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International Journal of Environmental... Jun 2020Adverse events are common in healthcare. Three types of victims of patient-related adverse events can be identified. The first type includes patients and their families,... (Review)
Review
Adverse events are common in healthcare. Three types of victims of patient-related adverse events can be identified. The first type includes patients and their families, the second type includes healthcare professionals involved in an adverse event and the third type includes healthcare organisations in which an adverse event occurs. The purpose of this integrative review is to synthesise knowledge, theory and evidence regarding action after adverse events, based on literature published in the last ten years (2009-2018). In the studies critically evaluated ( = 25), key themes emerged relating to the first, second and third victim elements. The first victim elements comprise attention to revealing an adverse event, communication after an event, first victim support and complete apology. The second victim elements include second victim support types and services, coping strategies, professional changes after adverse events and learning about adverse event phenomena. The third victim elements consist of organisational action after adverse events, strategy, infrastructure and training and open communication about adverse events. There is a lack of comprehensive models for action after adverse events. This requires understanding of the phenomenon along with ambition to manage adverse events as a whole. When an adverse event is identified and a concern expressed, systematic damage preventing and ameliorating actions should be immediately launched. System-wide development is needed.
Topics: Adaptation, Psychological; Adolescent; Child; Communication; Cross-Sectional Studies; Health Personnel; Humans; Learning; Medical Errors; Middle Aged
PubMed: 32630041
DOI: 10.3390/ijerph17134717 -
EClinicalMedicine May 2023With the increasing use of immune checkpoint inhibitors (ICIs) for tumour immunotherapy, the immune-related adverse events (irAEs) caused by their collateral effect on...
BACKGROUND
With the increasing use of immune checkpoint inhibitors (ICIs) for tumour immunotherapy, the immune-related adverse events (irAEs) caused by their collateral effect on the immune system pose a key challenge for the clinical application of ICIs. Psychiatric adverse events are a class of adverse events associated with ICIs that are realistically observed in the real world. We aim to provide a comprehensive study and summary of psychiatric adverse events associated with ICIs.
METHODS
We obtained ICI adverse reaction reports during January 2012-December 2021 from the FDA Adverse Event Reporting System (FAERS) database. ICI reports underwent screening to minimize the influence of other adverse reactions, concomitant medications, and indications for medication use that may also contribute to psychiatric disorders. Disproportionality analysis was performed to find psychiatric adverse events associated with ICIs by comparing ICIs with the full FAERS database using the reporting odds ratio (ROR). Influencing factors were explored based on univariate logistic regression analysis. Finally, the Cancer Genome Atlas (TCGA) pan-cancer transcriptome data were combined to explore the potential biological mechanisms associated with ICI-related pAEs.
FINDINGS
Reports of psychiatric adverse events accounted for 2.71% of the overall ICI adverse event reports in the FAERS database. Five categories of psychiatric adverse events were defined as ICI-related psychiatric adverse events (pAEs). The median age of reports with ICI-related pAEs was 70 (interquartile range [IQR] 24-95), with 21.54% of reports having a fatal outcome. Cases with indications for lung cancer, skin cancer and kidney site cancer accounted for the majority. The odds of ICI-related pAEs increased in older patients (65-74: OR = 1.44 [1.22-1.70], < 0.0001: ≥75: OR = 1.84 [1.54-2.20], < 0.0001). The occurrence of ICI-related pAEs may be related to NOTCH signalling and dysregulation of synapse-associated pathways.
INTERPRETATION
This study investigated psychiatric adverse events highly associated with ICI treatment, their influencing factors and potential biological mechanisms, which provides a reliable basis for further in-depth study of ICI-related pAEs. However, as an exploratory study, our findings need to be further confirmed in a large-scale prospective study.
FUNDING
This work was supported by the Natural Science Foundation of Guangdong Province (2018A030313846 and 2021A1515012593), the Science and Technology Planning Project of Guangdong Province (2019A030317020) and the National Natural Science Foundation of China (81802257, 81871859, 81772457, 82172750 and 82172811). Guangdong Basic and Applied Basic Research Foundation (Guangdong - Guangzhou Joint Fouds) (2022A1515111212). This work was supported by Key Research and Development Projects of Sichuan Science and Technology (2022YFS0221, 2022YFS0074, 2022YFS0156 and 2022YFS0378). Sichuan Provincial People's Hospital Hospital Young Talent Fund (2021QN08).
