The correlation of Esketamine with specific adverse events: a deep dive into the FAERS database.

Analyzing the vast data from FAERS database to evaluate the association between Esketamine and specific adverse events to guide clinical practice and regulatory decisions. Data related to Esketamine adverse events from 2019 Q1 to 2023 Q1 were collected from FAERS database. After data standardization, various signal quantification technologies, such as ROR, PRR, BCPNN, and MGPS, were employed to identify and evaluate adverse reaction signals closely related to the use of Esketamine comprehensively. A total of 5061 reports with Esketamine as the primary suspected drug were obtained, identifying 117 adverse reaction terms (PT) involving 27 system organ class (SOC) categories. Apart from the adverse events already mentioned in the drug's instructions, this study identified some new, clinically valuable potential AE signals, such as Flashback, Tachyphylaxis, and Autoscopy. In addition, high-ranking results included euphoric mood, feeling of relaxation, and feeling drunk. Notably, the occurrence frequencies of suicidal ideation and suicide attempt were relatively high, so clinicians should be particularly vigilant about these potential adverse reactions when using Esketamine. Moreover, since this drug is administered as a nasal spray, issues such as drug monitoring procedure incorrectly performed and nasal discomfort may arise. This study underscores the potential adverse reactions and risks of Esketamine in clinical applications, especially regarding long-term efficacy, addiction risks, and suicidal risks.

Increased complication rates of salvage reverse total shoulder arthroplasty (RTSA) after failed locked plate fixation compared with primary RTSA in the treatment of proximal humeral fractures in elderly patients.

HYPOTHESIS: Common surgical treatment options for proximal humeral fractures in elderly patients include locked plate fixation (LPF) and reverse total shoulder arthroplasty (RTSA). It was hypothesized that secondary RTSA after LPF would be associated with higher complication rates and costs compared with primary RTSA. METHODS: We analyzed the health insurance data of patients aged ≥65 years who received RTSA for the treatment of a proximal humeral fracture between January 2013 and September 2019 with a pre-study phase of 5 years. Multivariable Cox, logistic, and linear regression models were used to evaluate the association between treatment group and complications, hospital length of stay, charges, and mortality rate during a 34-month follow-up period. RESULTS: A total of 14,220 patients underwent primary RTSA and 1282 patients underwent secondary RTSA after prior surgery using LPF for the treatment of proximal humeral fractures. After adjustment for patient characteristics, more surgical complications were observed after secondary RTSA during index hospitalization (odds ratio, 4.62; 95% confidence interval [CI], 4.00-5.34; P < .001) and long-term follow-up (hazard ratio, 1.52; 95% CI, 1.27-1.81; P < .001). Moreover, secondary RTSA was associated with an increased cumulative total cost of €6638.1 (95% CI, €6229.9-€7046.5; P < .001). If conversion from LPF to secondary RTSA occurred during index hospitalization, more major adverse events, more thromboembolic events, and a higher mortality rate were found in the short and long term (all P < .05). CONCLUSION: Secondary RTSA is associated with higher total costs and more complications. Hence, if surgical treatment of a proximal humeral fracture in an elderly patient is needed, prognostic factors for LPF need to be evaluated carefully. If in doubt, the surgeon should opt to perform primary RTSA as patients will benefit in the long term.

Comprehensive evaluation of leuprorelin-associated adverse events: insights from FDA adverse event reporting system.

