| 1. |
- Zhai, Yinghong, et al.
(author)
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Atrial fibrillation increases the risk of all-cause dementia, Alzheimer's disease, and vascular dementia : A cohort study of 373, 415 participants in the UK Biobank
- 2024
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In: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 351, s. 323-330
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Journal article (peer-reviewed)abstract
- BACKGROUND: Accumulated evidence has highlighted the association between atrial fibrillation and the risk of developing dementia.METHODS: This current cohort study utilized data from the UK Biobank to explore the association between atrial fibrillation (AF) and all-cause dementia (ACD), encompassing its main subtypes (Alzheimer's disease (AD), and vascular dementia (VD)). Cox proportional hazards models were applied to examine the association of AF and dementia with its primary subtypes after adjusting for different sets of covariates. Hazard ratios (HRs) with 95 % confidential intervals (CIs) were estimated to quantify the associated risks. Competing risk model was applied in sensitivity analysis.RESULTS: After exclusion, 373, 415 participants entered the primary analysis. Among these, 27, 934 (7.48 %) were with a history AF at baseline, while 345, 481 (92.52 %) were without. During a mean follow-up of 13.45 years, ACD was diagnosed in 1215 individuals with AF and 3988 individuals without AF. Participants with AF had higher risks of ACD (1.79 [1.67-1.91]), AD (1.48 [1.32-1.65]), and VD (2.46 [2.17-2.80]) in the fully adjusted Cox regression models. Results of subgroup and sensitivity analyses predominantly aligned with the positive associations in primary analysis.LIMITATIONS: The applicability of our findings to diverse ethnicities might require careful consideration and the behind biological mechanisms need to be further revealed.CONCLUSIONS: It indicated that people with atrial fibrillation had an increased future risk of all-cause dementia, Alzheimer's disease, vascular dementia. Atrial fibrillation screening and prevention strategies should take into account to prevent and delay the onset of dementia.
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| 2. |
- Zhai, Yinghong, et al.
(author)
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Cardiovascular Toxicity of Carfilzomib : The Real-World Evidence Based on the Adverse Event Reporting System Database of the FDA, the United States
- 2021
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In: Frontiers in Cardiovascular Medicine. - : Frontiers Media S.A.. - 2297-055X. ; 8
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Journal article (peer-reviewed)abstract
- Background: Carfilzomib, an effective proteasome inhibitor agent for the therapy of relapsed and refractory multiple myeloma, has been related to a significant number of cardiovascular events. However, patterns of cardiovascular complications associated with this agent remain poorly characterized in real-world settings.Objective: To gain further insight into the frequency, spectrum, clinical features, timing, and outcomes of carfilzomib-related cardiovascular toxicities.Methods: This disproportionality (case/non-case) study was conducted leveraging records from FAERS database from 2014 to 2019. Cardiovascular events were defined and broadly categorized eight entities using narrow version of the Standardized MedDRA Queries (SMQs). Reporting odds ratios (ROR) and information component (IC) were calculated to measure disproportionality. Additionally, statistical shrinkage was applied to reduce false-positive signals.Results: The final number of records involved was 28,479,963, with 3,370 records submitted for carfilzomib related cardiovascular events. Significant disproportionality association between carfilzomib administration and cardiovascular events was captured (IC025/ROR025 = 0.85/1.95) when exploring in the entire database. Upon further analysis, all eight broad categories of cardiovascular toxicities were disproportionately associated with carfilzomib with varying frequencies, time-to-onset, and severities. Cardiomyopathy-related complications (N = 1,301, 38.61%), embolic and thrombotic events (N = 821, 24.36%), and cardiac failure (N = 765, 22.70%) largely comprised the reported problems. Notably, the strongest signal was detected for cardiac failure (IC025/ROR025 = 1.33/2.59), followed by pulmonary hypertension (IC025/ROR025 = 1.19/2.34). Median onset time of cardiovascular events was 41days (Q1-Q3: 9-114 days), with the shortest median time being 16 days (Q1-Q3: 4-85 days) for ischemic heart disease, with the longest time being 68 days (Q1-Q3: 21-139 days) for embolic and thrombotic events. Torsade de pointes/QT prolongation was identified as a new complication (IC025/ROR025 = 0.33/1.29) and was particularly noteworthy for highest death proportion (44.11%).Conclusions: Treatment with carfilzomib can lead to severe and versatile cardiovascular events. Early and intensive monitoring is important, particularly in the first 3 months after carfilzomib initiation. Maximizing the benefit while reducing potential cardiovascular harms of carfilzomib should become a priority.
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| 3. |
- Zhai, Yinghong, et al.
