Papers - Imai, Shungo

A Novel Approach to Analyze the Factors Affecting Adverse Drug Reactions by Combination of Electronic Medical Record Database and Machine Learning Method

Shungo Imai

Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan 143 ( 6 ) 485 - 489 2023.06

Research paper (conference, symposium, etc.), Single Work, Lead author, Last author, Corresponding author

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Detection of vaccine adverse events before package insert revisions using a Japanese spontaneous reporting system

Shimon Suzuki, Shungo Imai, Satoru Mitsuboshi, Hayato Kizaki, Masayuki Hashiguchi, Satoko Hori

The Journal of Clinical Pharmacology 63 ( 8 ) 903 - 908 2023.05

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

Exploring factors affecting the occurrence of hypersensitivity reactions induced by nonionic iodine contrast media

Ryouichi Chatani, Sakura Kondo, Tadamasa Kamimura, Shinya Suzuki, Eriko Komatsubara, Seiichi Hayashi, Masayuki Hashiguchi, Hayato Kizaki, Shungo Imai, Satoko Hori

The Journal of Clinical Pharmacology 63 ( 9 ) 1002 - 1008 2023.04

Research paper (scientific journal), Joint Work, Accepted

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Onset timing and duration of augmented renal clearance in a mixed intensive care unit

Ryusei Mikami, Mineji Hayakawa, Shungo Imai, Mitsuru Sugawara, Yoh Takekuma

Journal of Intensive Care 11 ( 1 ) 13 - 13 2023.03

Research paper (scientific journal), Joint Work, Accepted

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Dysautonomia associated with immune checkpoint inhibitors

Toshiki Tezuka, Shinichi Okuzumi, Chiho Nakajima, Toshihiro Ide, Shungo Imai, Satoru Mitsuboshi, Yuki Kuwahara, Tsubasa Takizawa, Morinobu Seki, Naoto Minematsu, Naoko Aragane, Jin Nakahara, Satoko Hori, Shunya Nakane, Shigeaki Suzuki

Journal of Neurology 270 ( 7 ) 3413 - 3423 2023.03

Research paper (scientific journal), Joint Work, Accepted

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Usefulness of the Albumin–Bilirubin Score in Determining the Initial Dose of Voriconazole for Patients with Liver Cirrhosis

Shunsuke Nashimoto, Shungo Imai, Mitsuru Sugawara, Yoh Takekuma

Biological and Pharmaceutical Bulletin 46 ( 2 ) 230 - 236 2023.02

Research paper (scientific journal), Joint Work, Accepted

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Increased risk of Lambert-Eaton myasthenic syndrome (LEMS) in small cell lung cancer patients treated with immune checkpoint inhibitor

Shungo Imai, Satoru Mitsuboshi, Satoko Hori, Shigeaki Suzuki

European Journal of Cancer 180   1 - 3 2023.02

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

Use of Japanese big data from electronic medical records to investigate risk factors and identify their high-risk combinations for linezolid-induced thrombocytopenia

Yuki Inoue, Yoh Takekuma, Takayuki Miyai, Hitoshi Kashiwagi, Yuki Sato, Mitsuru Sugawara, Shungo Imai

European journal of clinical pharmacology 79 ( 3 ) 415 - 425 2023.01

Research paper (scientific journal), Joint Work, Last author, Corresponding author, Accepted

Prediction and Implications of Edoxaban-Associated Bleeding in Patients after Critical Illness

Ryusei Mikami, Mineji Hayakawa, Shungo Imai, Kunihiko Maekawa, Kojiro Yamazaki, Mitsuru Sugawara, Yoh Takekuma

Journal of Clinical Medicine 12 ( 3 ) 860 2023.01

Research paper (scientific journal), Accepted

病院における造影剤副作用マネジメントと薬剤部門の関わり方に関する実態調査

近藤咲良，鈴木信也，上村忠聖，木﨑速人，今井俊吾，堀　里子

医薬品情報学 25 ( 1 ) 31 - 37 2023.01

Research paper (scientific journal), Joint Work, Accepted

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

平田彩乃，木﨑速人，矢野良太郎，山村真一，吉岡ゆうこ，鈴木順子，今井俊吾，堀　里子

医薬品情報学 25 ( 1 ) 1 - 11 2023.01

Research paper (scientific journal), Joint Work, Accepted

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

Keisuke Ikegami, Megumi Saito, Shungo Imai, Hayato Kizaki, Osamu Yasumuro, Ryohkan Funakoshi, Satoko Hori

Biological and Pharmaceutical Bulletin 46 ( 1 ) 95 - 101 2023.01

Research paper (scientific journal), Joint Work, Accepted

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Hepatic drug metabolism in older people with body composition changes.

