Oral alkalinizing supplementation suppressed intrarenal reactive oxidative stress in mild-stage chronic kidney disease: a randomized cohort study.

BACKGROUND: The beneficial effects of oral supplements with alkalinizing agents in patients with chronic kidney disease (CKD) have been limited to the severe stages. We investigated whether two types of supplements, sodium bicarbonate (SB) and potassium citrate/sodium citrate (PCSC), could maintain renal function in patients with mild-stage CKD. METHODS: This was a single-center, open-labeled, randomized cohort trial. Study participants with CKD stages G2, G3a, and G3b were enrolled between March 2013 and January 2019 and randomly assigned by stratification according to age, sex, estimated glomerular filtration rate (eGFR), and diabetes. They were followed up for 6 months (short-term study) for the primary endpoints and extended to 2 years (long-term study) for the secondary endpoints. Supplementary doses were adjusted to achieve an early morning urinary pH of 6.8-7.2. We observed renal dysfunction or new-onset cerebrovascular disease and evaluated urinary surrogate markers for renal injury. RESULTS: Overall, 101 participants were registered and allocated to three groups: standard (n = 32), SB (n = 34), and PCSC (n = 35). Two patients in the standard group attained the primary endpoints (renal stones and overt proteinuria) but were not statistically significant. There was one patient in the standard reduced eGFR during the long-term study (p = 0.042 by ANOVA). SB increased proteinuria (p = 0.0139, baseline vs. 6 months), whereas PCSC significantly reduced proteinuria (p = 0.0061, baseline vs. 1 year, or p = 0.0186, vs. 2 years) and urinary excretion of 8-hydroxy-2'-deoxyguanosine (p = 0.0481, baseline vs. 6 months). CONCLUSION: This study is the first to report supplementation of PCSC reduced intrarenal oxidative stress in patients with mild-stage CKD.

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.

Predictors for the Development of Hypoxia or Prolonged Acute Symptoms among Non-Hospitalized Mild-to-Moderate Patients with Coronavirus Disease 2019.

The coronavirus disease 2019 (COVID-19) pandemic remains a global public health concern. The clinical course and risk of developing severe illness among patients with COVID-19 who are at low-risk of severe COVID-19 remain uncertain. This retrospective cohort study from an isolation facility for low-risk COVID-19 patients in Japan evaluated the potential risks for severe disease with hypoxia (SpO2 ≤ 93%) or experiencing prolonged isolation period longer than 14 days with persistent acute symptoms. The study was performed before the spread of the alpha variant in the country and before the start of a nationwide mass vaccination campaign against COVID-19. Among the 929 participants with reliable outcome data regarding the development of hypoxia, 63 (6.8%) developed severe disease with hypoxia during their stays at the facility. Higher age [adjusted odds ratio (aOR), 1.08; 95% confidence interval (CI), 1.06-1.10] and male sex (aOR, 4.70; 95% CI, 2.39-9.22) were associated with this outcome. As for the experience of prolonged isolation period, higher age (aOR, 1.02; 95% CI, 1.01-1.04), atopic diseases (aOR, 1.69, 95% CI, 1.09-2.64), presence of cough at onset (aOR, 1.64; 95% CI, 1.09-2.48), and prescription of oral antibiotics before positive test results for COVID-19 (aOR, 2.37; 95% CI, 1.33-4.22) were associated with this outcome. In summary, 5-10% of low-risk COVID-19 patients later develop hypoxia. Older age and male sex were associated with both the development of hypoxia and prolonged acute symptoms. The unnecessary prescription of antibiotics before COVID-19 diagnosis may prolong COVID-19 symptoms.

Refractory Chest Pain in Mild to Moderate Coronavirus Disease 2019 Successfully Treated with Saikanto, a Japanese Traditional Medicine.