PubMed: 37131541
DOI: 10.1016/j.eclinm.2023.101967 -
Dermatology and Therapy Mar 2023Janus kinase (JAK) inhibitors are disease-modifying agents with efficacy in treating a spectrum of burdensome dermatologic conditions. The US Food and Drug... (Review)
Review
Janus kinase (JAK) inhibitors are disease-modifying agents with efficacy in treating a spectrum of burdensome dermatologic conditions. The US Food and Drug Administration (FDA) recently placed a black box warning on this class of medications due to safety concerns based on data from studies investigating tofacitinib in patients with rheumatoid arthritis. Here we provide an overview of the timeline of FDA approval of JAK inhibitors in dermatology. We also discuss the available safety profiles of approved oral JAK1 inhibitors, namely abrocitinib and upadacitinib, oral baricitinib, a JAK1/2 inhibitor, deucravacitinib, a Tyk2 inhibitor, and the topical JAK1/2 inhibitor ruxolitinib in dermatology patients. Additionally, we offer suggestions for initial screening and laboratory monitoring for patients receiving JAK inhibitors. We found that the rates of venous thromboembolism reported in trials ranged from no events to 0.1-0.5% in dermatology-specific phase 3 clinical trials compared with no events in the placebo. The rates of cardiovascular events ranged from no events to 0.4-1.2% compared with no events to 0.5-1.2% in the placebo. The rates of serious infections were 0.4-4.8% compared with no events to 0.5-1.3% in the placebo. The rates of nonmelanoma skin cancer (NMSC) ranged from no event to 0.6-0.9% compared with no events in the placebo. The rates of non-NMSC ranged from no event to 0.2-0.7% compared with no event to 0.6% in the placebo. Most patients who developed these adverse events had risk factors for the specific event. The most common adverse events of oral JAK inhibitors included upper respiratory infections, nasopharyngitis, nausea, headache, and acne. Dermatologists should consider patients' baseline risk factors for developing serious complications when prescribing oral JAK inhibitors.
PubMed: 36790724
DOI: 10.1007/s13555-023-00892-5 -
Scientific Reports Dec 2022Transcutaneous auricular vagus nerve stimulation (taVNS) has been investigated as a novel neuromodulation tool. Although taVNS is generally considered safe with only... (Meta-Analysis)
Meta-Analysis
Transcutaneous auricular vagus nerve stimulation (taVNS) has been investigated as a novel neuromodulation tool. Although taVNS is generally considered safe with only mild and transient adverse effects (AEs), those specifically caused by taVNS have not yet been investigated. This systematic review and meta-analysis on taVNS aimed to (1) systematically analyze study characteristics and AE assessment, (2) characterize and analyze possible AEs and their incidence, (3) search for predictable risk factors, (4) analyze the severity of AE, and (5) suggest an evidence-based taVNS adverse events questionnaire for safety monitoring. The articles searched were published through April 7, 2022, in Medline, Embase, Web of Science, Cochrane, and Lilacs databases. In general, we evaluated 177 studies that assessed 6322 subjects. From these, 55.37% of studies did not mention the presence or absence of any AEs; only 24.86% of the studies described that at least one adverse event occurred. In the 35 studies reporting the number of subjects with at least one adverse event, a meta-analytic approach to calculate the risk differences of developing an adverse event between active taVNS and controls was used. The meta-analytic overall adverse events incidence rate was calculated for the total number of adverse events reported on a 100,000 person-minutes-days scale. There were no differences in risk of developing an adverse event between active taVNS and controls. The incidence of AE, in general, was 12.84/100,000 person-minutes-days of stimulation, and the most frequently reported were ear pain, headache, and tingling. Almost half of the studies did not report the presence or absence of any AEs. We attribute this to the absence of AE in those studies. There was no causal relationship between taVNS and severe adverse events. This is the first systematic review and meta-analysis of transcutaneous auricular stimulation safety. Overall, taVNS is a safe and feasible option for clinical intervention.
Topics: Humans; Vagus Nerve Stimulation; Transcutaneous Electric Nerve Stimulation; Vagus Nerve; Pain Management; Headache
PubMed: 36543841
DOI: 10.1038/s41598-022-25864-1 -
Clinical Trials (London, England) Feb 2021The Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events is an item library designed for eliciting patient-reported adverse events in...
BACKGROUND
The Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events is an item library designed for eliciting patient-reported adverse events in oncology. For each adverse event, up to three individual items are scored for frequency, severity, and interference with daily activities. To align the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events with other standardized tools for adverse event assessment including the Common Terminology Criteria for Adverse Events, an algorithm for mapping individual items for any given adverse event to a single composite numerical grade was developed and tested.