Soyoko Kaburaki, Eri Yoshimura, Yasushi Miyamoto, Shungo Imai, Hitoshi Kashiwagi, Hidefumi Ueno, Mitsuru Sugawara, Yoh Takekuma

Geriatrics & gerontology international (Wiley)  22 ( 5 ) 449 - 454 2022.03

Research paper (scientific journal), Joint Work, Accepted,  ISSN  1444-1586

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AIM: Dosage adjustment is essential in older individuals because they are prone to experience a decline in liver function and changes in body composition. However, quantitative tests or equations for evaluating the activity of hepatic drug metabolism have not yet been clearly established. We examined hepatic drug metabolism activities in older individuals, focusing on changes in body composition parameters. METHODS: Lansoprazole and nifedipine, substrates of the metabolic enzymes cytochrome P450 (CYP) 2C19 and 3A4, respectively, were selected to study hepatic drug metabolism. Residual samples from blood test for older patients were evaluated to determine drug metabolism. The body composition of relevant patients was determined by analyzing characteristic parameters of skeletal muscle mass index (SMI), handgrip strength (HGS) and hepatic steatosis index (HSI). The differences in hepatic drug metabolism were studied statistically among categories in terms of the cut-off value of these parameters. RESULTS: Older male patients receiving lansoprazole and nifedipine in the low SMI (<7.0 kg/m2 ) category showed an 85-90% reduction in respective CYP2C19 and CYP3A4 metabolic activities compared with the normal SMI category. For the female patients, CYP2C19 and CYP3A4 metabolic activities showed no significant correlation with SMI and HGS. Fatty liver disease (HSI ≥36) was found to reduce CYP2C19 metabolic activity particularly in older female patients. CONCLUSIONS: Low CYP2C19 metabolic activity was statistically correlated with low SMI in male patients and high HSI in female patients, whereas low CYP3A4 metabolic activity was statistically correlated with low HGS in male patients.

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Using Japanese big data to investigate novel factors and their high-risk combinations that affect vancomycin-induced nephrotoxicity.

Shungo Imai, Shota Kadomura, Takayuki Miyai, Hitoshi Kashiwagi, Yuki Sato, Mitsuru Sugawara, Yoh Takekuma

British journal of clinical pharmacology 88 ( 7 ) 3241 - 3255 2022.02

Research paper (scientific journal), Lead author, Corresponding author, Accepted

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AIMS: Several factors related to vancomycin-induced nephrotoxicity (VIN) have not yet been clarified. In the present study, we used Japanese big data to investigate novel factors and their high-risk combinations that influence VIN. METHODS: We employed a large Japanese electronic medical record database and included patients who had been administered intravenous vancomycin between June 2000 and December 2020. VIN was defined as an increase in serum creatinine ≥0.5 mg/dL or 1.5-fold higher than the baseline. The outcomes were: (1) factors affecting VIN that were identified using multiple logistic regression analysis, and (2) combinations of factors that affect the risk of VIN according to a decision tree analysis, which is a typical machine learning method. RESULTS: Of the 7,306 patients that were enrolled, VIN occurred in 14.2% of them (1,035). A multivariate analysis extracted 22 variables as independent factors. Concomitant ramelteon use (odds ratio; 0.701, 95% confidence interval; 0.512-0.959), ward pharmacy service (0.741, 0.638-0.861), duration of VCM <7 days (0.748, 0.623-0.899) and trough concentrations 10-15 mg/L (0.668, 0.556-0.802) reduce the risk of VIN. Meanwhile, concomitant piperacillin-tazobactam use (2.056, 1.754-2.409) and piperacillin use (2.868, 1.298-6.338) increase the risk. The decision tree analysis showed that a combination of vancomycin trough concentrations ≥20 mg/L and concomitant piperacillin-tazobactam use was associated with the highest risk. CONCLUSIONS: We revealed that the concomitant ramelteon use and ward pharmacy service may decrease the risk of VIN, while the concomitant use of not only piperacillin-tazobactam but also piperacillin may increase the risk.

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Clinical applicability of urinary creatinine clearance for determining the initial dose of vancomycin in critically ill patients.

