Traditional Chinese medicine Jia Wei Gui Pi Tang improves behavioural and psychological symptoms of dementia and favourable positive emotions in patients.

BACKGROUND: Behavioural and psychological symptoms of dementia (BPSD) are challenging to manage, leading to caregiver burden and often to subsequent transfer of patients to a nursing home or psychiatric hospital for treatment. Eliciting favourable positive emotions should be an important goal in the treatment of negative emotions associated with BPSD. To date, no data have indicated that antipsychotic medications can improve positive emotions. BPSD are known to be associated with anxiety in patients with dementia. The traditional Chinese medicine Jia Wei Gui Pi Tang is officially indicated and approved for anxiety treatment in Japan. METHODS: Here, we performed a multicentre, randomised, observer-blind control study of the effect of Jia Wei Gui Pi Tang on BPSD in Alzheimer's disease (AD) patients. Patients with AD or AD with cerebral vascular disease were randomly divided into the Jia Wei Gui Pi Tang treatment group and the control group that received no traditional Chinese medicine. BPSD were scored using the Neuropsychiatric Inventory Nursing Home Version (NPI-NH) and by favourable positive emotions using the Delightful Emotional Index (DEI). RESULTS: A total of 63 participants (18 male and 45 female; mean age: 83.3 ± 6.0 years) were included in the study. Changes in NPI-NH scores differed significantly between the two groups (one-way analysis of variance, P < 0.001). Within the treatment group, there was a significant improvement in the NPI-NH score from 29.8 ± 17.3 at baseline to 13.2 ± 9.4 at the endpoint (paired t-test, P < 0.001), whereas there was no statistically significant change in the control group. Changes in DEI scores differed significantly between the two groups. Within the treatment group, there was a significant improvement in the DEI score from 24.3 ± 23.0 at baseline to 32.5 ± 21.2 at the endpoint (paired t-test, P = 0.001), whereas there was no statistically significant change in the control group. CONCLUSION: The traditional Chinese medicine Jia Wei Gui Pi Tang significantly improved both BPSD and positive emotions.

The development and clinical application of a novel schizophrenia screening system using yoga-induced autonomic nervous system responses.

Background: In severe cases, schizophrenia can result in suicide and social isolation. Diagnosis delay can lead to worsening symptoms, and often results in prolonged therapy. An estimated 50%-80% of patients with schizophrenia are unaware of their condition. Biomarkers for schizophrenia are important for receiving a diagnosis from a psychiatrist at an early stage. Although previous studies have investigated near-infrared spectroscopy as a biomarker for schizophrenia, the required equipment is expensive and not designed for home use. Hence, we developed a novel home-use schizophrenia screening system that uses a wearable device to measure autonomic nervous system responses induced by yoga, which is frequently adopted in rehabilitation for schizophrenia. Materials and methods: The schizophrenia screening system automatically distinguishes patients with schizophrenia from healthy subjects via yoga-induced transient autonomic responses measured with a wearable wireless electrocardiograph (ECG) using linear discriminant analysis (LDA; Z score ≥ 0 → suspected schizophrenia, Z-score < 0 → healthy). The explanatory variables of LDA are averages of four indicators: components of heart rate variability (HRV): the very low-frequency (VLF), the low-frequency (LF), HR, and standard deviation of the NN intervals (SDNN). In the current study, HRV is defined as frequency domain HRV, which is determined by integrating RRI power spectrum densities from 0.0033 to 0.04 Hz (VLF) and 0.04-0.15 Hz (LF), and as time domain HRV, SDNN of which is calculated as the mean of the standard deviations of the RR intervals. These variables were measured before (5 min), during (15 min), and after (5 min) yoga in a 15-min mindfulness-based yoga program for schizophrenia (MYS). The General Health Questionnaire-28 (GHQ28) score was used to assess the severity of mental disorders for patients with schizophrenia and healthy volunteers. Twelve patients with schizophrenia (eight female and four male, 23-60 years old) and 16 healthy volunteers (seven female and nine male, 22-54 years old) were recruited. Results: The schizophrenia screening system achieved sensitivity of 91% and specificity of 81%. Z-scores of LDA were significantly correlated with GHQ28 scores (r = 0.45, p = 0.01). Conclusion: Our proposed system appears to be promising for future automated preliminary schizophrenia screening at home.