METHODS
A five-step process was used: (1) All 179 possible Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events score combinations were presented to 20 clinical investigators to subjectively map combinations to single numerical grades ranging from 0 to 3. (2) Combinations with <75% agreement were presented to investigator committees at a National Clinical Trials Network cooperative group meeting to gain majority consensus via anonymous voting. (3) The resulting algorithm was refined via graphical and tabular approaches to assure directional consistency. (4) Validity, reliability, and sensitivity were assessed in a national study dataset. (5) Accuracy for delineating adverse events between study arms was measured in two Phase III clinical trials (NCT02066181 and NCT01522443).
RESULTS
In Step 1, 12/179 score combinations had <75% initial agreement. In Step 2, majority consensus was reached for all combinations. In Step 3, five grades were adjusted to assure directional consistency. In Steps 4 and 5, composite grades performed well and comparably to individual item scores on validity, reliability, sensitivity, and between-arm delineation.
CONCLUSION
A composite grading algorithm has been developed and yields single numerical grades for adverse events assessed via the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events, and can be useful in analyses and reporting.
Topics: Adverse Drug Reaction Reporting Systems; Algorithms; Antineoplastic Agents; Drug-Related Side Effects and Adverse Reactions; Humans; National Cancer Institute (U.S.); Neoplasms; Patient Reported Outcome Measures; Reproducibility of Results; United States
PubMed: 33258687
DOI: 10.1177/1740774520975120 -
Advances in Experimental Medicine and... 2020Checkpoint inhibitors are part of the family of immunotherapies and are increasingly being used in a wide variety of cancers. Immune-related adverse events pose a major... (Review)
Review
Checkpoint inhibitors are part of the family of immunotherapies and are increasingly being used in a wide variety of cancers. Immune-related adverse events pose a major challenge in the treatment of cancer patients. Pneumonitis is a rare immune-related adverse event that presents in distinct patterns. The goal of this chapter is to instruct readers on the incidence and clinical manifestations of pneumonitis and to offer guidance in the evaluation and treatment of patients with pneumonitis.
Topics: Humans; Immunotherapy; Incidence; Neoplasms; Pneumonia
PubMed: 32301020
DOI: 10.1007/978-3-030-41008-7_13 -
Cancers Mar 2020Tyrosine kinase inhibitors (TKIs), the treatment of choice for chronic myeloid leukemia (CML), can be associated to cardiovascular (CV) adverse events (AEs). A...
Tyrosine kinase inhibitors (TKIs), the treatment of choice for chronic myeloid leukemia (CML), can be associated to cardiovascular (CV) adverse events (AEs). A case/non-case study was performed using AE reports registered in the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database to compare the risk of CV event reports related to TKIs indicated in the management of chronic myeloid leukemia (CML). Disproportionality of CV event-related TKIs was computed using the Reporting Odds Ratio (ROR) as a measure of potential risk increase. Nilotinib accounts for more than half of reported cases related to TKIs. Signal of Disproportionate Reporting (SDR) was found for cardiac failure, ischemic heart disease, cardiac arrhythmias, /QT prolongation, hypertension, and pulmonary hypertension. Dasatinib and bosutinib were related to the highest disproportionality for cardiac failure. Nilotinib was associated with the highest SDR for ischemic heart disease, /QT prolongation and cardiac arrhythmias. Only ponatinib was related to an SDR for hypertension, while dasatinib and imatinib were related to pulmonary hypertension. In the context of CML, TKIs have different safety profiles related to CV events, among which nilotinib seems particularly related to. These results claim for a revision of its CV safety profile mainly for the risk of /QT prolongation.
PubMed: 32235443
DOI: 10.3390/cancers12040826 -
Therapeutic Advances in Endocrinology... 2019Immunotherapy with checkpoint inhibitors has transformed the treatment of cancer, but frequently results in immune-mediated adverse events affecting multiple organs,... (Review)
Review
Immunotherapy with checkpoint inhibitors has transformed the treatment of cancer, but frequently results in immune-mediated adverse events affecting multiple organs, amongst which endocrine adverse events are frequent. The patterns of endocrine adverse events differ between inhibitors of the CTLA-4 and PD-1/PD-L1 pathways, but most frequently involve the thyroid and pituitary with insulin deficient diabetes also emerging as an important adverse event. These frequently result in long-lasting hormone deficiency requiring replacement. This review explores the mechanism of action of checkpoint inhibitors and details the expected endocrine adverse events and typical presentations. The effect of high-dose glucocorticoids therapy to treat nonendocrine adverse events is also discussed.
PubMed: 31903179
DOI: 10.1177/2042018819896182