HOSOMI Kouichi

    Department of Pharmacy Professor
Last Updated :2023/12/05

Researcher Information

J-Global ID

Research Areas

  • Life sciences / Clinical pharmacy

Published Papers

  • Yuki Tanaka; Satoshi Yokoyama; Chihiro Nakagawa; Takaya Uno; Kouichi Hosomi
    International journal of clinical pharmacology and therapeutics 61 (11) 492 - 502 2023/11 
    OBJECTIVE: Pancreatic cancer-related mortality is increasing worldwide, and prevention methods and effective novel therapies are required. In pancreatic cancer, sodium-glucose cotransporters (SGLT) are involved in glucose uptake. This study aimed to clarify the association between SGLT2 inhibitors and pancreatic cancer development. MATERIALS AND METHODS: A nested case-control study was conducted using the JMDC administrative claims database (January 2005 to June 2020). Patients newly diagnosed with type 2 diabetes mellitus (T2DM) were included, and cases were defined as patients who developed pancreatic cancer. Patients with outcomes were randomly matched to a maximum of 20 controls according to age (± 5 years), sex, and calendar date (month and year) of the first T2DM diagnosis through risk set sampling. RESULTS: Of the 181,107 T2DM patients, 363 cases and 7,043 controls were selected with 14 and 457 patients prescribed SGLT2 inhibitors, respectively. Cumulative administration of SGLT2 inhibitors for > 180 days was significantly inversely associated with the development of pancreatic cancer (adjusted odds ratio: 0.58, 95% confidence interval: 0.31 - 0.99). CONCLUSION: SGLT2 inhibitors may reduce the risk of developing pancreatic cancer in T2DM patients. The number of patients over 65 years of age was small in this study due to the nature of the data source. Further studies with larger sample sizes including older patients are needed.
  • Satoshi Yokoyama; Chihiro Nakagawa; Kouichi Hosomi
    Scientific reports 13 (1) 11677 - 11677 2023/07 
    The association between statins and open-angle glaucoma (OAG) remains controversial. This study investigated the relationship between statins and OAG in Japanese patients with dyslipidemia using the Japanese administrative claims database. A nested case-control study using two models was conducted using the JMDC claims database (01/2005-01/2020). The onset of OAG: index date was defined as the diagnosis of glaucoma, prescription of anti-glaucoma drugs, or surgery of glaucoma. For each case, a maximum of 10 age-, sex-, and calendar year/month-matched controls were randomly selected by risk-set sampling with replacement. The number of statin prescriptions during the exposure assessment period, which was identified as the 12-month (model 1) or 24-month (model 2) periods prior to the index date, was used as an indicator for statin exposure. Adjusted odds ratios (aORs) and 95% confidence interval (CI) were estimated using conditional logistic regression analyses. We identified 375,373 patients with newly diagnosed dyslipidemia. Of these, 6180 cases and 61,792 controls (model 1) and 4153 cases and 41,522 controls (model 2) were selected. Statin use was not identified as a significant risk factor for OAG (model 1: aOR 0.98, 95% CI 0.93-1.03, model 2: aOR 0.97, 95% CI 0.91-1.04). Compared with nonexposure, short-term exposure (< 2 years) to statins was not related to an increased risk of OAG in the Japanese working-age population with dyslipidemia.
  • Noriaki Kataoka; Takeo Hata; Kouichi Hosomi; Atsushi Hirata; Emi Goto; Masami Nishihara; Teruo Inamoto; Haruhito Azuma; Masashi Neo
    International journal of clinical pharmacology and therapeutics 61 (9) 386 - 393 2023/07 
    OBJECTIVE: To determine the safety of cabazitaxel and predictors of severe neutropenia caused by cabazitaxel in a patient population that includes those with comorbidities. MATERIALS AND METHODS: Of 42 prostate cancer patients treated with cabazitaxel at Osaka Medical and Pharmaceutical University Hospital between September 2014 and June 2022, 33 were included in this study, whereas 6 patients who were outpatients and 3 who were discharged early within 7 days upon patient request were excluded. Logistic regression analysis was used to examine predictors of severe neutropenia. RESULTS: Of the 33 eligible patients, 24 had comorbidities, with hypertension being the most common (n = 19), followed by dyslipidemia (n = 14) and diabetes (n = 11). There was no statistically significant difference in the rate of severe neutropenia due to any of the comorbidities, depending on the presence or absence of the comorbidity. However, the rate of severe neutropenia was significantly higher in patients with baseline platelet levels < 22.4×104/μL and those receiving cabazitaxel doses > 34 mg/body. In the final model adjusted for age, body mass index, C-reactive protein, and monocyte count, lower baseline platelet levels and higher doses of cabazitaxel were also predictors of the development of severe neutropenia. CONCLUSION: Comorbidities such as hypertension, dyslipidemia, diabetes mellitus, cerebrovascular disease, chronic kidney disease, liver dysfunction, and cardiac disease did not affect the incidence of severe neutropenia in patients receiving cabazitaxel. The baseline platelet count and the dose of cabazitaxel were also suggested to be markers for the development of severe neutropenia.
  • Yuika Komatsu; Masahiro Yodoshi; Manabu Takegami; Satoshi Yokoyama; Kouichi Hosomi
    International journal of clinical pharmacology and therapeutics 61 (4) 148 - 158 2023/04 
    OBJECTIVE: The aim of this study was to investigate the risk of hemorrhage in concomitant therapy with direct oral anticoagulants (DOACs) and class IV antiarrhythmic drugs. MATERIALS AND METHODS: First, disproportionality analysis (DPA) was performed using the Japanese Adverse Drug Event Report (JADER) database to investigate the risk of hemorrhage with DOACs. Second, a cohort study was performed using electronic medical record data to confirm the results of the JADER analysis. RESULTS: In the JADER analysis, hemorrhage was significantly associated with treatment with edoxaban and verapamil (reporting odds ratio = 1.66; 95% confidence interval (CI) = 1.04 - 2.67). The cohort study revealed that hemorrhage incidence significantly differed between the verapamil-treated group and the bepridil-treated group, with a higher risk for hemorrhage in the verapamil group (log-rank test: p < 0.001). The multivariate Cox proportional hazards model also showed that the verapamil and DOAC combination was significantly associated with hemorrhage events compared with the bepridil and DOAC combination (hazard ratio (HR): 2.87, 95% CI: 1.17 - 7.07, p = 0.022). Furthermore, creatinine clearance (Ccr) ≥ 50 mL/min was significantly associated with hemorrhage events (HR: 2.72, 95% CI: 1.03 - 7.18, p = 0.043), and verapamil was significantly associated with hemorrhage in patients with Ccr ≥ 50 mL/min (HR: 3.58, 95% CI: 1.36 - 9.39, p = 0.010) but not in patients with Ccr < 50 mL/min. CONCLUSION: Verapamil increases the risk of hemorrhage in patients on DOACs. Dose adjustment of DOACs based on renal function may prevent hemorrhage when verapamil is concomitantly administered.
  • Satoshi Yokoyama; Kouichi Hosomi
    Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan 143 (6) 497 - 500 2023 
    With the development of information technology, patient information is stored as electronic data, and huge amounts of such data are collected every day. Such a collection compiled over the course of clinical practice is called real-world data and is expected to be used for evaluating drug efficacy and safety. Real-world data such as health insurance association-based administrative claims databases, pharmacy-based dispensing databases, and spontaneous reporting system databases are mainly used in pharmaceutical research. Among them, claims databases are used for various observational studies such as studies on nationwide prescription trends, pharmacovigilance studies, and studies on rare diseases due to their large sample size. Although the nature of omics data is different from that of real-world data, it has become accessible on cloud platforms and are being used to broaden the scope of research in recent years. In this paper, we introduce a method for generating and further testing hypotheses through integrated analysis of real-world data and omics data, with a focus on administrative claims databases.
  • フィブラート系薬剤pemafibrateによる筋肉系障害に対するスタチン系薬剤併用の影響
    早川 萌風; 飯間 杏奈; 西田 美沙緒; 前川 頼子; 河渕 真治; 伊藤 由佳子; 上田 ひかる; 横山 聡; 細見 光一; 高田 充隆; 栄田 敏之
    日本臨床薬理学会学術総会抄録集 (一社)日本臨床薬理学会 43回 1 - 010 2022/12
  • Takaya Uno; Kouichi Hosomi; Satoshi Yokoyama; Kazuyoshi Kawabata
    International journal of clinical pharmacology and therapeutics 2022/11 
    OBJECTIVE: To identify the trends in tolvaptan prescription and the association between aging and tolvaptan-induced hypernatremia. MATERIALS AND METHODS: A health insurance claims database and a spontaneous adverse drug reaction database were used. RESULTS: Of all patients who had been prescribed tolvaptan, the proportion of patients aged 60 - 79 years and ≥ 80 years was consistent at ~ 40%. Moreover, the prescription frequency of tolvaptan increased over time for patients in the same age groups. The adjusted reporting odds ratio of tolvaptan-induced hypernatremia was 5.54 (95% confidence interval, 3.31 - 9.25) in patients aged ≥ 60 years from among all patients and 2.09 (95% confidence interval, 1.59 - 2.75) in those aged ≥ 80 years from among those aged ≥ 60 years. CONCLUSION: It may be necessary to be aware of hypernatremia in elderly patients who are expected to have increased prescriptions of tolvaptan.
  • Kaito Yamashiro; Mika Jouta; Kouichi Hosomi; Satoshi Yokoyama; Yuu Ozaki; Atsushi Hirata; Fumihiko Ogata; Takehiro Nakamura; Shigeharu Tanei; Naohito Kawasaki
    Scientific Reports Springer Science and Business Media LLC 12 (1) 2022/10 
    Abstract Microscopic colitis (MC) is a chronic inflammatory bowel disease that is characterized by nonbloody watery diarrhea. The epidemiology in Japan differs from that in Europe and the United States, but little information is available from epidemiological surveys of MC in Japan. This study aimed to provide a new hypothesis regarding the factors associated with MC by using the Japanese Adverse Drug Event Report (JADER) database. “Colitis microscopic” (preferred term code: 10056979) cases entered into the JADER database between 2004 and 2021 were analyzed. Of the 246,997 cases in the JADER database, 161 cases were observed to be associated with MC. A Weibull analysis revealed that the median onset duration of MC (interquartile range) was 72.5 (36.0‒125.5) days in lansoprazole users and 116.0 (60.3‒1089.0) days in aspirin users. A multiple logistic regression analysis revealed that MC was significantly associated with the female sex, as well as ages ≥ 60 years and drugs including lansoprazole, aspirin, and nicorandil. A subset analysis revealed that MC was positively associated with obesity in female cases. Our study cannot demonstrate a causal inference between MC and each drug; however, the findings suggest that MC was associated with nicorandil as well as with lansoprazole and aspirin.
  • Chihiro Nakagawa; Satoshi Yokoyama; Kouichi Hosomi
    The Annals of pharmacotherapy 57 (6) 10600280221126971 - 10600280221126971 2022/09 
    BACKGROUND: Statins are expected to have beneficial effects on nonalcoholic fatty liver disease (NAFLD); however, evidence remains insufficient. OBJECTIVE: In this study, we aim to investigate the association between statin adherence and NAFLD development. METHODS: We conducted a nested case-control study of statin users using the Japan Medical Data Center administrative claims database (January 2005 to January 2020). Individuals who developed NAFLD were designated as cases. For each case, we randomly selected a maximum of 10 controls using risk set sampling. Good adherence was defined as the proportion of days covered (PDC) of ≥0.80. Higher intensity was defined as the median or higher of a cumulative defined daily dose (cDDD) per day covered by statin prescription. Conditional logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: In this study, 253 383 patients with the first statin prescription were identified. Of them, 7080 were selected and matched to 70 734 controls. The medians of PDC and intensity were 0.88 (interquartile range [IQR], 0.61-0.96) and 0.32 (IQR, 0.25-0.50) cDDD/day, respectively. Good adherence was significantly associated with a reduced risk of NAFLD development (adjusted OR, 0.82; 95% CI, 0.78-0.86). Higher intensity was not significantly associated with a reduced risk of NAFLD development (adjusted OR, 1.02; 95% CI, 0.97-1.08). CONCLUSION AND RELEVANCE: Good adherence to statins is associated with a reduced risk of NAFLD development, regardless of the statin intensity. Appropriate statin therapy could reduce the risk of NAFLD development.
  • Takaya Uno; Mitsutaka Takada; Satoshi Yokoyama; Kazuyoshi Kawabata; Kouichi Hosomi
    International journal of clinical pharmacology and therapeutics 60 (11) 477 - 485 2022/09 
    OBJECTIVE: Calcineurin inhibitors (CNIs), including cyclosporine and tacrolimus, are associated with an increased cancer risk. However, whether mammalian target of rapamycin inhibitors (mTORis), including sirolimus and everolimus, decrease the cancer risk in patients receiving CNIs remains uncertain. We aimed to determine whether mTORis are associated with a decreased cancer risk in patients receiving CNIs using data mining of a spontaneous adverse reaction database. MATERIALS AND METHODS: Disproportionality analysis was conducted using the U.S. Food and Drug Administration Adverse Event Reporting System database (2004 - 2019) with reporting odds ratio and information component being used to indicate a signal. RESULTS: Data subset analyses indicated that sirolimus and everolimus were not associated with a decreased cancer risk in patients receiving cyclosporine or tacrolimus but were associated with an increased risk of nonmelanoma skin cancer (NMSC) and Kaposi's sarcoma. CONCLUSION: mTORis are not associated with a decreased cancer risk but are associated with a further increase in the risk of NMSC and Kaposi's sarcoma in patients receiving CNIs. Further studies are necessary to clarify the mechanism underlying the association between mTORis and NMSC or Kaposi's sarcoma.
  • K Yamashiro; K Hosomi; S Yokoyama; F Ogata; T Nakamura; N Kawasaki
    Die Pharmazie 77 (7) 243 - 247 2022/09 
    Proton pump inhibitors (PPIs) are commonly used for the prevention or treatment of gastric ulcers, but they can induce hypomagnesemia. Little is known about the onset duration and risk factors related to patient characteristics of this adverse event in Japanese patients. Therefore, we analyzed the time-to-onset of PPI-induced hypomagnesemia and evaluated the association between hypomagnesemia and PPIs using the Japanese Adverse Drug Event Report (JADER) database. We analyzed hypomagnesemia cases between 2004 and 2021. The time-to-onset analysis was performed using the Weibull distribution, and the adjusted reporting odds ratio (aROR) or 95% confidence interval (95% CI) was calculated using a multiple logistic regression analysis. The analysis database comprised 236,525 cases, with 188 cases associated with hypomagnesemia. The median onset duration (interquartile range) of PPI-induced hypomagnesemia was 99.0 (51.8-285.5 ) days, which is considered the random failure type. The multiple logistic regression analysis revealed that hypomagnesemia is significantly associated with male sex (aROR, 95% CI: 1.66, 1.23-2.25) , age < 60 (1.59, 1.14-2.21) , estimated body-mass index (eBMI) (0.94, 0.91-0.98) , PPIs (1.66, 1.18-2.30) , and the interaction of age (<60)*PPIs (1.58, 1.13-2.19) . However, diuretics were not significantly associated with hypomagnesemia. Our results suggest that serum magnesium levels should be measured regularly regardless of the duration of PPI use, especially in patients with male sex, age < 60, or low BMI. These findings will assist health professionals in the adequate use of PPIs. These findings need to be evaluated by cohort studies and long-term clinical investigations.
  • Yuika Komatsu; Satoshi Yokoyama; Kouichi Hosomi; Mitsutaka Takada
