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Journal of Traditional Chinese Medicine... Jun 2024To explore the pharmacodynamic effects and potential mechanisms of Shuangling extract against ulcerative colitis (UC).
Investigation of the active ingredients and mechanism of Shuangling extract in dextran sulfate sodium salt induced ulcerative colitis mice based on network pharmacology and experimental verification.
OBJECTIVE
To explore the pharmacodynamic effects and potential mechanisms of Shuangling extract against ulcerative colitis (UC).
METHODS
The bioinformatics method was used to predict the active ingredients and action targets of Shuangling extract against UC in mice. And the biological experiments such as serum biochemical indexes and histopathological staining were used to verify the pharmacological effect and mechanism of Shuangling extract against UC in mice.
RESULTS
The Shuangling extract reduced the levels of seruminterleukin-1β (IL-1β), tumor necrosis factor-α (TNF-N), interleukin-6 (IL-6) and other inflammatory factors in UC mice and inhibited the inflammatory response. AKT Serine/threonine Kinase 1 and IL-6 may be the main targets of the anti-UC action of Shuangling extract, and the TNF signaling pathway, Forkhead box O signaling pathway and T-cell receptor signaling pathway may be the main signaling pathways.
CONCLUSION
The Shuangling extract could inhibit the inflammatory response induced by UC and regulate intestinal immune function through multiple targets and multiple channels, which provided a new option and theoretical basis for anti-UC.
Topics: Animals; Colitis, Ulcerative; Mice; Drugs, Chinese Herbal; Dextran Sulfate; Male; Network Pharmacology; Tumor Necrosis Factor-alpha; Humans; Interleukin-1beta; Interleukin-6; Disease Models, Animal; Signal Transduction
PubMed: 38767631
DOI: 10.19852/j.cnki.jtcm.20240408.003 -
Frontiers in Pharmacology 2024As a novel drug formulation, antibody drug conjugates (ADCs) are widely used in various types of cancer. However, clinically, there is a lack of attention to the CVD...
OBJECTIVE
As a novel drug formulation, antibody drug conjugates (ADCs) are widely used in various types of cancer. However, clinically, there is a lack of attention to the CVD produced by them, as well as a lack of research on the real-world situation. Using the Food and Drug Administration Adverse Event Reporting System (FAERS) database, to ensure its clinical safety application, we analyzed post-marketing data on antitumor ADCs to identify risk factors and drugs associated with the risk of cardiovascular events.
RESEARCH DESIGN AND METHODS
We used OpenVigil 2.1 to conduct a database query for adverse events (AEs) reported to the FAERS database between the time the drug was launched and the second quarter of 2023. Cardiovascular adverse events (AEs) were grouped into fourteen narrow categories using the Standardized Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQs), and the reporting odds ratio (ROR) and the proportional reporting ratio (PRR) for reporting the association between different drugs and cardiovascular disease (CVD) risk were calculated.
RESULTS
In the FAERS database, 1863 AEs associated with CVD we studied were identified in patients receiving ADC therapy. Most reports came from people aged ≥65, but a significant number of cases were found to be unknown. The number of patients with antibody-drug conjugates (ADCs)-related CVD cases aged <18 years, 18-64 years, and≥ 65 years was 52 (2.79%), 586 (31.45%), and 613 (32.90%), respectively. The proportion of female patients (834, 44.77%) was higher than that of male patients (752, 40.37%). Death (770 reports), disability (9 reports), Hospitalization initial or prolonged (407 reports), and life-threatening reactions (187 reports). Of the 770 deaths reported, 103 (31.7%) were associated with brentuximab vedotin, 10 (24.4%) with sacituzumab govitecan, 22 (19.3%) with enfortumab vedotin, and 35 (34.7%) with trastuzumab emtansine.49 (41.2%) cases were associated with polatuzumab vedotin, 62 (29%) with trastuzumab deruxtecan, 423 (54.3%) with gemtuzumab ozogamicin, and 66 (38.8%) with inotuzumab ozogamicin. In a disproportionate number of SMQS, cardiac failure ( = 277) and embolic and thrombotic events, venous ( = 446) were the most frequently reported CVD-related AEs in ADCs.
CONCLUSION
By mining the FAERS database, we provided relevant information on the association between ADC use and cardiovascular-associated AEs. ADCs were associated with increased cardiovascular toxicity, deserving distinct monitoring and appropriate management. Further research is needed to confirm these findings and assess causality.
