AREAS COVERED: Literature was searched in different resources for eligible studies. The pooled risk ratio was measured using RevMan software, with p<0.05 (two-sided) set as statistically significant.
EXPERT OPINION: The ABCB1 C3435T homozygous mutant (TT) was associated with significantly increased risk of MACE compared to either wild type genotype (CC) or the combination of wild type and heterozygous genotypes (TT vs. CC: RR 1.33; 95% CI 1.06-1.68; p=0.02; TT vs. CC+CT: RR 1.32; 95% CI 1.10-1.60; p=0.004). Safety outcomes, i.e. bleeding events were not significantly different between the genetic models investigated (TT vs. CC: RR 1.93; 95% CI 0.86-4.35; p=0.11; TT vs. CC+CT: RR 1.36; 95% CI 0.89-2.09; p=0.16; CT+TT vs. CC: RR 1.20; 95% CI 0.59-2.44; p=0.61). It is suggested that ABCB1 C3435T genotype should be tested for ACS/CAD patients undergoing PCI to ensure optimum therapy of clopidogrel.
METHODS: An electronic database search for RCTs was conducted on Medline via PubMed, Cochrane, and Clinicaltrials.gov using the terms 'Daridorexant,' 'RCT,' 'Insomnia' trials evaluating the efficacy and/or safety of daridorexant for insomnia were included. The data were synthesized using Cochrane review manager version 5.4.1. Cochrane risk of bias 2.0 tool and GRADEpro-GDT were used to assess the methodological and evidence quality, respectively.
RESULTS: Of 109 searched studies, four trials were included. The risk of treatment-emergent adverse events with 25 mg daridorexant [risk ratio (RR) = 1.12 (0.88, 1.43), p = 0.36; I2 = 0%] and 50 mg daridorexant [RR = 1.25 (0.88, 1.79), p = 0.22; I2 = 28%] and serious adverse events with 25 mg [RR = 0.86 (0.23, 3.19), p = 0.82, I2 = 56%] and 50 mg [RR = 1.32 (0.29, 6.08), p = 0.72, I2 = 52%] was comparable to placebo [Moderate quality evidence]. Risk of nasopharyngitis was also comparable to placebo. The efficacy parameters like wake after sleep onset, latency to persistent sleep, and subjective total sleep time showed significant improvement with daridorexant. The risk of bias is low for three studies and some concern for one.
CONCLUSION: Daridorexant is a safer and efficacious agent for induction and maintenance of sleep for chronic insomnia.
PROSPERO: The registration number is CRD42022335233.
CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifiers are NCT03575104, NCT03545191, NCT03679884, and NCT02839200).
RESEARCH DESIGN AND METHODS: All suspected ADEs associated with tocilizumab between April to August 2020 were analyzed based on COVID-19 patients' demographic and clinical variables, and severity of involvement of organ system.
RESULTS: A total of 1005 ADEs were reported among 513 recipients. The majority of the ADEs (46.26%) were reported from 18-64 years, were males and reported spontaneously. Around 80%, 20%, and 64% were serious, fatal, and administered intravenously, respectively. 'Injury, Poisoning, and Procedural Complications' remain as highest (35%) among categorized ADEs. Neutropenia, hypofibrinogenemia were common hematological ADEs. The above 64 years was found to have significantly lower odds than of below 45 years. In comparison, those in the European Region have substantially higher odds compared to the Region of Americas.
CONCLUSION: Neutropenia, superinfections, reactivation of latent infections, hepatitis, and cardiac abnormalities were common ADEs observed that necessitate proper monitoring and reporting.