    Drugs - real world outcomes 9 (3) 437 - 449 2022/09 
    BACKGROUND: Atrial fibrillation (AF) is a major risk factor for the development of stroke and silent cerebral infarct (SCI). Additionally, AF is independently associated with neurological disorders, including cognitive impairment and dementia. Although oral anticoagulants (OACs) are used to reduce the risk of development of stroke and SCI in patients with AF, it is unclear whether OACs reduce the risk of dementia. OBJECTIVE: This study aimed to investigate the association between OAC use and dementia in relatively young patients with AF. Moreover, the impact of medication adherence on the association between OAC use and the risk of dementia was examined. PATIENTS AND METHODS: This retrospective cohort study was conducted using a large claims database-Japan Medical Data Center, Inc. (JMDC)-from which newly diagnosed patients with AF younger than 75 years of age were identified. We analyzed medication adherence using the medication possession ratio (MPR). The dementia risk was compared between the OAC and non-OAC groups using Cox proportional hazards regression analysis and the Kaplan-Meier method after propensity score matching. Similarly, the MPR-classified and non-OAC groups were also compared. RESULTS: OAC administration was not associated with the risk of dementia in the entire cohort (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.40-1.08; p = 0.098); however, OAC administration in patients with an MPR ≥90% was significantly associated with a lower risk of dementia (HR 0.45, 95% CI 0.25-0.81; p = 0.008). Meanwhile, direct OAC (DOAC) and warfarin (WF) administration was not associated with the risk of dementia regardless of MPR. Kaplan-Meier analysis revealed a significant difference in the incidence of dementia between the MPR ≥ 90% OAC and non-OAC groups (log-rank test: p = 0.006). However, no difference was observed in the incidence of dementia between the MPR ≥ 90% WF and non-OAC groups, or between the MPR ≥ 90% DOAC and non-OAC groups. CONCLUSIONS: OAC administration was not associated with the risk of dementia in relatively young patients with AF; however, when limited to patients with an MPR ≥ 90%, OAC administration reduced the risk of dementia. Our results suggest that the association between OAC use and dementia should be evaluated while considering medication adherence.
  • コロナ禍の多職種連携教育における仮想空間実施の影響
    池田 行宏; 木村 貴明; 三井 良之; 藤田 貢; 梶 博史; 赤木 將男; 松村 到; 井上 知美; 細見 光一; 大鳥 徹; 小竹 武; 岩城 正宏
    医学教育 (一社)日本医学教育学会 53 (Suppl.) 233 - 233 0386-9644 2022/07
  • コロナ禍の多職種連携教育における仮想空間実施の影響
    池田 行宏; 木村 貴明; 三井 良之; 藤田 貢; 梶 博史; 赤木 將男; 松村 到; 井上 知美; 細見 光一; 大鳥 徹; 小竹 武; 岩城 正宏
    医学教育 (一社)日本医学教育学会 53 (Suppl.) 233 - 233 0386-9644 2022/07
  • 有害事象自発報告データベース(JADER)を用いたプロトンポンプ阻害薬による低マグネシウム血症の有害事象プロファイルの評価
    山城 海渡; 細見 光一; 横山 聡; 緒方 文彦; 中村 武浩; 川崎 直人
    日本薬学会年会要旨集 (公社)日本薬学会 142年会 26F - pm08S 0918-9823 2022/03
  • 電子カルテデータを用いた直接経口抗凝固薬と経口抗不整脈薬の併用による出血リスクに関する研究
    小松 唯可; 吉年 正宏; 淺野 肇; 柳江 正嗣; 竹上 学; 横山 聡; 細見 光一
    日本薬学会年会要旨集 (公社)日本薬学会 142年会 26F - pm09S 0918-9823 2022/03
  • レセプトデータベースを用いたSGLT2阻害薬と膵がんとの関連性についての研究
    田中 侑希; 横山 聡; 細見 光一
    日本薬学会年会要旨集 (公社)日本薬学会 142年会 26PO1 - 13S 0918-9823 2022/03
  • フィブラート系薬剤投与に伴う横紋筋融解症に対するスタチン系薬剤併用の影響
    大淵 亜美; 土井 彩奈; 大坂 歩; 飯間 杏奈; 河渕 真治; 伊藤 由佳子; 上田 ひかる; 横山 聡; 細見 光一; 高田 充隆; 栄田 敏之
    日本薬学会年会要旨集 (公社)日本薬学会 142年会 27PO5 - 07S 0918-9823 2022/03
  • 抗精神病薬と関節リウマチの関連性の検討 バイオインフォマティクスデータベースを活用したドラッグリポジショニング
    中川 千拓; 横山 聡; 細見 光一
    日本薬学会年会要旨集 (公社)日本薬学会 142年会 28PO6 - 05S 0918-9823 2022/03
  • 「医療ビッグデータ×AI×臨床」医療の発展に貢献するデータサイエンス レセプトデータベースを中心としたビッグデータの利活用
    横山 聡; 細見 光一
    日本薬学会年会要旨集 (公社)日本薬学会 142年会 S31 - 3 0918-9823 2022/03
  • Satoshi Yokoyama; Chihiro Nakagawa; Kouichi Hosomi
    Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 30 (2) 1765 - 1773 2022/02 
    PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse event of cancer treatment; however, no drug is recommended for the prevention of CIPN. In Japan, several drugs such as Gosha-Jinki-Gan and duloxetine are frequently administered as a treatment for CIPN. The aim of this study was to elucidate prescription patterns of drugs administered for CIPN caused by oxaliplatin and the association between these drugs and the duration of oxaliplatin treatment. METHODS: We conducted a retrospective nationwide study using the JMDC administrative claims database (January 2005-June 2020; JMDC Inc., Japan). Patients newly treated with oxaliplatin were identified, and prescription patterns of CIPN medication including Gosha-Jinki-Gan, pregabalin, duloxetine, mecobalamin, and mirogabalin were investigated. The primary outcome was the duration of oxaliplatin treatment. Multivariable logistic regression analysis was performed to examine the association between CIPN medication and duration of oxaliplatin treatment. RESULTS: A total of 4,739 patients who newly received oxaliplatin were identified. Of these, 759 (16.0%) had received CIPN medication. Duloxetine was administered in 99 (2.1%) patients. Multivariable logistic regression analysis revealed that CIPN medication was significantly associated with the prolonged duration of oxaliplatin treatment (odds ratio: 2.35, [95% confidence interval: 1.99-2.77]). CONCLUSION: Real-world data demonstrated that the administration rate of CIPN medication was higher in patients who received oxaliplatin treatment for over 6 months.
  • Ieda Shoko; Miyamoto Tomoyoshi; Hosomi Kouichi; Takegami Manabu; Kawabata Atsufumi
    The Journal of Community Pharmacy and Pharmaceutical Sciences Pharmacy Society of Japan advpub 1884-3077 2022 
    Objective: Pharmacy students learn the “brand names” of many drugs throughout clinical training, and their drug recognition skill in “generic names” might decline thereafter. To evaluate this, we conducted tests to assess students’ recognition of drugs in both “brand” and “generic” names before and after clinical training. Method: The participants were 64 students undergoing clinical pharmacy training at Kindai University Hospital. Mark-sheet tests concerning pharmacology of drugs in both “brand” and “generic” names were conducted 3 times, before and after community pharmacy training and after hospital pharmacy training. Results: After clinical pharmacy training, students’ drug recognition skill in “brand name” significantly elevated, but that in “generic name” remained constant. Conclusions: Unexpectedly, many students maintained their drug recognition skill in “generic name” after clinical pharmacy training. Nonetheless, educational programs to make students conscious of “generic name” linking with “brand name” during clinical training might be beneficial to promote overall skills in clinical pharmacy.
  • Shoko Ieda; Tomoyoshi Miyamoto; Kouichi Hosomi; Manabu Takegami; Atsufumi Kawabata
    Journal of palliative medicine 25 (4) 570 - 576 2021/10 
    Background: Accurate prognosis in terminal cancer patients is useful to improve their quality of life and also to decide the cessation of fluid administration. Nonetheless, few prognostic indicators are available for prediction of such a short-term life expectancy. Objectives: The present study aimed at evaluating the efficacy of C-reactive protein (CRP)/albumin (CRP/Alb) ratio, prognostic nutritional index (PNI), fibrosis-4 (FIB-4) index, and albumin-bilirubin (ALBI) score in identifying terminal cancer patients who have a life expectancy less than two weeks. Design: Retrospective study. Setting/Subjects: Of 483 patients who died between April 2019 and March 2020 at a single center in Japan, 102 who met the inclusion criteria were enrolled in this study. Measurements: CRP/Alb, PNI, FIB-4, and ALBI were calculated from the laboratory data collected 1-13, 14-27, 28-83, and 168-365 days before death and subjected to statistical analyses. Results: CRP/Alb, PNI, FIB-4, and ALBI values were significantly associated with the time before death during terminal 365 days. CRP/Alb ≥4.4, PNI <30, FIB-4 ≥ 9.4, and ALBI ≥ -1.26 were significantly associated with the transition from the first half to the second half of terminal four weeks. Of those prognostic indicators, three and four combinations provided significantly reliable estimation of a life expectancy less than two weeks. Conclusions: CRP/Alb, PNI, FIB-4, ALBI, and their combinations are considered to help identify cancer patients who have a life expectancy less than two weeks, which is useful to make appropriate end-stage treatment decisions, for example, cessation of artificial hydration therapy.
  • Takayuki Mabuchi; Kouichi Hosomi; Satoshi Yokoyama; Mitsutaka Takada
    International journal of clinical pharmacology and therapeutics 59 (5) 353 - 357 2021/05 
    A retrospective data analysis was performed to investigate the association between polypharmacy and adverse events using three different spontaneous adverse event reporting system databases. Multivariate logistic regression analyses were performed to investigate the association between the number of drugs and adverse events, including hepatic disorders, renal disorders, hypersensitivity, and extrapyramidal syndrome. The results showed that the risk of hepatic and renal disorders increased with the number of drugs. Thus, decreasing the number of drugs may reduce the risk of hepatic and renal disorders. Furthermore, attention should be given to specific drugs that may cause hypersensitivity and extrapyramidal syndrome.
  • フィブラート系薬剤の有害事象発現リスクに対するスタチン系薬剤併用の影響
    杉山 大介; 山嵜 伊織; 重村 敦史; 河渕 真治; 伊藤 由佳子; 上田 ひかる; 横山 聡; 細見 光一; 高田 充隆; 栄田 敏之
    日本薬学会年会要旨集 (公社)日本薬学会 141年会 29V07 - pm02S 0918-9823 2021/03
  • 服薬アドヒアランスを考慮した経口抗凝固薬における認知症リスクに関する研究
    小松 唯可; 細見 光一; 横山 聡; 高田 充隆
    日本薬学会年会要旨集 (公社)日本薬学会 141年会 27P02 - 213S 0918-9823 2021/03
  • レセプトデータを用いたSGLT2阻害薬と大腸がんとの関連性についての研究
    田中 侑希; 横山 聡; 細見 光一; 高田 充隆
    日本薬学会年会要旨集 (公社)日本薬学会 141年会 27P02 - 262S 0918-9823 2021/03
  • Chihiro Nakagawa; Satoshi Yokoyama; Kouichi Hosomi; Mitsutaka Takada
    Therapeutic advances in musculoskeletal disease 13 1759720X211047057  2021 
    INTRODUCTION: Treatment of rheumatoid arthritis (RA) has advanced with the introduction of biological disease-modifying antirheumatic drugs. However, more than 20% of patients with RA still have moderate or severe disease activity. Hence, novel antirheumatic drugs are required. Recently, drug repurposing, a process of identifying new indications for existing drugs, has received great attention. Furthermore, a few reports have shown that antipsychotics are capable of affecting several cytokines that are also modulated by existing antirheumatic drugs. Therefore, we investigated the association between antipsychotics and RA by data mining using real-world data and bioinformatics databases. METHODS: Disproportionality and sequence symmetry analyses were employed to identify the associations between the investigational drugs and RA using the US Food and Drug Administration Adverse Event Reporting System (2004-2016) and JMDC administrative claims database (January 2005-April 2017; JMDC Inc., Tokyo, Japan), respectively. The reporting odds ratio (ROR) and information component (IC) were used in the disproportionality analysis to indicate a signal. The adjusted sequence ratio (SR) was used in the sequence symmetry analysis to indicate a signal. The bioinformatics analysis suite, BaseSpace Correlation Engine (Illumina, CA, USA) was employed to explore the molecular mechanisms associated with the potential candidates identified by the drug-repurposing approach. RESULTS: A potential inverse association between the antipsychotic haloperidol and RA, which exhibited significant inverse signals with ROR, IC, and adjusted SR, was found. Furthermore, the results suggested that haloperidol may exert antirheumatic effects by modulating various signaling pathways, including cytokine and chemokine signaling, major histocompatibility complex class-II antigen presentation, and Toll-like receptor cascade pathways. CONCLUSION: Our drug-repurposing approach using data mining techniques identified haloperidol as a potential antirheumatic drug candidate.
  • Satoshi Yokoyama; Yuki Tanaka; Kouichi Hosomi; Mitsutaka Takada
    International journal of medical sciences 18 (15) 3574 - 3580 2021 
    Background: Amiodarone is rich in iodine, so in clinical practice amiodarone-induced hypothyroidism (AIH) is a major side effect. This drug is used in patients with arrhythmias, especially atrial fibrillation, the most common sustained arrhythmia. Polypharmacy, which can result in complex drug-drug interactions, occurs in more than 70% of the patients with atrial fibrillation. Therefore, polypharmacy may be involved in the expression of AIH. In this study, we investigated the association between polypharmacy and AIH. Methods: We conducted a retrospective study using data from January 2006 to May 2020 collected from a large, organized database of prescriptions constructed by the Japan Medical Information Research Institute, Inc. (Tokyo, Japan). To investigate the association between number of prescribed drugs with amiodarone and AIH, we divided patients into two groups: polypharmacy (≥ 5 prescribed drugs) and non-polypharmacy (< 5 prescribed drugs). We then performed a sequence symmetry analysis on the two groups: incident thyroxine after incident amiodarone and incident thyroxine before incident amiodarone. Finally, we conducted a case-control study on two further groups: those prescribed thyroxine after incident amiodarone (AIH group; n=555) and those not prescribed thyroxine after incident amiodarone (non-AIH group; n=6,192). Results: Sequence symmetry analysis revealed a significant association between amiodarone and thyroxine in both the polypharmacy and non-polypharmacy groups. The ranges for the adjusted sequence ratio in the two groups were 12.0-16.7 and 7.3-9.0, respectively. The case-control study showed that ≥5 prescribed drugs at the first prescription of amiodarone were found to significantly increase the odds of AIH (odds ratio: 1.48, 95% confidence interval: 1.18-1.84). Conclusion: Polypharmacy was suggested as an independent risk factor for AIH. Careful assessment of the appropriateness of prescription is warranted.
  • Kazuki Matsui; Yutaro Mukai; Kota Sakakura; Kyoichi Wada; Tsutomu Nakamura; Atsufumi Kawabata; Nobue Terakawa; Naoki Hayakawa; Kengo Kusano; Kouichi Hosomi; Satoshi Yokoyama; Mitsutaka Takada
    International journal of clinical pharmacology and therapeutics 59 (1) 63 - 70 2021/01 
    OBJECTIVE: Bepridil prolongs the QT interval and can induce torsade de pointes. Although increased bepridil concentration may be a primary cause of prolonged QT, the relationship between serum bepridil concentration and prolonged QT remains unclear. We investigated the relationship between serum bepridil concentration and the corrected QT (QTc) interval in patients treated with bepridil. MATERIALS AND METHODS: A retrospective study was performed at the National Cerebral and Cardiovascular Center in Japan. Patients with atrial fibrillation who were treated with bepridil from January 2014 to December 2015 were enrolled in the study. Serum bepridil concentrations and electrocardiogram data collected more than 21 days after the initiation of bepridil were used for analysis. RESULTS: A total of 60 patients were included in this study. There was a significant difference in mean QTc interval before and after initiation of bepridil (p < 0.0001). A significant relationship was observed between bepridil dose (p = 0.014) or serum bepridil concentration (p < 0.001) and QTc interval. Additionally, a significant relationship was observed between serum bepridil concentration and ΔQTc (p = 0.034). In the study, 4 patients developed QTc prolongation ≥ 500 ms after the initiation of bepridil. Serum bepridil concentration in this group was significantly higher compared with the group that did not display prolonged QTc (973 ± 651 vs. 526 ± 310 ng/mL, p = 0.01). CONCLUSION: This study revealed that the QTc interval was significantly associated with serum bepridil concentration. Serum bepridil concentration beyond a therapeutic range may be a critical risk factor for developing QTc prolongation.
  • Takayuki Mabuchi; Kouichi Hosomi; Satoshi Yokoyama; Mitsutaka Takada
    International journal of clinical pharmacology and therapeutics 58 (11) 601 - 607 2020/11 [Refereed]
     
