論文 - 河添　仁

Preventive effects of self-administered cryotherapy on paclitaxel-induced peripheral neuropathy in patients with early-stage breast cancer: a propensity score analysis

Shimanuki Y, Hashimoto H, Kawazoe H*, Uozumi R, Udagawa R, Watabe D, Nakamura T, Yamaguchi M, Terakado H

Pharmazie （Avoxa - Mediengruppe Deutscher Apotheker GmbH）  76 （ 6 ） 261 - 265 2021年06月

研究論文（学術雑誌）, 共著, 責任著者, 査読有り,  ISSN  0031-7144

　概要を見る

We hypothesized that suppression of peripheral circulation via cryotherapy may be effective in preventing paclitaxel-induced peripheral neuropathy (PIPN). Therefore, this study aimed to clarify whether self-administered cryotherapy could prevent PIPN in patients with early-stage breast cancer, using real-world data. A single-center, retrospective, observational study was conducted. Data from the electronic medical records of consecutive patients aged ≥ 20 years with early-stage breast cancer who received a regimen containing paclitaxel for 12 cycles with or without self-administered cryotherapy at the National Cancer Center Hospital from March 2018 to May 2019 were evaluated. The primary endpoint was the cumulative dose of paclitaxel until the onset of grade ≥ 2 PIPN. To compare the difference between the two groups, multivariable Cox proportional hazards models adjusted for prognostically important variables were used. Ninety Japanese patients were included in this study. The estimated incidence of grade ≥ 2 PIPN was 26.9% and 37.7% in the self-administered cryotherapy group and control group, respectively (P = 0.314). The multivariable Cox proportional hazards model showed that the self-administered cryotherapy group had a decreased risk of onset of grade ≥ 2 PIPN (hazard ratio: 0.63, 95% confidence interval: 0.25 to 1.39; P = 0.281). Sensitivity analyses using multivariable Cox proportional hazards models along with two propensity score-adjusted methods demonstrated consistent results. The findings suggest that the methods of self-administered cryotherapy may prevent PIPN and should be reinforced appropriately in clinical practice. A randomized controlled multicenter trial of self-administered cryotherapy is warranted.

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Absolute Lymphocyte Count Predicts Immune-related Adverse Events in Patients with Non-small-cell Lung Cancer Treated with Nivolumab Monotherapy: A Multicenter Retrospective Study

Egami S, Kawazoe H*, Hashimoto H, Uozumi R, Arami T, Sakiyama N, Ohe Y, Nakada H, Aomori T, Ikemura S, Fukunaga K, Yamaguchi M, Nakamura T

Frontiers in Oncology （FRONTIERS MEDIA SA）  11   618570 2021年05月

研究論文（学術雑誌）, 共著, 責任著者, 査読有り

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Background: Among patients with advanced non-small-cell lung cancer who were treated with nivolumab monotherapy, the association of peripheral blood count data (at baseline and 2 weeks after treatment initiation) with the early onset of immune-related adverse events (irAEs) and treatment efficacy has not been clearly established. This study aimed to identify peripheral blood count data that may be predictive of the development of nivolumab-induced irAEs in a real-world clinical setting.
Materials and Methods: This multicenter observational study retrospectively evaluated consecutive patients with advanced non-small-cell lung cancer undergoing nivolumab monotherapy in the second- or later-line setting between December 2015 and November 2018 at the National Cancer Center Hospital and Keio University Hospital in Japan. The primary endpoint was the association between peripheral blood count data and irAEs during the 6-week study period. Receiver operating characteristic curve and multivariable logistic regression analyses were performed.
Results: Of the 171 patients evaluated, 73 (42.7%) had ≥1 irAE during the first 6 weeks following treatment initiation. The median time to irAEs from the initiation of nivolumab was 15 (interquartile range: 13–28) days. Receiver operating characteristic curve analyses revealed that the optimal cut-off values of the absolute lymphocyte count, neutrophil-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio 2 weeks after treatment initiation for early irAE onset were 820, 4.3, and 2.2, respectively. In multivariable logistic regression analyses, absolute lymphocyte count >820 at 2 weeks after treatment initiation was significantly associated with an increased risk of early onset of any irAE. In contrast, no significant association was observed for the neutrophil-to-lymphocyte ratio (>4.3) or the lymphocyte-to-monocyte ratio (>2.2) at 2 weeks following treatment initiation.
Conclusions: The absolute lymphocyte count >820 at 2 weeks following nivolumab initiation predicts early onset of irAEs during a 6-week study period. Routinely available absolute lymphocyte count, which is measured after the initiation of nivolumab, may be useful for identifying patients at risk of early onset of irAEs.

