A Herbal Prescription of Insamyangyeongtang as a Therapeutic Agent for Frailty in Elderly: A Narrative Review.

Frailty is a major geriatric syndrome with a multifactorial etiology that induces a decline in multiple physiological and psychological functions. In traditional East Asian medicine (TEAM), qi and blood deficiency clinically represent as fatigue, anemia, anorexia, decreased strength after illness, and weakness, commonly interpretated as frailty. An herbal prescription of Insamyangyeongtang (IYT, Ninjin'yoeito in Japanese, Ren-Shen-Yang-Rong-Tang in Chinese) tonifies qi and blood and has the potential to treat multiple targets caused by qi and blood deficiency. As the population ages and frailty increases, there is an increase in the potential effectiveness of IYT in frailty. This study reviewed relevant clinical trials to provide an updated view on the effect of IYT on frailty. IYT has therapeutic effects on frailty associated with chronic respiratory diseases (e.g., chronic obstructive pulmonary disease) and cognitive impairments (e.g., Alzheimer's disease) and improves respiratory symptoms and cognition. IYT also has therapeutic effects on weight gain, muscle mass, and strength, and improves nutritional status in frail elderly individuals who have decreased muscle mass and strength, loss of appetite, and weight loss. The same effect has been shown in frailty in elderly individuals with rehabilitation treatment and chronic diseases. IYT also improves frailty associated with symptoms such as intractable dizziness and genitourinary symptoms. The beneficial effects of IYT in several diseases could be important for medication replacement, reduction, and prevention of polypharmacy. Based on the results of this review, we suggest that IYT has the potential to be a therapeutic agent against frailty.

Bioactivity Study of Tricyclic and Tetracyclic Genipin Derivatives as Anti-inflammatory Agents.

A series of genipin derivatives included tricyclic cyclopentaimidazopyridine, cyclopentapyridopyrimidine, octahydrocyclopentapyridodiazepine, and tetracyclic decahydrobenzoimidazocyclopentapyridine were synthesized and developed as anti-inflammatory agents. All of them were tested against NO production in LPS-induced RAW264.7 cells. Based on IC50 data and the SAR study, we found that tricyclic cyclopentaimidazopyridines 3d-f and 7-9 presented the better inhibitory activities (≦ 28.1 µM) in comparison with the reference standard Indomethacin (166 µM). On the other hand, all of them showed inactivity for in vitro cyclooxygenase COX-2 inhibition assays and compounds 8 and 9 possessed the cell toxity. To explore the further anti-inflammatory mechanism, Western blot analysis was carried out. Furthermore, compound 3d shown better bioactivity than Indomethacin. The suppression of NF-κB signal pathway by compound 3d was also determined. To sum-up, compound 3d would be the potential anti-inflammatory lead compound.

Pharmacists' perspectives on traditional, complementary, and integrative medicine in Japan with special reference to Kampo medicines: an internet survey with preliminary interviews.

BACKGROUND: Pharmacists guide patients in their use of traditional, complementary, and integrative medicine (TCIM). The present study aimed to evaluate the opinions of Japanese pharmacists regarding TCIM, and to evaluate the usability of the evidence-based Japanese Integrative Medicine (eJIM) website from the pharmacists' point of view. METHODS: We conducted a two-stage, mixed-method study using interviews and an internet-based survey. In-person interviews were conducted with 20 pharmacists working in hospitals, dispensing pharmacies, or retail pharmacies. We analyzed their perspectives on TCIM and the usability of the eJIM. Based on the interviews, questionnaires for an internet survey conducted in February 2019 were developed. RESULTS: In the interviews, 55% of pharmacists acknowledged TCIM as a supportive measure for modern medicine, and 45% responded that TCIM was efficacious. However, pharmacists' evaluation levels of Kampo medicine were high, whereas pharmacists' attitudes towards dietary supplements were primarily negative. There have been various proposals to improve the eJIM, such as highlighting important information and providing more specific information on TCIM in Japan. An internet survey of 365 pharmacists showed that 67.4% were consulted by patients regarding TCIM. Of these TCIM, pharmacists' evaluation levels of Kampo medicines were high. Only 5% of the respondents had visited the eJIM website prior to the survey, and the overall usability score of each web page was high. CONCLUSIONS: Kampo medicines and dietary supplements are common TCIMs that pharmacists use or advise on in Japan. Pharmacists' evaluation levels of Kampo medicine were high, whereas pharmacists' attitudes towards dietary supplements were generally negative.