PubMed: 38766629
DOI: 10.3389/fphar.2024.1378010 -
Perspectives in Clinical Research 2024
Impact of education on knowledge and attitude related to pharmacovigilance and reporting of adverse drug reactions among community pharmacists in Yemen: A pre- and postinterventional study.
PubMed: 38765543
DOI: 10.4103/picr.picr_160_23 -
Scientific Reports May 2024Capmatinib is a potent selective mesenchymal-epithelial transition inhibitor approved in 2020 for the treatment of metastatic non-small cell lung cancer. As real-world...
Capmatinib is a potent selective mesenchymal-epithelial transition inhibitor approved in 2020 for the treatment of metastatic non-small cell lung cancer. As real-world evidence is very limited, this study evaluated capmatinib-induced adverse events through data mining of the FDA Adverse Event Reporting System database. Four disproportionality analysis methods were employed to quantify the signals of capmatinib-related adverse events. The difference in capmatinib-associated adverse event signals was further investigated with respect to sex, age, weight, dose, onset time, continent, and concomitant drug. A total of 1518 reports and 4278 adverse events induced by capmatinib were identified. New significant adverse event signals emerged, such as dysphagia, dehydration, deafness, vocal cord paralysis, muscle disorder, and oesophageal stenosis. Notably, higher risk of alanine aminotransferase and aspartate aminotransferase increases were observed in females, especially when capmatinib was combined with immune checkpoint inhibitors. Compared with Europeans and Asians, Americans were more likely to experience peripheral swelling, especially in people > 65 years of age. Renal impairment and increased blood creatinine were more likely to occur with single doses above 400 mg and in Asians. This study improves the understanding of safety profile of capmatinib.
Topics: Humans; Male; Female; United States; Middle Aged; Aged; United States Food and Drug Administration; Pharmacovigilance; Adverse Drug Reaction Reporting Systems; Benzamides; Adult; Triazines; Carcinoma, Non-Small-Cell Lung; Aged, 80 and over; Young Adult; Lung Neoplasms; Adolescent; Imidazoles
PubMed: 38762672
DOI: 10.1038/s41598-024-62356-w -
Scientific Reports May 2024Fulvestrant, as the first selective estrogen receptor degrader, is widely used in the endocrine treatment of breast cancer. However, in the real world, there is a lack...
Fulvestrant, as the first selective estrogen receptor degrader, is widely used in the endocrine treatment of breast cancer. However, in the real world, there is a lack of relevant reports on adverse reaction data mining for fulvestrant. To perform data mining on adverse events (AEs) associated with fulvestrant and explore the risk factors contributing to severe AEs, providing a reference for the rational use of fulvestrant in clinical practice. Retrieved adverse event report information associated with fulvestrant from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database, covering the period from market introduction to September 30, 2023. Suspicious AEs were screened using the reporting odds ratio (ROR) and proportional reporting ratio methods based on disproportionality analysis. Univariate and multivariate logistic regression analyses were conducted on severe AEs to explore the risk factors associated with fulvestrant-induced severe AEs. A total of 6947 reports related to AEs associated with fulvestrant were obtained, including 5924 reports of severe AEs and 1023 reports of non-severe AEs. Using the disproportionality analysis method, a total of 210 valid AEs were identified for fulvestrant, with 45 AEs (21.43%) not listed in the product labeling, involving 11 systems and organs. The AEs associated with fulvestrant were sorted by frequency of occurrence, with neutropenia (325 cases) having the highest number of reports. By signal strength, injection site pruritus showed the strongest signal (ROR = 658.43). The results of the logistic regression analysis showed that concurrent use of medications with extremely high protein binding (≥ 98%) is an independent risk factor for severe AEs associated with fulvestrant. Age served as a protective factor for fulvestrant-related AEs. The co-administration of fulvestrant with CYP3A4 enzyme inhibitors did not show statistically significant correlation with the occurrence of severe AEs. Co-administration of drugs with extremely high protein binding (≥ 98%) may increase the risk of severe adverse reactions of fulvestrant. Meanwhile, age (60-74 years) may reduce the risk of severe AEs of fulvestrant. However, further clinical research is still needed to explore and verify whether there is interaction between fulvestrant and drugs with high protein binding through more clinical studies.
