論文 - 吉野　鉄大

Exploring Standardized Scales and Serum Biomarkers to Evaluate Changes in Pruritus due to Eczema after Japanese Kampo Treatment: A Prospective Case Series

Yoshino T., Horiba Y., Mimura M., Watanabe K.

Complementary Medicine Research 29 （ 5 ） 373 - 380 2022年10月

ISSN  25042092

　概要を見る

Background: We aimed to explore standardized scales and serum biomarkers for tracking changes in the symptoms and severity of pruritus due to eczema in patients treated with Kampo formulas. Patients and Methods: This prospective, single-arm, pre-post comparison case series recruited patients with pruritus mostly due to eczema who consulted the Kampo Clinic at the Keio University Hospital from June 2019 to March 2020. The participants were prescribed a personalized Kampo formula for 12 weeks. Patient profiles and symptoms were assessed every 4 weeks using the visual analog scale (VAS), patient-oriented eczema measure (POEM) scale, 5-D itch scale (5D), Skindex-16, and eczema area and severity index (EASI). Blood biomarkers and intestinal permeability indicators were measured at the first consultation and 12 weeks later. Results: Pruritus and eczema severity improved significantly over time. The VAS, POEM, 5D, and Skindex-16 scores were well-correlated. The serum interleukin-31 levels decreased significantly after a 12-week intervention. Changes in the interleukin-31 level correlated with the diamine oxidase level at week 0, suggesting the involvement of the Th2 immune system and intestinal permeability in the mechanism of Kampo formulas. Conclusion: The evaluated scales are suitable for evaluating subjective symptoms and eczema severity after Kampo treatment; further studies are required to verify the study findings.

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Climacteric symptoms in postoperative patients among endometrial cancer, cervical cancer, and ovarian cancer: a cross-sectional study

Horiba Y., Yoshino T., Yokota M., Iwata T., Watanabe K., Mimura M., Aoki D.

Supportive Care in Cancer 30 （ 8 ） 6785 - 6793 2022年08月

ISSN  09414355

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Purpose: To date, no studies have assessed climacteric symptoms after hystero-adnexectomy for endometrial, cervical, or ovarian cancer. Thus, this study aimed to compare climacteric symptoms among patients who underwent surgery for these three cancer types. Methods: In this cross-sectional study, we interviewed patients who were registered at a menopausal outpatient clinic between January 1999 and July 2016 after undergoing total hysterectomy, intrapelvic only or intrapelvic plus para-aortic lymph node dissection, and bilateral adnexectomy performed via laparotomy as a cancer treatment. Climacteric symptoms were assessed using a patient-reported questionnaire covering core domains with five symptoms only at the initial consultation. Each symptom was graded from 0 (no symptoms) to 3 (severe symptoms). We evaluated the frequency of symptom severity according to the time elapsed since surgery and the cancer type. Results: The numbers of patients with endometrial, ovarian, and cervical cancer were 328, 90, and 107, respectively. Overall, climacteric symptoms were more severe in patients with cervical cancer than in those with endometrial or ovarian cancer; symptom severity decreased with increasing time since surgery. However, symptom severity did not decrease significantly over time in patients with cervical cancer even after > 5 years had elapsed since surgery. Conclusion: The climacteric symptoms were less severe in patients with endometrial or ovarian cancer with longer time elapsed since surgery but not in those with cervical cancer. Patients with cervical cancer may require more prompt interventions, including symptomatic treatment and longer follow-up period, than those with endometrial or ovarian cancer.

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Conference report: Second annual young researcher forum of the Japan Society of Medical and Pharmaceutical Sciences for Traditional Medicine

Yoshino T., Yoneda T., Yang X., Nishihara M., Ogawa K., Kitamura M., Ando H., Nakashima S., Horie I.

