Kampo Risk Management Based on a Survey on Incident and Accident Cases at Specialized Kampo Medicine Facilities / 日本東洋医学雑誌

The Medical Safety Committee has conducted various activities for patient safety in Japanese traditional Kampo medicines. In this study, we conducted a questionnaire survey to promote the prevention of medical accidents and their recurrence. We received responses from 15 of 19 facilities specializing in Kampo medicine and collected a total of 247 incident and accident cases in the field of Kampo medicine. Cases of side effects included interstitial pneumonia caused by Kampo prescriptions containing Scutellariae Radix, aconite poisoning, and licorice-induced pseudoaldosteronism. Furthermore, we also collected decoction-specific cases, which are unique to facilities specializing in Kampo medicine, for the first time. From the results, we included the following seven points for risk management in the field of Kampo medicine : 1) insufficient recognition to the side effects of Kampo medicines, 2) misunderstanding of the dosages of Kampo products, 3) errors due to similarities in Kampo formulas and crude drug names, 4) preconception of frequently used Kampo prescriptions, 5) contamination in the decoctions, 6) errors related to crude drug items and their dosages that are frequently added or subtracted, 7) errors in hospital wards.

Medical Safety Committee Report :Medical Accident Information and Minor Incidents from Medical Institutions Related to Kampo Products / 日本東洋医学雑誌

The Medical Safety Committee analyzed the case reports of minor incidents from the pharmacies last time as part of an activity to promote patient safety in Japanese traditional Kampo medicine. This time, we analyzed the case reports of medical accidents and minor incidents from the medical institutions. We extracted 626 reports related to Kampo products from the public database, which the Japan Council for Quality Health Care has established based on the collected information related to the medical accidents and minor incidents. The medical accident information includes case reports related to drug-induced liver injury. The minor incident reports include prescribing error due to misinterpretation related to the quantity of one sachet of Kampo extract product, dispensing error due to similarity of product appearance, number or name, and administration error due to judging the medicine only by Kanji characters or product company names without checking the Kampo formula name. Additionally, the minor incidents were often discovered by people belonging to different professions or patients themselves. In order to promote patient safety, knowledge about these incidents should be shared among the people involved in the same or different professions.

The Significances of Water Volume to Decoct Formulas Described in Classical Chinese Medicine / 日本東洋医学雑誌

Although the descriptions of shigyakukachotanto in “Waitaimiyaofang” and tsumyakushigyakukachotanjuto in “Songban Shanghanlun” are quite similar to each other, the specifications of the dosages of crude drugs and the water volume in the books were considerably different. Focused on the specified water volume to decoct these formulas, each reasonable decocting period was estimated, then the decoctions were prepared using hard water that was common in mainland China. The dosages of aconite root were 2­-fold different between these two formulas, but the contents of aconitine-­type diester alkaloids (ADA) in both decoctions were found in the range of 1.2—1.4­-fold. It was suggested that in order to control the efficacy and the safety of aconite, the decocting period was well regulated by the specification of water volume for decocting at this ancient era. Moreover, the dosages of aconite root and glycyrrhiza in bukuryoshigyakuto (BSGT) formula of “Songban Shanghanlun” are equal to those of shigyakuto (SGT) but the specified water volume to begin decocting is as about twice as that of SGT. When prepared using hard water, BSGT resulted to make the contents of ADA lower and those of non-­ester alkaloids higher compared with those of SGT decoction. It was suggested the spe­cific water volume for each formula prescribed in classical Chinese medicine had considerable significance to determine the dosages of chemical ingredients in the decoctions especially in the circumstances using hard water to prepare them.

