Search

Objective: The purpose of this study was to predict the four cold–heat patterns in patients who have the subjective symptoms of the cold–heat pattern described in the International Classification of Diseases Traditional Medicine Conditions – Module 1 by applying a machine learning algorithm. Methods: Subjects were first-visit Kampo outpatients at six institutions who agreed to participate in this multicenter prospective observational study. The cold pattern model and the heat pattern model were created separately with 148 symptoms, body mass index, blood pressure (systolic and diastolic), age, and sex. Along with a single cold or heat pattern, the tangled heat/cold pattern is defined as being predicted by both cold and heat patterns, while the moderate (heat/cold) pattern is defined as being predicted by neither the cold pattern nor the heat pattern. Results: We included 622 participants (mean age ±standard deviation, 54.4 ± 16.9; with female 501). The accuracy, macro-recall, precision, and F1-score of a combination of the two prediction models were 96.7%, 93.2%, 85.6%, and 88.5% respectively. The important items were compatible with the definitions of the cold–heat pattern. Conclusion: We developed a prediction model on cold–heat patterns with data from patients whose subjective cold/heat-related symptoms matched the cold–heat pattern diagnosis by the physician. [ABSTRACT FROM AUTHOR]

Aim: We aimed to elucidate the present clinical situation, future challenges, and potential need for diagnostic support software in Kampo medicine. Methods: We conducted an online survey (comprising 28 questions) of Japanese physicians from the 23 to 24 January 2024 via MedPeer. The participants' responses were stratified according to their age distribution. Results: We evaluated data for 652 respondents. The most common respondent age groups were those in their 30s and 40s. The most common specialty of respondents was internal medicine (43.7%). Only 33.7% of respondents had received education on Kampo medicine at university. Most respondents (90.0%) were not licensed as certified physicians or members of the Japan Society for Oriental Medicine. Most respondents (86.7%) currently prescribed Kampo formulas (current users); only 3.8% had no experience in prescribing Kampo formulas. The conditions for which Kampo formulas were frequently prescribed were muscle cramps, constipation, medically unexplained symptoms/menopausal syndrome, appetite loss/malnutrition, and fatigue. However, 48.3% of current users did not use traditional Kampo patterns (sho). The most frequent issues reported by respondents were the lack of scientific evidence and standardization of diagnostic methods in Kampo medicine. Respondents indicated the need for postgraduate education and implementation of diagnostic support software for using Kampo patterns by non‐specialists in Kampo medicine. Conclusion: There was a discrepancy between the high frequency of Kampo formula prescriptions and the low use of traditional Kampo patterns in Japan. Diagnostic support software is likely to become a useful method of improving appropriate Kampo formula prescriptions by non‐specialists. [ABSTRACT FROM AUTHOR]

Background: Licorice‐induced pseudoaldosteronism has been identified as a side effect of excessive licorice consumption. This condition is often characterized by hypertension, hypokalemia, and hyporeninemic hypoaldosteronism. If left untreated, this condition can lead to severe complications, such as arrhythmia and rhabdomyolysis, which can be life‐threatening. Thus, it is critical to recognize the early symptoms of pseudoaldosteronism to facilitate prompt intervention and effective management. Here, we investigated the frequency of various accompanying symptoms by systematically reviewing case reports of licorice‐induced pseudoaldosteronism not covered in similar studies and comparing findings with the manual on pseudoaldosteronism published by the Ministry of Health, Labour and Welfare (MHLW). Methods: A comprehensive search was conducted using MEDLINE/PubMed to gather relevant human studies published between 1960 and July 2023 and written in English; data focusing on accompanying symptoms were summarized. Results: Thirty‐seven pertinent articles, encompassing 48 case reports (26 females and 1 unreported sex, mean age 64.6 ± 14.6), were identified and scrutinized. The analysis revealed that hypertension was the most prevalent followed by weakness and edema. None of the researched cases reported instances of spasticity or rigidity. Discussion: The study findings identified hypertension and weakness followed by edema as the predominant symptoms associated with pseudoaldosteronism which is in agreement with the MHLW manual. However, we doubt that spasticity, rigidity, and possibly numbness could be noticed by patients and their families as common initial symptoms outlined in the manual. [ABSTRACT FROM AUTHOR]