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Low-Dose Olanzapine Plus Graniseteron and Dexamethasone for Carboplatin-Induced Nausea and Vomiting in Patients with Thoracic Malignancies: A Prospective Multicenter Phase II Trial

Sakai C, Shimokawa M, Iihara H, Fujita Y, Ikemura S, Hirose C, Kotake M, Funaguchi N, Gomyo T, Imai H, Hakamata J, Kaito D, Minato K, Arai T, Kawazoe H, Suzuki A, Ohno Y, Okura H

Oncologist （WILEY）  26 （ 6 ） e1066 - e1072 2021年04月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  10837159

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Background: Olanzapine is an inexpensive and durable agent for the treatment of chemotherapy-induced nausea and vomiting and is also superior to neurokinin-1 receptor antagonists in the control of nausea. This study aimed to investigate the efficacy and safety of a low dose of 5 mg olanzapine plus granisetron and dexamethasone for treatment of carboplatin (CBDCA)-induced nausea and vomiting in patients with thoracic malignancies.
Materials and Methods: We conducted a prospective, open-label, single-arm, multicenter, phase II trial in four centers in Japan. Registered patients were scheduled to receive area under the curve (AUC) ≥5 mg/mL per minute of CBDCA and had never received moderately to highly emetogenic chemotherapy. Patients received olanzapine 5 mg/day orally after supper for 4 days, in combination with granisetron and dexamethasone. Primary endpoint was complete response (CR; no emesis and no use of rescue medication) rate during the overall phase (0–120 hours).
Results: Between February 2018 and June 2020, 51 patients were enrolled, and 50 patients were evaluated. The CR rates in the overall (0–120 hours), acute (0–24 hours), and delayed phases (24–120 hours) were 94.0%, 100%, and 94.0%, respectively. No grade 3 or higher adverse effects of olanzapine were observed.
Conclusion: Prophylactic antiemetic therapy with a low dose of 5 mg olanzapine plus granisetron and dexamethasone showed durable efficacy with an acceptable safety profile. This three-drug combination appears to be a reasonable treatment approach in patients with thoracic malignancies receiving an AUC ≥5 mg/mL per minute of CBDCA-based regimen. Clinical trial identification number: UMIN000031267.
Implications for Practice: The results of this phase II trial indicated that the prophylactic administration of low-dose of 5 mg olanzapine combined with granisetron and dexamethasone has promising activity with acceptable safety profile in patients with thoracic malignancy receiving high-dose carboplatin chemotherapy.

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Peripheral blood biomarkers predict immune-related adverse events in non-small cell lung cancer patients treated with pembrolizumab: a multicenter retrospective study

Egami S, Kawazoe H*, Hashimoto H, Uozumi R, Arami T, Sakiyama N, Ohe Y, Nakada H, Aomori T, Ikemura S, Fukunaga K, Yamaguchi M, Nakamura T

Journal of Cancer （IVYSPRING INTERNATIONAL PUBLISHER）  12 （ 7 ） 2105 - 2112 2021年02月

研究論文（学術雑誌）, 共著, 責任著者, 査読有り,  ISSN  1837-9664

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Background: Pembrolizumab is currently the standard treatment for patients with advanced non-small cell lung cancer (NSCLC). However, the association between immune-related adverse events (irAEs) and peripheral blood cell counts remains unclear. We aimed at identifying peripheral blood cell counts that may predict the development of pembrolizumab-induced irAEs.
Methods: We retrospectively analyzed data on consecutive patients with advanced NSCLC who received pembrolizumab monotherapy as first-line or later-line therapy at the National Cancer Center Hospital and Keio University Hospital. We used data between December 2015 and November 2018. The primary endpoint was the relationship between peripheral blood cell count data and early-onset irAEs during the 6-weeks study period. Receiver operating characteristic (ROC) curve and multivariable logistic regression analyses were performed.
Results: In total, 92 patients were evaluated, of whom 45 (48.9%) had at least one irAE during the first 6-weeks after treatment initiation. The ROC curves revealed that the optimal cutoff of pretreatment absolute lymphocyte count (ALC), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) for onset of irAEs were 1459, 2.320, 1.538, and 165, respectively. Multivariable logistic regression analyses revealed that pretreatment ALC>1450 and LMR>1.6 were significantly associated with a reduced risk for onset of any irAEs, whereas pretreatment NLR>2.3 and PLR>165 were significantly associated with an increased risk.
Conclusions: The findings suggest that considering the routine availability of blood cell count data before the initiation of treatment with pembrolizumab, it may be useful in identifying early-onset irAEs during the 6-weeks study period in clinical practice.