    OBJECTIVE: Polypharmacy has become a major problem in medical care worldwide, including in Japan. The purpose of this study was to investigate the current situation of polypharmacy using different spontaneous adverse drug event report databases. MATERIALS AND METHODS: A retrospective data analysis was performed using reports from 2007 to 2015 from three different spontaneous adverse drug event report databases: the Japanese Adverse Drug Event Report (JADER) constructed by the Pharmaceuticals and Medical Devices Agency in Japan, the US Food and Drug Administration (FDA) Adverse Drug Event Reporting System (FAERS) constructed by the FDA in the United States, and the Canada Vigilance Adverse Reaction Online Database (CVARD) constructed by the government of Canada. Polypharmacy trends during the study period were investigated. RESULTS: The mean numbers of drugs per report in the JADER, FAERS, and CVARD databases during the study period were 6.62, 3.76, and 3.44, respectively. The mean number of drugs per report increased with age in all three databases, with a peak at ages 70 - 79 years in all three databases (7.0 drugs for JADER, 4.7 drugs for FAERS, and 4.2 drugs for CVARD). CONCLUSION: Adverse event reports were more likely to develop in the patients treated through polypharmacy. Polypharmacy in Japan should be improved to prevent adverse events. Additionally, the patients aged ≥ 80 years tended to develop adverse events even if the number of prescribed drugs was relatively small. Therefore, polypharmacy should be noted in these patients to prevent adverse events.
  • Satoshi Yokoyama; Shoki Wakamoto; Yuki Tanaka; Chihiro Nakagawa; Kouichi Hosomi; Mitsutaka Takada
    ANNALS OF PHARMACOTHERAPY SAGE PUBLICATIONS INC 54 (10) 988 - 995 1060-0280 2020/10 [Refereed]
     
    Background: Osteoporosis, which is a major public health concern, has been known to reduce health-related quality of life. Some studies have suggested that antipsychotics could perhaps cause osteoporosis by increasing serum prolactin levels. However, the association between antipsychotics and the risk for developing osteoporosis has been controversial. Objective: The present study aimed to assess the association between antipsychotic use and onset of osteoporosis in real-world settings. Methods: A multimethod data-mining approach using different algorithms and databases was used. First, disproportionality analysis was conducted using the US Food and Drug Administration Adverse Event Reporting System (FAERS) database (2004-2017) with reporting odds ratio (ROR) and information component (IC) being used to indicate a signal. Furthermore, a sequence symmetry analysis using data from a large Japanese administrative claims database (2005-2017; JMDC Inc, Japan) was conducted. Short-term intervals (ie, 12, 24, and 36 months) were set to investigate the association between antipsychotic use and onset of osteoporosis using the adjusted sequence ratio (SR) to indicate a signal. Results: No potential association between osteoporosis and all antipsychotics was observed in the FAERS database, except for perphenazine, which exhibited significant signals using both ROR and IC. Moreover, no potential association between osteoporosis and antipsychotics was observed in the JMDC claims database, except for sulpiride and aripiprazole. None of the antipsychotics indicated significant signals using all analyzed items (ROR, IC, and adjusted SR). Conclusion and Relevance: Real-world data show no association between antipsychotic use and the onset of osteoporosis. Further pharmacoepidemiological studies are needed for causality assessment.
  • Takayuki Mabuchi; Kouichi Hosomi; Satoshi Yokoyama; Mitsutaka Takada
    Journal of clinical pharmacy and therapeutics WILEY 45 (5) 991 - 996 0269-4727 2020/10 [Refereed]
     
    WHAT IS KNOWN AND OBJECTIVE: Polypharmacy is associated with an increased risk of adverse drug reactions (ADRs) and drug interactions, decreased adherence to medication and increased medical cost. Recently, polypharmacy has become a major problem in medical care in Japan as a result of the increase in the ageing population. The purpose of this study was to investigate the current situation of polypharmacy and the association between polypharmacy and adverse events. METHODS: A retrospective data analysis was performed using two different real-world data from 2007 to 2015 in Japan. The Japanese Adverse Drug Event Report (JADER), a public spontaneous adverse drug reaction database constructed by the Pharmaceuticals and Medical Devices Agency (PMDA), and a large prescription database constructed by a database vendor (Japan Medical Information Research Institute, Inc Japan [JMIRI]) were analysed. Trends of polypharmacy during the study period were investigated. RESULTS AND DISCUSSION: The mean number of drugs per report in the JADER database and per prescription in the JMIRI databases during the study period ranged from 4.8 to 5.6 and 3.5 to 3.7, respectively. The mean number of drugs increased with age in both the JADER and JMIRI databases, and the peak of the mean number of drugs was at 80-89 years (5.74 drugs) in the JADER database and at 90-99 years (4.97 drugs) in the JMIRI database. WHAT IS NEW AND CONCLUSIONS: The number of drugs increased until age 90 years or more, even though adverse events are more likely to occur after the age of 80 in Japan. Therefore, polypharmacy in the elderly should be focused on the patients aged ≥80 years rather than patients aged ≥65 years from the viewpoint of the prevention of adverse events.
  • Ryosuke Ota; Atsushi Hirata; Keisuke Noto; Satoshi Yokoyama; Kouichi Hosomi; Mitsutaka Takada; Hiroshi Matsuoka
    INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS DUSTRI-VERLAG DR KARL FEISTLE 58 (5) 274 - 281 0946-1965 2020/05 [Refereed]
     
    Objective: The relationship between serum creatinine and calcium (Ca) was investigated in hematopoietic stem cell transplantation (HSCT) patients treated with foscarnet. Materials and methods: A retrospective study was performed to investigate the development of foscarnet-induced renal dysfunction in patients who received HSCT from April 2010 to November 2018 at the Kindai University Nara Hospital. A total of 80 patients were identified from the medical records, and 42 patients who met the inclusion criteria were enrolled in this study. Renal dysfunction was classified according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Results: A significant inverse relationship was observed between serum creatinine and Ca levels (r = -0.372; p < 0.0001; y = -0.537x + 9.268). A separate analysis divided into renal dysfunction and non-renal dysfunction groups showed that there was a significant relationship between serum creatinine and Ca levels in the renal dysfunction group (r = -0.531: p < 0.0001; y = -0.617x + 9.239) but not in the non-renal dysfunction group (r = -0.011; p = 0.561; y = -0.023x + 8.934). The optimal cutoff for the minimum Ca level was calculated to be 8.1 mg/mL. Conclusion: A significant inverse relationship was observed between serum creatinine and Ca levels in HSCT patients with foscarnet-induced renal dysfunction. Foscarnet-induced renal dysfunction should be noted if Ca levels fall below 8.1 mg/dL. Monitoring Ca levels may be useful for detecting renal dysfunction at early stages in patients treated with foscarnet.
  • Makiko Iwasawa; Keiko Sagami; Satoshi Yokoyama; Kouichi Hosomi; Mitsutaka Takada
    International journal of clinical pharmacology and therapeutics DUSTRI-VERLAG DR KARL FEISTLE 58 (4) 214 - 222 0946-1965 2020/04 [Refereed]
     
    OBJECTIVE: The purpose of this study was to examine whether co-initiation of antiulcer drugs (AUDs) and low-dose aspirin (LDA) therapy is beneficial for good adherence to LDA therapy. MATERIALS AND METHODS: A retrospective cohort study was conducted using the JMDC claims database. Patients for whom LDA therapy was newly initiated between January 2005 and April 2016 were selected from the JMDC database. The selected patients were divided into LDA and LDA+AUD groups and were followed up from the first prescription of LDA or LDA+AUD until the earliest of the following events: discontinuation or the end of the observation period. Unadjusted and multivariable Cox proportional hazards models controlling for all demographic and clinical characteristics were applied to examine whether the addition of an AUD to LDA improved adherence. A 1 : 1 propensity score matching analysis was conducted to balance confounders between the two groups. RESULTS: After the propensity score matching analysis, 4,089 patients were matched in each therapy group. The Kaplan-Meier curves for the rate of LDA continuation showed a sharp decline just after the initiation of LDA therapy. A significant difference was observed in the incidence of LDA therapy discontinuation between the LDA+AUD and LDA groups (HR: 0.87, 95% CI: 0.82 - 0.92), and the median duration of LDA therapy in the LDA+AUD and LDA groups were 18 and 11 months (log-rank test: p < 0.0001), respectively. CONCLUSION: The therapy persistence rate in the LDA+AUD group was significantly higher than that in the LDA group.
  • Ryo Inose; Natsue Hashimoto; Kouichi Hosomi; Satoshi Yokoyama; Mitsutaka Takada
    International journal of clinical pharmacology and therapeutics DUSTRI-VERLAG DR KARL FEISTLE 58 (3) 131 - 138 0946-1965 2020/03 [Refereed]
     
    OBJECTIVE: This study was aimed at investigating the risk of malignancies in rheumatoid arthritis patients treated with methotrexate (MTX), and whether the addition of biological disease-modifying antirheumatic drugs (bDMARDs) further increases the risk of malignancies in patients receiving MTX therapy, by using data from a spontaneous adverse reaction database. MATERIALS: Patient data from the U.S. Food and Drug Administration's Adverse Event Reporting System (FAERS) from the first quarter of 2004 to the end of 2015 were analyzed. METHODS: A data subset analysis was performed to investigate whether the use of bDMARDs further increased the risk of malignancies in patients receiving MTX therapy. RESULTS: MTX showed significant associations with all malignancies except liver cancer. bDMARDs showed significant associations with stomach cancer, colorectal cancer, prostate cancer, ovarian cancer, malignant melanoma, and lung cancer. In addition, bDMARD use increased the risk of breast, ovarian, and lung cancers in rheumatoid arthritis patients receiving MTX therapy. CONCLUSION: MTX use was significantly associated with various malignancies. Moreover, concomitant use of bDMARDs further increased the risk of breast, ovarian, and lung cancers in MTX-treated patients with rheumatoid arthritis.
  • Sayoko Kinoshita; Kouichi Hosomi; Satoshi Yokoyama; Mitsutaka Takada
    Journal of clinical pharmacy and therapeutics WILEY 45 (1) 65 - 71 0269-4727 2020/02 [Refereed]
     