BACKGROUND: Leuprorelin, a gonadotropin-releasing hormone agonist, is widely used to treat hormone-related disorders. This study aims to explore and analyze the safety profile of leuprorelin by examining adverse event reports from the FDA Adverse Event Reporting System (FAERS) database. METHODS: This study conducted a retrospective pharmacovigilance analysis using FAERS data from Q1 2004 to Q1 2024. Adverse drug events (ADEs) related to leuprorelin were identified and categorized by system organ class and specific adverse events. Statistical methods such as Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM) were used to detect safety signals. RESULTS: A total of 63,928 ADE reports implicated leuprorelin, with 500 preferred terms and 25 system organ classes showing significant disproportionality. Notable rare ADEs identified were bulbospinal muscular atrophy congenital (n = 26; ROR 1282.72, PRR 1282.52, IC 7.91, EBGM 241.28), follicular cystitis (n = 3; ROR 126.84, PRR 126.84, IC 6.48, EBGM 89.09), and anaplastic meningioma (n = 3; ROR 46.73, PRR 46.73, IC 5.34, EBGM 40.5). CONCLUSION: Most findings were expected, but new signals like follicular cystitis, previously unreported, emerged. Further studies are essential to validate these findings, crucial for clinical monitoring and risk identification of leuprorelin.

Signal mining and risk analysis of Alprazolam adverse events based on the FAERS database.

This study aims to evaluate the safety of Alprazolam by analyzing the FAERS database, provide data analysis for monitoring adverse drug reactions. This research encompasses adverse event (AE) reports related to Alprazolam from the first quarter of 2004 to the second quarter of 2023. Four signal mining and analysis methods were utilized, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayesian Geometric Mean (EBGM). Further exploration was conducted regarding patient characteristics and types of AEs. A total of 23,575 AE reports in which Alprazolam was the primary suspect drug were collected, identifying 347 Preferred Term (PT) signals and 27 System Organ Classes (SOCs). The number of AE reports increased annually, especially in 2015, 2018, 2019, and 2020. The main affected groups were females and the age range of 18 to 45. Psychiatric disorders, Nervous system disorders, and Gastrointestinal disorders were the most common the organ system in which the AEs occurred. There is a certain risk of drug abuse and suicide with Alprazolam. Most notably, several AEs not recorded in the Alprazolam leaflet appeared among the top 30 PTs in signal strength, including but not limited to Benzodiazepine drug level abnormal, Acquired amegakaryocytic thrombocytopenia, Cutaneous T-cell dyscrasia, and Coronary No-reflow Phenomenon. For the first time, AEs related to the cardiovascular system and platelet function were unveiled. The severe AE reports that resulted in "hospitalization" and "death" accounted for 30.96% and 21.86%. This study highlights the risks of suicide and misuse of Alprazolam. Other potential severe or fatal AEs, such as those related to the cardiovascular system, platelet function, and others, require further research to determine their precise mechanisms and risk factors.

Analysis of post-market adverse events of istradefylline: a real-world study base on FAERS database.

Analyze the adverse event (AE) signals of istradefylline based on the FAERS database. By extracting large-scale data from the FAERS database, this study used various signal quantification techniques such as ROR, PRR, BCPNN, and MGPS to calculate and evaluate the ratio and association between istradefylline and specific AEs. In the FAERS database, this study extracted data from the third quarter of 2019 to the first quarter of 2023, totaling 6,749,750 AE reports. After data cleansing and drug screening, a total of 3633 AE reports related to istradefylline were included for analysis. Based on four calculation methods, this study unearthed 25 System Organ Class (SOC) AE signals and 82 potential preferred terms (PTs) related to istradefylline. The analysis revealed new AEs during istradefylline treatment, including reports of Parkinsonism hyperpyrexia syndrome (n = 3, ROR 178.70, PRR 178.63, IC 1.97, EBGM 165.63), Compulsions (n = 5, ROR 130.12, PRR 130.04, IC 2.53, EBGM 123.02), Deep brain stimulation (n = 10, ROR 114.42, PRR 114.27, IC 3.33, EBGM 108.83), and Freezing phenomenon (n = 60, ROR 97.52, PRR 96.76, IC 5.21, EBGM 92.83). This study provides new risk signals and important insights into the use of istradefylline, but further research and validation are needed, especially for those AE that may occur in actual usage scenarios but are not yet explicitly described in the instructions.

Risk analysis of enfortumab vedotin: A real-world approach based on the FAERS database.

