Details of a Researcher - Yoshimura, Kimio

Papers - Yoshimura, Kimio

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Well-being of cancer survivors with exceptional longevity: A cross-sectional and prospective cohort study of centenarians and very old adults

Shikimoto R., Gondo Y., Yasumoto S., Abe Y., Yagasaki K., Yoshimura K., Mimura M., Hirose N., Arai Y.

Journal of Geriatric Oncology 16 ( 7 ) 2025.09

ISSN 18794068

Introduction: Studies on well-being and life expectancy of cancer survivors with exceptional longevity are scarce. We explored the relationship between cancer history and well-being and blood biomarkers in centenarians and very old adults. We also aimed to examine the life expectancy of cancer survivors. Materials and Methods: Within three population-based cohorts in Japan, we recruited very old adults (85–94 years) and centenarians (100–115 years) between 2000 and 2020, and followed them up. Cancer survivors were defined as having been diagnosed with cancer regardless of whether they had been treated or not. Participants lacking history of cancer diagnosis or those who were not assessed using the Philadelphia Geriatric Center (PGC) Morale Scale were excluded. Participants' well-being was measured using the PGC Morale Scale, which included three subcategories: age attitude, social well-being, and psychological well-being. Multivariate LASSO (Least Absolute Shrinkage and Selection Operator) regression analysis and linear regression analysis were used to investigate whether having been diagnosed with cancer predicted the total PGC Morale Scale score, and multivariate Cox regression analysis was performed to assess life expectancy from the baseline survey. Results: Among 1531 participants (very old, n = 532; centenarians, n = 999), 207 (13.5%) had been diagnosed with cancer. The association between cancer history and well-being differed significantly by age group. Very old individuals with a cancer history were not significantly associated with well-being scores. In contrast, centenarians with a cancer history had higher total well-being (B [95% CI] = 1.28 [0.08–2.49]) and showed a trend toward higher social well-being (B [95% CI] = 0.46 [−0.08–0.99]). No significant life expectancy differences were found between the very old and centenarian cancer survivors. Discussion: The impact of a history of cancer on well-being differed between very old adults and centenarians. Centenarian cancer survivors showed greater well-being, particularly in social well-being. Moreover, the life expectancy of cancer survivors did not differ significantly from that of individuals without a cancer history.

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Risk of falls associated with non-GABAergic hypnotics and benzodiazepines in hospitalized patients

Shishida K, Nishimura W, Shimomura Y, Murayama M, Yoshimura K, Uchida H, Mimura M, Takeuchi H.

General Hospital Psychiatry 94 ( May-June 2025 ) 10 - 15 2025.02

Objective: Non-GABAergic hypnotics introduced into clinical practice within the last two decades are pharmacologically presumed to have a lower risk of falls, but clinical investigations are scarce. We aimed to evaluate the risk of falls associated with different classes of hypnotics, namely benzodiazepines, ramelteon, suvorexant, and trazodone, in hospitalized individuals at a general hospital. Method: In this retrospective cohort study, data on the incidence of falls, hypnotic use, age, sex, body mass index (BMI), activities of daily living (ADL) score, presence of surgery, emergency admission, and ambulance use were collected for hospitalized patients aged 20 years or older who had been discharged from a tertiary general hospital in Japan between April 1, 2014, and March 31, 2019. The Cox proportional hazards model was used to examine factors associated with falls, adjusting for other demographics as covariates. Results: Among 28,029 patients, 383 falls occurred in 322 patients. Ramelteon or suvorexant was not associated with an elevated incidence of falls (adjusted hazard ratio [aHR], 0.78; 95 % CI, 0.34 to 1.81 and 0.44; 95 % CI, 0.13–1.46, respectively), in contrast to benzodiazepines (aHR, 2.17; 95 % CI 1.67–2.83) or trazodone (aHR, 1.96; 95 % CI 1.25–3.07). Advanced age, lower BMI, wheelchair dependency, non-surgical status, absence of emergency admissions, and ambulance use were also associated with the elevated incidence of falls. Conclusions: In hospitalized patients at general hospitals, ramelteon and suvorexant may not increase the risk of falls, while the use of benzodiazepines and trazodone requires careful attention to minimize this risk.

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Efficacy and safety of intravenous ketamine treatment in Japanese patients with treatment-resistant depression: A double-blind, randomized, placebo-controlled trial

Ohtani Y., Tani H., Nomoto-Takahashi K., Yatomi T., Yonezawa K., Tomiyama S., Nagai N., Kusudo K., Honda S., Moriyama S., Nakajima S., Yamada T., Morisaki H., Iwabuchi Y., Jinzaki M., Yoshimura K., Eiro T., Tsugawa S., Ichijo S., Fujimoto Y., Miyazaki T., Takahashi T., Uchida H.

