Details of a Researcher - Kizaki, Hayato

Papers - Kizaki, Hayato

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野呂幾久子, 飯岡緒美, 堀里子, 中野重行, 木﨑速人, 石崎雅人

臨床薬理 ((一社)日本臨床薬理学会) 56 ( 2 ) 97 - 108 2025.05

Research paper (scientific journal), Joint Work, Accepted, ISSN 03881601

It has been observed that CRCs, pivotal figures in clinical research, often grapple with a substantial mental burden. This study, which investigates the resilience factors of CRCs, aims to provide practical suggestions for their education and resilience development, empowering them with actionable knowledge. Ten CRCs, who had been working as CRCs for many years, were interviewed individually. They were asked about their challenging experiences while working as CRCs, how they successfully adapted to those challenges, and the factors involved in the process. We then inductively coded the factors involved in successfully adapting to challenges as the analysis theme. The qualitative analysis reveals that the factors of resilience of CRCs were classified into four groups(: 1)individual characteristics and ways of thinking,(2)meaning, goals, and motivation,(3)ways of dealing with work, and(4)support from those around them. Among the factors, the following were considered to be particularly important for CRCs: meaning, continuing attempt to find meaning in one's work, even in the face of adversity; metacognition, handling reflection on one's own and others' cognitive activities from a bird's-eye view; and balancing professional and patient perspectives that maintains the rigor of carrying out clinical research as a medical professional with empathy for patients' feelings.

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Incidence Status and Factors Associated With Tyrosine Kinase Inhibitor-Induced Hypertension in Patients With Renal Cell Carcinoma

Nakanishi S., Ikegami K., Imai S., Kizaki H., Hori S.

Cancer Reports 8 ( 5 ) e70219 2025.05

Research paper (scientific journal), Joint Work, Accepted

Background: Although hypertension is a common side effect of tyrosine kinase inhibitor (TKI) treatment for renal cell carcinoma (RCC), there is limited evidence regarding its occurrence and related risk factors. Preliminary studies suggest that proton pump inhibitors (PPIs) may mitigate the risk of TKI-induced hypertension; however, their clinical effectiveness remains unclear. Aims: In this study, we examined the prevalence of TKI-induced hypertension and the patterns of antihypertensive prescriptions among patients with RCC in Japan. Additionally, we investigated factors associated with TKI-induced hypertension to assess the potential impact of PPIs. Methods and Results: Data from patients diagnosed with RCC who were prescribed TKIs between April 2008 and July 2021 were retrospectively gathered from a Japanese administrative database. TKI-induced hypertension was detected following the diagnosis of hypertension and subsequently the prescription of an antihypertensive agent during TKI therapy. The prescription details for antihypertensive agents were organized in a tabular format. Cox proportional hazards regression analysis was conducted to examine factors contributing to TKI-induced hypertension. Among the 225 patients analyzed, 36.4% experienced hypertension, and calcium channel blockers were the most prescribed antihypertensive agents. Pre-existing hypertension was identified as a risk factor for TKI-induced hypertension, while the concurrent use of PPIs did not show a tendency to reduce the risk of TKI-induced hypertension. Conclusions: These findings indicate the importance of blood pressure management in patients with elevated baseline blood pressure.

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Accuracy of Diagnostic Coding for Acute Kidney Injury in Japan-Analysis of a Japanese Hospital-Based Database.

Mitsuboshi S, Imai S, Tsuchiya M, Kizaki H, Hori S

Pharmacoepidemiology and drug safety 34 ( 4 ) e70146 2025.04

Research paper (scientific journal), Joint Work, Accepted, ISSN 1053-8569

Purpose: To evaluate the accuracy of diagnostic coding for acute kidney injury (AKI) in Japan. Methods: The data analyzed were obtained from the JMDC hospital-based administrative claims database from cases registered between April 2014 and August 2022. Only patients who underwent serum creatinine measurements two or more times with intervals of 7 days or less were eligible for inclusion. AKIs were identified by International Classification of Diseases 10th Revision (ICD-10) codes N14 and N17. These were assessed according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Results: A total of 467 019 patients (median age, 74 [range, 20–99] years; male, 50.9%) were eligible for inclusion. Among these patients, 1849 (0.4%) were assigned ICD-10 codes for AKI. Among these 1849 patients, the code was assigned within 7 days of the occurrence of AKI (as defined by the KDIGO criteria) in 212 patients, within 14 days in 294 patients, and within 30 days in 386 patients. The positive predictive values and 95% confidence intervals of the ICD-10 code for AKI at these timepoints were as follows: within 7 days, 11.5% (10.1%–13.0%); within 14 days, 15.9% (14.3%–17.6%); and within 30 days, 20.9% (19.1%–22.8%). Conclusions: The ICD-10 codes for AKI showed poor positive predictive values for AKI as defined by the KDIGO criteria, suggesting that it may be difficult to identify AKI using ICD-10 codes alone in the Japanese context.

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Improving Systematic Review Updates With Natural Language Processing Through Abstract Component Classification and Selection: Algorithm Development and Validation.

Hasegawa T, Kizaki H, Ikegami K, Imai S, Yanagisawa Y, Yada S, Aramaki E, Hori S

JMIR medical informatics 13 e65371 2025.03

Research paper (scientific journal), Joint Work, Accepted

Background: A challenge in updating systematic reviews is the workload in screening the articles. Many screening models using natural language processing technology have been implemented to scrutinize articles based on titles and abstracts. While these approaches show promise, traditional models typically treat abstracts as uniform text. We hypothesize that selective training on specific abstract components could enhance model performance for systematic review screening. Objective: We evaluated the efficacy of a novel screening model that selects specific components from abstracts to improve performance and developed an automatic systematic review update model using an abstract component classifier to categorize abstracts based on their components. Methods: A screening model was created based on the included and excluded articles in the existing systematic review and used as the scheme for the automatic update of the systematic review. A prior publication was selected for the systematic review, and articles included or excluded in the articles screening process were used as training data. The titles and abstracts were classified into 5 categories (Title, Introduction, Methods, Results, and Conclusion). Thirty-one component-composition datasets were created by combining 5 component datasets. We implemented 31 screening models using the component-composition datasets and compared their performances. Comparisons were conducted using 3 pretrained models: Bidirectional Encoder Representations from Transformer (BERT), BioLinkBERT, and BioM- Efficiently Learning an Encoder that Classifies Token Replacements Accurately (ELECTRA). Moreover, to automate the component selection of abstracts, we developed the Abstract Component Classifier Model and created component datasets using this classifier model classification. Using the component datasets classified using the Abstract Component Classifier Model, we created 10 component-composition datasets used by the top 10 screening models with the highest performance when implementing screening models using the component datasets that were classified manually. Ten screening models were implemented using these datasets, and their performances were compared with those of models developed using manually classified component-composition datasets. The primary evaluation metric was the F10-Score weighted by the recall. Results: A total of 256 included articles and 1261 excluded articles were extracted from the selected systematic review. In the screening models implemented using manually classified datasets, the performance of some surpassed that of models trained on all components (BERT: 9 models, BioLinkBERT: 6 models, and BioM-ELECTRA: 21 models). In models implemented using datasets classified by the Abstract Component Classifier Model, the performances of some models (BERT: 7 models and BioM-ELECTRA: 9 models) surpassed that of the models trained on all components. These models achieved an 88.6% reduction in manual screening workload while maintaining high recall (0.93). Conclusions: Component selection from the title and abstract can improve the performance of screening models and substantially reduce the manual screening workload in systematic review updates. Future research should focus on validating this approach across different systematic review domains.

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Identifying Adverse Events in Outpatients With Prostate Cancer Using Pharmaceutical Care Records in Community Pharmacies: Application of Named Entity Recognition.

Yanagisawa Y, Watabe S, Yokoyama S, Sayama K, Kizaki H, Tsuchiya M, Imai S, Someya M, Taniguchi R, Yada S, Aramaki E, Hori S

JMIR cancer 11 e69663 2025.03

Research paper (scientific journal), Joint Work, Accepted

Background: Androgen receptor axis-targeting reagents (ARATs) have become key drugs for patients with castration-resistant prostate cancer (CRPC). ARATs are taken long term in outpatient settings, and effective adverse event (AE) monitoring can help prolong treatment duration for patients with CRPC. Despite the importance of monitoring, few studies have identified which AEs can be captured and assessed in community pharmacies, where pharmacists in Japan dispense medications, provide counseling, and monitor potential AEs for outpatients prescribed ARATs. Therefore, we anticipated that a named entity recognition (NER) system might be used to extract AEs recorded in pharmaceutical care records generated by community pharmacists. Objective: This study aimed to evaluate whether an NER system can effectively and systematically identify AEs in outpatients undergoing ARAT therapy by reviewing pharmaceutical care records generated by community pharmacists, focusing on assessment notes, which often contain detailed records of AEs. Additionally, the study sought to determine whether outpatient pharmacotherapy monitoring can be enhanced by using NER to systematically collect AEs from pharmaceutical care records. Methods: We used an NER system based on the widely used Japanese medical term extraction system MedNER-CR-JA, which uses Bidirectional Encoder Representations from Transformers (BERT). To evaluate its performance for pharmaceutical care records by community pharmacists, the NER system was first applied to 1008 assessment notes in records related to anticancer drug prescriptions. Three pharmaceutically proficient researchers compared the results with the annotated notes assigned symptom tags according to annotation guidelines and evaluated the performance of the NER system on the assessment notes in the pharmaceutical care records. The system was then applied to 2193 assessment notes for patients prescribed ARATs. Results: The F1-score for exact matches of all symptom tags between the NER system and annotators was 0.72, confirming the NER system has sufficient performance for application to pharmaceutical care records. The NER system automatically assigned 1900 symptom tags for the 2193 assessment notes from patients prescribed ARATs; 623 tags (32.8%) were positive symptom tags (symptoms present), while 1067 tags (56.2%) were negative symptom tags (symptoms absent). Positive symptom tags included ARAT-related AEs such as “pain,” “skin disorders,” “fatigue,” and “gastrointestinal symptoms.” Many other symptoms were classified as serious AEs. Furthermore, differences in symptom tag profiles reflecting pharmacists’ AE monitoring were observed between androgen synthesis inhibition and androgen receptor signaling inhibition. Conclusions: The NER system successfully extracted AEs from pharmaceutical care records of patients prescribed ARATs, demonstrating its potential to systematically track the presence and absence of AEs in outpatients. Based on the analysis of a large volume of pharmaceutical medical records using the NER system, community pharmacists not only detect potential AEs but also actively monitor the absence of severe AEs, offering valuable insights for the continuous improvement of patient safety management.

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Evaluating the Efficacy of Premedication in Preventing Hypersensitivity Reactions to Nonionic Contrast Agents

Suzuki S., Imai S., Omata A., Kamimura T., Kizaki H., Koinuma T., Hori S.