    WHAT IS KNOWN AND OBJECTIVE: Amiodarone (AMD) treatment is associated with a number of significant adverse effects including thyroid dysfunction. However, the relationship between the development of thyroid dysfunction and the dosage and treatment duration of AMD remains unclear. The purpose of this study was to examine the onset profiles of amiodarone-associated thyroid dysfunction using a spontaneous adverse drug reaction (ADR) reporting database. METHODS: Data were obtained from the US Food and Drug Administration Adverse Event Reporting System (FAERS). For signal detection of spontaneous ADRs, the reporting odds ratio (ROR) and information component (IC) were calculated. Cumulative incidences of hyperthyroidism and hypothyroidism were assessed using the Kaplan-Meier method, and time-to-onset profiles were analysed using the Weibull shape parameter (WSP) test. RESULTS AND DISCUSSION: The median time-to-onset of hyperthyroidism associated with AMD and other drugs was 720.0 (range: 225.5-1145.0) and 101.5 (range: 14.0-468.8) days, respectively. Patients treated with AMD showed a significantly longer time-to-onset of hyperthyroidism than those treated with other drugs (P < .001). The median time-to-onset of hypothyroidism associated with AMD and other drugs was 183.0 (range: 35.0-727.8) and 153.0 (range: 19.0-608.0) days, respectively. There was no significant difference in the time-to-onset of hypothyroidism between patients treated with AMD and those treated with other drugs (P = .13). For hyperthyroidism, the WSP test showed that AMD had a wear-out failure-type profile and other drugs had early failure-type profiles. For hypothyroidism, the WSP test showed that both AMD and other drugs had early failure-type profiles. WHAT IS NEW AND CONCLUSIONS: Amiodarone-associated hyperthyroidism had a different onset profile than hyperthyroidism associated with other drugs. Because the time-to-onset of AMD-associated hyperthyroidism is widely distributed, sustained and continuous attention is required to detect and treat hyperthyroidism during AMD treatment. In contrast, AMD-associated hypothyroidism had an onset profile that was similar to that of other drugs, suggesting that attention should be focused on the earlier stages of treatment.
  • Satoshi Yokoyama; Shoko Ieda; Mirai Nagano; Chihiro Nakagawa; Makoto Iwase; Kouichi Hosomi; Mitsutaka Takada
    INTERNATIONAL JOURNAL OF MEDICAL SCIENCES IVYSPRING INT PUBL 17 (4) 471 - 479 1449-1907 2020 [Refereed]
     
    Introduction: Warfarin and direct oral anticoagulants (DOACs) have been widely used in antithrombotic therapy. Although warfarin use has been suspected to be associated with osteoporosis risk, several studies have shown otherwise. Conversely, a few reports have found an association between DOACs and osteoporosis. This study therefore clarifies the association between oral anticoagulants and osteoporosis by analyzing real-world data using different methodologies, algorithms, and databases.Methods: Real-world data from the US Food and Drug Administration Adverse Event Reporting System (FAERS; 2004-2016) and Japanese administrative claims database (2005-2017; JMDC Inc., Tokyo) were used. Reporting odds ratio (ROR) and information component (IC) were calculated through disproportionality analysis (DPA) using reports recorded in the FAERS. Sequence symmetry analysis (SSA) was employed to calculate the adjusted sequence ratio (SR) using the JMDC Claims Database. For the adjusted SR and ROR, a significant signal was detected when the lower limit of the two-sided 95% confidence interval (CI) was more than 1. For the IC, a significant signal was detected when the lower limit of the 95% CI was more than 0.Results: DPA for warfarin found significant signals for osteoporosis in ROR (1.43, 95% CI: 1.32-1.54) and IC (0.50, 95% CI: 0.39-0.61). SSA showed a significant association between warfarin use and osteoporosis or bisphosphonate use. Moreover, a significant association was observed in males and females, albeit only for warfarin.Conclusion: Multi-methodological data mining revealed that warfarin use, not DOACs, is significantly associated with osteoporosis regardless of sex difference.
  • Sayoko Kinoshita; Kouichi Hosomi; Satoshi Yokoyama; Mitsutaka Takada
    International journal of medical sciences IVYSPRING INT PUBL 17 (3) 302 - 309 1449-1907 2020 [Refereed]
     
    Background: The association between metformin and amiodarone-induced adverse events was examined using spontaneous adverse event database. Additionally, the association between other antidiabetic drugs and amiodarone-induced adverse events were also examined. Methods: A total of 6,153,696 reports from the first quarter of 2004 through the fourth quarter of 2015 were downloaded from the US Food and Drug Administration adverse event reporting system. Reporting odds ratio (ROR) and information component (IC) were used to detect associations between antidiabetic drugs and amiodarone-associated adverse events. Additionally, subset data analysis was performed to investigate whether the use of antidiabetic drugs further increased or decreased the risk of adverse events in patients receiving amiodarone therapy. Next, the RORs were adjusted for coadministered antidiabetic drugs using logistic regression analysis. Results: By whole dataset analysis, significant inverse associations were found between metformin and interstitial lung disease (ROR 0.84, 95% confidence interval [CI] 0.79-0.90; IC -0.24, 95% CI -0.33 to -0.15). In the subset data analysis, metformin (ROR 0.62, 95%CI 0.43-0.89; IC -0.63, 95%CI -1.14 to -0.11), sulfonylureas (ROR 0.53, 95%CI 0.32-0.85; IC -0.85, 95%CI -1.53 to -0.17), and dipeptidyl peptidase-4 (DPP-4) inhibitors (ROR 0.25, 95%CI 0.08-0.78; IC -1.66, 95%CI -3.08 to -0.23) were inversely associated with hyperthyroidism. Additionally, metformin (ROR 0.43, 95%CI 0.33-0.57; IC -1.09, 95%CI -1.49 to -0.69), sulfonylureas (ROR 0.64, 95%CI 0.48-0.86; IC -0.59, 95%CI -1.00 to -0.17), and DPP-4 inhibitors (ROR 0.47, 95%CI 0.27-0.81; IC -0.99, 95%CI -1.76 to -0.22) were inversely associated with interstitial lung disease. In the logistic regression analyses, DPP-4 inhibitors (adjusted ROR 0.32, 95% CI 0.10-1.00) and metformin (adjusted ROR 0.46, 95% CI 0.34-0.62) were inversely associated with amiodarone-associated hyperthyroidism and interstitial lung disease, respectively. Conclusion: Metformin is a candidate drug to reduce the risk of amiodarone-induced hyperthyroidism and interstitial lung disease.
  • Takaya Uno; Kyoichi Wada; Kouichi Hosomi; Sachi Matsuda; Megumi Morii Ikura; Hiromi Takenaka; Nobue Terakawa; Akira Oita; Satoshi Yokoyama; Atsushi Kawase; Mitsutaka Takada
    EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY SPRINGER HEIDELBERG 76 (1) 117 - 125 0031-6970 2020/01 [Refereed]
     
    Purpose This study investigated the effects of clotrimazole troche on the risk of transplant rejection and the pharmacokinetics of tacrolimus. Methods The data mining approach was used to investigate whether the use of clotrimazole increased the risk of transplant rejection in patients receiving tacrolimus therapy. Patient data were acquired from the US Food and Drug Administration's Adverse Event Reporting System (FAERS) from the first quarter of 2004 to the end of 2017. Next, we retrospectively investigated the effect of clotrimazole troche on tacrolimus pharmacokinetics in seven patients who underwent heart transplantation between March and December 2017. Results The FAERS subset data indicated a significant association between transplant rejection and tacrolimus with clotrimazole [reporting odds ratio 1.92, 95% two-sided confidence interval (95% CI) 1.43-2.58, information component 0.81, 95% CI 0.40-1.23]. The pharmacokinetic study demonstrated a significant correlation between trough concentration (C-0) and area under the concentration-time curve of tacrolimus after discontinuation of clotrimazole (R-2 = 0.60, P < 0.05) but not before its discontinuation. Furthermore, the median clearance/bioavailability of tacrolimus after discontinuation of clotrimazole was 2.2-fold greater than that before its discontinuation (0.27 vs. 0.59 L/h/kg, P < 0.05). The median C-0 decreased from 10.7 ng/mL on the day after discontinuation of clotrimazole to 6.5 ng/mL at 1 day and 5.3 ng/mL at 2 days after its discontinuation. Conclusion Immediate dose adjustments of tacrolimus may be beneficial to avoid transplant rejection when clotrimazole troche is added or discontinued.
  • Satoshi Yokoyama; Yasuhiro Sugimoto; Chihiro Nakagawa; Kouichi Hosomi; Mitsutaka Takada
    SCIENTIFIC REPORTS NATURE PUBLISHING GROUP 9 (1) 16597 - 16597 2045-2322 2019/11 [Refereed]
     
    Cardiac glycosides, such as digoxin, inhibit Na+/K+-ATPases and cause secondary activation of Na+/Ca2+ exchangers. Preclinical investigations have suggested that digoxin may have anticancer properties. In order to clarify the functional mechanisms of digoxin in cancer, we performed an integrative analysis of clinical and bioinformatics databases. The US Food and Drug Administration Adverse Event Reporting System and the Japan Medical Data Center claims database were used as clinical databases to evaluate reporting odds ratios and adjusted sequence ratios, respectively. The BaseSpace Correlation Engine and Connectivity Map bioinformatics databases were used to investigate molecular pathways related to digoxin anticancer mechanisms. Clinical database analyses suggested an inverse association between digoxin and four cancers: gastric, colon, prostate and haematological malignancy. The bioinformatics database analysis suggested digoxin may exert an anticancer effect via peroxisome proliferator-activated receptor a and apoptotic caspase cascade pathways. Our integrative analysis revealed the possibility of digoxin as a drug repositioning candidate for cancers.
  • Ryosuke Ota; Atsushi Hirata; Keisuke Noto; Satoshi Yokoyama; Kouichi Hosomi; Mitsutaka Takada; Hiroshi Matsuoka
    INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS DUSTRI-VERLAG DR KARL FEISTLE 57 (11) 561 - 566 0946-1965 2019/11 [Refereed]
     
    Objective: We aimed to clarify the drug interaction between tacrolimus and voriconazole and investigate the relationship between blood concentrations of tacrolimus and voriconazole in hematopoietic stem cell transplantation (HSCT) patients. Materials and methods: A retrospective study was conducted to investigate the relationship between blood concentration of tacrolimus and that of voriconazole at the Kindai University Nara Hospital. Patients who received HSCT and tacrolimus and were prescribed voriconazole for the prevention or treatment of aspergillosis from April 2010 to July 2018 were identified from the medical records. A total of 13 patients (administration route of tacrolimus: intravenously in 6 patients. orally in 7 patients) were enrolled in the present study. Results: No significant correlation was observed between the blood concentration/dose (C/D) ratio of tacrolimus and the blood concentration of voriconazole (r = 0.38: p = 0.402; y = 102.8x + 928.1). However, a significant correlation was observed between the C/D ratio of tacrolimus and the blood concentration of voriconazole in the intravenous-administration group (r = 0.94; p = 0.0048; y = 421.9x + 810.5). Meanwhile, no significant correlation was observed in the oral-administration group (r = 0.43: p = 0.34; y = 7.9x + 719). Conclusion: The C/D ratio of tacrolimus was significantly correlated with the blood concentration of voriconazole when tacrolimus was intravenously administered. There was a difference in the mechanism of drug interaction between tacrolimus and voriconazole depending on the administration routes.
  • Takaya Uno; Kyoichi Wada; Sachi Matsuda; Megumi Ikura; Hiromi Takenaka; Nobue Terakawa; Akira Oita; Satoshi Yokoyama; Atsushi Kawase; Kouichi Hosomi; Mitsutaka Takada
    BRITISH JOURNAL OF CLINICAL PHARMACOLOGY WILEY 85 (9) 2176 - 2178 0306-5251 2019/09 [Refereed]
  • Makiko Iwasawa; Keiko Sagami; Satoshi Yokoyama; Kouichi Hosomi; Mitsutaka Takada
    International journal of clinical pharmacology and therapeutics DUSTRI-VERLAG DR KARL FEISTLE 57 (4) 197 - 206 0946-1965 2019/04 [Refereed]
     
    OBJECTIVE: Prevalence of guideline adherence for antiulcer drug prescription in patients receiving low-dose aspirin (LDA) therapy was examined and the association of risk factors with the adherence was assessed. MATERIALS AND METHODS: A retrospective cohort study using a population-based longitudinal healthcare database was conducted. Claims data between January 2005 and April 2016 were analyzed. A total of 3,079 patients were included in the study. The selected patients taking LDA were divided into two categories: those taking and those not taking antiulcer drugs in an inpatient setting. Additionally, they were classified into four groups according to the time antiulcer therapy was initiated. The risk factors for ulcer, such as history of gastrointestinal injuries; age ≥ 65 years; and concomitant use of anticoagulants, antiplatelets, oral corticosteroids, and nonsteroidal anti-inflammatory drugs except aspirin, were assessed. RESULTS: A total of 3,079 patients were included in the study. The rate of LDA patients using antiulcer drugs was 65.2%, with the strongest single factor associated with the use of antiulcer drugs being the concomitant use of corticosteroids. Among the LDA patients not taking antiulcer drugs, 66.8% had more than one risk factor. Irrespective of the use of concomitant treatment with antiulcer drug prior to hospital admission, 78.3% of the LDA patients continued their home regimen after hospital admission. CONCLUSION: Our results showed that the requirement of antiulcer therapy is not routinely evaluated at hospital admission, and antiulcer drugs for patients with ulcer risks are under-prescribed. Developing strategies to screen gastrointestinal risk factors at hospital admission is required to improve the guideline adherence for LDA-induced ulcer.
  • Atsushi Hirata; Keisuke Noto; Ryosuke Ota; Satoshi Yokoyama; Kouichi Hosomi; Mitsutaka Takada; Hiroshi Matsuoka
    International journal of clinical pharmacology and therapeutics DUSTRI-VERLAG DR KARL FEISTLE 57 (3) 135 - 143 0946-1965 2019/03 [Refereed]
     