Psychiatry and Clinical Neurosciences 78 ( 12 ) 765 - 775 2024.12

ISSN 13231316

Aim: Although the antidepressant effect of ketamine on treatment-resistant depression (TRD) has been frequently reported in North American and European countries, evidence is scarce among the Asian population. We aimed to evaluate the efficacy and safety of intravenous ketamine in Japanese patients with TRD. Methods: In this double-blind randomized placebo-controlled trial, 34 Japanese patients with TRD were randomized to receive either intravenous ketamine (0.5 mg/kg) or placebo, administered over 40 min, twice a week, for 2 weeks. The primary outcome was the change in the Montgomery Åsberg Depression Rating Scale (MADRS) total score from baseline to post-treatment. Secondary outcomes included changes in other depressive symptomatology scores and remission, response, and partial response rates. We also examined the association between baseline clinical demographic characteristics and changes in the MADRS total score. Results: Intention-to-treat analysis indicated no significant difference in the decrease in MADRS total score between the groups (−8.1 ± 10.0 vs −2.5 ± 5.2, t[32] = 2.02, P = 0.052), whereas per-protocol analysis showed a significant reduction in the ketamine group compared to the placebo group (−9.1 ± 10.2 vs −2.7 ± 5.3, t[29] = 2.22, P = 0.034). No significant group differences were observed in other outcomes. Adverse events were more frequent in the ketamine group than in the placebo group, and no serious adverse events were reported. A higher baseline MADRS total score and body mass index were associated with a greater reduction in the MADRS total score. Conclusion: Intravenous ketamine outperformed placebo in Japanese patients with TRD who completed the study, suggesting that ketamine could alleviate depressive symptoms of TRD across diverse ethnic populations.

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The spectrum of TP53 mutations in Rwandan patients with gastric cancer

Nzitakera A., Surwumwe J.B., Ndoricyimpaye E.L., Uwamungu S., Uwamariya D., Manirakiza F., Ndayisaba M.C., Ntakirutimana G., Seminega B., Dusabejambo V., Rutaganda E., Kamali P., Ngabonziza F., Ishikawa R., Rugwizangonga B., Iwashita Y., Yamada H., Yoshimura K., Sugimura H., Shinmura K.

Genes and Environment 46 ( 1 ) 2024.12

ISSN 18807046

Background: Gastric cancer is the sixth most frequently diagnosed cancer and third in causing cancer-related death globally. The most frequently mutated gene in human cancers is TP53, which plays a pivotal role in cancer initiation and progression. In Africa, particularly in Rwanda, data on TP53 mutations are lacking. Therefore, this study intended to obtain TP53 mutation status in Rwandan patients with gastric cancer. Results: Formalin-fixed paraffin-embedded tissue blocks of 95 Rwandan patients with histopathologically proven gastric carcinoma were obtained from the University Teaching Hospital of Kigali. After DNA extraction, all coding regions of the TP53 gene and the exon–intron boundary region of TP53 were sequenced using the Sanger sequencing. Mutated TP53 were observed in 24 (25.3%) of the 95 cases, and a total of 29 mutations were identified. These TP53 mutations were distributed between exon 4 and 8 and most of them were missense mutations (19/29; 65.5%). Immunohistochemical analysis for TP53 revealed that most of the TP53 missense mutations were associated with TP53 protein accumulation. Among the 29 mutations, one was novel (c.459_477delCGGCACCCGCGTCCGCGCC). This 19-bp deletion mutation in exon 5 caused the production of truncated TP53 protein (p.G154Wfs*10). Regarding the spectrum of TP53 mutations, G:C > A:T at CpG sites was the most prevalent (10/29; 34.5%) and G:C > T:A was the second most prevalent (7/29; 24.1%). Interestingly, when the mutation spectrum of TP53 was compared to three previous TP53 mutational studies on non-Rwandan patients with gastric cancer, G:C > T:A mutations were significantly more frequent in this study than in our previous study (p = 0.013), the TCGA database (p = 0.017), and a previous study on patients from Hong Kong (p = 0.006). Even after correcting for false discovery, statistical significance was observed. Conclusions: Our results suggested that TP53 G:C > T:A transversion mutation in Rwandan patients with gastric cancer is more frequent than in non-Rwandan patients with gastric cancer, indicating at an alternative etiological and carcinogenic progression of gastric cancer in Rwanda.

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Influence of dementia-specialized care team on clinical outcomes in a general hospital

Shimomura Y., Nishimura W., Murayama M., Yoshimura K., Mimura M., Uchida H., Takeuchi H., Shishida K.