Topics: Fulvestrant; Humans; Data Mining; Female; Adverse Drug Reaction Reporting Systems; Middle Aged; United States Food and Drug Administration; Databases, Factual; Adult; Aged; United States; Breast Neoplasms; Risk Factors; Antineoplastic Agents, Hormonal; Adolescent; Drug-Related Side Effects and Adverse Reactions; Young Adult
PubMed: 38762547
DOI: 10.1038/s41598-024-62238-1 -
Resuscitation Jul 2024Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has become a common intervention for patients with cardiogenic shock (CS), often complicated by cardiac arrest... (Randomized Controlled Trial)
Randomized Controlled Trial
AIM
Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has become a common intervention for patients with cardiogenic shock (CS), often complicated by cardiac arrest (CA). Moderate hypothermia (MH) has shown promise in mitigating ischemia-reperfusion injury following CA. The HYPO-ECMO trial aimed to compare the effect of MH versus normothermia in refractory CS rescued by VA-ECMO. The primary aim of this non-predefined post hoc study was to assess the treatment effect of MH in the subgroup of patients with cardiac arrest (CA) within the HYPO-ECMO trial. Additionally, we will evaluate the prognostic significance of CA in these patients.
METHODS
This post hoc analysis utilized data from the randomized HYPO-ECMO trial conducted across 20 French cardiac shock care centers between October 2016 and July 2019. Participants included intubated patients receiving VA-ECMO for CS for less than 6 h, with 334 patients completing the trial. Patients were randomized to early MH (33-34 °C) or normothermia (36-37 °C) for 24 h.
RESULTS
Of the 334 patients, 159 (48%) experienced preceding CA. Mortality in the CA group was 50.9% at 30 days and 59.1% at 180 days, compared to 42.3% and 51.4% in the no-CA group, respectively (adjusted risk difference [RD] at 30 days, 8.1% [-0.8 to 17.1%], p = 0.074 and RD at 180 days 7.0% [-3.0 to 16.9%], p = 0.17). MH was associated with a significant reduction in primary (RD -13.3% [-16.3 to -0.3%], p = 0.031) and secondary outcomes in the CA group only (p < 0.025 for all), with a significant interaction between MH and CA status for 180-day mortality [p = 0.03].
CONCLUSIONS
This post hoc analysis suggests that MH shows potential for reducing mortality and composite endpoints in patients with cardiac arrest and refractory CS treated with VA-ECMO without an increased risk of severe bleeding or infection. Further research is needed to validate these findings and elucidate underlying mechanisms.
Topics: Humans; Extracorporeal Membrane Oxygenation; Male; Female; Hypothermia, Induced; Middle Aged; Heart Arrest; Shock, Cardiogenic; Aged
PubMed: 38762081
DOI: 10.1016/j.resuscitation.2024.110235 -
Journal of the American Academy of... May 2024
PubMed: 38762011
DOI: 10.1016/j.jaad.2024.05.018 -
BMC Pediatrics May 2024Paediatric patients are especially prone to experiencing adverse drug reactions (ADRs), and the surgical environment gathers many conditions for such reactions to occur.... (Observational Study)
Observational Study
BACKGROUND
Paediatric patients are especially prone to experiencing adverse drug reactions (ADRs), and the surgical environment gathers many conditions for such reactions to occur. Additionally, little information exists in the literature on ADRs in the paediatric surgical population. We aimed to quantify the ADR frequency in this population, and to investigate the characteristics and risk factors associated with ADR development.
METHODS
A prospective observational study was conducted in a cohort of 311 paediatric patients, aged 1-16 years, admitted for surgery at a tertiary referral hospital in Spain (2019-2021). Incidence rates were used to assess ADR frequency. Odds ratios (ORs) were calculated to evaluate the influence of potential risk factors on ADR development.
RESULTS
Distinct ADRs (103) were detected in 80 patients (25.7%). The most frequent being hypotension (N = 32; 35%), nausea (N = 16; 15.5%), and emergence delirium (N = 16; 15.5%). Most ADRs occurred because of drug-drug interactions. The combination of sevoflurane and fentanyl was responsible for most of these events (N = 32; 31.1%). The variable most robustly associated to ADR development, was the number of off-label drugs prescribed per patient (OR = 2.99; 95% CI 1.73 to 5.16), followed by the number of drugs prescribed per patient (OR = 1.26, 95% CI 1.13 to 1.41), and older age (OR = 1.26, 95% CI 1.07 to 1.49). The severity of ADRs was assessed according to the criteria of Venulet and the Spanish Pharmacovigilance System. According to both methods, only four ADRs (3.9%) were considered serious.
