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Objectives: The current study assesses the utility of matrix metalloprotease-3 (MMP-3) as a biomarker for joint damage in patients with rheumatoid arthritis receiving peficitinib., Methods: Rheumatoid arthritis patients with inadequate response to methotrexate were randomised to peficitinib 100 mg, peficitinib 150 mg, or placebo, combined with methotrexate, for 52 weeks; patients receiving placebo switched to peficitinib 100/150 mg at Week (W)12/28. This post hoc analysis investigated association between MMP-3 above/below upper limit of normal (ULN) at W12/28 and radiographic progression [modified total Sharp score (mTSS), joint space narrowing score, or erosion score >0.5] at W52 or swollen joint count 66 at W28, stratified by baseline glucocorticoid use and renal function., Results: MMP-3 levels decreased in both peficitinib-treated groups but more slowly in patients with baseline glucocorticoids and those with radiographic progression at W52. There was no clear correlation between MMP-3 change from baseline (CFB) at W12, CFB in mTSS, joint space narrowing score, or erosion score at W52, or CFB in swollen joint count 66 at W28. More patients with MMP-3 ≤ULN versus >ULN at W12 had radiographic non-progression at W52. MMP-3 normalisation at W12 was significantly associated with mTSS non-progression at W52., Conclusions: Normalisation of MMP-3 at W12 may be a predictor for subsequent non-progression of joint damage at W52., (© Japan College of Rheumatology 2023. Published by Oxford University Press.)

Objective: To evaluate in-hospital fees and surgical outcomes of robot-assisted radical cystectomy (RARC), laparoscopic radical cystectomy (LRC) and open radical cystectomy (ORC) using a Japanese nationwide database., Methods: All data were obtained from the Diagnosis Procedure Combination database between April 2020 and March 2022. Basic characteristics and perioperative indicators, including in-hospital fees, were compared among the RARC, LRC and ORC groups. Propensity score-matched comparisons were performed to assess the differences between RARC and ORC., Results: During the study period, 2931, 1311 and 2435 cases of RARC, LRC and ORC were identified, respectively. The RARC group had the lowest in-hospital fee (median: 2.38 million yen), the shortest hospital stay (26 days) and the lowest blood transfusion rate (29.5%), as well as the lowest complication rate (20.9%), despite having the longest anesthesia time (569 min) among the three groups (all P < 0.01). The outcomes of LRC were comparable with those of RARC, and the differences in these indicators between the RARC and ORC groups were greater than those between the RARC and LRC groups. In propensity score-matched comparisons between the RARC and ORC groups, the differences in the indicators remained significant (all P < 0.01), with an ~50 000 yen difference in in-hospital fees., Conclusions: RARC and LRC were considered to be more cost-effective surgeries than ORC due to their superior surgical outcomes and comparable surgical fees in Japan. The widespread adoption of RARC and LRC is expected to bring economic benefits to Japanese society., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Objective: We evaluated remission rates and their relationship with baseline characteristics in patients with rheumatoid arthritis treated with the oral Janus kinase inhibitor peficitinib., Methods: This post hoc analysis of data from two Phase 3 studies (RAJ3 and RAJ4) of peficitinib (100 and 150 mg/day) in Asian rheumatoid arthritis patients investigated clinical disease activity index (CDAI) remission and low disease activity rates from baseline to Week 52. CDAI, Health Assessment Questionnaire-Disability Index, and van der Heijde-modified total Sharp score remission/low disease activity rates at Week 52 were evaluated among patients achieving CDAI remission at Weeks 12/28. Logistic regression analyses explored the relationship between baseline characteristics and CDAI remission/low disease activity rates., Results: CDAI remission rates increased over time in a dose-dependent manner in both peficitinib-treated groups. Most patients achieving CDAI remission at Weeks 12/28 also achieved remission at Week 52. Following the multivariate analysis of demographic and baseline characteristics, factors associated with the achievement of CDAI remission at Week 28 included male sex, low baseline prednisone dose (RAJ3 only), and low baseline Disease Activity Score 28-C-reactive protein (RAJ4 only)., Conclusions: Peficitinib demonstrated persistent efficacy in clinical remission to Week 52. Baseline characteristics associated with CDAI remission were mostly consistent with previous studies using other disease-modifying antirheumatic drugs., (© Japan College of Rheumatology 2023. Published by Oxford University Press.)