Asian Journal of Psychiatry 102 2024.12

ISSN 18762018

Background: Because of the increasing prevalence of dementia in Japan, the government introduced financial incentives for specialized care for dementia at acute care hospitals in 2016. Our hospital then introduced a multidisciplinary collaborative specialized team, referred to as dementia-specialized care team. The aim of this study is to examine the influence of dementia-specialized care team on clinical outcomes for elderly inpatients. Methods: In this retrospective observational study at a general hospital with 650 beds in Japan, we compared clinical outcomes such as incidence of falls, prescription of hypnotics, length of hospital stay, in-hospital mortality, and discharge destinations in inpatients aged 65 years and older between a two-year pre-intervention period (2014–2015) and a two-year post-intervention period (2017–2018). Results: During the observation period, a total of 34,097 patients were admitted, with 16,237 patients in the pre-intervention period and 17,860 patients in the post-intervention period. The proportion of patients receiving any hypnotics decreased from 21.2 % to 19.2 %, notably with benzodiazepine from 19.8 % to 13.2 %. The incidence of falls from a seated or lying position, particularly at night, was significantly lower (from 0.5 % to 0.2 %) as was the length of hospital stay (from 13.7 days to 13.2 days) during the post-intervention period. Conclusion: After the implementation of dementia-specialized care team, favorable outcomes such as a reduction in the use of hypnotics, the incidence of falls, and the length of hospitalization were observed. Introduction of the team and associated incentives may be effective in improving clinical outcomes in elderly inpatients.

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医事紛争が当事者となった病院の運営・医師その他の医療スタッフに及ぼす影響-損害賠償以外の側面からみた影響について　医事紛争が当事者に及ぼす影響　病院の公的資格認定の面から(解説)

吉村公雄

賠償科学 ( 50 ) 19 - 29 2024.04

Research paper (scientific journal)

病院の公的資格の代表として特定機能病院があり,そのほとんどが大学病院である.会計検査院は,群馬大学病院の医療事故に伴う経営等への影響について報告書を公開している.これによると,特定機能病院の承認取消しに伴う減収が当該年度で約2.4億円あり,そのほとんどはDPC医療機関別係数が約4割低下したことによる影響である.その他,がん診療連携拠点病院の指定がなくなることによる減収が1億円弱,補助金申請の取下げなどによる減収が約7.2億円あり,以上の合計で約10億円の減収と報告されている.加えて,患者数減少により年間で約8億円の減収となり,また,研修医の大幅減少,そして,先進医療に係る取扱患者数が半分近くに減少と,研究教育機能への影響もあった.さらに,特定機能病院の再承認までに4～5年かかっており,収入減は1年間だけでなく,長期に続く.以上のように,特定機能病院の承認取消しは医療機関にとって致命的とまでは言えないが極めて深刻な影響がある.特定機能病院の承認の取り消しあるいは返上の事例は過去に5件あり,すべて医療事故が発端となったが,直ちに医療過誤とは言えないことも多い.しかし,大々的に報道され紛争と言ってよい事態になり,取り消し・返上につながっている.医療事故防止のための医療安全体制整備だけでなく,紛争防止の観点からの体制整備も重要であろう.なお,保険医療機関の指定取消しは医療機関の存続に致命的であり,地域医療への影響もあるため,医療過誤による取消しは,ハードルが高く設定されている.(著者抄録)

Primary Cilia Are Frequently Present in Small Cell Lung Carcinomas but Not in Non–Small Cell Lung Carcinomas or Lung Carcinoids

Shinmura K., Kato H., Kawasaki H., Hariyama T., Yoshimura K., Tsuchiya K., Watanabe H., Ohta I., Asahina E., Sumiyoshi F., Hamada K., Kawanishi Y., Kawase A., Funai K., Sugimura H.