Traditional and Kampo Medicine （Wiley）  9 （ 2 ） 144 - 147 2022年08月

　概要を見る

Five young researchers presented their studies in the field of traditional Japanese herbal medicine (Wakan-yaku) at the second annual young researcher forum entitled “Growing Research Buds by Young Investigators,” held during the annual meeting of the Japan Society of Medical and Pharmaceutical Sciences for Traditional Medicine 2021. Mr. Yoneda presented exploratory research on new pharmaceutical seed compounds from garlic (Allium sativum). Dr. Yang investigated whether diosgenin promoted proper axonal regeneration in the brain using a mouse model of Alzheimer's disease. Her study clarified the molecular mechanisms of the diosgenin-driven accurate pathfinding of injured axons. Mr. Nishihara presented his research on promoting the effective utilization of Phellodendron trees in Nara Prefecture. His research team evaluated the possibility of short-term cultivation, screened for useful components in the leaves. Dr. Ogawa used the Japanese Adverse Drug Event Report (JADER) database, which contains reports of side effects associated with drug treatment, to demonstrate the effectiveness of hokizai in reducing side effects, particularly those of anticancer drugs. Dr. Kitamura reported that Cnidium monnieri (L.) Cusson fruit extract and the isolated active ingredients, osthol and imperatorin, strongly inhibited the activity of furin-like enzymes. Further screening indicated that root extracts of Paeonia lactiflora Pall. and Scutellaria baicalensis Georgi suppressed cell syncytial formation by the S protein. The event was held online, and we had 86 participants. We can improve this forum in terms of format, frequency, and publicity activities; however, we hope to hold this forum in 2022 and in the future.

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A prediction model of qi stagnation: A prospective observational study referring to two existing models

Maeda-Minami A., Ihara K., Yoshino T., Horiba Y., Mimura M., Watanabe K.

Computers in Biology and Medicine 146   105619 2022年07月

ISSN  00104825

　概要を見る

Objective: To establish a prediction model of qi stagnation referring to two existing models. Design: Prospective observational study. Setting: We recruited patients who visited the Kampo Clinic at Keio University from February 2011 to March 2013. Methods: We constructed a random forest algorithm with 202 items as independent variables to predict qi stagnation patterns using full agreement data of the physicians’ diagnosis and the result of two existing scores as a reference standard. To compare the new model with the two existing models, we calculated the discriminant ratio (prediction accuracy), precision, sensitivity (recall), specificity, and F-measure of these models. Results: The number of eligible participants was 1,194, and 29.1% of them were diagnosed with qi stagnation by Kampo physicians. The discriminant ratio, precision, sensitivity, specificity, and F-measure in our new model were 0.960, 0.672, 0.911, 0.964, and 0.774, respectively. Our new model had a significantly higher discriminant ratio than the two existing models. Conclusions: We constructed a better qi stagnation prediction model than the previously established ones. Our results can be utilized to reach an international agreement on qi stagnation pattern diagnosis in traditional East Asian medicine.

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Oral Astragalus Root Supplementation for Mild to Moderate Chronic Kidney Disease: A Self-Controlled Case-Series

Yoshino T., Horiba Y., Mimura M., Watanabe K.

Frontiers in Pharmacology 13   775798 2022年03月

ISSN  16639812

　概要を見る

In this self-controlled case series, we aimed to investigate the variation in estimated glomerular filtration rate (eGFR) after taking astragalus-containing preparations in patients with mild to moderate chronic kidney disease (CKD) by retrospectively reviewing their charts in our clinic. We set the inclusion criteria as first-visit patients aged 20 years or older presenting to our clinic between 1 October 2014, and 31 June 2019, and who were prescribed astragalus-containing herbal preparations for any reason. We calculated the mean eGFR from the readings taken 6 months before (pre) and after (post) the intake of astragalus-containing preparations for each participant. Among the 37 patients included in our final analysis, we found a statistically significant improvement in the eGFR after prescribing astragalus-containing preparations (pre, 66 ± 12 ml/min/1.73 m² vs. post, 70 ± 14 ml/min/1.73 m²; p < 0.001 by paired t-test). Our results were consistent regardless of age, sex, CKD stage of the participants (G2 or G3), daily dosage of astragalus root, or duration of astragalus-containing preparations. No severe adverse reactions were recorded in the charts of the study participants. Our results suggest that there is eGFR improvement after taking astragalus-containing preparations in mild to moderate CKD cases as reported previously. The findings should be considered with caution due to major limitations such as small sample size without optimum control, short follow-up period, and incomplete data. Further adequately powered and designed studies are needed to confirm the efficacy and safety of the long-term use of astragalus root in patients with mild to moderate CKD.