    OBJECTIVE: We aimed to investigate the relationship between voriconazole (VRCZ) trough concentrations and hepatotoxicity and to evaluate whether the recommended trough concentration is adequate in our clinical setting. MATERIALS AND METHODS: A retrospective study was performed to investigate the relationship between serum VRCZ concentrations and the development of hepatotoxicity at the Kindai University Nara Hospital. Patients treated with VRCZ from March 2010 to January 2018 were identified from the medical records. A total of 42 patients (mean age of 61.9 ± 16.9 years; 33 males and 9 females) were enrolled in this study. RESULTS: Hepatotoxicity developed in 28.6% (12/42) of patients treated with VRCZ, and 91.7% (11/12) of these patients developed hepatotoxicity within 3 weeks after initiating the treatment. Significantly increased aspartate aminotransferase (AST; p < 0.001), alkaline phosphatase (ALP; p < 0.001), and alanine aminotransferase (p = 0.001) levels were observed after the initiation of VRCZ therapy. In addition, significant positive correlations between AST and VRCZ trough concentrations (p = 0.017) and between ALP and VRCZ trough concentrations (p = 0.012) were observed. VRCZ trough concentration was identified as a significant independent risk factor for hepatotoxicity (adjusted odds ratio: 1.611, 95% confidence interval: 1.131 - 2.579, p = 0.006), and the cutoff serum trough concentration was calculated to be 4.2 μg/mL. CONCLUSION: VRCZ-induced hepatotoxicity should be noted in the early stages of therapy. A sustained VRCZ trough concentration of ~ < 4.2 μg/mL is recommended to prevent hepatotoxicity in patients with low serum albumin levels.
  • Ryo Inose; Kouichi Hosomi; Katsuyuki Takahashi; Satoshi Yokoyama; Mitsutaka Takada
    International journal of clinical pharmacology and therapeutics DUSTRI-VERLAG DR KARL FEISTLE 57 (2) 63 - 72 0946-1965 2019/02 [Refereed]
     
    OBJECTIVE: This study investigated whether using biological disease-modifying antirheumatic drugs (bDMARDs) further increases the risk of malignant lymphoma in patients with rheumatoid arthritis undergoing methotrexate therapy using spontaneous adverse reaction databases in different countries. MATERIALS AND METHODS: Patient data were acquired from the US Food and Drug Administration's Adverse Event Reporting System (FAERS), the Japanese Adverse Drug Event Report (JADER), and the Canada Vigilance Adverse Reaction Online Database (CVARD) from the first quarter of 2004 to the end of 2015. Data subset analysis was performed to investigate whether the use of bDMARDs further increased the risk of malignant lymphoma in patients receiving methotrexate therapy. RESULTS: The FAERS subset data indicated a significant association between Hodgkin lymphoma and methotrexate with infliximab (reporting odds ratio (ROR): 8.28. 95% CI: 5.70 - 12.02; information component (IC): 2.04, 95% CI: 1.59 - 2.49). In addition, signal scores suggested that methotrexate with infliximab (ROR: 3.26. 95% CI: 2.68 - 3.98; IC: 1.31, 95% CI: 1.04 - 1.58) was significantly associated with non-Hodgkin lymphoma (NHL). The CVARD subset data also indicated a significant association between NHL and methotrexate with infliximab (ROR: 22.82. 95% CI: 5.02 - 103.78; IC: 1.77, 95% CI: 0.13 - 3.41). However, the JADER subset data revealed no significant associations. CONCLUSION: The present study shows that using infliximab further increases the risk of malignant lymphoma in patients receiving methotrexate therapy.
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  • Takaya Uno; Kyoichi Wada; Sachi Matsuda; Yuka Terada; Nobue Terakawa; Akira Oita; Satoshi Yokoyama; Atsushi Kawase; Kouichi Hosomi; Mitsutaka Takada
    EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY SPRINGER HEIDELBERG 75 (1) 67 - 75 0031-6970 2019/01 [Refereed]
     
    PurposeThis study aimed to investigate the effects of clotrimazole on the pharmacokinetics of tacrolimus in Japanese patients with heart transplants with different CYP3A5 genotypes.MethodsTwenty-six patients who underwent heart transplantation between June 2012 and July 2017 were enrolled in this retrospective study. The CYP3A5 (rs776746; CYP3A5*3) genotype was determined after monitoring and analysing tacrolimus blood concentrations. The pharmacokinetic profile of tacrolimus was examined before and after the discontinuation of clotrimazole and in patients with different CYP3A5 genotypes.ResultsThe CYP3A5*1/*1, *1/*3 and *3/*3 genotypes were detected in 2, 8 and 16 patients, respectively. After clotrimazole was discontinued, the CYP3A5 expresser (CYP3A5*1/*1 or *1/*3) group had a 3.3-fold median increase in apparent oral clearance of tacrolimus (0.27 vs. 0.89L/h/kg, P=0.002) compared with the CYP3A5 non-expresser (CYP3A5*3/*3) group with a 2.2-fold median increase (0.18 vs. 0.39L/h/kg, P<0.0001). Significant correlations were observed between C-0 and area under the concentration-time curve (AUC(0-12)) of tacrolimus after the discontinuation of clotrimazole in the CYP3A5 expresser and non-expresser groups, respectively (R-2=0.49 and 0.42, all P<0.05), but not before the discontinuation of clotrimazole.ConclusionThe effects of clotrimazole on tacrolimus pharmacokinetics in the CYP3A5 expresser patients were significantly greater than those in the CYP3A5 non-expresser patients. In addition, clotrimazole disturbed the correlation between C-0 and AUC(0-12) of tacrolimus. Careful dose adjustment of tacrolimus based on CYP3A5 genotypes may be beneficial for the patients with heart transplants who are concomitantly treated with clotrimazole.
  • Comparison of the Perception between Pharmacy Students and Practicing Pharmacists in the Acquisition of Physical Assessment Skills
    Toru Otori
    社会薬学 37 (2) 127 - 133 2018/12 [Refereed]
  • Kouichi Hosomi; Mai Fujimoto; Kazutaka Ushio; Lili Mao; Juran Kato; Mitsutaka Takada
    PloS one PUBLIC LIBRARY SCIENCE 13 (10) e0204648  1932-6203 2018 [Refereed]
     
    Different computational approaches are employed to efficiently identify novel repositioning possibilities utilizing different sources of information and algorithms. It is critical to propose high-valued candidate-repositioning possibilities before conducting lengthy in vivo validation studies that consume significant resources. Here we report a novel multi-methodological approach to identify opportunities for drug repositioning. We performed analyses of real-world data (RWD) acquired from the United States Food and Drug Administration's Adverse Event Reporting System (FAERS) and the claims database maintained by the Japan Medical Data Center (JMDC). These analyses were followed by cross-validation through bioinformatics analyses of gene expression data. Inverse associations revealed using disproportionality analysis (DPA) and sequence symmetry analysis (SSA) were used to detect potential drug-repositioning signals. To evaluate the validity of the approach, we conducted a feasibility study to identify marketed drugs with the potential for treating inflammatory bowel disease (IBD). Primary analyses of the FAERS and JMDC claims databases identified psycholeptics such as haloperidol, diazepam, and hydroxyzine as candidates that may improve the treatment of IBD. To further investigate the mechanistic relevance between hit compounds and disease pathology, we conducted bioinformatics analyses of the associations of the gene expression profiles of these compounds with disease. We identified common biological features among genes differentially expressed with or without compound treatment as well as disease-perturbation data available from open sources, which strengthened the mechanistic rationale of our initial findings. We further identified pathways such as cytokine signaling that are influenced by these drugs. These pathways are relevant to pathologies and can serve as alternative targets of therapy. Integrative analysis of RWD such as those available from adverse-event databases, claims databases, and transcriptome analyses represent an effective approach that adds value to efficiently identifying potential novel therapeutic opportunities.
  • Satoshi Yokoyama; Yuki Tanaka; Kazuki Nakagita; Kouichi Hosomi; Mitsutaka Takada
    INTERNATIONAL JOURNAL OF MEDICAL SCIENCES IVYSPRING INT PUBL 15 (14) 1686 - 1693 1449-1907 2018 [Refereed]
     
    A historical cohort analysis of the Japan medical data center (JMDC) claims databases was performed to compare the incidence rates of bleeding events with warfarin (WF) versus direct oral anticoagulant (DOAC) treatment in patients with non-valvular atrial fibrillation. The aim of this study is to clarify the risk factors for bleeding events in younger patients newly treated with WF or DOAC in clinical practice setting. Patients who newly initiated WF or DOAC treatment from April 2012 to March 2015 were selected from the JMDC claims database. A 1:1 propensity score matching analysis was used for new users of WF or DOAC. Kaplan-Meier curves were generated to depict the time to bleeding event (total bleeding events, gastrointestinal hemorrhage, and intracranial hemorrhage) during the follow-up period. Cox proportional regression models were used to estimate the hazard ratios for total bleeding events caused by oral anticoagulants. Overall, 2,046 patients (503 WF and 1,543 DOAC) were included. After applying propensity score matching, Kaplan-Meier analysis of the WF and DOAC groups displayed comparable incidences of total bleeding events, gastrointestinal hemorrhage, and intracranial hemorrhage. Cox proportional hazards modeling showed that the use of WF was not associated with total bleeding events compared with DOAC (hazard ratio: 1.21, 95% confidence interval: 0.93-1.54, p = 0.15). This historical cohort study using a claims database indicates that the bleeding risk of DOAC was comparable to that of WF in Japanese younger population.
  • Mikie Yamato; Kyoichi Wada; Tomohiro Hayashi; Mai Fujimoto; Kouichi Hosomi; Akira Oita; Mitsutaka Takada
    CLINICAL DRUG INVESTIGATION ADIS INT LTD 38 (1) 39 - 48 1173-2563 2018/01 [Refereed]
     
    Objective This retrospective cohort study was performed to examine the association between serum amiodarone (AMD) and N-desethylamiodarone (DEA) concentrations and the development of thyroid dysfunction.Methods Patients treated with AMD from January 2012 to April 2016 were identified from the computerized hospital information system database at the National Cerebral and Cardiovascular Center. Only patients whose serum AMD and DEA concentrations had been determined at least once were included in the study.Results A total of 377 patients were enrolled. Consequently, 54 (14.3%) and 60 (15.9%) patients who developed AMD-induced thyrotoxicosis and hypothyroidism were included. The mean DEA/AMD ratio during the pre-index period in the thyrotoxicosis group (0.86 +/- 0.24) was significantly higher than in the hypothyroidism (0.68 +/- 0.27) and euthyroidism (0.78 +/- 0.30; p < 0.0001) groups. In addition, the mean DEA/AMD ratio during the post-index period in the thyrotoxicosis group (1.05 +/- 0.40) was significantly higher than in the hypothyroidism (0.81 +/- 0.24) and euthyroidism (0.88 +/- 0.22; p < 0.0001) groups. A persistently higher DEA/AMD ratio was observed throughout the study period in the thyrotoxicosis group. In addition, good correlations between the DEA/AMD ratio and the levels of free thyroxine, free triiodothyronine levels, and log (thyroid-stimulating hormone) were observed in the thyrotoxicosis and euthyroidism groups.Conclusion Patients with AMD-induced thyrotoxicosis had an increased DEA/AMD ratio and patients with AMD-induced hypothyroidism had a decreased DEA/AMD ratio before the development of thyroid dysfunction. The DEA/AMD ratio may be a predictive marker for AMD-induced thyroid dysfunction.
  • Yutaro Mukai; Kyoichi Wada; Koji Miyamoto; Kazuki Nakagita; Mai Fujimoto; Kouichi Hosomi; Takeshi Kuwahara; Mitsutaka Takada; Kengo Kusano; Akira Oita
    JOURNAL OF ARRHYTHMIA ELSEVIER SCIENCE BV 33 (5) 434 - 439 1880-4276 2017/10 [Refereed]
     
    Background: The periprocedural protocol for atrial fibrillation (AF) ablation commonly includes anticoagulation therapy. Apixaban, a direct oral anticoagulant, is currently approved for clinical use; however, little is known about the effects of residual apixaban concentration on bleeding complications during/after AF ablation. Therefore, we measured residual apixaban concentration by using mass spectrometry and examined the anticoagulant's residual effects on bleeding complications. Methods: Fifty-eight patients (Mean age of 64.7 +/- 12.5 years; 31 males, 27 females) were enrolled and administered apixaban twice daily. We analyzed trough apixaban concentration, activated clotting time (ACT), heparin dose, and bleeding complications during/after AF ablation. Apixaban concentrations were directly measured using mass spectrometry. Results: Bleeding complications were observed in 19 patients (delayed hemostasis at the puncture site, 16; hematuria, 3; hemosputum, 1). No patient required blood transfusion. The mean trough apixaban concentration was significantly lower in patients with bleeding complications than without (152.4 +/- 73.1 vs. 206.8 +/- 98.8 ng/mL respectively, P=0.037), while the heparin dose to achieve ACT > 300 s was significantly higher in patients with bleeding complications (9368.4 +/- 2929.0 vs. 7987.2 +/- 2135.2 U/body respectively, P=0.046). Interestingly, a negative correlation was found between the trough apixaban concentration and the heparin dose to achieve ACT > 300 s (P=0.033, R=-0.281). Conclusions: Low residual plasma apixaban is associated with a higher incidence of bleeding complications during/after AF ablation, potentially because of a greater heparin requirement during AF ablation. (C) 2017 Japanese Heart Rhythm Society. Published by Elsevier B.V.
  • Mitsutaka Takada; Mikie Yamato; Kyoichi Wada; Mai Fujimoto; Kouichi Hosomi; Tomohiro Hayashi; Akira Oita
    EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY SPRINGER HEIDELBERG 73 (8) 1053 - 1054 0031-6970 2017/08 [Refereed]
  • Mai Fujimoto; Migiwa Kanou; Kouichi Hosomi; Mitsutaka Takada
    INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS DUSTRI-VERLAG DR KARL FEISTLE 55 (4) 295 - 303 0946-1965 2017/04 [Refereed]
     
    Objective: The aim of this study was to examine the associations between angiotensin receptor blockers (ARBs) and the risk of 10 major cancers by employing different pharmacoepidemiological assessments. Materials & methods: Data from the first quarter of 2004 through 2012 were downloaded from the US Food and Drug Administration Adverse Event Reporting System (FAERS). The reporting odds ratio (ROR) and information component (IC) were used to detect the signals. Furthermore, symmetry analysis was applied to the claims database to identify the risk of cancer after using ARBs from January 2005 to July 2013. Results: Significant inverse associations were found for all cancer types assessed as a whole (ROR: 0.78, 95% confidence interval (CI): 0.75 - 0.80; IC: -0.36, 95% CI: -0.40 to -0.31) in the analyses of FAERS database. Likewise, significant inverse association was found for all cancer types assessed as a whole (adjusted sequence ratio: 0.89, 95% CI: 0.82 - 0.96) in claims database. In addition, a significantly decreased risk for breast cancer and increased risks for pancreatic and prostate cancer were found in patients treated with ARBs in the analyses of individual cancers. Conclusions: Significant inverse association was found between ARB use and all cancer types assessed as a whole. However, in the analyses of individual cancers, the risks of ARB-induced cancer may differ according to cancer site. It may be reasonable to assume that the risks ofARB-induced cancer may differ according to cancer site.
  • Mikie Yamato; Kyoichi Wada; Mai Fujimoto; Kouichi Hosomi; Tomohiro Hayashi; Akira Oita; Mitsutaka Takada
    EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY SPRINGER HEIDELBERG 73 (3) 289 - 296 0031-6970 2017/03 [Refereed]
     