Coronavirus disease 2019 (COVID-19) causes a variety of pain symptoms in the acute phase. Severe chest pain suddenly occurs even without abnormalities on examination and is sometimes refractory to analgesics. Such pain is a clinical concern in care facilities with limited resources, and this is the first report on the use of saikanto for its treatment. In Miyagi Prefecture, Japan, COVID-19 patients with mild symptoms were admitted to a hotel that operated as an isolation facility, and their symptoms were observed. In this article, we report four cases in which chest pain comorbid with mild to moderate COVID-19 was successfully treated with saikanto, a traditional Japanese (Kampo) medicine. The patients presented with chest pain and underwent medical examination at the facility. Two patients had severe chest pain refractory to acetaminophen. Critical cardiopulmonary diseases were ruled out in all the patients, and three patients had features of pneumonia on chest radiograph. Medications, including saikanto, were administered to the patients. The patients' chest pain and other symptoms improved 1-4 days after the administration of saikanto, and they left the care facility without hospitalization. The cause of the chest pain experienced by these patients is unclear, but we speculate that it could be minimal pleural inflammation or neuropathy. Previous pharmacological studies have suggested anti-inflammatory and analgesic properties of the crude drugs that constitute saikanto. This case report suggests that saikanto could be a treatment option for chest pain refractory to analgesics in patients with mild to moderate COVID-19.

Response to Glucocorticoid Therapy in Patients with Mild to Moderate Coronavirus Disease 2019 at a Japanese Care Facility.

The fifth wave of the coronavirus disease 2019 (COVID-19) pandemic caused by delta variant infection depleted medical resources, and the Japanese government announced glucocorticoid use for outpatients. An appropriate outpatient-glucocorticoid treatment for COVID-19 has not been established; therefore, we created treatment manuals with indications for glucocorticoid administration in a care facility adequately equipped to manage patients with mild to moderate COVID-19. Thirty-eight patients (24 males, 14 females; mean age 40.5 ± 11.8 years) were treated with glucocorticoids from August 1 to October 1, 2021 [COVID-19 staging, mild (n = 1), moderate I (n = 19), and moderate II (n = 18)]. Patients were treated with 6.6 mg/day d.i.v. or 6 mg/day p.o. dexamethasone, or 20-30 mg/day p.o. prednisolone. The median (25th-75th percentile) number of days from the date of onset to glucocorticoid administration was 8.0 days (7.0-11.25 days). While 24 patients were hospitalized, the condition of 14 improved without hospitalization. The median number of days from glucocorticoid administration to hospitalization was 1.0 day (range, 1.0-1.0 day). In the non-hospitalized patients, the median number of days of glucocorticoid administration was 5.0 days (5.0-5.25 days). The mean number of days from glucocorticoid administration to discharge from the care facility for non-hospitalized patients was 8.4 ± 3.3 days. The adverse reactions among non-hospitalized patients included insomnia (n = 1) and mild liver dysfunction (n = 3). The present method of glucocorticoid administration can be safely used for patients with COVID-19 in care facilities.

Application of objective structured clinical examination (OSCE) for the evaluation of Kampo medicine training.

BACKGROUND: The purpose of this study was to develop an objective, content-valid, and reliable assessment method for Kampo medicine using an objective structured clinical examination (OSCE) for the assessment of clinical competence in Kampo medicine. METHODS: We developed a blueprint followed by a list of 47 assessment items and three task scenarios related to clinical competence in Kampo medicine. An eight-member test committee checked the relevance of the assessment items on a Likert scale. We calculated a content validity index and content validity ratio, and used the Angoff method to set the passing threshold. We trained a total of nine simulated patients with three assigned to each scenario. We conducted an OSCE for 11 candidates with varying medical abilities, and conducted three stations per person, which were evaluated by one evaluator in one room by direct observation. We used video recordings to test the inter-rater reliability of the three raters. We used the test results to verify the reliability of the assessment chart. RESULTS: The inter-rater reliability (intraclass correlation coefficient [2,1]) was 0.973. The reliability of the assessment chart for each scenario (Cronbach's α) was 0.86, 0.89, and 0.85 for Scenarios 1, 2, and 3, respectively. The reliability of the assessment chart for the whole OSCE (Cronbach's α) was 0.90. CONCLUSIONS: We developed a content-valid new OSCE assessment method for Kampo medicine and obtained high inter-rater and test reliabilities. Our findings suggest that this is one of the most reliable evaluation methods for assessing clinical competence in Kampo medicine.