Acupuncture and Moxibustion in Hospitals—How have General Hospitals Changed after Introducing Acupuncture and Moxibustion in Routine Care? / 日本東洋医学雑誌

Although it is not yet common, certified Kampo (traditional Japanese medicine) doctors and acupuncturists are cooperating with each other to provide traditional medical treatment for patients in some general hospitals in Japan. In other hospitals, however, Kampo and acupuncture-moxibustion have not been introduced, and doctors only treat patients using modern Western medicine. Many doctors must already be aware that modern Western medicine is not the only approach for the treatment of patients, but they do not make any efforts to improve the situation by adopting traditional medicine. Here, we give some examples of hospitals in which acupuncture treatments are routinely provided, having a favorable effect on both patients as well as the hospitals themselves. We believe that these examples give us a good opportunity to consider the future of an ideal medical system in which modern Western medicine and traditional Japanese medicine are successfully integrated.

Representative Side Effects Caused by Kampo prescriptions :Pseudoaldosteronism, Drug-induced Liver Injury and Drug-Induced Lung Injury / 日本東洋医学雑誌

The Japan society of oriental medicine created a committee of medical safety in 2017. The first activity was to summarize the representative side effects of Kampo medicine and to enlighten members of our society about them. In this report, we documented the knowledge to keep in mind at present on pseudoaldosteronism, drug-induced liver injury, and drug-induced lung injury. Since these three major side effects may cause clinically severe conditions, it is very important to detect them early and take appropriate measures. Therefore, proper examinations at the right time are necessary while taking Kampo medicine.

Committee for Medical Safety Report : Example of Minor Incidents in the Preparation of Kampo Products in Pharmacy / 日本東洋医学雑誌

We collected and analyzed the case reports of minor incidents in the preparation of Kampo products in Japanese pharmacies in order to manage the medical safety control in Japanese traditional Kampo medicine. We extracted 2,166 reports that are related to Kampo products from the database of minor incidents in pharmacies supplied from The Japan Council for Quality Health Care from 2009 to 2019. Among the reports, we found the cases that pharmacists could find the mistakes about the name, dosage and administration of Kampo products or could prevent the appearance of adverse reaction when pharmacists check the prescription and ask prescription question for doctors. It is suggested that the system of separation of dispensing and prescribing functions would be well working in medical safety control. At the same time, we also found many cases that pharmacists have actually made mistakes by confusing the name of Kampo products and dosage. In this report, we summarized the cases of these minor incidents and frequently appearing confusions about the names of Kampo products.

The Decocting Time and the Contents of the Aconitine-type Diester Alkaloids in the Decoctions of the Formula Containing Unprocessed Aconite Root in “Songban Shanghanlun” / 日本東洋医学雑誌

We investigated the decocting time to prepare the formulas containing unprocessed aconite root, such as shigyakuto, tsumyaku shigyakuto, and kankyobushito, which had been registered in “Shanghanlun” edited in Song Dynasty, using the weights and measures in Houhan Dynasty when the original “Shanghanlun” was regarded to have been established. Also the contents of aconitine-type diester alkaloids (ADA) eluted from unprocessed aconite root in the decoction were analyzed in time-dependent manners. As regards the modified formula for the “physically strong patients” in the texts of tsumyakushigyakuto in “Shanghanlun”, adding dried ginger was found to lead the decocting time to be shorter and the sum of ADA content in the decoction of the modified formula to increase about 20%. It was also found that the compositions of diterpene alkaloids derived from aconite root in kankyobushito decoction were highly different from those in shigyakuto decoction, containing less ADA and more aconine and hypaconine, due to the high pH of the decoction, which was the consequence of lacking glycyrrhiza in kankyobushito formula. It is suggested that the doctors in the era of “Shanghanlun” establishment may have carefully adjusted the contents of ADA in the decoctions using unprocessed aconite root by choosing co-decocted crude drugs.