    We used a retrospective data mining approach to explore the association between serum amiodarone (AMD) and N-desethylamiodarone (DEA) concentrations and thyroid-related hormone levels.Laboratory data sets from January 2012 to April 2016 were extracted from the computerized hospital information system database at the National Cerebral and Cardiovascular Center (NCVC). Data sets that contained serum AMD and DEA concentrations and thyroid function tests, including thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3), were analyzed.A total of 1831 clinical laboratory data sets from 330 patients were analyzed. Data sets were classified into five groups (euthyroidism, hyperthyroidism, subclinical hyperthyroidism, hypothyroidism, and subclinical hypothyroidism) based on the definition of thyroid function in our hospital. Most abnormal levels of thyroid hormones were observed within the therapeutic range of serum AMD and DEA concentrations. The mean DEA/AMD ratio in the hyperthyroidism group was significantly higher than that in the euthyroidism group (0.95 +/- 0.42 vs. 0.87 +/- 0.28, p = 0.0209), and the mean DEA/AMD ratio in the hypothyroidism group was significantly lower than that in the euthyroidism group (0.77 +/- 0.26 vs. 0.87 +/- 0.28, p = 0.0038). The suppressed TSH group (0.98 +/- 0.41 vs. 0.87 +/- 0.28, p < 0.001) and the elevated FT4 level group (0.90 +/- 0.33 vs. 0.84 +/- 0.27, p = 0.0037) showed significantly higher DEA/AMD ratios compared with normal level groups. The elevated TSH group showed a significantly lower DEA/AMD ratio compared with the normal group (0.81 +/- 0.25 vs. 0.87 +/- 0.28, p < 0.0001).High and low DEA/AMD ratios were associated with AMD-induced hyperthyroidism and hypothyroidism, respectively. The DEA/AMD ratio may be a predictive marker for AMD-induced thyroid dysfunction.
  • Sayoko Kinoshita; Tomohiro Hayashi; Kyoichi Wada; Mikie Yamato; Takeshi Kuwahara; Toshihisa Anzai; Mai Fujimoto; Kouichi Hosomi; Mitsutaka Takada
    JOURNAL OF ARRHYTHMIA WILEY 32 (6) 474 - 480 1880-4276 2016/12 [Refereed]
     
    Background: Amiodarone is associated with a number of significant adverse effects, including elevated transaminase levels, pulmonary fibrosis, arrhythmia, and thyroid dysfunction. Although thyroid dysfunction is considered to be a common and potentially serious adverse effect of amiodarone therapy, the exact pathogenesis remains unknown because of its complex manifestations. Therefore, the prevalence of, and risk factors for, amiodarone-induced thyroid dysfunction in Japanese patients were investigated in the present study.Methods: A retrospective analysis of patients treated with amiodarone between January 2012 and December 2013 was performed. A total of 317 patients with euthyroidism, or subclinical hyperthyroidism or hypothyroidism, were enrolled in this study.Results: After being treated with amiodarone, 30 (9.5%) and 60 patients (18.9%) developed amiodarone-induced hyperthyroidism and amiodarone-induced hypothyroidism, respectively. Ten (33.3%) patients with amiodarone-induced hyperthyroidism and 40 (66.6%) with amiodarone-induced hypothyroidism were diagnosed within two years of the initiation of amiodarone therapy. Dilated cardiomyopathy (DCM) [Adjusted odds ratio (OR) 3.30 (95% confidence interval (CI): 1.26-8.90)1, and cardiac sarcoidosis [Adjusted OR 6.47 (95% Cl: 1.60-25.77)] were identified as predictors of amiodarone-induced hyperthyroidism. The baseline free thyroxine (T4) level [Adjusted OR 0.13 (95% Cl: 0.03-0.68)], and thyroid stimulating hormone (TSH) level [Adjusted OR1.47 (95% Cl: 1.26-1.74)] were identified as predictors of amiodarone-induced hypothyroidism.Conclusion: DCM and cardiac sarcoidosis were identified as risk factors for amiodarone-induced hyperthyroidism. Risk factors for amiodarone-induced hypothyroidism included higher baseline TSH level and lower baseline free T4 level, suggesting that subclinical hypothyroidism may be a potential risk factor for the development of amiodarone-induced hypothyroidism. (C) 2016 Japanese Heart Rhythm Society. Published by Elsevier B.V.
  • Yutaro Mukai; Kyoichi Wada; Mai Fujimoto; Kouichi Hosomi; Takeshi Kuwahara; Mitsutaka Takada
    INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS DUSTRI-VERLAG DR KARL FEISTLE 54 (10) 795 - 803 0946-1965 2016/10 [Refereed]
     
    Objective: The purpose of this study was to evaluate the long-term impact of therapeutic drug monitoring (TDM) services on the risk of hypoglycemia in cibenzoline therapy. In addition, we evaluated the impact of changes in clinical setting or patient background on the risk of hypoglycemia in patients receiving cibenzoline. Methods: TDM services for cibenzoline have been performed at the Japan National Cerebral and Cardiovascular Center since March 1998. A case-control study was performed from September 2012 to February 2013, and the calculated risk of hypoglycemia associated with cibenzoline use was compared with data from our previous studies, which were performed similar to 15 years ago. Results: A significantly increased risk for hypoglycemia was observed for users of cibenzoline (adjusted OR: 2.6; 95% CI: 1.5 -4.7). In an additional analysis, the calculated risk was slightly reduced (adjusted OR; 2.1, 95% CI; 1.1 -3.8) and hypertrophic obstructive cardiomyopathy (HOCM) was identified as a possible risk factor for hypoglycemia (adjusted OR: 4.7, 95% CI: 1.8 -12.3). There was a significant difference in the mean level of cibenzoline between outpatients with and without HOCM (360.5 +/- 166.9 ng/mL vs. 276.4 +/- 136.3 ng/ mL). An inverse relationship was observed between the percentage of outpatients whose cibenzoline serum level had been measured and their risk of hypoglycemia. Conclusions: Consistent TDM services for cibenzoline have contributed to a reduced risk of hypoglycemia associated with cibenzoline therapy. Patients with HOCM have a higher risk of developing hypoglycemia. Clinicians should therefore carefully monitor serum glucose levels in patients with HOCM taking cibenzoline.
  • Hosomi Kouichi
    Iryo Yakugaku (Japanese Journal of Pharmaceutical Health Care and Sciences) Japanese Society of Pharmaceutical Health Care and Sciences 42 (2) 87 - 97 1346-342X 2016/02 
    Atypical antipsychotics are less likely to cause extrapyramidal symptoms (EPS) compared to typical antipsychotics. However, recent studies have suggested that both atypicals and typicals produce a similar risk for EPS. We performed data mining using the Japanese national insurance claims database (NDB) constructed by the Ministry of Health, Labour and Welfare in Japan. Sequence symmetry analysis was performed to identify the risk of EPS after antipsychotic use. In this study, antiparkinsonian drugs with anticholinergic action were used as a marker of EPS. Antipsychotics in combination with antiparkinsonians was examined by prescription sequence symmetry analysis (PSSA). Likewise, event sequence symmetry analysis (ESSA) was undertaken to evaluate the association between antipsychotics and EPS diagnosis. Adjusted sequence ratios (ASRs) with 95% confidence intervals (CI) were calculated. In PSSA, significant associations with antiparkinsonians were found for the whole class of antipsychotics and atypicals with ASRs of 4.82 (95%CI 4.74-4.91) and 2.97 (2.93-3.01), respectively. A significant association between typicals and antiparkinsonians was not found. In ESSA, significant associations with EPS were found for the whole class of antipsychotics and atypicals with ASRs of 1.67 (1.65-1.69) and 1.49 (1.47-1.50), respectively. A significant association between typicals and EPS was not found. The number of patients who were prescribed atypicals first was 1.5 times larger than the number of patients who had typicals initially prescribed. Analysis of NDB demonstrated that antipsychotics increase the risk of EPS. Significant associations between EPS and atypicals (but not typicals) were found. This finding may be attributed to the prescribing sequence of antipsychotics.
  • Mitsutaka Takada; Mai Fujimoto; Kouichi Hosomi
    INTERNATIONAL JOURNAL OF MEDICAL SCIENCES IVYSPRING INT PUBL 13 (11) 825 - 834 1449-1907 2016 [Refereed]
     
    Purpose: Some studies have suggested that the use of benzodiazepines in the elderly is associated with an increased risk of dementia. However, this association might be due to confounding by indication and reverse causation. To examine the association between benzodiazepine anxiolytic drug use and the risk of dementia, we conducted data mining of a spontaneous reporting database and a large organized database of prescriptions.Methods: Data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) from the first quarter of 2004 through the end of 2013 and data from the Canada Vigilance Adverse Reaction Online Database from the first quarter of 1965 through the end of 2013 were used for the analyses. The reporting odds ratio (ROR) and information component (IC) were calculated. In addition, prescription sequence symmetry analysis (PSSA) was performed to identify the risk of dementia after using benzodiazepine anxiolytic drugs over the period of January 2006 to May 2014.Results: Benzodiazepine use was found to be associated with dementia in analyses using the FAERS database (ROR: 1.63, 95% CI: 1.61-1.64; IC: 0.66, 95% CI: 0.65-0.67) and the Canada Vigilance Adverse Reaction Online Database (ROR: 1.88, 95% CI: 1.83-1.94; IC: 0.85, 95% CI: 0.80-0.89). ROR and IC values increased with the duration of action of benzodiazepines. In the PSSA, a significant association was found, with adjusted sequence ratios of 1.24 (1.05-1.45), 1.20 (1.06-1.37), 1.23 (1.11-1.37), 1.34 (1.23-1.47), 1.41 (1.29-1.53), and 1.44 (1.33-1.56) at intervals of 3, 6, 12, 24, 36, and 48 months, respectively. Furthermore, the additional PSSA, in which patients who initiated a new treatment with benzodiazepines and anti-dementia drugs within 12- and 24-month periods were excluded from the analysis, demonstrated significant associations of benzodiazepine use with dementia risk.Conclusion: Multi-methodological approaches using different methods, algorithms, and databases suggest that long-term use of benzodiazepines and long-acting benzodiazepines are strongly associated with an increased risk of dementia.
  • Mitsutaka Takada; Mai Fujimoto; Haruka Motomura; Kouichi Hosomi
    INTERNATIONAL JOURNAL OF MEDICAL SCIENCES IVYSPRING INT PUBL 13 (1) 48 - 59 1449-1907 2016 [Refereed]
     
    Purpose: Voltage-gated sodium channels (VGSCs) are drug targets for the treatment of epilepsy. Recently, a decreased risk of cancer associated with sodium channel-blocking antiepileptic drugs (AEDs) has become a research focus of interest. The purpose of this study was to test the hypothesis that the use of sodium channel-blocking AEDs are inversely associated with cancer, using different methodologies, algorithms, and databases.Methods: A total of 65,146,507 drug-reaction pairs from the first quarter of 2004 through the end of 2013 were downloaded from the US Food and Drug Administration Adverse Event Reporting System. The reporting odds ratio (ROR) and information component (IC) were used to detect an inverse association between AEDs and cancer. Upper limits of the 95% confidence interval (CI) of < 1 and < 0 for the ROR and IC, respectively, signified inverse associations. Furthermore, using a claims database, which contains 3 million insured persons, an event sequence symmetry analysis (ESSA) was performed to identify an inverse association between AEDs and cancer over the period of January 2005 to May 2014. The upper limit of the 95% CI of adjusted sequence ratio (ASR) < 1 signified an inverse association.Results: In the FAERS database analyses, significant inverse associations were found between sodium channel-blocking AEDs and individual cancers. In the claims database analyses, sodium channel-blocking AED use was inversely associated with diagnoses of colorectal cancer, lung cancer, gastric cancer, and hematological malignancies, with ASRs of 0.72 (95% CI: 0.60 - 0.86), 0.65 (0.51 - 0.81), 0.80 (0.65 - 0.98), and 0.50 (0.37 - 0.66), respectively. Positive associations between sodium channel-blocking AEDs and cancer were not found in the study.Conclusion: Multi-methodological approaches using different methodologies, algorithms, and databases suggest that sodium channel-blocking AED use is inversely associated with colorectal cancer, lung cancer, gastric cancer, and hematological malignancies.
  • Hosomi Kouichi; Park Binawool; Inose Ryo; Fujimoto Mai; Takada Mitsutaka
    Iyakuhin Johogaku Japanese Society of Drug Informatics 17 (3) 125 - 132 1345-1464 2015/11 
    Objective: To examine the association between atypical and typical antipsychotics and extrapyramidal symptoms (EPS), we analyzed the US Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report database (JADER) from the Pharmaceuticals and Medical Devices Agency (PMDA).
    Methods: A reporting odds ratio was calculated and used to detect spontaneous report signals, with detection defined as a lower limit >1 in a 95% confidence interval.  In addition, time to onset and age at onset of EPS were investigated.
    Results: Drug-reaction pairs were identified in both FAERS (n=29,017,485) and JADER (n=2,079,653).  In analyses of both databases, significant associations were found between atypical and typical antipsychotics and EPS.  Atypical antipsychotics cause EPS with a longer duration of therapy compared to typical ones.  EPS in patients treated with atypical antipsychotics was observed at a broad range of ages compared to the patients treated with typical ones.
    Conclusion: Atypical antipsychotics, like typical ones, may increase the risk of EPS.  Because of the longer latency of onset, it may be difficult to find EPS associated with atypical antipsychotics.  Therefore, the severe symptom may be developed in patients treated with atypical antipsychotics.  The attention should be paid to the EPS in patients of all ages treated with atypical antipsychotics.
  • Mitsutaka Takada; Mai Fujimoto; Migiwa Kanou; Kouichi Hosomi
    PHARMACOEPIDEMIOLOGY AND DRUG SAFETY WILEY-BLACKWELL 24 451 - 452 1053-8569 2015/09 [Refereed]
  • Mai Fujimoto; Tomoya Higuchi; Kouichi Hosomi; Mitsutaka Takada
    PHARMACOEPIDEMIOLOGY AND DRUG SAFETY WILEY-BLACKWELL 24 474 - 474 1053-8569 2015/09 [Refereed]
  • Hosomi Kouichi; Arai Mari; Fujimoto Mai; Takada Mitsutaka
    Iyakuhin Johogaku Japanese Society of Drug Informatics 17 (1) 15 - 20 1345-1464 2015/05 
    Objective: Signal detection by analyzing adverse event spontaneous report databases is used to monitor drug safety.  One of the major spontaneous report databases is the FDA Adverse Event Reporting System (FAERS).  Recently, the Japanese Adverse Drug Event Report database (JADER) was released.  To compare FAERS and JADER, we calculated the signals of adverse events by new quinolones (NQs).
    Methods: We extracted reports of adverse events by NQs from FAERS and JADER, and analyzed them using the ROR data mining algorithm.  Thirteen kinds of NQs were extracted, and the terms of adverse events extracted were defined by MedDRA.
    Results: There were 35,990,645 reports in FAERS and 1,643,404 reports in JADER.  Significant RORs were found for hypersensitivity (FAERS: 1.78, JADER: 1.47), arrhythmia (1.07, 0.68), hypoglycemia (1.80, 2.03), hyperglycemia (0.72, 0.78), rhabdomyolysis (1.01, 0.78), tendon disorders (15.18, 6.59), psychiatric symptoms (1.12, 0.45) and convulsion (0.99, 1.31).  We identified 4 types of adverse events by comparing FAERS and JADER: 1) Signal detection in both, 2) No signal detection in either, 3) Signal detection only in FAERS, 4) Signal detection only in JADER.
    Conclusion: Analyzing spontaneous report databases has several limitations, but is still a valuable tool for identifying potential associations between drugs and adverse events.  Spontaneous report databases may also be useful for detecting differences in adverse events between different races, countries and regions.
  • Mai Fujimoto; Tomoya Higuchi; Kouichi Hosomi; Mitsutaka Takada
    INTERNATIONAL JOURNAL OF MEDICAL SCIENCES IVYSPRING INT PUBL 12 (3) 223 - 233 1449-1907 2015 [Refereed]
     