Background: Patients with locomotive syndrome (LS) are poor ambulatory status and a high risk of requiring nursing care. The purpose of this study is to investigate the relationship between LS and fall risk among community-dwelling elderly individuals., Methods: The subjects were Japanese elderly individuals aged 65 and over who participated in Yakumo study 2019 (N = 189). We defined the fall risk index 5 items version (FRI-5) ≥6 points as the fall risk group. LS was evaluated by stand-up test, two-step test, and 25-Geriatric Locomotive Function Scale (GLFS-25). We divided the subjects into two groups according to the presence or absence of fall risk, and investigated factors associated with fall risk., Results: The fall risk group (30 patients, 15.9%) had higher GLSF-25 (P = 0.001). The results of logistic regression analysis adjusted for age, sex, BMI, and knee osteoarthritis revealed that GLFS-25 (OR: 1.052; 95%CI: 1.009-1.097) was independent factor associated with fall risk. In the ROC analysis, the optimal cut-off value of the GLFS-25 to predict fall risk was 12, which is equivalent to LS stage 1 (AUC 0.688; 95% CI: 0.588-0.787; sensitivity: 0.467, specificity: 0.836)., Conclusions: GLFS-25 was associated with fall risk among community-dwelling elderly individuals aged 65 and over., Competing Interests: Conflict of interest statement Hiroki Iida, Taisuke Seki, Yasuhiko Takegami, Yusuke Osawa, Kato Daisaku, Genta Takemoto, Kei Ando, Shinya Ishizuka, Yukiharu Hasegawa, and Shiro Imagama declare that they have no conflict of interest., (Copyright © 2022 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Japanese species of the genus Dactylolabis Osten Sacken, 1860 are revised. One new species, D. kyororo sp. nov. is described and the two other species of the genus, D. diluta Alexander, 1922 and D. longicauda Alexander, 1922, are redescribed, with images of the habitus and wings, and drawings of the terminalia. A subspecies of D. longicauda Alexander, 1922 described from Yakushima Island, D. longicauda megastylata Alexander, 1930, is synonymized with the nominotypical subspecies. A key to the species is provided.

Antidepressants are one of the most commonly prescribed pharmaceuticals. Although they have been frequently detected in aquatic environments around the globe, little is known regarding their adverse effects on humans and aquatic organisms. Recently, an in vitro monoamine transporter inhibition assay was developed to detect transporter-inhibitory activities of antidepressants in wastewater in Japan. However, it was unclear which antidepressants were responsible for transporter-inhibitory activities in wastewater. Herein, the per capita consumption of 32 antidepressants, their excretion of unchanged parent compounds, per capita water consumption, removal rate during wastewater treatment processes, and potency values from the monoamine transporter inhibition assay were used to prioritize antidepressants of concern in effluent wastewater in England and Japan. In both countries, sertraline and O -desmethylvenlafaxine had the highest contribution to inhibitory activities against the human serotonin transporter (hSERT) and zebrafish SERT (zSERT), respectively. It was found that the antidepressants inhibited the zSERT more strongly than the hSERT. The inhibitory activities found against the zSERT in wastewater in England and Japan were higher than thresholds for abnormal behavior in fish. The antidepressants prioritized in this study provide insight into launching environmental monitoring and ecotoxicological studies of antidepressants.