Clinical studies of traditional Japanese herbal medicines (Kampo): Need for evidence by the modern scientific methodology.

BACKGROUND: Japanese Kampo medicine is a traditional medicine with roots in ancient Chinese medicine. Because traditional physicians had been abolished in Japan, the present mainstream of Kampo treatment is that physicians who learned modern Western medicine prescribe Kampo extract products based on Western medical diagnosis. This situation is different from that in other east Asian countries, and the physicians require scientific clinical evidence. METHODS: Clinical studies were searched from literature databases, clinical trial registry sites, and "Evidence Reports of Kampo Treatment (EKAT)" published by the Japan Society for Oriental Medicine. RESULTS: At the approval of Kampo products, scientific clinical evidence was not required because they have a long-period experience as a decoction. However, in the 1990s, Kampo products became a subject for national reevaluation; double-blind and placebo-controlled clinical trials. At the time, a methodological foundation for conducting clinical assessments of Kampo medicines was established. From 2000 onwards, with the evidence-based medicine era, the field of Kampo medicine also saw many randomized controlled trials, and their evidence was collected and published as EKAT. In the 2010s, post-marketing clinical trials of Kampo products also had to be conducted in this environment due to the need for ethical and scientific assurance. Currently, there are numerous clinical trials of Kampo products being conducted with high-grade trial designs. CONCLUSION: The situation of Kampo clinical studies reflects the unique history and position of Kampo medical system and Kampo products in Japan.

Physician perspectives on traditional, complementary, and integrative medicine and the national evidence-based Japanese integrative medicine information website: A mixed-method study.

BACKGROUND: The evidence-based Japanese integrative medicine (eJIM) website was launched by the Japanese government in 2014 to provide information on integrative medicine to the general public and physicians. While Japanese physicians discourage the use of traditional, complementary, and integrative medicine (TCIM), there are very few reports that explore this issue. We aimed to understand the attitudes of Japanese physicians towards TCIM and evaluate the usability of the eJIM website according to physicians. METHODS: We conducted a two-staged, mixed-method study with interviews and an internet-based survey. Face-to-face interviews were conducted with 12 physicians who worked for large-scale hospitals in two different areas of Japan. We assessed their understanding of TCIM and the usability of the eJIM website. Based on the interviews, the internet survey was developed and was conducted in February 2019. RESULTS: In the interviews, 12 physicians provided their opinion on TCIM and highlighted important areas, such as increasing the resources available for patients, and ensuring more information on TCIM is available. The internet survey of 231 physicians showed that 35% of the physicians used or advised on TCIM in clinical practice. Kampo medicines (87.8%) and dietary supplements (24.7%) were common. The physicians did not use TCIM primarily because of concerns regarding its efficacy, safety, and cost. Most physicians were not aware of which TCIM their patients used. CONCLUSION: Physicians in Japan may not have comprehensively understood TCIM and do not actively use TCIM. The eJIM website could help physicians to gain a better understanding of TCIM if improvements are made.

The impact of uncertainty in society on the use of traditional, complementary and alternative medicine: a comparative study on visits to alternative/traditional/folk health care practitioners.

BACKGROUND: While traditional, complementary and alternative medicine (TCAM) is gaining increased interest worldwide, the structural factors associated with the usage of TCAM at the social level have not been sufficiently explored. We aim to understand the social structure of uncertainty in society that affects the TCAM usage for men and women. METHODS: We studied 32 countries using data from the International Social Survey Programme and the World Bank. In this study, we defined TCAM usage as visits to an alternative/traditional/folk health care practitioner during the past 12 months. We performed a correlation analysis and used a generalized linear model . RESULTS: The prevalence of TCAM usage in terms of visits to practitioners was 26.1% globally, while usage varied across the 32 countries. Generalized linear models showed that unemployment rate was associated with the prevalence of TCAM usage in terms of visits to practitioners. CONCLUSIONS: At the social-structural level TCAM usage involving visits to practitioners was related to job insecurity. Job insecurity led to a decrease in TCAM usage regarding visits to practitioners. These findings suggest that it is necessary to consider the social-structural factors of uncertainty in society when designing health policies related to TCAM.

The utilization of complementary and alternative medicine in Taiwan: An internet survey using an adapted version of the international questionnaire (I-CAM-Q).