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代表的8疾患と薬局実習が病院実習の到達度に与える影響

清宮啓介, 津田壮一郎, 池淵由香, 鈴木小夜, 地引　綾, 岩田紘樹，横山雄太, 河添　仁, 小林典子, 藤本和子, 山浦克典, 中村智徳, 村松　博, 青森　達, 望月眞弓

医療薬学 （(一社)日本医療薬学会）  46 （ 12 ） 715 - 721 2020年12月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1346-342X

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The Model Core Curriculum for Pharmacy Education (2013 version) presents eight disease areas as the minimum medical conditions that require student trainees to be continuously engaged in pharmacotherapy, during practical training at a community pharmacy followed by a hospital-based pharmacy. However, the relationship of the number of those who continuously experienced the minimum medical conditions and the outcome of rubric assessment that is newly introduced in this study remain unknown. We clarify the effect of the number of those who continuously experienced the minimum medical conditions and pharmacy training on rubric assessment using the uniquely developed “Individual Student Report Form.” Twenty inexperienced students and 21 experienced students in pharmacy practice were evaluated on the following subjects related to medication guidance: “(2)-2 Medication Order Review and Medication Therapy Management,” “(2)-4 Professional Attitudes and Behaviors of Practice, Patient Education, and Counseling,” “(3)-1 Collection of Patient Information,” “(3)-2 Management of Drug Information,” “(3)-3 Pharmaceutical Care Plans and Recommendations,” and “(3)-4 Evaluation of Effectiveness and Safety.” The number of eight disease experiences in any subjects were not shown to affect the students’ rubric evaluation. On the other hand, the pharmacy practice experiences were significantly increased in the “(3)-1 Collection of Patient Information” (partial regression coefficient B = 1.305, P = 0.044; 95％CI: 0.036-2.575). It is important to be flexible in the eight disease areas as the minimum medical conditions and to practice the problem solving of the patient with a certified pharmacist.

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医療従事者および医療系学生に対する国際ジャーナルクラブ活動とそのアウトカム

土屋雅美†, 河添　仁†, 江面美緒, 橋口宏司, 飯原大稔, 橋本浩伸

医療薬学 （(一社)日本医療薬学会）  46 （ 11 ） 664 - 671 2020年11月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1346-342X

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We developed an international journal club, using an online meeting tool, as an evidence-based medicine training program intended for healthcare professionals and students. This study aimed to evaluate the outcome of the journal club via a questionnaire survey. We administered the questionnaire to 53 healthcare professionals and students who participated in the journal club between February 2019 and April 2020. Respondents showed positive improvement scores after participating in the journal club, compared with those before, as conveyed through the use of a seven-point Likert scale. The median scores of critical thinking skills, discussion skills in English, evidence-based practice skills, and the sense of freedom to ask questions and make comments after participating in the journal club were significantly improved from 4 (interquartile range [IQR]: 2 - 5) to 5 (IQR: 4 - 6); 3 (IQR: 2 - 4) to 3 (IQR: 2 - 5); 3 (IQR: 2 - 5) to 4 (IQR: 3 - 6); and 3 (IQR: 1 - 5) to 3 (IQR: 2 - 6), respectively. Moreover, they expressed interest in the opportunity to share articles on topics of interest with other professionals from different disciplines, to exchange clinical practice ideas concerning topics of interest, and to explore differences in clinical settings between Asia and the MD Anderson Cancer Center. They also expressed great appreciation for the online meeting format, novelty, and overall qualities of the journal club. These findings suggest that an international journal club for healthcare professionals and students could be useful in an evidence-based medicine training program and communication in English.

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Patient-related Risk Factors for Nausea and Vomiting with Standard Antiemetics in Patients with Cancer Receiving Carboplatin: A Retrospective Study

Nasu I†, Shimano R†, Kawazoe H†, Nakamura T, Miura Y, Takano T, Hayashi M

Clinical Therapeutics （ELSEVIER）  42 （ 10 ） 1975 - 1982 2020年10月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0149-2918

