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Current Hematologic Malignancy Reports Apr 2021Reporting of adverse events on hematology clinical trials is crucial to understanding the safety of standard treatments and novel agents. However, despite the importance... (Review)
Review
PURPOSE OF REVIEW
Reporting of adverse events on hematology clinical trials is crucial to understanding the safety of standard treatments and novel agents. However, despite the importance of understanding toxicities, challenges in capturing and reporting accurate adverse event data exist.
RECENT FINDINGS
Currently, adverse events are reported manually on most hematology clinical trials. Especially on phase III trials, the highest grade of each adverse event during a reporting period is typically reported. Despite the effort committed to AE reporting, studies have identified underreporting of adverse events on hematologic malignancy clinical trials, which raises concern about the true understanding of safety of treatment that clinicians have in order to guide patients about what to expect during therapy. In order to address these concerns, recent studies have piloted alternative methods for identification of adverse events. These methods include automated extraction of adverse event data from the electronic health record, implementation of trigger or alert tools into the medical record, and analytic tools to evaluate duration of adverse events rather than only the highest adverse event grade. Adverse event reporting is a crucial component of clinical trials. Novel tools for identifying and reporting adverse events provide opportunities for honing and refining methods of toxicity capture and improving understanding of toxicities patients experience while enrolled on clinical trials.
Topics: Clinical Trials as Topic; Delivery of Health Care; Drug-Related Side Effects and Adverse Reactions; Hematologic Diseases; Humans; Quality Improvement; Risk Management
PubMed: 33786724
DOI: 10.1007/s11899-021-00627-3 -
Journal of Ophthalmic Inflammation and... Feb 2023Immune checkpoint inhibitors (ICIs) have become an important part of the treatment of multiple cancers, especially for advanced melanoma and non-small cell lung cancer.... (Review)
Review
INTRODUCTION
Immune checkpoint inhibitors (ICIs) have become an important part of the treatment of multiple cancers, especially for advanced melanoma and non-small cell lung cancer. Some tumors are capable of escaping immunosurveillance by stimulating checkpoints on T-cells. ICIs prevent activation of these checkpoints and thereby stimulate the immune system and indirectly the anti-tumor response. However, the use of ICIs is associated with various adverse events. Ocular side effects are rare but may have a major impact on the quality of life of the patient.
METHODS
A comprehensive literature search of the medical databases Web of Science, Embase and PubMed was performed. Articles that provided a comprehensive description of a case report containing 1) cancer patient(s) treated with (a combination of) immune checkpoint inhibitors, and 2) assessed occurrence of ocular adverse events, were included. A total of 290 case reports were included.
RESULTS
Melanoma (n = 179; 61.7%) and lung cancer (n = 56; 19.3%) were the most frequent reported malignancies. The primary used ICIs were nivolumab (n = 123; 42.5%) and ipilimumab (n = 116; 40.0%). Uveitis was most the common adverse event (n = 134; 46.2%) and mainly related to melanoma. Neuro-ophthalmic disorders, including myasthenia gravis and cranial nerve disorders, were the second most common adverse events (n = 71; 24.5%), mainly related to lung cancer. Adverse events affecting the orbit and the cornea were reported in 33 (11.4%) and 30 cases (10.3%) respectively. Adverse events concerning the retina were reported in 26 cases (9.0%).
CONCLUSION
The aim of this paper is to provide an overview of all reported ocular adverse events related to the use of ICIs. The insights retrieved from this review might contribute to a better understanding of the underlying mechanisms of these ocular adverse events. Particularly, the difference between actual immune-related adverse events and paraneoplastic syndromes might be relevant. These findings might be of great value in establishing guidelines on how to manage ocular adverse events related to ICIs.
PubMed: 36811715
DOI: 10.1186/s12348-022-00321-2 -
Frontiers in Pharmacology 2023To mine the adverse drug event (ADE) signals of upadacitinib based on the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database to provide...
