Objective: To investigate the impact of body mass index (BMI) and exercise habits on readmission rates among older patients with heart failure. Methods: Ninety-seven older patients admitted for heart failure (median age: 81 years; 57.7% male) were included in the study. Patients were categorized into four groups based on the presence or absence of lower BMI and/or the absence of exercise habits. Lower BMI was defined as BMI<20.3 kg/m2 at discharge and exercise habits were defined as engaging in 30 or more minutes of moderate or vigorous exercise at least once a week. The primary outcome was all-cause readmission during the 1-year follow-up period. Results: The patients were distributed across four groups: lower BMIon-exerciser (n=24, 24.7%), lower BMI/exerciser (n=22, 22.7%), non-lower BMIon-exerciser (n=21, 21.6%), and non-lower BMI/exerciser (n=30, 30.9%). Forty-six patients (47.4%) experienced readmission during the 1-year follow-up period. In a cox proportional hazard analysis, non-lower BMI/exerciser remained an independent prognostic factor even after adjusting for confounding factors (non-lower BMI/exerciser vs. lower BMIon-exerciser: hazard ratio, 0.26; 95% confidence interval, 0.08–0.83; p=0.022). Conclusion The coexistence of non-lower BMI and regular exercise habits may reduce readmission during the 1-year in older patients with heart failure. Therefore, it is imperative to conduct appropriate nutritional assessments for patients with lower BMI at discharge. Additionally, promoting and monitoring sustained physical activity after discharge is crucial for older patients with heart failure.

Purpose: The objective of this study was to assess the performance of ChatGPT (GPT-4) on all items, including those with diagrams, in the Japanese National License Examination for Pharmacists (JNLEP) and compare it with the previous GPT-3.5 model’s performance. Methods: The 107th JNLEP, conducted in 2022, with 344 items input into the GPT-4 model, was targeted for this study. Separately, 284 items, excluding those with diagrams, were entered into the GPT-3.5 model. The answers were categorized and analyzed to determine accuracy rates based on categories, subjects, and presence or absence of diagrams. The accuracy rates were compared to the main passing criteria (overall accuracy rate ≥62.9%). Results: The overall accuracy rate for all items in the 107th JNLEP in GPT-4 was 72.5%, successfully meeting all the passing criteria. For the set of items without diagrams, the accuracy rate was 80.0%, which was significantly higher than that of the GPT-3.5 model (43.5%). The GPT-4 model demonstrated an accuracy rate of 36.1% for items that included diagrams. Conclusion Advancements that allow GPT-4 to process images have made it possible for LLMs to answer all items in medical-related license examinations. This study’s findings confirm that ChatGPT (GPT-4) possesses sufficient knowledge to meet the passing criteria.

Objective: The wrong dose of high-risk drugs such as oral steroids is a serious issue that needs to be addressed. This study aims to determine the appropriate upper tolerable dose threshold and to develop a multi-variable logistic regression model to detect dose-errors in oral prednisolone tablets.Methods: Data on Prednisolone prescriptions were obtained from a single center. Out of the data collected, positive cases consisted of cases where dose-related modifications were made. A univariate logistic regression model was developed with the current daily dose. In the model, the Youden Index was used to determine the upper tolerable dose threshold. The investigation was done to determine whether the performance of the multivariate model was improved by adding clinical department and previous prescription information as variables.Results: Univariate models (AUC: 0.645) with only current daily doses and estimated optimal thresholds of 6 mg/day or 11 mg/day, respectively were determined to be appropriate. Including variables improved the performance of the predictive model; the best performing model (AUC: 0.840) was derived when the following variables were entered: “current daily dose,” “current prescription days,” “clinical department,” “daily dose of the previous prescription,” and “prescription days of the previous prescription”.Conclusion: A single upper tolerance limit is insufficient to determine dose adequacy for prednisolone tablets owing to their broad clinical dose range. Itmay be possible to develop a high-performance dose audit support model by adding information.

Drug therapy is necessary to treat metastatic and recurrent breast cancer. In Japan, two types of cyclin-dependent kinases (i.e., CDK4/6 inhibitors) are covered under the national healthinsurance system: palbociclib (since December 2017) and abemaciclib (since November 2018). Although there are many reports on the use and side effects of palbociclib in clinical practice, there are few such reports on abemaciclib. Therefore, we investigated the rate of neutropenia and associated background factors in patients taking abemaciclib. Of the 39 patients taking abemaciclib recruited for the study, 22 satisfied the inclusion criteria. Of these, 7 developed Grade 3 or higher neutropenia and had a significantly lower body weight and body mass index (BMI). Furthermore, the white blood cell and neutrophil counts before administration were significantly lower in the expression group compared with the non-expressing group. To predict the development of Grade 3 or higher neutropenia, the receiver operating characteristic (ROC) curve was used to calculate a BMI cut-off value of 23.9 (specificity 85.7%, sensitivity 73.3%, area under the ROC curve 0.80). Based on this cut-off value, BMI was divided into two groups (<23.9 and ≥23.9) and Fisher's exact test was performed. Patients with a low body mass index were more likely to develop Grade 3 or higher neutropenia as a result of increased dosage per kilogram body weight, while among patients with BMI < 25, those with BMI < 23.9 were at high risk of developing Grade 3 or higher neutropenia. Accordingly, caution is required in the treatment of such patients.

