Publications by authors named "Kotoe Katayama"

17 Publications

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Application of targeted nanopore sequencing for the screening and determination of structural variants in patients with Lynch syndrome.

J Hum Genet 2021 May 6. Epub 2021 May 6.

Division of Clinical Genome Research, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan.

Lynch syndrome is a hereditary disease characterized by an increased risk of colorectal and other cancers. Germline variants in the mismatch repair (MMR) genes are responsible for this disease. Previously, we screened the MMR genes in colorectal cancer patients who fulfilled modified Amsterdam II criteria, and multiplex ligation-dependent probe amplification (MPLA) identified 11 structural variants (SVs) of MLH1 and MSH2 in 17 patients. In this study, we have tested the efficacy of long read-sequencing coupled with target enrichment for the determination of SVs and their breakpoints. DNA was captured by array probes designed to hybridize with target regions including four MMR genes and then sequenced using MinION, a nanopore sequencing platform. Approximately, 1000-fold coverage was obtained in the target regions compared with other regions. Application of this system to four test cases among the 17 patients correctly mapped the breakpoints. In addition, we newly found a deletion across an 84 kb region of MSH2 in a case without the pathogenic single nucleotide variants. These data suggest that long read-sequencing combined with hybridization-based enrichment is an efficient method to identify both SVs and their breakpoints. This strategy might replace MLPA for the screening of SVs in hereditary diseases.
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http://dx.doi.org/10.1038/s10038-021-00927-9DOI Listing
May 2021

COVID-19 risk assessment at the opening ceremony of the Tokyo 2020 Olympic Games.

Microb Risk Anal 2021 Mar 21:100162. Epub 2021 Mar 21.

Division of Health Medical Intelligence, Human Genome Center, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.

The 2020 Olympic/Paralympic Games have been postponed to 2021, due to the COVID-19 pandemic. We developed a model that integrated source-environment-receptor pathways to evaluate how preventive efforts can reduce the infection risk among spectators at the opening ceremony of Tokyo Olympic Games. We simulated viral loads of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emitted from infectors through talking/coughing/sneezing and modeled temporal environmental behaviors, including virus inactivation and transfer. We performed Monte Carlo simulations to estimate the expected number of newly infected individuals with and without preventive measures, yielding the crude probability of a spectator being an infector among the 60,000 people expected to attend the opening ceremony. Two indicators, i.e., the expected number of newly infected individuals and the newly infected individuals per infector entry, were proposed to demonstrate the extent of achievable infection risk reduction levels by implementing possible preventive measures. A no-prevention scenario produced 1.5-1.7 newly infected individuals per infector entry, whereas a combination of cooperative preventive measures by organizers and the spectators achieved a 99% risk reduction, corresponding to 0.009-0.012 newly infected individuals per infector entry. The expected number of newly infected individuals was calculated as 0.005 for the combination of cooperative preventive scenarios with the crude probability of a spectator being an infector of 1 × 10. Based on our estimates, a combination of cooperative preventions between organizers and spectators is required to prevent a viral spread at the Tokyo Olympic/Paralympic Games. Further, under the assumption that society accepts < 10 newly infected persons traced to events held during the entire Olympic/Paralympic Games, we propose a crude probability of infectors of < 5 × 10 as a benchmark for the suppression of the infection. This is the first study to develop a model that can assess the infection risk among spectators due to exposure pathways at a mass gathering event.
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http://dx.doi.org/10.1016/j.mran.2021.100162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981581PMC
March 2021

Functional Restoration of Bacteriomes and Viromes by Fecal Microbiota Transplantation.

Gastroenterology 2021 May 9;160(6):2089-2102.e12. Epub 2021 Feb 9.

Department of Immunology and Genomics, Osaka City University, Graduate School of Medicine, Abeno-ku, Osaka, Japan; Division of Metagenome Medicine, Human Genome Center, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan; Division of Innate Immune Regulation, International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo, Japan; Collaborative Research Institute for Innovative Microbiology, The University of Tokyo, Bunkyo-ku, Tokyo, Japan. Electronic address:

Background & Aims: Fecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridioides difficile infection (rCDI). However, the overall mechanisms underlying FMT success await comprehensive elucidation, and the safety of FMT has recently become a serious concern because of the occurrence of drug-resistant bacteremia transmitted by FMT. We investigated whether functional restoration of the bacteriomes and viromes by FMT could be an indicator of successful FMT.