Retrospective study revealed that Zn relate to improvement of swallowing function in the older adults.

BACKGROUND: Zinc is an essential micronutrient for maintaining biological activity. The level of zinc in the blood is known to decrease with age, especially in those over 75 years of age. In older adults patients with impaired functional status, aspiration pneumonia based on dysphagia often becomes problematic. However, the relationship between zinc deficiency and swallowing function has not been studied before. METHODS: A total of 52 older adults subjects (15 males and 37 females) living in a nursing home were enrolled for this study. At the time of enrollment, data of gender, age, body weight, serum zinc levels, serum albumin levels, and the time in a simple 2-step swallowing provocation test (S-SPT) were collected. In patients with serum zinc levels < 60 µg/dL, we initiated 2 months of oral zinc supplementation therapy with a 34 mg/day zinc load. Those who underwent zinc supplementation were re-evaluated after the treatment period and serum zinc levels and S-SPT time were measured. RESULTS: At the time of enrollment, serum zinc level was significantly correlated with serum albumin levels (Pearson's R = 0.58, p < 0.0001) and time in the S-SPT (Spearman's rho = - 0.32, p = 0.0219). Twenty-five of the 52 patients had zinc deficiency with a serum zinc level < 60 µg/dL. After 2 months of oral zinc supplementation, both serum zinc levels (p < 0.0001) and time in the S-SPT (p = 0.04) significantly improved. Meanwhile, serum albumin level (p = 0.48) or body weight (p = 0.07) did not significantly change following zinc supplementation. Zinc supplementation significantly improved swallowing function, especially in the older adults who had comorbid dysphagia and zinc deficiency. CONCLUSIONS: Zinc deficiency is associated with compromised swallowing function in older adults patients with impaired general functions. Oral zinc supplementation can alleviate dysphagia in older adults patients with zinc deficiency even though this is a retrospective study. Further study will be needed to confirm this positive effect.

Two Cases of Multiple Chemical Sensitivity Successfully Treated With Kampo Medicine.

CONTEXT: Multiple chemical sensitivity (MCS) is a chronic disorder in which minimal but sustained exposure to particular chemicals causes headaches, vertigo, and multiple other symptoms. Up to 10% of cases are clinically unresponsive to treatment. Kampo medicines include multiple crude components with many applications for organ disorders. OBJECTIVE: The research team aimed to assess the efficacy of goreisan, a Japanese Kampo medicine, for 2 patients diagnosed with intractable cases of MCS. DESIGN: The research team conducted case studies with 2 female patients. SETTING: The study took place at the Kampo clinic in the Department of Gynecology and Obstetrics at the Japanese Red Cross Maebashi Hospital in Maebashi, Gunma, Japan. PARTICIPANTS: The participants were patients at the clinic. INTERVENTION: The first participant received the Kampo formula goreisan for her headaches and keigairengyoto for her mucosal discomfort; the second received goreisan for her headaches and kakkonto to reduce her shoulder-muscle stiffness. The participants received Kampo treatments for one month. OUTCOME MEASURES: The first participant's MCS symptoms were evaluated with the Quick Environment Exposure Sensitivity Inventory questionnaire (QEESI); the second using a numeric rating scale (NRS). RESULTS: After the Kampo treatments, the first participant's QEESI scores for chemical intolerance, symptom severity, and life impact were reduced from 47, 92, and 76 to 37, 39, and 55 points, respectively. The second participant's NRS scores were likewise reduced from 6, 8, and 8 out of 10 to 1, 2, and 1 out of 10. Symptoms were relieved in both patients, and didn't recur. CONCLUSIONS: These results highlight the potential benefits of Kampo medicine for the treatment of intractable MCS. Further investigations will be needed to confirm the mechanism of action, thereby improving the understanding of the effectiveness of Kampo medicine for MCS therapy.