Ryusei Mikami, Shungo Imai, Mineji Hayakawa, Mitsuru Sugawara, Yoh Takekuma

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 28 ( 2 ) 199 - 205 2022.02

Research paper (scientific journal), Accepted

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INTRODUCTION: The purpose of this study was to evaluate the clinical applicability of urinary creatinine clearance (CrCl) for determining the initial dose of vancomycin (VCM) in critically ill patients and to assess VCM trough plasma concentration/maintenance daily dose (C/D) ratio in patients with augmented renal clearance (ARC). METHODS: As the primary outcome measure, correlations between estimated renal function and the VCM C/D ratio were compared using the following formulas: CrCl, Cockcroft-Gault equation (eCrClC-G) and KineticGFR equation (KeGFR). Patients were divided into those with or without changes in renal function. The patients were further classified based on the presence or absence of ARC. The secondary outcome was the comparison of VCM C/D ratio between ARC and Non-ARC patients. RESULTS: A total of 65 patients were enrolled for analysis. In all groups, CrCl tended to correlate better with the VCM C/D ratio than eCrClC-G and KeGFR. A significantly lower VCM C/D ratio was observed in patients with persistent ARC than in the Non-ARC group (0.24 versus 0.52 kg/L). CONCLUSIONS: The clinical applicability of CrCl for the initial dosing design of VCM in critically ill patients was shown. Furthermore, the results indicated that patients with persistent ARC required a higher VCM dose than Non-ARC patients. Although our findings are limited, they have a value for further verification.

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Investigation of the risk factors of vomiting during linezolid therapy: a retrospective observational study.

Takezo Tsutsumi, Shungo Imai, Hitoshi Kashiwagi, Yuki Sato, Mitsuru Sugawara, Yoh Takekuma

European journal of clinical pharmacology (Springer Science and Business Media LLC)  78 ( 2 ) 279 - 286 2022.02

Research paper (scientific journal), Accepted,  ISSN  0031-6970

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PURPOSE: Some clinical studies have reported the occurrence of nausea and vomiting with linezolid (LZD) administration. However, no studies have evaluated nausea and vomiting as primary endpoints. In a previous study, we noted a possible relationship between LZD and vomiting, but risk factors were not identified. Therefore, the aim of the present study was to identify them. METHODS: Patients who received LZD 600 mg twice daily at Hokkaido University Hospital from September 2008 to April 2019 were enrolled in this retrospective observational study. Patient characteristics, concomitant medications, laboratory data, and the occurrence of vomiting were obtained from electronic medical records. Logistic regression analysis was performed to identify risk factors for vomiting, including age, sex, body weight, concomitant medications, and surgeries. RESULTS: A total of 496 patients were included in this study, of which 90 experienced vomiting. By multivariate logistic regression analysis, female sex (adjusted odds ratio [aOR], 2.69; 95% confidence interval [CI], 1.62-4.47), ≥ 10 days of LZD administration (aOR, 2.57; CI, 1.46-4.50), and hyponatraemia (aOR, 2.96; CI, 1.72-5.10) were identified as independent risk factors for vomiting; administration of serotonergic agents (aOR, 0.23; CI, 0.07-0.82) was negatively associated. CONCLUSIONS: This study is the first to successfully identify risk factors for LZD-induced vomiting. Careful monitoring of patients with these risk factors may lead to safer and sustainable LZD administration.

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Prescription and Therapeutic Drug Monitoring Status of Valproic Acid among Patients Receiving Carbapenem Antibiotics: A Preliminary Survey Using a Japanese Claims Database

Shungo Imai, Kenji Momo, Hitoshi Kashiwagi, Yuki Sato, Takayuki Miyai, Mitsuru Sugawara, Yoh Takekuma

Annals of Clinical Epidemiology (Society for Clinical Epidemiology)  4 ( 1 ) 6 - 10 2022.01

Research paper (scientific journal), Lead author, Accepted

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Evaluation of the strategies to reduce third-generation oral cephalosporins in dentistry at a Japanese academic hospital: An interrupted time series analysis

Akira Yamagami, Katsuya Narumi, Yoshitaka Saito, Ayako Furugen, Shungo Imai, Yoshimasa Kitagawa, Yoichi Ohiro, Ryo Takagi, Yoh Takekuma, Mitsuru Sugawara, Masaki Kobayashi