Objectives: There is limited information on the clinical use of Janus kinase inhibitors (JAKis) for rheumatoid arthritis treatment in Japan. The aim of this study was to identify disease-modifying antirheumatic drug (DMARD) treatment patterns in Japan., Methods: This retrospective, longitudinal study extracted data from the Japan Medical Data Center database. Patients with rheumatoid arthritis diagnosis were enrolled 2016-19, during which patients had a first prescription of a major DMARD, split into six mutually exclusive classes: methotrexate (MTX); other conventional synthetic DMARDs; tumour necrosis factor alpha inhibitors; cytotoxic T-lymphocyte-associated antigen-4-immunoglobulin; anti-interleukin-6 receptor therapies; and JAKis. The primary objective was to describe DMARD treatment patterns, especially for JAKis., Results: Overall, 10,399 patients were included in the analysis. The most common treatments were MTX, other conventional synthetic DMARDs, and tumour necrosis factor alpha inhibitors. The total number of JAKi prescriptions increased approximately 8-fold during 2016-19. Most (61.1%) patients who received JAKis had prior MTX or tumour necrosis factor alpha inhibitor treatment. The duration of JAKi treatment was longer than for biologics and other conventional synthetic DMARDs and comparable to that of MTX., Conclusions: The sequence of drug class prescriptions for rheumatoid arthritis in Japan during 2016-19 followed clinical guidelines. Over this period, JAKis were increasingly used as a second-line treatment following MTX., (© Japan College of Rheumatology 2022. Published by Oxford University Press.)

Introduction: Rapid qualitative antigen testing is essential in the clinical management of COVID-19. However, most evaluations of antigen tests have been performed before the emergence of the Omicron variant., Methods: This prospective observational study evaluated QuickNavi-COVID19 Ag, a rapid antigen detection test between December 2021 and February 2022 in Japan, using real-time reverse transcription (RT)-PCR as a reference. Two nasopharyngeal samples were simultaneously collected for antigen testing and for RT-PCR. Variant analysis of the SARS-CoV-2 genomic sequencing was also performed., Results: In total, nasopharyngeal samples were collected from 1073 participants (417 positive; 919 symptomatic; 154 asymptomatic) for analysis. Compared with those of RT-PCR, the sensitivity, specificity, positive predictive value, and negative predictive value were 94.2% (95% CI: 91.6%-96.3%), 99.5% (95% CI: 98.7%-99.9%), 99.2% (95% CI: 97.8%-99.8%), and 96.5% (95% CI: 94.8%-97.7%), respectively. The sensitivity among symptomatic individuals was 94.3% (95% CI: 91.5%-96.4%). Overall, 85.9% of sequences were classified as Omicron sublineage BA.1, 12.4% were Omicron sublineage BA.2, and 1.6% were Delta B.1.617.2. (Delta variant). Most of the samples (87.1%) had Ct values of <25, and the sensitivity was 47.4% for low viral load samples (Ct ≥ 30); a similar trend has been observed in both symptomatic and asymptomatic groups., Conclusions: The QuickNavi-COVID19 Ag test showed sufficient diagnostic performance for the detection of the SARS-CoV-2 Omicron sublineages BA.1 and BA.2 from nasopharyngeal samples. However, the current study was mainly performed in symptomatic patients and the results are not sufficiently applicable for asymptomatic patients., Competing Interests: Declaration of competing interest Denka Co., Ltd. provided funds for research expenses the QuickNavi-COVID19 Ag tests without charge. Hiromichi Suzuki received a lecture fee from Otsuka Pharmaceutical Co., Ltd. Daisuke Kato, Miwa Kuwahara and Shino Muramatsu work for Denka Co., Ltd., the developer of the QuickNavi-COVID19 Ag tests. The Ct values for RT-PCR were determined using the NIID (N2 gene), Japan method [22], 6 positive samples were excluded because the samples were found to be negative by the NIID method, and positive results were determined by Xpert Xpress SARS-CoV-2 and the GeneXpert System. The Ct values for RT-PCR were determined using the NIID (N2 gene), Japan method [22], 5 positive samples were excluded because the samples were found to be negative by the NIID method, and positive results were determined by Xpert Xpress SARS-CoV-2 and the GeneXpert System. The Ct values for RT-PCR were determined using the NIID (N2 gene), Japan method [22], 1 positive sample was excluded because the samples were found to be negative by the NIID method, and positive results were determined by Xpert Xpress SARS-CoV-2 and the GeneXpert System., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