Four young researchers presented their studies in the field of traditional Japanese herbal medicine (Wakan‐yaku) at the Fourth Annual Young Researcher Forum held the day before the 2023 annual meeting of the Japan Society of Medical and Pharmaceutical Sciences for Traditional Medicine. Mr Sakoda outlined his research plan, emphasizing the potential of yokukansan to enhance palliative care for cancer patients. Meanwhile, Ms Tanide and Mr Nishihara explored the correlation among component contents in Coptis japonica on Sado Island. Additionally, Mr Okayama presented his study, focusing on the use of Sinomenium acutum‐derived compounds to inhibit the Wnt/β‐catenin pathway and eradicate cancer stem cells. Finally, Mr Muraoka shared insights from his research on the inhibitory properties of Cassia obtusifolia sprout components. The event, conducted both in person and online, attracted a total of 58 participants. Looking ahead, we aim to further develop and continue hosting this forum in 2024 and beyond, fostering the advancement of research in this field. [ABSTRACT FROM AUTHOR]

Background: The source of yokukansan (YKS) is thought to be Baoying‐Jinjiang (Hoeikinkyōroku in Japanese) by Xue Ji. YKS was originally designed for children and indicated for spasms, clenching of teeth, digestive dysfunction due to mental instability, and insomnia. Key Findings: YKS formula consists of seven types of crude drugs. Clinical studies have revealed that YKS exerts physiological effects including the treatment of behavioral and psychiatric symptoms of dementia (BPSD), preoperative sedation and anxiety, and postoperative delirium. A meta‐analysis showed that YKS could improve BPSD and daily living activities; however, no improvement in cognitive function was observed. Preclinical studies have also reported that YKS modulates neuronal pathways in the central nervous system, including the serotonergic, glutamatergic, GABAergic, and other neurotransmitter pathways. The incidence of adverse events associated with YKS was 5.17%, with the major adverse effect being pseudoaldosteronism. Routine blood sampling is considered for hypokalemia prevention. Conclusion: YKS is useful for BPSD and perioperative mental instability. The modulation of the serotonergic and glutamatergic neural pathways is one of mechanisms. Pseudoaldosteronism is one of the side effects. [ABSTRACT FROM AUTHOR]

Background: Kampo medicine is widely used in Japan; however, most physicians and pharmacists have insufficient knowledge and experience in it. Although a chatbot-style system using machine learning and natural language processing has been used in some clinical settings and proven useful, the system developed specifically for the Japanese language using this method has not been validated by research. The purpose of this study is to develop a novel drug information provision system for Kampo medicines using a natural language classifier® (NLC®) based on IBM Watson. Methods: The target Kampo formulas were 33 formulas listed in the 17th revision of the Japanese Pharmacopoeia. The information included in the system comes from the package inserts of Kampo medicines, Manuals for Management of Individual Serious Adverse Drug Reactions, and data on off-label usage. The system developed in this study classifies questions about the drug information of Kampo formulas input by natural language into preset questions and outputs preset answers for the questions. The system uses morphological analysis, synonym conversion by thesaurus, and NLC®. We fine-tuned the information registered into NLC® and increased the thesaurus. To validate the system, 900 validation questions were provided by six pharmacists who were classified into high or low levels of knowledge and experience of Kampo medicines and three pharmacy students. Results: The precision, recall, and F-measure of the system performance were 0.986, 0.915, and 0.949, respectively. The results were stable even with differences in the amount of expertise of the question authors. Conclusions: We developed a system using natural language classification that can give appropriate answers to most of the validation questions. [ABSTRACT FROM AUTHOR]