Purpose: To analyze the risk of enfortumab vedotin (EV), a targeted therapy for advanced bladder cancer, using real-world data from the U.S. Food and Drug Administration's Federal Adverse Event Reporting System (FAERS). Methods: A retrospective pharmacovigilance analysis was conducted using FAERS data from Q1 2020 to Q1 2024. Adverse drug events (ADEs) related to EV were identified and categorized according to the System Organ Classes (SOCs) and specific events. Statistical methods, such as the proportional reporting ratio, reporting odds ratio (ROR), Bayesian confidence propagation neural network, and empirical Bayesian geometric mean were used to detect safety signals. Results: Of the 7,449,181 FAERS case reports, 1,617 EV-related ADEs were identified, including 101 preferred terms and 22 SOCs. The key SOCs included skin and subcutaneous tissue, metabolic, and nutritional disorders. Rare ADEs, such as lichenoid keratosis (n = 4; ROR 26.89), small intestinal perforation (n = 3; ROR 24.51), pigmentation disorder (n = 9; ROR 18.16), and cholangitis (n = 8; ROR 17.48), showed significant disproportionality. Conclusion: While most findings aligned with the existing data, new signs such as lichenoid keratosis and small intestinal perforation were identified. Further studies are necessary to validate these findings and emphasize the need for the clinical monitoring of EV-related ADEs.

Comprehensive understanding of the adverse effects associated with temozolomide: a disproportionate analysis based on the FAERS database.

Background: Temozolomide, which is the standard drug for glioma treatment, has several Adverse events (AEs) in the treatment of gliomas and other tumors that are not yet fully understood. This is due to the pharmacological nature of the alkylating agent. A significant proportion of these effects have not been systematically documented or reported. Methods: We selected data from the United States FDA Adverse Event Reporting System (FAERS) database from the first quarter of 2004 to the fourth quarter of 2023. Four algorithms were used for disproportionate analysis, with the objective of assessing the association between temozolomide and related adverse events. Results: In this study, 20,079,906 case reports were collected from the FAERS database, of which 15,152 adverse events related to temozolomide were reported. A total of 352 preferred terms (PTs) and 24 system organ classes (SOCs) that were significantly disproportionally related to the four algorithms were included. The SOCs included blood and lymphatic system disorders (χ2 = 18,220.09, n = 4,325); skin and subcutaneous tissue disorders (χ2 = 408.06, n = 1,347); investigations (χ2 = 639.44, n = 3,925); musculoskeletal and connective tissue disorders (χ2 = 1,317.29, n = 588); and psychiatric disorders (χ2 = 1,098.47, n = 877). PT levels were screened for adverse drug reaction signals consistent with drug inserts, such as anemia, thrombocytopenia, liver function abnormalities, nausea and vomiting, as well as rarely reported adverse drug reactions, such as aplastic anemia, myelodysplastic syndromes, electrolyte disorders, cerebral edema, and high-frequency mutations. Conclusion: The results of our investigation demonstrated both adverse effects that had been reported and a multitude of unreported adverse effects that were serious in nature and lacked a clear cause. These novel findings suggest that more attention should be given to the clinical conditions of patients after treatment to provide a more comprehensive perspective and understanding for further clarifying the safety of temozolomide.

Investigating drug-induced urinary retention: a pharmacovigilance analysis of FDA adverse event reports from 2004 to 2024.