To maintain a surgeon's concentration, reduce fatigue, and train young surgeons, surgical procedures for bladder cancer are divided into the following parts: robot-assisted radical cystectomy (RARC), bowel reconstruction, and totally intracorporeal urinary diversion (ICUD) (RARC+ICUD). Each part is performed by a different surgeon (Trisection method). We retrospectively evaluated the efficacy and safety of this approach at a single institution in Japan. One hundred consecutive patients who underwent RARC+ICUD at Gifu University Hospital between November 2018 and August 2022 were included in this study. The patient background, surgical outcomes, and postoperative complications were compared between surgeries by first-, second-, and third-generation surgeons. The overall survival (OS) and recurrence-free survival (RFS) were compared between surgeries by each generation. Of the 100 patients, 19, 38, and 43 RARCs were performed by first-, second-, and third-generation surgeons, respectively. There were 35, 25, and 39 patients who underwent ileal conduit, neobladder, and ureterocutaneostomy, respectively. No significant differences were found among the patients respective to the type of ICUDs. Although the first-generation surgeon had a significantly shorter operative time with RARC, the surgical time for bowel reconstruction, length of hospital stays, and incidence of postoperative complications were not significantly different among the groups. Additionally, OS and RFS did not differ significantly among the generations. The "Trisection method" is an effective and safe concept with no difference in outcomes between the generations of surgeons.

Introduction: Although robot-assisted radical prostatectomy (RARP) has become a standard treatment modality in patients with prostate cancer (PCa), RARP is a complicated and difficult surgical procedure due to the risk of serious surgery-related complications. This study aimed to evaluate the validation of a standardized training system for RARP in patients with PCa at a single institute., Material and Methods: We retrospectively reviewed the clinical and pathological records of 155 patients with PCa who underwent RARP at Gifu University between August 2018 and April 2021. We developed an institutional program for new surgeons based on the separation of the RARP procedure into six checkpoints. The primary endpoints were surgical outcomes and perioperative complications among three groups (expert, trainer, and novice surgeon groups)., Results: The console time was significantly longer in the novice surgeon group than in the other groups. Regarding bladder neck dissection, ligation of lateral pedicles, and vesicourethral anastomosis, the operative time was significantly shorter in the expert group than in the other groups. Surgery-related complications occurred in 15 patients (9.7%)., Conclusions: Our training system for RARP might help reduce the influence of the learning curve on surgical outcomes and ensure that the surgeries performed at low-volume institutions are safe and effective.

Introduction: We evaluated oncological outcomes of patients undergoing robot-assisted radical prostatectomy (RARP) for prostate cancer (PCa) and their perioperative complications in Japan. We investigated clinical and pathological covariates to predict biochemical recurrence (BCR) after RARP., Methods: A retrospective multicenter cohort study was conducted in RARP patients with PCa at 10 institutions in Japan. Pre- and postoperative covariates were collected from enrolled patients. The primary endpoint was defined as biochemical recurrence-free survival (BRFS). Additionally, the association between BCR and clinicopathological covariates was determined., Results: We enrolled 2670 patients in this study. The median follow-up period was 26.0 months. RARP-related perioperative complications were identified in 198 patients (7.4%), including 69 patients (2.6%) with grade 3/4 complications according to the Clavien-Dindo classification. The 2-year BRFS was 88.0%. Using the Kaplan-Meier method, initial prostate-specific antigen (PSA) level of ≤7.6 ng/mL, biopsy and pathological Gleason score (GS) of ≤7, clinical and pathological T1/2, and low/intermediate risks according to the National Comprehensive Cancer Network risk classification, and negative surgical margin status had significant BRFS than their counterparts. In multivariate analysis, initial PSA, biopsy and pathological GS, clinical and pathological T stage, and surgical margin status significantly correlated with BCR after RARP., Conclusion: In this study, RARP achieved a lower incidence of perioperative complications than other studies., (© 2022 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Four limoniid genera are added to Japan for the first time. Four new species, Crypteria nippon sp. nov., Dasymallomyia tachii sp. nov., Eupilaria japonica sp. nov., and Protohelius japonicus sp. nov. are described, and Dasymallomyia ditenostyla Alexander, 1964 is recorded from Japan for the first time. Images of the habitus and wings and drawings of the male and female terminalia are provided.

