Reporting System Research Articles

Leveraging Multiple Administrative Data Sources to Reduce Missing Race and Ethnicity Data: A Descriptive Epidemiology Cross-Sectional Study of COVID-19 Case Relative Rates.

Understanding race and ethnicity (RE) differentials improves health outcomes. However, RE data are consistently missing from electronic laboratory reports, the primary source of COVID-19 case metrics. We addressed the missing RE differentials and compared vaccinated and unvaccinated cases from March 1, 2020, to May 30, 2023, in New York State (NYS), excluding New York City. This descriptive epidemiology cross-sectional study linked the NYS Electronic Clinical Laboratory Reporting System (ECLRS) with NYS Immunization Information System (NYSIIS) to address the missing RE data in the ECLRS system. The primary metric was the COVID-19 case relative risk (RR) for each RE relative to white individuals. There were 4,212,741 COVID-19 cases with 39% (1,624,818) missing RE data in ECLRS; missing RE data declined to 17% (726,023) after matching with NYSIIS. For those aged 65years or older (after matching), 42% were missing in 2020, which declined by 17% by 2023. In May 2021, COVID-19 RRs for vaccinated individuals were 1.09 (95% CI 0.90-1.32), 1.11 (95% CI 0.87-1.43), 1.13 (95% CI 0.93-1.39), and 1.89 (95% CI 1.01-3.52), and for unvaccinated individuals were 1.73 (95% CI 1.66-1.82), 0.84 (95% CI 0.78-0.92), 3.10 (95% CI 2.98-3.22), and 3.49 (95% CI 3.05-3.98) respectively for Hispanic, Asian/Pacific Islander, Black people, and American Indian/Alaska Native individuals. Matching case data with vaccine registries reduce missing RE data for COVID-19 cases. Disparity was lower in vaccinated than in unvaccinated individuals indicating that vaccination mitigated RE disparities early in the pandemic. This underscores the value of interoperable systems with automated matching for disparity analyses.

Adverse events associated with carbamazepine: a pharmacovigilance study using the FDA Adverse Event Reporting System

ABSTRACT Introduction Carbamazepine (CBZ) is a commonly used antiseizures medications (ASM), but its adverse drug reactions (ADRs) can impact the successful management of epilepsy. There are currently limited systematic studies on ADRs related to CBZ, necessitating further investigation. Areas covered Using the FDA Adverse Event Reporting System (FAERS) database , we extracted reports where CBZ was the primary suspect, conducting subgroup analyses stratified by sex and age. Four risk signal detection methods ROR, PRR, BCPNN, and EGBM were employed to systematically analyze the ADRs associated with CBZ. Expert opinion In the epilepsy population, ADRs related to CBZ often involve examinations, hereditary disorders, and infections. Subgroup analysis showed differences in ADR signals among male, female, elderly, and young patients. Human Herpesvirus 6 Infection and Dermatitis Exfoliative were consistent CBZ-induced ADRs, unaffected by age or sex. The study also identified previously overlooked ADRs such as bone metabolism abnormalities, ocular toxicity, and ototoxicity. Many ADRs linked to CBZ remain underreported. It is crucial to enhance monitoring and information dissemination about CBZ use in epileptic patients. Adjusting medication regimens for high-risk individuals, potentially incorporating acupuncture, traditional Chinese medicine, or alternative anti-seizure medications, should be considered when necessary.

Cardiovascular adverse events associated with norepinephrine-dopamine reuptake inhibitors: a pharmacovigilance study of the FDA Adverse Event Reporting System.

