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The most common toxicities associated with cyclin‐dependent kinase (CDK) 4/6 inhibitor therapy include decreased leukopenia and neutropenia due to the inhibition of CDK6 of leukocyte and neutrophil precursors in bone marrow. These hematological toxicities are more commonly observed with palbociclib administration than with abemaciclib administration, which is approximately 13 times more selective against CDK4 than CDK6. Thus, even though both successfully inhibit CDK4/6, the side effects of palbociclib and abemaciclib differ due to differences in selectivity. Recent reports have suggested an association between palbociclib and medication‐related osteonecrosis of the jaw; however, reports on this association are inconsistent. This study investigated the potential association of palbociclib and abemaciclib with MRONJ using the FAERS. Signals of "Osteonecrosis of jaw" were detected only in females using palbociclib (cROR025: 2.08). Other signals detected included stomatitis‐related adverse events with abemaciclib and intraoral soft tissue damage and infection with palbociclib. As previous exploratory studies have reported MRONJ signals for bisphosphonates and denosumab, we calculated the aROR for palbociclib‐induced osteonecrosis of the jaw using concomitant bisphosphonates and denosumab as covariates. A signal was detected even after adjusting for sex, age, and concomitant medications as covariates (aROR0025: 5.74). A proper understanding of the differences in CDK selectivity is necessary for the appropriate use of CDK4/6 inhibitors. To the best of our knowledge, this is the first report on CDK4/6 inhibitors and drug‐related osteonecrosis of the jaw. We believe that these results will offer new insights into adverse events related to the use of CDK4/6 inhibitors, and may aid in the proper use of CDK4/6 inhibitors. [ABSTRACT FROM AUTHOR]

Parkinson's disease affects millions of people worldwide, and without significant progress in disease prevention and treatment, its incidence and prevalence could increase by more than 30% by 2030. Researchers have focused on targeting sleep and the circadian system as a novel treatment strategy for Parkinson's disease. This study investigated the association between melatonin receptor agonists and Parkinson's disease, using the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS). The target drugs were melatonin receptor agonists including ramelteon, tasimelteon, and agomelatine. Parkinson's disease cases were defined according to the Medical Dictionary for Regulatory Activities (MedDRA) 25.0; Standardized MedDRA Query (SMQ) using both the "narrow" and "broad" preferred terms (PTs) associated with Parkinson's disease. The association between melatonin receptor agonists (ramelteon, tasimelteon, and agomelatine) and Parkinson's disease was evaluated by the reporting odds ratio. Upon analyzing the data from all patients registered in the FAERS, ramelteon (ROR: 0.66, 95% confidence interval [95% CI]: 0.51–0.84) and tasimelteon (ROR: 0.49, 95% CI: 0.38–0.62) showed negative correlations with Parkinson's disease. Conversely, only agomelatine was positively correlated with Parkinson's disease (ROR: 2.63, 95% CI: 2.04–3.40). These results suggest that among the melatonin receptor agonists, ramelteon and tasimelteon are negatively correlated with Parkinson's disease. In contrast, agomelatine was shown to be positively correlated with Parkinson's disease. These results should be used in research to develop drugs for the treatment of Parkinson's disease, fully considering the limitations of the spontaneous reporting system. [ABSTRACT FROM AUTHOR]

This article explores the connection between the duration of action of benzodiazepine hypnotic drugs and blepharospasm, a type of eye muscle spasm. The study analyzed reports from the FDA Adverse Events Reporting System and found that benzodiazepine drugs had a higher number of reports and signal scores for blepharospasm compared to other hypnotic drugs. The study suggests that ultrashort-acting and short-acting benzodiazepines may be associated with drug-induced blepharospasms. It also notes that the incidence of blepharospasm was higher in females. However, the study acknowledges that the data used is based on spontaneous reports and further research is needed for stronger evidence. [Extracted from the article]

The letter to the editor discusses a study on drugs associated with epidermal necrolysis in children. The authors of the letter point out some issues with the statistical analysis used in the study and suggest alternative methods for detecting signals specific to the pediatric population. They recommend using relative reported odds ratio (ROR) and information component delta (ICΔ) to reduce false positive signals. The authors conclude by stating that using these alternative methods would lead to a better hypothesis that more readers would accept. [Extracted from the article]

Aim: Several interferon (IFN)‐free, all‐oral regimens with direct acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection also include ribavirin (RBV). We investigated the influence of renal dysfunction on virologic efficacy and adverse effects in 189 patients with HCV genotype 2 infection who received combination RBV–DAA regimens. Methods: The incidence of RBV‐induced anemia, RBV dose reduction, and virologic efficacy were compared according to baseline renal function as defined by the estimated glomerular filtration rate (eGFR). Results: Patients with renal dysfunction (eGFR = 30–59 mL/min/1.73 m2) had higher rate of RBV dose reduction and more marked decreases in hemoglobin levels. These findings were more pronounced in patients with the ITPA CC genotype, who are more sensitive to RBV‐induced anemia. Although there were no statistically significant differences in sustained virologic response (SVR) rates according to renal function overall (P = 0.1650), the SVR rate was significantly lower in patients who required RBV dose reduction than in those who did not (P < 0.0001). Conclusions: Baseline renal dysfunction could unfavorably affect the outcomes of RBV–DAA in patients with chronic HCV infection due to the increased risk of RBV dose reduction, even in the era of IFN‐free DAA regimens. [ABSTRACT FROM AUTHOR]

Questioning Bayesian Inference-Based Models for Estimating Culprit Drugs for Adverse Drug Reactions Although there are many algorithms for detecting safety signals from spontaneous reporting systems, there is still no definitive algorithm. Several comparative studies of detection algorithms have already been reported.[2] In all of those reports, the Bayesian Confidence Neural Network (BCPNN)[2] and the Gamma-Poisson Shrinker (GPS),[2] showed better performance than the proportional reporting ratio (PRR). [Extracted from the article]

Exposure of human breast cancer cells (MCF-7) to tumor promoters such as 12-O-tetradecanoyl phorbol 13-acetate (TPA) for 24 h at concentrations of 1–100 nM resulted in marked inhibition of DNA synthesis but a 3–5-fold increase in the amount of pS2 protein is not involved in the mechanism controlling proliferation of MCF-7 cells. During treatment with TPA, the intracellular content of pS2 protein was constant, suggesting that TPD did not induce secretion of pS2 protein but rather de novo synthesis of the protein. The increase in the pS2 protein content of the medium by TPS was inhibited by simultaneous addition of cycloheximide, but not by that of actinomycin D. Nothern-blot hybridization analysis showed that the amount of pS2 mRNA was unchanged by treatment of the cells with TPA. These results indicate that TPA does not induce transcription of the pS2 gene, and suggest that the main effect of TPA results from the induction of translation of pS2 mRNA. [ABSTRACT FROM AUTHOR]