A pharmacovigilance study of drug-reduced male semen quality based on the Food and Drug Administration adverse event reporting system database.

BACKGROUND: Real-world big data studies on drug-reduced male semen quality are few and far between, with most studies based on animal trials, small scale retrospective studies, or a limited number of pre-market clinical trials. METHODS: This study aimed to identify culprit drugs that reduced male semen quality based on the United States Food and Drug Administration adverse event reporting system. The Medical Dictionary for Regulatory Activities preferred terms and standardized Medical Dictionary for Regulatory Activities queries were used to define reduced male semen quality. Adverse events related to drug-reduced male semen quality were then analyzed by disproportionality analysis using the United States Food and Drug Administration adverse event reporting system data between 2004 and 2023. RESULTS: At the preferred term level, 59 drugs with risk signals were detected to be associated with drug-reduced male semen quality, with the three most frequently reported second-level Anatomical Therapeutic Chemical groups being antineoplastic agents (n = 16, 27.12%), psychoanaleptics (n = 9, 15.25%), and psycholeptics (n = 6, 10.17%). At the standardized Medical Dictionary for Regulatory Activities queries level, the five drugs with the greatest number of cases were finasteride (845 cases, IC025 = 7.72), dutasteride (163 cases, IC025 = 7.22), tamsulosin (148 cases, IC025 = 5.99), testosterone (101 cases, IC025 = 4.08), and valproic acid (54 cases, IC025 = 2.44). Additionally, clinical information about drug-reduced male semen quality is absent from the Summary of Product Characteristics of 41 drugs in our study. CONCLUSIONS: Using the United States Food and Drug Administration adverse event reporting system database, we offer a list of drugs with risk signals for reducing male semen quality. In the future, there is still a need for more studies on drugs whose effects on male semen quality are not fully understood.

A real-world pharmacovigilance study of drug-induced QT interval prolongation: analysis of spontaneous reports submitted to FAERS.

Purpose: To identify the most commonly reported drugs associated with QT interval prolongation in the FDA Adverse Event Reporting System (FAERS) and evaluate their risk for QT interval prolongation. Methods: We employed the preferred term (PT) "electrocardiogram QT prolonged" from the Medical Dictionary for Regulatory Activities (MedDRA) 26.0 to identify adverse drug events (ADEs) of QT interval prolongation in the FAERS database from the period 2004-2022. Reporting odds ratio (ROR) was performed to quantify the signals of ADEs. Results: We listed the top 40 drugs that caused QT interval prolongation. Among them, the 3 drugs with the highest number of cases were quetiapine (1,151 cases, ROR = 7.62), olanzapine (754 cases, ROR = 7.92), and citalopram (720 cases, ROR = 13.63). The two most frequently reported first-level Anatomical Therapeutic Chemical (ATC) groups were the drugs for the nervous system (n = 19, 47.50%) and antiinfectives for systemic use (n = 7, 17.50%). Patients with missing gender (n = 3,482, 23.68%) aside, there were more females (7,536, 51.24%) than males (5,158, 35.07%) were involved. 3,720 patients (25.29%) suffered serious clinical outcomes resulting in deaths or life-threatening conditions. Overall, most drugs that caused QT interval prolongation had early failure types according to the assessment of the Weibull's shape parameter (WSP) analysis. Conclusions: Our study offered a list of drugs that frequently caused QT interval prolongation based on the FAERS system, along with a description of some risk profiles for QT interval prolongation brought on by these drugs. When prescribing these drugs in clinical practice, we should closely monitor the occurrence of ADE for QT interval prolongation.

Interactive effects of vitamin D and serum uric acid concentration on protein-energy wasting in maintenance hemodialysis patients.

This study aimed to explore the influence of the interaction between vitamin D level and blood uric acid level on protein-energy wasting (PEW) in patients with Maintenance hemodialysis (MHD), in order to provide a solution for disease prevention. For this aim, a total of 150 patients with maintenance hemodialysis aged 30-79 years in a hospital were included in the study. The logistic regression model was used to analyze the relationship between vitamin D level, blood uric acid level and PEW, and the additive interaction was evaluated by calculating the relative excess risk ratio (RERI) attributive ratio (AP) and synergy index (S) of the interaction. Finally, the ROC curve was drawn to evaluate the diagnostic value of vitamin D level and blood uric acid level for PEW. In this study, the detection rate of PEW was 68%, low vitamin D level was 57.33%, and high blood uric acid level was 64.67%. Compared with non-low vitamin D levels, the PEW risk was OR=16.794, 95%CI: 4.973-60.356; Compared with those without high uric acid levels, the PEW risk was OR=7.599, 95%CI: 2.460-23.468. However, there was no multiplicative interaction between the two on PEW risk (OR=0.345, 95%CI: 0.060-1.983, P=0.233). In the additive interaction analysis, the PEW risk OR=43.992,95%CI: 12.795-151.253, higher than those with only high uric acid levels or only low vitamin D levels, the combination of the two had a summative interaction with PEW risk, with a RERI of 20.599 (95%CI: -26.158-67.356) API was 0.468 (-0.159-1.095) and S was 1.920 (0.569-6.483). In conclusion, both vitamin D deficiency and high uric acid levels were associated with an increased risk of PEW in MHD patients, and low vitamin D and high uric acid levels had a summative interaction with protein-energy expenditure risk.

Study of the protective effects of dexamethasone on ileum mucosa injury in rats with severe acute pancreatitis.

OBJECTIVES: To study the protecting effects of dexamethasone on ileum mucosa injury of rats with severe acute pancreatitis (SAP). METHODS: The SAP rats were prepared by improved Aho's methods. The plasma endotoxin and inflammatory mediators in serum were determined. The rat mortality, pathological changes of terminal ileum, nuclear factor kappa B (NF-kappaB), apoptotic indexes, and apoptotic related protein expression were observed. RESULTS: The plasma endotoxin, inflammatory mediators, and NF-kappaB protein expression as well as pathological scores of the treatment group of ileum mucosa were lower than those of the model group at different time points. P selectin in model group significantly exceeded the dexamethasone treatment group at 3 and 6 hours (P < 0.01, P < 0.05). Caspase-3 protein expression in dexamethasone treatment group significantly exceeded the model group at 3 and 6 hours (P < 0.05), and apoptotic indexes were higher than those of the model group at 6 hours (P < 0.05), but Bax protein has shown no marked difference among groups. CONCLUSIONS: Dexamethasone can reduce the endotoxin level and inflammatory mediators and down-regulate NF-kappaB protein expression of ileum mucosa, and ileum mucosa epithelial cell apoptosis induction was involved as well. The tissue microarrays technique is of advantage in SAP study.