    Purpose: In recent years, the potential risk of cancer associated with statin use has been a focus of much interest. However, it remains uncertain whether statin therapy is associated with cancer risk. To examine the association between statin use and the risk of cancer, we conducted data mining using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and a large organized database of claims constructed by a database vendor (The Japan Medical Data Center Co., Ltd, Tokyo, Japan [JMDC]).Methods: Relevant reports in the FAERS, which included data from the first quarter of 2004 through the end of 2012, were identified and analyzed. The reporting odds ratio (ROR) was used to detect spontaneous report signals and was calculated using the case/non-case method. Additionally, signals were detected via the information component (IC) using the IC025 metric. Furthermore, event sequence symmetry analysis (ESSA) was applied to identify the risk of cancer following treatment with statins over the period January 2005 to July 2013.Results: In the FAERS database analyses, significant signals for colorectal cancer and pancreatic cancer were found for statins as a class. In the ESSA, significant associations between statin use and colorectal cancer and pancreatic cancer were found, with adjusted sequence ratios (95% confidence intervals) of 1.20 (1.08-1.34) and 1.31 (1.13-1.53), respectively, at an interval of 48 months.Conclusions: Multi-methodological approaches using different algorithms and databases suggest that statin use is associated with an increased risk for colorectal cancer and pancreatic cancer.
  • Mai Fujimoto; Tomoya Higuchi; Kouichi Hosomi; Mitsutaka Takada
    INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS DUSTRI-VERLAG DR KARL FEISTLE 52 (9) 762 - 769 0946-1965 2014/09 [Refereed]
     
    Objective: The efficacy and safety of statins have been studied in a number of clinical trials and epidemiological studies. In recent years, the Medicine and Healthcare Products Regulatory Agency (MHRA) has assessed the evidence available on the following adverse reactions associated with the use of statins: sleep disturbances, memory loss, micturition disorders (problems with urination), sexual disturbances, depression, and interstitial pneumopathy. However, the association between statin use and the risk of these adverse reactions remains unclear. To examine the association between statin use and the risk of lower urinary tract symptoms (LUTS) or the disorder causing LUTS, we carried out data mining using a prescription database. Methods: A large organized database of prescriptions constructed by a database vendor was used in the study. Symmetry analysis was used to identify the risk of LUTS after using statins over the period January 2006 to August 2013. Statin use in combination with drugs administered for storage LUTS was examined by prescription sequence symmetry analysis (PSSA). Results: A significant association between statins and drugs for storage LUTS was found, with adjusted sequence ratios (ASRs) of 1.21 (95% CI, 1.00-1.46), 1.19(95% CI, 1.04-1.38), and 1.17 (95% CI, 1.05-1.30) for intervals of 91, 182, and 365 days, respectively. In the analyses of individual statins, significant associations were found only for pravastatin. Significant associations with individual drugs for storage LUTS were found for solifenacin succinate with ASRs of 1.36 (95% CI, 1.02-1.81), 1.48 (95% CI, 1.19-1.84), and 1.47 (95% CI, 1.25-1.73) for intervals of 91, 182, and 365 days, for fiavoxate hydrochloride with an ASR of 1.56 (95% CI, 1.13-2.17) at an interval of 182 days, and for oxybutynin hydrochloride with ASRs of 2.06(95% CI, 1.11-3.94) and 1.71 (95% CI, 1.09-2.72) at intervals of 182 and 365 days. Significant associations with gender were found only in females with ASRs of 1.25(95% CI, 1.04-1.51) and 1.23(95% CI, 1.07-1.41) at intervals of 182 and 365days, respectively. Conclusions: Analysis of the prescription database showed significant association for storage LUTS in statin users.
  • Mitsutaka Takada; Mai Fujimoto; Kohei Yamazaki; Masashi Takamoto; Kouichi Hosomi
    DRUG SAFETY ADIS INT LTD 37 (8) 653 - 653 0114-5916 2014/08 [Refereed]
  • Fujimoto Mai; Takamoto Masashi; Hosomi Kouichi; Takada Mitsutaka
    Iyakuhin Johogaku Japanese Society of Drug Informatics 16 (2) 53 - 62 1345-1464 2014/08 
    Objective: To examine the association between statin use and the risk of sleep disturbances, data mining was performed on a claims database.
    Methods: Symmetry analysis was carried out to identify the risk of sleep disturbances after statin use during the period from January 2005 to December 2011.  Statin use in combination with hypnotic drugs was examined by prescription sequence symmetry analysis.  In this study, hypnotic drugs that are commonly prescribed for the treatment of insomnia were used as markers of sleep disturbances produced by statins. Likewise, event sequence symmetry analysis was undertaken to evaluate the association between statin use and the diagnosis of sleep disturbances.
    Results: Significant associations of statin use with short-acting hypnotic drugs were found, with an adjusted SR (sequence ratio) of 1.23 (95%CI: 1.04-1.45) at an interval of 12 months.  Otherwise, significant associations between individual statin use and hypnotic drug use were not found.  Significant associations between use of statins and the diagnosis of sleep disturbances were not also found in this study.
    Conclusions: Analysis of the claim database demonstrated that statin therapy might be associated with an emergence of sleep disturbances.  Therefore, individuals prescribed statins should be considered as having an increased risk of sleep disturbances.
  • Mitsutaka Takada; Mai Fujimoto; Kohei Yamazaki; Masashi Takamoto; Kouichi Hosomi
    DRUG SAFETY ADIS INT LTD 37 (6) 421 - 431 0114-5916 2014/06 [Refereed]
     
    Particular interest has been generated regarding the possible influence of statin use on sleep quality. However, no conclusive evidence exists that a particular statin is more likely to be associated with sleep disturbances versus others. It remains uncertain whether different statins produce different risks for sleep disturbance.To examine the association between statin use and the risk of sleep disturbances, we conducted data mining using the US Food and Drug Administration Adverse Event Reporting System (FAERS) and a large organized database of prescriptions constructed by a database vendor (Japan Medical Information Research Institute, Inc. Japan).Relevant reports in the FAERS were identified and analyzed. Data from the first quarter of 2004 through the end of 2013 were included in this study. The reporting odds ratio (ROR) was used to detect spontaneous report signals, calculated using the case/non-case method. For the ROR, a signal was detected if the lower limit of 95 % two-sided confidence interval (95 % CI) was > 1. Additionally, signal detection using the IC was conducted using the IC025 metric, a lower limit of the 95 % CI of the IC, where a signal is detected if the IC025 value exceeds 0. In addition, symmetry analysis was used to identify the risk of insomnia after using statins over the period of January 2006 to August 2013.In the analyses of the FAERS database, significant signals for sleep disturbances including disturbances in initiating and maintaining sleep, sleep disorders NEC, sleeping disorders due to a general medical condition, and parasomnias were found. In the prescription sequence symmetry analysis, a significant association between statin use and hypnotic drug use was found, with adjusted sequence ratios of 1.14 (1.03-1.26), 1.20 (1.11-1.29), and 1.18 (1.11-1.25) at intervals of 91, 182, and 365 days, respectively.Multi-methodological approaches using different algorithms and databases strongly suggest that statin use is associated with an increased risk for sleep disturbances including insomnia.
  • Inose Ryo; Hosomi Kouichi; Park Binawool; Fujimoto Mai; Takada Mitsutaka
    Iryo Yakugaku (Japanese Journal of Pharmaceutical Health Care and Sciences) Japanese Society of Pharmaceutical Health Care and Sciences 40 (5) 268 - 277 1346-342X 2014/05 
    Several case reports of hepatitis B virus reactivation after rituximab administration have been documented. We investigated the association between hepatitis B and C and 15 kinds of molecular-targeted drugs for cancer. We compared two databases, the Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report database (JADER) of the Pharmaceuticals and Medical Devices Agency (PMDA). Quantitative analysis involved calculating the reporting odds ratio (ROR) and 95% confidence interval (95% CI) as a measure of disproportionality. ROR is a tool that detects signals of adverse events for individual drugs, with signals detected when the lower limit of the 95% CI of ROR is > 1. We also investigated the timing of the adverse events and the age of the patients. There were 29,017,485 reports in FAERS and 2,079,653 reports in JADER. Signals were detected for rituximab-associated hepatitis B and hepatitis C, trastuzumab-associated hepatitis B, and imatinib-associated hepatitis B. In FAERS, hepatitis B often occurred within 1 month, whereas rituximab-associated hepatitis B often occurred 2-6 months after administration. In JADER, hepatitis B and rituximab-associated hepatitis B often occurred 1-3 months after administration. We conclude that signals of rituximab-associated hepatitis B and hepatitis C, trastuzumab-associated hepatitis B, and imatinib-associated hepatitis B are marked. Analyzing the timing and age of the patient at the occurrence of adverse events may suggest a relationship between drugs and these events.
  • Mai Fujimoto; Kouichi Hosomi; Mitsutaka Takada
    INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS DUSTRI-VERLAG DR KARL FEISTLE 52 (4) 259 - 266 0946-1965 2014/04 [Refereed]
     
    Objective: To examine the association between statin use and the risk of lower urinary tract symptoms (LUTS) in reports submitted to the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) between 2004 and 2011.Methods: Relevant reports in the FAERS were identified and analyzed. The reporting odds ratio (ROR) was used to detect spontaneous report signals, calculated using the case/non-case method. Cases were identified by the presence of reports of an adverse drug reaction (ADR) in which statins were the suspected drug. Non-cases were all the reports of the same reactions induced by drugs other than statins. The reporting odds ratio (ROR) and 95% confidential interval (CI) was calculated as a measure of disproportionality.Results: A total of 44,959,104 drug-reaction pairs was found in 2,681,739 reports. Significant RORs were found for both voiding (ROR; 1.16,95% CI; 1.10 - 1.23) and storage symptoms (ROR; 1.25, 95% CI; 1.20 - 1.30). Analysis of individual statins showed that rosuvastatin, atorvastatin, and lovastatin had significant disproportionality for voiding symptoms, while simvastatin, rosuvastatin, pravastatin, atorvastatin, pitavastatin, and lovastatin had significant disproportionality for storage symptoms. Of the four voiding symptoms, significant RORs were found for urine flow decrease and dysuria. Of the four storage symptoms, significant RORs were found for pollakiuria and nocturia. No fundamental differences in disproportionality were observed between genders.Conclusions: Analysis of the FAERS database showed small but reliable signals for LUTS in statin users. The mechanism responsible for these reactions is unknown. However, these adverse events should be monitored closely.
  • Mitsutaka Takada; Mai Fujimoto; Kouichi Hosomi
    INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS DUSTRI-VERLAG DR KARL FEISTLE 52 (3) 181 - 191 0946-1965 2014/03 [Refereed]
     