BACKGROUND: In Taiwan, numerous studies have been conducted to investigate the use of complementary and alternative medicine (CAM). However, most of them focused on specific diseases or the use of particular methods. Therefore, the results of those studies were quite different and difficult to compare with those of studies from other countries. The International CAM Questionnaire (I-CAM-Q), meanwhile, is a unified tool that can provide comparable results for studies conducted worldwide. Thus, the aim of this study was to discover the proportions of people in Taiwan receiving CAM treatments from different types of health care providers by using an adapted version of I-CAM-Q (I-CAM-QT). METHODS: I-CAM-QT was developed by translating the Korean version of I-CAM-Q (I-CAM-QK) into traditional Chinese language because of the similarity of CAM usage and doctor licensing system. This study had two stages: the first was a pretest survey used to adjust the questionnaire, while the second was an internet-based survey used to collect data from the community. RESULTS: Of the 1200 survey respondents, 37% and 37.7% were prescribed or advised to use Chinese herbal medicine (CHM) by Western medicine (WM) physicians and traditional Chinese medicine (TCM) doctors, respectively. Other than CHM, dietary supplements and massage were the forms of CAM most commonly prescribed or recommended by WM physicians or TCM doctors. Overall, walking and relaxation techniques were the most commonly used self-help practices (used by 61.9% and 40.4% of the respondents, respectively). Additionally, 70.3% of the respondents had used at least one kind of dietary supplement in the past 12 months. CONCLUSION: Regarding the utilization of CAM in Taiwan, this internet-based survey revealed that CHM, dietary supplements, and massage were the types of CAM most commonly prescribed or recommended by WM physicians or TCM doctors.

Efficacy of daikenchuto, a traditional Japanese Kampo medicine, for postoperative intestinal dysfunction in patients with gastrointestinal cancers: meta-analysis.

BACKGROUND: The Japan Society for Oriental Medicine makes a compilation of structured abstracts of randomized controlled trials (RCTs) of Kampo medicines available on its Evidence Reports of Kampo Treatment (EKAT) website. METHODS: Using EKAT, we conducted a systematic review and meta-analysis on the efficacy of using daikenchuto ( https://mpdb.nibiohn.go.jp/stork ) for bowel dysfunction after surgery for gastrointestinal cancer. The primary outcomes were the time to first postoperative flatus and the time to first postoperative bowel movement (BM). RESULTS: We found nine relevant RCTs. The mean differences between the daikenchuto group and control group (daikenchuto was not administered) were - 0.43 (95% CI: - 0.77 to - 0.09) days for the time to first postoperative flatus, - 0.29 (95% CI: - 0.59 to 0.01) days for the time to first postoperative BM, and - 0.95 (95% CI: - 1.70 to - 0.21) days for the length of postoperative hospital stay, and the risk ratio of the incidence of intestinal obstruction was 0.60 (95% CI: 0.35-1.03). The time to first postoperative flatus and the length of postoperative hospital stay were significantly shorter in the daikenchuto group than those in the control group (P = 0.01). However, only double-blind studies were evaluated; the results turned to be non-significant. CONCLUSION: As a result of meta-analysis by all retrieved according to the registered protocol, daikenchuto was efficacious in improving postoperative bowel dysfunction in patients with gastrointestinal cancers. However, limiting to articles with description of COI and blindness, significance disappeared.

Use of Complementary and Alternative Medicine in Japan: A Cross-sectional Internet Survey Using the Japanese Version of the International Complementary and Alternative Medicine Questionnaire.

INTRODUCTION: Although there have been several national survey studies on complementary and alternative medicine (CAM) use in Japan, previous studies have not been compared with investigations conducted in other countries. An international CAM questionnaire known as I-CAM-Q was developed through a two-day international workshop in 2006. The purpose of this study was to investigate the use of CAM by the general Japanese population using a modified version of the I-CAM-Q for the Japanese (I-CAM-QJ). METHODS: We developed the I-CAM-QJ to conduct an internet survey of 3,208 participants from the general population of Japan in February 2016. The respondents included 1,592 males (49.6%), 1,348 university graduates (38.8%), 1,105 individuals in good health (34.4%), and 1,028 individuals with long-term illness or disability (32.0%). RESULTS: Of the 3,208 respondents, 411 participants reported CAM use during the past 12 months (12.8%). The following therapies and products were used: Kampo medicines (over-the-counter Kampo medicines: 15.7%; prescribed Kampo medicines: 15.4%), dietary supplements 11.8%, massage services 3.9%, and physical therapy 3.5%. Regarding the use of self-care methods during the last 12 months, the following methods and products were used: bath salts 25.8% and walking 25.3%. CONCLUSIONS: An internet survey on CAM use by the general Japanese population with a modified I-CAM-Q (I-CAM-QJ) revealed that Kampo medicines and dietary supplements were the most commonly used CAMs in Japan.