Methods: The human intestinal bacteriomes and viromes from 9 patients with rCDI who had undergone successful FMT and their donors were analyzed. Prophage-based and CRISPR spacer-based host bacteria-phage associations in samples from recipients before and after FMT and in donor samples were examined. The gene functions of intestinal microorganisms affected by FMT were evaluated.

Results: Metagenomic sequencing of both the viromes and bacteriomes revealed that FMT does change the characteristics of intestinal bacteriomes and viromes in recipients after FMT compared with those before FMT. In particular, many Proteobacteria, the fecal abundance of which was high before FMT, were eliminated, and the proportion of Microviridae increased in recipients. Most temperate phages also behaved in parallel with the host bacteria that were altered by FMT. Furthermore, the identification of bacterial and viral gene functions before and after FMT revealed that some distinctive pathways, including fluorobenzoate degradation and secondary bile acid biosynthesis, were significantly represented.

Conclusions: The coordinated action of phages and their host bacteria restored the recipients' intestinal flora. These findings show that the restoration of intestinal microflora functions reflects the success of FMT.
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http://dx.doi.org/10.1053/j.gastro.2021.02.013DOI Listing
May 2021

Generation of a p16 Reporter Mouse and Its Use to Characterize and Target p16 Cells In Vivo.

Cell Metab 2020 Nov 18;32(5):814-828.e6. Epub 2020 Sep 18.

Division of Molecular Regulation of Inflammatory and Immune Diseases, Research Institute of Biomedical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-0022, Japan.

Cell senescence plays a key role in age-associated organ dysfunction, but the in vivo pathogenesis is largely unclear. Here, we generated a p16-Cre-tdTomato mouse model to analyze the in vivo characteristics of p16 cells at a single-cell level. We found tdTomato-positive p16 cells detectable in all organs, which were enriched with age. We also found that these cells failed to proliferate and had half-lives ranging from 2.6 to 4.2 months, depending on the tissue examined. Single-cell transcriptomics in the liver and kidneys revealed that p16 cells were present in various cell types, though most dominant in hepatic endothelium and in renal proximal and distal tubule epithelia, and that these cells exhibited heterogeneous senescence-associated phenotypes. Further, elimination of p16 cells ameliorated nonalcoholic steatohepatitis-related hepatic lipidosis and immune cell infiltration. Our new mouse model and single-cell analysis provide a powerful resource to enable the discovery of previously unidentified senescence functions in vivo.
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http://dx.doi.org/10.1016/j.cmet.2020.09.006DOI Listing
November 2020

Discrimination of prediction models between cold-heat and deficiency-excess patterns.

Complement Ther Med 2020 Mar 20;49:102353. Epub 2020 Feb 20.

Center for Kampo Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Electronic address:

Objective: The purpose of this study was to extract important patient questionnaire items by creating random forest models for predicting pattern diagnosis considering an interaction between deficiency-excess and cold-heat patterns.

Design: A multi-centre prospective observational study.

Setting: Participants visiting six Kampo speciality clinics in Japan from 2012 to 2015.

Main Outcome Measure: Deficiency-excess pattern diagnosis made by board-certified Kampo experts.

Methods: We used 153 items as independent variables including, age, sex, body mass index, systolic and diastolic blood pressures, and 148 subjective symptoms recorded through a questionnaire. We sampled training data with an equal number of the different patterns from a 2 × 2 factorial combination of deficiency-excess and cold-heat patterns. We constructed the prediction models of deficiency-excess and cold-heat patterns using the random forest algorithm, extracted the top 10 essential items, and calculated the discriminant ratio using this prediction model.

Results: BMI and blood pressure, and subjective symptoms of cold or heat sensations were the most important items in the prediction models of deficiency-excess pattern and of cold-heat patterns, respectively. The discriminant ratio was not inferior compared with the result ignoring the interaction between the diagnoses.

Conclusions: We revised deficiency-excess and cold-heat pattern prediction models, based on balanced training sample data obtained from six Kampo speciality clinics in Japan. The revised important items for diagnosing a deficiency-excess pattern and cold-heat pattern were compatible with the definition in the 11 version of international classification of diseases.
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http://dx.doi.org/10.1016/j.ctim.2020.102353DOI Listing
March 2020

Integrated exome and RNA sequencing of dedifferentiated liposarcoma.

Nat Commun 2019 12 12;10(1):5683. Epub 2019 Dec 12.

Laboratory of DNA Information Analysis, Institute of Medical Science, University of Tokyo, Tokyo, 108-8639, Japan.

