer, and the secondary endpoint was PV of other cardiovascular events. The software implemented was STATA 17.0 MP.
RESULTS
A total of 278,031 suspected drug-adverse event pairs related to drug treatment in patients with prostate cancer were identified, of which 10,861 reports were cardiovascular events, including 5800 reports of MACE and 5061 reports of other cardiovascular events. The majority of these cardiovascular adverse event reports came from the United States (36.6%) and were mostly older men (age 76.0 ± 8.6 years). Compared with enzalutamide, the constituent ratio of MACE caused by abiraterone acetate and apalutamide was significantly increased, but the incidence of severe MACE decreased significantly. The PV signal regarding MACE was detected in abiraterone acetate and apalutamide but not in enzalutamide.
CONCLUSION
Abiraterone acetate and apalutamide presumably are associated with a higher risk of MACE than enzalutamide in new-generation ARPI for prostate cancer. More extensive prospective studies and more extended follow-up periods need to confirm this further.
PubMed: 37482524
DOI: 10.1016/j.clgc.2023.07.003 -
International Journal of Cardiology May 2024Psoriasis is a chronic skin condition characterized by hyperproliferation of epidermal keratinocytes, resulting in erythematous and scaling lesions. The US Food and Drug...
INTRODUCTION
Psoriasis is a chronic skin condition characterized by hyperproliferation of epidermal keratinocytes, resulting in erythematous and scaling lesions. The US Food and Drug Administration (FDA) has approved nine biologic agents to address the burden of psoriasis, but their cardiovascular risks remain poorly studied.
METHODS
This retrospective pharmacovigilance study utilized the FDA Adverse Event Reporting System (FAERS) database to analyze adverse events associated with newly approved therapeutic agents for psoriasis. We employed disproportionally signal analysis, calculating the reporting odds ratio (ROR) with a 95% confidence interval.
RESULTS
Among the vast FAERS database, which contained >25 million adverse events, a total of 334,399 events were associated with newly approved therapeutic agents for psoriasis. Cardiac adverse events accounted for 3852 cases, including pericarditis, atrial fibrillation, and coronary artery disease. Secukinumab had the highest number of reported adverse events, followed by brodalumab, while tildrakizumab had the lowest. Coronary artery disease was the most reported adverse event (1438 cases), followed by pericarditis (572 cases) and atrial fibrillation (384 cases). Secukinumab had the highest incidence of coronary artery disease, pericarditis, and atrial fibrillation. Risankizumab was significantly associated with an increased risk of coronary artery disease and atrial fibrillation, while tildrakizumab and Ixekizumab were associated with atrial fibrillation. Secukinumab was associated with an elevated risk of pericarditis.
CONCLUSIONS
The study uncovers the cardiovascular adverse effects related to biologic agents used in psoriasis treatment. These findings emphasize the importance of monitoring and evaluating the cardiovascular safety profiles of biological agents used in psoriasis treatment.
Topics: Humans; United States; Cardiotoxicity; Atrial Fibrillation; Retrospective Studies; Coronary Artery Disease; Psoriasis; Pharmacovigilance; Pericarditis; Biological Products; United States Food and Drug Administration
PubMed: 38301830
DOI: 10.1016/j.ijcard.2024.131819