Background: With the aging of populations worldwide, the extension of people's working lives has become a crucial policy issue. The aim of this study is to assess the impact of complex multimorbidity (CMM) as a predictor of working status among retirement-aged adults in Japan., Methods: Using a nationwide longitudinal cohort study of people aged over 65 who were free of documented disability at baseline, we matched individuals with respect to their propensity to develop CMM. The primary outcome of the study was working status after the six-year follow-up., Results: Among 5613 older adults (mean age: 74.2 years) included in the study, 726 had CMM and 2211 were still working at the end of the follow-up. In propensity-matched analyses, the employment rate was 6.4% higher in the CMM-free group at the end of the six-year follow-up compared to the CMM group (725 pairs; 29.5% vs. 35.9%; p = 0.012). Logistic regression analysis showed that CMM prevented older people from continuing to work beyond retirement age and was a more important factor than socioeconomic factors (income or educational attainment) or psychological factors (depressive symptoms or purpose in life)., Conclusions: Our study found that CMM has an adverse impact on the employment rate of older adults in Japan. This finding suggests that providing appropriate support to CMM patients may extend their working lives.

Background: To prevent recurrence of medical accidents, the Medical Accident Investigating System was implemented in October 2015 by the Japan Medical Safety Research Organization (Medsafe Japan) to target deaths from medical care that were unforeseen by the administrator. Medsafe Japan analyzed the 10 cases of central venous catheterization-related deaths reported in the system and published recommendations in March 2017. However, the particular emphasis for the prevention of central venous catheterization-related deaths is unclear., Methods: This study aimed to identify the recommendation points that should be emphasized to prevent recurrence of central venous catheterization-related deaths. We assessed central venous catheterization in 8530 closed-claim cases between January 2002 and December 2016 covered by the medical insurer Sompo-Japan. Moreover, we compared central venous catheterization-related death in closed-claim cases with death in reported cases., Results: The background, error type, anatomic insertion site, and fatal complication data were evaluated for 37 closed-claim cases, of which 12 (32.4%) were death cases. Of the 12 closed-claim cases and 10 reported cases, 9 (75.0%) closed-claim cases and 9 (90.0%) reported cases were related to vascular access. Among these, 5 closed-claim cases (41.7%) and 7 reported cases (77.8%) were related to internal jugular vein catheterization (p = 0.28). Coagulopathy was observed in 3 (60.0%) of 5 closed-claim cases and 6 (85.7%) of 7 reported cases., Conclusions: The risk of internal jugular catheterization in patients with coagulopathy must be carefully considered., Competing Interests: Yasuaki Oyama is an employee of Sompo-Japan Insurance Incorporated, which provided the claim files for the analysis in the present study. Yasuhiro Otaki serves independently as a medical and legal consultant for Sompo Japan Insurance Incorporated on an as-needed basis receiving appropriate fees. Other authors have declared that no competing interests exist. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Complex multimorbidity (CMM) has been proposed as a more nuanced concept of multimorbidity (MM). We sought to quantify the association of CMM and MM on the incidence of long-term care (LTC) needs in a cohort of older Japanese people. Our follow-up was based on a nationwide longitudinal cohort study of people aged over 65 years who were functionally dependent at baseline. Our outcome was incident LTC needs, based on certification under the Japanese LTC insurance scheme. We used both propensity score matching and inverse probability of treatment weights (IPTW) to compare individuals with and without MM versus CMM. A total of 38,889 older adults were included: 20,233 (52.0%) and 7565 (19.5%) adults with MM and CMM, respectively. In propensity-matched analyses, both MM ( n = 15,666 pairs) and CMM ( n = 7524 pairs) were statistically significantly associated with the six-year LTC insurance certification rate (MM, hazard ratio (HR) 1.07, 95% confidence interval (95%CI) 1.02-1.12; CMM, HR 1.10, 95%CI 1.04-1.16). Both MM and CMM were associated with a modest but statistically significantly higher rate of LTC insurance certification. These findings support the inclusion of multimorbidity in the assessment of LTC insurance needs, although the Japanese government currently has not adopted this.

