Shoji SERA

Objectives To examine the incidence of stroke or systemic embolic events (SSEs) and bleeding events in untreated patients with non-valvular atrial fibrillation (NVAF) after widespread use of direct oral anticoagulant agents (DOACs). Design Multicentre, non-interventional, observational, retrospective cohort study using real-world data in Japan (2016-2018). Setting The Mie, Musashino University study of NVAF, which used the Mie-Life Innovation Promotion Center Database. This is a regional clinical database involving one university hospital and eight general hospitals in Mie Prefecture in Japan. Participants Japanese patients with NVAF (n=7001). Primary and secondary outcome The incidence of SSEs and bleeding events. Results A total of 7001 patients with NAVF were registered, and 53.0% were treated with DOACs, 10.6% were treated with warfarin and 36.4% had no treatment. Additionally, 29.5% of patients with a CHADS2 (congestive heart failure, hypertension, age≥75 years, diabetes, previous stroke or transient ischemic attack) score of 3–6 were untreated. In the no treatment group, the SSE rates by the CHADS2 score (0, 1, 2 and 3–6) were 1.4%, 1.4%, 3.2% and 8.0%, respectively. The rates of bleeding events by the CHADS2 score (0, 1, 2 and 3–6) in the no treatment group were 0.7%, 1.0%, 1.2% and 2.9%, respectively. A multivariate analysis of SSEs in components of the CHADS2 showed that the adjusted HRs were 2.32 for heart failure, 1.66 for an age ≥75 years, 1.81 for diabetes mellitus and 5.84 for prior stroke or transient ischaemic attack. Conclusions Approximately one-third of the patients do not receive any anticoagulation in the modern DOAC era in Japan. The SSE rate increases by the CHADS2 score. The SSE rate is low in patients with a CHADS2 score <1, supporting no indication of anticoagulation in current guidelines. In patients with a CHADS2 score >1, the use of anticoagulant drug therapy is recommended because of a higher risk of stroke.

医療系学生を対象にした情報リテラシー教育支援システム(Wed-ED)を開発した.Wed-EDは教員と学生全員に1台ずつの専用パーソナルコンピュータが用意できれば,各種アンケート,試験,提出ファイルの収集等を容易に行なうことができる.これらは全てWedサーバ上のデータベースに登録され,その内容や状況を随時監視することができる.Wed-EDのソフトは全て無料で利用でき,その構築方法,スクリプトをページ上で公開し,システム構築方法も解説しているため,各自の環境に合わせたシステム構築が可能である.実際に薬学部情報処理の講義に使用し,小テストを行なったが,十分な実用性を認めた

The quantitative determination of serum fentanyl (FT), urinary FT and its main metabolite, Nor-FT was examined to ascertain the individual variation in the elimination process of FT among 17 patients. The pharmacokinetics of FT was solved from the obtained data using 2-compartment model including the metabolic process. Furthermore, we compared Nor-FT excretion with CYP3A4 activity based on urinary 6&beta;-hydroxycortisol (6&beta;-OHF) and cortisol (F) excretion ratio.<BR> FT and Nor-FT were determined by isotope dilution analysis using deuterium labeled FT (FT-²H₁₉) or Nor-FT (Nor-FT-²H₁₀) as internal standards. The isotopic fractionation was achieved by a capillary gas chromatograph equipped with a surface ionization detector. The pharmacokinetic parameters were calculated from serum FT concentration time profiles and excreted amount of FT and Nor-FT in urine, using the pharmacokinetic data analysis software, WinNonlin standard Ver. 1.5 (Scientific Consulting). Urinary F and 6&beta;-OHF concentrations were determined by HPLC using fludrocortisone as an internal standard after conversion to fluorescence derivative using 1, 2-diamino-4, 5-methylenedioxybenzene.<BR> The obtained pharmacokinetic parameters showed considerable difference between individuals. The predicted time course for FT and Nor-FT was adapted to FT kinetics. The predicted final excretion rates of FT and Nor-FT were 0.14-15.77% (mean 4.30%) and 7.36-99.38% (mean 55.12%), respectively. The CYP3A4 activity obtained from steroid excretion was not reflected by FT elimination in this study for a low dose of FT (5&mu;g/kg).

安定同位体希釈分析により,麻薬性鎮痛薬フェンタニル(FT)の血清中濃度を測定した.19個の重水素を標識したFT-2H19とFTは,表面電離型イオン化検出器装備キャピラリGCにより15分以内で分離測定可能であった.ヒト血清1mlに対してFTを0.2-40ng,FT-2H19を20ng添加し抽出後GC測定したところ,ピーク面積比と重量比の間には優れた直線関係が認められた(r=0.999).FTの構造類似物質を内部標準に用いた場合と本方法を比較検討し,本方法の有用性を示した.外科手術時にFT投与を受けた患者の血清中濃度を測定したところ,生体内物質や併用薬物の影響を受けず正確な測定が可能であり,FTの体内動態解析に有用である

Isotope dilution analysis was applied to determine urinary excretion of fentanyl (FT) and its main metabolite, norfentanyl (Nor-FT), by isotopic fractionation using a capillary gas chromatograph equipped with a surface ionization detector (SID) . Urinary FT was determined quantitatively in the range of 0.4-40 ng/ml using deuterium labeled FT (FT-²H₁₉), as an internal standard.<BR>We also performed isotope dilution analysis of Nor-FT in urine. NV Alkylation was necessary to sensitively detect Nor-FT with SID. Methyl derivative was selected from 3 kinds of NV alkyl derivatives to increase sensitivity and peak resolution, and to prevent interference with urinary compound. Nor-FT concentration was quantitatively determined in the range of 10-400 ng/ml using deuterium labeled Nor-FT (Nor-FT-²H₁₀) . No endogenous compounds or concomitant drugs interfered with the detection of FT and Nor-FT in the urine of patients. The present method will be useful for pharmacokinetic studies and the evaluation of drug interactions in FT metabolism.

Isotopic fractionation of benzoic acid (BA) and hippuric acid (HA) from their deuterated analogues (BA-d₅ and HA-d₅) were examined by high performance liquid chromatography (HPLC) . Reversed-phase HPLC was used with C₁₈column and McOH-phosphoric acid solution mixture as mobile phase. The resolution coefficients between protio-and deutero forms were 1.22 for BA and 1.05 for HA respectively<BR>The present isotopic fractionation procedure was applied to the isotopic dilution analysis of BA and HA. Measurement of the samples contained known amount of protio-and deutero-forms allowed observation of linear relationship between peak area ratio and added amount ratio in the case of both compounds. The correlation coefficients obtained by regression analysis were 0.9995 for BA and 0.9999 for HA, respectively. The present method was applied to determine the urinary excretion of HA-d₅in man after oral administration of BA-d₅. Two methods were examined for determination of HA-d₅. One was the measurement of BA-d₅after hydrolysis of HA-d₅, and another was direct measurement of HA-d₅. Former method is superior to latter method in the separation of protio-and deutero-forms, while, requires the complex procedures, conversion, extraction and evaporation. These isotopic fractionation of BA from BA-d₅and HA from HA-d₅by HPLC are simple and specific methods for determination of exogenous HA without the interference of endogenous HA.