Laboratory Investigation 103 ( 2 ) 2023.02

ISSN 00236837

Most human malignant neoplasms show loss of primary cilia (PC). However, PC are known to be retained and involved in tumorigenesis in some types of neoplasms. The PC status in lung carcinomas remains largely uninvestigated. In this study, we comprehensively assessed the PC status in lung carcinomas. A total of 492 lung carcinomas, consisting of adenocarcinomas (ACs) (n = 319), squamous cell carcinomas (SCCs) (n = 152), and small cell lung carcinomas (SCLCs) (n = 21), were examined by immunohistochemical analysis using an antibody against ARL13B, a marker of PC. The PC-positive rate was markedly higher in SCLCs (81.0%) than in ACs (1.6%) and SCCs (7.9%). We subsequently performed analyses to characterize the PC-positive lung carcinomas further. PC-positive lung carcinomas were more numerous and had longer PC than normal cells. The presence of PC in these cells was not associated with the phase of the cell cycle. We also found that the PC were retained even in metastases from PC-positive lung carcinomas. Furthermore, the hedgehog signaling pathway was activated in PC-positive lung carcinomas. Because ARL13B immunohistochemistry of lung carcinoids (n = 10) also showed a statistically significantly lower rate (10.0%) of PC positivity than SCLCs, we searched for a gene(s) that might be upregulated in PC-positive SCLCs compared with lung carcinoids, but not in PC-negative carcinomas. This search, and further cell culture experiments, identified HYLS1 as a gene possessing the ability to regulate ciliogenesis in PC-positive lung carcinomas. In conclusion, our findings indicate that PC are frequently present in SCLCs but not in non-SCLCs (ACs and SCCs) or lung carcinoids, and their PC exhibit various specific pathobiological characteristics. This suggests an important link between lung carcinogenesis and PC.

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Comparable Psychotropic Prescription Rates after Hospital Discharge between Patients with COVID-19 and Those with Non-COVID-19-Related Respiratory Infection

Takahashi Y., Yatomi T., Yamaguchi N., Yoshimura K., Hori S., Uchida H.

Pharmacopsychiatry 2023

ISSN 01763679

Introduction Whether psychiatric symptoms after recovery from coronavirus disease 2019 (COVID-19) are specific to this illness remains unclear. Methods In this retrospective study, the Diagnosis Procedure Combination data and outpatient clinic data were used for patients who received inpatient treatment in Saiseikai-affiliated hospitals for COVID-19 or other respiratory tract infections (non-COVID) from 2020 to 2022. The primary outcome was new prescriptions of psychotropic drugs after discharge (i. e., prescriptions of psychotropics to patients who had not received them before or during their hospitalization). Values of interest were compared between groups using the chi-square test or Fisher's exact test. A COX proportional-hazards model was used to examine factors associated with psychotropic prescriptions after discharge in age- and sex-matched COVID-19 and non-COVID patients. Results Of 31,993 chart records, 19,613 were excluded due to a positive history with psychiatric disorders (n = 2,445), prescriptions of psychotropics (n = 744), and no follow-ups (n = 16,424). Thus, 3,648 COVID-19 and 8,732 non-COVID patients were included (mean [range] duration of follow-up, days: 146.9 [1-727] and 239.2 [1-729], respectively). Two hundred and four (5.6 %) of the 3,648 patients with COVID-19 received psychotropic prescriptions after discharge. No statistically significant differences were observed in the prescription rates of any psychotropic category between the COVID-19 and non-COVID groups. An increase in severity during hospitalization was significantly associated with more frequent psychotropic prescriptions (hazard ratio 1.83, p < 0.001). Discussion The development of psychiatric symptoms should be closely observed, especially in patients who experienced increased severity during hospitalization, regardless of whether they suffered from COVID-19.

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病院医師の職場満足度に影響を与える要因に関する研究　「済生会病院医師の働き方の実態と今後の在り方に関する研究」第2回医師調査のデータを用いた解析(原著論文)

吉村公雄, 山口直人, 持田勇治, 松原了, 炭谷茂

済生会総合研究所報 ( 2 ) 26 - 33 2022.06

病院の提供する医療の質を確保するためには医師の職務満足度を維持向上させることが必要と考えられる。本研究では、2021年度「済生会病院医師の働き方の実態と今後の在り方に関する研究」第2回医師調査のデータを用いて、医師の職務満足度の1つである職場満足度と働き方の諸要因との関連について分析した。この調査は76病院1,468人の常勤医師が回答した無記名自己記入式質問紙調査で、回答率は35.0%であった。
　医師の職場に対する総合的な満足度を目的変数、満足度以外のほぼ全ての変数（性・年齢、所属病院の病床数・医師数、医師の働き方に関する諸要因）を説明変数としてClassification and regression tree (CART)による回帰木を作成したところ、医師の疲労、医師自身の心身への不安、眠気、医師の高ストレス状態などは満足度に大きな影響を与える一方、病院の医師数や病床数、勤務時間や勤務形態、通勤時間、睡眠時間、運動習慣など客観的に把握可能な指標は直接的にはあまり大きな影響を与えていないことがわかった。
　済生会医師の職場に対する総合的な満足度を上げるためには、まずは、医師の疲労の蓄積の軽減に注意を向ける必要があると思われる。さらに、自身の心身への不安が高い医師、家族の世話の負担が大きい医師への援助も必要であろう。

病院医師の睡眠時間に対する勤務時間、勤務間インターバル、自己研鑽、家族の世話の負担の影響に関する研究(原著論文)