Incidence of Herb-induced Liver Injury Caused by Kampo Formulae Containing Scutellariae Radix.

OBJECTIVE: Herb-induced liver injury due to Kampo formulae is a clinically relevant adverse effect, which may be associated with formulae containing Scutellariae Radix. We explored this incident relationship further by surveying outpatients treated with a Kampo formula containing Scutellariae Radix (KFCSR) at our clinic. METHODS: We included patients who had been treated with a novel KFSCR formulation between November 2014 and October 2015. The participants underwent liver injury-related blood tests (examining the aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, and total bilirubin levels, as well as the percentage of eosinophils in the white blood cell count) before and after treatment to evaluate its efficacy. RESULTS: In total, 43 of the 363 patients treated during the study period received KFCSRs and 37 underwent blood tests before and after treatment. Liver injury occurred in four patients (10.8%) and all patients recovered quickly after cessation of the formula. CONCLUSIONS: We found that 10.8% of patients treated with KFCSR developed liver injury, which was higher than that reported previously. We believe that herb-induced liver injury should be seriously considered as a risk factor for KFCSRs. Further investigation is warranted to verify these results.

Kampo Formula-Pattern Models: The Development of 13 New Clinically Useful Standard Abdominal Pattern Models in the Fukushin Simulator.

Aim: In Kampo medicine, there exists an important system of diagnosis called Fukushin, or abdominal diagnosis or palpation. By applying pressure to the abdomen of the patient, the physician can gain important information on the patient's physical state and use those indications to choose a suitable Kampo formulation. We have previously developed a Fukushin simulator, a teaching tool that reproduces the important abdominal patterns that doctors will encounter in clinical practice and that has received favourable feedback for students and practitioners. In order to make diagnosis and prescription easier, it is desirable to have matched formula-pattern pairings. The present study aims to develop such pairings. Methods: With the previously developed models as a foundation, in the present study the production team (two members) used materials such as urethane foam and silicone rubber to build an additional 13 standard abdominal pattern models matched to Kampo herbal formulas commonly used by practitioners in Japan. Subsequently, the evaluation team (the remaining 10 authors) investigated the viability of these models. Results: The evaluation team determined that abdominal pattern models matched to the following typical Kampo formulas were created successfully: Dai-saiko-To (), Dai-joki-To (), Shigyaku-San (), Saiko-ka-ryukotsu-borei-To (), Keishi-bukuryo-Gan (), Hachimi-jio-Gan (), Hange-shashin-To (), Sho-saiko-To (), Hochu-ekki-To (), Sho-kenchu-To (), Toki-shakuyaku-San (), Ninjin-To (), and Dai-kenchu-To (). Conclusion: We suggest that these new formula-pattern models can make an important contribution to the standardization of abdominal diagnosis and prescription and to Kampo education.

Evidence-based clinical practice guidelines for functional dyspepsia 2021.

BACKGROUND: Functional dyspepsia (FD) is a disorder that presents with chronic dyspepsia, which is not only very common but also highly affects quality of life of the patients. In Japan, FD became a disease name for national insurance in 2013, and has been gradually recognized, though still not satisfactory. Following the revision policy of Japanese Society of Gastroenterology (JSGE), the first version of FD guideline was revised this time. METHOD: Like previously, the guideline was created by the GRADE (grading of recommendations assessment, development and evaluation) system, but this time, the questions were classified to background questions (BQs, 24 already clarified issues), future research questions (FRQs, 9 issues cannot be addressed with insufficient evidence), and 7 clinical questions that are mainly associated with treatment. RESULTS AND CONCLUSION: These revised guidelines have two major features. The first is the new position of endoscopy in the flow of FD diagnosis. While endoscopy was required to all cases for diagnosis of FD, the revised guidelines specify the necessity of endoscopy only in cases where organic disease is suspected. The second feature is that the drug treatment options have been changed to reflect the latest evidence. The first-line treatment includes gastric acid-secretion inhibitors, acetylcholinesterase (AChE) inhibitors (acotiamide, a prokinetic agent), and Japanese herbal medicine (rikkunshito). The second-line treatment includes anxiolytics /antidepressant, prokinetics other than acotiamide (dopamine receptor antagonists, 5-HT4 receptor agonists), and Japanese herbal medicines other than rikkunshito. The patients not responding to these treatment regimens are regarded as refractory FD.

