Objective: Using the Food and Drug Administration Adverse Event Reporting System (FAERS) database, four signal detection methods were applied to mine adverse drug events (ADEs) related to use of dual orexin receptor antagonists (DORAs) to provide reference for safe clinical use.Research design and Methods: Data collected from Q3rd 2014 to Q4th 2023 were obtained from the FAERS database. According to the preferred terminology (PT) and systematic organ classification (SOC) of MedDRA v.26.0, the reporting odds ratio (ROR), proportional reporting ratio (PRR), multi-item gamma Poisson shrinker (MGPS), and Bayesian confidence propagation neural network (BCPNN) were used to detect ADE signals.Results: A total of 11,857 DORAs-related adverse reactions were detected, reported with suvorexant, lemborexant, and daridorexant as the main suspected drugs was 8717584, and 2556, respectively. A higher proportion of females than males were reported (57.27% vs. 33.04%). The top 20 positive PT signals from three DORAs showed that “sleep paralysis” ranked first. “Brain fog” was stronger following daridorexant but was not detected for the other two drugs, and “sleep sex” and “dyssomnia” were stronger in suvorexant but not in the other two drugs. Additionally, some PTs occurred that were not included in drug instructions, such as “hangover” and “hypnagogic hallucination.”Conclusion: In this study, four algorithms (ROR, PRR, BCPNN, and MGPS) were used to mine the safety signals of DORAs. We identified some potential ADE signals that can promote the rational use of DORAs and improve their safety.

Objective: Studies on anti-Aβ drugs for the treatment of Alzheimer’s disease (AD) have garnered significant attention; however, their safety still requires further research and monitoring. Although recent studies have analyzed the adverse drug events (ADEs) of lecanemab and aducanumab separately, there is a lack of comparison between these two drugs, and no exploration of gender differences. This study aims to compare the adverse reaction signals of lecanemab and aducanumab, also exploring the differences between genders.Research design and methods: We analyzed ADEs reported by patients using lecanemab and aducanumab, using the FDA adverse event reporting system (FAERS). The data was classified using the preferred terms (PTs) and systemic organ categories (SOCs). Four positive signal detection algorithms were used, namely, the Ratio-to-Ratio (ROR), proportional reporting ratio (PRR), multi item gamma poisson shrinker (MGPS), and bayesian belief propagation neural network (BCPNN). Additionally, the time-to-onset of ADEs was also compared between the two drugs and between male and female patients.Results: A total of 1,409 ADE reports in which an anti-Aβ antibody drug was primarily suspected were included in the study, comprising 892 cases (63.31%) of lecanemab and 517 cases (36.69%) of aducanumab. For both lecanemab and aducanumab, only the SOC ‘nervous system disorders’ met the criteria for positive signal for all four algorithms. The number of positive PT signals related to lecanemab and aducanumab was 40 and 33, respectively. Among them, “cerebral microbleeds,” “amyloid protein related imaging abnormalities (ARIA),” and “central nervous system superficial squamous cell hyperplasia” all exhibited strong signals, regardless of drug or sex of the patient. Additionally, there were some differences in PT signals between male and female patients, and some new PT signals that were not included in the drug labels were identified. The median time-to-onset of lecanemab was shorter than that of aducanumab (33 days vs. 146 days).Conclusion: Four signal calculation methods were used to assess potential adverse reaction signals of lecanemab and aducanumab. This study identified some new PT signals and some PT signals showed gender differences. The median time-to-onset of ADEs due to lecanemab is shorter than that due to aducanumab.

Objective: We investigated the pharmacokinetic (PK) and pharmacodynamic (PD) parameters of linezolid in patients who had suffered cerebral hemorrhage after lateral ventricular drainage. Materials and methods: Ten patients with cerebral hemorrhage after lateral ventricular drainage with stroke-associated pneumonia who were given linezolid were enrolled. Plasma and cerebrospinal fluid (CSF) samples were taken at appropriate intervals after the first administration of linezolid and assayed by high-performance liquid chromatography (HPLC). Then, PK parameters were estimated, and a Monte Carlo simulation was used to calculate the probability of target attainments (PTAs) for linezolid achieving the PK/PD index at different minimal inhibitory concentrations (MICs). Results: The maximum concentration of linezolid in plasma and CSF was reached at 1.00 h and 3.10 h, respectively. The average penetration of linezolid in CSF was 56.81%. If the area under the plasma concentration vs time curve from zero to the final sampling time (AUC_{0–24 h})/MIC ≥ 59.1 was applied as a parameter, the PTA of linezolid in plasma could provide good coverage (PTA ≥ 90%) only for pathogens with a MIC of ≤2 µg/mL, whereas it could be achieved in CSF with a MIC of ≤1 µg/mL. If %T > MIC ≥ 40% was applied as a parameter, the PTA of linezolid in plasma/CSF could provide good coverage if the MIC was ≤4 µg/mL. Conclusions: For patients with infection of the central nervous system and who are sensitive to the drug, the usual dosing regimens of linezolid can achieve a good therapeutic effect. However, for critically ill or drug-resistant patients, an increase in dose, the frequency of administration, or longer infusion may be needed to improve the curative effect.