Efficacy and Safety of Goreisan for Chronic Heart Failure Patients with Chronic Kidney Disease / 日本東洋医学雑誌

Although evidence of Western therapy for heart failure has been established, evidence of treatment for heart failure with chronic kidney disease (CKD) has still not been established. The efficacy of additional Oriental medicine to standard therapy for heart failure with CKD is unclear. To address this issue, we retrospectively evaluated 20 consecutive heart failure patients with CKD (≧stage 3) who were orally administered goreisan (7.5 g/day) due to insufficient efficacy of standard therapy in our hospital from November 2015 to December 2017. We assessed symptoms, chest X-ray, BNP concentration, serum electrolytes, eGRF, plasma osmolality, and side effects. Goreisan improved heart failure in 11 of 20 patients, did not significantly deteriorate renal function, plasma osmolality, and did not clinically affect electrolytes. In conclusion, the present study suggested that additional use of goreisan to Western standard therapy is safe and useful for heart failure with CKD.

Relationship Between Neurological Degenerative Disorders and a Blood Deficiency Using ki-ketsu-sui Score / 日本東洋医学雑誌

We evaluated body constituents patterns of 74 consecutive patients with neurological degenerative disorders. They comprise Parkinson's disease (n = 38), amyotrophic lateral sclerosis (n = 19), and multiple system atro­phy (n = 17). We compared body constituents patterns between them and 149 consecutive patients with other neurological diseases of the same age. We used ki-ketsu-sui scores to evaluate body constituents patterns in all cases. Ki-ketsu-sui scores measure six factors : qi deficiency (kikyo), qi stagnation (kiutsu), qi counterflow (kigyaku), blood deficiency (kekkyo), blood stasis (oketsu), and fluid retention (suitai). As a result of multi­variate analysis, neurological degenerative disorders had large weight of blood deficiency, fluid retention and qi stagnation. Their adjusted odds ratios (95% confidence interval) were 3.02 (1.43-­6.48), 2.37 (1.13-­5.11), 2.33 (1.01-­5.44), respectively. Most relevant factor to neurological degenerative disorders was a blood defi­ciency. Taking into consideration a prescription of “shimotsuto rui” may contribute to alleviate patient's suf­fering. In addition to subjective symptoms, we need an oriental medicine scale such as pulse, tongue, and ab­dominal examinations to judge a therapeutic effect of Kampo medicine.

Seven Infertility Cases Treated by Kampo Medicine for Stagnation of Liver qi / 日本東洋医学雑誌

ART (Assisted Reproductive Technology) is making impressive advancements. However, not all patients will successfully conceive even with this technique. Patients undergoing infertility treatment are predominantly in a state of mental stress for being unable to conceive, and the importance of stress care in treating infertility has been reported. This time, to investigate the relationship between infertility, mental stress and Kampo treatment, we have conducted a retrospective study on 7 patients who achieved conception by a combination treatment of Kampo medicine and ovulation day prediction. Patients'occupation, menstruation history, pregnancy history, premenstrual symptoms, and oriental medical examination findings were extracted from their medical records. The clinical background were age (mean age: 36 [29-39]), time to pregnancy (mean: 6 months [2-9 months]), and outcome (normal vaginal delivery [3 cases], caesarean section [2 cases], abortion [1 case], transfer to other facility [1 case]). The oriental medical diagnosis in all cases found stagnation of liver qi. Two cases had only stagnation of liver qi. As comorbidities, kidney deficiency (3 cases), blood stasis syndrome (1 case), and blood stasis syndrome with syndrome of dual deficiency of qi and blood (1 case) were found. The Kampo prescriptions were as follows: nyoshinsan (2), kamishoyosan (2), tsudosan (1), shigyakusan (1) and kyukichoketsuin (1). Stagnation of liver (TM) qi was considered to play a role in infertility and is one of the important factors in Kampo prescriptions.