Objectives: This is a narrative review of the integration of traditional medicine with conventional biomedicine in present day Japan, whose aging population is considered one of the largest globally. Design: It is focused on the aging population because this age group most avails of healthcare. We also tried to describe the unique Japanese medical situations, clinical outcome of Japanese traditional medicine (Kampo medicine) which may include acupuncture, and education of Kampo medicine workforce. Results: Conventional schools of medicine in Japan are required to teach Kampo medicine, and most Japanese physicians (>80%) prescribe traditional medicine, especially in primary care settings. The universal national healthcare system covers Kampo medicine prescribed by physicians and treatment by acupuncturists (they sometimes refer patients who may need evaluation by physicians), enhancing access to primary healthcare. Additionally, pharmacists who graduated from conventional schools of pharmacy also select and sell Kampo medicine as over-the-counter (OTC) medication. Kampo medicine available as prescription drugs and OTC is effective, and has been proven to be economically beneficial in several clinical settings. Conclusions: An aging population is a global concern for both developed and developing countries. Japan, having a significantly-large aging population, integrates conventional biomedicine and traditional medicine in its universal national healthcare coverage, through its biomedically-trained physicians and pharmacists who also learned traditional medicine, as well as the acupuncturists. By reviewing the current situation in Japan, the authors hope to introduce the future of the global contribution of traditional, complementary, and integrative medicine in primary care. [ABSTRACT FROM AUTHOR]

Four young researchers presented their studies in the field of traditional Japanese herbal medicine (Wakan‐yaku) at the third annual young researcher forum entitled "Respecting and Breaking Traditions," held 1 week before the 2022 annual meeting of the Japan Society of Medical and Pharmaceutical Sciences for Traditional Medicine. Dr. Yokogawa presented her research focusing on the mechanism of the Ayurveda drug‐eluting string, Kshara Sutra, in treating anal fistulas, reporting on its effects on the anal tissue in an anal fistula rat model and its antibacterial activity against Escherichia coli and Staphylococcus aureus, the causative organisms of anal fistulas. Mr. Nakamichi presented his research focusing on the relationship between the efficacy of Kampo medicines with anti‐obesity effects and intestinal microbiota composition. His results partially revealed that bofutsushosan and boiogito affect lipid metabolism in mice and correlate with the intestinal microbiota composition. Dr. Manse reported the anti‐inflammatory activity of diterpenoid components in Enmei‐so (Isodonis Herba), revealing its novel inhibitory activity on nitric oxide released from activated macrophages and on inflammatory cytokines, and identified active components contributing to the inhibition and the mechanism of action. Mr. Yoshikawa reported the anticancer activity of small molecular compounds isolated from the medicinal plants, Valeriana fauriei and Hypericum erectum. His results suggest that five compounds may increase the sensitivity of human cervical carcinoma cells to adriamycin via HSP105 expression suppression. The event was conducted online, and included 78 participants. We intend to hold and improve this forum in 2023 and the future. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Liquorice [main ingredient, glycyrrhizin (GL)] is widely used as a food sweetener and herbal medicine. Occasionally, liquorice consumption causes pseudoaldosteronism as a side effect which causes oedema, hypokalaemia, and hypertension due to hyperactivity of mineral corticoid receptor. We aimed to detect GL metabolites in human blood and urine samples and to determine the pathological relationship between GL metabolites and pseudoaldosteronism. For this multi-centre, retrospective, cross-sectional study, we recruited patients who had visited Center for Kampo Medicine in Keio University Hospital, Department of Japanese Oriental (Kampo) Medicine in Chiba University Hospital, Clinic of Japanese Oriental (Kampo) Medicine in Kanazawa University Hospital, and Department of Oriental Medicine in Kameda Medical Center from November 2011 to July 2018. We collected laboratory data including concentration of serum potassium, plasma activity of renin and aldosterone, and residual blood and/or urine samples of participants who had experienced symptoms/signs of pseudoaldosteronism in the form of increase in blood pressure and occurrence or aggregation of oedema while taking liquorice-containing herbal preparations, and measured GL metabolites using a highly selective liquid chromatography tandem mass spectrometer system. We registered 97 participants (mean age 60 ± 15 years; male:female 14:83). 18β-glycyrrhetinic acid (GA) was detected in 67 serum samples (median 122 nM, range 5 nM–1.8 µM) and 18β-glycyrrhetyl-3-O-sulfate (compound 3) in 68 samples (median 239 nM, range 2 nM–4.2 µM). 3-Monoglucuronyl 18β-glycyrrhetinic acid, 22α-hydroxy-18β-glycyrrhetyl-3-O-sulfate-30-glucuronide, 22α-hydroxy-18β-glycyrrhetyl-3-O-sulfate, and GL itself were not or rarely detected. We could not find any correlation between blood pressure or peripheral oedema and serum concentration of GL metabolites. Sulfotransferase 2A1 catalysed the metabolic reaction of GA to compound 3, a major GL metabolite in human blood. High serum concentration of compound 3 was related to lower renin, aldosterone, and potassium levels, suggesting a pathological relationship between compound 3 and liquorice-induced pseudoaldosteronism. This is the first study to identify the association between a novel metabolite, compound 3, and the incidence of pseudoaldosteronism, highlighting it as a promising biomarker. [ABSTRACT FROM AUTHOR]