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総合診療病棟　大柴胡湯去大黄による薬剤性間質性肺炎を早期診断加療し、救命できた1例

石田 洋子, 吉野 鉄大, 正木 克宜, 渡辺 賢治, 福永 興壱

総合診療 （(株)医学書院）  32 （ 2 ） 252 - 255 2022年02月

ISSN  2188-8051

　概要を見る

症例は76歳男性で、某年X月に39℃超の発熱が出るようになった。2週間後に呼吸困難が出現し、階段昇降時などの労作で症状が悪化した。咳嗽や喀痰は認めなかった。X+1月に夜間就寝中に強い呼吸困難が出現したため救急要請し、低酸素血症と両側肺野の浸潤影があり、肺炎の診断で緊急入院となった。入院時のCTで両側肺野にび漫性にすりガラス陰影と小葉間隔壁の肥厚を認めた。血液ガス所見ではI型呼吸不全を認めた。各種検査結果と経過も合わせて、薬剤性間質性肺炎およびその急性増悪が疑われた。被疑薬である大柴胡湯去大黄を中止した。予断を許さない呼吸状態であったため、第1病日からm-PSL 1000mg/日のステロイドパルスを3日間施行した。第4病日よりPSL 65mg/日(1mg/kg/日)を開始し、以降は第11病日よりPSL 60mg/日、第18病日よりPSL 50mg/日と漸減した。入院時にはリザーバーマスク15L/分で使用していた酸素需要は漸減し、第8病日には酸素投与不要となった。呼吸不全の悪化リスクがあり、気管支鏡検査は実施できなかったが、後日結果が判明した薬剤誘発性リンパ球刺激試験で大柴胡湯去大黄が陽性であり、経過なども踏まえて総合的に、漢方薬による薬剤性間質性肺炎と診断した。第19病日に独歩退院となった。

Climacteric symptoms in postoperative patients among endometrial cancer, cervical cancer, and ovarian cancer: A cross-sectional study

Horiba, Y. and Yoshino, T. and Yokota, M. and Iwata, T. and Watanabe, K. and Mimura, M. and Aoki, D.

ResearchSquare 2022年

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Relationship Between Conventional Medicine Chapters in ICD-10 and Kampo Pattern Diagnosis: A Cross-Sectional Study

Wu X., Le T.K., Maeda-Minami A., Yoshino T., Horiba Y., Mimura M., Watanabe K.

Frontiers in Pharmacology （Frontiers in Pharmacology）  12   751403 2021年12月

ISSN  16639812

　概要を見る

Objectives: The newest revision to the International Classification of Diseases, the 11th edition (ICD-11) includes disease classifications from East Asian medicine, including traditional Japanese medicine (Kampo medicine). These disease classifications allow for comparisons between disease classifications from conventional medicine and Kampo medicine. Design/Location/Subjects/Interventions: This is an exploratory, cross-sectional study exploring the relationship between conventional medicine diagnoses and Kampo medicine diagnoses at a large Kampo clinic in Japan. Patients were seen from October 1st, 2014 to June 30th, 2019 and were 20 years of age or older. Outcome measures: Patients presented with one or more conventional medicine ICD-10 codes into the clinic and were given one descriptor from the ICD-11 within the heat-cold module, excess-deficiency module, and an optional body constituents module. The distribution of these Kampo medicine codes was examined in relation to conventional medicine chapters. Results: 1,209 patients were included in our final analysis. Patient number, ages, sex ratio, and BMI varied within conventional medicine ICD-10 chapters and Kampo medicine descriptor codes. Certain conventional medicine chapters are related to specific Kampo medicine descriptor codes, such as chapter IV (endocrine, nutritional, and metabolic diseases) with excess, heat, and kidney qi deficiency. Conclusion: The advent of the ICD-11 allows for systematic, standardized comparisons between Kampo medicine, and contemporary medicine. In this exploratory study, our findings support the independence of Kampo medicine pattern descriptors with ICD-10 conventional medicine chapters. Code overrepresentations in relation to conventional medicine diseases and by age and sex should be an area of future investigation to best understand how to synergize and improve patient care.

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Clinical Risk Factors of Licorice-Induced Pseudoaldosteronism Based on Glycyrrhizin-Metabolite Concentrations: A Narrative Review

Yoshino T., Shimada S., Homma M., Makino T., Mimura M., Watanabe K.