    Objective: Difference in the risk of gastrointestinal (GI) complications between users of enteric-coated and buffered low-dose aspirin (LDA) is unclear. The purpose of the study is to examine the difference in risk of GI damage between enteric-coated and buffered LDA products. Methods: A large and chronologically organized receipt database constructed by a database vendor was utilized. Prescription and event sequence symmetry analysis was used to identify the risk of LDA-induced GI complications over the period from January 2005 to July 2011. LDA use in combination with H2-receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) was examined by prescription sequence symmetry analysis. Likewise, symmetry analysis was undertaken to evaluate the association between the diagnosis of GI disease and the prescription of LDA products. Results: In July 2011, enteric-coated LDA users were more frequently co-administered PPIs than buffered LDA users (25.4% vs. 14.4%). Prescription sequence symmetry analysis of acid inhibitor use found no significant associations with enteric-coated LDA use and buffered LDA use. The event sequence symmetry analysis of ulcer, gastritis and duodenitis, and melena found significant associations with enteric-coated LDA use, with adjusted sequence ratios (ASRs) of 1.58 (1.23 - 2.06), 1.30 (1.03 - 1.65), and 14.38 (2.19 - 607.95), respectively, at the 6-month interval. At the 12-month interval, analysis of ulcers and melena found significant associations for enteric-coated LDA users, with ASRs of 1.39 (1.13 - 1.73) and 20.83 (3.33 - 863.25), respectively. Conclusions: Our findings do not support that there is no difference in the risk of GI complications between enteric-coated LDA and buffered LDA, but rather may imply that the risk of GI complications associated with enteric-coated LDA is higher than that with buffered LDA.
  • Hosomi Kouichi; Fujimoto Mai; Hachiken Hiroko; Sumitoko Keita; Takada Mitsutaka
    Iyakuhin Johogaku Japanese Society of Drug Informatics 15 (4) 147 - 154 1345-1464 2014/02 
    Objective: To examine the signal of gastrointestinal tract injury induced by aspirin and other drugs, we analyzed the US FDA Adverse Event Reporting System (FAERS).
    Methods: After deleting duplicate submissions, we analyzed the reports involving gastrointestinal tract injury associated with aspirin, H2-receptor antagonists (H2RAs), proton pump inhibitors (PPIs), ACE inhibitors, angiotensin II receptor blockers (ARBs), and antiplatelet and antithrombotic drugs.  The reporting odds ratio (ROR), a recognized pharmacovigilance tool, was used for the quantitative detection of signals.
    Results: Based on 29,017,485 co-occurrences, i.e., drug-adverse event pairs, found in 1,645,605 reports from 2004 to 2009, the ROR-associated gastrointestinal tract injury for aspirin alone, aspirin with H2RAs, aspirin with PPIs, aspirin with ACE inhibitors, aspirin with ARBs, and aspirin with antiplatelet and antithrombotic drugs were 2.88, 1.42, 1.46, 1.00, 1.05, and 2.98-8.26, respectively.  The following summarizes the types of listed reports: 86 reports described the daily aspirin doses, and 36/86 were between 75 and 100 mg; 343 reports described the periods between the start-date for aspirin and the date when gastrointestinal tract injury occurred, of which 128/343 were within one month while 215/343 were over one month; additionally, 78 reports described the total cumulative doses of aspirin, and 17/78 were between 1 and 5 g.
    Conclusion: The data suggest that H2RAs, PPIs, ACE inhibitors, and ARBs may reduce gastrointestinal tract injury associated with aspirin in possibility.
  • 豕瀬諒; 細見光一; PARK Binawool; 藤本麻依; 高田充隆
    医療薬学 Japanese Society of Pharmaceutical Health Care and Sciences 40 (10) 586 - 594 1346-342X 2014 
    To examine the association between biologics for rheumatoid arthritis and serious infections (hepatitis B, hepatitis C, tuberculosis, pneumonia and sepsis), we analyzed the US Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report database (JADER) of Pharmaceuticals and Medical Devices Agency (PMDA). The reporting odds ratio was calculated and used to detect spontaneous report signals, with detection defined as a lower limit >1 in a 95% confidence interval. In addition, time to onset and age at onset of tuberculosis were investigated. Drug-reaction pairs were identified in both FAERS (n = 29,017,485) and JADER (n = 2,079,653). In both databases, significant associations were observed between biologics and infections (hepatitis B, tuberculosis, pneumonia and sepsis). JADER data revealed a significant association of etanercept with hepatitis C. In FAERS, the majority of tuberculosis events, associated with all drugs, were observed within 1 month of administration, whereas most tuberculosis infections associated with biologics were observed during the 5 months following administration. In JADER, most cases of tuberculosis associated with all drugs and with biologics, respectively, were observed during the 2 months after administration. In conclusion, hepatitis C associated with etanercept treatment should be closely monitored in clinical practice. In addition, tuberculosis associated with biologics should be carefully monitored for 5 months following drug administration. Further studies are needed to confirm these findings.
  • Hiroko Hachiken; Ai Murai; Kyoichi Wada; Takeshi Kuwahara; Kouichi Hosomi; Mitsutaka Takada
    INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS DUSTRI-VERLAG DR KARL FEISTLE 51 (10) 807 - 815 0946-1965 2013/10 [Refereed]
     
    Objective: To provide further insights on the risks of gastrointestinal (GI) complications in individuals using low-dose aspirin (LDA), we investigated the concomitant use of LDA and antisecretory drugs. Additionally, we examined the frequency distributions of prescribing sequences for LDA and antisecretory drugs. Methods: Data from a computerized prescription order entry system was analyzed at the National Cerebral and Cardiovascular Center of Japan. LDA use in combination with H2-receptor antagonists (H2RAs) and proton pomp inhibitors (PPIs) was examined over the period from January 2001 to December 2010. Prescription sequence symmetry analyses were used to identify LDA-induced H2RAs or PPIs users. Results: In December 2010, PPIs accounted for 9.9% of the prescriptions for buffered LDA users and 16.1% of those for enteric-coated LDA users. Incident use of PPIs occurred more frequently among enteric-coated LDA users than buffered LDA users (17.6% vs. 11.0%, respectively). Prescription sequence symmetry analyses of PPI use revealed significant associations with enteric-coated LDA use, resulting in adjusted sequence ratios of 1.82 (95%CI, 1.11 - 3.03) and 1.87 (95% CI, 1.26 - 2.83) at intervals of 182 and 365 days, respectively. Enteric-coated LDA users tended to initiate PPI therapy on the same date more frequently than buffered LDA users (35.1% vs. 10.8%, respectively). Conclusions: Our findings do not support the notion that enteric-coated LDA products confer a lower risk for GI complications than buffered formulations, but may conversely imply that the risk of GI complications associated with buffered LDA is lower than that of enteric-coated LDA.
  • 大鳥徹; 村上悦子; 北小路学; 細見光一; 井上知美; 小竹武; 高田充隆; 松山賢治
    J Pharm Commun 日本ファーマシューティカルコミュニケーション学会 9 (1) 17 - 26 2011/11 
    薬学教育モデル・コアカリキュラムに沿った実習の実施状況を検証し、6年制長実務実習の問題点の検討と改善を目的に学生アンケートを実施した。アンケート結果は、薬学教育において改善項目の抽出などに使用されている顧客満足度(CS)分析より検討した。病院実務実習の実習内容は、「TDMについての演習あるいは実習を受けましたか?」が「要改善項目」として抽出され、薬局実務実習の実習内容は、「薬品管理に関する説明を受けましたか?」が「要改善項目」として抽出された。また、実務実習の指導にあたる指導薬剤師に関しては病院薬局共に、「指導薬剤師の言動に不快だと感じたことがありましたか?」が「改善検討項目」として抽出された。言動は実務実習を円滑に遂行する上で非常に重要かつ基本的な問題で、大学教員と実習指導薬剤師がワークショップなどで共にコミュニケーションとは何かを学び、スキルを検討する必要があった。
  • HOSOMI Kouichi; MUROI Nobuyuki; AZUMA Kazuo; IKEDA Rikiko; UOMOTO Michiko; OHKAWA Kyoko; MIYAKE Keiichi; NAKAGAWA Motoko; KAWAMOTO Yukiko; KIYOHARA Yoshifumi; KIM Ke-Ih; SAWASAKI Takashi; ONO Tatsuya; NISHIDA Hideyuki; OHNO Mariko; OGATA Sonoko; FUKUSHIMA Shoji; TOKUYAMA Shogo; OHNISHI Noriaki; HIRAI Midori; MATSUYAMA Kenji
    Iryo Yakugaku (Japanese Journal of Pharmaceutical Health Care and Sciences) Japanese Society of Pharmaceutical Health Care and Sciences 32 (1) 64 - 72 1346-342X 2006/01 
    We conducted a survey on the practical training of pharmacy students in 47 community pharmacies and 76 hospital pharmacies in Hyogo Prefecture. Items surveyed included the acceptance system for pharmacy students, practical training curriculum, problems and difficulties. In many community pharmacies and hospital pharmacies, instruction in practical training was recognized as worthwhile despite the workload involved. Though the content of the practical training varied, dispensing and medication instruction were the most common items in the practical training for both community pharmacies and hospital pharmacies. Communication with patients and management of medication history were the focus of training in community pharmacies, while the major aspects of training in hospital pharmacies were dispensing of injections and TDM (therapeutic drug monitoring).
    Many pharmacists were of the opinion that the content and goals of the training should be reviewed and that it needed to be further evaluated. Revision of the practical training in universities was also recommended. Further, in order to achieve an efficient practical training curriculum it was felt that the training should be more linked to the special characteristics of community pharmacies and hospital pharmacies.
  • HOSOMI Kouichi; KUBO Yoshiyasu; OKUNO Akihiro; UMETANI Yoshiharu; HASHIMOTO Masaru; ARAYA Teruhisa; KOMORI Hideshi; HIRAI Midori; MATSUYAMA Kenji
    Iryo Yakugaku (Japanese Journal of Pharmaceutical Health Care and Sciences) Japanese Society of Pharmaceutical Health Care and Sciences 31 (3) 228 - 232 1346-342X 2005/03 
    We examined the clinical efficacy of shitei-decoction in 108 patients with hiccups with respect to various factors influencing them : sex, age, other drugs for hiccups, use of benzodiazepines, malignant tumors, use of antitumor agents, metastasis, complications and stress. Hiccups completely disappeared in 63 of the 108 patients following the administration of shitei-decoction, a rate of 58.3%. However, if we judge efficacy by the sum of patients whose hiccups disappeared and those who experienced remission, the efficacy rate for shitei-decoction was 82.4%. The chi-square test showed that there was no significant correlation between the above hiccup influencing factors and the efficacy of shitei-decoction. Despite previous reports to the contrary, there was no correlation between the efficacy of shitei-decoction and co-administration of benzodiazepines. However, the efficacy of shitei-decoction tended to be higher in patients with brain metastasis, suggesting that efficacy may be greater for central hiccups than peripheral hiccups.
  • OKUNO Akihiro; HOSOMI Kouichi; MAEKAWA Megumi; UMETANI Yoshiharu; TSUDA Yasuo; OHNISHI Shinsaku; ARAYA Teruhisa; YAMAMOTO Kinya; TAKAMIYA Shizuo; SATO Michiaki; MATSUYAMA Kenji
    Iryo Yakugaku (Japanese Journal of Pharmaceutical Health Care and Sciences) Japanese Society of Pharmaceutical Health Care and Sciences 30 (10) 656 - 665 1346-342X 2004/10 
    This report describes how good medication guidance may be provided to patients with blood cancer and discusses the role of the pharmacist in raising the satisfaction of patients and family members with treatment. Chemotherapy for blood cancer causes a variety of severe adverse reactions, giving patients and their families a feeling of anxiety towards it. It is therefore necessary for pharmacists to provide medication guidance in order to reduce anxiety towards drugs during long-term chemotherapy.
    In the present study, we examined questions regarding chemotherapy from patients and their families for 32 cases in the past 3 years. The 485 questions asked were classified according to subject as follows : 1) Adverse reactions-40%, 2) Chemotherapy protocol-12%, 3) Blood transfusions-7%, 4) Effects of chemotherapy-6%, 5) Granulocyte-colony stimulating factor (G-CSF) -6%, 6) Method of use-4%, 7) Drugs preventing opportunistic infections-4%, 8) Administration method-3%, 9) Chemotherapy in outpatient ward-3 %, 10) High-dose chemotherapy-3 %, 11) Discharge and short stay at home-1%, 12) Drop-out-1 %, 13) Drawing blood-1 %, 14) Color of chemotherapy agents for injection-1%, and 15) Differences between treatment strategies at other hospitals-1%.
  • Kouichi Hosomi; Akihiro Okuno; Yoshiharu Umetani; Teruhisa Araya; Kenji Matsuyama; Jun Haginaka; Masaki Mifune; Yutaka Saito
    Yakugaku Zasshi The Pharmaceutical Society of Japan 124 (9) 587 - 598 0031-6903 2004/09 [Refereed]
     
    We studied the color change of phenothiazines and metal-containing drugs after compound formation, followed by use of FT-Raman spectrocopy to observe any structural changes in them. When 6 phenothiazines (thioridazine hydrochloride, prochlorperazine maleate, levomepromazine maleate, chlorpromazine phenolphthalinate, fluphenazine maleate and perphenazine fendiate) formed compounds with natural aluminum silicate, the color change was accompanied by a shift of FT-Raman signals. These changes could be attributed to the structural changes of phenothiazines. This present observation can be then used in advance to avoid coloration of phenothiazines during preparative procedures with metal-containing drugs such as antacids. © 2004 The Pharmaceutical Society of Japan.
  • Kiyoharu Nishide; Ryuichi Kurosaki; Kouichi Hosomi; Hitoshi Imazato; Takehisa Inoue; Manabu Node; Toshiumi Ohmori; Kaoru Fuji
    Tetrahedron 51 (40) 10857 - 10866 0040-4020 1995/10 [Refereed]
     
    New chiral nitroenamines 4a,b having (S)-2-t-butyldimethylsiloxymethylpyrrolidine as an auxiliary were found to be very effective for asymmetric nitroolefination of α-alkyl-γ- and δ-lactones. The enantiomeric excess of the product increased remarkably in the reaction with γ-lactones compared with previous nitroenamines 1a,b. A possible chelation model for the transition state of the asymmetric nitroolefination is discussed. © 1995 Elsevier Science Ltd.
  • Manabu Node; Ryuichi Kurosaki; Kouichi Hosomi; Takehisa Inoue; Kiyoharu Nishide; Toshiumi Ohmori; Kaoru Fuji
    Tetrahedron Letters 36 (1) 99 - 102 0040-4039 1995/01 [Refereed]
     
    New chiral nitroenamines 4a,b were found to be very effective for asymmetric nitroolefination of α-alkyl-γ- and δ-lactones. The enantiomeric excess of the product ran up to 99 %. A possible chelation model for the transition state of the asymmetric nitroolefination was discussed. © 1994.
  • Takehisa Inoue; Kouichi Hosomi; Mamoru Araki; Kiyoharu Nishide; Manabu Node
    Tetrahedron: Asymmetry 6 (1) 31 - 34 0957-4166 1995/01 [Refereed]
     
    σ-Symmetric bicyclic diketones 8a-c were enantioselectively reduced with baker's yeast to give the chiral hydroxy ketones 7a-c in 74-;100% ee. The reduction product (+)-7a and (-)-7′c were shown to be the chiral intermediates for the total synthesis of cantabrenonic acids derivatives 3 and hirsutene (4), respectively. The subsequent transformation of (+)-7a gave the intermediate (+)-5 for the total synthesis of capnellenols (1, 2). © 1994.

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