To mine the adverse drug event (ADE) signals of upadacitinib based on the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database to provide a reference for the safe clinical use of the drug. The ADE data for upadacitinib from Q1 2004 to Q1 2023 in the FAERS database were retrieved, and data mining was performed using the reporting odds ratio and proportional reporting ratio. A total of 21,213 ADE reports for the primary suspect drug upadacitinib were obtained, involving 444 ADEs. Patients aged ≥60 years (21.48%) and female (70.11%) patients were at a higher risk of ADEs with upadacitinib. After data cleaning, 182 ADE signals from 19 system organ classes (SOCs) were obtained. Six of these SOCs that occurred more frequently and were not mentioned in the drug labeling information included renal and urinary system (1.09%), reproductive and breast diseases (1.14%), ear and labyrinth disorders (0.57%), psychiatric disease (0.57%), blood and lymphatic system disorders (0.57%), and endocrine disorders (0.57%). The top ten most frequent ADE signals reported for upadacitinib were mainly related to: infections and infestations (7), investigations (2), and skin and subcutaneous tissue disorders (1). The top 10 ADEs in signal intensity ranking were lip neoplasm, ureteral neoplasm, eczema herpeticum, vulvar dysplasia, mediastinum neoplasm, eosinopenia, herpes zoster cutaneous disseminated, eye ulcer, acne cystic, and infection. The top 10 high-frequency events leading to serious adverse events were urinary tract infection (2.74%), herpes zoster (1.63%), diverticulitis (1.19%), bronchitis (0.68%), nasopharyngitis (0.68%), localised infection (0.66%), nephrolithiasis (0.66%), pulmonary thrombosis (0.66%), blood cholesterol increased (0.55%), and pneumonia (0.53%). Clinicians should be vigilant to upadacitinib-induced events in systems not covered in the drug labeling information and to new and highly signaled ADEs to ensure the safe and effective use of upadacitinib.
PubMed: 37663269
DOI: 10.3389/fphar.2023.1200254 -
Journal of Clinical Pharmacology Jun 2021The efficacy and safety of a drug is dose or exposure related, and both are used to assess the benefit-risk balance of a given drug and ultimately to decide on the... (Review)
Review
The efficacy and safety of a drug is dose or exposure related, and both are used to assess the benefit-risk balance of a given drug and ultimately to decide on the specific drug license, including its dose and indication(s). Unfortunately, both efficacy and safety are much more difficult to establish in neonates, resulting in very few drugs licensed for use in this vulnerable population. This review will focus on dose-related adverse events in neonates. Besides the regulatory classification on seriousness, adverse event assessment includes aspects related to signal detection, causality, and severity. Disentangling confounders from truly dose-related adverse drug events remains a major challenge, as illustrated for drug-induced renal impairment, drug-induced liver injury, and neurodevelopmental outcome. Causality assessment, using either routine tools (Naranjo algorithm, World Health Organization's Uppsala Monitoring Center causality tool) or a Naranjo algorithm tailored to neonates, still does not sufficiently and reliably document causality in neonates. Finally, very recently, a first neonatal severity-grading tool for neonates has been developed. Following the development of advanced pharmacokinetic approaches and techniques to predict and assess drug exposure, additional efforts are needed to truly and fully assess dose adverse drug events. To further operationalize the recently developed tools on causality and severity, reference databases on a palette of biomarkers and outcome variables and their covariates are an obvious next step. These databases should subsequently be integrated in modeling efforts to truly explore safety outcome, including aspects associated with or caused by drug dose or exposure.
Topics: Causality; Chemical and Drug Induced Liver Injury; Drug-Related Side Effects and Adverse Reactions; Humans; Infant, Newborn; Kidney; Neurocognitive Disorders; Pharmacovigilance
PubMed: 34185907
DOI: 10.1002/jcph.1827 -
Journal of Psychiatric Research May 2024Neuromodulatory interventions are relatively novel and approaches to studying harms and tolerability have varied. Using a checklist based on guidelines from Good... (Review)
Review
Neuromodulatory interventions are relatively novel and approaches to studying harms and tolerability have varied. Using a checklist based on guidelines from Good Clinical Practice and the Harms Extension of the CONSORT (Consolidated Standards of Reporting Trials) Statement, we identified how adverse events are measured, assessed, and reported in studies evaluating neuromodulation for the treatment of mental and neurodevelopmental disorders among children and adolescents. A systematic literature review identified 56 experimental and quasi-experimental studies evaluating transcranial magnetic stimulation (TMS), transcranial alternating (tACS) or direct (tDCS) current stimulation, transcranial pulse stimulation (TPS), and vagus or trigeminal nerve stimulation (VNS or TNS). For 22 studies (39%), the types of adverse events to be monitored were identified, and for 31 studies (55%), methods for collecting adverse event data were described. Methods for assessing adverse events were less commonly described with 23 studies (41%) having details on assessing event severity, and 11 studies (20%) having details on assessing event causality. Among 31 studies with reported results, headache, skin irritation, and general pain or discomfort were the most reported across studies. Seizure, untoward medical occurrences, and intracranial bleeding, edema, or other intracranial pathology were considered serious events, but these events were not reported as occurring in any results-based papers. Taken together, the findings from this review indicate that most studies of pediatric neuromodulatory interventions did not include descriptions of adverse event monitoring and evaluation. Comprehensive event monitoring and reporting across studies can significantly augment the current knowledge base.