Glycyrrhizin is used to treat chronic hepatitis, but it also plays an important role in pseudoaldosteronism. Multidrug resistance‐associated protein 2 is important for glycyrrhizin excretion. Dysfunction of this transporter increases the serum levels of direct bilirubin, glycyrrhizin and its metabolites. Hence, elevated direct‐bilirubin levels could predict the risk of pseudoaldosteronism. This study aimed to evaluate the relationship between elevated direct‐bilirubin levels and hypokalaemia, which is the most sensitive marker of pseudoaldosteronism. This retrospective cohort study was conducted in a Japanese university hospital. The occurrence of hypokalaemia is defined as a serum potassium level of ≤3.5 mEq/L after the administration of a glycyrrhizin‐containing medication, and a further decline of ≥0.5 mEq/L or an increase of ≥0.5 mEq/L after discontinuing the glycyrrhizin‐containing medication was examined in patients with chronic hepatitis between January 2009 and December 2015. This analysis involved 1392 patients, including 596 women. Hepatitis C virus infections were the most common cause of chronic hepatitis in this study. Seventy‐nine patients received glycyrrhizin (exposed group; mean age: 60.5 ± 14.2) and 1313 did not receive glycyrrhizin (control group; mean age: 58.3 ± 15.8 years). Synergistic effects of glycyrrhizin‐containing medications and elevated direct‐bilirubin levels were associated with hypokalaemia. Elevated direct‐bilirubin levels and hypoalbuminaemia were associated with hypokalaemia in the exposed group. Older age, female sex, high daily glycyrrhizin dosage, longer duration of glycyrrhizin intake, and potassium‐lowering medications were not associated with hypokalaemia after the model adjustment. Elevated direct‐bilirubin levels and hypoalbuminaemia may predict pseudoaldosteronism caused by glycyrrhizin. [ABSTRACT FROM AUTHOR]