Internet survey on the provision of complementary and alternative medicine in Japanese private clinics: a cross-sectional study.

OBJECTIVE: Although the use of complementary and alternative medicine (CAM) by the general population has been surveyed previously, the provision of CAM by Japanese physicians in private clinics has not been studied. Universal health insurance system was established in Japan in 1961, and most CAMs are not on the drug tariff. We aimed to clarify the current status of CAM provided by physicians at private clinics in Japan. METHODS: We conducted an internet survey on 400 directors/physicians of private clinics nationwide on the provision of CAM from February 6 to February 10, 2017. Survey items included attributes of subjects, presence/absence of sections or facilities for provision of CAM, proportions of health insurance coverage for medical practices, and source of information. Private clinic was defined as a clinic run by one physician, with less than 20 beds. RESULTS: Commonly provided CAMs were Kampo (traditional Japanese herbal) medicines (34.8%) and supplements/health foods (19.3%). CAMs on the drug tariff were provided in 46.5% of cases at the clinics, but only 16.5% of cases were provided CAMs which were not on the drug tariff, at different neighboring facilities. Among different specialties, Kampo medicines were prescribed at obstetrics/gynecology (54.0%), orthopedics (44.4%), and dermatology (43.0%). Clinics not providing any CAM accounted for 53.5%. With regard to health insurance coverage, 96.8% of the clinics provided only or mainly health services on the universal national health insurance tariff (29.8% and 67.0%, respectively). CONCLUSION: Kampo medicines represent the most commonly used CAM in private clinics in Japan, and universal national health insurance coverage is considered to be the reason for the high rate of their use.

Usability of the evidence-based Japanese integrative medicine (eJIM) information site: analysis with focus group discussion and internet survey on the general population.

BACKGROUND: The information site for evidence-based Japanese Integrative Medicine (eJIM) was launched by the Japanese Ministry of Health, Labour and Welfare to enable patients, medical staff, and others to obtain appropriate information, but it has not been objectively evaluated by users. The present study aimed to assess the usability of the eJIM website from the viewpoint of the general population. METHODS: We held a focus group discussion with 12 persons in November 2016, conducted an Internet survey of 1107 people (general population) in February 2017, and assessed their understanding of basic concepts of complementary and alternative medicine and usefulness of the contents after browsing the eJIM website. Levels of functional, communicative, and critical health literacy were also assessed. RESULTS: Most patients had never visited the eJIM website, because basic terms such as "integrative medicine" and "evidence" were not fully understood. Most overseas information in English was difficult to understand for the general Japanese population, although approximately 50% of the information was translated into Japanese. The degree of appropriate responses depended on health literacy level. CONCLUSION: The usability of eJIM website was low, because the currently available information did not meet the needs of the general population. Moreover, simpler expressions and visual tools would help the general population to understand the website contents more easily. A further survey that considers cultural and quantitative perspectives is warranted.

An assessment of the use of complementary and alternative medicine by Korean people using an adapted version of the standardized international questionnaire (I-CAM-QK): a cross-sectional study of an internet survey.

BACKGROUND: In Korea, there are two types of medical doctors: one practises conventional medicine (hereafter called a physician), and the other practises traditional medicine (hereafter called a Korean medical doctor). This study aimed to compare the provision of complementary and alternative medicine (CAM) by these providers to CAM use per self-judgement in Korea. METHODS: We analysed 1668 Korean people via an internet survey with the Korean adopted version of the I-CAM-Q, namely, the International Questionnaire to measure use of CAM, to understand whether respondents used CAM based either on a prescription or advice from a physician or a Korean medical doctor or on self-judgement. RESULTS: In the previous 12 months, the proportions of respondents who were treated by a physician, who were treated by a Korean medical doctor and who were not treated by anyone were 67.9, 20.7 and 14.2%, respectively. Among the respondents who received CAM based on a prescription or advice from a physician, traditional Korean medicine practices and dietary supplements were commonly used; only a small percentage used other CAM therapies. Respondents who received CAM based on a prescription or advice from a Korean medical doctor showed similar results. Acupuncture and moxibustion, traditional Korean medicines (decoction), or cupping were more commonly used. Korean traditional medicines as over-the-counter (OTC) drugs were more commonly used by respondents who received CAM therapy based on a prescription or advice from a physician than by those who received CAM therapy based on a prescription or advice from a Korean medical doctor. A total of 74% of the responders used any CAM by self-judgement in the previous 12 months. CONCLUSIONS: For the use of CAM in Korea, in addition to the Korean traditional medical care provided by Korean medical doctors, general physicians advised people regarding Korean traditional medical care and dietary supplements.