Influence of Water Properties on the Contents of Aconitine-Type Diester Alkaloids in the Decoctions of Unprocessed Aconite Root / 日本東洋医学雑誌

The decoctions of unprocessed aconite root (uzu) were prepared with the tap water samples collected in Tianjin and Shanghai in China, and the contents of alkaloids in the decoctions were compared to those prepared with purified water or with tap water collected in Niigata, Japan. The contents of aconitine-type diester alkaloids (ADA) in the decoctions prepared with tap water collected in China were significantly lower than those with purified water or tap water in Niigata. It was speculated that this difference appeared by buffering effect of bicarbonic anion in tap water in China to decline pH of the decoction. When uzu was decocted with glycyrrhiza, ginger, or jujube, the contents of ADA in the decoctions exhibited the tendency to have higher levels than those prepared using unprocessed aconite root singly, and also this tendency was observed more remarkably when the decoctions were prepared with tap water collected in China. It was suggested that even the decocting period was fixed, unexpected change of the contents of ADAs might be induced by the differences in the properties of water used for decoction or the crude drugs decocted with aconite root. The physicians in the era when “Songban Shanghanlun” had established may have adjusted the contents of ADA in the decoction by carefully choosing the crude drugs combined to aconite root.

Characterization of the Body Constituent Patterns for Symptomatic Acute Cerebral Infarction Using qi-ketsu-sui Score / 日本東洋医学雑誌

We evaluated body constituent patterns of 130 consecutive patients with symptomatic acute cerebral infarction. They comprise lacunar infarction (n = 47), atherothrombotic infarction (n = 70), cardiogenic embolism (n = 11), and other type of infarction (n = 2). We compared body constituent patterns between them and 93 consecutive patients with other neurological diseases of the same age. We used qi-ketsu-sui scores to evaluate body constituent patterns in all cases. Qi-ketsu-sui scores measure six factors : qi deficiency (kikyo), qi stagnation (kiutsu), qi counterflow (kigyaku), blood deficiency (kekkyo), blood stasis (oketsu), and fluid retention (suitai). As a result of multivariate model analysis, symptomatic acute cerebral infarction had the largest weight of blood stasis and an adjusted odds ratio (95% confidence interval) was 4.6 (2.45-8.91). Even when gender as a confounding factor was adjusted by stratified analysis, adjusted odds ratios of blood stasis (95% confidence interval) were 7.46 (3.02-20.25) for males and 2.63 (1.02-7.11) for females, and those were maximum. The point (median, interquartile range) of blood stasis was more severe in acute cerebral infarction (24 points, 18-33 points) than other neurological diseases (16 points, 9-23 points). We examined relationships between body constituent patterns and clinical disease type, severity at hospitalization, and sex in patients with symptomatic acute cerebral infarction. Ratio of blood stasis was the largest in any clinical disease type, severity and sex. Blood stasis seemed to be the most important factor in symptomatic acute cerebral infarction.

Implications of the Origin of “Gui” in the “Bencaojingjizhu” / 日本東洋医学雑誌

Crude drugs that feature the name “gui” have appeared in classical medicinal textbooks with different names,and the correspondence between their names and origins remains the subject of research and discussion. In the present study, we investigated these correspondences using the descriptions in the annotations of the Bencaojingjizhu and through our previous study that revealed the standards of weights and measures in this book. Based on this investigation, we strongly speculate that “gui” in the Bencaojingjizhu was the branch skin of Cinnamomum cassia (C. cassia) (corresponding to cinnamon sticks in the market), which fits with the descriptions about the length and weight of “gui” -related crude drugs in this book. We measured the contents of cinnamic aldehyde and coumarin in the branch skin of C. cassia, and compared these to contents in other crude drugs related to “gui” that can be obtained on the market. The contents of these two compounds in the branch skin of C. cassia were similar to those in the bark of C. cassia from Vietnam that meets the standards for cinnamon bark in the Japanese Pharmacopoeia and is regarded as high-grade in the market. These results support our speculation, and it might be possible that the branch skin of C. cassia can be used as medicine instead of cinnamon bark.

