Contribution of traditional Japanese Kampo medicines, kakkonto with shosaikotokakikyosekko, in treating patients with mild-to-moderate coronavirus disease 2019: Further analysis of a multicenter, randomized controlled trial.

We previously reported the finding of symptom relief in a randomized controlled trial with the combined use of kakkonto and shosaikotokakikyosekko added to conventional treatment in patients with coronavirus disease 2019 (COVID-19). For further evaluation, we performed post hoc analysis focused on symptom disappearance without recurrence, to determine a clearer effect of Kampo medicine. Patients with mild and moderate COVID-19 were randomly allocated to a control group receiving symptomatic therapy or a Kampo group receiving kakkonto (2.5 g) with shosaikotokakikyosekko (2.5 g) three times daily in addition to symptomatic therapy. The data of 161 patients (Kampo group, n = 81; control group, n = 80) were analyzed post hoc for the time to symptom disappearance. Kaplan-Meier and Cox proportional hazard estimates of disappearance of symptoms showed that all and each symptom targeted in this study disappeared faster in the Kampo group than in the control group, although not statistically significant (all symptomatic cases; hazard ratio [HR] 3.73, 95% confidence interval [CI] 0.46-29.98, log-rank p = 0.1763). In a supplemental assessment using covariate adjustment and competing risk analysis, fever disappeared faster in the Kampo group than in the control group (all symptomatic cases, HR 1.62, 95% CI 0.99-2.64, p = 0.0557; unvaccinated cases, HR 1.68, 95% CI 1.00-2.83, p = 0.0498) and shortness of breath disappeared significantly faster in Kampo group than in control group (all symptomatic cases, HR 1.92, 95% CI 1.07-3.42, p = 0.0278; unvaccinated cases, HR 2.15, 95% CI 1.17-3.96, p = 0.0141). These results demonstrate the advantages of Kampo treatment for acute COVID-19.

Conventional and Kampo Medicine Treatment for Mild-to-moderate COVID-19: A Multicenter, Retrospective, Observational Study by the Integrative Management in Japan for Epidemic Disease (IMJEDI Study-observation).

Objective Patients in whom coronavirus disease 2019 (COVID-19) was suspected or confirmed between January 1, 2020, and October 31, 2021, were enrolled from Japanese hospitals in this multicenter, retrospective, observational study. Methods Data on the treatment administered (including conventional and Kampo medicine) and changes in common cold-like symptoms (such as fever, cough, sputum, dyspnea, fatigue, and diarrhea) were collected from their medical records. The primary outcome was the number of days without a fever (with a body temperature <37°C). The secondary outcomes were symptomatic relief and the worsening of illness, defined as the presence of a condition requiring oxygen inhalation. The outcomes of patients treated with and without Kampo medicine were compared. Patients We enrolled 962 patients, among whom 528 received conventional and Kampo treatment (Kampo group) and 434 received conventional treatment (non-Kampo group). Results Overall, after adjusting for the staging of COVID-19 and risk factors, there were no significant between-group differences in the symptoms or number of days being afebrile. After performing propensity score matching and restricting the included cases to those with confirmed COVID-19 who did not receive steroid administration and initiated treatment within 4 days from the onset, the risk of illness worsening was significantly lower in the Kampo group than in the non-Kampo group (odds ratio=0.113, 95% confidence interval: 0.014-0.928, p=0.0424). Conclusion Early Kampo treatment may suppress illness worsening risk in COVID-19 cases without steroid use. Further randomized controlled studies are needed to confirm the clinical benefit of Kampo medicine for COVID-19.

Multicenter, randomized controlled trial of traditional Japanese medicine, kakkonto with shosaikotokakikyosekko, for mild and moderate coronavirus disease patients.

The traditional Japanese (Kampo) medicine, kakkonto with shosaikotokakikyosekko, has antiviral and anti-inflammatory effects. In this randomized trial, patients with mild and moderate coronavirus disease (COVID-19) were randomly allocated to the control group receiving conventional treatment for symptom relief such as antipyretics and antitussives or the Kampo group receiving mixed extract granules of kakkonto (2.5 g) and shosaikotokakikyosekko (2.5 g) three times a day for 14 days in addition to conventional treatment. The main outcome was the number of days until total symptom relief. The secondary outcome was the number of days until each symptom's relief and whether the disease progressed to respiratory failure. We enrolled a total of 161 patients (Kampo group, n = 81; control group, n = 80). The results from Kaplan-Meier estimates of symptom relief showed that there are no significant differences between the groups. However, covariate-adjusted cumulative incidence of fever relief considering competitive risk showed that the recovery was significantly faster in the Kampo group than in the control group (HR 1.76, 95% CI 1.03-3.01). Additionally, the risk of disease progression to moderate COVID-19 requiring oxygen inhalation was lower in the Kampo group than in the control group (Risk Difference -0.13, 95% CI -0.27-0.01). No significant drug-related side effects were observed. Kakkonto with shosaikotokakikyosekko is effective for fever relief with suppression of disease progression in COVID-19 patients. Clinical Trial Registration: https://jrct.niph.go.jp/en-latest-detail/jRCTs021200020, identifier [jRCTs021200020].