山口直人, 吉村公雄, 持田勇治, 松原了, 炭谷茂

済生会総合研究所報 ( 2 ) 15 - 25 2022.06

医師の働き方改革では、長時間労働による慢性的な睡眠不足を防ぎ、循環器疾患などのリスク増加を予防することを目指している。本研究では、労働時間、勤務間インターバルとともに、育児、介護など家族の世話の負担、自発的な自己研鑽にも焦点を当てて、睡眠時間との関連を分析する。そして、今後、勤務医師の睡眠時間の確保に、どのような取組みが重要であるかを考察する。

Validation of a novel online depression symptom severity rating scale: the R8 Depression

Takao Y., Figueroa E., Berna K.F.J., Jo Y., Kissane L.A., Yoshimura K., Tranter R., Porter R.J.

Health and Quality of Life Outcomes 19 ( 1 ) 2021.12

Background: An automated web-based assessment and monitoring system (www.psynary.com) has been developed to assist non-specialist clinicians in managing common mood and anxiety disorders. Psynary promotes the use of standardised outcome measures to assess symptom severity and optimise treatments with the aim of improving outcomes and enabling faster recovery. This paper analyses the results from two parallel studies in New Zealand and Japan (OptiMA-1 NZ and Japan) to assess the validity of the R8 Depression scale, one of the system’s core outcome measures. Methods: Clinical samples were recruited from a public secondary care and a private psychiatry clinic. Participants completed the outcome measures for the study via the online Psynary system. The R8 Depression scale is a 30-item questionnaire which includes all symptom domains covered in the ICD-10 classification of depression. The Patient Health Questionnaire (PHQ-9) was completed at the same time points as the R8 Depression, with a smaller sample also completing a paper-based Quick Inventory of Depressive Symptomatology (QIDS-SR16). Internal validity was quantified via Cronbach’s alpha and Guttman lower bounds method. External validation against the PHQ-9 and QIDS used the Pearson’s and Kendall’s correlation coefficients. Severity categories were set using a multivariate regression model. Results: 270 patients participated in the study and completed a maximum of 1 baseline and 5 reviews within a 90-day period, giving a total of 1124 assessments with the PHQ-9 also being completed in 1053 of these assessments. R8 Depression normative data was also collected from 204 non-clinical volunteers with 187 of these also completing the PHQ9. Internal reliability scores were all higher than 0.9 (n = 1328). There was overall good external validity when comparing the R8 Depression to the PHQ-9, with a correlation of 0.91 for the combined normative and clinical samples (n = 1240). Conclusions: The R8 Depression has been developed as a patient-rated outcome measure for depression for administration on an online system called “Psynary”. It has high internal and external validity against current widely used scales. Further work is underway to determine the sensitivity to change of the R8 Depression.

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Pre-existing psychiatric disorder is related to lower mortality from road traffic accident: A Japanese nationwide retrospective cohort study

Ishida T., Kuwahara Y., Shibahashi K., Okura Y., Sugiyama K., Yoshimura K., Hamabe Y., Mimura M., Suzuki T., Uchida H.

Injury 52 ( 6 ) 1390 - 1395 2021.06

ISSN 00201383

Background: Previous studies have reported inconsistent results on the mortality from trauma among psychiatric patients comparing to non-psychiatric population, which may be partly explained by the inclusion of both suicidal and accidental trauma. This study aimed to investigate the association of psychiatric diagnoses on admission with the outcomes of hospitalized patients for accidental trauma, namely road traffic injury. Methods: Detailed information of patients aged 15 years or older who were hospitalized for road traffic injury between 2004 and 2017 was extracted from the Japan Trauma Data Bank. The primary outcome was to compare in-hospital mortality between patients with and without a psychiatric disorder. We also conducted a subgroup analysis among patients with and without a serious head injury. Results: Altogether, 85,069 patients were included. Of these, 3,895 patients (4.6%) had a psychiatric diagnosis. The in-hospital mortality rate was significantly lower among patients with a psychiatric diagnosis than those without (5.4% vs. 8.3%; adjusted odds ratio [OR] 0.57, 95% confidence interval [CI] 0.47-0.70, p<0.001). In a subgroup analysis of patients with a serious head injury, in-hospital mortality was significantly lower in patients with a psychiatric diagnosis than in those without (10.5% vs. 17.3%; adjusted OR 0.48, 95% CI 0.37-0.62, p<0.001); in-hospital mortality of patients without a serious head injury showed no differences between patients with or without a psychiatric diagnosis (2.8% vs. 3.5%; adjusted OR 0.84, 95% CI 0.61-1.16, p=0.295). Conclusions: In-hospital mortality from road traffic injury was significantly lower among patients with a psychiatric diagnosis than those without, which was primarily evident in a subgroup of patients with a serious head injury. While further replication is necessary, results might be indicative of the neuroprotective effect of psychotropic medications.

