研究者詳細 - 木崎　速人

論文 - 木崎　速人

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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年04月

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年03月

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年03月

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年03月

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年02月

研究論文（学術雑誌）, 査読有り, 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年02月

研究論文（学術雑誌）, 査読有り, 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年01月

研究論文（学術雑誌）, 共著, 査読有り, ISSN 1346-342X

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.

Journal of Cancer 16 （ 5 ） 1413 - 1419 2025年01月

研究論文（学術雑誌）, 共著, 査読有り, 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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診療情報データベースを用いた非小細胞肺がん患者に対するペメトレキセド含有化学療法における血液毒性へのメトホルミン併用の影響評価

早船真弘, 今井俊吾, 木﨑速人, 土屋雅美, 堀里子

薬学雑誌（(公社)日本薬学会） 145 （ 1 ） 61 - 70 2025年

研究論文（学術雑誌）, 査読有り, 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年

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年12月

研究論文（学術雑誌）, 査読有り

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年12月

研究論文（学術雑誌）, 査読有り, 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年12月

研究論文（学術雑誌）, 共著, 査読有り, 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年11月

研究論文（学術雑誌）, 査読有り, 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年07月

研究論文（学術雑誌）, 筆頭著者, 責任著者, 査読有り, 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年07月

研究論文（学術雑誌）, 査読有り

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年07月

研究論文（学術雑誌）, 共著, 査読有り

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年07月

研究論文（学術雑誌）, 共著, 査読有り, 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.

Biological and Pharmaceutical Bulletin 47 （ 8 ） 1460 - 1466 2024年07月

研究論文（学術雑誌）, 共著, 査読有り, 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年07月

研究論文（学術雑誌）, 共著, 査読有り

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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