Comparison of the 2011 and 2019 Kampo Medicine Curricula Across All Japanese Medical Schools.

OBJECTIVE: To examine how Kampo education in Japanese medical schools changed between 2011 and 2019. METHODS: We administered nationwide postal questionnaire surveys about current characteristics of Kampo medicine education in all 82 Japanese medical schools, directed to the persons responsible for Kampo education at each university. One survey was conducted in 2011 and one in 2019. Analysis used Welch's t-test and a chi-squared test. RESULTS: The average class meeting time was shorter in 2019 than in 2011. The proportion of class meetings that were about Kampo saw a statistically significant increase in the third year and a significant decrease in the fourth and sixth years of medical school. Curriculum standardisation, preparation of simple textbooks, and fostering Kampo medicine instructors were the primary problems in both years. The proportion of mainstream medical education contents focusing on traditional Japanese Kampo medicine did not change over time, nor did the percentage of those considering using standardised textbooks. Other changes were statistically nonsignificant. CONCLUSION: In Japanese medical schools, the number of class meetings teaching Kampo medicine has increased; however, this number is not statistically significant. Persistent problems in Kampo education, including curriculum standardisation, need to be addressed.

Changes in Japanese Medical Students' Attitudes Toward Traditional Japanese Medicine over the Course of Medical School.

OBJECTIVE: No report of newly enrolled medical students discusses their attitudes toward traditional Japanese medicine (TJM), Kampo medicine, or acupuncture and moxibustion (AM), or their changes over the course of medical school. This study evaluates these changing attitudes. METHODS: At Tokai University School of Medicine, from 2006 through 2015, 852 students were analyzed 3 times, pre-1st-year introduction Kampo lecture, pre-4th-year 6-hour lectures, and post-3-hour experience-based learning (EBL) course. The 7-item questionnaire included: general impression about Kampo medicine, interest, learning motivation, future involvement, and image, interest in AM, and learning motivation. RESULTS: Their attitudes toward TJM became positive during the 3 years even without TJM education. The 4th-year TJM lectures and EBL course significantly changed their attitudes toward more positive. Females' attitudes were more positive regarding TJM from the 1st year than were the males which became more positive after the EBL course. Students with TJM learning or work experience had positive attitudes from their 1st year and throughout medical school. Students with less positive attitudes became more active in TJM and positive at graduation. CONCLUSION: Appropriate TJM education and standard medical education in preclinical years of medical school has helped make students' attitudes toward Kampo medicine and AM more positive.

Vitamin B6 deficiency hyperactivates the noradrenergic system, leading to social deficits and cognitive impairment.

We have reported that a subpopulation of patients with schizophrenia have lower levels of vitamin B6 (VB6) in peripheral blood than do healthy controls. In a previous study, we found that VB6 level was inversely proportional to the patient's positive and negative symptom scale (PANSS) score for measuring symptom severity, suggesting that the loss of VB6 might contribute to the development of schizophrenia symptoms. In the present study, to clarify the relationship between VB6 deficiency and schizophrenia, we generated VB6-deficient (VB6(-)) mice through feeding with a VB6-lacking diet as a mouse model for the subpopulation of schizophrenia patients with VB6 deficiency. After feeding for 4 weeks, plasma VB6 level in VB6(-) mice decreased to 3% of that in control mice. The VB6(-) mice showed social deficits and cognitive impairment. Furthermore, the VB6(-) mice showed a marked increase in 3-methoxy-4-hydroxyphenylglycol (MHPG) in the brain, suggesting enhanced noradrenaline (NA) metabolism in VB6(-) mice. We confirmed the increased NA release in the prefrontal cortex (PFC) and the striatum (STR) of VB6(-) mice through in vivo microdialysis. Moreover, inhibiting the excessive NA release by treatment with VB6 supplementation into the brain and α2A adrenoreceptor agonist guanfacine (GFC) suppressed the increased NA metabolism and ameliorated the behavioral deficits. These findings suggest that the behavioral deficits shown in VB6(-) mice are caused by enhancement of the noradrenergic (NAergic) system.

