Delirium risk of histamine-2 receptor antagonists and proton pump inhibitors: A study based on the adverse drug event reporting database in Japan.

OBJECTIVE: Although histamine-2 receptor antagonists (H2RAs) have been shown to be more likely to cause delirium than proton pump inhibitors (PPIs), these results were not adjusted for potential confounding factors. Accordingly, we investigated whether H2RAs and PPIs are risk factors for delirium, even when adjusting for other risk factors by analyzing adverse drug event reports compiled in the post-marketing stages of drugs provided by the Japanese regulatory authorities. METHOD: We analyzed 577,431 reports in the Japanese Adverse Drug Event Report database from April 2004 to July 2020. RESULTS: Of all reports analyzed, 2532 described delirium, and 574,899 described other adverse events. Delirium was associated with H2RAs (crude reporting odds ratio, ROR, 4.17; 95% CI, 3.34-5.22) but not PPIs (crude ROR 0.62; 95% CI 0.43-0.90). Even with adjustment for age, sex, history of dementia or depression, and concomitant drugs reported as risk factors for delirium, the use of H2RAs showed a significantly higher adjusted ROR than that of PPIs (H2RAs: adjusted ROR 3.99; 95% CI 3.18-5.01 and PPIs: adjusted ROR 0.58; 95%CI 0.40-0.84). CONCLUSIONS: These results suggest that, from a cognitive perspective, PPIs may be preferable to H2RAs for patients with or at risk for delirium.

ATP generation in a host cell in early-phase infection is increased by upregulation of cytochrome c oxidase activity via the p2 peptide from human immunodeficiency virus type 1 Gag.

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) must take advantage of its own proteins with two or more functions to successfully replicate. Although many attempts have been made to determine the function of viral proteins encoded in the HIV-1 genome, the role of the p2 peptide, a spacer between the capsid and the nucleocapsid in HIV-1 Gag in early-phase HIV infection still remains unclarified. RESULTS: In this study, we show that the p2 peptide enhances HIV-1 acute infection by increasing intracellular ATP production via the activation of mitochondrial cytochrome c oxidase (MT-CO) involved in the respiratory chain. We found that cell-permeable p2-peptide-treated cells were more effectively infected by HIV-1 than control cells. To characterize the effect of the p2 peptide on HIV-1 replication in MAGIC-5 cells, various HIV-1 cDNA products were measured by quantitative real-time PCR. The levels of the late (R/gag), 2-LTR circular (2-LTR), and integrated (Alu) forms of viral cDNAs increased in the presence of the p2 peptide. Interestingly, yeast two-hybrid analysis revealed a novel interaction between the p2 peptide and the mitochondrial intermembrane space domain (N(214)-F(235)) of MT-CO subunit I (MT-CO1). Mutational analysis indicated that Gln(6) in the p2 peptide is important for the interaction with MT-CO1. The p2 peptide activated MT-CO1 in vitro in a concentration-dependent manner, and fluorescence-microscopy analysis demonstrated that the p2 peptide had a significant effect on mitochondrial targeting. Furthermore, the analysis of HIV-1 lacking a functional p2 peptide demonstrated the inhibition of intracellular ATP production in MT-4 cells and monocyte-derived macrophages (MDMs) and a decrease in reverse transcription efficiency following infection of MT-4 cells and MDMs. CONCLUSIONS: These findings provide evidence that the p2 peptide is a viral positive allosteric modulator of MT-CO and the increased intracellular ATP production after HIV infection in a p2-peptide-dependent manner is essential for efficient reverse transcription in early-phase HIV-1 infection.

[Efficacy of aprepitant for quality of life of outpatients receiving moderately emetogenic chemotherapy].

We examined the antiemetic effect and impact of aprepitant on the quality of life (QOL) of outpatients receiving moderately emetogenic chemotherapy (MEC). Data were compared between patients who received aprepitant (aprepitant group, n=30, treated May to September 2010) and those who did not (control group, n=14, treated February to April 2010). Controls received antiemetic treatment with a serotonin receptor antagonist and dexamethasone on Day 1. The aprepitant group received oral aprepitant (125 mg) concomitantly with these drugs on Day 1, and aprepitant (80 mg) on Days 2 and 3. The percentages of subjects without vomiting and nausea during the overall phase (0-96 h), acute phase (0-24 h), and delayed phase (24-96 h), and without loss of appetite during the entire period and delayed phase, were significantly higher in the aprepitant group. A QOL evaluation using the Functional Living Index-Emesis (FLIE) questionnaire showed a significantly higher percentage of subjects without the impact of nausea and vomiting disturbing their daily lives during the overall phase, and a significant decrease in QOL disturbance in the aprepitant group. Our results suggest that nausea, vomiting, loss of appetite, and QOL disturbance occur in many outpatients undergoing MEC, and that concomitant therapy with 3 drugs including aprepitant can improve symptoms and QOL of these patients.