Biological and Pharmaceutical Bulletin 48 ( 3 ) 241 - 245 2025.03

Research paper (scientific journal), Joint Work, Accepted, ISSN 09186158

Iodine-based contrast agents can induce various acute hypersensitivity reactions ranging from mild itching or vomiting shortly after administration to severe hypotension or loss of consciousness. In Japan, steroid premedication is commonly used to prevent acute hypersensitivity reactions. However, little clear evidence supporting its efficacy is available. In this study, we evaluated the effectiveness of premedication for acute hypersensitivity reactions induced by nonionic iodine contrast agents using propensity score matching. The participants included patients who were administered nonionic iodine contrast agents at Yokohama City Minato Red Cross Hospital between April 1, 2016 and March 31, 2022. Only first-time patients with no history of hypersensitivity reactions to contrast agents were included. The patients were classified into premedication and non-premedication groups, and the incidence proportions of acute hypersensitivity reactions were compared after matching. Of the 19976 patients, 422 (211 in each group) were matched. In the premedication group, 7 cases (3.32%) of hypersensitivity reactions occurred. In contrast, only 2 cases (0.95%) were observed in the non-premedication group. The odds ratio for the occurrence of hypersensitivity reactions in the premedication group was 3.500 (95% confidence interval, 0.727–16.848), with no significant difference. Therefore, premedication did not demonstrate the efficacy in preventing acute hypersensitivity reactions induced by nonionic iodine contrast agents. Based on the results of this study and guidelines, a recommendation for premedication was not reached for patients with a history of allergies, including asthma and atopy, as well as those with a history of drug or food allergies.

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薬名類似に起因する薬剤誤処方の傾向分析 - 薬剤師による誤調剤事例との比較-

森部詩月，今井俊吾，佐山杏子，上村忠聖，林誠一，木崎速人，堀里子

医薬品情報学（in press） ((一社)日本医薬品情報学会) 26 ( 4 ) 178 - 185 2025.02

Research paper (scientific journal), Joint Work, Accepted, ISSN 1345-1464

Exploration of factors affecting denosumab-induced hypocalcemia in male patients with osteoporosis using a hospital-based administrative claims database

Kamimura Y., Ikegami K., Kizaki H., Imai S., Hori S.

Maturitas 193 108190 2025.02

Research paper (scientific journal), Joint Work, Accepted, ISSN 03785122

Objectives: Factors affecting denosumab-induced hypocalcemia in male patients with osteoporosis remain unclear because of the small patient population. Nevertheless, it is important to explore male-specific risk factors. This study aimed to identify the factors affecting the development of denosumab-induced hypocalcemia in male patients with osteoporosis and compare them with those in female patients with osteoporosis. Study design: This retrospective, observational study used data from a hospital-based administrative claims database. Patients with osteoporosis undergoing denosumab treatment between April 2008 and May 2020 were enrolled. Data on age, inpatient/outpatient status, laboratory data, drug use, and disease status were collected. Main outcome measures: Patients were classified as those with hypocalcemia and without hypocalcemia, and variables with P < 0.2 and missing proportions <30 % on univariate analysis were entered into multivariate logistic regression analysis. The multiple imputation method was used to compensate for missing data. Results: Overall, 175 males and 1335 females were included in the analysis, and hypocalcemia developed in 52 and 247 patients, respectively. In the multivariate analysis, prior use of preventive medicine (calcium supplements or activated vitamin D) decreased the risk of osteoporosis only in male patients. Low corrected levels of calcium and albumin and low estimated glomerular filtration rates increased the risk in both sexes. Conclusions: Prior use of preventive medicine may be a factor that decreases the risk of denosumab-induced hypocalcemia in male patients. Low corrected levels of calcium and albumin, and low estimated glomerular filtration rates are common risk factors in both male and female patients.

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病院における医薬品関連のインシデントレポート分析の現状と課題に関する全国調査

江原沙也加，柳澤友希，木﨑速人，今井俊吾，安室修，舟越亮寛，堀里子

医療薬学 ((一社)日本医療薬学会) 51 ( 1 ) 10 - 19 2025.01

Research paper (scientific journal), Joint Work, Accepted, ISSN 1346-342X

ランダム抽出した全国の病院2000施設を対象に、医薬品使用に関連したインシデント・アクシデントのインシデントレポートの作成から分析、対策案の立案に至るまでのプロセスの実態とその課題についてアンケート調査を行った。有効回答409施設について集計した結果、患者への影響度にかかわらず、多くのインシデント・アクシデントの対応は、当事者や事例が発生した各部署内において医療安全管理委員会と共同して行われており、病床数や加算算定状況によらず、インシデントレポートの作成と分析は9割以上の病院で実施されていた。患者の影響レベルに関わらず半数近くは分析手法を活用しており、その奥が根本原因分析法であった一方で、影響レベルが低い事例では、あまり分析手法が活用されていなかった。全国の病院において、分析手法が有効に活用されるために改善の余地があることが示された。

Factors Affecting Delayed Recovery from Neutropenia in Patients with Pancreatic Cancer Receiving Gemcitabine plus Nab-Paclitaxel

Yoshida N, Imai S, Kawakami K, Yokokawa T, Nakamura M, Aoyama T, Shimizu H, Naito R, Teramae M, Tsuchiya M, Kizaki H, Ozaka M, Sasahira N, Yamaguchi M, Hori S.

J Cancer 16 ( 5 ) 1413 - 1419 2025.01

Research paper (scientific journal), Joint Work, Accepted, ISSN 1837-9664

Background: Many studies have identified risk factors for neutropenia associated with various chemotherapies, including gemcitabine plus nab-paclitaxel (GnP). However, few studies have focused on the delayed recovery from neutropenia, which frequently leads to treatment discontinuation. We aimed to examine whether the risk factors for neutropenia affect delayed recovery following development. Material and Methods: Data were collected from patients with pancreatic cancer who received GnP therapy between December 2014 and March 2019 at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research. In the present study, we investigated the following: (1) risk factors for grade 3 or higher neutropenia and (2) factors affecting delayed recovery in patients who developed neutropenia in (1). Results: Of the 638 patients who underwent GnP therapy, 364 developed neutropenia and 29 experienced delayed recovery. Most patients with delayed recovery experienced neutropenia on day 8 of the first course; therefore, we focused on this group. Among the 111 patients who developed neutropenia on day 8 of the first course, 22 experienced delayed recovery after excluding those who received granulocyte-colony stimulating factor. Low baseline neutrophil, platelet, and red blood cell counts were identified as risk factors for neutropenia. Although multivariate analysis could not be conducted due to the limited number of patients, these three factors were also associated with delayed recovery. Conclusion: Low neutrophil, platelet, and red blood cell counts at baseline were identified as risk factors for neutropenia and affecting delayed recovery.

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Effect of Concomitant Metformin Use on Hematologic Adverse Events in Non-Small-Cell Lung Cancer Patients Undergoing Pemetrexed-Based Chemotherapy: A Study Using a Japanese Claims Database

Hayafune M., Imai S., Kizaki H., Tsuchiya M., Hori S.

Yakugaku Zasshi ((公社)日本薬学会) 145 ( 1 ) 61 - 70 2025

Research paper (scientific journal), Accepted, ISSN 00316903

Pemetrexed is a folate analog inhibitor for the treatment of non-small-cell lung cancer (NSCLC). Prophylactic supplementation with vitamin B12 and folic acid reduces hematotoxicity associated with pemetrexed. Metformin, the antidiabetic agent, has been associated with the potential side effect of vitamin B12 deficiency. This retrospective observational study aimed to evaluate the effect of concomitant metformin use on hematologic adverse events in patients with NSCLC undergoing pemetrexed-based chemotherapy using the Medical Data Vision Database. Patients with stage III or higher NSCLC who received pemetrexed from April 2008 to May 2021 were categorized into metformin-treated (MTF) and non-metformin-treated (non-MTF) groups. The primary outcome was the proportion of granulocyte colony-stimulating factor (G-CSF) administration during cycle (C) 1 to C2 or C2 to C3 of pemetrexed therapy. Propensity score matching (PSM) was used to balance the baseline characteristics between the groups. A total of 1174 patients met the inclusion criteria (54 in MTF and 1120 in non-MTF). After PSM, 52 patients were included in each group. The median metformin dosage in the MTF group was 500 mg/d before and 625 mg/d after PSM. There were no significant differences between the MTF and non-MTF groups in G-CSF administration (15.4 vs. 21.2%, p=0.446). Multivariate logistic regression analysis also showed that metformin use did not significantly affect hematologic toxicity (odds ratio: 1.208, 95% CI: 0.554–2.634). This suggests that the concomitant use of a relatively low dose of metformin is unlikely to significantly increase the risk of hematotoxicity in Japanese patients with NSCLC receiving pemetrexed-based chemotherapy.

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Development of a Patient-Centered Symptom-Reporting Application in Pharmacy Settings Using a Hierarchical Patient-Friendly Symptom List: Developmental and Usability Study

Watanabe S., Kizaki H., Hori S.

JMIR Human Factors 12 e71439 2025

Background: Effective symptom identification, a key responsibility for community pharmacists, requires patients to describe their symptoms accurately and comprehensively. However, current practices in pharmacies may be insufficient in capturing patient-reported symptoms comprehensively, potentially affecting the quality of pharmaceutical care and patient safety. Objective: This study aimed to construct a new, hierarchical symptom list derived from the Patient-Friendly Term List of the Medical Dictionary for Regulatory Activities (MedDRA) and to develop and evaluate a mobile app incorporating this list for facilitating symptom reporting by patients in pharmacy settings. The study also aimed to assess the usability and acceptance of this app among potential users. Methods: Subjective symptom-related terms were extracted from the Patient-Friendly Term List version 23.0 of the MedDRA. These terms were systematically consolidated and organized into a hierarchical, user-friendly symptom list. A mobile app incorporating this list was developed for pharmacy settings, featuring a symptom selection interface and a free-text input field for additional symptoms. The app included an instructional video explaining the importance of symptom reporting and guidance on navigation. Usability tests and semistructured interviews were conducted with participants aged >20 years. Interview transcripts were analyzed using the Unified Theory of Acceptance and Use of Technology (UTAUT) model to evaluate factors influencing the acceptance of technology. Results: From the initial 1440 terms in the Patient-Friendly Term List, 795 relevant terms were selected and organized into 40 site-specific subcategories, which were then grouped into broader site categories (mental, head, trunk, upper limb, lower limb, physical condition, and others). These terms were further consolidated into 211 patient-friendly symptom terms, forming a hierarchical symptom list. The app’s interface design limited options to 10 items per screen to assist with decision-making. A total of 5 adults participated in the usability test. Participants found the interface intuitive and easy to use, requiring minimal effort, and provided positive feedback regarding the potential utility of the app in pharmacy settings. The UTAUT analysis identified several facilitating factors, including ease of use and the potential for enhanced pharmacist-patient communication. However, concerns were raised about usability for older adults and the need for simplified technical terminology. Conclusions: The user-friendly app with a hierarchically structured symptom list and complementary free-text entry has potential benefits for improving the accuracy and efficiency of symptom reporting in pharmacy settings. The positive user acceptance and identified areas for improvement provide a foundation for further development and implementation of this technology to enhance communication between patients and pharmacists. Future improvements should focus on addressing usability for older adults and simplifying technical terminology.

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Identifying the Relative Importance of Factors Influencing Medication Compliance in General Patients Using Regularized Logistic Regression and LightGBM: Web-Based Survey Analysis.