Norepinephrine-dopamine reputake inhibitors (NDRIs), including bupropion, methylphenidate, atomoxetine, and reboxetine, are commonly prescribed for psychiatric disorders such as narcolepsy, attention-deficit/hyperactivity disorder, and depression. Cardiovascular adverse events have been reported to the FDA despite their effectiveness. This pharmacovigilance study analyzed cardiovascular adverse events associated with NDRIs using the FDA Adverse Event Reporting System data from January 2004 to December 2021. A retrospective analysis of adverse event reports was conducted, employing time-trend analysis and disproportionality evaluation to assess cardiovascular risks. Bupropion had the greatest reported odds ratios (RORs) for tachycardia (ROR=4.2, 95% CI: 4.0-4.4) and hypertension (ROR=3.5, 95% CI: 3.3-3.7), while methylphenidate showed greater ROR for arrhythmias (ROR=2.8, 95% CI: 2.6-3.0) and palpitations (ROR=3.1, 95% CI: 2.9-3.3). Reboxetine had signals for palpitations (ROR=3.0, 95% CI: 2.8-3.2) and myocardial infarction (ROR=2.7, 95% CI: 2.5-2.9), whereas atomoxetine revealed signals for hypertension (ROR=2.9, 95% CI: 2.7-3.1) and syncope (ROR=2.5, 95% CI: 2.3-2.7). Time-trend analysis revealed temporal variability in the cardiovascular risks connected with NDRIs. Our research elucidates cardiovascular safety profiles for NDRIs, highlighting the necessity for continuous pharmacovigilance. The observed variations in adverse events emphasize the need for ongoing surveillance to mitigate potential cardiovascular risks and enhance patient safety and treatment outcomes.

Completeness and Timeliness of Vietnam's National COVID-19 Reporting System Among Schoolchildren in Thai Nguyen City, Vietnam During the Omicron Variant Epidemic.

Completeness and Timeliness of Vietnam's National COVID-19 Reporting System Among Schoolchildren in Thai Nguyen City, Vietnam During the Omicron Variant Epidemic.

Adverse events associated with herbal medicine products reported in the Korea Adverse Event Reporting System from 2012 to 2021.

Systematic collection of diverse adverse events during herbal medicine administration is crucial. The Korea Adverse Event Reporting System (KAERS) compiles spontaneously reported adverse event data for medicinal products including herbal medicines. This study focused on extracting and analyzing adverse event data specifically related to herbal medicine products from the KAERS database. Individual case safety reports (ICSRs) encompassing 84 types of herbal medicine products, identified by item codes from 2012 to 2021, were extracted from the KAERS database. Descriptive statistics were employed to analyze the characteristics of the extracted reports, and adverse event information was systematically categorized and analyzed based on the MedDRA System Organ Class and preferred term classification. In total, 1,054 ICSRs were extracted, with some documenting multiple adverse events in a single ICSR, resulting in 1,629 extracted adverse events. When categorized by the MedDRA System Organ Class, gastrointestinal disorders were the most prevalent (28.7%), followed by skin and subcutaneous tissue disorders (20.1%). Based on the preferred terms, the most frequently reported adverse events were diarrhea (5.8%), urticaria (5.3%), pruritus (4.7%), rash (4.4%), and abdominal discomfort (4.2%). The most frequently reported herbal medicines were Bangpungtongseong-san (297 cases), Kyeongok-go (144 cases), and Eunkyo-san (108 cases). Spontaneously reported adverse events associated with herbal medicine products were systematically documented using the KAERS database. This study, which focused on voluntarily reported adverse reactions, underscores the need for additional research to estimate the incidence rate of adverse events and assess causality.

Ring-Enhancement on CEUS: Is it Useful in the Differential Diagnosis of Solid Thyroid Nodules?