Treatment of COVID-19-Related Olfactory Disorder Promoted by Kakkontokasenkyushin'i: A Case Series.

Olfactory disorders are one of the characteristic symptoms of the coronavirus disease of 2019 (COVID-19), which causes infection and inflammation of the upper and lower respiratory tract. To our knowledge, there are no treatments for COVID-19-related olfactory disorder. Here, we report five olfactory disorder cases in COVID-19, treated using the Japanese traditional (Kampo) medicine, kakkontokasenkyushin'i. We treated five patients with mild COVID-19 at an isolation facility using Kampo medicine, depending on their symptoms. Patients with the olfactory disorder presented with a blocked nose, nasal discharge or taste impairment. Physical examination using Kampo medicine showed similar findings, such as a red tongue with red spots and sublingual vein congestion, which presented as blood stasis and inflammation; thus, we prescribed the Kampo medicine, kakkontokasenkyushin'i. After administration, the numeric rating scale scores of the smell impairment improved within 3 days from 9 to 3 in case 1, from 10 to 0 in case 2, from 9 to 0 in case 3, from 5 to 0 in case 4, and from 9 to 0 within 5 days in case 5. Following the treatment, other common cold symptoms were also alleviated. Kakkontokasenkyushin'i can be used for treating nasal congestion, rhinitis, and inflammation in the nasal mucosa. The olfactory disorder in COVID-19 has been reportedly associated with inflammation and congestion, especially in the olfactory bulb and olfactory cleft. Kakkontokasenkyushin'i may be one of the treatment alternatives for the olfactory disorder with rhinitis in patients with COVID-19.

The use of maoto (Ma-Huang-Tang), a traditional Japanese Kampo medicine, to alleviate flu symptoms: a systematic review and meta-analysis.

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.

Improving the Quality of Postgraduate Education in Traditional Japanese Kampo Medicine for Junior Residents: An Exploratory Survey Conducted in Five Institutions in the Tohoku Area.

Traditional Japanese (Kampo) medicine has been widely applied in general medicine in Japan. In 2001, the model core curriculum for Japanese medical education was revised to include Kampo medicine. Since 2007, all 80 Japanese medical schools have incorporated it within their programs. However, postgraduate training or instruction of Kampo medicine has not been recognized as a goal for the clinical training of junior residents by Japan's Ministry of Health, Labour and Welfare; little is known about postgraduate Kampo medicine education. This exploratory study investigated attitudes about Kampo medicine among junior residents in Japanese postgraduate training programs. A questionnaire survey was administered to junior residents at five institutions in the Tohoku area of Japan. Questions evaluated residents' experiences of prescribing Kampo medicines and their expectations for postgraduate Kampo education and training. As a result, 121 residents responded (response rate = 74%). About 96% of participants had previously received Kampo medicine education at their pre-graduate medical schools and 64% had prescribed Kampo medications. Specifically, daikenchuto was prescribed to prevent ileus and constipation after abdominal surgery and yokukansan was prescribed to treat delirium in the elderly. Residents received on-the-job instruction by attending doctors. Over 70% of participants indicated that there was a need for postgraduate Kampo medicine education opportunities and expected lectures and instruction on how to use it to treat common diseases. In conclusion, we have revealed that junior residents require Kampo medicine education in Japanese postgraduate training programs. The programs for comprehensive pre-graduate and postgraduate Kampo education are expected.

Questionnaire-Based Development of an Educational Program of Traditional Japanese Kampo Medicine.