Objective: We aimed to test our hypothesis that traditional Japanese (Kampo) medicine, hochuekkito (Hochu-ekki-to: HET) has a preventive effect for the symptoms on COVID-19.Trial Design: The study is designed as a multi-center, interventional, parallel-group, randomized (1:1 ratio), investigator sponsored, two-arm study.Participants: Six thousand participants will be recruited from healthy hospital workers in 7 Japanese University Hospitals.Inclusion Criteria: 1. Age from 20 to 75 years old at the time of registration 2. Asymptomatic and body temperature below 37°C at the time of registration 3. Capable of eating orally Exclusion criteria: 1. Previous upper respiratory inflammation due to viral infection (including suspected COVID-19) 2. Taking immunosuppressants 3. Allergic to the Kampo medicines used in this study 4. History of hypokalaemia, severe hypertension, severe liver dysfunction, and interstitial pneumonia 5. Regularly taking other Kampo medicines 6. Pregnant or possibly pregnant 7. Participating in other research 8. Judged to be unsuitable for this study by the doctor in charge INTERVENTION AND COMPARATOR: Kampo group: participants receive HET in 9 tablets 2 times per day for 8 weeks.Control Group: participants receive placebo in the same dosage as the Intervention group - 9 tablets 2 times per day for 8 weeks. Placebo tablets are identical in appearance and package to HET. Taste of placebo is different from that of HET. The Ohsugi Pharmaceutical Co. Ltd, Osaka, Japan manufactured the placebo and HET.Main Outcomes: Primary outcome: Number of patients with a SARS-CoV-2 RNA by ploymerase chain reaction (PCR) positive result with at least one symptom (fever, cough, sputum, malaise, shortness of breath) during the 12-week study period (including the 4-week observation period after oral administration).Secondary Outcomes: 1. Period from infection to onset 2. Period from the appearance of symptoms to the disappearance of PCR positive 3. Number of days until the appearance or improvement of symptoms 4. Severe stage: presence of hospitalization 5. Shock stage: ICU management required for mechanical ventilation, shock vitals or failure of organ(s) other than lungs Safety endpoints include numbness in the hands and/or feet, edema, skin rash or other allergic symptoms, and gastric discomfort.Randomisation: Patients are randomized (1:1 ratio) to each group using minimization implemented with the Electric data capture system (DATATRAK Enterprise Cloud), with balancing of the arms with age range (under 50 years of age or not) and having a history of risk factors for COVID-19 (cardiovascular disease, hypertension, diabetes, respiratory diseases).Blinding (masking): Only participants will be randomized.Numbers To Be Randomised (sample Size): The main research hypothesis of this study is that Kampo medicines significantly prevent the onset of COVID-19. It is assumed that the infection rate before the administration of the drug under consideration will be 0% and that the incidence of COVID-19 thereafter will be 2- 3%, of which 70%-80% will show symptoms of COVID-19. Assuming that the pharmaceutical effect of the drug will be effective in 50% of patients and that the incidence rates in the placebo and drug groups will be 1.4%-2.4% and 0.7%-1.2%, respectively, the placebo is calculated at 2%, and the study drug at 1%. Since the frequency of verification is low and the number of cases will be large, we set a total of 10 analyses (9 interim analyses and a final analysis). Since the number of cases at the time of the final analysis will be 4,986 under the conditions of α = 0.05 and a power of 80% by the Peto method. We set at 600 cases in each interim analysis with an estimated dropout rate of 16.9%. Finally, the total number of cases is set to 6,000 with 3,000 in the placebo group and 3,000 in the HET group.Trial Status: Protocol version 1.3 of October 23rd , 2020. Recruitment start (expected): December 1st, 2020. Recruitment finish (expected): December 31st, 2022.Trial Registration: This trial is registered in the Japan Registry of Clinical Trials (jRCT) ( jRCTs031200150 ) on 14 October 2020.Full Protocol: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

ABSTRACT: Aim: Kampo medicine, a Japanese traditional medicine, is a leading candidate in alternative medicine for treating dysmenorrhea. The efficacy of some formulas has been reported in randomized placebo‐controlled trials, but the effectiveness and safety of Kampo treatment with regard to specialist selection of an appropriate formula remain unclear. We therefore conducted a single‐center observational study to evaluate the effectiveness and safety of Kampo treatment for dysmenorrhea. Methods: A retrospective chart review was performed of patients with dysmenorrhea at Keio University Hospital between May 2008 and March 2015. Exclusion criteria were age >50 years and failure to attend follow up. Patients with any degree of improvement in dysmenorrhea by ≤90 days after the first consultation were categorized in the effective dysmenorrhea treatment group. We also examined any improvement in other symptoms after the prescription of medicine for the patients not included in the aforementioned group. Adverse reactions were also investigated. Results: We examined 157 patients, with a median age of 33 years (range, 12–49 years) at the time of the first consultation. A total of 122 patients (77.7%) were diagnosed with primary dysmenorrhea, 99 of whom (63.1%) were categorized in the effective dysmenorrhea treatment group. In addition, loss of appetite, premenstrual symptoms, and cold sensations were improved in the patients not in the effective dysmenorrhea treatment group. Adverse, but mild, reactions were reported in 15.9% of patients. Conclusion: Kampo treatment by specialists can be a safe treatment option for dysmenorrhea. [ABSTRACT FROM AUTHOR]

