Published papers

Background: Potential novel strategies for adverse event (AE) management of osimertinib therapy, including therapeutic drug monitoring and the use of biomarkers, have not yet been fully investigated. This study aimed to evaluate (1) the relationship between exposure to osimertinib, especially its active metabolites (AZ5104 and AZ7550), and AEs, and (2) the relationship between germline polymorphisms and AEs. Methods: We conducted a prospective, longitudinal observational study of 53 patients with advanced non-small cell lung cancer receiving osimertinib therapy from February 2019 to April 2022. A population pharmacokinetic model was developed to estimate the area under the serum concentration–time curve from 0 to 24 h (AUC0–24) of osimertinib and its metabolites. Germline polymorphisms were analyzed using TaqMan® SNP genotyping and CycleavePCR® assays. Results: There was a significant association between the AUC0–24 of AZ7550 and grade ≥ 2 paronychia (p = 0.043) or anorexia (p = 0.011) and between that of osimertinib or AZ5104 and grade ≥ 2 diarrhea (p = 0.026 and p = 0.049, respectively). Furthermore, the AUC0–24 of AZ5104 was significantly associated with any grade ≥ 2 AEs (p = 0.046). EGFR rs2293348 and rs4947492 were associated with severe AEs (p = 0.019 and p = 0.050, respectively), and ABCG2 rs2231137 and ABCB1 rs1128503 were associated with grade ≥ 2 AEs (p = 0.008 and p = 0.038, respectively). Conclusion: Higher exposures to osimertinib, AZ5104, and AZ7550 and polymorphisms in EGFR, ABCG2, and ABCB1 were related to higher severity of AEs; therefore, monitoring these may be beneficial for osimertinib AE management.

Study Objective: Establish methods for measuring cefmetazole (CMZ) concentrations conduct a pharmacokinetic/pharmacodynamic (PK/PD) analysis using unbound CMZ concentrations for extended-spectrum β-lactamase producing enterobacterales (ESBL-E) and investigate optimal dosing regimens for not undergoing hemodialysis (non-HD) and undergoing hemodialysis (HD) patients. Design: Prospective observational study. Patients: Included patients treated with CMZ who provided written informed consent and were admitted to the Tokyo Bay Urayasu Ichikawa Medical Center between August 2021 and July 2022. Measurements: Total and Unbound CMZ concentration was measured by high-performance liquid chromatography (HPLC) with solid-phase extraction and ultrafiltration. Setting: Determining the CMZ dosing regimen involved modified creatinine clearance (CLCR) with measured body weight (BW) using the Cockcroft–Gault equation. For non-HD patients, blood samples were collected during at least three points. For patients undergoing HD, 1 g was administered via intravenous infusion, or rapid intravenous injection after HD, or 30 min before the end of HD. Blood samples were collected before HD (pre-HD), and 1 and 3 h after starting HD and post-HD. All blood samples were collected at steady-state. Patient information was collected from electronic medical records. An unbound PK model was constructed for the non-HD patients. A nomogram was constructed using Monte Carlo simulations with a 90% probability of target attainment at 70% free time above the minimum inhibitory concentration (MIC). For the HD patients, a nomogram was used to determine the optimal dosing regimen for each HD schedule. Main Results: CMZ measurement methods were established. A model analysis of unbound PK in 37 non-HD patients incorporated creatinine clearance (CLCR) using the Cockcroft–Gault equation, albumin (ALB) for clearance and body weight (BW) for the volume of distribution. In Monte Carlo simulations, nomograms corresponding to the MIC (known and unknown) were generated for each covariate. Using the nomogram, non-HD patients with an ESBL-E MIC of 8 mg/L, a BW of 60 kg, an ALB of 25 g/L, and a CLCR of 60 mL/min required administration of 2 g every 6 h (1- and 3-h infusions). Unbound PK model parameters were calculated for 7 HD patients, and the optimal dosing regimens following PK/PD were determined for each HD schedule. In HD patients, the regimen after and during HD was established using a treatment that was effective up to an ESBL-E MIC of 4 mg/L. Conclusions: The nomogram for CMZ regimens established by PK/PD analysis of measured CMZ concentrations enables optimal CMZ dosing for ESBL-E-infected patients.

