Papers - Kizaki, Hayato

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

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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

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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

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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

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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

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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

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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

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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

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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

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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

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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