ABSTRACT Aim Acute upper respiratory tract infections (URI) are a common problem in primary care settings. In traditional East Asian medicine, URI are categorized into three major disorders: influenza-like; common cold; and warmth disorders. The categorization of acute febrile URI, however, is yet to be ascertained. Here, we conducted a single-center retrospective chart review and classification of the various symptoms of acute phase febrile URI. Methods A retrospective chart review between December 2013 and May 2015 was performed. We included febrile (≥38°C) patients with upper respiratory symptoms within 48 h from the onset of fever. Patient profile and symptoms were investigated at the first consultation and clusters were constructed based on symptoms. Results The study included 135 patients. Patients were divided into two groups, day 1 and day 2, according to the time from fever onset. The incidence rate of symptoms, such as general fatigue and muscle pain, were higher in day 1 visitors. Local symptoms, including cough, sore throat, and nasal symptoms, were more frequent in day 2 visitors. Three clusters were observed: chills without sweating (60.0%); chills with sweating (23.0%); and without chills (17.0%). Conclusion Symptoms in acute fever vary. The present three clusters observed suggest that the classical classification of febrile disease is still true. Further studies are necessary to confirm the course of febrile URI described in classical textbooks. [ABSTRACT FROM AUTHOR]

The main research activity in MBK focuses on overseas plant inventories, such as in Myanmar and the Solomon Islands, for medicinal plant resources in collaboration with various academic and industrial institutes. In the medicinal plant garden, which today only covers a small part of the garden area, the medicinal plants of Haller's time - still used today in European Traditional Herbal Medicine (ETHM) - are cultivated to this day. During the Edo period, Saheiji Uemura was the shogunate's envoy for collecting medicinal herbs all over Japan. [Extracted from the article]

Objectives: Low back pain (LBP) is a chronic condition. Although Western treatments are available, Kampo (traditional Japanese) medicine is widely prescribed and covered by health insurance in Japan. Goshajinkigan (GJG), a Kampo formula, is commonly used to treat LBP. However, cases we have occasionally been encountered in which GJG did not show the expected effects. Hence, the purpose of this retrospective study was to investigate patient factors important in developing the effects of GJG. Methods: This was a retrospective observational study based at the Center for Kampo Medicine, Keio University Hospital. Data were retrieved from the medical records of 28 patients who visited our hospital between May 2008 and March 2013 and who received GJG for LBP. The patients were divided into responders and non-responders based on whether their LBP improved post treatment. The groups were compared with respect to daily GJG dose, incidence of spine disease, and side effects. Results: Ten patients (responders) reported an improvement in LBP within 6 months. One patient experienced decreased appetite as a side effect. Nine patients reported no improvement (non-responders). The number of patients prescribed the usual daily dose of GJG (7.5 g) was significantly higher among responders than it was among non-responders ( p = 0.023), and the number of patients with spine disease was significantly greater among non-responders than it was among responders ( p = 0.020). The number of patients with spinal stenosis was significantly higher among non-responders than it was among responders ( p = 0.011). Therefore, the usual daily dose of GJG provided significant relief of LBP, particularly in patients without any spine disease. Conclusions: Routine daily administration of GJG in patients without spine disease seems to lead to the effects of the product. However, further investigations using the above-mentioned parameters are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: Approximately 90 % of physicians in Japan use Kampo medicine in daily practice. However, it is a challenge for physicians who do not specialize in Kampo medicine to select a proper Kampo formula out of the 148 officially approved formulas, as the decision relies on traditional measurements and traditional medicine pattern diagnoses. The present study tries to evaluate the feasibility of a decision support system for frequently used Kampo formulas.Methods: Our study included 393 patients who visited the Kampo Clinic at Keio University Hospital for the first time between May 2008 and March 2013. We collected medical records through a browser-based questionnaire system and applied random forests to predict commonly prescribed Kampo formulas.Results: The discriminant rate was the highest (87.0 %) when we tried to predict a Kampo formula from two candidates using age, sex, body mass index, subjective symptoms, and the two essential and predictable traditional medicine pattern diagnoses (excess-deficiency and heat-cold) as predictor variables. The discriminant rate decreased as the candidate Kampo formulas increased, with the greatest drop occurring between three (76.7 %) and four (47.5 %) candidates. Age, body mass index, and traditional medicine pattern diagnoses had higher importance according to the characteristics of each Kampo formula when we utilized the prediction model, which predicted a Kampo formula from among three candidates.Conclusions: These results suggest that our decision support system for non-specialist physicians works well in selecting appropriate Kampo formulas from among two or three candidates. Additional studies are required to integrate the present statistical analysis in clinical practice. [ABSTRACT FROM AUTHOR]