CONCLUSIONS
ADRs have a high incidence rate in the paediatric surgical population. The off-label use of drugs is a key risk factor for ADRs development.
Topics: Humans; Prospective Studies; Child; Child, Preschool; Female; Male; Risk Factors; Infant; Adolescent; Drug-Related Side Effects and Adverse Reactions; Spain; Surgical Procedures, Operative; Incidence; Drug Interactions; Off-Label Use; Emergence Delirium
PubMed: 38760745
DOI: 10.1186/s12887-024-04803-1 -
Scientific Reports May 2024With its increasing use in the treatment of thrombocytopenia, avatrombopag's associated adverse events (AEs) pose a major challenge to its clinical application. This...
With its increasing use in the treatment of thrombocytopenia, avatrombopag's associated adverse events (AEs) pose a major challenge to its clinical application. This study aims to comprehensively study AEs associated with avatrombopag by using real-world evidence. We curated AE reports for avatrombopag from the first quarter of 2018 to the fourth quarter of 2023 in the US Food and Drug Administration's Adverse Event Reporting System (FAERS) database. AEs were coded using the Medical Dictionary for Regulatory Activities of Preferred Terms and System Organ Classes. The reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item Gamma-Poisson Shrinker were used to investigate the relationship between avatrombopag and AE reports. Among 9,060,312 reported cases in the FAERS database, 1211 reports listed avatrombopag as "primary suspected" drug. Disproportionality analysis identified 44 preferred terms across 17 organ systems met the criteria for at least one of the four algorithms. The most commonly reported AEs were platelet count decreased (20.2%), headache (16.7%), platelet count increased (11.9%), platelet count abnormal (6.3%), contusion (2.7%), pulmonary embolism (2.3%), and deep vein thrombosis (2.1%). Unexpected AEs such as seasonal allergy, rhinorrhea, antiphospholipid syndrome, ear discomfort, and photopsia were also observed. Excluding the other serious outcomes, hospitalization (34.6%) was the most frequently reported serious outcome, followed by death (15.4%). Most reported AEs occurred within the first 2 days of initiating avatrombopag therapy, and the median onset time was 60 days. We identified new and unexpected AEs with clinical use of avatrombopag, and our results may provide valuable information for clinical monitoring and identifying risks associated with avatrombopag.
Topics: Humans; Pharmacovigilance; United States Food and Drug Administration; United States; Adverse Drug Reaction Reporting Systems; Retrospective Studies; Data Mining; Male; Female; Middle Aged; Aged; Adult; Thrombocytopenia; Databases, Factual; Thiazoles; Young Adult; Adolescent; Child; Thiophenes
PubMed: 38760419
DOI: 10.1038/s41598-024-62129-5 -
Journal of Medical Systems May 2024Reports from spontaneous reporting systems (SRS) are hypothesis generating. Additional evidence such as more reports is required to determine whether the generated...
Reports from spontaneous reporting systems (SRS) are hypothesis generating. Additional evidence such as more reports is required to determine whether the generated drug-event associations are in fact safety signals. However, underreporting of adverse drug reactions (ADRs) delays signal detection. Through the use of natural language processing, different sources of real-world data can be used to proactively collect additional evidence for potential safety signals. This study aims to explore the feasibility of using Electronic Health Records (EHRs) to identify additional cases based on initial indications from spontaneous ADR reports, with the goal of strengthening the evidence base for potential safety signals. For two confirmed and two potential signals generated by the SRS of the Netherlands Pharmacovigilance Centre Lareb, targeted searches in the EHR of the Leiden University Medical Centre were performed using a text-mining based tool, CTcue. The search for additional cases was done by constructing and running queries in the structured and free-text fields of the EHRs. We identified at least five additional cases for the confirmed signals and one additional case for each potential safety signal. The majority of the identified cases for the confirmed signals were documented in the EHRs before signal detection by the Dutch Medicines Evaluation Board. The identified cases for the potential signals were reported to Lareb as further evidence for signal detection. Our findings highlight the feasibility of performing targeted searches in the EHR based on an underlying hypothesis to provide further evidence for signal generation.
Topics: Electronic Health Records; Humans; Adverse Drug Reaction Reporting Systems; Pharmacovigilance; Netherlands; Natural Language Processing; Drug-Related Side Effects and Adverse Reactions; Data Mining
PubMed: 38753223
DOI: 10.1007/s10916-024-02070-2