A structured summary of a study protocol for a multi-center, randomized controlled trial (RCT) of COVID-19 prevention with Kampo medicines (Integrative Management in Japan for Epidemic Disease by prophylactic study: IMJEDI P1 study).

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

Changes in Heart Rate Variability after Yoga are Dependent on Heart Rate Variability at Baseline and during Yoga: A Study Showing Autonomic Normalization Effect in Yoga-Naïve and Experienced Subjects.

BACKGROUND: Yoga therapy is widely applied to the maintenance of health and to treatment of various illnesses. Previous researches indicate the involvement of autonomic control in its effects, although the general agreement has not been reached regarding the acute modulation of autonomic function. AIM: The present study aimed at revealing the acute effect of yoga on the autonomic activity using heart rate variability (HRV) measurement. METHODS: Twenty-seven healthy controls participated in the present study. Fifteen of them (39.5 ± 8.5 years old) were naïve and 12 (45.1 ± 7.0 years old) were experienced in yoga. Yoga skills included breath awareness, two types of asana, and two types of pranayama. HRV was measured at the baseline, during yoga, and at the resting state after yoga. RESULTS: In both yoga-naïve and experienced participants, the changes in low-frequency (LF) component of HRV and its ratio to high-frequency (HF) component (LF/HF) after yoga were found to be correlated negatively with the baseline data. The changes in LF after yoga were also correlated with LF during yoga. The changes in HF as well as the raw HRV data after yoga were not related to the baseline HRV or the HRV during yoga. CONCLUSION: The results indicate that yoga leads to an increase in LF when LF is low and leads to a decrease in LF when it is high at the baseline. This normalization of LF is dependent on the autonomic modulation during yoga and may underlie the clinical effectiveness of yoga therapy both in yoga-naïve and experienced subjects.

"Kampo-sommelier Practice": A Trial for an Active Learning Program in Kampo (Japanese Traditional) Medicine.

OBJECTIVE: This study aimed to assess the effectiveness of Kampo-sommelier practice, an active learning program on crude drugs used in Kampo formulations. METHODS: The participants were fourth-year Tokai University School of Medicine students as of 2017. Eighteen small teams attended a 20-minute Kampo-sommelier practice session and were provided 10 kinds of crude drugs (Licorice, Cinnamon, Ginger, etc.) in three forms, original, cut, and powdered, while blinded to the drugs. Each team was asked to distinguish each drug in terms of form, scent, flavor, and color with reference to described characteristics. The ability to match the names of the drugs with their descriptions was assessed in the participants one month later, and also in human science "A" and medicine "B" students, without prior education, and pharmacy "C" students, with professional education. RESULTS: The 117 participants received an average score of 6.2 ± 2.4 (mean ± S.D.) out of 10, which was significantly higher than 3.4 ± 1.8 in 97 "A" students and 3.1 ± 2.4 in 85 "B" students and lower than 8.4 ± 2.1 in 135 "C" students (p < 0.05 for all). CONCLUSIONS: The effectiveness of this team-based learning approach is suggested by the significantly higher scores of the participants.

Switching to systemic therapy after locoregional treatment failure: Definition and best timing.

In patients with unresectable hepatocellular carcinoma (HCC) without both macrovascular invasion and extrahepatic metastasis, the initial treatment choice recommended is transarterial chemoembolization (TACE). Before sorafenib came into wide use, TACE had been pointlessly carried out repeatedly. It was in the early 2010s that the concept of TACE refractory was advocated. Two retrospective studies from Japan indicated that conversion from TACE to sorafenib the day after patients were deemed as TACE refractory improved overall survival compared with continued TACE, according to the definition by the Japan Society of Hepatology. Nowadays, phase 3 trials have shown clinical benefits of several novel molecular target agents. Compared with the era of sorafenib, sequential treatments with these molecular target agents have gradually prolonged patients' survival and have become major strategies in patients with HCC. Taking these together, conversion from TACE to systemic therapies at the time of TACE refractory, compared with before, may have a greater impact on survival and may be considered deeper in the decisions-making process in patients with unresectable HCC who are candidate for TACE. Up-to-date information on the concept of TACE refractory is summarized in this review. We believe that the survival of patients with unresectable HCC without both macrovascular invasion and extrahepatic metastasis may be dramatically improved by optimal timing of TACE refractory and switching to systemic therapies.