ABSTRACT Aim Millions of Japanese people suffer from influenza every year. Many of these patients are treated with neuraminidase inhibitors, particularly with oseltamivir. In traditional Japanese herbal medicine (Kampo medicine), maoto is effective against influenza; it can be administered to children and adolescents, and is much cheaper than oseltamivir or other neuraminidase inhibitors. We estimated the annual savings in medical costs ( ASMC) at a national level when oseltamivir was partly replaced with maoto in influenza treatment. Methods We estimated the following variables: (i) number of influenza patients in a normal (non-pandemic) year in Japan; (ii) number of patients who would be prescribed oseltamivir; (iii) number of patients who could be prescribed maoto instead of oseltamivir; and (iv) medical cost reduction per patient when maoto extract is prescribed instead of oseltamivir. ASMC were calculated by multiplying (iii) and (iv). Results An approximate estimate of the ASMC was as high as 9 billion yen, given that an estimated 3 million patients were prescribed maoto rather than oseltamivir, with a medical cost reduction of 3000 yen per patient. Conclusion The direct medical cost reduction with maoto and the magnitude of ASMC were considerably large. Influenza treatment can be more efficient if maoto is introduced into practice. [ABSTRACT FROM AUTHOR]

Background: The pathogenesis of licorice-induced pseudoaldosteronism is thought to involve the inhibition of 11β-hydroxysteroid dehydrogenase type 2 by glycyrrhetinic acid. Some risk factors have been reported, but differences between Japan and other countries have not been reported. Case Presentation: A 79-year-old woman was hospitalized because of pseudoaldosteronism with rhabdomyolysis caused by ingestion of herbal medicines containing licorice. She had been prescribed shakuyakukanzobushito (decocted, 3 g of licorice) and keishikajutsubuto (decocted, 2 g of licorice) for the treatment of lower back pain and had been taking antihypertensive agents for the treatment of essential hypertension. After taking the herbal medicines for 2 weeks, the patient developed weakness of the extremities and pain in both thighs. On admission, she had hypertension, oliguria, an elevated serum creatine kinase level, hypokalemia, alkalemia associated with metabolic alkalosis, low plasma renin activity, and low plasma aldosterone levels. Intravenous and oral potassium supplementation and the administration of spironolactone resulted in the normalization of her condition within approximately 2 weeks. Discussion: An analysis of case reports of pseudoaldosteronism with rhabdomyolysis revealed that in Japan, most cases occurred in elderly women with essential hypertension and were caused by drugs such as herbal medicines. In contrast, in other countries, many cases involved younger men, and the dominant causes were foods containing licorice. The use of herbal medicines is increasing all over the world, and when a patient with risk factors is prescribed an herbal medicine containing licorice, careful follow-up is required. [ABSTRACT FROM AUTHOR]