Objectives: There are limitations to defining multimorbidity (MM) based on a simple count of diseases. To address these limitations, the concept of complex MM (CMM) focuses on how many body systems are affected in a single patient, rather than counting comorbid conditions. This study compared the prediction of mortality among older Japanese adults between CMM and conventional MM., Design: A population-based prospective cohort study., Setting: The Japan Gerontological Evaluation Study, a nationwide longitudinal cohort study, which ran from 2010 to 2016., Participants: Functionally independent individuals who were older than 65 and had complete illness data at the time of baseline survey were eligible., Outcomes Measure: CMM was defined as the coexistence of 3 or more body system disorders at baseline. We calculated the propensity for each individual to develop CMM based on a wide array of characteristics, including socioeconomic status and health behaviours. Individuals with and without CMM were then matched on their propensity scores before we estimated overall survival using a log-rank test., Results: Our 6-year follow-up included 38 889 older adults: 20 233 (52.0%) and 7565 (19.5%) adults with MM and CMM, respectively. In the MM-matched cohort (n=15 666 pairs), the presence of MM was significantly associated with increased mortality (HR 1.07; 95% CI 1.01 to 1.14; p=0.02 by the log-rank test). A similar mortality association was found in the CMM-matched cohort (n=7524 pairs, HR, 1.07; 95% CI 0.99 to 1.16; p=0.08 by the log-rank test)., Conclusion: This is the first study to report the association between CMM and mortality among older adults in Japan. MM and CMM predict mortality in older adults to a similar degree. This finding needs to be replicated with more precision in larger samples., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Japanese species of the genus Eloeophila are revised. Five new species, E. apicisetula sp. nov., E. canidorsalis sp. nov., E. enischnophallus sp. nov., E. hadrophallus sp. nov., and E. tergilobellus sp. nov. are described. One subspecies and two species are synonymized, E. subaprilina yezoensis (Alexander, 1924) with the nominotypical subspecies, E. hidana (Alexander, 1970) with E. persalsa (Alexander, 1940), and E. mishimai (Alexander, 1969) with E. kintaro (Alexander, 1957). Images of the habitus and wings, and drawings of the male terminalia of the Japanese species are shown. Distributions and a key to the Japanese species are provided.