Objective: The differences in clinical outcomes in hospitalized patients with hematological disorders (HD) who developed either coronavirus disease 2019 (COVID-19) or seasonal influenza (SI) are not fully understood. To examine these differences, we retrospectively analyzed the baseline characteristics and clinical outcomes of hospitalized patients with HD admitted from 2016 to 2021.Patients and Methods: Patients with HD who developed COVID-19 (in the past 1 year) (n=21) or SI (in the past 5 years) (n=23) in the Department of Hematology/Oncology, Asahikawa Kosei General Hospital were evaluated.Results: The median ages of the patients with HD with either COVID-19 or SI were 80 and 68 years, respectively (P=0.03). The groups showed no significant differences in sex ratio, body mass index, or Eastern Cooperative Oncology Group performance status. In the COVID-19 and SI groups, the most common primary diseases were diffuse large B-cell lymphoma (43%) and multiple myeloma (39%), respectively. The median numbers of days of oxygen administration (8 vs. 0 days), quarantine (25 vs. 6 days), and hospitalization (72 vs. 21 days) were significantly higher in HD patients with COVID-19 than those in HD patients with SI (all P<0.001). The overall 90-day survival of patients with HD and COVID-19 was significantly shorter than that of patients with HD and SI (P=0.019). Moreover, patients with HD and COVID-19 had a higher risk of in-hospital mortality (43% vs. 9%; odds ratio, 7.50; 95% confidence interval, 1.26–82.4; P=0.01) compared to patients with HD and SI.Conclusion: Patients with HD and COVID-19 required longer periods of in-hospital medical and showed poorer survival than those with SI. During the COVID-19 pandemic, hematologists should closely monitor the condition of patients with COVID-19 to closely monitor their condition to prevent deaths.

Engaru-Kosei General Hospital expanded its pharmacist duties in hospital wards in April 2018 following the nationwide switch to out-of-hospital prescriptions. The purpose of this study was to examine the effect of pharmacists’ ward duties on nursing duties. Pharmacists expanded their duties to cover drug distribution management, infusions of total parenteral nutrition (TPN) mixed with drugs, and aseptic preparation of 24-h infusions (including peripheral parenteral nutrition). The effects were compared between April 2018 before the expansion of duties and May-September 2018 after the expansion, and we compared the number of meetings set up to discuss nurses’ overtime hours and patient problems. In addition, interviews were conducted about the changes experienced on site. Drug distribution management averaged 3,150 cases/month. The number of TPN mixed infusions was 25 cases/month before expansion and this increased to 88 cases/month after expansion. The number of mixed injections of 24-h infusions was 296/month. Nurses' overtime hours did not decrease significantly, but the number of meetings increased from 47/month to 79.4/month. In the interviews, positive responses were obtained about, for example, the increased number of meetings held and more time for patient care. The pharmacist and the nurse collaborated to improve work by using their expertise, we think that the results obtained from work improvement contributed to the improvement of medical quality and medical safety.

Objective: Risk Management Plan (RMP) is created and submitted by a pharmaceutical company while applying for new drug approval; it is published to be used by healthcare professionals. For example, healthcare professionals utilize RMP when considering whether to adopt a drug. However, there is no stipulation for the release date of RMPs; moreover, surveys regarding this are limited. We conducted a cross-sectional survey on the relationship between RMP-related timing and regulatory affairs-related timing.Methods: The surveyed drugs were those for which the first version of RMP was notified by PMDA Medinavi (mail delivery service) in FY2014 and FY2018. We examined regulatory affairs-related timing (i.e., “manufacturing and marketing approval date,” “drugprice standards listing date,” and “release date”) and RMP-related timing (i.e., “RMP creation date” and “Medinavi delivery date”).Results: For 7 of 43 items in FY2014 and 5 of 41 items in FY2018, the “RMP creation date” occurred later than the “drug-price standards listing date.” For one item in FY2014, the “RMP creation date” occurred later than the “release date.” For 12 items in FY2014 and 13 items in FY2018, the “Medinavi delivery date” occurred later than the “release date.”Conclusion: No considerable difference was confirmed between FY2014 and FY2018 regarding RMP-related timing and regulatory affairs timing. It was confirmed that there were several items for which the RMP creation occurred later than drug-price standard listing and items for which the publishing notice by Medinavi was delayed for drug marketing release. To promote the utilization of RMPs by healthcare professionals, RMPs must be created and published without delay.