A social contract based on “mutual trust” between professionals and society constitutes a fundamental concept of professionalism. Altruism and empathy are the essential elements of medical professionalism. It is necessary for healthcare professionals to manage their emotions and perform emotional labor to demonstrate professionalism in clinical settings that are uncertain and challenging and where many factors, such as human relationships with patients, patients’ families, and other professionals, the work environment, and social and legal factors, are intricately intertwined. I believe that the ability to recognize such harsh situations and manage emotions in response is also an essential aspect of the professionalism that pharmacists must possess. Numerous initiatives have focused on the emotional labor of doctors, particularly nurses; however, very little attention has been devoted to the emotional labor of pharmacists. In this symposium, we will examine pharmacists’ professionalism through the lens of emotional labor a perspective not yet explored in the field of pharmacy, and offer suggestions for pharmacy education.

Two representative Kampo formulas, keishibukuryogan and tokishakuyakusan, are frequently prescribed for patients with dysmenorrhea. We previously constructed a model that could predict which of these 2 formulas was most suitable, which is based on 4 subjective symptoms and 3 objective signs. To evaluate the prognosis of patients with dysmenorrhea using the established prediction model and assess the treatment outcomes between those treated in accordance with the prediction model and those who received various other treatments. In this retrospective, observational study, we included patients with menstrual pain who visited the Kampo Clinic at the Keio University Hospital for the first time between October 2014 and December 2020. These patients were monitored over a 90-day follow-up period. Participants were categorized into 2 groups: model-accordance and various-options. The progression of visual analogue scale (VAS) values was evaluated by determining the slopes from regression analysis between these 2 groups, with changes corroborated by the medical records. The study comprised 57 patients: 37 in the model-accordance group and 20 in the various-options group. Notably, the various-options group reported a significantly higher number of subjective symptoms (P = .03). The VAS value showed a decline, as indicated by the negative slope value of the regression line, across both groups - irrespective of their classification. There were no significant differences in the occurrence of adverse events between the 2 groups. The prognosis of patients with dysmenorrhea and the incidence of adverse events remained consistent, regardless of whether the treatment approach was in accordance with the prediction model or varied. Further studies are warranted to assess the prognosis when Kampo formulas are chosen based on the prediction model in the various-options population.

Worldwide interest in teaching medical professionalism has increased drastically over the past two decades and is recognized as an important core competency. It is also essential in pharmacy education. However, there is no single definition of medical professionalism owing to its multifaceted nature, leading to difficulty in understanding it. The foundational concept of professionalism are the social contract and accountability, which describe the relationship between the profession and the society which it serves. Profession must understand expectations from the society, which is trustworthy, assures competence, and devoted to the public good for the contract based on their mutual trust. In “teaching,” three basic educational actions (“setting expectations,” “providing experiences,” and “evaluating outcomes”) are required. There are two learning goals of professionalism education: the minimum goal of not doing unprofessional acts and the aspirational goal of pursuing a higher level of interiorized professionalism which leads to the professional identity formation. The true professionals are “reflective practitioners,” who have the ability to manage ambiguous problems using their interiorized professionalism in complicated situations. Therefore, reflection is one of the central concepts of professionalism education. The Professionalism Mini-Evaluation Exercise (P-MEX), an observational tool to evaluate medical professionalism, has some favorable aspects; the Japanese version is available and is a guide to specific actions for professionalism through its items, although some cautions must be exercised when using it. Considering that teaching professionalism includes not only formal but informal and hidden curricula, all of the staff in the educational environments should consider professionalism education by understanding professionalism.