To investigate the efficiency of contrast-enhanced ultrasound (CEUS) features, particularly ring-enhancement patterns, in the differential diagnosis of thyroid nodules. 302 nodules with CEUS ring-enhancement were retrospectively enrolled, including 135 benign and 167 malignant ones. The ring-enhancement patterns were classified into regular and irregular hyper- or hypo-ring enhancement. Comparative analyses of ultrasound (US) and CEUS features between benign and malignant nodules were performed. The diagnostic performances of the ring-enhancement patterns and Chinese Thyroid Imaging Reporting and Data System (C-TIRADS) were compared in nodules with different sizes. Irregular hypo-ring enhancement was much more common in malignancies than that in benign ones, and it was an independent predictor for thyroid malignant nodules. With irregular hypo-ring enhancement as the diagnostic criteria for malignant nodules, the specificity was higher than that of C-TIRADS (85.2% vs. 75.6%, p = .037) while the AUC was comparable (0.845 vs. 0.803, p = .136) in all nodules. When the nodule size was taken into account, the specificity and AUC were both significantly higher than those of C-TIRADS (92.8% vs. 81.1%, p = .021; 0.907 vs. 0.823, p = .026) in nodules ≥10 mm, which can decrease the unnecessary FNA rate. Irregular hypo-ring enhancement was a valuable CEUS feature for the differential diagnosis of thyroid nodules, especially in nodules ≥10 mm.

Diabetic adverse events associated with three commonly used statins: a disproportionality analysis based on the FDA adverse event reporting system database

ABSTRACT Background The increasing prevalence of statin use for cardiovascular disease management has raised concerns regarding their safety profile, particularly regarding the potential risk of diabetes. Our study aims to analyze diabetic adverse event reports related to statins using a large pharmacovigilance database to provide timely insights into this significant issue. Methods We analyzed data from the FDA Adverse Event Reporting System (FAERS) database from 2004 to 2023. Disproportionality analyses were performed to detect signals of diabetic adverse events associated with the three most commonly prescribed statins: atorvastatin, rosuvastatin, and simvastatin. Results We identified 11,364 cases of statin-related diabetic adverse events across the three statins. Disproportionality analyses revealed a significant association between these statins and four specific diabetic adverse events: type 2 diabetes mellitus, impaired glucose tolerance, diabetic neuropathy, and diabetic retinal edema. Notable sex differences emerged, with females exhibiting an overall significantly higher propensity for diabetes-related adverse events. Conclusions Our study is timely and relevant as it addresses growing concerns about the safety of widely prescribed statins and their association with diabetes. By highlighting these critical issues, the study seeks to contribute valuable insights to practitioners, ultimately guiding better clinical practices and enhancing pharmacovigilance efforts.

A Clustering Ensemble Method for Drug Safety Signal Detection in Post-Marketing Surveillance.

Post-marketing surveillance refers to the process of monitoring the safety of drugs once they reach the market, after the successful completion of clinical trials. In this work, we investigate a computational approach using data mining tools to detect safety signals from post-market safety databases, or in other words, to identify adverse events (AEs) with disproportionately high reporting rates compared to other AEs, associated with a particular drug or a drug class. Essentially, we view this as a problem of cluster analysis-based anomaly detection on post-market safety data, where the goal is to 'unsupervisedly' detect the anomalous or the signal AEs. Our findings demonstrate the potential of using a clustering ensemble method to detect drug safety signals. It employs multiple clustering or anomaly detection algorithms, followed by a performance comparison of the candidate algorithms based on a collection of appropriate measures of goodness of clustering results. The method is general enough to include any number of clustering or anomaly detection algorithms and goodness measures, and performs better than any of the candidate algorithms in identifying the signal AEs. Extensive simulation studies illustrate that the ensemble method detects the AE signals from synthetic post-market safety datasets pretty accurately across the different scenarios explored. Based on the cases reported to the FDA Adverse Event Reporting System (FAERS) between 2013 and 2022, we further demonstrate that the ensemble method successfully identifies and confirms most of the adverse events that are known to occur most frequently in reaction to antiepileptic drugs and -lactam antibiotics.