ABSTRACT Aim Pseudoaldosteronism is a known side-effect of licorice, and Japanese traditional Kampo medicine is one of the major areas of use of licorice in Japan. Multidrug resistance protein 2 ( Mrp2) dysfunction is important for pseudoaldosteronism. Congenital deficiency of Mrp2 causes constitutional jaundice with elevated direct bilirubin. Hence, elevated direct bilirubin can be a biomarker of Mrp2 dysfunction. The relationship between pseudoaldosteronism and elevated direct bilirubin, however, has not been studied as yet. The aim of the present study was therefore to evaluate the relationship between elevated direct bilirubin and hypokalemia, an important characteristic of pseudoaldosteronism. Methods This retrospective observational study included patients who first visited the Kampo Clinic at Keio University Hospital between May 2008 and March 2015. Inclusion criteria were Kampo formulas including licorice prescribed for >2 weeks, and availability of laboratory data on direct bilirubin and change in serum potassium. Results Data from 243 patients (57 men, 186 women) were used in the analysis. Mean age was 52.0 ± 16.2 years. Hypokalemia was noted in three patients (1.3%), among whom elevated direct bilirubin was noted in two (0.9%). The remaining patient with hypokalemia was diagnosed with pseudo- Bartter's syndrome because of loop diuretic use. The remaining 240 patients had neither hypokalemia nor elevated direct bilirubin ( P = 0.0001, Fisher's exact test). Conclusion Elevated direct bilirubin is an important predictor of pseudoaldosteronism. [ABSTRACT FROM AUTHOR]

Background: Influenza is a common viral infection worldwide. Maoto (ma-huang-tang) was developed in ancient China and is used to alleviate flu symptoms. Currently, no meta-analyses have evaluated the efficacy and safety of maoto for alleviating flu symptoms. Methods: In the present study, we searched MEDLINE/PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, a Japanese database (Ichushi), two Chinese databases (China National Knowledge Infrastructure and VIP), and two Korean databases (Korean Medical database and Korean Association of Medical Journal Editors) for studies published in or before October 2017. Clinical studies that compared maoto plus neuraminidase inhibitors (NAIs) vs. NAIs alone, or maoto alone vs. NAIs alone, were included in the present analysis. The primary outcome measure (efficacy) was the length of time from the start of medication to resolution of influenza symptoms (fever, headache, malaise, myalgia, and chills) and virus isolation. The secondary outcome measures (safety) were as follows: (1) side effects and adverse reactions, such as nausea, abnormal behaviour, or discontinuation of symptomatic treatment; (2) morbidity (complications caused by influenza infection) or mortality; and (3) hospitalisation for any reason. Results: Twelve relevant studies were identified, including two randomised controlled trials (RCTs, N = 60) and ten non-randomised studies (NRSs, N = 1110). We found that maoto plus NAIs was superior to NAIs alone in terms of the duration of fever in one RCT (P < 0.05, median difference = − 6 h) and four NRSs (P = 0.003, weighted mean difference = − 5.34 h). The duration of symptoms or virus isolation did not differ between maoto and NAIs. No severe side effects or adverse reactions were reported related to maoto or NAIs. Conclusions: Although we could not reach a definitive conclusion because of the small sample sizes and high risk of bias in the analysed studies, maoto may lower the duration of fever when it is used alone or in combination with NAIs and may be a well-tolerated treatment. More RCTs are needed to determine the efficacy and safety of maoto. [ABSTRACT FROM AUTHOR]

Menstrual pain is one of the common symptoms among women. It is estimated that 5–14% of women are sometimes absent from school or work because of pain. Usually gynecologists prescribe analgesics and/or low-dose oral contraceptives. However, such treatment is not always effective and sometimes causes an adverse effect, such as stomach pain or low body temperature. Kampo medicine is one of the choices for the menstrual pain in Japan. Tokishakuyakusan, kamishoyosan, or keishibukuryogan is commonly used for the treatment of menstrual pain. Here we report a case of menstrual pain successfully treated with daisaikoto which is not commonly used for such a case. Twenty-five-year-old woman suffered from severe menstrual pain and stress at company. She also had constipation and abdominal distension. We prescribed daisaikoto extract 7.5 g per day. Not only menstrual pain but also constipation and abdominal distension improved within 6 months. Here we propose that daisaikoto is one of the choices for the treatment of menstrual pain with mental stress. [ABSTRACT FROM AUTHOR]