PubMed: 38761518
DOI: 10.1016/j.jpsychires.2024.05.035 -
Current Reviews in Clinical and... 2022Several studies reported that abnormal behavior was noted in pediatric patients receiving several drugs, including neuraminidase inhibitors (NIs). However, the...
BACKGROUND
Several studies reported that abnormal behavior was noted in pediatric patients receiving several drugs, including neuraminidase inhibitors (NIs). However, the information on drugs associated with abnormal behavior in a real-world setting remains limited. The purpose of this study was to clarify the drugs associated with abnormal behavior using a spontaneous reporting system database.
METHODS
We performed a retrospective pharmacovigilance disproportionality analysis using the Japanese Adverse Drug Event Report database. Adverse event reports submitted to the Pharmaceuticals and Medical Devices Agency were analyzed, and the reporting odds ratio at 95% confidence interval were calculated.
RESULTS
A total of 1,144 reports of abnormal behavior were identified. The signals were detected through the association of 4 neuraminidase inhibitors (oseltamivir, zanamivir, laninamivir, and peramivir) with the abnormal behaviour. These signals were stronger for oseltamivir than other neuraminidase inhibitors. The signals were also detected for acetaminophen and montelukast.
CONCLUSION
Our results should be able to raise physicians' awareness of drugs associated with abnormal behavior, but further investigation of these medications is warranted.
Topics: Child; Drug-Related Side Effects and Adverse Reactions; Humans; Oseltamivir; Pharmacovigilance; Retrospective Studies; Zanamivir
PubMed: 33588740
DOI: 10.2174/1574884716666210215104540 -
Medical Science Monitor : International... Nov 2021Healthcare professionals have an ethical, medico-legal, and professional responsibility to report all suspected adverse events following immunization to relevant...
Healthcare professionals have an ethical, medico-legal, and professional responsibility to report all suspected adverse events following immunization to relevant national reporting agencies as part of the process of post-marketing drug safety monitoring. In the US, the Vaccine Adverse Event Reporting System (VAERS) is co-sponsored by the Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA). Data from VAERS and other national and global reporting systems show very low rates of adverse events related to currently approved SARS-CoV-2 vaccines. Populations studies have supported the findings from adverse event reporting systems. The presentation, monitoring, and reporting of adverse events related to SARS-CoV-2 vaccines may have future applications in vaccine monitoring for several other potential pandemic zoonotic infections. This editorial aims to summarize the current understanding of adverse events from current COVID-19 vaccines from global adverse event reporting systems, rather than individual case reports or anecdotal reporting in the media.
Topics: Adverse Drug Reaction Reporting Systems; COVID-19; COVID-19 Vaccines; Humans; International Agencies; SARS-CoV-2; Vaccination; COVID-19 Drug Treatment
PubMed: 34719663
DOI: 10.12659/MSM.935299 -
Journal of Personalized Medicine Jul 2021Cytochrome P450 (CYP) is involved in the metabolism of statins; CYP3A5 is the main enzyme responsible for lipophilic statin metabolism. However, the evidence of the... (Review)
Review
Cytochrome P450 (CYP) is involved in the metabolism of statins; CYP3A5 is the main enzyme responsible for lipophilic statin metabolism. However, the evidence of the association between polymorphism and the risk of statin-induced adverse events remains unclear. Therefore, this study aimed to perform a systematic review and meta-analysis to investigate the relationship between the polymorphism and the risk of statin-induced adverse events. The PubMed, Web of Science, and EMBASE databases were searched for qualified studies published until August 2020. Observational studies that included the association between statin-induced adverse events and the polymorphism were reviewed. The odds ratios (ORs) and 95% confidence intervals (CIs) were evaluated to assess the strength of the relationship. The Mantel-Haenszel method was used to provide the pooled ORs. Heterogeneity was estimated with I statistics and publication bias was determined by Begg's and Egger's test of the funnel plot. Data analysis was performed using Review Manager (version 5.4) and R Studio (version 3.6). In total, data from 8 studies involving 1614 patients were included in this meta-analysis. The polymorphism was found to be associated with the risk of statin-induced adverse events (*3/*3 vs. *1/*1 + *1/*3: OR = 1.40, 95% CI = 1.08-1.82). For myopathy, the pooled OR was 1.30 (95% CI: 0.96-1.75). The subgroup analysis of statin-induced myopathy revealed a trend, which did not achieve statistical significance. This meta-analysis demonstrated that the polymorphism affected statin-induced adverse event risk. Therefore, genotyping may be useful to predict statin toxicity.