Frontiers in Nutrition （Frontiers in Nutrition）  8   719197 2021年09月

ISSN  2296861X

　概要を見る

Licorice, the dried root or stolon of Glycyrrhiza glabra or G. ularensis, is commonly used worldwide as a food sweetener or crude drug. Its major ingredient is glycyrrhizin. Hypokalemia or pseudoaldosteronism (PsA) is one of the most frequent side effects of licorice intake. Glycyrrhizin metabolites inhibit type 2 11β-hydroxysteroid dehydrogenase (11βHSD2), which decomposes cortisol into inactive cortisone in the distal nephron, thereby inducing mineralocorticoid receptor activity. Among the several reported glycyrrhizin-metabolites, 18β-glycyrrhetyl-3-O-sulfate is the major compound found in humans after licorice consumption, followed by glycyrrhetinic acid. These metabolites are highly bound to albumin in blood circulation and are predominantly excreted into bile via multidrug resistance-associated protein 2 (Mrp2). High dosage and long-term use of licorice are constitutional risk factors for PsA. Orally administered glycyrrhizin is effectively hydrolyzed to glycyrrhetinic acid by the intestinal bacteria in constipated patients, which enhances the bioavailability of glycyrrhizin metabolites. Under hypoalbuminemic conditions, the unbound metabolite fractions can reach 11βHSD2 at the distal nephron. Hyper direct-bilirubin could be a surrogate marker of Mrp2 dysfunction, which results in metabolite accumulation. Older age is associated with reduced 11βHSD2 function, and several concomitant medications, such as diuretics, have been reported to affect the phenotype. This review summarizes several factors related to licorice-induced PsA, including daily dosage, long-term use, constipation, hypoalbuminemia, hyper direct-bilirubin, older age, and concomitant medications.

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Inter-Rater Reliability of Kampo Diagnosis for Chronic Diseases

Maeda-Minami A., Yoshino T., Horiba Y., Nakamura T., Watanabe K.

Journal of Alternative and Complementary Medicine （Journal of Alternative and Complementary Medicine）  27 （ 7 ） 613 - 616 2021年07月

ISSN  10755535

　概要を見る

This single-center observational study aimed to assess the inter-rater reliability (IRR) of Kampo medicine pattern diagnosis, which is modularized into three modules for chronic diseases, using 64 participants' information documents. The linearly weighted percentage of agreement and Gwet's agreement coefficient (AC) 2 for the deficiency-excess module, among three specialists, were 85.9% and 0.708, respectively. The unweighted percentage of agreement and Gwet's AC1 were 64.6% and 0.542 for the cold-heat, and 35.9% and 0.254 for the qi-blood-fluid modules, respectively. Our findings suggest that our modularization method may improve the IRR of Kampo medicine pattern diagnosis.

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不登校の孫と易疲労の祖母に柴胡加竜骨牡蛎湯が奏効した症例

沢井 かおり, 吉野 鉄大, 大岸 美和子, 渡辺 賢治

日本東洋医学雑誌 （(一社)日本東洋医学会）  72 （ 3 ） 235 - 238 2021年07月

ISSN  0287-4857

　概要を見る

漢方治療では、異なる病状の症例でも漢方的病態が同じであれば同一処方が有効であり、これを異病同治と称する。特に家族では、遺伝的素因や生活環境の共通性から漢方的病態が類似しやすい。今回、不登校の孫と易疲労の祖母に対する異病同治の症例を経験したので報告する。症例1(孫)は13歳女性、主訴は不登校である。やや実証、寒熱中間証、気逆、気滞、血虚と診断して柴胡加竜骨牡蛎湯を処方したところ、次第に登校できるようになり、集中力がついて成績もよくなった。症例2(祖母)は73歳女性、主訴は易疲労である。虚実中間証、寒熱中間証、気滞、気虚と診断して柴胡加竜骨牡蛎湯を処方したところ、体調がよくなり元気になった。不登校の孫と易疲労の祖母に対して、柴胡加竜骨牡蛎湯がいずれも奏効した。これは血縁であるということと、家庭内のトラブルという背景の一致によって、漢方的病態が似ていたためと思われた。(著者抄録)

Identification of an Alternative Glycyrrhizin Metabolite Causing Liquorice-Induced Pseudohyperaldosteronism and the Development of ELISA System to Detect the Predictive Biomarker

Ishiuchi K., Morinaga O., Yoshino T., Mitamura M., Hirasawa A., Maki Y., Tashita Y., Kondo T., Ogawa K., Lian F., Ogawa-Ochiai K., Minamizawa K., Namiki T., Mimura M., Watanabe K., Makino T.