Traditional Japanese Kampo medicine has been widely used in clinical practice in Japan. Though it is a compulsory subject in Japanese medical schools, a standard educational program in Kampo medicine does not exist. Tohoku University has incorporated Kampo medicine into clinical education via didactic lectures since 2003; however, student evaluations have been lower for Kampo than for all other clinical specialties. We administered a questionnaire about a Kampo medicine course for fifth-year students from 2009 to 2012 and developed an educational program based on feedback obtained. The questionnaire consisted of nine questions (a clear training plan; opportunities for learning, practice, and patient contact; acquisition of medical knowledge and physical examination; learning professionalism; understanding the specialty; overall assessment) that were rated on a 5-point Likert scale along with open-ended questions about the course's strengths and weaknesses. The students responded to the questionnaire after clinical practice in Kampo medicine and other clinical specialty courses. Scores for Kampo medicine and the average of other clinical specialties were compared. All 389 students who participated in Kampo clinical practice answered the questionnaire. In 2009, scores for Kampo medicine for nine questions were lower than for the average of the other clinical specialties. After curriculum reformation involving hands-on training in 2012, all scores except "opportunities to learn about clinical cases" and "opportunities to practice involvement" were higher than the average of all other clinical specialties. In conclusion, we have successfully developed a Kampo medicine educational program for our university through this survey study.

Effect of ninjin'yoeito, a Kampo (traditional Japanese) medicine, on cognitive impairment and depression in patients with Alzheimer's disease: 2 years of observation.

BACKGROUND: Only a few approved drugs are capable of alleviating the cognitive and behavioural symptoms of people living with Alzheimer's disease (AD). In recent years, however, the number of studies examining the clinical effects of herbal medicines on cognitive function in patients with AD has increased considerably. This study evaluated the long-term effects of a traditional Japanese medicine (Kampo medicine) known as ninjin'yoeito (NYT) on cognitive impairment and mood status in patients with AD over a 2-year period. METHODS: Twenty-three patients with mild-to-moderate probable AD according to the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association criteria were included. Each participant had exhibited an insufficient response to treatment with donepezil alone before the start of the trial. Eleven patients received treatment with donepezil alone, and the remaining patients received a combined treatment of donepezil and NYT for 2 years. Patients were assessed by the Mini-Mental State Examination and the Alzheimer's Disease Assessment Scale-cognitive component-Japanese version for cognitive function, and the Neuropsychiatric Inventory was used to evaluate the patients' mood status at baseline and every 6 months for 2 years. RESULTS: The Mini-Mental State Examination results showed no significant differences between the two groups. Significant improvements were observed on the Alzheimer's Disease Assessment Scale-cognitive component-Japanese version and the Neuropsychiatric Inventory depression scores of patients who received the combined therapy with donepezil and NYT (Alzheimer's Disease Assessment Scale-cognitive component-Japanese version, 12 months: P < 0.01, 18 months: P = 0.04, 24 months: P < 0.01; Neuropsychiatric Inventory depression, 6 months: P < 0.05, 24 months: P < 0.05). CONCLUSIONS: A 2-year follow-up of patients receiving donepezil and NYT treatment showed an improved cognitive outcome and alleviation of AD-related depression.

Growth Differentiation Factor-15 Is Considered a Predictive Biomarker of Long COVID in Non-hospitalized Patients.

Mitochondrial dysfunction is associated with various diseases. Mitochondria plays a regulatory role during infection. The association between mitokines and subsequent COVID progression has not been previously studied. The retrospective cohort study aimed to investigate the potential of serum mitokines as long COVID biomarkers in non-hospitalized patients. Patients with confirmed SARS-CoV-2 infection and blood test reports between January 2021 and April 2023 were included. Patients were categorized into two groups, the recovered and long COVID groups, based on fatigue, decline in focus, and pain. Serum levels of growth differentiation factor 15 (GDF-15) and fibroblast growth factor-21 (FGF-21), which are affected by mitochondrial function, along with inflammatory and vascular endothelium markers, were measured using enzyme-linked immunosorbent assays (ELISA). A receiver operating characteristic curve was used to screen the biomarkers. The threshold value of GDF-15 in the acute phase was 965 pg/mL (sensitivity: 71.4%, specificity: 83.3%), indicating that GDF-15 may be associated with the presence of symptoms three months post onset. No association with inflammatory markers and vascular structures was observed. Therefore, elevated GDF-15 levels in the acute phase may act as a predictive biomarker of long COVID.