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Purpose: This study aimed to identify patient-related risk factors for chemotherapy-induced nausea and vomiting (CINV) in patients with cancer receiving carboplatin in addition to standard antiemetics, using real-world data.
Methods: In this single-center, observational study, data from electronic medical records of consecutive patients with solid tumors who had received their first cycle of a carboplatin-based regimen and were treated with a 2- or 3-drug combination of antiemetics from January 2014 to January 2019 at Toranomon Hospital were retrospectively analyzed. The primary end point was the occurrence of a complete response (CR) within 5 days after the first cycle, which was defined as no vomiting and no use of rescue medication for CINV. A receiver operating characteristic curve, univariable, and multivariable logistic regression analyses were used.
Findings: A total of 314 patients were evaluated in this study. The proportion of patients who had a CR in the overall, acute, and delayed phases was 76.8% (n = 241), 98.7% (n = 310), and 77.4% (n = 243), respectively. Similar to univariable logistic regression analysis, multivariable logistic regression analysis revealed that age ≥70 years and total dexamethasone dose ≥14.6 mg were significantly associated with a non-CR in the overall phase, whereas female sex, history of habitual alcohol intake, and history of smoking were not associated with a non-CR in the overall phase.
Implications: Our study findings suggest that a patient age of <70 years and a total dexamethasone dose of <14.6 mg are high-risk factors for carboplatin-induced CINV.

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ヒノキ科花粉大量飛散年における2019年の花粉情報メール配信の評価

岡田啓司, 河添　仁, 高取真吾, 豊田芳彦, 清水秀樹, 宮野良隆, 難波弘行

日本花粉学会会誌 （日本花粉学会）  66 （ 1 ） 25 - 31 2020年09月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0387-1851

　概要を見る

我々は,ヒノキ科花粉の飛散が多かった2019年の,メール配信の「登録群」と「非登録群」における初期療法の実施状況と花粉症症状の評価,および登録前後のセルフメディケーションを含めた花粉症治療の患者満足度を比較検討した.花粉症症状の評価が最も高かったのは,「登録+初期療法」群であり,「登録+非初期療法」群,「非登録+初期療法」群,「非登録+非初期療法」群の順であった.さらに,セルフメディケーションを含めた花粉症治療の患者満足度も,「登録後」が「登録前」より高かった.以上より,ヒノキ科花粉飛散情報メール配信は,ヒノキ科花粉大量飛散年においても,患者の花粉回避に対する意識を高め,患者満足度の向上に寄与すると考えられる.(著者抄録)

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実務実習生の薬学専門科目に対する自己効力感は実務実習での成功体験に影響を与える

菊山史博, 鈴木小夜，地引　綾，横山雄太，河添　仁, 中村智徳

薬学雑誌 （(公社)日本薬学会）  140 （ 6 ） 799 - 808 2020年06月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0031-6903

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Pharmacy practice experience (PPE) is essential in the six-year course of pharmaceutical education in Japan. We previously found that PPE reinforced students' self-efficacy for curriculums (SECs), leading robust acquisition and reconstruction of pharmaceutical expertise. In this study, we aimed to clarify whether students' SECs affect successful experiences as enactive attainments in PPE. We distributed survey questionnaires to the fifth-year students in Keio University in 2016-2017 before and after PPE. The students made a self-assessment of their psychological state “expect to do well” on a seven-point Likert scale for each curriculum (C1 to C18), and their successful experiences were also collected from free description type questionnaire. We could follow up 139 students. The SEC scores increased from pre-PPE to post I (p<0.001) and II terms (p<0.01). The increase in SEC scores during PPE was associated with the rate of students' successful experiences in the first-term PPE (p=0.04). The path analysis revealed the following as significant predictive factors of SECs for successful experiences: basic sciences (C1, C2, C3, C4, C5, and C6) with stand-ardizing coefficient 0.35, health and environmental sciences (C11 and C12) with 0.39, and pharmaceutical sciences (C7, C8, C9, C10, C13, and C14) with −0.51. Students in the first-term PPE tended to experience successful performance in medical professions by using their pharmaceutical expertise that they had learned. In this study, for the first time, we demonstrated that Japanese students' SECs for pharmaceutical expertise affected successful experiences, leading better outcomes of PPE.