Frontiers in Pharmacology （Frontiers in Pharmacology）  12   688508 - 688508 2021年05月

ISSN  16639812

　概要を見る

Liquorice is usually used as crude drug in traditional Japanese Kampo medicine and traditional Chinese medicine. Liquorice-containing glycyrrhizin (GL) can cause pseudohyperaldosteronism as a side effect. Previously, we identified 18β-glycyrrhetyl-3-O-sulfate (3) as a GL metabolite in Eisai hyperbilirubinuria rats (EHBRs) with the dysfunction of multidrug resistance-related protein (Mrp2). We speculated that 3 was associated with the onset of liquorice-induced pseudohyperaldosteronism, because it was mainly detected in serum of patients with suspected to have this condition. However, it is predicted that other metabolites might exist in the urine of EHBRs orally treated with glycyrrhetinic acid (GA). We explored other metabolites in the urine of EHBRs, and investigated the pharmacokinetic profiles of the new metabolite in EHBRs and normal Sprague-Dawley rats. We further analyzed the serum concentrations of the new metabolite in the patients of pseudohyperaldosteronism. Finally, we developed the analyzing method of these metabolites as a preventive biomarker for the onset of pseudohyperaldosteronism using an enzyme-linked immunosorbent assay (ELISA). We isolated a new GL metabolite, 18β-glycyrrhetyl-3-O-sulfate-30-O-glucuronide (4). Compound 4 significantly inhibited rat type-2 11β-hydroxysteroid dehydrogenase (11β-HSD2) and was a substrate of both organic anion transporter (OAT) 1 and OAT3. Compound 4 was also detected in the serum of patients with suspected pseudohyperaldosteronism at an approximately 10-fold lower concentrations than 3, and these concentrations were positively correlated. Compound 4 showed a lower serum concentration and weaker inhibitory titer on 11β-HSD2 than 3. We developed an enzyme-linked immunosorbent assay system using an anti-18β-glycyrrhetyl-3-O-glucuronide (3MGA) monoclonal antibody to measure the serum concentration of 3 to facilitate the measurement of biomarkers to predict the onset of pseudohyperaldosteronism. Although we found 4 as the secondary candidate causative agent, 3 could be the main potent preventive biomarker of liquorice-induced pseudohyperaldosteronism. Compound 3 was detected in serum at a higher concentration than GA and 4, implying that 3 may be a pharmacologically active ingredient mediating not only the development of pseudohyperaldosteronism but anti-inflammatory effects in humans administered GL or other liquorice-containing preparations.

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Conventional and Kampo medicine in the treatment of mild to moderate COVID-19: A multicenter, retrospective observational study protocol by the Integrative Management in Japan for Epidemic Disease (IMJEDI study-Observation)

Takayama S., Kashima M., Namiki T., Ito T., Ono R., Arita R., Saito N., Nakae H., Irie Y., Kobayashi S., Yoshino T., Ishigami T., Tanaka K., Nogami T., Minakawa S., Nagase M., Kashio A., Ishige T., Maehara H., Saito T., Sempuku S., Yamazaki M., Tahara E., Suda N., Nakamoto K., Mitsuma T., Sato H., Shimooki O., Nakada Y., Abe S., Masuda T., Kai H., Yokota K., Chiba S., Saitoh F., Tanaka Y., Koizumi S., Fujii S., Katori R., Kainuma M., Nochioka K., Chiu S.W., Kikuchi A., Suzuki T., Mimura M., Yamaguchi T., Ishii T.

Traditional and Kampo Medicine 8 （ 1 ） 106 - 110 2021年04月

　概要を見る

Aim: We present the study protocol of a multicenter, retrospective observational study that aims to investigate the efficacy of the actual treatment (the efficacy of conventional and Kampo medicines) of patients with mild to moderate or suspected coronavirus disease (COVID-19). Methods: This study is designed as a multicenter, retrospective observational study. Outpatients and inpatients will be recruited from Japanese hospitals. The inclusion criteria are as follows: having or suspected to have COVID-19, mild to moderate COVID-19, symptomatic, ≥20 years of age, male or female, able to communicate in Japanese, and treated with conventional and Kampo medicine. The exclusion criteria are: unable to provide informed consent due to dementia, psychosis, or psychiatric symptoms, severe COVID-19, or determined unsuitable for this study. The sample size is set at 1000, as this number of people can be treated at the collaborating medical institutions during the study period. Results: The main outcome is the number of days without fever, with a body temperature of less than 37°C. The secondary outcome is set at common cold-like symptoms other than fever (fatigue, cough, shortness of breath, sputum, diarrhea) and severity of illness and hospitalization up to 14 days after the visit. Trial registration: The trial was registered in the University Hospital Medical Information Network (Reservation No. UMIN000041301) on August 4, 2020. Conclusion: Our study will explore the contribution of conventional and Kampo medicine in the treatment of patients with mild and moderate COVID-19.