Iino H, Kizaki H, Imai S, Hori S

JMIR formative research 8 e65882 2024.12

Research paper (scientific journal), Accepted

Background: Medication compliance, which refers to the extent to which patients correctly adhere to prescribed regimens, is influenced by various psychological, behavioral, and demographic factors. When analyzing these factors, challenges such as multicollinearity and variable selection often arise, complicating the interpretation of results. To address the issue of multicollinearity and better analyze the importance of each factor, machine learning methods are considered to be useful. Objective: This study aimed to identify key factors influencing medication compliance by applying regularized logistic regression and LightGBM. Methods: A questionnaire survey was conducted among 638 adult patients in Japan who had been continuously taking medications for at least 3 months. The survey collected data on demographics, medication habits, psychological adherence factors, and compliance. Logistic regression with regularization was used to handle multicollinearity, while LightGBM was used to calculate feature importance. Results: The regularized logistic regression model identified significant predictors, including "using the drug at approximately the same time each day" (coefficient 0.479; P=.02), "taking meals at approximately the same time each day" (coefficient 0.407; P=.02), and "I would like to have my medication reduced" (coefficient -0.410; P=.01). The top 5 variables with the highest feature importance scores in the LightGBM results were "Age" (feature importance 179.1), "Using the drug at approximately the same time each day" (feature importance 148.4), "Taking meals at approximately the same time each day" (feature importance 109.0), "I would like to have my medication reduced" (feature importance 77.48), and "I think I want to take my medicine" (feature importance 70.85). Additionally, the feature importance scores for the groups of medication adherence-related factors were 77.92 for lifestyle-related items, 52.04 for awareness of medication, 20.30 for relationships with health care professionals, and 5.05 for others. Conclusions: The most significant factors for medication compliance were the consistency of medication and meal timing (mean of feature importance), followed by the number of medications and patient attitudes toward their treatment. This study is the first to use a machine learning model to calculate and compare the relative importance of factors affecting medication adherence. Our findings demonstrate that, in terms of relative importance, lifestyle habits are the most significant contributors to medication compliance among the general patient population. The findings suggest that regularization and machine learning methods, such as LightGBM, are useful for better understanding the numerous adherence factors affected by multicollinearity.

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A cross-sectional survey of hepatitis B virus screening in patients who received immunosuppressive therapy for rheumatoid arthritis in Japan

Yanagisawa Y., Imai S., Kizaki H., Hori S.

Journal of Pharmaceutical Health Care and Sciences (Journal of Pharmaceutical Health Care and Sciences) 10 ( 1 ) 18 2024.12

Research paper (scientific journal), Accepted, ISSN 2055-0294

Background: Patients with a history of hepatitis B virus (HBV) infection who are receiving immunosuppressive therapy are at risk of HBV reactivation and disease. Therefore, HBV screening is required prior to administering antirheumatic drugs with immunosuppressive effects. This study aimed to determine the status of hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), and hepatitis B surface antibody (HBsAb) screening prior to the initiation of drug therapy, including new antirheumatic drugs, in patients with rheumatoid arthritis. Methods: This retrospective cross-sectional study used data from April 2014 to August 2022 from the Japanese hospital-based administrative claims database. The inclusion criteria were rheumatoid arthritis and first prescription date of antirheumatic drugs. Results: A total of 82,282 patients with rheumatoid arthritis who were first prescribed antirheumatic drugs between April 2016 and August 2022 were included. Of the eligible patients, 9.7% (n=7,959) were screened for all HBV (HBsAg, HBsAb, and HbcAb) within 12 months prior to the date of initial prescription. The HBsAg test was performed in 30.0% (n=24,700), HBsAb test in 11.8% (n=9,717), and HBcAb test in 13.1% (n=10,824) of patients. The proportion of patients screened for HBV infection has been increasing since 2018; however, the proportion of patients screened for rheumatoid arthritis remains low. Conclusions: Our findings suggest that HBV screening may be insufficient in patients who received antirheumatic drugs. With the increasing use of new immunosuppressive antirheumatic drugs, including biological agents, healthcare providers should understand the risk of HBV reactivation and conduct appropriate screening.

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ソーシャルメディアにおける過量服薬（オーバードーズ）に関連する発信の解析

佐藤隆哉，土屋雅美，市山凜太郎，久村颯海，渡部哲，柳澤友希，西山智弘，矢田竣太郎，荒牧英治，木﨑速人，今井俊吾，堀里子

薬学雑誌 ((公社)日本薬学会) 144 ( 12 ) 1125 - 1135 2024.12

Research paper (scientific journal), Joint Work, Accepted, ISSN 0031-6903

日本での過量服薬(OD)の実態把握においてソーシャルネットワーキングサービス(SNS)の利用可能性があるかどうか検討した。Twitter APIを利用して取得した2023年1月10日～2月8日の投稿データのうち、日本語で記載され「OD」という単語を含むリツイート以外の投稿29980件を解析対象とした。解析対象のOD関連投稿に対してガイドラインに従って研究者2名がアノテーションを行った後、ラベルの一致度を確認した。さらに、自然言語処理技術を用いて、収集した投稿データのODに関する投稿を分類する分類器の構築を試みた。アノテーションの一致度に関して、全体の重みづけをした際のκ係数は0.81であった。それぞれのラベルについてκ係数を算出した結果、「ODをしている投稿」のκ係数は0.81、「ODをしていない投稿」のκ係数は0.94といずれも評価者間で高い一致度を示し、「ODをしていた投稿」のκ係数は0.33と評価者間で評価が分かれていた。「ODをしている投稿」のラベルが付与された投稿5283件に対し、医薬品名やそれに類する表現の記述が含まれる投稿は1543件であった。SNSの投摘に基づいて、受診を要さない軽症の事例やこれからODをしようとしている・過去にODをしていたとする、いわゆるODハイリスク群による投稿を精度よく抽出することが可能であった。

Association between gastroprotective agents and acute kidney injury in patients receiving non-steroidal anti-inflammatory drugs: Analysis of a Japanese hospital-based database

Mitsuboshi S., Imai S., Kizaki H., Hori S.

Pharmacotherapy 44 ( 11 ) 851 - 860 2024.11

Research paper (scientific journal), Accepted, ISSN 02770008

Introduction: The concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) and proton pump inhibitors (PPIs) potentially increases the risk of acute kidney injury (AKI). However, the risk of AKI has not been comprehensively assessed for the concomitant use of NSAIDs with gastroprotective agents such as misoprostol and PPIs. The objective of this study was to evaluate whether the use of various gastroprotective agents affects the risk of AKI in patients receiving NSAIDs. Methods: The data analyzed were obtained from the JMDC hospital-based administrative claims database between April 2014 and August 2022. Histamine-2 receptor antagonists (H2RAs) were compared with PPIs or misoprostol in patients receiving NSAIDs. The primary outcome was the incidence of AKI. The covariates considered were age and sex, admission to intensive care unit, presence of comorbidities based on the modified Charlson Comorbidity Index, and use of renin-angiotensin system inhibitors, loop diuretics, other diuretics, and lithium. AKI was identified by changes in serum creatinine. The distribution of AKI was analyzed using the log-rank test, and estimates of the incidence of AKI were compared among the groups using a Cox proportional hazards model with time-varying variables. Models were adjusted using a doubly robust method that accounts for the inverse probability of treatment weighting at baseline while adjusting for covariates. Results: After screening, 11,688 patients were eligible for inclusion (1729 for H2RAs, 368 for misoprostol, and 9591 for PPIs). AKI occurred in 0.5% of H2RA recipients and 1.1% of PPI recipients; no AKI was observed in the misoprostol group. Compared with H2RAs, the risk of AKI tended to be higher with PPIs (adjusted hazard ratio 1.83, 95% confidence interval 0.92–3.63, p = 0.08). Conclusion: Compared with H2RAs, PPIs may increase the risk of AKI in patients receiving NSAIDs, although no statistically significant difference was observed. Further research is required to assess the risk trade-off with consideration of both peptic ulcer prevention and the increased risk of AKI in patients concurrently treated with NSAIDs and H2RAs, misoprostol, or PPIs.

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Construction of a Multi-Label Classifier for Extracting Multiple Incident Factors From Medication Incident Reports in Residential Care Facilities: Natural Language Processing Approach.

Kizaki H, Satoh H, Ebara S, Watabe S, Sawada Y, Imai S, Hori S

JMIR medical informatics 12 e58141 2024.07

Research paper (scientific journal), Lead author, Corresponding author, Accepted, ISSN 2291-9694

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External Validation and Update of the Risk Prediction Model for Denosumab-Induced Hypocalcemia Developed From a Hospital-Based Administrative Database.

Ikegami K, Imai S, Yasumuro O, Tsuchiya M, Henmi N, Suzuki M, Hayashi K, Miura C, Abe H, Kizaki H, Funakoshi R, Sato Y, Hori S

JCO clinical cancer informatics (JCO clinical cancer informatics) 8 e2400078 2024.07

Research paper (scientific journal), Accepted

PURPOSE: Denosumab is used to treat patients with bone metastasis from solid tumors, but sometimes causes severe hypocalcemia, so careful clinical management is important. This study aims to externally validate our previously developed risk prediction model for denosumab-induced hypocalcemia by using data from two facilities with different characteristics in Japan and to develop an updated model with improved performance and generalizability. METHODS: In the external validation, retrospective data of Kameda General Hospital (KGH) and Miyagi Cancer Center (MCC) between June 2013 and June 2022 were used and receiver operating characteristic (ROC)-AUC was mainly evaluated. A scoring-based updated model was developed using the same data set from a hospital-based administrative database as previously employed. Selection of variables related to prediction of hypocalcemia was based on the results of external validation. RESULTS: For the external validation, data from 235 KGH patients and 224 MCC patients were collected. ROC-AUC values in the original model were 0.879 and 0.774, respectively. The updated model consisting of clinical laboratory tests (calcium, albumin, and alkaline phosphatase) afforded similar ROC-AUC values in the two facilities (KGH, 0.837; MCC, 0.856). CONCLUSION: We developed an updated risk prediction model for denosumab-induced hypocalcemia with small interfacility differences. Our results indicate the importance of using data from plural facilities with different characteristics in the external validation of generalized prediction models and may be generally relevant to the clinical application of risk prediction models. Our findings are expected to contribute to improved management of bone metastasis treatment.

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マスメディアの「医薬品」に関する報道が患者に及ぼす影響-インターネットパネルと保険薬局の来局者を対象としたアンケート調査- 医療薬学

今井俊吾;小野貴登;阿部真也;松井洸;卯田健太;佐山杏子;木﨑速人;山口浩;野村和彦;堀里子

医療薬学 50 ( 7 ) 319 - 327 2024.07

Research paper (scientific journal), Joint Work, Accepted

薬学部を有する大学を対象とした副作用報告に関連した薬学教育の実態調査

堀里子;土屋雅美;木崎速人;橋口正行;佐藤倫広;目時弘仁;小原拓;眞野成康

医薬品情報学（accepted for publication） ((一社)日本医薬品情報学会) 26 ( 3 ) 128 - 135 2024.07

Research paper (scientific journal), Joint Work, Accepted, ISSN 1345-1464

全国の大学薬学部・薬科大学77校を対象に、薬学生への副作用報告に関連する教育の現状について質問紙調査を行い、45校より回答を得た。その結果、「副作用報告制度」に関する授業は、医薬品情報学や薬事・法規など複数の授業科目を通じて、ほぼ全て(94%)の大学で実施されており、その大半が4年次(実務実習前)までに実施されていた。授業の特徴や工夫として、症例を用いた副作用の因果関係評価や副作用報告の模擬実習などが行われており、これらの授業に医療現場の薬剤師が講師として参画しているケースもみられた。副作用評価における副作用の因果関係評価や重篤度判定は、副作用報告用紙に症例ごとの評価結果を記載する上で重要であり、今回の調査では、副作用の因果関係評価に関する授業は40校(83%)、副作用の重篤度の判定基準等に関する授業は33校(69%)で実施されていたが、「副作用報告用紙への記載方法」に関する授業を実施している大学は18校(38%)に留まっていた。これらは主に、実務実習事前学習の中で、演習・実習形式で実施されていた。追加で実施した薬学の実務実習生の受け入れが年1回以上ある病院や薬局の薬剤師を対象とした調査(有効回答22名)では、副作用報告に関して「大学でどの程度学習して実習に臨んでいるのかを知りたい」といった意見や、「副作用報告の経験が少ないため指導が難しい」といった指導方法への戸惑い、薬剤師自身の副作用報告に対する研鑽が必要であるといった意見が寄せられた。