Risk of Major Congenital Malformations Associated with the Use of Japanese Traditional (Kampo) Medicine Containing Ephedra During the First Trimester of Pregnancy.

BACKGROUND: Japanese traditional (Kampo) medicines containing ephedra may be used to treat colds during pregnancy. There are reports that ephedrine, a component of ephedra, has a risk of teratogenicity; however, the evidence remains equivocal. OBJECTIVE: This study aimed to evaluate the risk of major congenital malformations (MCMs) associated with exposure to Kampo medicines containing ephedra during the first trimester of pregnancy using the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study). METHODS: To 23,730 mother-infant pairs who participated in the TMM BirThree Cohort Study from July 2013 to March 2017, questionnaires in early and middle pregnancy were distributed approximately at weeks 12 and 26 of pregnancy, respectively. Infants' risk of MCMs in women who used Kampo medicines containing ephedra or acetaminophen during the first trimester was assessed, and the odds ratios (ORs) were estimated with unadjusted and adjusted analyses. RESULTS: Among 20,879 women, acetaminophen and Kampo medicines containing ephedra were used in 665 (3.19%) and 376 (1.80%) women, respectively, in the first trimester. Among the infants born to the mothers who used acetaminophen or Kampo medicine containing ephedra during the first trimester, 11 (1.65%) and 8 (2.13%), respectively, had overall MCMs. OR of overall MCMs was higher in women who used Kampo medicines containing ephedra than in those who used acetaminophen in the first trimester (adjusted OR, 1.45; 95% confidence interval (CIs), 0.57-3.71); however, the difference was not statistically significant. CONCLUSIONS: In this study, there was no statistically significant association between the use of Kampo medicines containing ephedra during the first trimester of pregnancy and the risk of MCMs. Although some point estimates of ORs exceeded 1.00, the absolute magnitude of any increased risks would be low.

The Integration of Traditional Medicine with Conventional Biomedicine: A Narrative Review of the Japanese Perspective.

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.

Press needle for aspiration pneumonia prevention in older adults: Study protocol for a randomized double-blind placebo-controlled trial.

BACKGROUND: Pneumonia is the fifth most common cause of death among the Japanese population, with 97% of the deaths occurring among older adults aged ≥65 years. The incidence ratio of aspiration pneumonia is high among the older adults. Therefore, its prophylaxis is important in geriatric medicine. In our previous studies, we reported that stimulation of acupoints at stomach meridian 36 and kidney meridian 3 of the lower limbs with a press needle improved the swallowing function of patients with dysphagia. Improvements in swallowing function may prevent aspiration pneumonia. This study aims to investigate the protective efficacy of press needle stimulation in the lower limbs for aspiration pneumonia. METHODS/DESIGN: This is a multicenter, randomized, double-blind, placebo-controlled trial. A total of 140 patients with cerebrovascular disorder and a history of aspiration pneumonia will be recruited from 6 centers and randomly assigned to either the real or sham press needle group in a 1:1 ratio. The press needle will be replaced twice a week. The treatment will be administered bilaterally at acupoints stomach meridian 36 and kidney meridian 3. The primary outcome is the frequency of aspiration pneumonia onset. The secondary outcome is the improvement of the latent time of the swallowing reflex. The study period is of 12-month. The primary outcome will be evaluated throughout the study period, while the secondary outcomes will be assessed at baseline, 1st month, 6th month, and at the end of the investigation period. DISCUSSION: This study will evaluate the effects of press needle on the prevention of aspiration pneumonia and the improvement of swallowing function in patients. The results of this study will help support the prophylaxis of aspiration pneumonia.