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タッチパネル式患者参画型問診票共有システムを用いた化学療法有害事象の把握と評価

中内香菜, 井門静香, 済川聡美, 河添　仁, 長谷部晋士, 朝井洋晶, 竹内一人, 松尾真由美, 薬師神芳洋

癌と化学療法 （癌と化学療法社）  47 （ 5 ） 801 - 806 2020年05月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0385-0684

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Screening for total pain and sharing of patient information including adverse events for patients receiving chemotherapy by medical staff is needed in clinical practice. We introduced a sharing system for patient-oriented outcome sheets via a touch panel at an outpatient chemotherapy clinic. This study aimed to assess whether the system contributes to the improved management of treatment-related adverse events. We retrospectively analyzed data from a total of 215 patients at Ehime University Hospital using their electronic medical records from April to August 2015. Forty of these patients had received interventions relating to treatment-related adverse events. The proportion of a total number of interventions before and after the sharing system was 42/282(14.9%)and 45/215(20.9%), respectively. The proportion of a total number of interventions at the first course of outpatient chemotherapy also increased from 9/40(22.5%)to 14/40(35%)compared with before the sharing system. The purpose of interventions were for insomnia, anorexia, and cancer-related pain, etc., listed in order of degree of frequency. These results suggest that a sharing system of patient-reported interview sheets contributes to tracking treatment -related adverse events and aids in ensuring interventions can be efficiently performed by multidisciplinary team members.

デキサメタゾン配合後における先発及び後発品のゲムシタビン注射剤の製剤学的安定性の評価

吉浦誠海, 河添　仁*, 鈴木小夜, 横山雄太, 地引　綾, 中村智徳

日本臨床腫瘍薬学会雑誌 （(一社)日本臨床腫瘍薬学会）  14 （ 4 ） 1 - 7 2020年04月

研究論文（学術雑誌）, 共著, 責任著者, 査読有り

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ゲムシタビン誘発性血管痛は末梢静脈投与で生じ、臨床上未解決のままとなっている。エピルビシンとオキサリプラチンにおける先行研究によれば、抗炎症作用とpH調整目的にデキサメタゾンがオプションとなる。本研究の目的は、先発及び後発品のゲムシタビンとデキサメタゾン配合の製剤学的安定性を調査することであった。我々はデキサメタゾン配合後の凍結乾燥製剤及び液体製剤のゲムシタビン先発及び後発品11品目の濃度、pH及び外観変化を生理食塩液及び5%ブドウ糖液希釈において24時間後まで評価した。濃度とpHはそれぞれ高速液体クロマトグラフィーとpHメータで測定した。配合液の濃度及びpHは生理食塩液及び5%ブドウ糖液希釈において24時間後まで変化しなかった。ゲムシタビンの液体製剤のpHは凍結乾燥製剤と比較して、生理食塩液及び5%ブドウ糖液希釈においてわずかに低かった。さらに、生理食塩液及び5%ブドウ糖液希釈において外観変化はなかった。これらの結果は、すべての先発及び後発品のゲムシタビンの製剤学的安定性はデキサメタゾン配合によって影響を受けなかった。本研究は、実臨床においてゲムシタビン誘発性血管痛の可能性を減らすために、先発及び後発品のゲムシタビンはデキサメタゾンと配合投与できることを示唆する。(著者抄録)

Liquid Formulation of Gemcitabine Increases Venous Pain in Patients With Cancer: A Retrospective Study

Kawazoe H, Mori N, Ido S, Uozumi R, Tsuneoka K, Takeuchi A, Matsuo M, Yamauchi M, Nakai M, Sumikawa S, Nakamura T, Yakushijin Y

Clinical Therapeutics （ELSEVIER）  42 （ 4 ） 712 - 719 2020年04月

研究論文（学術雑誌）, 共著, 筆頭著者, 査読有り

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Purpose: Venous pain induced by peripheral intravenous infusion of gemcitabine has remained an unresolved issue in clinical practice. This study aimed to identify differences between gemcitabine formulations as well as risk factors associated with gemcitabine-induced venous pain in patients with cancer.
Methods: We retrospectively analyzed data from consecutive patients with cancer who had received chemotherapy including a lyophilized or liquid formulation of gemcitabine diluted with 5% glucose solution via a peripheral vein. The study was conducted at Ehime University Hospital using electronic medical records dated between January 2015 and July 2017. The primary end point was the prevalence of venous pain at the administration site during gemcitabine infusion, classified as injection site reaction of grade ≥2 according to the Common Terminology Criteria for Adverse Events, version 4.0. A multivariate logistic regression analysis with generalized estimating equations for longitudinal data was used to identify risk factors for venous pain during all courses of gemcitabine treatment.
Findings: A total of 1150 treatment courses in 141 Japanese patients were evaluated in this study. Venous pain occurred in 115 courses (10.0%) and in 49 patients (34.8%). The multivariate logistic regression analysis with generalized estimating equations revealed that a dose increase of gemcitabine and use of the liquid formulation of gemcitabine were significantly associated with an increased risk for venous pain (dose increase, adjusted odds ratio [OR] = 1.25; 95% CI, 1.11–1.40 [P < 0.001]; and liquid formulation, adjusted OR = 12.43, 95% CI, 5.61–27.51 [P < 0.001]), whereas age, course number of gemcitabine, and use of the soft-back product of 5% glucose solution were significantly associated with a reduced risk for venous pain (age, adjusted OR = 0.75; 95% CI, 0.57–0.98 [P = 0.037]; course number, adjusted OR = 0.96; 95% CI, 0.92–0.99 [P = 0.023]; and soft back, adjusted OR = 0.39; 95% CI, 0.21–0.74 [P = 0.004]).
Implications: The use of the liquid formulation of gemcitabine was associated with a significant increase in the frequency of gemcitabine-induced venous pain despite dilution with 5% glucose solution compared to that with the lyophilized formulation. The lyophilized formulation of gemcitabine should hence be used in peripheral intravenous infusion for the treatment of patients with cancer.