Sequential therapy with sorafenib and regorafenib for advanced hepatocellular carcinoma: a multicenter retrospective study in Japan.

Background Conversion from sorafenib to regorafenib is primarily an evidence-based treatment strategy in patients with advanced hepatocellular carcinoma (HCC). This study aimed to assess the safety and efficacy of sequential therapy with sorafenib and regorafenib in patients with advanced HCC by analysis of outcomes in clinical practice with the aim to complement phase III findings. Methods The medical records of patients with advanced HCC receiving regorafenib were retrieved to collect data on sorafenib administration at seven Japanese institutions. Radiological responses and adverse events were evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1 and the Common Terminology Criteria for Adverse Events version 4.0, respectively. Results Before March 2018, 44 patients were administered regorafenib for advanced HCC. The median sorafenib treatment duration was 8.4 months. The most common adverse events were similar to those reported by the RESORCE trial. The median overall survival (OS) was 17.3 months (95% confidence interval [CI] 11.4-22.9), and 17 of 37 patients (45.9%) discontinued regorafenib and received sequential systemic therapy after regorafenib. These patients had significantly longer OS than those who were treated by the best supportive care or sub-optimal therapy (not reached versus 8.7 months [95% CI 5.8-11.7]; P < 0.001). Conclusion The results based on Japanese clinical practices verified the tolerability of regorafenib in advanced HCC. Major regorafenib-associated adverse events were similar to those related to sorafenib. OS was significantly longer than expected, which might be associated with the sequential systemic therapies after regorafenib, mainly lenvatinib.

The actual conditions of traditional Japanese Kampo education in all the pharmacy schools in Japan: a questionnaire survey after the enforcement of the new national 2015 core curriculum.

BACKGROUND: To investigate the present status of Kampo education, which has still not been elucidated, after the introduction of the new core national curriculum of 2015 into nationwide pharmacy education, in all 74 pharmacy schools in Japan. METHODS: A postal questionnaire survey was conducted from August 2015 to January 2016. The completed questionnaires were returned by mail. Web-based syllabi were also investigated to ascertain the detailed lecture curricula in each school. Descriptive analyses were conducted without statistics. RESULTS: A total of 74 questionnaires were collected (response rate, 100%). In 2015, the numbers of clinical Kampo classes as required subjects during the 6 years of regular pharmacy school education ranged from 0 to 36 (median, 13; mean, 11.8 ± 7.6). Of the 74 schools, 49 schools (66%) provided Kampo education from a clinical standpoint. Pharmacists employed in pharmacies and physicians taught most of these classes. The major problems to be solved first are: selecting and retaining teachers to teach clinical Kampo medicine (43 of 74 schools, 58%), preparing standard textbooks (37 schools, 50%), and improving the environment for practical Kampo training (30 schools, 41%). CONCLUSIONS: Curricula for teaching Kampo medicine significantly differ at each of the 74 Japanese pharmacy schools. In addition to selecting teachers who can adequately teach clinical Kampo medicine, improving training environments, and nationwide standardization of the curricula and textbooks are critical.

Clinical Reasoning in Kampo Education for Teaching Kampo Beginners.

OBJECTIVES: Japanese traditional (Kampo) medicine has its own theories that are quite different from those of Western medicine. For many students and medical doctors, mastering it is a painstaking task. We examined the similarities in clinical reasoning between Western and Kampo medicine, and developed an easy-to-understand method to teach Kampo theories enabling physicians to make accurate diagnoses and choose suitable Kampo formulae. METHODS: We developed a teaching method for Kampo medicine along clinical reasoning for beginners and evaluate its availability and effectiveness in an actual team-based learning class. RESULTS: A Kampo diagnostic procedure similar to that in Western medicine was developed. In this method, some Kampo formulae, are chosen according to the chief complaint, concomitant symptoms, characteristics, and distribution and exacerbation factors. Subsequently, from a point of view of the chosen Kampo formulae, patients' signs and symptoms are matched to find the most suitable formula. Students chose the same suitable formula among 6 groups and gained confidence to choose the correct Kampo formulae. CONCLUSIONS: A new Kampo educational method was developed that raises students' and physicians' confidence in making diagnoses and prescribing Kampo medicines.