Purpose: Hypertension (HT), dyslipidemia (DL), and diabetes mellitus (DM) are major risk factors for cardiovascular diseases. Despite the wide availability of medications to reduce this risk, poor adherence to medications remains an issue. The aim of this study is to evaluate medication adherence of prevalent users in these disease medications (HT, DL, DM) using claims data. Factors associated with non-adherence were also examined. Methods: Of 7538 participants of the Tsuruoka Metabolomics Cohort Study, 3693 (HT: 2702, DL: 2112, DM: 661) were identified as prevalent users of these disease medications. Information on lifestyle was collected through a questionnaire. Adherence was assessed by a proportion of days covered (PDC) and participants with PDC ≥0.8 were defined as adherent. Predictors of non-adherence were determined by performing multivariable logistic regression. Results: Medication adherence differed by treatment status. Among those without comorbidities, those with HT-only showed the highest adherence (90.2%), followed by those with DM-only (81.2%) and those with DL-only (80.8%). Factors associated with non-adherence in each medication group were skipping breakfast and poor understanding of medications among those with HT medications, females, having comorbidities, having a history of heart disease, and drinking habit among those with DL medications, and good sleep quality and skipping breakfast among those with DM medications. Conclusion: While participants showed high medication adherence, differences were observed across medication groups. The identified predictors of non-adherence could help target those in need of adherence support.

A 0.04% mitomycin C (MMC) ophthalmic solution is not commercially available and is prepared in hospitals as required. The physical properties and stability of the MMC ophthalmic solution have not been clarified because of a lack of data. This study aimed to assess the stability of the MMC ophthalmic solution under various storage conditions. The MMC ophthalmic solution was prepared by dissolving 2 mg of MMC in 5 mL of saline solution. Each batch of ophthalmic solution was stored under three conditions [cold/shaded light, room temperature/shaded light, and room temperature/scattered light (approximately 4000 lx)], and MMC concentration was determined using high-performance liquid chromatography on days 0, 1, 3, 5, 7, 14, and 21. The expiry date was calculated based on the results of the degradation analysis. pH measurements and bacterial culture tests were conducted for each storage condition. The MMC concentrations on day 21 under cold/shaded light, room temperature/shaded light, and room temperature/scattered light were 340, 287, and 227 µg/mL, respectively. MMC concentrations decreased over time, and the decrease was highest when the samples were stored at room temperature and exposed to light, and lowest under cold conditions and protected from light. The pH of MMC solutions was 5.8 after preparation, which increased to 6.9 with time under all storage conditions. Culture tests did not detect any bacteria under any storage conditions. The MMC ophthalmic solution was most stable under cold/shaded conditions, and our study clarifies its expiry date for clinical use.

Patient risk factors related to coagulopathy and bleeding when using cefmetazole (CMZ) have not yet been identified, and no models exist to predict side effects during CMZ treatment. Moreover, reports that examine which patients should be careful when using CMZ to ensure safety are lacking. Our objective was to understand risk factors for elevated international normalized ratio (INR) in patients using CMZ and to develop a predictive model for INR elevation using a risk score to enable safe administration of CMZ. This multicenter, retrospective, and observational study was conducted in Tokyo Bay Urayasu Ichikawa Medical Center and Keio University Hospital using data from patients being treated with CMZ. Patients were classified into INR-elevated or non-INR-elevated groups. Univariate and multivariate analyses were performed to calculate the adjusted odds ratios (aOR) and 95% confidence intervals (CI). The actual probability of an elevated INR and probability of an elevated INR predicted by the regression β coefficients were calculated and classified into four categories according to the risk score. Binomial logistic regression analysis revealed that liver disorder (aOR, 5.65; 95% CI, 1.69–18.91; risk scores, 2), nutritional risk (aOR, 6.32; 95% CI, 3.14–12.74; risk scores, 2), no-diabetes mellitus (aOR, 4.53; 95% CI, 1.34–15.26; risk scores, 2), and warfarin use (aOR, 98.44; 95% CI, 7.05–1375.50; risk scores, 5) were significantly associated with INR elevation. The predicted incidence probabilities of INR elevation were<5% (low risk), 5–<30% (medium risk), 30–<90% (high risk), and ≥ 90% (very high risk). The model validity showed a good fit (AUC, 0.79; 95% CI, 0.73–0.85, P<0.001). We identified risk factors that contribute to INR elevation and constructed a model to predict INR elevation using the risk score. Using this predictive model enables the appropriate use of CMZ in a safe manner.