Objective: The use of generic drugs is promoted to reduce medical costs and copayments. However, tumor agents are expensive and generic drugs are not widelyused. Thus, it is necessaryto evaluate the safetyof generic drugs in more detail. We compared the incidence of adverse events between the original drug (Gemzar®: GEM) and generic drug (Gemcitabine [Sandoz]: GE-GEM) using propensityscore (PS) matching.Methods: We investigated adverse events in patients who received one course of GEM or GE-GEM. The patient background (age,sex, BSA, cancer type, stage, metastasis, surgical history, and radiotherapy) and administration status (administration route and RDI) were used to calculate the PS.Results: Among all patients (GEM: 51, GE-GEM: 54), a significantlygreater number in the GE-GEM group had cancer metastasis. On comparison of adverse events, there were significantlymore cases of vascular pain (p＜0.05) in the GEM group, and manycases of nausea (p＝0.08) and rash (p＝0.08). Fortypatients in each group were extracted byPS matching. There were no significant differences in the patient background between the groups, and on comparison of adverse events, the two groups did not significantly differ.Conclusion: Our studysuggested that there is no difference in side effects between Gemzar® and gemcitabine [Sandoz]. To compare the incidence of adverse events, it is useful to use PS matching in clinical practice.

Objective: Maternal embryonic leucine zipper kinase (MELK) is receiving an attention as a therapeutic target in various types of cancers. In this study, we aimed to evaluate the prognostic significance of MELK expression in ovarian cancer using clinical samples, and assessed the efficacy of a small molecule MELK inhibitor, OTS167, using patient-derived ovarian cancer cells as well as cell lines. Methods: Expression levels of MELK in 11 ovarian cancer cell lines were confirmed by western blotting. Inhibitory concentration of OTS167 was determined by colorimetric assay.MELK messenger RNA (mRNA) expression was evaluated in 228 ovarian cancer patients by quantitative polymerase chain reaction. Growth inhibition of OTS167 was also evaluated using freshly-isolated primary ovarian cancer cells including spheroid formation condition. Results: MELK mRNA expression was significantly higher in ovarian cancer than in normal ovaries (p<0.001), and high MELK mRNA expression was observed in patients with advanced stage, positive ascites cytology and residual tumor size. Patients with high MELK mRNA expression showed shorter progression-free survival (p=0.001). Expression of MELK was also confirmed in 10 of 11 ovarian cancer cell lines tested, and the half maximal inhibitory concentration of MELK inhibitor, OTS167, ranged from 9.3 to 60 nM. Additionally, OTS167 showed significant growth inhibitory effect against patient-derived ovarian cancer cells, regardless of their tumor locations, histologic subtypes and stages. Conclusions We demonstrated MELK as both a prognostic marker and a therapeutic target for ovarian cancer using clinical ovarian cancer samples. MELK inhibition by OTS167 may be an effective approach to treat ovarian cancer patients.

Objective: The risk management plan (RMP) is a useful information source for healthcare professionals, including pharmacists, to ensure drug safety. The “risk minimization activities” (RMA) of the RMP are especially important elements for healthcare professionals. It is known that “Medication Guides for Patients” (MGP) and “Early post-marketing phase vigilance” (EPPV) are items listed as part of the RMA. However, the creation of MGPs and the implementation of EPPVs are not performed for all medicines. In a previous study, it was difficult to evaluate this sufficiently with the safety specifications. The aim of this investigation was to evaluate RMAs, especially MGPs and EPPVs, not in terms of the safety specifications of RMP.Methods: The previously published RMPs of 177 drugs were obtained on February 22,2016, and used in the analysis. The relationship between the creation of the MGP and the description in the RMA and the relationship between the conduct described in the EPPV and the description in RMA was investigated for each medicine.Results: An MGP was created in 151 of the analyzed drugs. Of these, it was not listed in the RMA of 40 drugs. In contrast, EPPV was not listed in RMA in 2 out of 33 drugs when underway. EPPV was described in the RMA of 33 of the EPPV finished drugs. The time lag from the end of EPPV until the revision of the RMP was 4.5 month son average.Conclusion: MGPs and EPPVs are created especially for drugs requiring patient education, information provision, or safety monitoring. Therefore, for drugs for which MGPs or EPPVs are required, they should be listed in the RMA. In this study, the time lag of RMP revision was also highlighted as a problem. In order to promote the utilization of RMP by pharmacists, these issues should be resolved.