Functional analysis of HpMYB72 showed its positive involvement in high-temperature resistance via repressing the expression of HpCYP73A

Global warming has led to occasional occurrence of extreme climates, especially summer high temperature, which constrains crops in growth and development. Pitaya (Hylocereus polyrhizus) characterizes in excellent tolerance to high temperature and drought stresses. Previously, a differentially expressed R2R3-MYB transcription factor gene, designated as HpMYB72, was identified in pitaya as exposure to high temperature. To elucidate the function of HpMYB72, currently, its spatiotemporal expression, as well as the roles involving in high-temperature response and regulating the downstream genes were conducted. The data from RT-qPCR and GUS reporter system showed that HpMYB72 was mainly expressed in rapidly developing tissues, particularly, in the flowers. It was activated by high temperature, and the coded proteins were accumulated in nucleus, indicating that HpMYB72 may act as a positive regulator involved in the high-temperature response of pitaya. Ectopic overexpression of HpMYB72 in Arabidopsis thaliana improved the growth performance and increased the germination rate as exposure to 42 °C; reduced the accumulation of reactive oxygen species under high-temperature stress thus alleviated the oxidative damage; increased the content of osmotic regulators, thereby relieved the water loss as exposure to high temperature. The available evidences comprehensively reflected that overexpression of HpMYB72 improved the tolerance of Arabidopsis against high temperature, supporting the hypothesis that HpMYB72 is a positive regulator of high-temperature response. The results of yeast one-hybrid assay and luciferase reporter system demonstrated that HpMYB72 bound directly to the promoter of pitaya cinnamate 4-hydroxylase gene HpCYP73A and inhibited its transcription. In this way, the NADPH which ought to be the substrate of cinnamate 4-hydroxylase was reassigned to ROS scavenging, and led the conversion of cinnamoyl-CoA to pinocembrin chalcone, which protects pitaya flowers from malformation under high temperature.

Pathological response following neoadjuvant immune checkpoint inhibitors in patients with hepatocellular carcinoma: a cross-trial, patient-level analysis

Neoadjuvant use of immune checkpoint inhibitors (ICIs) before liver resection results in pathological tumour regression in patients with hepatocellular carcinoma. We aimed to describe the characteristics of pathological responses after preoperative ICI therapy for hepatocellular carcinoma and to evaluate the association between the depth of tumour regression and relapse-free survival. In this cross-trial, patient-level analysis, we performed a pooled analysis of data from patients with hepatocellular carcinoma receiving ICI therapy before liver resection as part of a global collaborative consortium (NeoHCC) of five phase 1 and 2 clinical trials and standardised observational protocols conducted in 12 tertiary referral centres across the USA, UK, and Taiwan. Eligible patients were adults (aged ≥18 years) diagnosed with hepatocellular carcinoma by tissue core biopsy before treatment initiation, a Liver Imaging Reporting and Data System score of 5 on imaging, or both, with an Eastern Cooperative Oncology Group performance status score of 0-1, and no extrahepatic spread or previous ICI treatment. Pathological response was measured as the percentage of non-viable tumour in the resected surgical specimen, with major pathological response corresponding to at least 70% tumour regression and pathological complete response corresponding to 100% tumour regression. We correlated pathological response with radiological overall response using RECIST criteria (version 1.1) and relapse-free survival, and evaluated the threshold of tumour regression that could be optimally associated with relapse-free survival. At data cutoff on Jan 31, 2024, 111 patients were included in the study, of whom data on pathological response were available for 104 (94%) patients. Patients received treatment from Oct 5, 2017, to Nov 15, 2023, mostly ICI combinations (76 [69%]), for a median of 1·4 months (IQR 0·7-2·9). 87 (78%) patients were men and 24 (22%) were women. Most patients had underlying viral chronic liver disease (73 [66%]) and Barcelona Clinic Liver Cancer stage A hepatocellular carcinoma (61 [55%]), without portal vein thrombosis (87 [78%]). We observed major pathological response in 33 (32%) patients and pathological complete response in 19 (18%) patients. Radiological overall response was associated with major pathological response, with 23 (74%) of 31 patients with radiological response showing major pathological response compared with ten (14%) of 73 patients without radiological response (p<0·0001). However, ten (30%) of 33 major pathological responses were not predicted by radiological response. After a median follow-up of 27·2 months (95% CI 22·3-32·1), median relapse-free survival for the whole cohort was 43·6 months (95% CI 28·3-not evaluable). Relapse-free survival was significantly longer in patients with major pathological response than in those who did not have a major pathological response (not reached [95% CI not evaluable-not evaluable] vs 28·3 months [12·8-43·8]; hazard ratio 0·26 [0·10-0·66]; p=0·0024) and in patients with pathological complete response than in those who did not have a pathological complete response (NR [95% CI not evaluable-not evaluable] vs 32·8 months [15·0-50·5]; 0·19 [0·05-0·78]; p=0·010). Unbiased recursive partitioning of the cohort for the risk of relapse, death, or both identified a threshold of 90% as the optimal cutoff of pathological tumour regression to predict improved relapse-free survival. The extent of tumour regression following neoadjuvant ICI therapy could identify patients with improved relapse-free survival following liver resection. The threshold of at least 90% tumour regression should be validated for its surrogate role for relapse-free survival in phase 3 randomised controlled trials. None.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and suicidality: A replication study using reports to the World Health Organization pharmacovigilance database (VigiBase®)