BACKGROUND: Drug-induced urinary retention (DIUR) can severely impact patient quality of life and complicate treatment. This study investigates the incidence and characteristics of DIUR using data from the FDA Adverse Event Reporting System (FAERS) over 20 years. METHODS: FAERS reports related to urinary retention (UR) from Q1 2004 to Q1 2024 were analyzed. Potential causative drugs were identified, and the top 30 drugs with the most UR reports were ranked. Statistical disproportionality analyses, including Proportional Reporting Ratio (PRR) and Reporting Odds Ratio (ROR), were conducted to detect significant safety signals. RESULTS: Out of 17,703,515 reports in the FAERS database 28,423 cases of UR were identified. Anticholinergics, antidepressants, and opioids were the most frequently implicated drug classes. The highest ROR and PRR values were observed for drugs like ezogabine. Additionally, less commonly associated drugs, such as adalimumab and others, were implicated, suggesting potential under-recognition of this adverse effect. However, these associations should be interpreted with caution, as they do not confirm a direct causal relationship. CONCLUSION: This study underscores the importance of pharmacovigilance in identifying and understanding DIUR. Further research is needed to confirm these findings and develop strategies to manage and reduce the risk, improving patient outcomes.

Association between atorvastatin and erectile dysfunction: a comprehensive analysis incorporating real-world pharmacovigilance and Mendelian randomization.

Background: Atorvastatin is a commonly prescribed medication for the prevention of cardiovascular diseases. Recent observational studies have suggested a potential association between atorvastatin use and the occurrence of Erectile Dysfunction (ED). In this study, we aimed to explore the relationship between atorvastatin and ED using real-world data from the FAERS database and employed Mendelian randomization to assess causality. Methods: To evaluate the disproportionality of atorvastatin in relation to ED, we conducted several pharmacovigilance analyses, including odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence propagation neural network (BCPNN), and gamma-Poisson contractile apparatus (GPS). Additionally, we employed Mendelian randomization to investigate the causal relationship between atorvastatin and ED. Results: Pharmacovigilance disproportionality analysis revealed a significant association between atorvastatin and ED, as indicated by the following results: ROR [3.707078559, 95% CI (3.33250349, 4.123756054)], PRR [3.702969038, χ2 (669.2853829)], IC [1.870490139, IC025 (1.702813857)], and EBGM [3.656567867, EBGM05 (3.28709656)]. Furthermore, the two-sample Mendelian randomization analysis provided evidence supporting a causal relationship between atorvastatin use and ED, with an inverse variance weighted estimate of ß = 3.17 (OR = 23.91, p = 0.02 < 0.05). Conclusion: Based on comprehensive analyses incorporating pharmacovigilance and Mendelian randomization, our findings suggest that atorvastatin use is associated with an increased risk of ED and indicate a causal relationship. These results emphasize the importance of considering potential adverse effects, such as ED, when prescribing atorvastatin for cardiovascular disease prevention. Further research and clinical monitoring are warranted to better understand the underlying mechanisms and develop appropriate strategies to mitigate this side effect.

Unveiling potential adverse events associated with escitalopram oxalate: A real-world analysis based FDA adverse event reporting system database.

OBJECTIVE: The study aimed to conduct a multidimensional evaluation of potential adverse events (AEs) of escitalopram oxalate based on the FDA adverse event reporting system (FAERS) database. METHODS: This study utilized the reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma-poisson shrinker (MGPS) to mine and analyze data from the FAERS database from the first quarter of 2004 to the second quarter of 2023. RESULTS: There was a total of 19,854 AE reports related to escitalopram oxalate, extracting 625 preferred terms (PTs), and covering 27 system organ classes (SOCs). The results showed that the number of reports by females was significantly higher than males, accounting for 57.68%. The reporting number was higher in 2018 and 2019, accounting for 9.50% and 10.18% of the total reports, respectively. The main reporters were consumers and other health professionals, accounting for 26.99% and 26.75% respectively. The majority of the reports were primarily from the United States. Newly emerging AE signals such as intentional overdose (n = 691, ROR 8.51, PRR 8.45, IC 3.05, Empirical Bayesian Geometric Mean (EBGM) 8.35), suicide attempt (n = 665, ROR 8.58, PRR 8.52, IC 3.06, EBGM 8.42), serum serotonin (n = 5, ROR 1044.78, PRR 1044.71, IC 2.56, EBGM 392.39), anti-actin antibody positive (n = 5, ROR 626.87, PRR 626.83, IC 2.56, EBGM 313.91), among others, were not mentioned in the drug's label. CONCLUSION: While escitalopram oxalate has clear benefits in the treatment of depression and other mental health disorders, the presence of AEs also suggests risks associated with its use. Particularly concerning are risks of suicide and changes in serum serotonin levels.

