Changes in Pharmacy Students' Awareness of Hepatitis B Patients through Patient Lectures as Humanity Education: Findings from Questionnaire Surveys of Face-to-Face and Simultaneous Remote Classes.

In 2020, the coronavirus disease 2019 (COVID-19) pandemic made social distancing compulsory. In patient lectures by hepatitis B patients (Patient Lectures)-a humanity education initiative that had traditionally been delivered face-to-face to assembled students-it was necessary to divide the students into two groups, one that attended the Patient Lectures in person (face-to-face group) and another that assembled in a separate room to view the delivered lecture simultaneously and remotely via a teleconferencing platform (remote group). To investigate possible changes in students' awareness of hepatitis B patients before (pre-) and after (post-) the lecture that year, the face-to-face and remote-attendance groups were analyzed separately. The participants were 203 fourth-year students belonging to the Faculty of Pharmaceutical Sciences at Japan's Setsunan University, whose pre-clinical education curriculum prior to pharmacy practice experience included a Patient Lecture. The students were divided into two groups based on their student-ID numbers. Survey questionnaires were completed anonymously before and after the Patient Lecture. The students' awareness of hepatitis B patients' experience changed significantly after attending the Patient Lectures; this change was similar in both the face-to-face and remote-attendance groups. Regarding the possibility of hepatitis B virus infection, the remote group selected fewer answers implying strong convictions than did the face-to-face group, and both groups perceived several issues incorrectly. Although slight differences were observed between the two groups, the changes before and after the lectures were similar, indicating that humanity-education lectures are worthwhile not only when delivered in face-to-face contexts but also when delivered and viewed remotely within a class setting.

Effect of Dietary Fiber on the Level of Free Hypoglycemic Agents in Vitro.

We studied the effect of dietary fibers (DFs) on the levels of free hypoglycemic agents in vitro, i.e., glimepiride and the biguanides buformin and metformin. The levels of free buformin and free metformin were not affected by mixtures of DFs, i.e., cellulose, chitosan, pectin (PE), and glucomannan (GM), in fluids of pH 1.2 and 6.8 (similar to the pH of the stomach and intestines, respectively). However, the free biguanide level was significantly reduced by mixing with PE or sodium alginate (AL), in water. The free glimepiride level was reduced in the mixture of AL, PE, and GM (in a solution with a pH of 6.8). The changes in aqueous AL solution pH seemed to reflect the free metformin levels. Therefore, the effects of DFs on free drug levels were dependent on drug type, hypoglycemic agent, and mixing solution. In this study, the oral regimen concentrations of the drug and DFs were used. Based on these results, it is important to consider the interactions between hypoglycemic agents and DFs.

[Learning Strategy for Pharmacy Students to Develop Empathy for Hepatitis B Patients through a Lecture Presented by Patients Describing Their Daily Lives].

In April 2018, as part of their fifth-year pre-clinical education curriculum, pharmacy students at Setsunan University attended a lecture presented by hepatitis B patients and their lawyer entitled "Lecture by Hepatitis B Patients". This lecture was intended to help the students to understand the circumstances and difficulties encountered by hepatitis B patients on a daily basis. For this study, we conducted questionnaire surveys of the pharmacy students before and after the lecture. The survey items pertained to students' knowledge about hepatitis B (e.g., its spread and infection possibility in daily life). Students' responses before and after the lecture varied depending on the survey topic. Hepatitis B knowledge acquired by the students in their junior year increased after the lecture; moreover, attitudes to hepatitis B patients and understanding of the difficulties and prejudice that they experienced showed a significant change. For example, responses to the items, "Feel sympathy for patients suffering from discrimination and prejudice" and "Hard to work…" were much more sympathetic after the lecture; additionally, students were less likely to "Fear infection when near patients" and more likely "… to associate with patients". Thus, the "Lecture by Hepatitis B Patients" had a significant impact on the pharmacy students' perceptions of these patients, allowing them to cultivate greater empathy. From an educational standpoint, it is of the utmost importance for pharmacy/medical students to develop their humanity as members of healthcare teams. Educational real-world experiences, such as the "Lecture by Hepatitis B Patients", provide opportunities for this development.

Population pharmacokinetics of afatinib and exposure-safety relationships in Japanese patients with EGFR mutation-positive non-small cell lung cancer.