The genomic characteristics of dedifferentiated liposarcoma (DDLPS) that are associated with clinical features remain to be identified. Here, we conduct integrated whole exome and RNA sequencing analysis in 115 DDLPS tumors and perform comparative genomic analysis of well-differentiated and dedifferentiated components from eight DDLPS samples. Several somatic copy-number alterations (SCNAs), including the gain of 12q15, are identified as frequent genomic alterations. CTDSP1/2-DNM3OS fusion genes are identified in a subset of DDLPS tumors. Based on the association of SCNAs with clinical features, the DDLPS tumors are clustered into three groups. This clustering can predict the clinical outcome independently. The comparative analysis between well-differentiated and dedifferentiated components identify two categories of genomic alterations: shared alterations, associated with tumorigenesis, and dedifferentiated-specific alterations, associated with malignant transformation. This large-scale genomic analysis reveals the mechanisms underlying the development and progression of DDLPS and provides insights that could contribute to the refinement of DDLPS management.
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http://dx.doi.org/10.1038/s41467-019-13286-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6908635PMC
December 2019

Replication stress triggers microsatellite destabilization and hypermutation leading to clonal expansion in vitro.

Nat Commun 2019 09 2;10(1):3925. Epub 2019 Sep 2.

Division of Carcinogenesis and Cancer Prevention, National Cancer Center Research Institute, Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.

Mismatch repair (MMR)-deficient cancers are characterized by microsatellite instability (MSI) and hypermutation. However, it remains unclear how MSI and hypermutation arise and contribute to cancer development. Here, we show that MSI and hypermutation are triggered by replication stress in an MMR-deficient background, enabling clonal expansion of cells harboring ARF/p53-module mutations and cells that are resistant to the anti-cancer drug camptothecin. While replication stress-associated DNA double-strand breaks (DSBs) caused chromosomal instability (CIN) in an MMR-proficient background, they induced MSI with concomitant suppression of CIN via a PARP-mediated repair pathway in an MMR-deficient background. This was associated with the induction of mutations, including cancer-driver mutations in the ARF/p53 module, via chromosomal deletions and base substitutions. Immortalization of MMR-deficient mouse embryonic fibroblasts (MEFs) in association with ARF/p53-module mutations was ~60-fold more efficient than that of wild-type MEFs. Thus, replication stress-triggered MSI and hypermutation efficiently lead to clonal expansion of cells with abrogated defense systems.
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http://dx.doi.org/10.1038/s41467-019-11760-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718401PMC
September 2019

Classification of patients with cold sensation by a review of systems database: A single-centre observational study.

Complement Ther Med 2019 Aug 11;45:7-13. Epub 2019 May 11.

Center for Kampo Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan; Faculty of Environmental and Information Study, Keio University, 5322 Endo, Fujisawa, Kanagawa, 252-0882, Japan. Electronic address:

Objectives: In Kampo medicine, a traditional medicine pattern refers to the complete clinical presentation of the patient at a given moment in time. Candidate herbal formulas are chosen for a chief complaint, and an appropriate formula is determined on the basis of the pattern diagnosis. In this study, we demonstrated the importance of accompanying symptoms in diagnosing traditional medicine patterns.

Design: Single centre observational study.

Setting: We analysed data from 524 new patients with a hypersensitivity to cold sensation as their primary diagnosis (mean age 51.6 ± 17.8 years; female ratio 82.1%) who visited the Keio University Hospital Kampo Clinic between 2008 and 2013.

Main Outcome Measures: Accompanying symptoms were recorded on the browser-based e-questionnaire system, which contained 128 items. The Japan Society for Oriental Medicine's board certified Kampo specialists diagnosed the traditional medicine patterns.

Results: When participants were classified according to the origin of their cold sensation, there were no differences in their traditional medicine patterns. In contrast, when patients were classified based on the number of accompanying symptoms, a significant difference in the patterns was identified. An increasing number of accompanying symptoms was associated with more frequent qi stagnation and blood stasis pattern. Patients with a qi stagnation pattern had higher rates of depression and insomnia. In contrast, patients with a blood stasis pattern, had higher rates of acne, body stiffness, and menstrual abnormality.

Conclusions: Qi stagnation and blood stasis patterns are related to a number of different accompanying symptoms in the patients with hypersensitivity to cold sensation.
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http://dx.doi.org/10.1016/j.ctim.2019.05.011DOI Listing
August 2019

Prediction of deficiency-excess pattern in Japanese Kampo medicine: Multi-centre data collection.