A Case of Fatigue-Related Gingival Bleeding with Spleen Failing to Control the Blood Successfully Treated with Kamikihito During theTreatment of Other Symptoms / 日本東洋医学雑誌

In dentistry, it is empirically known that the acute exacerbation of periodontal disease often occurs at the time of fatigue, but scientific verification has never been made about the relationship of fatigue and bleeding. In Kampo medicine, there is the concept of spleen failing to control the blood as bleeding at the time of fatigue. Kihito and kamikihito are often used for this condition. Spleen failing to control the blood means that lack of vital energy causes the bleeding. Kamikihito is most often used in the treatment of idiopathic thrombocytopenic purpura. Moreover, there have been some reports on the use of kamikihito in the treatment of gynecological fraud bleeding and aplastic anemia. However, there has been no report on the use of it in the treatment of gingival bleeding. In this case, neither cytopenia nor obvious coagulopathy was recognized. In Kampo medicine, not only spleen failing to control the blood but also blood stasis or blood heat is considered to be the cause of bleeding, but the effectiveness of kamikihito for this case suggested pathophysiology of spleen failing to control the blood. Kamikihito could be a choice to treat gingival bleeding at the time of fatigue.

<b>Patient Taking Daikenchuto for More than 10 years Suffers from Excess H</b><b>eat</b> / 日本東洋医学雑誌

<p>A 54-year-old female had cesarean sections at ages 26 and 29, a left salpingophrectomy for left ovarian cyst at age 31, and a total abdominal hysterectomy for fibroids at age 41. After total abdominal hysterectomy, she had repeated bouts of ileus and started taking daikenchuto (DKT), which is commonly used to prevent ileus. At age 54, she visited our hospital when DKT failed to relieve her constipation and lower abdominal pain and had occasional heat flash above her neck. Tongue examination revealed pale red tongue and fissured tongue signs with yellow fur and dilation of the sublingual collateral vessels. Kampo diagnosis was blood stasis and excess heat, for which keishibukuryogan was prescribed to be taken daily and with which her symptoms dissipated after 7 days. Despite the popular use of DKT, its potential to cause excess heat after long-term use is not as well known. It is extremely important to warn clinicians who prescribe Kampo not to focus solely on a disease-to-prescription model but also to be learned of the discipline and to take measures to prevent adverse long-term effects and complications.</p>

<b>A Case of Low Vision with Tonic Accommodation Exacerbated by Fatigue and Successfully Treated by </b><b>Shokenchuto</b> / 日本東洋医学雑誌

<p>An 8-year-old girl was admitted with vision loss. She had no history of amblyopia or other eye diseases. On examination, both eyes showed vision loss and uncorrected myopia, regardless of visual acuity correction by glasses. Her symptoms were considered exacerbated by fatigue. We diagnosed tonic accommodation because a regulatory paralysis agent provided relief. The patient had been treated with tropicamide methyl sulfate and neostigmine, but her visual acuity did not change. Based on a Kampo diagnosis, she was prescribed Shokenchuto. After 4 months' administration, her uncorrected vision improved by 1.2 in both eyes, and her visual acuity was maintained even when fatigued. Kampo medicine can be a treatment option for tonic accommodation in cases where standard treatments are ineffective.</p>

<b>Development of a Quick High-Yield Method for the Preparation of Decoctions, Inspired by the “Zhu san Fa” of the Song Period (Part 2)</b> / 日本東洋医学雑誌

The IPCD (Immersing Powdered Crude Drugs) method, inspired by the “zhu san fa” which was widely used in the Song period of China, has been developed to prepare Kampo decoctions quickly and easily, with highyield extract from crude drugs. One trouble with the IPCD method occurs when separating the decoction from the muddy residue of the crude drug powder. When powdered ephedra herb is packed in a nonwoven fabric bag and immersed in hot water, yield of the marker compounds is much lower than that obtained when ephedra herb powder is dispersed freely in hot water without a nonwoven fabric bag. Thus the use of a nonwoven fabric bag was shown to be unsuitable with the IPCD method. In investigating an easy and more efficient separation method, we tried decanting with a commercially available wine carafe to separate the decoction and residue. With IPCD followed by decantation using the wine carafe, yields of about 80% decoction volume were obtained as compared with those when cut crude drugs are decocted and filtered using a tea strainer, in 6 of the 7 formulas tried. We find that decantation using a wine carafe is a more practical way of separation in the IPCD method.