Since 2015, in Keio University, we have developed a set of holistic rubrics for assessing students' performance in practical training in their fifth year. We have administered it on a series of trials in Keio University Hospital in 2016 and 2017 to prepare for the practical training in 2019, which is based on a "revised model core curriculum for pharmaceutical education" incorporating out-come based education. The first and second trials in 2016 identified some problems. The mentors felt burdened, and the rubrics did not work well because the descriptions of performance at each achievement level were unclear. To address these issues, first, we revised the rubrics and added examples to help mentors with the assessment. Second, the assessment frequency was decreased. Furthermore, we also organized faculty-led orientation sessions on using the rubrics not only for mentors but for all pharmacists in the facility. These efforts have resulted in the effective use of the rubrics in the subsequent 2017 trial, thus reducing the mentors' burden of using the rubrics. This is not so different from using the rating scale of Specific Behavioral Objectives (SBOs). Furthermore, to mentors, the rubrics seemed to be more proper and objective for assessing students' performance than the SBOs' rating scale.Based on these results, it is feasible to use rubrics for assessing pharmaceutical students' performance in practical training. However, effective efforts, as follows, are needed: (a) making rubrics clearer and more user-friendly, (b) familiarizing the rubrics, and (c) building unity of purpose among relevant staff.

Purpose: In 2021, we introduced a new simulation-based learning program focusing on a roleplay conference before patient discharge. This study aimed to evaluate the program’s effectiveness and highlight the significance of cross-training in interprofessional education (IPE). Methods: In September 2023, the program included 346 students (98 medical, 110 nursing, and 138 pharmacy students). The students’ reflective writing was analyzed using inductive content analysis to describe their learning and perspectives. The original items, subcategories, and main categories were extracted. The simulation involved the students role-playing various healthcare professionals during a discharge-planning conference for a stroke patient. This allowed them to experience the challenges and dynamics of interprofessional collaboration. Results: Student feedback emphasized the importance of understanding what constitutes a good healthcare team. A total of 203 items were grouped into eight main categories and 17 subcategories, including patient-centered care (related to the importance of patient-centered care, supporting patient decision-making, communicating with patients during conferences, and facilitating decision-making processes), contrasts in patient and interprofessional communication, conference communication (challenge of building consensus, the way to proceed conferences, importance of conference preparation, and process of information aggregation and realization of outcomes), mutual recognition and role contribution, building relationships (importance of daily interprofessional communication), understanding one’s profession (reflection on one’s own profession, understanding the roles of different professions, and communication within one’s own professional context), recursion into learning (motivation for continuous learning and improvement), and understanding other professions (understanding the role and perspectives of other professions and recognizing professional differences). Specific feedback highlighted improved empathy and communication skills. Students recognized the value of each profession’s contribution to patient care. Moreover, students reported a deeper appreciation of patient-centered approaches and the complexities of coordinating care across different healthcare roles. Conclusion: Simulated interprofessional team conferences using cross-training effectively taught junior students to understand the essence of a good healthcare team and the importance of a patient-centered approach. Cross-training significantly enhanced students’ interprofessional competencies, communication skills, and empathy toward other professions. This case underscores the necessity of incorporating cross-training into IPE to prepare healthcare professionals for collaborative practice and improve patient outcomes. Future research should consider expanding the scope to include more diverse scenarios and longitudinal assessments to measure longterm impacts on professional practice.