A real-world pharmacovigilance study of FDA adverse event reporting system events for diazepam.

Background: Diazepam, one of the benzodiazepines, is widely used clinically to treat anxiety, for termination of epilepsy, and for sedation. However, the reports of its adverse events (AEs) have been numerous, and even fatal complications have been reported. In this study, we investigated the AEs of diazepam based on real data from the U.S. Food and Drug Administration (FDA) adverse event reporting system (FAERS). Methods: Disproportionality in diazepam-associated AEs was assessed through the calculation of reporting odds ratios (RORs), proportional reporting ratios (PRRs), Bayesian confidence-propagation neural networks (BCPNNs), and gamma-Poisson shrinkage (GPS). Results: Among the 19,514,140 case reports in the FAERS database, 15,546 reports with diazepam as the "principal suspect (PS)" AEs were identified. Diazepam-induced AEs occurred targeting 27 system organ categories (SOCs). Based on four algorithms, a total of 391 major disproportionate preferred terms (PTs) were filtered out. Unexpectedly significant AEs such as congenital nystagmus, developmental delays, and rhabdomyolysis were noted, which were not mentioned in the drug insert. Conclusion: Our study identified potential signals of new AEs that could provide strong support for clinical monitoring and risk identification of diazepam.

Safety assessment of Brexpiprazole: Real-world adverse event analysis from the FAERS database.

OBJECTIVE: This study aims to analysis adverse drug events (ADE) related to Brexpiprazole from the third quarter of 2015 to the first quarter of 2023 from FAERS database. METHODS: The ADE data related to Brexpiprazole from 2015 Q3 to 2023 Q1 were collected. After standardizing the data, a variety of signal quantification techniques, including ROR, PRR, BCPNN, and MGPS were used for analysis. RESULTS: Among the 8559 ADE reports with Brexpiprazole as the primary suspected drug, 178 preferred terms (PT) of adverse reactions spanning 27 different system organ classes (SOC) were identified. Specifically, Metabolism and nutrition disorders and Reproductive system and breast disorders were unique adverse reactions to Brexpiprazole, with the latter not mentioned in the official drug label. Moreover, uncommon but significantly strong ADE signals, such as Egocentrism, Pharmacophobia, and Compulsions were observed. Notably, Tardive dyskinesia (n = 317, ROR 103.87, PRR 102.21, IC 6.21, EBGM 96.17) and Extrapyramidal disorder (n = 104, ROR 31.17, PRR 31.00, IC 4.57, EBGM 30.44) exhibited relatively high occurrence rates and signal strengths. Additionally, Lactation disorder (n = 6, ROR 48.09, PRR 48.07, IC 2.63, EBGM 46.71) and Breast discharge (n = 10, ROR 23.18, PRR 23.17, IC 2.94, EBGM 22.86) were observed, both presenting strong ADE signals. CONCLUSION: Brexpiprazole poses risks of various adverse reactions while providing therapeutic effects. In clinical applications, practitioners should closely monitor occurrences of Psychiatric disorders, Metabolism and nutrition disorders, Reproductive system and breast disorders, and other events.

Mining and analysis of adverse event signals of Cariprazine based on the real-world data of FAERS database.