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A Nationwide, Multicenter Registry Study of Antiemesis for Carboplatin-Based Chemotherapy-Induced Nausea and Vomiting in Japan

Iihara H, Shimokawa M, Hayashi T, Kawazoe H, Saeki T, Aiba K, Tamura K.

Oncologist （WILEY）  25 （ 2 ） e373 - e380 2020年02月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  10837159

　概要を見る

© 2019 The Authors. The Oncologist published by Wiley Periodicals, Inc. on behalf of AlphaMed Press. Background: We previously reported the results of a prospective study of chemotherapy-induced nausea and vomiting (CINV) in a cohort of patients who received carboplatin-based chemotherapy and were selected from a nationwide registry of those scheduled for moderately (MEC) or highly emetogenic chemotherapy (HEC) by the CINV Study Group of Japan. Of 1,910 previously registered patients (HEC: 1,195; MEC: 715), 400 patients received carboplatin-based chemotherapy. The frequency of CINV was determined, and the risk factors for CINV were assessed. Materials and Methods: CINV data were collected from 7-day diaries. Risk factors for CINV were identified using logistic regression models. Results: Of 400 patients scheduled for carboplatin-based chemotherapy, 267 patients received two antiemetics (5-hydroxytryptamine-3 receptor antagonist [5-HT3 RA] and dexamethasone [DEX]), 118 patients received three antiemetics (5-HT3 RA, DEX, and neurokinin-1 receptor antagonist [NK1 RA]), and 15 were nonadherent to the treatment. In these patients, the CINV overall, acute, and delayed phase rates of complete response (CR), defined as no vomiting with no rescue medication, were 67.0%, 98.2%, and 67.5%, respectively. The rates of no nausea were 55.6%, 94.0%, and 56.1%, respectively, and those of no vomiting were 81.3%, 99.0%, and 81.8%, respectively. Older age was associated with a decreased non-CR, whereas female sex, history of pregnancy-related emesis, and dual antiemetic therapy were associated with an increased non-CR during the overall period. Conclusion: In a clinical practice setting, in patients who received carboplatin-based chemotherapy, adherence is quite high and appropriate antiemetic prophylaxis requires a triple antiemetic regimen including NK1 RA. Implications for Practice: For patients receiving carboplatin-based chemotherapy, triple antiemetic therapy with 5-hydroxytryptamine-3 receptor antagonist, dexamethasone, and neurokinin-1 receptor antagonist should be given prophylactically regardless of risk factor status.

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外来がん化学療法患者に対する診察後から診察前への薬剤師面談の変更とその効果

芳野知栄, 田坂友紀, 小池香苗, 矢野安樹子, 白石沙弥, 河添　仁, 山本祐司, 井門敬子, 田中　守, 飛鷹範明, 田中亮裕, 渡部祐司, 荒木博陽

日本臨床腫瘍薬学会雑誌 （(一社)日本臨床腫瘍薬学会）  10 （ 4 ） 1 - 7 2019年04月

研究論文（学術雑誌）, 共著, 査読有り

　概要を見る

愛媛大学医学部附属病院では、2016年6月より消化管・腫瘍外科の外来がん化学療法施行患者を対象に、薬剤師による面談を診察後から前へ変更した。そこで、診察前面談の有用性を評価し、改善点を明らかにすることを目的に変更前後6ヵ月間(前:2015年12月〜2016年5月、後:2016年7月〜12月)を比較検討した。変更前は延べ84名中47名、変更後は延べ139名中70名に面談を実施した。提案割合は変更前(23.4%、11/47名)と比較して変更後(40.0%、28/70名)で増加し、医師に当日採択された割合も変更後有意に上昇した(診察後面談:54.5%、6/11件vs診察前面談:100.0%、39/39件、p<0.001)。また、医師へのインタビューからも薬剤師の診察前面談内容が医師の診察時に共有されることで医師の業務負担軽減にも繋がり、患者の安全な薬物療法遂行に早期から貢献できていることが考えられた。(著者抄録)