Analyzing the Impact of Drug Name Similarity on Dispensing Errors: An Examination Using a Drug Name Similarity Index

Sagawa H;Kizaki H;Yoshikawa K;Kamimura T;Suzuki S;Hayashi S;Tamaki H;Satoh H;Sawada Y;Hori S

Biol. Pharm. Bull. (accepted for publication) 47 ( 8 ) 1460 - 1466 2024.07

Research paper (scientific journal), Joint Work, Accepted, ISSN 09186158

Dispensing errors pose a significant health risk, with drug name similarity being a potential contributory factor. To determine the impact of drug name similarity on dispensing errors within clinical settings, we analyzed 563 dispensing errors at an acute hospital in Japan from April 2015 to June 2018. Drug name similarity between two drugs was classified into Name-Similar and Name-Dissimilar groups using the m2-vwhtfrag index, the value of the drug name similarity. Drug efficacy similarity was categorized into Efficacy-Same, Efficacy-Close, and Efficacy-Far. The drug name similarity and drug efficacy similarity of all possible pair combinations were obtained and similarly classified. The proportion of the number of pairs with dispensing errors per the total number of drug pairs in the hospital’s drug formulary in each category was calculated. The highest proportion of the number of pairs with dispensing errors was 36% for the Efficacy-Same and Name-Similar group, and the lowest proportion was 0.022% for the Efficacy-Far and Name-Dissimilar group. The proportion of the number of pairs with dispensing errors was significantly higher in the Name-Similar category than in the Name-Dissimilar category for all drug efficacy categories. Our results indicate that drug name similarity increases the risk of dispensing errors, and that m2-vwhtfrag is a useful indicator to assess dispensing errors in clinical practice. Such drug name and efficacy similarity evaluations can help identify factors causing dispensing errors, and predict the risk of dispensing errors for newly adopted drugs, considering the relationship with the whole drug formulary in the hospital dispensary.

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Exploring a method for extracting concerns of multiple breast cancer patients in the domain of patient narratives using BERT and its optimization by domain adaptation using masked language modeling

Watabe S;Watanabe T;Yada S;Aramaki E;Yajima H;Kizaki H;Hori S

PLOS ONE 19 ( 9 ) e0305496 2024.07

Research paper (scientific journal), Joint Work, Accepted

Narratives posted on the internet by patients contain a vast amount of information about various concerns. This study aimed to extract multiple concerns from interviews with breast cancer patients using the natural language processing (NLP) model bidirectional encoder representations from transformers (BERT). A total of 508 interview transcriptions of breast cancer patients written in Japanese were labeled with five types of concern labels: "treatment," "physical," "psychological," "work/financial," and "family/friends." The labeled texts were used to create a multi-label classifier by fine-tuning a pre-trained BERT model. Prior to fine-tuning, we also created several classifiers with domain adaptation using (1) breast cancer patients’ blog articles and (2) breast cancer patients’ interview transcriptions. The performance of the classifiers was evaluated in terms of precision through 5-fold cross-validation. The multi-label classifiers with only fine-tuning had precision values of over 0.80 for "physical" and "work/financial" out of the five concerns. On the other hand, precision for "treatment" was low at approximately 0.25. However, for the classifiers using domain adaptation, the precision of this label took a range of 0.40–0.51, with some cases improving by more than 0.2. This study showed combining domain adaptation with a multi-label classifier on target data made it possible to efficiently extract multiple concerns from interviews.

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Evaluation of Patient Outcomes after Pharmacological Intervention in Home Health Care Utilizing Pharmaceutical Care Records

柳澤友希, 横川祐希, 木﨑速人, 佐山杏子, 横山さくら, 佐々木剛, 染谷光洋, 谷口亮央, 今井俊吾, 堀里子

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan ((公社)日本薬学会) 144 ( 8 ) 839 - 845 2024.07

Research paper (scientific journal), Joint Work, Accepted, ISSN 0031-6903

薬剤服用歴(薬歴)には患者の主訴が記載されるだけでなく、薬剤師によるアセスメントが経時的に記載されることから、薬剤師の介入による患者の転帰が追跡できる可能性がある。今回、在宅患者に対し薬剤師が医師と連携して服用薬の減薬や医薬品の適正使用推進に取り組んだ事例を対象とし、経時的に記録された薬歴をもとに、薬剤師介入後のフォローアップ実施状況や患者アウトカムの変化について調査した。対象は、株式会社ナカジマ薬局において在宅医療対応件数の多い7店舗で2020年4月～2021年12月に薬歴が記録された当該患者366例とした。調査の結果、薬剤師の介入内容として最も多かったのは「症状の発生に対する介入で」あり、介入後の転帰は半数以上で症状の改善が認められていた。薬剤師の介入によって症状は安定しているが、投与継続されていた薬剤の中止や減量がなされた事例も多くあり、介入後の転帰は9割以上が症状に変化なく経過していたことから、患者の症状コントロールを保ちながら多剤併用解消の一助になっていたと考えられた。

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Concomitant use of lansoprazole and ceftriaxone is associated with an increased risk of ventricular arrhythmias and cardiac arrest in a large Japanese hospital database.

Mitsuboshi S, Imai S, Kizaki H, Hori S

The Journal of infection (Journal of Infection) 89 ( 2 ) 106202 2024.06

Research paper (scientific journal), Accepted, ISSN 0163-4453

Objectives: To determine whether concomitant use of ceftriaxone and oral or intravenous lansoprazole increases the risk of ventricular arrhythmia and cardiac arrest in the real-world setting in Japan. Methods: The data analyzed were obtained from the JMDC hospital-based administrative claims database for the period April 2014 to August 2022. Patients who received a proton pump inhibitor (PPI) while receiving ceftriaxone or sulbactam/ampicillin were identified. The frequency of ventricular arrhythmia and cardiac arrest was analyzed according to whether oral or intravenous PPI was concomitant with ceftriaxone or sulbactam/ampicillin. Estimates of the incidence of ventricular arrhythmia and cardiac arrest were then compared among the groups, using the Fine–Gray competing risk regression model. Results: The results showed that the risk of ventricular arrhythmia and cardiac arrest was significantly higher with concomitant ceftriaxone and oral lansoprazole (hazard ratio 4.57, 95% confidence interval 1.99–4.29, P < 0.01) or intravenous lansoprazole (hazard ratio 4.57, 95% confidence interval 1.24–16.80, P = 0.02) than with concomitant sulbactam/ampicillin and oral or intravenous lansoprazole. Conclusions: Oral and intravenous lansoprazole may increase the risk of ventricular arrhythmia and cardiac arrest in patients who are receiving ceftriaxone.

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病院における造影剤による即時型アレルギー対策の現状と課題　病院薬剤部門を対象とした質問紙調査

鈴木信也, 木崎速人, 上村忠聖, 男全昭紀, 今井俊吾, 堀里子

医薬品情報学 ((一社)日本医薬品情報学会) 26 ( 1 ) 19 - 27 2024.05

Research paper (scientific journal), Accepted, ISSN 1345-1464

造影剤副作用マネジメントの実態や薬剤部門が造影剤投与に関わる機会ならびに造影剤の副作用リスクに対する薬剤師の意識を調査した。医療機関マスタを用いて無作為に抽出した2000施設の病院の薬剤部門を対象にアンケートを依頼し、96施設から回答を得た。造影剤の副作用発症リスクの高い患者への対応などについて、院内で統一された内規やマニュアルがあるのは41施設(42.7%)であり、造影剤による副作用の既往を持つ患者については67施設(69.8%)が施設でとるべき対応を定めていた。薬剤部門として所属病院内で造影剤投与による副作用のリスク管理やその方法に関する議論を行っていたのは39施設(40.6%)であり、外来患者における造影剤投与時に薬剤部の介入が必要と考えるかについては45施設(46.9%)が「とてもそう思う」「ややそう思う」と回答した。「どちらともいえない」が42施設(43.8%)と同程度であり、「あまりそう思わない」「まったくそう思わない」と回答した施設もあった。

Medication incidents associated with the provision of medication assistance by non-medical care staff in residential care facilities.

Kizaki H, Yamamoto D, Maki H, Masuko K, Konishi Y, Satoh H, Hori S, Sawada Y

Drug discoveries & therapeutics 18 ( 1 ) 54 - 59 2024.03

Research paper (scientific journal), Accepted, ISSN 1881-7831

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Detection of Adverse Event Signals with Severity Grade Classification from Cancer Patient Narrative.

Nishioka S, Asano M, Yada S, Aramaki E, Yajima H, Kizaki H, Hori S

Studies in health technology and informatics 310 554 - 558 2024.01

Research paper (international conference proceedings), Accepted, ISSN 0926-9630

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Factor Analysis of Patients Who Find Tablets or Capsules Difficult to Swallow Due to Their Large Size: Using the Personal Health Record Infrastructure of Electronic Medication Notebooks

Asano M., Imai S., Shimizu Y., Kizaki H., Ito Y., Tsuchiya M., Kuriyama R., Yoshida N., Shimada M., Sando T., Ishijima T., Hori S.

Journal of Medical Internet Research (Journal of Medical Internet Research) 26 ( 1 ) e54645 2024.01

Research paper (scientific journal), Accepted, ISSN 1439-4456

Background: Understanding patient preference regarding taking tablet or capsule formulations plays a pivotal role in treatment efficacy and adherence. Therefore, these preferences should be taken into account when designing formulations and prescriptions. Objective: This study investigates the factors affecting patient preference in patients who have difficulties swallowing large tablets or capsules and aims to identify appropriate sizes for tablets and capsules. Methods: A robust data set was developed based on a questionnaire survey conducted from December 1, 2022, to December 7, 2022, using the harmo smartphone app operated by harmo Co, Ltd. The data set included patient input regarding their tablet and capsule preferences, personal health records (including dispensing history), and drug formulation information (available from package inserts). Based on the medication formulation information, 6 indices were set for each of the tablets or capsules that were considered difficult to swallow owing to their large size and concomitant tablets or capsules (used as controls). Receiver operating characteristic (ROC) analysis was used to evaluate the performance of each index. The index demonstrating the highest area under the curve of the ROC was selected as the best index to determine the tablet or capsule size that leads to swallowing difficulties. From the generated ROCs, the point with the highest discriminative performance that maximized the Youden index was identified, and the optimal threshold for each index was calculated. Multivariate logistic regression analysis was performed to identify the risk factors contributing to difficulty in swallowing oversized tablets or capsules. Additionally, decision tree analysis was performed to estimate the combined risk from several factors, using risk factors that were significant in the multivariate logistic regression analysis. Results: This study analyzed 147 large tablets or capsules and 624 control tablets or capsules. The “long diameter + short diameter + thickness” index (with a 21.5 mm threshold) was identified as the best indicator for causing swallowing difficulties in patients. The multivariate logistic regression analysis (including 132 patients with swallowing difficulties and 1283 patients without) results identified the following contributory risk factors: aged <50 years (odds ratio [OR] 1.59, 95% CI 1.03-2.44), female (OR 2.54, 95% CI 1.70-3.78), dysphagia (OR 3.54, 95% CI 2.22-5.65), and taking large tablets or capsules (OR 9.74, 95% CI 5.19-18.29). The decision tree analysis results suggested an elevated risk of swallowing difficulties for patients with taking large tablets or capsules. Conclusions: This study identified the most appropriate index and threshold for indicating that a given tablet or capsule size will cause swallowing difficulties, as well as the contributory risk factors. Although some sampling biases (eg, only including smartphone users) may exist, our results can guide the design of patient-friendly formulations and prescriptions, promoting better medication adherence.