Complement Ther Med 2019 Aug 5;45:228-233. Epub 2019 Jul 5.

Center for Kampo Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan; Faculty of Environmental and Information Study, Keio University, 5322 Endo, Fujisawa, Kanagawa, 252-0882, Japan. Electronic address:

Objective: The purpose of the present study was to compare important patient questionnaire items by creating a random forest model for predicting deficiency-excess pattern diagnosis in six Kampo specialty clinics.

Design: A multi-centre prospective observational study.

Setting: Participants who visited six Kampo specialty clinics in Japan from 2012 to 2015.

Main Outcome Measure: Deficiency-excess pattern diagnosis made by board-certified Kampo experts.

Methods: To predict the deficiency-excess pattern diagnosis by Kampo experts, we used 153 items as independent variables, namely, age, sex, body mass index, systolic and diastolic blood pressures, and 148 subjective symptoms recorded through a questionnaire. We extracted the 30 most important items in each clinic's random forest model and selected items that were common among the clinics. We integrated participating clinics' data to construct a prediction model in the same manner. We calculated the discriminant ratio using this prediction model for the total six clinics' data and each clinic's independent data.

Results: Fifteen items were commonly listed in top 30 items in each random forest model. The discriminant ratio of the total six clinics' data was 82.3%; moreover, with the exception of one clinic, the independent discriminant ratio of each clinic was approximately 80% each.

Conclusions: We identified common important items in diagnosing a deficiency-excess pattern among six Japanese Kampo clinics. We constructed the integrated prediction model of deficiency-excess pattern.
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http://dx.doi.org/10.1016/j.ctim.2019.07.003DOI Listing
August 2019

Massively parallel sequencing of tenosynovial giant cell tumors reveals novel CSF1 fusion transcripts and novel somatic CBL mutations.

Int J Cancer 2019 12 31;145(12):3276-3284. Epub 2019 May 31.

Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.

Tenosynovial giant cell tumor (TSGCT) is a rare neoplasm. Although surgical resection is the widely accepted primary treatment for TSGCT, recurrences are frequent, and patients' joint function may be severely compromised. Previous studies reported that CSF1-COL6A3 fusion genes were identified in approximately 30% of TSGCTs. The aim of our study was to comprehensively clarify the genomic abnormalities in TSGCTs. We performed whole exome sequencing in combination with target sequence validation on 34 TSGCT samples. RNA sequencing was also performed on 18 samples. RNA sequencing revealed fusion transcripts involving CSF1, including novel CSF1-VCAM1, CSF1-FN1 and CSF1-CDH1 fusions, in 13/18 (72%) cases. These fusion genes were validated by chromogenic in situ hybridization. All CSF1 fusions resulted in the deletion of CSF1 exon 9, which was previously shown to be an important negative regulator of CSF1 expression. We also found that 12 (35%) of the 34 TSGCT samples harbored CBL missense mutations. All mutations were detected in exons 8 or 9, which encode the linker and RING finger domain. Among these mutations, C404Y, L380P and R420Q were recurrent. CBL-mutated cases showed higher JAK2 expression than wild-type CBL cases (p = 0.013). CSF1 fusion genes and CBL mutations were not mutually exclusive, and both alterations were detected in six of the 18 (33%) tumors. The frequent deletion of CSF1 exon 9 in the fusion transcripts suggested the importance of this event in the etiology of TSGCT. Our results may contribute to the development of new targeted therapies using JAK2 inhibitors for CBL-mutated TSGCT.
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http://dx.doi.org/10.1002/ijc.32421DOI Listing
December 2019

Genomic Heterogeneity Within Individual Prostate Cancer Foci Impacts Predictive Biomarkers of Targeted Therapy.

Eur Urol Focus 2019 05 15;5(3):416-424. Epub 2018 Feb 15.

Laboratory for Genome Sequencing Analysis, RIKEN Center for Integrative Medical Sciences, RIKEN, Yokohama City , Kanagawa, Japan.

Background: Most lethal prostate cancers progress from relapse of aggressive primary disease. Recently, the most significant advances in survival benefit from systemic therapy have come from moving the administration of therapy to an earlier disease state. There is movement toward using biomarkers from the intraprostatic index lesion to guide early systemic therapy.

Objective: To determine the genomic heterogeneity, including the heterogeneity of predictive biomarkers, within the index focus of treatment-naïve prostate cancer.