To investigate the exposure-safety relationships of afatinib in Japanese population, we performed population pharmacokinetics (PK) analysis of afatinib in Japanese advanced non-small cell lung cancer patients harboring epidermal growth factor receptor mutation. Plasma samples were collected at 0.5-1, 2-3, 8-12, and 24 h after oral afatinib (40 mg) administration on day 1 and day 8. Plasma afatinib concentrations were determined using high-performance liquid chromatography. Data was analyzed following the population approach and using the software Phoenix® NLMETM Version 7.0 software (Certara USA, Inc., Princeton, NJ, USA). From 34 patients, a total of 354 afatinib plasma concentration values were available for the population PK analysis. Significant covariates in the population PK model included aspartate aminotransferase and creatinine clearance on CL/F, and age and body mass index on V/F. Results of simulation based on final PK model indicated that hepatic impairment had a significant effect on afatinib levels in plasma after multiple dosing. Afatinib trough plasma concentrations on day 8 were higher in patients with adverse events of grade 3 or higher. The population PK analysis showed that hepatic impairment affected afatinib PK parameters and contributed to the high inter-patient variability and high plasma concentrations of afatinib following multiple treatments.

Cerebrospinal Fluid Penetration Rate and Efficacy of Afatinib in Patients with EGFR Mutation-positive Non-small Cell Lung Cancer with Leptomeningeal Carcinomatosis: A Multicenter Prospective Study.

BACKGROUND: Afatinib is an effective first-line treatment for epidermal growth factor receptor (EGFR) mutation-positive advanced non-small cell lung cancer (NSCLC). However, few reports have addressed the influence of cerebrospinal fluid (CSF) penetration rate on the efficacy of afatinib in patients with central nervous system metastases. Therefore, we conducted a prospective multicenter trial to evaluate the CSF penetration rate and efficacy of afatinib in patients with EGFR mutation-positive NSCLC with leptomeningeal carcinomatosis. PATIENTS AND METHODS: Eleven patients with histologically-proven EGFR mutation-positive NSCLC with leptomeningeal carcinomatosis were enrolled in the study between April 2014 and November 2015. They were treated with afatinib (40 mg/day), and blood and CSF levels of afatinib were analyzed on day 8. The primary endpoint was CSF penetration rate. Secondary endpoints included the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). RESULTS: The median age of patients was 66 years. Five patients harbored an exon 19 deletion, three harbored a p.L858R point mutation, and three harbored an uncommon exon 18 mutation. The levels of afatinib in blood and CSF (mean±SD) were 233.26±195.40 nM and 3.16±1.95 nM, respectively. The CSF penetration rate was 2.45±2.91%. The ORR was 27.3% (three out of 11 patients), and two out of these three responders had uncommon EGFR mutations. The median PFS and OS were 2.0 and 3.8 months, respectively. CONCLUSION: The median CSF penetration rate of afatinib was higher than previously reported. Afatinib was effective against leptomeningeal carcinomatosis particularly in patients with NSCLC harboring uncommon EGFR mutations. The criteria for selecting a specific EGFR tyrosine kinase inhibitor for therapy of NSCLC should include its ability to penetrate CSF and its efficacy against specific mutation types.

Effect of dietary fibers on losartan uptake and transport in Caco-2 cells.

The objective of this study was to assess the effect of dietary fibers on the transport of losartan, an angiotensin II type 1 receptor blocker, in small intestinal cells. Using Caco-2 cells in vitro, losartan uptake and transport were evaluated in the presence of various fibers (cellulose, chitosan, sodium alginate and glucomannan). Dietary fibers caused a decrease in the uptake of losartan, with chitosan causing a significant reduction. Chitosan and glucomannan significantly reduced the transport of losartan, while cellulose or sodium alginate did not. Dietary fibers also reduced the level of free losartan; however, this did not correlate with the observed reduction in losartan uptake and transport. In summary, chitosan had the greatest inhibitory effect on losartan uptake and transport, and this potential interaction should be considered in patients taking losartan. Copyright © 2016 John Wiley & Sons, Ltd.

[Acid-neutralizing capacity of over-the-counter gastrointestinal medications].

  There is little information regarding the acid-neutralizing capacity of over-the-counter (OTC) gastrointestinal medicines. In this study, we assessed the acid-neutralizing capacity of OTC and prescribed gastrointestinal drugs based on the Japanese Pharmacopoeia 16th Edition. The acid-neutralizing capacity of the OTC drugs was calculated using experimental results for the crude materials found in the prescribed drugs based on OTC antacid quantity. The measured acid-neutralizing capacities of the OTC drugs agreed with the respective calculated values. These results indicate that the acid-neutralizing capacity of OTC drugs labeled as an antacid without information on their capacity can be estimated based on the quantity and capacity of the antacid components.