No association between major congenital malformations and exposure to Kampo medicines containing rhubarb rhizome: A Japanese database study.

Traditional Japanese (Kampo) medicines containing rhubarb rhizome are prescribed for constipation during pregnancy; however, detailed safety information of their use for pregnant women is lacking. The aim of current study was to clarify the association between prescription Kampo-containing rhubarb rhizome (KRR) in the first trimester of pregnancy and congenital malformations in newborns. Using a large Japanese health insurance claims database, we included pregnant women who enrolled the same health insurance society from 3 months before pregnancy to the delivery date, who gave birth between 2010 and 2019, and those with data related to their infants. Pregnant women who were prescribed magnesium oxide (MgO), commonly used for constipation, during the first trimester of pregnancy and their infants were extracted as controls. Associations between KRR prescribed in the first pregnancy trimester and major congenital malformations (MCM) in the infants were examined using multivariate logistic regression analysis. Of 75,398 infants, 4,607 (6.1%) were diagnosed with MCMs within the first year after birth. Furthermore, 9,852 infants were born to women prescribed MgO, among whom 680 (6.9%) had MCMs; 450 infants were born to women prescribed KRR, among whom 28 (6.2%) had MCMs. Multivariate logistic regression analysis identified no difference in MCM risk between the two types of prescriptions [crude odds ratio (OR) 0.895, 95% confidence interval (CI) 0.606-1.322, adjusted OR 0.889, 95% CI 0.599-1.320]. In conclusion, the risk of MCMs did not differ between those prescribed KRR or MgO in the first trimester of pregnancy.

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.

Case Report: Prolonged Anorexia With Nausea Caused by Immune Checkpoint Inhibitors for Malignant Melanoma Treated Using Kampo Medicines Bukuryoingohangekobokuto and Ninjin'yoeito.

Immune checkpoint inhibitors (ICIs) are indicated for several cancers, including malignant melanoma. Anorexia and nausea resulting in malnutrition are side effects of ICIs. In such cases, conventional drugs are used for symptom relief, but the symptoms may persist. We report a case of advanced malignant melanoma with prolonged anorexia and nausea, which occurred after nivolumab administration, and was successfully treated using Kampo medicines. A 75-year-old man with nasal bleeding visited our hospital. A nasal scope revealed an obstructive tumor in the left nasal concha. Tissue biopsy showed malignant melanoma, and computed tomography showed metastasis to the liver and bone. Thus, the patient was diagnosed with stage IV malignant melanoma. He received radiotherapy (30 Gy) and nivolumab with ipilimumab four times, followed by nivolumab administration alone. During the administration of nivolumab, he complained of severe anorexia and nausea, with a numeric rating scale (no symptoms, 0; severe symptoms, 10) score of 10. He could not consume food because of these symptoms, even after nivolumab administration was discontinued. His blood pressure was 92/59 mmHg, his performance status (PS; no fatigue, 0; bedridden or disabled, 4) was 4, and his body weight gradually decreased from 60 to 39 kg in a month. The patient showed malnutrition and dehydration and experienced anxiety and depression. Nivolumab was terminated, and conventional symptomatic drugs were prescribed, but the symptoms persisted. We then prescribed 9.0 g/day of ninjin'yoeito (TJ-108, Tsumura and Co.) to allow recovery from anorexia and subsequently added bukuryoingohangekobokuto (TJ-116, Tsumura and Co.) to treat the persistent nausea. After treatment with these two Kampo medicines, the patient's appetite gradually recovered. Along with the recovery of nutritional status, his PS improved to 0, his anxiety and depressive state improved, and his body weight increased to 60 kg. The patient remained in good condition without cancer recurrence. The patient's clinical course shows the usefulness of Kampo medicine as supportive care for symptom relief and maintenance of nutritional and mental status during cancer treatment.