IntroductionReports of suicidality associated with glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have been reported to the European Medicines Agency (EMA) and the United States Food and Drug Administration (FDA). We previously reported an increased reporting odds ratio (ROR) of some measures of suicidality with semaglutide and liraglutide using the FDA Adverse Event Reporting System (FAERS). Notwithstanding the increased ROR, causality between GLP-1 RAs exposure and any aspect of suicidality is not established. Research design and methodsThe analysis herein aims to extend a previous analysis of the FAERS by evaluating the ROR for suicidality reported to the World Health Organization (WHO) Pharmacovigilance Database (VigiBase). We aimed to characterize the ROR of suicidality associated with GLP-1 RAs, as extrapolated from spontaneous reports. As per our previous report, the ROR was considered significant when the lower limit of the 95 % confidence (CI) was >1.0. ResultsWe searched VigiBase reports from inception to January 2024. The RORs for suicidal ideation were significantly increased for semaglutide (5.82), liraglutide (4.03) and tirzepatide (2.25). For “depression/suicidal”, the ROR was significantly increased for semaglutide (14.74) and liraglutide (5.86); and for suicidal behaviour, the ROR was significantly increased for semaglutide (6.52) and liraglutide (3.90). However, for suicide attempts, the ROR was significantly decreased for semaglutide (0.11), dulaglutide (0.075), exenatide (0.047) and liraglutide (0.15). For completed suicide, the ROR was also significantly decreased for semaglutide (0.01), dulaglutide (0.003), exenatide (0.002) and liraglutide (0.008). ConclusionUnlike our previous report with FAERS, a mixed pattern of ROR emerged in the WHO VigiBase with respect to suicidality and exposure to select GLP-RAs. Causation between GLP-1 RA exposure and suicidality (either increased or decreased) cannot be ascertained from ROR data.

Differences in safety profiles of anti-herpesvirus medications: a real-world pharmacovigilance study based on the FAERS database