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Exploring the factors associated with difficulties in extracting tablets or capsules from press-through-package sheets

Tsuchiya M., Imai S., Asano M., Shimizu Y., Kizaki H., Ito Y., Tsuchiya M., Kuriyama R., Yoshida N., Shimada M., Sando T., Ishijima T., Hori S.

British Journal of Clinical Pharmacology 91 ( 2 ) 479 - 484 2024

Research paper (scientific journal), Accepted, ISSN 03065251

Exploring factors related to difficulties in extracting tablets or capsules from press-through-packages is essential for optimizing the dosage form. To achieve this, the involvement of patient insight is important. In the present study, the preferences of patients regarding drugs that are difficult to extract from their packaging were collected using an electronic medication notebook (‘harmo®’) based on dispensing data. We found that approximately 30% of respondents had difficulty removing tablets or capsules from their packaging, with 125 specific drugs identified as ‘hard to push out’. Independent factors related to ‘hard-to-push-out’ drugs were female sex and feeling of weakness in the hands or fingers. Furthermore, several ‘hard-to-push-out’ drugs had characteristics such as a spherical shape or small major axis or small major axis drug-to-pocket size ratio. The findings of this study may help improve the quality of drug packaging, thus enhancing the patients' medication experience.

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Adverse Event Signal Detection Using Patients’ Concerns in Pharmaceutical Care Records: Evaluation of Deep Learning Models

Nishioka S., Satoshi W., Yanagisawa Y., Sayama K., Kizaki H., Imai S., Someya M., Taniguchi R., Yada S., Aramaki E., Hori S.

Journal of Medical Internet Research (Journal of Medical Internet Research) 26 ( 1 ) e55794 2024

Research paper (scientific journal), Accepted, ISSN 1439-4456

Background: Early detection of adverse events and their management are crucial to improving anticancer treatment outcomes, and listening to patients’ subjective opinions (patients’ voices) can make a major contribution to improving safety management. Recent progress in deep learning technologies has enabled various new approaches for the evaluation of safety-related events based on patient-generated text data, but few studies have focused on the improvement of real-time safety monitoring for individual patients. In addition, no study has yet been performed to validate deep learning models for screening patients’ narratives for clinically important adverse event signals that require medical intervention. In our previous work, novel deep learning models have been developed to detect adverse event signals for hand-foot syndrome or adverse events limiting patients’ daily lives from the authored narratives of patients with cancer, aiming ultimately to use them as safety monitoring support tools for individual patients. Objective: This study was designed to evaluate whether our deep learning models can screen clinically important adverse event signals that require intervention by health care professionals. The applicability of our deep learning models to data on patients’ concerns at pharmacies was also assessed. Methods: Pharmaceutical care records at community pharmacies were used for the evaluation of our deep learning models. The records followed the SOAP format, consisting of subjective (S), objective (O), assessment (A), and plan (P) columns. Because of the unique combination of patients’ concerns in the S column and the professional records of the pharmacists, this was considered a suitable data for the present purpose. Our deep learning models were applied to the S records of patients with cancer, and the extracted adverse event signals were assessed in relation to medical actions and prescribed drugs. Results: From 30,784 S records of 2479 patients with at least 1 prescription of anticancer drugs, our deep learning models extracted true adverse event signals with more than 80% accuracy for both hand-foot syndrome (n=152, 91%) and adverse events limiting patients’ daily lives (n=157, 80.1%). The deep learning models were also able to screen adverse event signals that require medical intervention by health care providers. The extracted adverse event signals could reflect the side effects of anticancer drugs used by the patients based on analysis of prescribed anticancer drugs. “Pain or numbness” (n=57, 36.3%), “fever” (n=46, 29.3%), and “nausea” (n=40, 25.5%) were common symptoms out of the true adverse event signals identified by the model for adverse events limiting patients’ daily lives. Conclusions: Our deep learning models were able to screen clinically important adverse event signals that require intervention for symptoms. It was also confirmed that these deep learning models could be applied to patients’ subjective information recorded in pharmaceutical care records accumulated during pharmacists’ daily work.

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Medication Management Initiatives Using Wearable Devices: Scoping Review

Iino H., Kizaki H., Imai S., Hori S.

JMIR Human Factors 11 e57652 2024

Research paper (scientific journal), Accepted

Background: Wearable devices (WDs) have evolved beyond simple fitness trackers to sophisticated health monitors capable of measuring vital signs, such as heart rate and blood oxygen levels. Their application in health care, particularly medication management, is an emerging field poised to significantly enhance patient adherence to treatment regimens. Despite their widespread use and increasing incorporation into clinical trials, a comprehensive review of WDs in terms of medication adherence has not been conducted. Objective: This study aimed to conduct a comprehensive scoping review to evaluate the impact of WDs on medication adherence across a variety of diseases, summarizing key research findings, outcomes, and challenges encountered. Methods: Adhering to PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines, a structured search was conducted across MEDLINE, Web of Science, and Embase databases, covering the literature from January 1, 2010, to September 30, 2022. The search strategy was based on terms related to WDs and medication adherence, specifically focusing on empirical studies to ensure the inclusion of original research findings. Studies were selected based on their relevance to medication adherence, usage of WDs in detecting medication-taking actions, and their role in integrated medication management systems. Results: We screened 657 articles and identified 18 articles. The identified studies demonstrated the diverse applications of WDs in enhancing medication adherence across diseases such as Parkinson disease, diabetes, and cardiovascular conditions. The geographical distribution and publication years of these studies indicate a growing interest in this research area. The studies were divided into three types: (1) studies reporting a correlation between data from WDs or their usage and medication adherence or drug usage as outcomes, (2) studies using WDs to detect the act of medication-taking itself, and (3) studies proposing an integrated medication management system that uses WDs in managing medication. Conclusions: WDs are increasingly being recognized for their potential to enhance medication management and adherence. This review underscores the need for further empirical research to validate the effectiveness of WDs in real-life settings and explore their use in predicting adherence based on activity rhythms and activities. Despite technological advancements, challenges remain regarding the integration of WDs into routine clinical practice. Future research should focus on leveraging the comprehensive data provided by WDs to develop personalized medication management strategies that can improve patient outcomes.

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Adverse event signal extraction from cancer patients’ narratives focusing on impact on their daily-life activities

Nishioka S., Asano M., Yada S., Aramaki E., Yajima H., Yanagisawa Y., Sayama K., Kizaki H., Hori S.

Scientific Reports (Scientific Reports) 13 ( 1 ) 15516 2023.12

Research paper (scientific journal), Accepted

Adverse event (AE) management is important to improve anti-cancer treatment outcomes, but it is known that some AE signals can be missed during clinical visits. In particular, AEs that affect patients’ activities of daily living (ADL) need careful monitoring as they may require immediate medical intervention. This study aimed to build deep-learning (DL) models for extracting signals of AEs limiting ADL from patients’ narratives. The data source was blog posts written in Japanese by breast cancer patients. After pre-processing and annotation for AE signals, three DL models (BERT, ELECTRA, and T5) were trained and tested in three different approaches for AE signal identification. The performances of the trained models were evaluated in terms of precision, recall, and F1 scores. From 2,272 blog posts, 191 and 702 articles were identified as describing AEs limiting ADL or not limiting ADL, respectively. Among tested DL modes and approaches, T5 showed the best F1 scores to identify articles with AE limiting ADL or all AE: 0.557 and 0.811, respectively. The most frequent AE signals were “pain or numbness”, “fatigue” and “nausea”. Our results suggest that this AE monitoring scheme focusing on patients’ ADL has potential to reinforce current AE management provided by medical staff.

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Influence of Participation in a Medical-Themed Science Café on Patient Activation

Okazawa Y., Kizaki H., Suzuki N., Osaka W., Hori S.

Patient Preference and Adherence (Patient Preference and Adherence) 17 3093 - 3106 2023.11

Research paper (scientific journal), Joint Work, Accepted, ISSN 1177-889X

Purpose: This study aims to investigate the impact of a Science Café (SC) dealing with medical topics on participants’ patient activation (PA), a concept that refers to patients’ involvement in managing their own health, working with their healthcare providers, and maintaining their health. Material and Methods: Semi-structured interviews were conducted with patients who had participated in a medical SC (n = 10) to identify the medical SC-associated factors that influenced PA. Through a questionnaire of medical SC participants (n = 23), the impact on PA and correlations with relevant psychological measures were quantitatively assessed. Results: The interviews revealed three factors: “Experience & acceptance of chronic conditions”, “Features of medical SC” and “Changes as a result of participation.” The questionnaire results showed a positive correlation between PA and resilience and a negative correlation with decision regret. Conclusions: Participation in a medical SC by people with illnesses can improve PA by improving knowledge and skills for self-management and increasing self-awareness of illness in a supportive environment. The study highlights the potential benefits of using medical SC as a strategy for healthcare providers to improve PA and health outcomes.

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Comparison of different sustained-release opioids and acute respiratory conditions in patients with cancer and chronic kidney disease

Mitsuboshi S., Imai S., Kizaki H., Hori S.

Pharmacotherapy (Pharmacotherapy) 44 ( 2 ) 122 - 130 2023.11

Research paper (scientific journal), Accepted, ISSN 02770008

Study Objective: Few data are available on the association between the use of oxycodone in patients with chronic kidney disease (CKD) and acute respiratory conditions. The aim of this study was to investigate whether oxycodone is associated with an increased risk of acute respiratory conditions in patients with cancer and CKD compared with other opioids. Design and Setting: The data were obtained from a claims database in Japan. Patients with cancer and CKD who had received sustained-release opioids, including oral oxycodone, oral morphine, or transdermal fentanyl, between April 2014 and May 2021 were selected. The primary outcome was defined as an acute respiratory condition. Data for age and sex, morphine equivalent daily dose, concomitant use of specified medications, comorbidities defined based on the modified Charlson comorbidity index, substance use disorder, and lung cancer or metastatic lung cancer were investigated as covariates. Distribution of acute respiratory conditions was compared among the three sustained-release opioid groups using the log-rank test. Estimates of the incidence of acute respiratory conditions were compared among the groups using a Cox proportional hazards model with time-varying variables. Main Results: A significant difference in the distribution of acute respiratory conditions was found among the three groups (p < 0.01). Cox regression analysis showed a significantly higher risk of acute respiratory conditions with morphine (hazard ratio [HR]: 3.04, 95% confidence interval [CI]: 1.07–8.65, p = 0.04) compared with oxycodone but no significant difference in risk with oxycodone (HR 0.67, 95% CI: 0.32–1.38, p = 0.27) compared with fentanyl. Conclusions: The findings suggest that the risk of acute respiratory conditions may be lower in patients with CKD who use oxycodone for cancer pain than in those who use morphine. Additionally, no difference in the risk of acute respiratory conditions was found between oxycodone and fentanyl use.

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Influence of Voiced and Semi-voiced Sounds on the Subjective Similarity of Different Drug Names: A Cognitive Psychological Experiment

Yoshikawa K., Kizaki H., Imai S., Hori S.

