Impact of interventions targeting the inappropriate use of proton-pump inhibitors by clinical pharmacists in a hepatobiliary surgery department.

WHAT IS KNOWN AND OBJECTIVE: At present, studies on the usage of proton-pump inhibitors (PPIs) have universal significance. In clinical practice, PPIs are widely used to treat a variety of acid-related diseases, but they can be inappropriately prescribed, leading to increased medical costs and patient harm. The study comprehensively evaluated the clinical effects of a clinical pharmacist intervention on inappropriate PPI prescriptions in a tertiary general hospital hepatobiliary surgery ward. METHODS: A retrospective, single-centre intervention study covering the periods of July-December 2018 and July-December 2019 was conducted. In the intervention group, clinical pharmaceutical care was initiated by a clinical pharmacist in the hepatobiliary surgery ward. Outcomes, including the clinical pattern of PPI utilization, the rate of inappropriate PPI use and safety outcomes, were compared between the two periods. RESULTS AND DISCUSSION: In total, 1150 patients were admitted to the hepatobiliary surgery ward in our hospital in the study periods. Of these, 717 patients met the inclusion criteria for this study, and 420 and 297 patients were included in the preintervention and post-intervention groups, respectively. The PPI utilization rates before and after the intervention were 82.0% and 55.0%, respectively. The rates of inappropriate PPI use before and after the intervention were 48.9 and 22.7 per 100 patient-days, respectively. Clinical safety outcomes were nearly identical between before and after the intervention, but patients treated with PPIs were more likely to experience nosocomial pneumonia (2.4% vs. 0.6%). WHAT IS NEW AND CONCLUSION: The implementation of a clinical pharmacist intervention for PPI use decreased inappropriate PPI use during hospitalization without sacrificing clinical safety outcomes.

Iron-Catalyzed Synthesis of the Hexahydrocyclopenta[c]furan Core and Concise Total Synthesis of Polyflavanostilbene†B.

The first synthesis of polyflavanostilbene B (1), which has seven contiguous stereocenters including two quaternary carbon centers, from abundant polymeric (-)-epicatechin gallate on a gram scale in three steps without the use of protecting groups is reported. The key transformations of this strategy include a regioselective and stereoselective substitution of resveratrol to give the 4-derivative of (-)-epicatechin 3-gallate and an iron-catalyzed cyclization reaction. The possible radical cyclization mechanism in the formation of the hexahydrocyclopenta[c]furan core is also discussed.

Voriconazole-induced central nervous system toxicity: a pharmacovigilance study based on FDA adverse event reporting system (FAERS) database.

BACKGROUND: This study aims to evaluate the relationship between voriconazole (VRC) and central nervous system (CNS) toxicity based on the real world data. RESEARCH DESIGN AND METHODS: The reports of FAERS from January 2004 to March 2022 were included in our study. The CNS toxicity events were identified by using Medical Dictionary for Regulatory Activities terms. Reporting odds ratios corresponding to 95% confidence intervals were employed to quantify the signals of VRC-associated CNS events. RESULTS: The overall RORs (95%CI) for psychiatric disorders, nervous system disorders, and eye disorders were 1.84 (1.70, 2.00), 1.09 (1.01, 1.18), and 3.84 (3.48, 4.23), respectively (p < 0.05). The median time to the CNS events of VRC was 1(IQR 0-5) day. Top six signals were macular opacity, chloropsia, scintillating scotoma, toxic optic neuropathy, corneal bleeding, and dyschromatopsia, all of them grouped as eye disorders. Compared with itraconazole, fluconazole, posaconazole, and isavuconazole, VRC shows significant relationship and higher incidence rate of psychiatric disorders, nervous system disorders, and eye disorders, respectively (p < 0.05). CONCLUSIONS: VRC was significantly associated with the CNS toxicity. Dosing adjustment, model-based individualized treatment project, and the therapeutic drug monitoring-guided individualized medication regime could be good strategies for efficacy improvement and the adverse events of reducing of VRC.

Synthesis of 4-thiosubstituted flavan derivatives and their hypoglycemic activities.

A series of 4-thiosubstituted flavan derivatives (1-44) were designed and synthesized. The target compounds were assayed for inhibitory activity against α-glucosidase in vitro, and the results indicated that all compounds displayed significant effects in the range of IC50 = 1.03-7.48 µM compared to that of acarbose, the positive control drug. Structure-activity relationship (SAR) studies indicated that the hydroxyl groups in the flavan B ring, the electron withdrawing groups, and the length of the alkyl chains are important for this biological activity. In addition, some compounds were tested for their tolerance to sucrose in mice, and compound 44 exhibited activity comparable to that of acarbose. Docking analysis indicated that compound 44 binds to the enzyme in a pocket close to the catalytic site, similar to acarbose.

A novel ECG analog 4-(S)-(2,4,6-trimethylthiobenzyl)-epigallocatechin gallate selectively induces apoptosis of B16-F10 melanoma via activation of autophagy and ROS.

Autophagy-induced cancer cell death has become a novel strategy for the development of cancer therapeutic drugs. Numerous studies have indicated that green tea polyphenols induce both autophagy and apoptosis in a variety of cancer cells. Here, we synthesized a series of green tea polyphenol analogues, among which JP8 was shown to potently activate autophagy. JP8 treatment had a stronger effect on apoptosis in B16-F10 melanoma cells than that in normal AML-12 hepatocytes. JP8 selectively resulted in reactive oxygen species (ROS) accumulation in B16-F10 cells, and this effect was associated with corresponding increases in key components of the ER stress-mediated apoptosis pathway. Pharmacological inhibition of ROS by N-acetyl-L-cysteine (NAC) attenuated JP8-induced autophagy and apoptosis, indicating an upstream role of ROS in JP8-induced autophagy. An in vivo study showed that JP8 had significant antitumor effects in a B16-F10 xenograft mouse model. Our results indicate that JP8 is a novel anticancer candidate with both autophagy and ROS induction activities.