改訂薬学教育モデル・コアカリキュラムに準拠した実務実習に向けたルーブリック形式の概略評価を用いたパフォーマンス評価の先行導入：学生視点に基づくアウトカム評価と教育効果向上のための提案

鈴木小夜†, 河添　仁†, 地引　綾, 横山雄太, 中村智徳

医療薬学 （(一社)日本医療薬学会）  45 （ 4 ） 228 - 239 2019年04月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  1346-342X

　概要を見る

To prepare for a new practical training scheme starting in 2019 based on a revised-model core curriculum for pharmaceutical education that incorporates outcome-based education, rubric-based assessment of student performance was implemented in practical training between May and July of 2018. The goals were to evaluate the rubric-based assessment to identify ways to improve it for appraising pharmaceutical students. All fifth-year students of the Keio University Faculty of Pharmacy in 2018 (n = 160) self-assessed their performance during practical training using evaluation sheets in a rubric form comprising three general instructional objectives with 10 task descriptions developed by the Japanese Pharmaceutical Association or Japanese Society of Hospital Pharmacists. Compared to the commencement of the training, the median evaluations in all tasks significantly increased at the completion of the practical training in the community pharmacy and the hospital settings. Survey questionnaires were administered to the students after the practical training. Customer satisfaction analysis identified two main areas for improvement of the rubric-based assessment for student growth: (1) students' lack of understanding of the rubric-based assessment in hospitals and (2) mentors' lack of understanding of it in both settings. The results suggest that rubric-based assessment is a feasible method for assessing pharmaceutical student performance during practical training. Additionally, the Faculty of Pharmacy should provide and disseminate information to students and mentors about rubric-based assessment and support mentors' efforts for student progress during practical training.

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Impact of e-mail-delivered Cupressaceae pollen dispersal data on prophylactic treatment and patient satisfaction

Okada K, Takatori S, Kawazoe H, Toyota Y, Ishida N, Shimizu H, Obana E, Kashiwagi S, Miyano Y, Namba H

Japanese Journal of Palynology （The Palynological Society of Japan）  64 （ 2 ） 55 - 62 2019年03月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  0387-1851

Association Between Immune-Related Adverse Events and Clinical Efficacy in Patients with Melanoma Treated With Nivolumab: A Multicenter Retrospective Study

Okada N, Kawazoe H, Takechi K, Matsudate Y, Utsunomiya R, Zamami Y, Goda M, Imanishi M, Chuma M, Hidaka N, Sayama K, Kubo Y, Tanaka A, Ishizawa K.

Clinical Therapeutics （ELSEVIER）  41 （ 1 ） 59 - 67 2019年01月

研究論文（学術雑誌）, 共著, 査読有り,  ISSN  01492918

　概要を見る

© 2018 Elsevier Inc. Purpose: Nivolumab, an anti–programmed death 1 antibody, produces antitumor effects by activating host immunity, which also causes immune-related adverse events (irAEs). The aim of this study was to analyze the association between antitumor effect and irAEs induced by nivolumab in patients with melanoma. Methods: Fifteen patients with melanoma who had received nivolumab at Tokushima University Hospital or Ehime University Hospital between January 2015 and December 2016 were enrolled in this study. Patients who had and did not have irAEs during nivolumab treatment were classified into an irAEs-positive group (n = 8) and an irAEs-negative group (n = 7), respectively. We compared the disease control rate (DCR) and overall survival (OS) between the 2 groups. Data on blood cell counts were also analyzed. Findings: After a median of 4 cycles of nivolumab treatment, irAEs occurred. The DCRs were 75% and 14% in the irAEs-positive and irAEs-negative groups, respectively (p < 0.05). OS in the irAEs-positive group was higher than that in the irAEs-negative group (p < 0.05). Multivariable Cox proportional hazards regression analysis revealed that irAE occurrence affected OS with nivolumab treatment. Moreover, the increase in baseline peripheral lymphocyte count at the time of onset of irAEs was significantly greater in the irAEs-positive group than in the irAEs-negative group after 4 cycles of nivolumab treatment (p < 0.05). Implications: Our study indicated that clinical response with nivolumab treatment improves with irAE occurrence in patients with melanoma. Moreover, the early increase in peripheral lymphocyte count may act as a biomarker for predicting the occurrence of irAEs induced by nivolumab.