OBJECTIVE: This study aims to analyze the adverse events (AEs) of Cariprazine based on the FAERS database, providing evidence for its safety surveillance. METHODS: For signal quantification of Cariprazine-related AEs, we used disproportionality analysis including the Ratio of Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinker (MGPS) algorithms. RESULTS: We selected Cariprazine-related AE reports from the FAERS database from the fourth quarter of 2015 to the first quarter of 2023, and performed a detailed data analysis. Out of a total of 12,278,580 case reports, 3659 were found to be directly related to Cariprazine. We identified 140 Preferred Terms (PT) to describe these AEs, finding that they involved 27 organ systems. Specifically, AEs related to eye disorders such as Cataract cortical, Cataract nuclear, Accommodation disorder, Lenticular opacities, Oculogyric crisis, Dyschromatopsia were not explicitly mentioned in the drug's leaflet, indicating the presence of new ADR signals. CONCLUSION: Analysis of the FAERS database identified AEs associated with Cariprazine, notably in eye disorders not previously documented in the drug's official leaflet. These findings emphasize the need for continuous post-market surveillance and awareness among healthcare professionals regarding potential new ADR signals.

Analysis of Inclisiran in the US FDA Adverse Event Reporting System (FAERS): a focus on overall patient population and sex-specific subgroups.

BACKGROUND: Our study aimed to identify inclisiran-related adverse events(AEs) for primary hypercholesterolemia and arteriosclerotic cardiovascular disease(ASCVD) from the US FDA Adverse Event Reporting System (FAERS) database, analyzing its links to AEs in the overall patient population and sex-specific subgroups to improve medication safety. METHODS: We analyzed inclisiran-related AEs signals by using statistical methods like Reporting Odds Ratio (ROR), Proportional Reporting Ratios (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma-Poisson Shrinker (MGPS). RESULTS: Analyzing 2,400 AE reports with inclisiran as the primary suspected drug in the FAERS database, we identified 70 AE signals over 13 organ systems using the above four methods. Notable findings were strong signals for systemic diseases and various reactions at the site of administration (ROR 1.49, 95% CI 1.41-1.57), and various musculoskeletal and connective tissue diseases (ROR 4.07, 95% CI 3.83-4.03) in overall and gender-specific populations. Myalgia, a new ADE signal not in the drug insert, was a top signal by intensity and frequency (ROR 14.76, 95% CI 12.84-16.98). CONCLUSION: Our study revealed the strongest AE signals associated with inclisiran in both the overall population and gender subgroups, highlighting potential risks in clinical medication use and guiding balanced clinical decision-making.

Mining and analysis of security alert signals of valbenazine based on the Food and Drug Administration Adverse Event Reporting System database.

BACKGROUND: Valbenazine is used for tardive movement disorders in adults. Current studies on its safety are mostly from clinical trials and small case reports, limiting information on rare adverse reactions. This study investigated valbenazine-related adverse event (AE) risk signals using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database. METHODS: Valbenazine AEs data were collected from the FAERS database from 2017 Q2 to 2023 Q1, employing methods like reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network, and empirical Bayesian geometric mean. RESULTS: After data cleaning and drug screening, there were 20,837 AEs primarily suspecting valbenazine, involving 26 system organ classes and 125 AEs related to valbenazine at the preferred terms level. AEs related to valbenazine were mainly concentrated in nervous system disorders, general disorders and administration site conditions, and psychiatric disorders. Eye disorders and gastrointestinal disorders are new AEs not labeled in the valbenazine instructions. In addition, some new potential AE signals were found, such as Tardive dyskinesia and eyelid function disorder. CONCLUSION: The common AEs of valbenazine in the real world are consistent with the instructions, but there are some newly discovered suspicious AEs.

A real-world data analysis of tirzepatide in the FDA adverse event reporting system (FAERS) database.