This study aimed to clarify the optimal value for the unbound cefmetazole concentration to remain above the minimum inhibitory concentration (MIC) (fT ≥ MIC) for efficacy of de-escalation to cefmetazole in patients with bacteremic urinary tract infection by extended-spectrum β-lactamase-producing Escherichia coli. This double-center retrospective observational study was conducted at Tokyo Bay Urayasu Ichikawa Medical Center and Keio University Hospital from January 2012 to October 2022. Efficacy was determined via clinical evaluation (mortality rate, recurrence rate, vital changes) and bacteriological evaluation, and the optimal fT ≥ MIC was calculated via receiver operating characteristic curve analysis. As a result, the number of patients evaluated were 40 (35 and 5 in the treatment success and treatment failure groups, respectively). Univariate analysis showed that fT ≥ MIC, recurrence rate, and MIC for cefmetazole against bacteria were significantly different for the two groups (p < 0.05). Receiver operating characteristic curve analysis showed that the optimal fT ≥ MIC indicating efficacy was 57% (area under the curve: 0.94, 95% confidence interval: 0.86–1.00, p = 0.002). All patients with fT ≥ MIC ≥ 57% had successful treatment, whereas the frequency of treatment failure was high among those with fT ≥ MIC <57%. The optimal fT ≥ MIC for the clinical efficacy of de-escalation to cefmetazole in patients with bacteremic urinary tract infection by extended-spectrum β-lactamase-producing E. coli was fT ≥ MIC ≥ 57%. This finding would be useful for optimal dosing of cefmetazole.

Inhibiting body fat accumulation is important for the prevention of obesity. In Japan, three Kampo medicines are commonly used to treat obesity: bofutsushosan, boiogito, and daisaikoto. To compare the influences of these Kampo medicines on the intestinal microbiota, it is necessary to conduct a simultaneous investigation using the same mouse model under the same experimental conditions. C57BL/6J mice were divided into five groups: normal chow (NC), high-fat diet (HFD), HFD + 3% bofutsushosan extract (BTS), HFD + 3% boiogito extract (BOT), and HFD + 3% daisaikoto extract (DST). Epididymal white adipose tissue (WAT) weight, mesenteric WAT weight, serum triglyceride levels, and serum total cholesterol levels were measured. Additionally, total bacteria, alpha diversity, beta diversity, and bacterial composition in stool samples were measured. Body weight and epididymal WAT weight gain were significantly inhibited in the BTS-treated group and DST-treated group, but not in the BOT-treated group, compared with the HFD control group. Additionally, serum total cholesterol levels were significantly lower in the DST-treated group than in the HFD group. Specific intestinal bacteria, Clostridium sensu stricto 1, Erysipelatoclostridium, Roseburia, and the Lachnospiraceae NK4A136 group, were significantly changed in the Kampo-treated groups compared with the HFD group, and each of them was correlated with body weight gain, body fat rate, epididymal WAT weight, or mesenteric WAT weight. Our simultaneous investigation of BTS, BOT, and DST under the same conditions clearly demonstrated different changes in the intestinal microbiota and different effects on fat accumulation as well as their association among the three Kampo medicines.

Background: Individual responses to oxaliplatin (L-OHP)-based chemotherapy remain unpredictable. Our recent proteomics studies have demonstrated that intracellular protein expression levels of S100A10 are significantly correlated with the sensitivity of colorectal cancer (CRC) cells to L-OHP, but not 5-FU, suggesting that S100A10 is a candidate predictive marker for the response to L-OHP. In this study, we investigated whether S100A10 is involved in L-OHP sensitivity or not.Results: Forced expression of S100A10 in COLO-320 CRC cells significantly increased the 50% inhibitory concentration (IC50) for L-OHP (P = 0.003), but did not change that for 5-FU, indicating that S100A10 is more specific to L-OHP than 5-FU. Silencing of the S100A10 gene showed no apparent effect on sensitivity to L-OHP in HT29 cells. Silencing of the annexin A2 (a binding partner of S100A10) gene alone downregulated both annexin A2 and S100A10 protein levels, with no change in S100A10 gene expression. However, original levels of intact S100A10 protein in CRC cells positively correlated with S100A10 mRNA levels (P = 0.002, R = 0.91).Conclusions: The present results have shown that protein expression of S100A10 was associated with resistance to L-OHP, but not 5-FU, supporting the hypothesis that S100A10 expression may predict L-OHP sensitivity. Thus, our present study provides basic findings to support that S100A10 expression can be used as a predictive marker for tumor sensitivity to L-OHP. © 2014 Suzuki and Tanigawara; licensee BioMed Central Ltd.