ABSTRACT Background Anti-herpesvirus drug safety profiles have not been systematically compared. Understanding variations in adverse events (AEs) could provide reference for rational clinical use. Methods We collected data on acyclovir, ganciclovir, valaciclovir, and foscarnet from the FDA Adverse Event Reporting System (FAERS) database from Q1 2004 to Q3 2023. Disproportionality analyses were conducted to evaluate the risk of AEs. Results All drugs exhibited significant associations with hematotoxicity, with ganciclovir and foscarnet being more myelosuppressive. The correlation with renal impairment ranked as follows: foscarnet, ganciclovir, valaciclovir, and acyclovir (ROR = 16.72, 7.06, 3.51, and 2.02, respectively). Regarding hepatotoxicity, ganciclovir was associated with acute-on-chronic liver failure (ROR = 52.83), and foscarnet was associated with fulminant hepatitis (ROR = 49.91). In the nervous system, acyclovir showed the highest intensity of neurotoxicity (ROR = 14.95). Valaciclovir ranked first in toxic encephalopathy (ROR = 64.70). Foscarnet showed the highest intensity of status epilepticus (ROR = 6.45). Besides, acyclovir showed the strongest association with severe cutaneous adverse reactions (SCARs). Conclusions Our study revealed differences in safety profiles of four anti-herpesvirus medications. Ganciclovir exhibited the highest risk of hematotoxicity but appeared relatively safe in seizures and SCARs. Foscarnet was more likely to induce nephrotoxicity, seizures, and electrolyte imbalances than others. Acyclovir and valaciclovir were strongly associated with plasmacytosis, neurotoxicity, and SCARs.

Prediction of aviation safety incident risk level based on ECSDNN

Prediction of aviation safety incident risk level is an important means of active risk management. Considering the high-dimensional complexity and class imbalance of massive aviation safety incident data, a prediction method for aviation safety incident risk level based on integrated cost-sensitive deep neural network (ECSDNN) is proposed. The feature representation of aviation safety incident data is realized by using the method of embedded coding of categorical attributes and splicing of numerical attributes; the cost-sensitive matrix and cost-sensitive loss function are designed by comprehensively considering the misclassification ratio and fixed cost, and the base classifier model based on cost-sensitive deep neural network (CSDNN) is constructed; the hard voting method is used to integrate multiple base classifiers with different parameters and performances to construct the integrated prediction model ECSDNN for aviation safety incident risk level. The experimental results on the Aviation Safety Incident Reporting System (ASRS) dataset show that compared with the optimal prediction ability of the baseline algorithm, the prediction accuracy of the ECSDNN model is improved 4.51%; compared with the single CSDNN base classifier, the prediction accuracy is improved 3.17%.

Adverse reaction of specific acute kidney injury caused by atorvastatin: an actual study based on the database of the US FDA adverse event reporting system

ABSTRACT Introduction Atorvastatin, one of the most widely used drugs, has attracted controversy regarding its potential adverse reactions to acute kidney injury(AKI). This study aims to provide evidence in support of the safe use of atorvastatin. Areas Covered Using the FDA Adverse Event Reporting System (FAERS) database (Q1 2004 to Q1 2024), we extracted reports where atorvastatin was the primary suspect and categorized them into five populations: the general population, acute myocardial infarction (AMI), ischemic stroke (IS), type 2 diabetes mellitus (T2DM), and hyperlipidemia (HLD). We performed subgroup analyses by gender and age strata within these populations, assessing positive signals through disproportionality analysis using four criteria: Ratio of Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Empirical Bayes Geometric Mean (EGBM). The statistical analysis evaluated differences between adverse drug reaction (ADR) occurrence and nonoccurrence, as well as between high and low induction time groups. Expert Opinion In the general population, evidence for a positive signal of AKI was insufficient. However, the sub-group analysis revealed a risk in males, with older individuals more often affected in both AMI and IS populations. In T2DM, positive signals were evident in younger age groups. For the HLD population, evidence of a positive AKI signal was insufficient across gender and age strata. Overall, atorvastatin is generally safe, but clinical vigilance for AKI is warranted in T2DM, AMI, and IS populations, particularly in older adults (65+ years).