PubMed: 34357144
DOI: 10.3390/jpm11070677 -
The Journal of Cardiovascular Nursing 2019The number of individuals with advanced heart failure (HF) receiving left ventricular assist devices (LVADs) is growing. Postimplantation LVAD recipients return home to... (Comparative Study)
Comparative Study
BACKGROUND
The number of individuals with advanced heart failure (HF) receiving left ventricular assist devices (LVADs) is growing. Postimplantation LVAD recipients return home to both rural and urban locations. The impact of rural or urban living on postimplantation outcomes has not been adequately explored.
OBJECTIVE
This cohort study examined adverse event-free survival, hospitalization-free survival, and all-cause mortality between rural and urban LVAD recipients in the first 2 years after implantation.
METHODS
Data from LVAD recipients (N = 141) implanted at a single center in the northeastern United States were analyzed. Recipients of LVAD were designated as rural or urban by county of residence. Adverse events, hospitalizations, and survival time were examined using multivariate Cox proportional hazards models.
RESULTS
Thirty-seven percent of LVAD recipients in the cohort were rural. Two-thirds of all LVAD recipients experienced at least 1 adverse event (96/141, 68.1%). Although more urban recipients experienced adverse events, including death, rural versus urban models of both adverse events and survival were nonsignificant (adverse events: log-rank = 1.18, P = .28; hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.57-1.63; P = .89; survival: log-rank =2.81, P = .09; HR, 0.45; 95% CI, 0.17-1.23; P = .12). Rural LVAD recipients experienced significantly more hospitalizations and shorter hospitalization-free survival (log-rank = 6.67, P = .009). However, the HR for survival was nonsignificant (HR, 1.5; 95% CI, 0.94-2.39; P = .08).
CONCLUSIONS
Frequent adverse events and hospitalizations are of ongoing concern for LVAD recipients. More data are necessary to understand why urban LVAD recipients may experience shorter survival time compared with rural counterparts. Hospitalization may serve as a protective factor for rural LVAD recipients.
Topics: Aged; Cohort Studies; Disease-Free Survival; Female; Heart Failure; Heart-Assist Devices; Hospitalization; Humans; Male; Middle Aged; Progression-Free Survival; Rural Health; Urban Health
PubMed: 31365445
DOI: 10.1097/JCN.0000000000000597 -
Epilepsy Research Aug 2022There have been several reports that switching formulations of antiseizure medications (ASMs) has been associated with a deterioration of seizure control, seizure...
There have been several reports that switching formulations of antiseizure medications (ASMs) has been associated with a deterioration of seizure control, seizure relapse or increased adverse effects. Considering recent findings that excipients, namely purported inactive ingredients, may nevertheless exert biological effects, it is possible that the variation in adverse event profile of antiseizure drugs may be related to differences in excipients. To test our hypothesis, we constructed a new research tool to connect FDA-compiled adverse event reports to the excipient in the medicine. Analysis of adverse events to formulations of five different second-generation antiseizure drugs - gabapentin, lamotrigine, levetiracetam, oxcarbazepine, and topiramate - showed several significant associations between specific excipient in the formulations and an adverse event when compared to the same medicine formulated with other excipients. Epilepsy and seizure adverse events were associated with multiple excipients across gabapentin, lamotrigine, and levetiracetam formulations. A different group of excipients were associated with reports of hypersensitivity reactions including urticaria, rash, erythema, and Stevens-Johnson syndrome. Our study provides a novel approach to analyzing post-market surveillance reports by including excipients. It may be useful to clinicians when evaluating select patient groups that may be refractory to pharmacological treatment or experience worsening adverse events when switching formulations of the same antiseizure medicine.
Topics: Anticonvulsants; Drug Compounding; Excipients; Gabapentin; Humans; Lamotrigine; Levetiracetam; Seizures
PubMed: 35661571
DOI: 10.1016/j.eplepsyres.2022.106947