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Bilateral pneumothorax after acupuncture treatment

Nishie M., Masaki K., Kayama Y., Yoshino T.

BMJ Case Reports （BMJ Case Reports）  14 （ 3 ）  2021年03月

ISSN  1757790X

　概要を見る

A 31-year-old female physician was diagnosed with bilateral pneumothorax a day after her acupuncture treatment. Her body mass index was 16.9 and she did not have a prior history of respiratory disease or smoking. Acupuncture needles may easily reach the pleura around the end of the suprascapular angle of the levator scapulae muscle where the subcutaneous tissue is anatomically thin. In our patient, the thickness between the epidermis and the visceral pleura in this area was only 22 mm as confirmed by an ultrasound scan. Although she felt chest discomfort 30 min after the procedure, she assumed the symptom to be a reaction to the acupuncture. In light of our case, we advise practitioners to select appropriate acupuncture needles for patients based on the site of insertion and counsel them regarding the appearance of symptoms such as chest pain and dyspnoea immediately after the procedure.

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薬局薬剤師を対象とした漢方薬の書籍等情報源認知度調査

前田 絢子, 湯本 哲郎, 里 香世子, 稲葉 健二郎, 小湊 英範, 木村 隆夫, 中村 智徳, 吉野 鉄大, 堀場 裕子, 渡辺 賢治 and 亀井 淳三

未病と抗老化 （(一財)博慈会老人病研究所）  30   52 - 58 2021年

ISSN  1347-667X

　概要を見る

[目的]漢方薬に興味がある薬剤師、苦手意識がある薬剤師はともに7割を超えており、西洋薬よりも服薬指導が難しいとする薬剤師が半数を超えている。薬局薬剤師の漢方薬服薬指導の質的向上を図るため、漢方薬を対象とした書籍等情報源認知度の現状を把握し、抽出された課題への解決策を検討した。[方法]保険薬局に勤務する薬剤師を対象とし、webアンケート調査を実施した。薬局に一般的に所蔵されている情報源の記載項目を参考に臨床現場で直面するシナリオを10問(西洋薬との併用、漢方薬との併用、禁忌、適応外処方、小児用量、副作用、妊婦への使用、組成・性状(構成生薬)、重要な基本的注意、副作用の好発時期)設定した。シナリオ提示後、対象者に各シナリオを解決するための情報検索方法を知っているか質問し、知っていると申告した場合は検索する情報源も質問した。対象者を認定や刻み生薬調剤経験または、漢方処方取り扱いが多い群(A群)と少ない群(B群)に分類した。項目別認知度は、質問毎に、情報検索方法を知っており、書籍等の情報源を回答した人数の有効回答数に対する割合とした。A群とB群で比較した。[結果]456名(A群:141名、B群:315名)より解答が得られた。項目別認知度は全体で35-70%であった。西洋薬との併用、漢方薬との併用(P<0.01)、適応外処方、副作用、組成・性状(構成生薬)、小児用量、禁忌(P<0.05)で、B群の項目別認知度の方がA群より有意に低かった。[考察]漢方薬の項目別認知度は、今後改善の余地があると考える。大学における漢方薬の情報源及び記載内容の知識を向上させる教育の拡充、生涯学習を通した薬局薬剤師の能力の改善が未病社会における漢方薬の適正使用のために必要であると考える。(著者抄録)

甘草の副作用、偽アルドステロン症の発症メカニズムとその予防

吉野鉄大

（ シンポジウム 15「生薬・漢方薬の医薬品情報最前線」 ）  2021年

しくじり先生　俺みたいになるな

吉野鉄大

2021年

漢方薬の選びかた風邪＆インフルエンザ そしてCOVID-19/POST COVID-19

吉野鉄大

2021年

漢方製剤の処方選択支援モデルの開発とそのビジョン

吉野鉄大

2021年

A multi-center, randomized controlled trial by the Integrative Management in Japan for Epidemic Disease (IMJEDI study-RCT) on the use of Kampo medicine, kakkonto with shosaikotokakikyosekko, in mild-To-moderate COVID-19 patients for symptomatic relief and prevention of severe stage: A structured summary of a study protocol for a randomized controlled trial

Takayama S., Namiki T., Ito T., Arita R., Nakae H., Kobayashi S., Yoshino T., Ishigami T., Tanaka K., Kainuma M., Nochioka K., Takagi A., Mimura M., Yamaguchi T., Ishii T.