Biological and Pharmaceutical Bulletin (Biological and Pharmaceutical Bulletin) 46 ( 11 ) 1630 - 1634 2023.11

Research paper (scientific journal), Accepted, ISSN 09186158

The similarity of drug names is one of the common causes of medication error. In Japan, similarity evaluation is performed prior to approval of new drugs in order to avoid potential confusion. However, existing indices do not take account of the difference between characters that contain voiced or semi-voiced and unvoiced sounds, so it is not clear whether such sounds influence the subjective similarity of drug names. Thus, we performed a cognitive psychological experiment to investigate this issue, using participants who had not received any education in medicine, nursing, or pharmacy. An analogue scale questionnaire was used to evaluate the subjective similarity of the names of drug pairs. Drug pairs for the main analysis were prepared by matching the first 0 to 3 characters, and then varying the difference in the number of voiced and semi-voiced characters from 0 to 3 in these matched characters. By means of this procedure, the drug pairs were classified into a total of 10 groups. Then, a total of 60 drug pairs were created by assigning 6 drugs to each group. The subjective similarity tended to increase with increasing number of common characters among the first three characters. When classified according to the number of these common characters, the subjective similarity was significantly decreased when voiced or semi-voiced sounds were present, as compared with when they were absent. These results indicate that a new drug name similarity index that takes account of voiced and semi-voiced sound differences should be developed to minimize medication errors.

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A Survey of the Status of Methadone Switching in Japan Using a Hospital-Based Administrative Claims Database

Imai S., Aoki N., Ikegami K., Kizaki H., Hori S.

Journal of Clinical Pharmacology (Journal of Clinical Pharmacology) 64 ( 2 ) 189 - 195 2023.09

Research paper (scientific journal), Joint Work, Accepted, ISSN 00912700

Methadone is generally used for the management of cancer pain in patients who cannot obtain adequate analgesia from other strong opioids; however, it has a complicated and inconsistent conversion ratio from pre-switching opioid dosage to methadone. This issue may be pronounced in Japan because only oral tablets are commercially available. We aimed to elucidate the status of methadone switching in Japan, focusing on its dosage. Using a Japanese hospital-based administrative claims database, we included patients who switched to methadone between April 2008 and January 2021. The proportion of methadone switching completion that required more than the defined conversion ratio in the Japanese package insert (called “high-dose methadone switching”) was evaluated as a primary endpoint. Other endpoints included “the duration from initiation to completion of methadone switching” and “factors affecting high-dose methadone switching by using multivariate logistic regression analysis”. Of 1585 patients who received methadone, 370 were enrolled. Among those, 130 (35.1%) received high-dose methadone switching. The median duration of methadone switching completion (12 days) was longer in the high-dose methadone switching group than in other patients. Four variables were identified as factors affecting high-dose methadone switching. Younger age and outpatient status increased the risk of requiring high-dose methadone switching, whereas the concomitant use of nonsteroidal anti-inflammatory drugs and fentanyl as a pre-switching opioid decreased the risk. In conclusion, more than 30% of the patients underwent high-dose methadone switching and required long completion periods, suggesting that methadone switching remains challenging in Japan.

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Exploring Factors Affecting the Occurrence of Hypersensitivity Reactions Induced by Nonionic Iodine Contrast Media

Chatani R., Kondo S., Kamimura T., Suzuki S., Komatsubara E., Hayashi S., Hashiguchi M., Kizaki H., Imai S., Hori S.

Journal of Clinical Pharmacology (Journal of Clinical Pharmacology) 63 ( 9 ) 1002 - 1008 2023.09

Research paper (scientific journal), Accepted, ISSN 00912700

Hypersensitivity reactions induced by nonionic iodine contrast media sometimes occur and can be life threatening. However, independent factors affecting their occurrence remain to be fully established. Therefore, the purpose of this study was to clarify independent factors affecting the occurrence of hypersensitivity reactions induced by nonionic iodine contrast media. Patients who received nonionic iodine contrast media at Keiyu Hospital from April 2014 to December 2019 were included. The adjusted odds ratio (OR) and 95% confidence interval (CI) for factors affecting hypersensitivity reactions induced by contrast media were calculated by logistic regression analysis. The multiple imputation method was used to impute missing data. Hypersensitivity reactions occurred in 0.72% (163 cases) of 22,695 cases enrolled in this study. In univariate analysis, 10 variables met the criteria of P <.05 and proportion of missing data <50%. In multivariate analysis, age (OR, 0.98; 95% CI, 0.97–0.99), outpatient status (OR, 2.08; 95% CI, 1.20–3.60), contrast medium iodine content (OR, 1.02; 95% CI, 1.01–1.04), history of drug allergy (OR, 2.41; 95% CI, 1.50–3.88), and asthma (OR, 17.4; 95% CI, 7.53–40.1) were identified as independent factors affecting contrast media–induced hypersensitivity reactions. Among these factors, history of drug allergy and asthma appear to be clinically relevant and reliable due to their high OR and plausible biological mechanisms, but the other three factors require further validation.

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Detection of Vaccine Adverse Events Before Package Insert Revisions Using a Japanese Spontaneous Reporting System

Suzuki S., Imai S., Mitsuboshi S., Kizaki H., Hashiguchi M., Hori S.

Journal of Clinical Pharmacology (Journal of Clinical Pharmacology) 63 ( 8 ) 903 - 908 2023.08

Research paper (scientific journal), Accepted, ISSN 00912700

The usefulness of disproportionality analysis for the pharmacovigilance of vaccines in the Japanese Adverse Drug Event Report (JADER) database is yet to be proven. This study aimed to verify whether significant disproportionality could be detected before adding new vaccine adverse event information to package inserts. Information on package insert revisions related to vaccine adverse drug events from January 2013 to March 2023 was extracted from the Pharmaceuticals and Medical Devices Agency website. This period was set as the maximum period for which early disproportionalities could be detected by the latest JADER database (April 2004 to December 2022). From JADER data, 15 revision histories (10 types of vaccines) of package inserts were identified, and 823,662 cases were obtained. Of the 15, 12 (80%) adverse events were identified as significant disproportionalities before package insert revisions were made. Nine of the 15 (60%) events were identified as significant disproportionalities earlier than at least 12 months. These findings suggest that the JADER database may detect vaccine adverse events earlier than package insert revisions, indicating its usefulness for the safety surveillance of vaccines.

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Reply to: Comment: Detection of Vaccine Adverse Events Before Package Insert Revisions Using a Japanese Spontaneous Reporting System.

Suzuki S, Imai S, Mitsuboshi S, Kizaki H, Hashiguchi M, Hori S

Journal of clinical pharmacology 63 ( 10 ) 1171 2023.07

Research paper (scientific journal), Accepted, ISSN 0091-2700

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病院における造影剤副作用マネジメントと薬剤部門の関わり方に関する実態調査

近藤咲良, 鈴木信也, 上村忠聖, 木崎速人, 今井俊吾, 堀里子

医薬品情報学 ((一社)日本医薬品情報学会) 25 ( 1 ) 31 - 37 2023.05

Research paper (scientific journal), Accepted, ISSN 1345-1464

首都圏の急性期病院10施設の薬剤部門にアンケートを行い、「造影剤投与に関する内規やマニュアルの有無」「造影剤副作用リスク因子を有する患者への各施設の対応、薬剤部門の介入」などについて調査した。結果、内規やマニュアルの有無については、院内で統一された内規やマニュアルがあると答えたのが5施設、放射線科で統一された内規やマニュアルがあると答えたのが2施設、内規やマニュアルはないと答えたのが3施設であった。造影剤副作用リスク因子として「副作用の既往」「喘息の既往」「造影剤以外によるアナフィラキシーショックの既往」等を有する患者に対しては、半数以上の施設で取るべき対応が定められていた。薬剤部門の介入として、副作用・喘息既往や薬剤アレルギー既往の聴取が7施設で行われており、副作用予防薬の投与が内規やマニュアルで推奨されているのは4施設であった。

薬局におけるリフィル処方箋への対応に関する実態と薬剤師の意識　横断的質問紙調査

平田彩乃, 木崎速人, 矢野良太郎, 山村真一, 吉岡ゆうこ, 鈴木順子, 今井俊吾, 堀里子

医薬品情報学 ((一社)日本医薬品情報学会) 25 ( 1 ) 1 - 11 2023.05

Research paper (scientific journal), Accepted, ISSN 1345-1464

薬局団体連絡協議会の加盟団体に所属する薬剤師、および同団体に所属する薬局経営者が経営する薬局の管理薬剤師にアンケートを行い、リフィル処方箋(R処方箋)の受付状況、R処方箋応需に関する薬局の対応状況、R処方箋に対する不安などについて調査した。全国34都道府県の薬局から377件の回答が得られた。R処方箋に関する質問等を受付けたことが「ある」と答えたのは164件(44%)、R処方箋を応需したことが「ある」と答えたのは116件(31%)であった。応需したことのある薬局の対応状況(複数回答)は、患者初回来局時の対応として、「患者にR処方箋について説明する」と答えたのが98件(84%)、「次回も同じ薬局に来ることが推奨されていると伝える」が100件(86%)、「次回来局予定日を確認する」が109件(94%)、「R処方箋が適切であるか確認する」が101件(87%)などであった。R処方箋に不安が「ある」と答えた割合は回答者全体の79%(297件)であった。

薬局薬剤師による患者フォローアップの現状と課題　保険薬局を対象とした質問紙調査

川上未知, 木崎速人, 矢野良太郎, 山村真一, 吉岡ゆうこ, 鈴木順子, 宮本光雄, 藤田道男, 堀里子

医療薬学 ((一社)日本医療薬学会) 49 ( 4 ) 161 - 172 2023.04

Research paper (scientific journal), Accepted, ISSN 1346-342X

保険薬局を対象とした質問紙調査により、フォローアップに関する法施行後における患者フォローアップの実施状況を調査した。一般社団法人薬局団体連絡協議会に加盟している4団体の法人会員が運営する各薬局の管理薬剤師および同協議会に加盟している4団体の個人会員の薬剤師に調査協力依頼を送付し、318店舗の薬局から回答が得られた。患者フォローアップが義務化されて以降にフォローアップを「行ったことがある」との回答は89.0%を占めており、ほとんどのケースで事前に同意がとられていた。フォローアップの手段としてはほぼすべての薬局が電話を利用していた。医薬品適正使用に役立ったと感じたフォローアップ事例として「副作用の有無やその症状の確認」「アドヒアランス不良またはその懸念に対する薬の服用・使用の確認」「患者が抱いた薬の服用・使用に対する不安への対応」などが挙げられた。

Investigation of Prescription Status and Exploration of Risk Factors Related to Denosumab-induced Hypocalcemia in Combination Therapy with 1α,25-Dihydroxy-vitamin D3

Ikegami K, Saito M, Imai S, Kizaki H, Yasumuro O, Funakoshi R, Hori S

Biol Pharm Bull. (Biological and Pharmaceutical Bulletin) 46 ( 1 ) 95 - 101 2023.01

Research paper (scientific journal), Joint Work, Accepted, ISSN 09186158

To prevent denosumab-induced hypocalcemia in patients with renal dysfunction, combination therapy with 1α,25-dihydroxy-vitamin D3 (active vitamin D) is recommended. We previously developed a risk prediction model for hypocalcemia in patients with cholecalciferol/calcium (natural vitamin D). However, the prescription status and the risk factors of patients with active vitamin D have not been identified, so we designed this retrospective observational study using a large practice database covering June 2013 to May 2020 to analyze prescription status and risk factors. Patients were classified according to vitamin D type. After that, factors associated with development of hypocalcemia in patients with active vitamin D were explored. Univariate analysis was conducted to compare patient backgrounds between the hypocalcemia and nonhypocalcemia groups. Receiver operating characteristic analysis was conducted to evaluate the predictive potential of the extracted factors. Of the 33442 patients who received denosumab, 22347 and 3560 patients were co-administered natural and active vitamin D, respectively. Patients with active vitamin D had significantly lower renal function (estimated glomerular filtration rate (eGFR) median: 74.0 vs. 69.7 mL/min/1.73 m2), but some patients (23.6%) with sufficient renal function (eGFR _90) were also receiving active vitamin D. Of the 3560 patients with active vitamin D, non-hypocalcemia (n _ 166) and hypocalcemia (n _ 17) groups who met the study criteria were analyzed. Renal function was lower in the hypocalcemia group, and alkaline phosphatase gave the best discrimination. High aspartate aminotransferase (AST), renal dysfunction, high alkaline phosphatase (ALP), and low hemoglobin may be significant factors in risk prediction for hypocalcemia in patients with active vitamin D.