Prevention and Recovery of COVID-19 Patients With Kampo Medicine: Review of Case Reports and Ongoing Clinical Trials.

Coronavirus disease 2019 (COVID-19) spread to Japan in 2020, where the number of infected patients exceeded 250,000 and COVID-related deaths exceeded 3,500 in one year. Basic guidelines for infection control were implemented in Japan, and research and development of effective drugs and vaccines were promoted. This included considering Kampo medicine, which has a long history of treating recurring emerging viral infections. Considering the characteristics of the disease (inflammation of the upper and lower respiratory tract as well as potential neural damage and vasculitis), Kampo medicine could be considered as a treatment strategy due to its antiviral and anti-inflammatory effects induced by multiple active substances that could aid in disease prevention and recovery. In this study, case reports on the management of COVID-19 with Kampo medicine, which were published until March 31, 2021, were reviewed. The search strategy involved the use of Medline and hand-searching. Twenty two patients were treated using Kampo medicines with or without Western medicine, based on individual conditions. On the other hand, the effects of Kampo medicines as a potential preventive treatment (pre-infection), active treatment (especially in the acute and subacute stage), or treatment of sequelae to aid recovery (after infection) in the different stages of COVID-19 are being studied as research projects in the Japan Society for Oriental Medicine (JSOM). JSOM has also organized a pioneering project of clinical trials for COVID-19, some of which are now in progress.

Identification of a predictive biomarker for the beneficial effect of keishibukuryogan, a kampo (Japanese traditional) medicine, on patients with climacteric syndrome.

Keishibukuryogan (KBG; Guizhi-Fuling-Wan in Chinese) is one of the Kampo (Japanese traditional) medicines used to treat patients with climacteric syndrome. KBG can be used by patients who cannot undergo hormone replacement therapy due to a history of breast cancer. We evaluated whether cytosine-adenine (CA) repeat polymorphism of the estrogen receptor ß gene can be a predictor of the beneficial effect of KBG on climacteric syndrome. We also investigated the relationship between CA repeat polymorphism, the patients' profiles, and the therapeutic effect. We found that CA was an SS, SL, or LL genotype according to the number of repeats. We studied 39 consecutive patients with climacteric disorders who took KBG for 12 weeks. The diagnosis of climacteric disorders was made on the basis of the Kupperman index. KBG significantly improved the patients' climacteric symptoms (i.e., vasomotor symptoms in the patients with the LL genotype and melancholia in the patients with the SL genotype). No relationship between the patients' profiles and CA repeat polymorphism was recognized. CA repeat polymorphism could thus be a potential biomarker to predict the efficacy of KBG in climacteric syndrome, and its use will help to reduce the cost of treating this syndrome by focusing the administration of KBG on those most likely to benefit from it.

Multicentre population-based dementia prevalence survey in Japan: a preliminary report.

Community-based surveys were performed in seven rural areas in Japan to investigate the prevalence of dementia and illnesses causing dementia. A total of 5431 elderly subjects were selected based on census data from 1 October 2009. In total, 3394 participants were examined (participation rate: 62.5%), and 768 dementia cases and 529 mild cognitive impairment cases were identified. Of the illnesses causing dementia, Alzheimer's disease was the most frequent (67.4%), followed by vascular dementia (18.9%), dementia with Lewy body disease (4.6%), mixed dementia (4.2%) and other illnesses. The prevalence of dementia according to 5-year age strata between 65 and 99 years was 5.8-77.7% among the participants. The prevalence of dementia in this study was higher than in previous reports in Japan and other countries. To verify the upward trend of dementia prevalence and its background factors, we have scheduled surveys for three other urban areas in 2011-2012.

Four cases of panic disorder successfully treated with Kampo (Japanese herbal) medicines: Kami-shoyo-san and Hange-koboku-to.

Kampo medicines have been used to treat patients with psychogenic disorders from ancient times. In the present report the cases are described of four patients with panic disorder successfully treated with Kampo medicines. These four patients fulfilled the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for panic disorder with agoraphobia. The Kampo medicine Kami-shoyo-san (TJ-24) relieved panic attacks, anticipatory anxiety and agoraphobia in two patients, and Hange-koboku-to (TJ-16) relieved these symptoms in the other two patients. The patients in whom Kami-shoyo-san was effective were older and complained of more symptoms than those in whom Hange-koboku-to was effective. These Kampo medicines may be useful as additional or alternative treatments for panic disorder.

A case of sleep choking syndrome improved by the Kampo extract of Hange-koboku-to.

A case of sleep choking syndrome with typical symptoms is presented. A 44-year-old Japanese male suffered from multiple episodes of choking, which suddenly appeared with fear of impending death about 30 min after falling asleep almost every night. Overnight polysomnography showed an apnea index of 0.92 events/h, an apnea-hypopnea index of 2.77 events/h, and normal respiration during sleep with the exception of the episodes of apnea and hypopnea. No choking episode occurred in the sleep laboratory. The administration of 500 mg of acetazolamide was ineffective, but the choking episode improved after the administration of Kampo extract of Hange-koboku-to (Ban-xia-hou-pu-tang). Hange-koboku-to may be effective in treating choking sensation during sleep as well as during wakefulness.