Background: Individual responses to oxaliplatin (L-OHP)-based chemotherapy remain unpredictable. The objective of our study was to find candidate protein markers for tumor sensitivity to L-OHP from intracellular proteins of human colorectal cancer (CRC) cell lines. We performed expression difference mapping (EDM) analysis of whole cell lysates from 11 human CRC cell lines with different sensitivities to L-OHP by using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS), and identified a candidate protein by liquid chromatography/mass spectrometry ion trap time-of-flight (LCMS-IT-TOF).Results: Of the qualified mass peaks obtained by EDM analysis, 41 proteins were differentially expressed in 11 human colorectal cancer cell lines. Among these proteins, the peak intensity of 11.1 kDa protein was strongly correlated with the L-OHP sensitivity (50% inhibitory concentrations) (P < 0.001, R 2 = 0.80). We identified this protein as Protein S100-A10 (S100A10) by MS/MS ion search using LCMS-IT-TOF. We verified its differential expression and the correlation between S100A10 protein expression levels in drug-untreated CRC cells and their L-OHP sensitivities by Western blot analyses. In addition, S100A10 protein expression levels were not correlated with sensitivity to 5-fluorouracil, suggesting that S100A10 is more specific to L-OHP than to 5-fluorouracil in CRC cells. S100A10 was detected in cell culture supernatant, suggesting secretion out of cells.Conclusions: By proteomic approaches including SELDI technology, we have demonstrated that intracellular S100A10 protein expression levels in drug-untreated CRC cells differ according to cell lines and are significantly correlated with sensitivity of CRC cells to L-OHP exposure. Our findings provide a new clue to searching predictive markers of the response to L-OHP, suggesting that S100A10 is expected to be one of the candidate protein markers. © 2011 Suzuki et al; licensee BioMed Central Ltd.

Reports on the therapeutic drug monitoring (TDM) of second- and third-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer patients are limited and are required to improve the safety of EGFR-TKI therapy. Some EGFR-TKIs have active metabolites with similar or higher potency compared with the parent compounds; thus, monitoring the parent compound as well as its active metabolites is essential for truly effective TDM. In this study, we developed and validated a method that simultaneously quantifies second- and third-generation EGFR-TKIs (afatinib, dacomitinib, and osimertinib) and the active metabolites of osimertinib, AZ5104 and AZ7550, in the human serum using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The clinical application of the method was also evaluated. The analytes were extracted from a 100 μL serum sample using a simple protein precipitation method and analyzed using LC-MS/MS. Excellent linearity of calibration curves was observed at ranges of 2.5–125.0 ng/mL for afatinib, 2.5–125.0 ng/mL for dacomitinib, 4.0–800.0 ng/mL for osimertinib, 1.0–125.0 ng/mL for AZ5104, and 2.5–125.0 ng/mL for AZ7550. The precision and accuracy were below 14.9% and within ± 14.9% of the nominal concentrations, respectively. The mean recovery was higher than 94.7% and the coefficient of variation (CV) was lower than 8.3%. The mean internal-standard normalized matrix factors ranged from 94.6 to 111.9%, and the CVs were lower than 9.7%. This analytical method met the acceptance criteria of the U.S. Food and Drug Administration guidelines. The method was also successfully applied to the analysis of 45 clinical samples; it supports the efficient and valuable analysis for TDM investigations of EGFR-TKIs.