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臨床研究コーディネーターが治験における被験者ケアにおいて抱える課題の抽出　フォーカスグループインタビュー法を用いた研究

木崎速人, 角田望, 大島央子, 石崎雅人, 野呂幾久子, 飯岡緒美, 中野重行, 堀里子

臨床薬理 ((一社)日本臨床薬理学会) 53 ( 4 ) 137 - 145 2022.07

Research paper (scientific journal), Accepted, ISSN 0388-1601

Extracting Multiple Worries From Breast Cancer Patient Blogs Using Multilabel Classification With the Natural Language Processing Model Bidirectional Encoder Representations From Transformers: Infodemiology Study of Blogs.

Watanabe T, Yada S, Aramaki E, Yajima H, Kizaki H, Hori S

JMIR cancer (JMIR Cancer) 8 ( 2 ) e37840 2022.06

Research paper (scientific journal), Accepted, ISSN 2369-1999

Background: Patients with breast cancer have a variety of worries and need multifaceted information support. Their accumulated posts on social media contain rich descriptions of their daily worries concerning issues such as treatment, family, and finances. It is important to identify these issues to help patients with breast cancer to resolve their worries and obtain reliable information. Objective: This study aimed to extract and classify multiple worries from text generated by patients with breast cancer using Bidirectional Encoder Representations From Transformers (BERT), a context-aware natural language processing model. Methods: A total of 2272 blog posts by patients with breast cancer in Japan were collected. Five worry labels, “treatment,” “physical,” “psychological,” “work/financial,” and “family/friends,” were defined and assigned to each post. Multiple labels were allowed. To assess the label criteria, 50 blog posts were randomly selected and annotated by two researchers with medical knowledge. After the interannotator agreement had been assessed by means of Cohen kappa, one researcher annotated all the blogs. A multilabel classifier that simultaneously predicts five worries in a text was developed using BERT. This classifier was fine-tuned by using the posts as input and adding a classification layer to the pretrained BERT. The performance was evaluated for precision using the average of 5-fold cross-validation results. Results: Among the blog posts, 477 included “treatment,” 1138 included “physical,” 673 included “psychological,” 312 included “work/financial,” and 283 included “family/friends.” The interannotator agreement values were 0.67 for “treatment,” 0.76 for “physical,” 0.56 for “psychological,” 0.73 for “work/financial,” and 0.73 for “family/friends,” indicating a high degree of agreement. Among all blog posts, 544 contained no label, 892 contained one label, and 836 contained multiple labels. It was found that the worries varied from user to user, and the worries posted by the same user changed over time. The model performed well, though prediction performance differed for each label. The values of precision were 0.59 for “treatment,” 0.82 for “physical,” 0.64 for “psychological,” 0.67 for “work/financial,” and 0.58 for “family/friends.” The higher the interannotator agreement and the greater the number of posts, the higher the precision tended to be. Conclusions: This study showed that the BERT model can extract multiple worries from text generated from patients with breast cancer. This is the first application of a multilabel classifier using the BERT model to extract multiple worries from patient-generated text. The results will be helpful to identify breast cancer patients’ worries and give them timely social support.

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保険薬局の薬剤師によるがん薬物療法に関する疑義照会の実態調査

明貝怜美、澤井夏海、須藤洋行、佐藤宏樹、藤田行代志、三島八重子、木崎速人、堀里子、澤田康文

医薬品情報学 ((一社)日本医薬品情報学会) 24 ( 1 ) 11 - 16 2022.05

Research paper (scientific journal), Joint Work, Accepted, ISSN 1345-1464

保険薬局の薬剤師による癌薬物療法に関する疑義照会の実態を明らかにすることを目的に、癌連携拠点病院である群馬県立がんセンターの処方箋を応需している保険薬局1店が2015年1月～2018年5月末に扱っていた経口抗癌薬20剤とその支持療法に関する疑義照会がなされた事例440件を対象に検討した。その結果、薬局からの疑義照会による処方変更割合は、経口抗癌薬20剤で平均92.7%と高く、また、「未然回避」「経済的損失の軽減あるいは回避」「精神的不安の軽減あるいは回避」といった薬局プレアボイドが多く行われており、外来癌薬物療法における薬物療法適正化に大きく寄与していることが分かった。

Identification of hand-foot syndrome from cancer patients' blog posts: BERT-based deep-learning approach to detect potential adverse drug reaction symptoms.

Nishioka S, Watanabe T, Asano M, Yamamoto T, Kawakami K, Yada S, Aramaki E, Yajima H, Kizaki H, Hori S

PloS one (PLoS ONE) 17 ( 5 ) e0267901 2022.05

Research paper (scientific journal), Accepted

Early detection and management of adverse drug reactions (ADRs) is crucial for improving patients’ quality of life. Hand-foot syndrome (HFS) is one of the most problematic ADRs for cancer patients. Recently, an increasing number of patients post their daily experiences to internet community, for example in blogs, where potential ADR signals not captured through routine clinic visits can be described. Therefore, this study aimed to identify patients with potential ADRs, focusing on HFS, from internet blogs by using natural language processing (NLP) deep-learning methods. From 10,646 blog posts, written in Japanese by cancer patients, 149 HFS-positive sentences were extracted after pre-processing, annotation and scrutiny by a certified oncology pharmacist. The HFS-positive sentences described not only HFS typical expressions like “pain" or “spoon nail”, but also patient-derived unique expressions like onomatopoeic ones. The dataset was divided at a 4 to 1 ratio and used to train and evaluate three NLP deep-learning models: long short-term memory (LSTM), bidirectional LSTM and bidirectional encoder representations from transformers (BERT). The BERT model gave the best performance with precision 0.63, recall 0.82 and f1 score 0.71 in the HFS user identification task. Our results demonstrate that this NLP deep-learning model can successfully identify patients with potential HFS from blog posts, where patients’ real wordings on symptoms or impacts on their daily lives are described. Thus, it should be feasible to utilize patient-generated text data to improve ADR management for individual patients.

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Development of Risk Prediction Model for Grade 2 or Higher Hypocalcemia in Bone Metastasis Patients Treated with Denosumab plus Cholecalciferol (Vitamin D3)/Ca Supplement.

Ikegami K, Hashiguchi M, Kizaki H, Yasumuro O, Funakoshi R, Hori S

Journal of clinical pharmacology (Journal of Clinical Pharmacology) 62 ( 9 ) 1151 - 1159 2022.03

Research paper (scientific journal), Accepted, ISSN 0091-2700

Denosumab-induced hypocalcemia is sometimes severe, and although a natural vitamin D/calcium combination is used to prevent hypocalcemia, some patients rapidly develop severe hypocalcemia even under supplementation. It is clinically important to predict this risk. This study aimed to develop a risk prediction model for grade ≥2 hypocalcemia within 28 days after the first denosumab dose under natural vitamin D/calcium supplementation. Using a large database containing multicenter practice data, 2399 patients with bone metastasis who were treated with denosumab between June 2013 and May 2020 were retrospectively analyzed. Background factors in patients who developed grade ≥2 hypocalcemia within 28 days after the first denosumab dose and those who did not were compared by univariate analysis. Multivariate analysis was conducted to develop a risk prediction model. The model was evaluated for discriminant performance (receiver operating characteristic–area under the curve, sensitivity, specificity) and predictive performance (calibration slope). A total of 124 patients in the hypocalcemia group and 1191 patients in the nonhypocalcemia group were extracted. A risk prediction model consisting of sex, calcium, albumin, alkaline phosphatase, osteoporosis, breast cancer, gastric cancer, proton pump inhibitor combination, and pretreatment with zoledronic acid was developed. The receiver operating characteristic–area under the curve was 0.87. Sensitivity and specificity were 83% and 81%, respectively, and the calibration slope indicated acceptable agreement between observed and predicted risk. This model appears to be useful to predict the risk of denosumab-induced hypocalcemia and thus should be helpful for risk management of denosumab treatment in patients with bone metastases.

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Analysis of contributory factors to incidents related to medication assistance for residents taking medicines in residential care homes for the elderly: a qualitative interview survey with care home staff

Kizaki H,Yamamoto D, Satoh H, Masuko K Maki H, Konishi Y, Hori S, Sawada Y.

BMC Geriatrics (accepted for publication) (BMC Geriatrics) 22 ( 1 ) 352 2022.03

Research paper (scientific journal), Joint Work, Lead author, Accepted

Background: In Japan, staff who are not doctors or nurses can assist the elderly in residential care facilities to take their pre-packaged medicines. Therefore, there is a potential risk of incidents specific to staffs. The aim of this study was to clarify the causes of incidents related to medication assistance by staff in residential care facilities. Method: Semi-structured interviews with staff involved in medication incidents in long-term care facilities, focusing on how and why each incident happened, were conducted. The interview covered basic information about the subject and resident, the circumstances under which the incident had occurred, contributing factors, and countermeasures put in place. Verbatim transcripts of the interviews were prepared. Based on thematic analysis, codes and themes were created. Results: Twelve subjects participated in this study. All subjects were staffs (not doctors or nurses) in long-term care facilities. All incidents covered in this study were incidents in which the wrong resident was given the medication. The incidents arose because of “not following procedures”, such as lack of “self-check of residents’ faces/residents’ names/residents’ medicine envelopes” or “double-check with other staff” or “using a device for medication intake”. Contributory factors were grouped into four categories: individual resident factor items such as “decreased ability to understand their medication” or “refusal to take medicines”, individual staff factor items such as “lack of knowledge related to medication” or “mental burden” or “experience in medication assistance”, team factor items such as “failure to communicate with other staff”, work environment factor items such as “presence of other residents” or “other work besides medication assistance” or “not enough time” or “little understanding of fostering a safety culture at the facility”. Conclusion: This study identified four categories of contributory factors that may lead to incidents during medication assistance by caregivers for residents of care homes. These findings should be helpful for risk management in residential care facilities where staff usually provide medication assistance. Separation of meal times and medication assistance, and professional review to stagger the timing of administration of residents’ medication may be effective in reducing incidents.

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Latent Class Analysis of Patients’ Background Factors Affecting the Risk of Specific Adverse Drug Reactions to Dipeptidyl Peptidase 4 Inhibitors

Kaseda D, Hashiguchi M, Kizaki H, Hori S.