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Associations of cardiovascular biomarkers and plasma albumin with exceptional survival to the highest ages

Hirata T., Arai Y., Yuasa S., Abe Y., Takayama M., Sasaki T., Kunitomi A., Inagaki H., Endo M., Morinaga J., Yoshimura K., Adachi T., Oike Y., Takebayashi T., Okano H., Hirose N.

Nature Communications (Nature Communications) 11 ( 1 ) 2020.12

Accepted

© 2020, The Author(s). Supercentenarians (those aged ≥110 years) are approaching the current human longevity limit by preventing or surviving major illness. Identifying specific biomarkers conducive to exceptional survival might provide insights into counter-regulatory mechanisms against aging-related disease. Here, we report associations between cardiovascular disease-related biomarkers and survival to the highest ages using a unique dataset of 1,427 oldest individuals from three longitudinal cohort studies, including 36 supercentenarians, 572 semi-supercentenarians (105–109 years), 288 centenarians (100–104 years), and 531 very old people (85–99 years). During follow-up, 1,000 participants (70.1%) died. Overall, N-terminal pro-B-type natriuretic peptide (NT-proBNP), interleukin-6, cystatin C and cholinesterase are associated with all-cause mortality independent of traditional cardiovascular risk factors and plasma albumin. Of these, low NT-proBNP levels are statistically associated with a survival advantage to supercentenarian age. Only low albumin is associated with high mortality across age groups. These findings expand our knowledge on the biology of human longevity.

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Comorbidities associated with nontuberculous mycobacterial disease in Japanese adults: A claims-data analysis

Uno S., Asakura T., Morimoto K., Yoshimura K., Uwamino Y., Nishimura T., Hoshino Y., Hasegawa N.

BMC Pulmonary Medicine (BMC Pulmonary Medicine) 20 ( 1 ) 2020.10

Accepted

© 2020 The Author(s). Background: Nontuberculous mycobacterial (NTM) lung disease is one of a growing number of chronic health problems that is difficult to cure in aging societies. While it is important to be vigilant about associated comorbidities in order to provide better patient care, data on the prevalence of comorbidities stratified by country or region are scarce. We aimed to elucidate the comorbidities associated with NTM disease based on Japanese health insurance claims data. Methods: Cross-sectional analyses were performed using the claims data for 2014 provided by the Japan Medical Data Center Co., Ltd. Patients aged 20-75 years with ≥3 claims associated with NTM disease were identified and matched to 10 sex-and-age-matched controls that had never made a claim for NTM disease. Thirty-one comorbidities previously suspected to be associated with NTM disease were selected, and the prevalence of these comorbidities compared between cases and controls. Result: Overall, 419 NTM patients (134 males and 285 females) and 4190 non-NTM controls were identified from the JMDC database. Aspergillosis, asthma, chronic heart failure, diffuse panbronchiolitis, gastroesophageal reflux, interstitial pneumonia, lung cancer, cancer other than breast, lung, ovary, or prostate cancer, and rheumatoid arthritis were associated with NTM disease in both males and females. Chronic obstructive pulmonary disease was associated with NTM in males while chronic kidney disease, osteoporosis, and Sjögren syndrome were associated with NTM in females. Conclusion: NTM disease was associated with multiple comorbidities that should be considered when providing medical care to individuals with NTM disease.

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Prescription patterns of psychotropics in patients receiving synthetic glucocorticoids

Yatomi T., Uchida T., Takeuchi H., Kuramochi S., Yoshimura K., Mimura M., Uchida H.

Acta Psychiatrica Scandinavica (Acta Psychiatrica Scandinavica) 142 ( 3 ) 242 - 248 2020.09