Standards of Reporting Kampo Products (STORK) in research articles.

There had been no standardized rules for citing ethical Kampo products used in clinical trials in journal articles. Although the name of a Kampo manufacturer was described in 77.9% of research articles, the name and ratios of crude drug components of Kampo formulas were not described in 77.5% of these papers. Considering the importance of proper characterization of interventions in the Consolidated Standards of Reporting Trials (CONSORT) checklist, we hereby propose the use of the Standards of Reporting Kampo Products (STORK) website, http://mpdb.nibiohn.go.jp/stork, as a reference for Kampo products. This will provide an official source on the internet for verified information on individual Kampo formulations for citation purposes in clinical research articles.

Use of Kampo diagnosis in randomized controlled trials of Kampo products in Japan: a systematic review.

BACKGROUND: The Committee for Evidence-based Medicine (EBM) of the Japan Society for Oriental Medicine started compiling Evidence Reports of Kampo Treatment (EKAT) in 2007. EKAT is a compilation of structured abstracts of randomized controlled trials (RCTs), along with comments by a third party reviewer. As of 31 December, 2012, there were 378 RCTs of Kampo medicines in Japan. The primary research question of this study is "How frequently is Kampo diagnosis used in RCTs of Kampo medicines?" The secondary research question is "When is Kampo diagnosis used in RCTs?" MATERIALS AND METHODS: The structured abstract (SA) of each RCT article was reviewed to examine how Kampo diagnosis was used in RCTs, especially how Kampo diagnosis was used in the randomization process. RESULTS: Kampo diagnosis was used before randomization in 27 RCTs (7.1%), after randomization in 31 RCTs (8.2%), and not used in 320 RCTs (84.7%). Before randomization, Kampo diagnosis was used as a criterion for inclusion in 10 RCTs, criterion for exclusion in 9 RCTs, and criteria for both inclusion and exclusion in 2 RCTs. Kampo formulas were determined according to Kampo diagnosis in 7 RCTs. After randomization, subgroup analyses according to Kampo diagnosis were done in 27 RCTs, and grade of disease severity at Kampo diagnosis was used for analysis as an endpoint in 4 RCTs. CONCLUSIONS: Kampo diagnosis was used before randomization only in approximately 15% of RCTs, and the number of RCT articles using Kampo diagnosis after randomization was almost the same as that before randomization. Further studies to determine the good RCTs conforming to CONSORT requirements and good systematic reviews conforming to PRISMA requirements are needed to clarify the significance of Kampo diagnosis.

Current status of Kampo (Japanese herbal) medicines in Japanese clinical practice guidelines.

BACKGROUND AND AIMS: Kampo (Japanese herbal) medicines are often used in clinical practice in Japan. However, it is unclear how Kampo medicines are quoted and evaluated in current clinical practice guidelines (CPGs). Here, we systematically reviewed Japanese CPGs, and aimed to reveal how Kampo medicines are described in the CPGs. MATERIALS AND METHODS: We reviewed the quasi-comprehensive list of Japanese CPGs available from the Toho University Medical Media Center (TUMMC) having the largest data base on Japanese CPGs, and also used a hand search. CPGs containing Kampo products were classified into three types based on how Kampo was handled. CPGs that provided recommendations based on evidence were classified as "type A". Those which cited references but did not provide any recommendations were classified as "type B". Those which described the Kampo practice or Kampo-related terms without providing any relevant references were classified as "type C". RESULTS: By the end of March of 2007, 35 (10.1%) of 346 CPGs listed by TUMMC contained descriptions of Kampo products. We discovered one Kampo-related CPGs in a hand search process. Of these 36 CPGs, 6 were "type A", 13 were "type B", and 17 were "type C". Although results from pertinent randomized controlled trials (RCTs) were available, we noticed that some well-known RCTs studying Kampo medicines are missing in corresponding CPGs. CONCLUSIONS: We revealed that the citation rate of Kampo medicines in CPGs was approximately 10% and that some pivotal trials for Kampo medicines were not quoted in CPGs. Kampo medicines in CPGs should be assessed more comprehensively and scientifically.