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Patient-related Risk Factors for Nausea and Vomiting with Standard Antiemetics in Patients with Breast Cancer Receiving Anthracycline-based Chemotherapy: A Retrospective Observational Study

Kawazoe H, Murakami A, Yamashita M, Nishiyama K, Kobayashi-Taguchi K, Komatsu S, Aoki R, Kusakabe E, Yamasawa H, Yakushijin Y, Nakamura T, Kamei Y.

Clinical Therapeutics （ELSEVIER）  40 （ 12 ） 2170 - 2179 2018年12月

研究論文（学術雑誌）, 共著, 筆頭著者, 査読有り,  ISSN  01492918

　概要を見る

© 2018 Elsevier Inc. Purpose: The aim of this study was to identify a high-risk or low-risk population for chemotherapy-induced nausea and vomiting among patients with breast cancer treated with a current standard 3-drug antiemetic regimen and receiving anthracycline. Methods: We analyzed data from chemotherapy-naive Japanese patients with breast cancer, who had received the first cycle of anthracycline-based regimen and were treated with a 3-drug combination of aprepitant, palonosetron, and dexamethasone. This study was carried out at Ehime University Hospital (Toon, Japan) using electronic medical records from May 2011 to June 2017. The primary end point was complete response (CR), which was defined as no emesis and no use of rescue medication. Findings: A total of 103 patients were included in this study. The percentages of patients who had a CR in the overall, acute, and delayed phases were 35.0%, 40.8%, and 50.5%, respectively. Multivariate logistic regression analysis revealed that age <55 years and body mass index <27.5 kg/m2 were significantly associated with an increased risk for CR failure in the overall and acute phases. In contrast, a history of alcohol habit was significantly associated with a decreased risk for CR failure in overall phase. Implications: The present findings suggest that, among patients with breast cancer receiving anthracycline and treated with aprepitant, palonosetron, and dexamethasone, patients younger than 55 years and having a body mass index <27.5 kg/m2 are high-risk populations for chemotherapy-induced nausea and vomiting, whereas those with a history of habitual alcohol consumption is a low-risk one.

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Olanzapine plus aprepitant, palonosetron, and dexamethasone for nausea and vomiting in patients with breast cancer receiving anthracycline: A retrospective study

Kawazoe H, Uozumi R, Murakami A, Yamashita M, Kobayashi-Taguchi K, Kusakabe E, Yamasawa H, Yakushijin Y, Nakamura T, Kamei Y.

Scientific Reports （NATURE PORTFOLIO）  8   16232 2018年11月

研究論文（学術雑誌）, 共著, 筆頭著者, 査読有り

　概要を見る

© 2018, The Author(s). This study aimed to compare the antiemetic efficacy and safety of a four-drug combination with those of a standard three-drug combination in Japanese patients with breast cancer treated with anthracycline. We retrospectively analyzed data from Japanese patients with breast cancer, who had received their first cycle of anthracycline and were treated with aprepitant, palonosetron, and dexamethasone with or without olanzapine. This retrospective observational study was performed at Ehime University Hospital using the electronic medical records. Multivariable and propensity score-adjusted analyses were performed to compare the onset of complete response (CR) failure between the groups. One-hundred and thirty patients were included in this study and the four- and three-drug group had 22 and 108 patients, respectively. Similar to multivariable logistic regression analysis, propensity-adjusted logistic regression analysis revealed that the four-drug group was markedly associated with a decreased odds of CR failure in the overall, acute, and delayed phases (odds ratio [OR]: 0.27, 95% confidence interval [CI]: 0.10–0.73; OR: 0.28, 95% CI: 0.10–0.76; and OR: 0.15, 95% CI: 0.04–0.57, respectively). Additionally, treatment-related adverse events were well tolerated in both the groups. These findings suggest that the antiemetic efficacy of the four-drug combination is superior to that of the standard three-drug combination.

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改訂薬学教育モデル・コアカリキュラムに向けた外来化学療法室実習プログラムに対する実習生からのフィードバック評価

白石沙弥, 河添　仁, 矢野安樹子, 済川聡美, 安永大輝, 飛鷹範明, 井門敬子, 田中　守, 田中亮裕, 荒木博陽

愛媛県病薬会誌 （(一社)愛媛県病院薬剤師会）  124 （ 2 ） 5 - 12 2018年09月

研究論文（学術雑誌）, 共著, 査読有り