Background: Tirzepatide, a glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor agonist, is indicated for chronic weight management in adults with obesity or overweight as an adjunct to a reduced-calorie diet and increased physical activity. However, the safety profile of Tirzepatide-associated adverse events requires comprehensive evaluation. Methods: The AE reports from the first quarter of 2022 to the third quarter of 2023 were selected by exploring the FDA Adverse Event Reporting System (FAERS) database. The new and unexpected potenial AE signals were detected using the disproportionality analysis, including reporting odds ratio(ROR), the proportional reporting ratio (PRR) the Bayesian confidence propagation neural network (BCPNN) and the empirical Bayes geometric mean(EBGM). Then the MedDRA was used to systematically classify the results. Results: A total of 1,904,481 case reports were obtained from 2022Q2 to 2023Q3. Forty-sixth tirzepatide-induced ADRs at the preferred terms (PTs) level are associated with 8 system organ class In addition, this study uncovered multiple anticipated ADRs, such as gastrooesophageal reflux disease, dyspepsia, and vomiting, in line with the drug labels. Moreover, unexpected and significant ADRs at PTs level, such as incorrect dose administered, injection site haemorrhage, and increased appetite, were discovered and linked to Injury, poisoning, and procedural complications, General disorders and administration site conditions, and Metabolism and nutrition disorders at the System Organ Class level. Conclusion: This study offered new perspectives on the monitoring, surveillance, and management of adverse drug reactions related to tirzepatide. The outcomes of severe adverse events and their respective detection signals, along with unexpected significant adverse event signals, are important to consider in efforts to enhance clinical medication safety when using tirzepatide.

Clinical adverse events to dexmedetomidine: a real-world drug safety study based on the FAERS database.

Objective: Adverse events associated with dexmedetomidine were analyzed using data from the FDA's FAERS database, spanning from 2004 to the third quarter of 2023. This analysis serves as a foundation for monitoring dexmedetomidine's safety in clinical applications. Methods: Data on adverse events associated with dexmedetomidine were standardized and analyzed to identify clinical adverse events closely linked to its use. This analysis employed various signal quantification analysis algorithms, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-Item Gamma Poisson Shrinker (MGPS). Results: In the FAERS database, dexmedetomidine was identified as the primary suspect in 1,910 adverse events. Our analysis encompassed 26 organ system levels, from which we selected 346 relevant Preferred Terms (PTs) for further examination. Notably, adverse drug reactions such as diabetes insipidus, abnormal transcranial electrical motor evoked potential monitoring, acute motor axonal neuropathy, and trigeminal cardiac reflex were identified. These reactions are not explicitly mentioned in the drug's specification, indicating the emergence of new signals for adverse drug reactions. Conclusion: Data mining in the FAERS database has elucidated the characteristics of dexmedetomidine-related adverse drug reactions. This analysis enhances our understanding of dexmedetomidine's drug safety, aids in the clinical management of pharmacovigilance studies, and offers valuable insights for refining drug-use protocols.

Interoperability of phenome-wide multimorbidity patterns: a comparative study of two large-scale EHR systems.

Background: Electronic health records (EHR) are increasingly used for studying multimorbidities. However, concerns about accuracy, completeness, and EHRs being primarily designed for billing and administrative purposes raise questions about the consistency and reproducibility of EHR-based multimorbidity research. Methods: Utilizing phecodes to represent the disease phenome, we analyzed pairwise comorbidity strengths using a dual logistic regression approach and constructed multimorbidity as an undirected weighted graph. We assessed the consistency of the multimorbidity networks within and between two major EHR systems at local (nodes and edges), meso (neighboring patterns), and global (network statistics) scales. We present case studies to identify disease clusters and uncover clinically interpretable disease relationships. We provide an interactive web tool and a knowledge base combining data from multiple sources for online multimorbidity analysis. Findings: Analyzing data from 500,000 patients across Vanderbilt University Medical Center and Mass General Brigham health systems, we observed a strong correlation in disease frequencies (Kendall's τ = 0.643) and comorbidity strengths (Pearson ρ = 0.79). Consistent network statistics across EHRs suggest similar structures of multimorbidity networks at various scales. Comorbidity strengths and similarities of multimorbidity connection patterns align with the disease genetic correlations. Graph-theoretic analyses revealed a consistent core-periphery structure, implying efficient network clustering through threshold graph construction. Using hydronephrosis as a case study, we demonstrated the network's ability to uncover clinically relevant disease relationships and provide novel insights. Interpretation: Our findings demonstrate the robustness of large-scale EHR data for studying phenome-wide multimorbidities. The alignment of multimorbidity patterns with genetic data suggests the potential utility for uncovering shared biology of diseases. The consistent core-periphery structure offers analytical insights to discover complex disease interactions. This work also sets the stage for advanced disease modeling, with implications for precision medicine. Funding: VUMC Biostatistics Development Award, the National Institutes of Health, and the VA CSRD.