Int. J. Clin. Pharmacol. Ther (accepted for publication) (International Journal of Clinical Pharmacology and Therapeutics) 60 ( 8 ) 346 - 357 2022.03

Research paper (scientific journal), Joint Work, Accepted, ISSN 0946-1965

Background and purpose: Spontaneous reporting is widely used to identify adverse drug reactions (ADRs), but relatively little is known about the relationships between specific ADRs and background factors of affected patients. Here, we applied latent class analysis (LCA) to identify background factors associated with different ADRs in type 2 diabetes patients treated with dipeptidyl peptidase 4 (DPP-4) inhibitors, using the Japanese Adverse Drug Event Report (JADER) database. Materials and methods: Patients using only a DPP-4 inhibitor who encountered ADRs were selected from the JADER database up to April 2019 (N = 3,577). LCA was employed to classify these cases based on underlying diseases and lifestyle factors (alcohol, tobacco, diet, and exercise) and to identify characteristic ADRs in each class. The optimum number of classes was determined by selecting the model with the lowest value of the Bayesian information criterion (BIC). Results: A six-class model had the lowest BIC, and these classes were characterized by specific background factors and ADRs. For example, one class included diabetes complications, while another class included exercise and diet as background factors. Increased risk of a specific ADR(s), such as pancreatitis or pemphigoid, was found in each class. The nine DPP-4 inhibitors were not uniformly distributed among the classes, though individual classes included patients receiving different inhibitors. Conclusion: Our findings indicate that characteristic background factors of patients experiencing specific DPP-4 inhibitor-induced ADRs reported in the JADER database are different and can be classified by LCA. This methodology may be useful for predicting ADRs not detected during drug development.

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Telepharmacy in mountainous depopulated areas of Japan: an exploratory interview study of patients' perspectives.

Matsumoto Y, Kizaki H, Ikeda Y, Nakamura S, Kina S, Nagai T, Nasu T, Miyamoto K, Hori S

Drug discoveries & therapeutics 15 ( 6 ) 337 - 340 2022.01

Research paper (scientific journal), Accepted, ISSN 1881-7831

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Questionnaire survey investigation of the present status of dietetic consultation at community pharmacies from the perspectives of registered dietitians and pharmacists

Kizaki H., Ota T., Mashima S., Nakamura Y., Kiyokawa S., Kominato H., Satoh H., Sawada Y., Hori S.

BMC Health Services Research (BMC Health Services Research) 21 ( 1 ) 935 2021.12

Research paper (scientific journal), Lead author, Accepted

Background: Registered dietitians are rarely employed at community pharmacies in Japan, even though dietetic advice might benefit some patients. Objective: To clarify the present status of dietetic consultation provided by registered dietitians and their collaboration with pharmacists in community pharmacies. Methods: We conducted a cross-sectional questionnaire-based survey of pharmacists and registered dietitians who work in community pharmacies. The surveyed items were: frequency of dietetic consultation, awareness of one’s knowledge and ability to conduct dietetic consultation, concerns, pharmacists’ recognition of the need for nutritional support at community pharmacies, and cooperation between registered dietitians and pharmacists. Results: Sixty-six registered dietitians, 53 pharmacists in pharmacies with registered dietitians/dietitians, and 110 pharmacists in pharmacies without registered dietitians/dietitians responded. The frequency of dietetic consultation regarding obesity and hypertension was significantly higher for registered dietitians than for pharmacists. The ability to conduct dietetic consultation regarding diseases/conditions such as kidney disease not requiring dialysis, hyperuricemia, gout, obesity and hypertension was also significantly higher for dietitians than pharmacists. More than 70% of pharmacists recognized the importance of nutritional support at community pharmacies, while 56.1% of registered dietitians noted that they were not able to fully utilize their occupational abilities. Registered dietitians were divided into two groups: registered dietitians who answered that they were able to utilize their occupational abilities and those that answered they were not. The former group was more likely to ask pharmacists about patients’ medication for dietetic consultation and to be asked to provide dietetic consultation to patients. The latter group was more likely to find difficulty in scheduling dietetic consultation. Conclusion: Our results suggest that registered dietitians in community pharmacies have a greater explanatory ability than pharmacists concerning nutritional and dietary management for patients. It may be important for pharmacists to improve cooperation with registered dietitians by providing more opportunities for dietetic consultation.

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Information provision and retrieval by registered salespersons from consumers during over-the-counter drug sales – a questionnaire survey

Kizaki H., Mochizuki M., Yoshida Y., Ishikawa K., Ohishi M., Satoh H., Sawada Y., Hori S.

BMC Health Services Research (BMC Health Services Research) 21 ( 1 ) 1333 2021.12

Research paper (scientific journal), Lead author, Accepted

Background: In Japan, non-pharmacists who are accredited as registered salespersons can sell over-the-counter (OTC) drugs, and they play a very important role in supporting proper OTC drug use by consumers. The purpose of this study was to evaluate information provided to and information collected from consumers, and cooperation with pharmacists during OTC drug sales by registered salespersons, and to clarify their related concerns and behaviors. Methods: A cross-sectional questionnaire-based survey of 385 registered salespersons working at 56 drugstores throughout Japan was conducted. Based on the questionnaire survey, the frequency of information provision/collection in various categories was determined for the registered salespersons. The relation between concerns of registered salespersons relating to OTC drug sales and the frequency of information provision/collection was examined. The frequency of consultation of registered salespersons with a pharmacist was calculated for registered salespersons with/without in-store pharmacists. The χ-square test or Fisher’s exact test was performed to assess the significance of differences. Results: Two hundred and seven registered salespersons (53.7%) responded completely. A greater number of OTC drug purchasers per day was associated with a greater frequency of information provision about “side effects” and information collection about “favorite items” (alcohol, tobacco, health foods, etc.) (p < 0.05). One hundred and thirty-nine (67.2%) participants had concerns about “interactions between OTC drugs and prescription drugs”, and these concerns were related to the frequency of information provision/collection (p < 0.05). Regarding the frequency of consultation with a pharmacist, 35 of 46 participants (76.1%) working with pharmacists answered “always” or “usually”, whereas only 19 of 161 participants (11.8%) working without full-time pharmacists answered “always” or “usually”. More than half of the registered salespersons thought that cooperation with a pharmacist was necessary when they were “asked about concomitant use with prescription drugs” or “told that side effects happened.” Conclusions: The results of this study show that experienced registered salespersons selling OTC drugs are more likely to collect information from consumers and to provide information to consumers. It appears to be important for registered salespersons to cooperate with pharmacists in order to provide and collect appropriate information about concomitant medications.

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Risk factors for severe neutropenia in pancreatic cancer patients treated with gemcitabine/nab-paclitaxel combination therapy.

Ito G, Kawakami K, Aoyama T, Yokokawa T, Nakamura M, Ozaka M, Sasahira N, Hashiguchi M, Kizaki H, Hama T, Hori S

PloS one (PLoS ONE) 16 ( 7 ) e0254726 2021

Research paper (scientific journal), Accepted

Aim Combination therapy with gemcitabine and nanoparticle albumin-bound paclitaxel (nabpaclitaxel), known as GnP therapy, significantly prolongs the survival of pancreatic cancer patients compared with gemcitabine monotherapy. However, it may cause severe neutropenia, requiring discontinuation of treatment. This study aimed to clarify the risk factors for Grade 3/4 neutropenia during GnP therapy. Methods Clinical data of pancreatic cancer patients who underwent GnP therapy at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research from December 2014 to December 2016 were retrospectively collected. The relationship of Grade 3/4 neutropenia onset to laboratory values and patient background factors was investigated by multivariate logistic regression analysis. Results Clinical data of 222 patients were analyzed. Grade 3/4 neutropenia occurred in 118 patients (53.2%) in the first cycle of GnP therapy. Multivariate analysis identified low absolute neutrophil count (ANC), high total bilirubin (T-Bil), and low C-reactive protein (CRP) as risk factors for Grade 3/4 neutropenia. Age was not a risk factor. The incidence of neutropenia was 85.7% in patients with all three risk factors, but only 27.7% in patients with none of them. Conclusion Low ANC, high T-Bil, and low CRP may be risk factors for Grade 3/4 neutropenia in patients receiving GnP therapy, even if these laboratory values are within normal reference ranges. Patients with these risk factors should be carefully monitored for adverse events.

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ワークショップを用いた、介護施設における介護スタッフ・看護師・薬剤師の連携に関する問題点の抽出とその対応策の検討　介護施設入居者の適正な服薬を目指した取り組み

木崎速人, 白石朗, 鳥居雄治, 石井貴之, 馬来秀行, 三木晶子, 佐藤宏樹, 山本大輔, 小西ゆかり, 舟橋健一, 臼井順信, 堀里子, 澤田康文

医薬品情報学 ((一社)日本医薬品情報学会) 22 ( 1 ) 44 - 52 2020.05

Research paper (scientific journal), Accepted, ISSN 1345-1464

三者連携による服薬支援に関する問題点を抽出し、その対応策について検討することを目的として、介護スタッフ(CW)・看護師・薬剤師を一堂に会したワークショップ(WS)を開催した。CW 9名、看護師4名、薬剤師8名の計21名がWSに参加し、四つのグループに分けた。各グループで抽出された問題点は「服薬介助に関する問題」、「薬の知識に関する問題」、「薬の管理に関する問題」、「情報把握に関する問題」、「コミュニケーションに関する問題」、「その他の問題」に分類された。また、各グループで検討した対応策が介護施設で実施されているか調査したところ、「施設ごとに気になることはなんでも書ける連絡ノートを作成する」、「バイタル・食事・排泄・水分量のチェックシートを薬剤師に開示する」、「薬剤師とCW同士で自己紹介を行い、CWから会話のきっかけをつくる」、「特定の入居者を選び看護師、CWの連携に薬剤師が参加する」などが実践されていた。

Cell-Surface Phenol Soluble Modulins Regulate Staphylococcus aureus Colony Spreading

Hayato Kizaki, Yosuke Omae, Fumiaki Tabuchi, Yuki Saito, Kazuhisa Sekimizu, and Chikara Kaito.

PLos One 11 ( 10 ) 2016.10

Research paper (scientific journal), Lead author, Accepted

Novel Nucleoside Diphosphatase Contributes to Staphylococcus aureus Virulence.

Kenta Imae, Yuki Saito, Hayato Kizaki, Hiroki Ryuno, Han Mao, Atsushi Miyashita, Yutaka Suzuki, Kazuhisa Sekimizu, and Chikara Kaito.

The Journal of biological chemistry 291 ( 36 ) 18608 - 18619 2016.09

Research paper (scientific journal), Accepted

Body-enlarging effect of royal jelly in a non-holometabolous insect species, Gryllus bimaculatus.

Atsushi Miyashita, Hayato Kizaki, Kazuhisa Sekimizu, and Chikara Kaito.

Biology Open 5 ( 6 ) 770 - 776 2016.06

Research paper (scientific journal), Accepted

Multidrug-Resistance Transporter AbcA Secretes Staphylococcus aureus Cytolytic Toxins.

Hirono Yoshikai, Hayato Kizaki, Yuki Saito, Yosuke Omae, Kazuhisa Sekimizu, and Chikara Kaito.

The Journal of Infectious Diseases 213 ( 2 ) 295 - 304 2016.01

Research paper (scientific journal), Accepted

No Effect of Body Size on the Frequency of Calling and Courtship Song in the Two-Spotted Cricket, Gryllus bimaculatus.

Atsushi Miyashita, Hayato Kizaki, Kazuhisa Sekimizu, and Chikara Kaito.

Plos One 11 ( 1 ) 2016.01

Research paper (scientific journal), Accepted

16SrRNA methyltransferase KsgA contributes to oxidative stress resistance and virulence in Staphylococcus aureus.

Tatsuhiko Kyuma, Hayato Kizaki, Hiroki Ryuno, Kazuhisa Sekimizu, and Chikara Kaito.

Biohimie 119 166 - 174 2015.12

Research paper (scientific journal), Accepted

Primed immune responses to Gram-negative peptidoglycans confer infection resistance in silkworms.

Atsushi Miyashita, Hayato Kizaki, Kiyoshi Kawasaki, Kazuhisa Sekimizu, and Chikara Kaito.

The Journal of biological chemistry 289 ( 20 ) 14412 - 14421 2014.05

Research paper (scientific journal), Accepted

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