Clinical adverse events to letairis: a real-world drug safety study based on FDA Adverse Event Reporting System (FAERS)

ABSTRACT Background Letairis (ambrisentan), an endothelin receptor antagonist (ERA), is a critical medication for pulmonary arterial hypertension (PAH). Despite its efficacy, its safety profile is under scrutiny, warranting a detailed analysis. Research design and methods This study leveraged the FDA Adverse Event Reporting System (FAERS) from Q1 2007 to Q4 2023, focusing on Letairis as the primary suspect in adverse events. Employing advanced data mining techniques, such as Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS), the study aimed to uncover safety signals. Results A total of 43,774 cases were identified, with Letairis implicated in 16,038,963 adverse event reports. There was a notable predominance of female patients (75.30%), with a median age around 64 years. Severe outcomes, including hospitalization (51.63%) and fatalities (20.44%), were prevalent. Signal strength analysis highlighted concerns in infections and infestations, as well as cardiac disorders. Conclusion The analysis underscores the need for vigilant pharmacovigilance and highlights Letairis’s potential to induce serious AEs, particularly in female and elderly populations. These findings are instrumental in guiding clinical practice and future drug safety assessments.

Real-World Data Mining for Signal Detection of Antipsychotics-Associated Adverse Events Using the Korea Adverse Event Reporting System (KAERS) Database.

Background and Objectives: Recent studies suggest that the binary categorization of first-generation antipsychotics (FGAs) as being primarily responsible for extrapyramidal symptoms (EPSs) and second-generation antipsychotics (SGAs) for cardiometabolic abnormalities is an oversimplification. SGAs also demonstrate antagonistic affinity for D2 receptors, indicating their potential to induce EPSs. This study utilized the Korea Adverse Event Reporting System (KAERS) database to explore adverse drug event (ADE) signals related to both FGAs and SGAs. Materials and Methods: Relevant ADE reports from January 2013 to December 2022 were extracted from the KAERS database and analyzed using disproportionality analysis, employing the proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC) with its 95% lower confidence interval (LCI) indices. Results: Of the initial dataset of 2,890,702 ADE reports, those with insufficient data and duplicates were removed, resulting in a final dataset of 5249 reports for analysis. Aripiprazole, an SGA, showed signals for movement disorders, including EPSs (PRR 4.7, ROR 4.8, IC 2.2), tremors (PRR 5.3, ROR 5.4, IC 2.4), and akathisia (PRR 18.6, ROR 19.3, IC 3.5). Notably, for quetiapine, cardiovascular signals were detected, including increased blood pressure (PRR 2.1, ROR 2.3, IC 0.5), and tachyarrhythmia (PRR 13.9, ROR 14.1, IC 1.8), along with peripheral edema (PRR 2.5, ROR 2.5, IC 0.2). Metabolic abnormalities, such as weight gain and increased appetite, were identified for four SGAs: aripiprazole, olanzapine, quetiapine, and risperidone. Safety signals related to movement disorders were not detectable for FGAs, likely due to the limited number of ADE reports available for analysis. Conclusions: Our study findings support that the distribution of ADEs between FGAs and SGAs is not strictly binary. Aripiprazole, despite being an SGA, showed signals for extrapyramidal movement disorders. Four SGAs (aripiprazole, olanzapine, quetiapine, and risperidone) were linked to metabolic side effects, while quetiapine was associated with cardiovascular safety signals.

Combined nephrotoxicity of Polymyxins and Vancomycin: a study on adverse event reporting for monotherapy versus combinations using the FDA adverse event reporting system (FAERS)

ABSTRACT Background Multidrug-resistant (MDR) infections pose a global public health crisis with significant mortality and economic burdens. Combination of polymyxins and vancomycin has shown effectiveness against MDR infections. However, their combined nephrotoxicity complicates clinical use. Given these concerns, we conducted a pharmacovigilance analysis using the FDA Adverse Event Reporting System (FAERS) to assess the nephrotoxicity of combinations of polymyxins and vancomycin compared to monotherapy. Research design and methods In this retrospective study, data from FAERS reports (2012 Q4 to 2023 Q2) were deduplicated and analyzed for adverse events (AEs) related to vancomycin, polymyxin B, and colistin. Disproportionality analyses were performed to evaluate the association between drugs and nephrotoxicity. Results A total of 9,796,784 adverse event reports, including 73,009 reports associated with nephrotoxicity, were included. All three drugs showed significant associations with nephrotoxicity. In combination therapy, polymyxin B-vancomycin exhibited a stronger association with nephrotoxicity compared to monotherapy, whereas colistin-vancomycin demonstrated a lower association with nephrotoxicity than colistin monotherapy. Conclusions This study found that combining vancomycin with colistin alleviated colistin-induced nephrotoxicity, while combining vancomycin with polymyxin B worsened polymyxin B-induced nephrotoxicity.