Design, Setting, And Participants: Ten patients with treatment-naïve prostate cancer underwent prostatectomy. DNA was extracted from 70 spatially distinct regions of the 10 index foci.

Outcome Measurements And Statistical Analysis: Single nucleotide mutations, small indels, and copy number changes were identified. Intrafocal genomic heterogeneity and heterogeneity of alterations that predict response to therapy was determined.

Results And Limitations: Exome sequencing and copy number estimates demonstrate branched evolution with >75% of point mutations being subclonal, including numerous pathways associated with castrate-resistant prostate cancer. Seven of 10 patients harbor alterations in one of five genes that predict response to targeted therapies with survival benefit in prostate cancer. Within biomarker-positive cases, 25% of intraprostatic regions are biomarker negative, with discordance between intraprostatic regions and lymph node metastases.

Conclusions: Treatment-naïve, nonmetastatic prostate cancer has marked intrafocal heterogeneity. Numerous alterations in pathways associated with castration-resistant prostate cancer are present in subclonal populations, including biomarkers predictive of response to targeted therapy.

Patient Summary: Untreated patients' tumors have alterations that predict response to targeted therapies, but the presence of a biomarker is dependent on what region of the tumor was evaluated.
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http://dx.doi.org/10.1016/j.euf.2018.01.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6586528PMC
May 2019

Predicting Japanese Kampo formulas by analyzing database of medical records: a preliminary observational study.

BMC Med Inform Decis Mak 2016 09 13;16:118. Epub 2016 Sep 13.

Center for Kampo Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.

Background: Approximately 90 % of physicians in Japan use Kampo medicine in daily practice. However, it is a challenge for physicians who do not specialize in Kampo medicine to select a proper Kampo formula out of the 148 officially approved formulas, as the decision relies on traditional measurements and traditional medicine pattern diagnoses. The present study tries to evaluate the feasibility of a decision support system for frequently used Kampo formulas.

Methods: Our study included 393 patients who visited the Kampo Clinic at Keio University Hospital for the first time between May 2008 and March 2013. We collected medical records through a browser-based questionnaire system and applied random forests to predict commonly prescribed Kampo formulas.

Results: The discriminant rate was the highest (87.0 %) when we tried to predict a Kampo formula from two candidates using age, sex, body mass index, subjective symptoms, and the two essential and predictable traditional medicine pattern diagnoses (excess-deficiency and heat-cold) as predictor variables. The discriminant rate decreased as the candidate Kampo formulas increased, with the greatest drop occurring between three (76.7 %) and four (47.5 %) candidates. Age, body mass index, and traditional medicine pattern diagnoses had higher importance according to the characteristics of each Kampo formula when we utilized the prediction model, which predicted a Kampo formula from among three candidates.

Conclusions: These results suggest that our decision support system for non-specialist physicians works well in selecting appropriate Kampo formulas from among two or three candidates. Additional studies are required to integrate the present statistical analysis in clinical practice.
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http://dx.doi.org/10.1186/s12911-016-0361-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5020542PMC
September 2016

The Difference between the Two Representative Kampo Formulas for Treating Dysmenorrhea: An Observational Study.

Evid Based Complement Alternat Med 2016 24;2016:3159617. Epub 2016 Feb 24.

Department of Neuropsychiatry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.

In Kampo medicine, two different formulas are effective for treating dysmenorrhea-tokishakuyakusan and keishibukuryogan; however, the criteria by which specialists select the appropriate formula for each patient are not clear. We compared patients treated with tokishakuyakusan and those with keishibukuryogan and proposed a predictive model. The study included 168 primary and secondary dysmenorrhea patients who visited the Kampo Clinic at Keio University Hospital. We collected clinical data from 128 dysmenorrhea patients, compared the two patient groups and selected significantly different factors as potential predictors, and used logistic regression to establish a model. An external validation was performed using 40 dysmenorrhea patients. Lightheadedness, BMI < 18.5, and a weak abdomen were significantly more frequent in the tokishakuyakusan group; tendency to sweat, heat intolerance, leg numbness, a cold sensation in the lower back, a strong abdomen, and paraumbilical tenderness and resistance were more frequent in the keishibukuryogan group. The final model fitted the data well. Internally estimated accuracy was 81.2%, and a leave-one-out cross-validation estimate of accuracy was 80.5%. External validation accuracy was 85.0%. We proposed a model for predicting the use of two Kampo formulas for dysmenorrhea, which should be validated in prospective trials.
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http://dx.doi.org/10.1155/2016/3159617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4783569PMC
March 2016

Analysis of questionnaire for traditional medicine and development of decision support system.