Trials （Trials）  21 （ 1 ） 827 - 827 2020年10月

　概要を見る

Objectives: We aimed to test our hypothesis that additional administration of traditional Japanese (Kampo) medicine, kakkonto (kakkon-To: KT) and shosaikotokakikyosekko (sho-saiko-To-ka-kikyo-sekko: SSKKS), is more effective in relieving symptoms and preventing the onset of severe infection in mild-To-moderate COVID-19 patients compared to those treated only with conventional treatment. Trial design: The study is designed as a multi-center, interventional, parallel-group, randomized (1:1 ratio), investigator-sponsored, two-Arm study. Participants: Patients and inpatients will be recruited from 8 Japanese academic and non-Academic hospitals. The inclusion and exclusion criteria are as follows: Inclusion criteria: 1. Diagnosed as positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 2. Clinical stages of mild-To-moderate COVID-19 3. Symptomatic 4. ≥ 20 years of age 5. Male or female 6. Ability to communicate in Japanese 7. Outpatients and inpatients 8. Provided informed consent Exclusion criteria: 1. Difficulty in providing informed consent due to dementia, psychosis, or psychiatric symptoms 2. Allergic to Kampo or Western medicines used in this study 3. Pregnant and lactating 4. Unable to follow up 5. Participating in another clinical trial or interventional study 6. Hypokalemic or taking oral furosemide or steroids 7. Determined unsuitable for this study by the physician Intervention and comparator: Patients in the control group will receive conventional treatment with antipyretics, painkillers, or antitussives for symptoms that occurred after they contracted the SARS-CoV-2 infection. Patients in the Kampo group will receive 2.5 g of KT (TJ-1@TSUMURA and Co.) and 2.5 g of SSKKS (TJ-109@TSUMURA and Co.) 3 times a day, orally, for 14 days in addition to the conventional treatment as mentioned above. Main outcomes: The number of days till at least one of the symptoms (fever, cough, sputum, malaise, shortness of breath) improves in the first 14 days of treatment. To assess the cough, sputum, malaise, and shortness of breath, a numeric rating scale will be used to define improvement in terms of a 2-point decrease in the number of days from the start of treatment for at least 2 days. Fever will be defined as an improvement when the temperature is less than 37 °C. Randomization: Patients are randomized (1:1 ratio) to each group using the minimization method, with balancing of the arms with severity of disease stage and patient age (< 65, 65 to < 75, or ≥ 75 years). Computer-generated random numbers will be used for the minimization method. Blinding (masking): Open-label with no blinding Numbers to be randomized (sample size): The main research hypothesis of this study is that the combination of Kampo medicine and conventional treatment will significantly improve the patients' symptoms (fever, fatigue, cough, sputum, and shortness of breath) during the first 14 days of treatment as compared with conventional treatment alone. Concerning the analysis of the primary endpoint, the duration of time before improvement of at least one of the common cold-like symptoms (fever, malaise, cough, sputum, and shortness of breath) will be estimated using the Kaplan-Meier method, and the survival curves will be compared between groups using the log-rank test. Assuming this method of analysis and based on previous studies reporting the efficacy of Kampo medicine for COVID-19 and H1N1 influenza patients, the median survival time in the Kampo medicine group is estimated as 3 days; this time will be 1.5 times longer in the control group. Assuming a one-sided significance level of 5%, a power of 70%, and an allocation ratio of 1:1, the required sample size is calculated as 126 cases. To compensate for a loss in follow-up, we plan to include 150 cases in both groups (Kampo group = 75, control group = 75). Trial status: Protocol version 1.2 as of August 20, 2020 Recruitment start (expected): October 1, 2020 Recruitment finish (expected): October 31, 2023 Trial registration: Japan Registry of Clinical Trials (jRCT) jRCTs021200020. Registered on August 25, 2020 Full protocol: The full protocol is attached as an additional file and is accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

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