Pancreatic cancer is associated with a poor prognosis; thus, there is an urgent need to develop new and effective treatments. Ingenol mebutate (IM), which is isolated from the latex of Euphorbia peplus, was recently shown to be effective against pancreatic cancer cell lines; however, its mechanism of action has not been fully elucidated. In this study, we focused on the less drug-sensitive pancreatic cancer cell line Panc-1 and compared IM to commercially available anticancer drugs using cell survival assays. In addition, we aimed to identify novel biomolecules that may be involved in the mechanism of action of IM using RNA sequencing, western blotting, and inhibition assays. The IC50 values after 72 h of exposure to IM and SN-38, drugs to which the Panc-1 cells are most sensitive among the tested anticancer agents, were 43.1 ± 16.8 nM and 165 ± 37 nM, respectively. IM showed a cytostatic effect equal to or greater than that of the clinically used pancreatic cancer therapeutic drugs. RNA sequencing and protein expression analysis revealed that expression of stimulator of interferon genes (STING) increased at low IM concentration, whereas cell viability decreased. Co-exposure of IM and STING inhibitor, H-151, to Panc-1 or MIA PaCa-2 cell lines canceled the growth-inhibitory effects of IM alone. In conclusion, IM may have an efficacy comparable to that of existing pancreatic cancer therapeutic agents on the less drug-sensitive Panc-1 cell line and the immune-related molecule STING plays a role in the mechanism of action of IM.

In the pharmacy practice experience (PPE) component of the pharmaceutical education model core curriculum, factors by which achievement can best be evaluated in rubric format have not been empirically determined. In this study, multivariate analysis was conducted based on characteristic information obtained from PPEs.Data were analyzed from a total of 146 fifth-year students of Keio University Faculty of Pharmacy who completed PPEs in 2021. Using “Learning Results Prior to PPE”, “Presence / Absence of Role Model in PPE”, “Number of Experience Areas focused on Representative Eight Diseases”, and “Number of People who were Provided Medication Instruction” as the explanatory variables, and “Number of Mentor-provided Performance Evaluations with Scores ≥3” and “Sum of Mentor-provided Performance Evaluation Scores” as the objective variables, multiple regression analysis was performed. For “Number of Mentor-provided Performance Evaluations with Scores ≥3” predictions in training at a pharmacy, training at a hospital, or both, the respective probability values were <0.001, 0.189, and 0.012. For “Sum of Mentor-provided Performance Evaluation Scores”, the respective probability values were 0.005, 0.046, and 0.048. The effect of “Number of Experience Areas focused on Representative Eight Diseases” on each objective variable was consistently large.Multivariate analysis using PPE-relevant collected information identified factors that improve the evaluation of achievement at the end of a PPE.

Objective: Platinum- and anthracycline-based chemotherapy regimens cause nausea and vomiting in clinical practice, resulting in the deterioration of patients’ QoL, discontinuation of chemotherapy, and reduced therapeutic outcomes. Using pica behavior as an indicator, we aimed to clarify whether anamorelin, an orally active ghrelin receptor agonist, exerts antiemetic effects against cisplatin-induced nausea and vomiting in rats. Materials and Methods: Sprague–Dawley rats were treated with cisplatin (5 mg/kg, i.p.), three-drug or four-drug antiemetics (granisetron [0.3 mg/kg, p.o.], dexamethasone [1.5 mg/kg, p.o.], fosaprepitant [12.5 mg/kg, i.p.], with or without anamorelin [30 mg/kg, p.o.]). Data on kaolin intake, normal food intake, and spontaneous motor activity (SMA) were recorded 1 d before and 5 d after cisplatin administration. Body weight (BW) was measured daily, and the percentage change in BW from baseline was calculated. Results: At the primary endpoint, kaolin intake was significantly higher in the cisplatin-only group than in the pretreatment and vehicle groups (p < 0.05). Additionally, kaolin food intake was not significantly low in cisplatin-treated mice treated with three-drug antiemetics with or without anamorelin. At the secondary endpoints, normal food intake, SMA, and percentage change in BW were significantly lower in the cisplatin-only group than in the vehicle group. Conclusion: Our findings suggest that the prophylactic administration of standard three-drug antiemetics, besides anamorelin, may not improve cisplatin-induced nausea and vomiting. Further studies using methods suitable for evaluating anamorelin levels are required.