Accepted, ISSN 0001690X

© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd Objective: Synthetic glucocorticoids cause various psychiatric symptoms. Prescription of psychotropic drugs could be considered to be a proxy for manifestation of psychiatric symptoms. The aim of this study was to investigate the prescriptions of psychotropics in outpatients receiving synthetic glucocorticoids. Methods: We used the claims sampling data during January 2015 from the National Database of Health Insurance Claims and Specific Health Checkups of Japan made by the Ministry of Health, Labor, and Welfare in Japan. We compared the prescription rates of psychotropics between outpatients receiving oral synthetic glucocorticoids and age- and sex-matched controls and the prescription rates of psychotropics among the eight dosage groups of synthetic glucocorticoids by chi-squared test, and chlorpromazine/imipramine/diazepam equivalent doses (or daily defined doses) of respective psychotropics among these groups using Welch's t-test. Results: Synthetic glucocorticoids were prescribed to 3.1% (n = 18 122) of 581 990 patients. The prescription rates of psychotropics were significantly higher among the synthetic glucocorticoid recipients than among the non-recipients: antipsychotics, 1.8% (n = 321) vs. 1.1% (n = 201) (P = 1.4 × 10−7); antidepressants, 4.0% (n = 724) vs. 2.0% (n = 359) (P = 8.7 × 10−30); anxiolytics/hypnotics, 16.7% (n = 3029) vs. 10.2% (n = 1841) (P = 2.7 × 10−75); and mood stabilizers, 1.3% (n = 238) vs. 0.7% (n = 120) (P = 3.6 × 10−10) respectively. There was no significant difference in the prescription rates of any psychotropic drugs, other than anxiolytics/hypnotics, among the eight synthetic glucocorticoid dosage groups. Conclusion: Prescriptions of oral synthetic glucocorticoids were found to be associated with the use of any of the types of psychotropic drugs, other than anxiolytics/hypnotics, although a causal relationship could not be confirmed due to the retrospective and cross-sectional nature of this study.

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Circadian patterns of hallucinatory experiences in patients with schizophrenia: Potentials for chrono-pharmacology

Koizumi T., Suzuki T., Pillai N.S., Bies R.R., Takeuchi H., Yoshimura K., Mimura M., Uchida H.

Journal of Psychiatric Research (Journal of Psychiatric Research) 117 1 - 6 2019.10

Accepted, ISSN 00223956

© 2019 Elsevier Ltd The objective of this study was to investigate possible circadian pattern of psychotic symptoms in patients with schizophrenia, which could be reflected on the dosing schedule/regimen, i.e. chrono-pharmacology. Patients with schizophrenia (ICD-10) who reported having auditory hallucination, receiving monotherapy with risperidone, olanzapine or paliperidone for at least two weeks were included. The subjects were provided a diary and asked to record the time and duration of auditory hallucinations during the eight time periods (i.e. 00:00–03:00, 03:00–06:00, 06:00–09:00, 09:00–12:00, 12:00–15:00, 15:00–18:00, 18:00–21:00, and 21:00–24:00). In the diary, times of medication doses and sleep were also recorded. Time and degree of peak and trough dopamine D2 receptor blockade with antipsychotics were estimated from 2 sparsely collected plasma drug concentrations. The prevalence and duration of auditory hallucinations were statistically examined among the eight time periods, respectively. Forty-nine patients participated in this study (mean ± SD age, 50.7 ± 14.8 years; 36 men (73.5%); 34 inpatients (69.4%)). Auditory hallucinations occurred most frequently and lasted for the longest duration in the period of 18:00–21:00 (75.5% (37/49) and 1.37 ± 1.67 h). This happened despite the fact that the difference in D2 receptor occupancy between the peak and trough was less than 2%, indicating a stable drug delivery. Since the dopamine D2 receptor blockade by antipsychotics was stable, the nocturnal circadian pattern found in this study may reflect intrinsic dopaminergic fluctuation or generally quieter environments at night. These circadian patterns may be considered to devise individualized treatment approach in the context of “chrono-pharmacology” for patients with schizophrenia.

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The estimated cost of dementia in Japan, the most aged society in the world

Sado M., Ninomiya A., Shikimoto R., Ikeda B., Baba T., Yoshimura K., Mimura M.

PLoS ONE (PLoS ONE) 13 ( 11 ) 2018.11

Accepted

© 2018 Sado et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Objective Dementia has become a global critical issue. It is estimated that the global cost of dementia was 818 billion USD in 2015. The situation in Japan, which is the most aged country in the world, should be critical. However, the societal cost of dementia in Japan has not yet been estimated. This study was designed to estimate cost of dementia from societal perspective. Design We estimated the cost from societal perspective with prevalence based approach. Setting, participants and measures Main data sources for the parameters to estimate the costs are the National Data Base, a nationwide representative individual-level database for healthcare utilization, the Survey of Long-Term Care Benefit Expenditures, a nationwide survey based on individual-level secondary data for formal long-term care utilization, and the results of an informal care time survey for informal care cost. We conducted the analyses with ‘probabilistic modeling’ using the parameters obtained to estimate the costs of dementia. We also projected future costs. Results The societal costs of dementia in Japan in 2014 were estimated at JPY 14.5 trillion (se 66.0 billion). Of these, the costs for healthcare, long-term care, and informal care are JPY 1.91 trillion (se 4.91 billion), JPY 6.44 trillion (se 63.2 billion), and JPY 6.16 trillion (se 12.5 billion) respectively. The cost per person with dementia appeared to be JPY5.95 million (se 27 thousand). The total costs would reach JPY 24.3 trillion by 2060, which is 1.6 times higher than that in 2014. Conclusions The societal cost of dementia in Japan appeared to be considerable. Interventions to mitigate this impact should be considered.