Real-world safety profile of zanubrutinib: a disproportionality analysis based on the FAERS database

ObjectiveZanubrutinib is a second-generation Bruton’s tyrosine kinase inhibitor that has been approved for the treatment of several B cell malignancies. The aim of this study was to evaluate adverse events...

Novel regulation pathway of eclosion hormones in Tribolium castaneum by distinct transcription factors through the initiation of 20-hydroxyecdysone

Eclosion hormone (EH) is not only a key trigger of insect ecdysis, but is also involved in the regulation of important physiological processes such as development, diapause, metamorphosis and reproduction. EH is an ideal target for RNAi treatment and prevention of the Tribolium castaneum. However, two EH genes in Tribolium castaneum demonstrate distinct replication and functional conversion relationships, and the mechanisms of transcriptional regulation of eclosion hormone remain largely unexplored and poorly understood. In this study, the activity of highly active promoter fragments and potential transcription factors of TcEH and TcEHL were identified using the Dual-Luciferase reporter system and TANSFAC. TcSlbo and TcCAD were revealed to be important transcription factors for TcEH and TcEHL, respectively. Knockdown of TcSlbo failed to slough off the old epidermis of Tribolium castaneum and prevented them from developing into adults. Furthermore, we demonstrated for the first time that 20-hydroxyecdysone (20E) affects the expression of TcEH and TcEHL by regulating the transcriptional activities of TcSlbo and TcCAD. This study provides new insights into the transcription regulation of TcEH and TcEHL, their roles in insect growth and development, and the involvement of 20E in eclosion regulation, offering potential molecular targets for future pest management strategies.

Neurotoxicity associated with chimeric antigen receptor T-cell therapy: a real-world study leveraging the FDA Adverse Event Reporting System

ABSTRACT Background CAR-T-associated neurotoxicity is extremely frequent with highly variable clinical presentation. Research design and methods Disproportionality analysis was conducted leveraging the FDA Adverse Event Reporting System (FAERS), covering the period from 1 January 2017, through 31 March 2023. The reporting odds ratio (ROR) and the information component (IC) were utilized to assess the adverse signals in total/individual CAR-T product. The lower limit of the ROR and IC 95% confidence interval (ROR025 and IC025) both exceeding threshold value (1 and 0, respectively) was considered a significant signal. Results Of the 60, 730 records associated with CAR-T, 11, 037 (18.17%) pertained to neurological events. Tisagenlecleucel exhibited the highest percentage of death (38.02%) and life‐threatening (12.90%) outcomes. Notably, it also displayed the broadest distribution of neurotoxicity. Additionally, distinct adverse signals unique to individual CAR-T products were identified. For instance, paraparesis, cerebral hemorrhage, impaired pupillary reflex, Guillain-Barre syndrome, brain death following tisagenlecleucel; dysarthria, orthostatic hypotension, and spinal cord edema after axicabtagene; parkinsonism, Bell’s palsy, and cranial nerve paralysis post ciltacabtagene. Conclusions Axicabtagene ciloleucel, tisagenlecleucel, brexucabtagene autoleucel, lisocabtagene maraleucel, idecabtagene vicleucel, and ciltacabtagene autoleucel exhibited increased odds of neurotoxicity, with some discrepancies in their characteristics, profiles, and severity.