<b>The Investigation of Metrological Standard in “</b><b><i>Songban Shanghanlun</i></b><b>” :Focus on the Absorbed Liquid in the Decoction Residues and the </b><b>Extraction Efficiency of Ephedra-alkal / 日本東洋医学雑誌

The dosage of crude drugs described in the <i>Shanghanlun </i>has long been discussed, and a conversion ratio for 1 liang in the <i>Songban Shanghanlun </i>into modern grams has not been established yet. <i>Ekisai Kariya</i>, a bibliologist in Edo period Japan, claimed that the formulas in the <i>Songban Shanghanlun </i>could not be decocted when weighed with the “Han shu (lu li zhi)” scale (1 liang = 14 g, “regular scale”), and the weight scale in the text should be “Scale of Shen nong” (1/10 scale of the regular scale). This claim leads to the standards for Kampo prescription dosages. We inspected this matter by focusing on the amount of liquid absorbed by decoction residues, and demonstrated that the formulas in <i>Songban Shanghanlun </i>could actually be decocted when weighed with the “regular scale”. In addition, we calculated the quantities of Ephedra-alkaloids in the one-time dose of “Ma huang tang” of the several books written in the Song period, and the <i>Songban Shanghanlun </i>text, with results showing that Chinese doctors in the Song period recognized 1 liang in the <i>Songban Shanghanlun </i>as 14 grams in modern terms, and that the “regular scale” could be applied clinically. This strongly suggests that the metrological standard in the <i>Songban Shanghanlun </i>should be the “regular scale”.

The Weights in <I>Ben Cao Jing Ji Zhu</I> (Dun Huang Version) and the Volume of a <I>Fang Cun Bi</I> (One Cun Square Spoon) : Weights and Measures in the Period when the <I>Shan Han Lun</I> was Written / 日本東洋医学雑誌

For the purpose of investigating weights in the era when the <i>Shan Han Lun </i>was set forth, the weight and measures described in the <i>Ben Cao Jing Ji Zhu</i>, written in the period slightly after the <i>Shan Han Lun</i>, were studied. Some descriptions of the metrological standards are confusing in the <I>Ben Cao Jing Ji Zhu</i>. We focused on the measuring container, whose volume is equal to that of the one cun square spoon (fang cun bi), shown in the dun huang version of the <i>Ben Cao Jing Ji Zhu</i>. The volume of this measuring container was calculated on the assumption that the measures in this text follow those of the <i>Han Shu Li Li Shi</i>, and a result of 5.07 cm³was obtained. The result was confirmed by using the actual measured values of the crude drugs. The result was also considered to support measurements of the volume in the <i>Ben Cao Jing Ji Zhu </i>as following the <i>Han Shu Li Li Shi</i>. With those results, descriptions of the density of honey and lard were examined, and the weight in the <i>Ben Cao Jing Ji Zhu </i>was clarified to follow that in the <i>Han Shu Li Li Shi</i>.

<b>On Ryokyu ARIMA, Tenmin NAMIKAWA's Mentor </b> / 日本東洋医学雑誌

Tenmin NAMIKAWA (並河天民) thought the <i>Shanghanlun</i> (傷寒論) was an important text. He also taught his pupils the importance of prescribing Zhongjing ZHANG's (張仲景) medicines. Ryokyu ARIMA (有馬凉及) was a physician-teacher, who prescribed Chengqitang (承気湯) for the emperor without conferring with other doctors. His chengqitang formulary was derived from medical texts by Zhongjing ZHANG. Kyugo GODA (合田求吾) on the other hand, was a pupil of Ikkannsai MATSUBARA (松原一閑斎), who wrote in the <i>Idokikigaki</i> (医道聞書) : the<i>Koho</i> (古方) school started by Ryokyu ARIMA. He was a hero who was punished by the Goseiin (後西院) emperor. He taught <i>Koho </i>to Tenmin. This therefore reveals that Ryokyu ARIMA was a teacher who taught the importance of the <i>Shanghanlun</i>.