Characteristics of patients with sorafenib-treated advanced hepatocellular carcinoma eligible for second-line treatment.

Background Regorafenib has been investigated for its efficacy and safety as a second-line treatment in patients with advanced hepatocellular carcinoma (HCC). We assessed the characteristics of patients with HCC treated with sorafenib who might be eligible for second-line treatment in general and regorafenib in particular. Methods Patients with HCC treated with sorafenib were retrospectively analyzed. We defined second-line candidate patients as maintaining Child-Pugh A and ECOG-PS ≤1 at the time of sorafenib failure. We also defined regorafenib candidate patients as follows: 1) continuing sorafenib at the time of radiological progression, 2) maintaining Child-Pugh A and ECOG-PS ≤ 1 at the time of sorafenib failure, and 3) continuing sorafenib 400 mg or more without intolerable adverse events at least 20 days of the last 28 days of treatment. Results Of 185 patients, 130 (70%) and 69 (37%) were candidates for second-line treatment and regorafenib. Child-Pugh score 6 and ECOG-PS 1 at the time of starting sorafenib were significantly lower in both second-line treatment and regorafenib candidate patients. Moreover, hand-foot skin reaction and liver failure during sorafenib treatment were associated with significantly low and high probabilities, respectively, of both Child-Pugh score > 6 and ECOG-PS > 1 at the time of sorafenib failure. Conclusion Regorafenib candidate patients after sorafenib failure are limited, and generally fewer than those who are candidates for second-line treatment. A lower Child-Pugh score and a better ECOG-PS were predictors of eligibility for second-line therapy and regorafenib treatment in sorafenib-treated patients with advanced HCC patients.

Pyridoxamine: A novel treatment for schizophrenia with enhanced carbonyl stress.

AIM: The aim of this clinical trial was to obtain proof of concept for high-dose pyridoxamine as a novel treatment for schizophrenia with enhanced carbonyl stress. METHODS: Ten Japanese schizophrenia patients with high plasma pentosidine, which is a representative biomarker of enhanced carbonyl stress, were recruited in a 24-week, open trial in which high-dose pyridoxamine (ranging from 1200 to 2400 mg/day) was administered using a conventional antipsychotic regimen. Main outcomes were the total change in Positive and Negative Syndrome Scale score and the Brief Psychiatric Rating Scale score from baseline to end of treatment at week 24 (or at withdrawal). RESULTS: Decreased plasma pentosidine levels were observed in eight patients. Two patients showed marked improvement in their psychological symptoms. A patient who harbors a frameshift mutation in the Glyoxalase 1 gene also showed considerable reduction in psychosis accompanied with a moderate decrease in plasma pentosidine levels. A reduction of greater than 20% in the assessment scale of drug-induced Parkinsonism occurred in four patients. Although there was no severe suicide-related ideation or behavior, Wernicke's encephalopathy-like adverse drug reactions occurred in two patients and were completely suppressed by thiamine supplementation. CONCLUSION: High-dose pyridoxamine add-on treatment was, in part, effective for a subpopulation of schizophrenia patients with enhanced carbonyl stress. Further randomized, placebo-controlled trials with careful monitoring will be required to validate the efficacy of high-dose pyridoxamine for these patients.

Medical residents' interest in and current status of Japanese postgraduate education in acupuncture and moxibustion: a follow-up survey.