High-risks drug adverse events associated with Cetirizine and Loratadine for the treatment of allergic diseases: A retrospective pharmacovigilance study based on the FDA adverse event reporting system database.

BACKGROUND: Cetirizine and Loratadine are the two best-selling second-generation antihistamines for allergic diseases. This study aims to provide a comparative analysis of the differences in adverse drug events (ADEs) between these two medications, which can assist clinicians in making appropriate treatment decisions. METHODS: ADE reports related to Cetirizine and Loratadine obtained from the FDA adverse event reporting system (FAERS) database were analyzed using disproportionality analysis and Bayesian analysis to evaluate and compare the ADE signals of both drugs. RESULTS: A total of 28,051 and 28,073 ADE reports were retrieved from the FAERS database related to Cetirizine and Loratadine, respectively, with both drugs showing a predominance of middle-aged females. Specifically, Loratadine was associated with respiratory symptoms, mainly nasal symptoms such as rhinorrhea (n = 326, ROR 6.75), sneezing (n = 251, ROR 15.24), and nasal congestion (n = 185, ROR 4.25), while Cetirizine did not show this association. Notably, both drugs exhibited strong signals for somnolence in the nervous and psychiatric systems, especially Cetirizine (Cetirizine, n = 2556, ROR 10.52 vs. Loratadine, n = 1200, ROR 7.76). Additionally, Cetirizine itself showed strong signals for attention disturbance (n = 233, ROR 3.3), while Loratadine was associated with nervousness (n = 145, ROR 3.3). Further exploration revealed more severe adverse reactions closely associated with Cetirizine, including hallucinations, aggression, and abnormal behavior. Importantly, Cetirizine was significantly associated with the occurrence of pericarditis (n = 138, ROR 8.13), potentially leading to serious adverse consequences. CONCLUSION: Compared to Loratadine, Cetirizine poses a greater potential risk in the nervous and psychiatric systems. Additionally, this study reveals previously underestimated potential cardiac toxicity of Cetirizine; albeit at a relatively low incidence rate, the high signal intensity warrants further attention and exploration. These findings highlight the need for enhanced patient monitoring and therapy optimization when prescribing these medications, ensuring better management of allergic diseases while minimizing risks.

Evaluating drug withdrawal syndrome risks through food and drug administration adverse event reporting system: a comprehensive disproportionality analysis.

Objective: The study aims to identify the drugs associated with drug withdrawal syndrome in the Food and Drug Administration Adverse Event Reporting System (FAERS) and estimate their risks of causing withdrawal syndrome. Methods: All the data were collected from FAERS from the first quarter of 2004 to the third quarter of 2023. Disproportionality analyses of odds ratio (ROR) and proportional reported ratio were conducted to identify potential adverse effects signal of drug withdrawal syndrome. Results: A total of 94,370 reports related to withdrawal syndrome from the data. The top 50 drugs with most frequency reported were analyzed, and 29 exhibited a positive signal based on the number of reports. The top three categories of drugs with positive signals included opioids, antidepressant drugs and antianxiety drugs. Other classifications included opioid antagonist, muscle relaxant, antiepileptic drugs, analgesics, hypnotic sedative drugs and antipsychotic drugs. Conclusion: Our analysis of FAERS data yielded a comprehensive list of drugs associated with withdrawal syndrome. This information is vital for healthcare professionals, including doctors and pharmacists, as it aids in better recognition and management of withdrawal symptoms in patients undergoing treatment with these medications.