Journal of Clinical Pharmacy and Therapeutics 47 ( 7 ) 1010 - 1019 2022

Research paper (scientific journal), Accepted

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WHAT IS KNOWN AND OBJECTIVE: Third-generation oral cephalosporins, especially cefcapene-pivoxil (CFPN-PI), have been used frequently in the Japanese dental field. In December 2014 and April 2016, the newly published clinical guidelines recommended the use of amoxicillin (AMPC). Thus, it is important to evaluate the impact of these guidelines on the prescription profiles of prophylactic antibiotics, clinical outcomes and cost-effectiveness of antibiotics. METHODS: We conducted a retrospective study to analyse an interrupted time series analysis from April 2013 to March 2020 at the Department of Dentistry of Hokkaido University Hospital. A segmented regression model was used to estimate the changes in the incidence of infectious complications following tooth extraction. Prescribed antibiotic data were evaluated via days of therapy (DOT). Antibiotic costs were calculated in terms of the Japanese yen (JPY). RESULTS AND DISCUSSION: We identified 17,825 eligible patients. The incidence rates of infectious complications (SSI + dry socket) and SSI after tooth extraction were 3.2% and 2.2%, respectively, during the entire period. The extraction of impacted third molars corresponded to 5.0% and 3.4%, respectively. However, their incidence rates were not significantly different during this period. The use of prophylactic antibiotics and antibiotic cost showed consistent trends following the implementation of guidelines. The mean DOT of CFPN-PI decreased (ranging from 4893.6 DOTs/1000 patients [March 2013 to November 2014] to 3856.4 DOTs/1000 patients [December 2014 to March 2016]; p < 0.001, and from 3856.4 DOTs/1000 patients [December 2014 to March 2016] to 2293.9 DOTs/1000 patients [April 2016 to March 2020]; p < 0.001). In contrast, the mean DOT of AMPC was found to be increased (ranging from 1379.7 DOTs/1000 patients [March 2013 to November 2014] to 3236.3 DOTs/1000 patients [December 2014 to March 2016]; p < 0.001, and from 3236.3 DOTs/1000 patients [December 2014 to March 2016] to 4597.8 DOTs/1000 patients [April 2016 to March 2020]; p < 0.001). The mean monthly cost was decreased (ranging from 905.3 JPY [March 2013 to November 2014] to 788.7 JPY [December 2014 to March 2016]; p = 0.003, and from 788.7 JPY [December 2014 to March 2016] to 614.0 JPY [April 2016 to March 2020]; p < 0.001). WHAT IS NEW AND CONCLUSION: After December 2014, prophylactic antibiotics were switched from CFPN-PI to AMPC, and the incidence rate of infectious complications was not significantly different over time. However, changing antibiotics is useful from a cost-effectiveness perspective.

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Development of a method of liquid chromatography coupled with tandem mass spectrometry for simultaneous determination of linezolid and tedizolid in human plasma

Yuki Sato, Yoh Takekuma, Takayuki Daisho, Hitoshi Kashiwagi, Shungo Imai, Mitsuru Sugawara

Biological and Pharmaceutical Bulletin 45 ( 4 ) 421 - 428 2022

Research paper (scientific journal), Accepted

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It is important to select appropriate antibiotics for infection control. Linezolid and tedizolid are newly developed and synthesized oxazolidinone antibacterial agents. It has been pointed out that there is a relationship between a high plasma concentration of the target drug and incidence of adverse effects, although it has been reported that neither linezolid nor tedizolid requires dose adjustment according to renal function. Due to the high incidence of adverse effects, both are often switched. Precise plasma concentration control by therapeutic drug monitoring (TDM) is desirable for reducing the adverse effects of both drugs and obtaining a better therapeutic effect. In this study, we aimed to establish a method for simultaneous quantification of linezolid and tedizolid in human plasma using LC coupled with tandem mass spectrometry. Sample preparation was performed by a simple operation with acetonitrile. Linezolid and tedizolid were separated by an octadecylsilyl column using a gradient elution of acetonitrile in aqueous 0.1% formic acid solution and were detected in the positive ion electrospray mode with multiple reaction monitoring. Quantification of linezolid and tedizolid ranged from 0.5 to 50 and 0.5 to 20 µg/mL, respectively. The intra-day and inter-day precision and accuracy of data were assessed and found to be acceptable. The developed method was successfully applied to measurement of the concentrations of linezolid and tedizolid. This simple method, which can simultaneously quantify both drug concentrations for daily TDM, could contribute to safer treatment of patients.

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Efficacy survey of Naldemedine in the Poor-Performance Status Group

Shintaro Kato, Yoshitaka Saito, Hiroko Onoda, Masayoshi Kumai, Shungo Imai, Kenkichi Tsuruga, Yoh Takekuma, Mitsuru Sugawar

YAKUGAKU ZASSHI 142 ( 7 ) 755 - 760 2022

Research paper (scientific journal), Accepted