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Predictive factors associated with psychological distress of caregivers of people with dementia in Japan: A cross-sectional study

Shikimoto R., Sado M., Ninomiya A., Yoshimura K., Ikeda B., Baba T., Mimura M.

International Psychogeriatrics (International Psychogeriatrics) 30 ( 8 ) 1089 - 1098 2018.08

Accepted, ISSN 10416102

© 2017 International Psychogeriatric Association. Background: Caregivers of people with dementia are likely to have psychological distress that sometimes results in mental health problems, such as depression. The objective of this study was to examine some predictive factors that are thought to be associated with psychological distress of caregivers of people with dementia in Japan. Methods: Design: A cross-sectional study. Sample: As part of a study to estimate the cost of dementia in Japan, 1,437 people with dementia-caregiver dyads were enrolled in the current informal care time study. The measurements in the study included were the basic characteristics of the caregivers and the people with dementia, and the informal care time during a week.Analysis: Factors that predict caregivers' psychological distress, which was measured by Kessler's Psychological Distress scale (K6) score, were evaluated using univariate and multivariate regression analyses. Results: Approximately 69% of the caregivers recorded a K6 score higher than 4, while 18% scored higher than 12. According to the results of the logistic regression analysis (cut-off 4/5), the K6 score was associated with mental and comorbid diseases of people with dementia, informal care time, its lower number of caregivers, and the level of nursing care. According to the results of logistic regression analysis (cut-off 12/13), the K6 score was associated with mental symptoms and comorbid disease of people with dementia, sex of caregivers, informal care time, and its lower number of caregivers. Conclusion: Our findings indicated that the psychological distress of the caregivers is quite high and that informal care time and behavioral and psychological symptoms of dementia are associated with it. These results corroborate with previous findings.

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Mindfulness-based cognitive therapy for Japanese breast cancer patients-a feasibility study

Park S., Sado M., Fujisawa D., Sato Y., Takeuchi M., Ninomiya A., Takahashi M., Yoshimura K., Jinno H., Takeda Y.

Japanese Journal of Clinical Oncology (Japanese Journal of Clinical Oncology) 48 ( 1 ) 68 - 74 2018.01

Accepted, ISSN 03682811

© The Author 2017. Published by Oxford University Press. All rights reserved. Objectives: Mindfulness-based intervention has been receiving growing attention in cancer care. This study aimed to examine feasibility and to preliminary explore effectiveness of mindfulnessbased cognitive therapy (MBCT) in Japanese breast cancer patients, and to explore possible modification of the program so that it fits better with this population. Methods: Twelve participants with diagnosis of Stage I-III breast cancer received an eight session, weekly MBCT intervention in a group therapy format. The participants were followed up until 3 months after the completion of the program. Results: All the participants completed the program with high attendance rate (mean number of attended sessions = 7.7). Significant improvement in anxiety (Hospital Anxiety and Depression Scale (HADS) - anxiety subscale; effect size Cohen's d = 0.88, P < 0.05), trauma-related psychological symptoms (Impact of Event Scale-revised; d = 0.64, P < 0.01) and quality of life (Functional Assessment of Cancer Therapy-Breast Cancer: FACT-B; d = 0.72, P < 0.01), and trend-level improvement in depression (HADS - depression subscale; d = 0.53, P = 0.054) were observed. Qualitative analyses suggested the program may be beneficial for alleviating fear of cancer recurrence and for increasing spiritual well-being. Some recommended modification of the program was indicated from the post-intervention interviews. Conclusions: Mindfulness-based cognitive therapy was well accepted by Japanese breast cancer patients and yielded favorable effect on their psychological status and quality of life. Further effectiveness study in a randomized-control design is warranted.

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Reduced expression of the DNA glycosylase gene MUTYH is associated with an increased number of somatic mutations via a reduction in the DNA repair capacity in prostate adenocarcinoma

Kazuya Shinmura , Hisami Kato , Yuichi Kawanishi , Kimio Yoshimura , Hisaki Igarashi , Masanori Goto , Hong Tao , Yusuke Inoue , Takayuki Sugiyama , Hiroshi Furuse , Seiichiro Ozono , Haruhiko Sugimura

Mol Carcinog 56 781 - 788 2017

Accepted

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