BACKGROUND: Japanese traditional medicine (Kampo medicine) is an important subject in Japanese medical schools. Acupuncture and moxibustion (AM), essential categories of Kampo medicine, are taught in a few medical schools today. However, the current state of postgraduate AM education is unknown. OBJECTIVE: To compare medical residents' awareness of AM before their AM education in the 4th year of medical school with that after completion of their 2-year postgraduate medical residency. METHODS: We conducted a postal questionnaire survey of medical residents at the end of their 2-year residency. We required a signature on this questionnaire so that we could examine for changes in their awareness of AM with those determined by similar, signed, former questionnaire surveys conducted before and at the end of their 4th-year AM lectures in medical school (reported previously). The completed questionnaires were returned by mail or facsimile. RESULTS: Among 93 residents, there were 72 (77.4%) effective responses. Only three residents (4%) had opportunities to learn AM during residency. Among the 68 residents who were not afforded the opportunity to do so, after completing their two-year residency, 32(47%) stated that they would like to study AM. Interest in AM was significantly less than that of the proportion of medical students (81%) who were initially interested in AM when surveyed just before their fourth year lectures on AM. CONCLUSIONS: Postgraduate AM education for medical residents appears to be relatively scarce in Japan. Moreover, medical residents' levels of interest in AM were lower than those demonstrated before their 4th-year AM lectures in medical school.

The education of traditional Japanese (Kampo) medicine: surveys of training hospitals and residents.

BACKGROUND: Japanese physicians prescribe Kampo medicine, but Kampo education is not standardized. We surveyed training hospitals and residents to identify problems and suggest solutions to promote Kampo education during and after residency. METHODS: This was a double questionnaire survey of 1011 training hospitals in Japan and 93 Tokai University School of Medicine graduates of 2011. RESULTS: There were 816 effective responses (81%) from the training hospitals. Most instructors (84%) thought physicians should have Kampo clinical skills; 67% thought positively about introducing Kampo education into clinical training; 23% of the hospitals provided Kampo education; 70% of instructors at hospitals without Kampo education indicated the lack of Kampo instructors, 16% lack of time, and 7% no necessity for Kampo education; hospitals permitted Kampo education through voluntary study (42%), lectures sponsored by Kampo manufacturers (35%), and study sessions with other hospitals (32%); independent study sessions (10%); smaller hospitals were less active in Kampo education than larger ones. The survey of residents had 72 effective responses (77%): 91% were interested in Kampo medicine; 96% thought it worth learning; 31% could learn it during residency; 52% were not satisfied with the training, 83% wanted to learn it; 73% thought it should be introduced into the curricula; 93% prescribed Kampo medicine, and residents who learned it prescribed it more; 48% were reluctant to prescribe it after residency; 89% thought Western and Kampo medicine should be integrated. CONCLUSIONS: Instructors knew Kampo education was needed, but little of it was taught, especially in small hospitals, because of the lack of Kampo instructors. Residents recognized the need for Kampo medicine and were motivated to learn it. Kampo medicine was mostly prescribed because instructors suggested it. Because of the limited opportunities to learn Kampo medicine, it should be taught during residency. In small hospitals, cooperation with other hospitals could be a solution to teach Kampo medicine.

Music-evoked emotions in schizophrenia.

BACKGROUND/OBJECTIVES: Previous studies have reported that people with schizophrenia have impaired musical abilities. Here we developed a simple music-based assay to assess patient's ability to associate a minor chord with sadness. We further characterize correlations between impaired musical responses and psychiatric symptoms. METHOD: We exposed participants sequentially to two sets of sound stimuli, first a C-major progression and chord, and second a C-minor progression and chord. Participants were asked which stimulus they associated with sadness, the first set, the second set, or neither. The severity of psychiatric symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS). Study participants were 29 patients diagnosed with schizophrenia and 29 healthy volunteers matched in age, gender and musical background. RESULT: 37.9% (95% confidence interval [CI]:19.1-56.7) of patients with schizophrenia associated the minor chord set as sad, compared with 97.9% (95%CI: 89.5-103.6) of controls. Four patients were diagnosed with treatment-resistant schizophrenia, and all four failed to associate the minor chord with sadness. Patients who did not recognize minor chords as sad had significantly higher scores on all PANSS subscales. CONCLUSIONS: A simple test allows music-evoked emotions to be assessed in schizophrenia patient, and may show potential relationships between music-evoked emotions and psychiatric symptoms.