(author)
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Metabolic and Nutritional Disorders Following the Administration of Immune Checkpoint Inhibitors : A Pharmacovigilance Study
- 2021
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In: Frontiers in Endocrinology. - : Frontiers Media S.A.. - 1664-2392. ; 12
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Journal article (peer-reviewed)abstract
- Background: Although several metabolic and nutritional disorders (MNDs) have been reported in the recipients of immune checkpoint inhibitors (ICIs), these events have not been fully captured and comprehensively characterized in real-world population.Objectives: To provide complete metabolic and nutritional toxicity profiles after ICIs (single and combined) initiation through an integrated big database.Methods: Reporting odds ratios (ROR) and information component (IC) based on statistical shrinkage transformation were utilized to perform disproportionality analysis using the US Food and Drug Administration Adverse Events Reporting System. Both ROR and IC were used to calculate disproportionality when compared with the whole database, but only ROR was used when comparison was made for different ICI strategies. Only when both the lower limits of 95% confidence intervals (CIs) for ROR (ROR025) and IC (IC025) exceeded specified threshold values (1 and 0, respectively) was regarded as a signal.Results: A total of 29,294,335 records were involved and 8,662 records were for MNDs in patients exposed to ICIs. Statistically significant association was detected between ICIs use and total MNDs (IC025/ROR025 = 1.06/2.19). For monotherapy, three ICI monotherapies (anti-PD-1, anti-PDL-1, and anti-CTLA-4) were all disproportionately associated with MNDs. Statistically significant differences in reporting frequencies also emerged when comparing anti-PD-1 with anti-PD-L1/anti-CTLA-4 monotherapy, with RORs of 1.11 (95%CI 1.01-1.21), and 1.35 (95%CI 1.23-1.48), respectively. Notably, combination therapy was associated with a higher reporting frequency of theses toxicities compared to monotherapy with a ROR of 1.56 (95%CI 1.48-1.64). Additionally, disproportionality analysis at High-level Group Term level highlighted eight broad entities of MNDs. Further disproportionality analysis at Preferred Term level indicated a wide range and varied strength of signals. For ICI monotherapy, nivolumab and pembrolizumab showed the broadest spectrum of MNDs. For combination therapy, a variety of signals were detected for nivolumab + ipilimumab therapy even comparable to two PD-1 monotherapies.Conclusion: Metabolic and nutritional complications could be provoked by ICI monotherapy (especially anti-PD-1) and further reinforced by combination therapy. Clinicians and patients should be informed about these potential risks that might be encountered in real-world practice. Aforehand education and regular monitoring of related biochemical parameters (calcium, sodium, potassium, protein) are recommended to ensure better cancer survivorship.
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| 4. |
- Zhai, Yinghong, et al.
(author)
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Pharmacovigilance analysis of cardiac risks associated with Bruton tyrosine kinase inhibitors
- 2023
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In: Expert Opinion on Drug Safety. - : Ashley Mark Publishing Company. - 1474-0338 .- 1744-764X. ; 22:9, s. 857-869
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Journal article (peer-reviewed)abstract
- BACKGROUND: Bruton tyrosine kinase inhibitors (BTKIs) can be associated with several cardiac risks.RESEARCH DESIGN AND METHODS: This study was conducted based on records from a large spontaneous reporting database, the Food and Drug Administration Adverse Event Reporting System, for cardiac events reported for several BTKI agents. Reporting odds ratio and information components based on statistical shrinkage transformation were utilized to measure disproportionality.RESULTS: The final number of records for BTKI-related cardiac events was 10 320. Death or life-threatening events occurred in 17.63% of all associated cardiac records. Significant reporting was captured between BTKI (total/specific) and cardiac events, with the strongest association for ibrutinib. A total of 47 positive signals were evacuated for ibrutinib, with atrial fibrillation being the most commonly reported one. Concomitantly, cardiac failure congestive, cardiac disorder, arrhythmia, pericardial effusion, and atrial flutter, were also noticed for relatively stronger signal and disproportionality. Atrial fibrillation was over-reported in the 3 groups (ibrutinib, acalabrutinib, zanubrutinib), and acalabrutinib had statistically significant lower reporting compared with ibrutinib.CONCLUSIONS: Receiving ibrutinib, acalabrutinib or zanubrutinib might increase the chance of cardiac complications, with ibrutinib posing the highest risk. The type of cardiotoxicity involved in ibrutinib was highly variable.
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| 5. |
- Zhai, Yinghong, et al.
(author)
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Updated Insights on Cardiac and Vascular Risks of Proton Pump Inhibitors : A Real-World Pharmacovigilance Study
- 2022
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In: Frontiers in Cardiovascular Medicine. - : Frontiers Media S.A.. - 2297-055X. ; 9
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Journal article (peer-reviewed)abstract
- Background: Proton pump inhibitors (PPIs) are among the most widely prescribed medications in clinical practice. However, there are also concerns about the potential risks of long-term PPI use. The present study aimed to examine the safety of PPIs and summarize their potential cardiac and vascular risks in a real-world setting.Methods: This pharmacovigilance study extracted records between January 2015 and December 2019 from the FDA Adverse Event Reporting System (FAERS) database. The association of seven PPI medications with cardiac and vascular events (CVEs) were evaluated. Two established pharmacovigilance methods, reporting odds ratio (ROR) and information components (IC) based statistical shrinkage, were used to measure disproportionality.Results: In total 62,140 CVE records associated with PPI use were investigated. Women showed a higher proportion (54.37%) of PPI-associated CVEs. The median time from PPI initiation to CVE onset was 97 [interquartile range (IQR): 8-491] days, with the shortest median time of 42 days (IQR: 2-277 days) for esomeprazole, and the longest time of 389 days (IQR: 0-525 days) for dexlansoprazole. Although PPIs were not associated with elevated CVE risks compared those of the whole database (IC025/ROR025 = -0.39/0.74), various signals emerged. Despite some similarities exist between the PPIs, their cardiac and vascular safety profiles varied significantly. Pantoprazole showed the broadest spectrum of signals, from thrombotic thrombocytopenic purpura (IC025/ROR025 = 0.01/1.08) to renal haemangioma (IC025/ROR025 = 3.14/9.58). Esomeprazole showed the second-broadest spectrum of toxicities, ranging from duodenal ulcer hemorrhage (IC025/ROR025 = 0.07/1.28) to hypertensive nephropathy (IC025/ROR025 = 4.09/18.72). Vascular signals were more dominant than cardiac signals, suggesting that vascular function was more heavily affected. Hypertensive nephropathy, renal haemangioma, renal artery stenosis, and renal infarct had strong signals across most PPI regimens and merited further attention.Conclusions: PPIs may inflict various CVEs, particularly those involving the vascular system, on the users. Given the wide range of onset times and different toxicity profiles for various PPI medications, they should be prescribed with caution.
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