Evid Based Complement Alternat Med 2014 29;2014:974139. Epub 2014 Jan 29.

Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.

Kampo medicine is the Japanese adaptation of traditional medicine. In Kampo medicine, "medical interview" plays an important role. "Medical interview" in Japanese traditional medicine includes not only chief complaint but also a questionnaire that asked about the patient's lifestyle and subjective symptoms. The diagnosis by Kampo is called "Sho" and determined by completely different view from Western medicine. Specialists gather all available information and decide "Sho." And this is the reason why non-Kampo specialists without technical knowledge have difficulties to use traditional medicine. We analyzed "medical interview" data to establish an indicator for non-Kampo specialist without technical knowledge to perform suitable traditional medicine. We predicted "Sho" by using random forests algorithm which is powerful algorithm for classification. First, we use all the 2830 first-visit patients' data. The discriminant ratio of training data was perfect but that of test data is only 67.0%. Second, to achieve high prediction power for practical use, we did data cleaning, and discriminant ratio of test data was 72.4%. Third, we added body mass index (BMI) data to "medical interview" data and discriminant ratio of test data is 91.2%. Originally, deficiency and excess category means that patient is strongly built or poorly built. We notice that the most important variable for classification is BMI.
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http://dx.doi.org/10.1155/2014/974139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3926230PMC
March 2014

Prescription of kampo drugs in the Japanese health care insurance program.

Evid Based Complement Alternat Med 2013 30;2013:576973. Epub 2013 Nov 30.

Center for Kampo Medicine, Keio University School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160-8582, Japan ; Faculty of Environment and Information Study, Keio University, 5322 Endo, Fujisawa, Kanagawa 252-0882, Japan.

Kampo medicine or traditional Japanese medicine has been used under Japan's National Health Insurance scheme for 46 years. Recent research has shown that more than 80% of physicians use Kampo in daily practice. However, the use of Kampo from the patient perspective has received scant attention. To assess the current use of Kampo drugs in the National Health Insurance Program, we analysed a total of 67,113,579 health care claim records, which had been collected by Japan's Ministry of Health, Labour and Welfare in 2009. We found that Kampo drugs were prescribed for 1.34% of all patients. Among these, 92.2% simultaneously received biomedical drugs. Shakuyakukanzoto was the most frequently prescribed Kampo drug. The usage of frequently prescribed Kampo drugs differed between the youth and the elderly, males and females, and inpatients and outpatients. Kampo medicine has been employed in a wide variety of conditions, but the prescription rate was highest for disorders associated with pregnancy, childbirth, and the puerperium (4.08%). Although the adoption of Kampo medicine by physicians is large in a variety of diseases, the prescription rate of Kampo drugs is very limited.
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http://dx.doi.org/10.1155/2013/576973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3914391PMC
February 2014

Statistical analysis of hie (cold sensation) and hiesho (cold disorder) in kampo clinic.

Evid Based Complement Alternat Med 2013 30;2013:398458. Epub 2013 Dec 30.

Center for Kampo Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan ; Faculty of Environmental and Information Study, Keio University, 5322 Endo, Fujisawa, Kanagawa 252-0882, Japan.

A cold sensation (hie) is common in Japanese women and is an important treatment target in Kampo medicine. Physicians diagnose patients as having hiesho (cold disorder) when hie disturbs their daily activity. However, differences between hie and hiesho in men and women are not well described. Hie can be of three types depending on body part where patients feel hie. We aimed to clarify the characteristics of patients with hie and hiesho by analyzing data from new patients seen at the Kampo Clinic at Keio University Hospital between 2008 and 2013. We collected information about patients' subjective symptoms and their severity using visual analogue scales. Of 4,016 new patients, 2,344 complained about hie and 524 of those were diagnosed with hiesho. Hie was most common in legs/feet and combined with hands or lower back, rather than the whole body. Almost 30% of patients with hie felt upper body heat symptoms like hot flushes. Cold sensation was stronger in hiesho than non-hiesho patients. Patients with hie had more complaints. Men with hiesho had the same distribution of hie and had symptoms similar to women. The results of our study may increase awareness of hiesho and help doctors treat hie and other symptoms.
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http://dx.doi.org/10.1155/2013/398458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3893778PMC
February 2014