Effect of dietary fiber on the level of free angiotensin II receptor blocker in vitro.

The interaction between angiotensin II type 1 (AT1) receptor blockers (ARBs), such as losartan potassium (LO), candesartan (CA), and telmisartan (TE), and dietary fiber was studied as to the level of free ARB in vitro. When ARB was incubated with soluble (sodium alginate, pectin, and glucomannan) or insoluble (cellulose and chitosan) dietary fiber, the levels of free LO, TE, and CA decreased. This resulted only from mixing the dietary fiber with the ARBs and differed among the types of dietary fiber, and the pH and electrolytes in the mixture. The levels of free LO and TE tended to decrease with a higher concentration of sodium chloride in pH 1.2 fluid. These results suggest that it is important to pay attention to the possible interactions between ARBs and dietary fiber.

Intravenously administered 2'-deoxycytidine suppresses mouse myeloma tumor growth.

We examined the in vivo effects of intravenously administered 2'-deoxycytidine (dCyd) on tumor growth and survival time in mice bearing SP2/0-Ag14 (SP2/0) myeloma tumors. Administration of dCyd tended to decrease the tumor volume and significantly decreased the tumor weight. A single intravenous administration of dCyd significantly increased survival time of the tumor-bearing mice. The effect of dCyd on tumor growth was maintained for at least 1 week after the final administration. The net amount of dCyd in the kidney, liver, and spleen of the tumor-bearing mice increased 2.5 to 5.3 fold compared with the amount in non-tumor-bearing mice. Our results suggest that the increase in dCyd in the mice inoculated SP2/0 myeloma cells plays an important role for the growth suppression of the tumor.

2'-Deoxycytidine decreases the anti-tumor effects of 5-fluorouracil on mouse myeloma cells.

2'-Deoxycytidine (dCyd), a pyrimidine nucleoside found at high concentrations in the plasma of cancer patients with a poor prognosis after chemotherapy, is considered to be a biomarker for breast cancer. 5-Fluorouracil (5FU) is a nucleoside analog and is used as an anti-tumor agent in patients whose plasma dCyd concentrations are increased. Because both dCyd and 5FU are pyrimidine analogues, it is possible that they have pharmacokinetic/ pharmacodynamic interaction, by which the anti-cancer efficacy of 5FU would be reduced. Here, we examined the effects of dCyd on the cytotoxicity of 5FU on mouse myeloma SP2/0-Ag14 (SP2/0) cells lacking hypoxanthine-guanine-phosphoribosyl transferase (HGPRT) and RH4 hybridomas with HGPRT under asynchronized conditions. The reduced cell viability by 5FU was restored by co-, but not pre-, treatment of dCyd in both SP2/0 and RH4 cells, but this effect in the former tended to be greater than that in the latter, suggesting a possible involvement of HGPRT in the interaction, although this might not be a major mechanism. Moreover, dCyd administration to SP2/0 myeloma-bearing mice tended to shorten their 5FU-induced prolonged survival in vivo. Collectively, these results indicate that dCyd decreases the anti-tumor efficacy of 5FU and that a metabolic pathway via HGPRT is involved partially in this interaction. The evaluation of dCyd as a biomarker is believed to provide valuable information for effective and safe chemotherapy with 5FU.

Changes in 2'-deoxycytidine levels in various tissues of tumor-bearing mice.

The nucleoside 2'-deoxycytidine (dCyd) increases in the plasma of cancer patients with poor prognoses. 5-fluorouracil (5FU) is one of the anti-cancer agents used in chemotherapy for patients whose plasma dCyd is elevated. We examined the free dCyd level in various tissues of mice, with and without tumors, and in mice with and without the administration of 5FU or of dCyd, and investigated the effects of dCyd in tumor-bearing animals. SP2/0-Ag14 mouse myeloma cells were transplanted subcutaneously into mice and 5FU or dCyd was administered intraperitoneally. Free dCyd was measured in blood and tissues by HPLC at two time points, once when mouse body weight was maximally decreased (1 day after the last administration of 5FU, day 16) and again when it returned to control level at 1 week after the last 5FU treatment (day 22). Results showed that in tumor-bearing mice, the level of dCyd (per g wet weight) increased in the spleen. The change in liver weight caused by the administration of 5FU correlated with the level of dCyd in the liver. Notably, the relative tumor volume and tumor weight was decreased in dCyd-treated animals in comparison with controls. In conclusion, the levels of dCyd were markedly altered in the tissues of the reticuloendothelial and lymphatic systems, such as liver and spleen, and dCyd apparently had the ability to inhibit tumor growth in the body.