Introduction: Several antigen tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed worldwide, but their clinical utility has not been well established. In this study, we evaluated the analytical and clinical performance of QuickNavi™-COVID19 Ag, a newly developed antigen test in Japan., Methods: This prospective observational study was conducted at a PCR center between October 7 and December 5, 2020. The included patients were referred from a local public health center and 89 primary care facilities. We simultaneously obtained two nasopharyngeal samples with flocked swabs; one was used for the antigen test and the other for real-time reverse transcription PCR (RT-PCR). Using the results of real-time RT-PCR as a reference, the performance of the antigen test was evaluated., Results: A total of 1186 patients were included in this study, and the real-time RT-PCR detected SARS-CoV-2 in 105 (8.9%). Of these 105 patients, 33 (31.4%) were asymptomatic. The antigen test provided a 98.8% (95% confidence interval [CI]: 98.0%-99.4%) concordance rate with real-time RT-PCR, along with a sensitivity of 86.7% (95% CI: 78.6%-92.5%) and a specificity of 100% (95% CI: 99.7%-100%). False-negatives were observed in 14 patients, 8 of whom were asymptomatic and had a low viral load (cycle threshold (Ct) > 30). In symptomatic patients, the sensitivity was 91.7% (95% CI: 82.7%-96.9%)., Conclusion: QuickNavi™-COVID19 Ag showed high specificity and sufficient sensitivity for the detection of SARS-CoV-2. This test is a promising potential diagnostic modality especially in symptomatic patients., Competing Interests: Declaration of competing interest Denka Co., Ltd., provided fees for research expenses and the QuickNavi™-COVID19 Ag kits without charge. Hiromichi Suzuki received a lecture fee from Otsuka Pharmaceutical Co., Ltd., regarding this study. Daisuke Kato, Miwa Kuwahara and Shino Muramatsu belong to Denka Co., Ltd., the developer of the QuickNavi™-COVID19 Ag., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: First-line chemoimmunotherapy (CIT) has improved overall survival (OS) and progression-free survival (PFS) outcomes among patients with non-small cell lung cancer (NSCLC). The immunological and nutritional statuses of patients fluctuate during treatment using immune checkpoint inhibitors, and are closely related to treatment outcomes. However, it is unclear whether these markers are significant in patients who are receiving CIT., Methods: This retrospective single-center study evaluated 34 consecutive Japanese patients with NSCLC who were treated using first-line CIT. Previously reported markers that reflect immunological and nutritional statuses were evaluated at three time points: at the start of CIT, after three weeks, and at the end of induction therapy., Results: The median PFS was 7.2 months (95% confidence interval: 6.3 months-not reached) and the median OS was not reached (95% confidence interval: 9.6 months-not reached). The PFS duration was significantly associated with the baseline neutrophil-to-lymphocyte ratio and the three-week values for the modified Glasgow prognostic score, C-reactive protein-albumin ratio, prognostic nutrition index, and advanced lung cancer inflammation index. The OS duration was significantly associated with the pre-treatment values for the neutrophil-to-lymphocyte ratio and advanced lung cancer inflammation index, as well as the prognostic nutrition index at the end of induction therapy., Conclusions: Immunological and nutritional markers could be useful for predicting the outcomes of CIT for Japanese patients with advanced non-small cell lung cancer. The timing of their evaluation may also be important., Key Points: SIGNIFICANT FINDINGS OF THE STUDY: Overall survival in patients receiving first-line chemoimmunotherapy for advanced lung cancer were associated with pretreatment values of neutrophil-to-lymphocyte ratio, advanced lung cancer inflammation index, and the prognostic nutrition index at the end of induction therapy., What This Study Adds: Repetitive evaluation of immunological and nutritional markers may be useful for guiding prognostication and treatment selection for Japanese patients with advanced lung cancer., (© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Background: This study aimed to evaluate predictive factors for graft loss in patients who received kidney transplantation (KT) from living kidney donors (LKDs) at a single institute in Japan., Methods: Our study focused on patients with end-stage renal disease who underwent KT from LKDs and were followed up for at least 1 year after surgery. The primary end point was graft survival (GS). GS after KT was analyzed using the Kaplan-Meier method. GS according to subgroup classification was analyzed using the log-rank test. A multivariate analysis was performed using a Cox proportional hazard model., Results: The median follow-up period was 105.5 months after KT. The 5- and 10-year GS rates were 97.8% and 96.0% in KT recipients (KTRs) without posttransplant diabetes mellitus (PTDM) and 89.9% and 63.2% in those with PTDM, respectively. The rate of graft loss was significantly higher in KTRs with PTDM than in those without PTDM (P < .001). Of the KTRs whose diabetes mellitus (DM) was cured after KT, those who underwent dialysis because of diabetic nephropathy had no graft loss. In the multivariate analysis, the serum creatinine level at 1 month after KT, PTDM, and human leukocyte antigen mismatches were significantly associated with graft loss after KT., Conclusions: In this study, the rate of graft loss in KTRs with PTDM was significantly higher than that of KTRs without PTDM. However, among KTRs whose DM was cured after KT, those who underwent dialysis because of diabetic nephropathy had no graft loss., (Copyright © 2019. Published by Elsevier Inc.)

We previously reported that anticholinergic (AC) drug use increases with age in the elderly Japanese population. In this analysis, we investigated attribution for each AC drug type to total AC burden using different elderly age groups. Prescription records (from 09/23/2015 to 12/31/2016) for outpatients using any AC were extracted from pharmacy claims (primary source) and hospital-based databases. AC burden (number of AC drugs and AC score) and AC type were assessed using the Anticholinergic Cognitive Burden (ACB) scale, Anticholinergic Drug Scale (ADS), Anticholinergic Risk Scale (ARS), and Beers criteria. Age was categorized using three subgroups (65-74, 75-84, and ≥85 years). Overall, 125426, 140634, 35628, and 23149 of the pharmacy outpatients received ≥1 AC drug from the ACB scale, ADS, ARS, or Beers criteria, respectively. The number of AC drugs increased with age for the ACB scale and ADS groups; but decreased for the ARS and Beers criteria. Antihypertensives provided the biggest contribution to AC score using the ACB scale and ADS, and antihistamines for the ARS. Proportional attribution to AC score typically increased with age for antihypertensives (ADS highest proportion: 34.6% for ≥85 years) and cardiac agents, but decreased for antihistamines (ARS lowest proportion: 15.3% for ≥85 years), corticosteroids, and antiepileptics. Similar findings were typically observed for the hospital database. In conclusion, antihypertensives were the principal type of AC drugs using the ACB scale and ADS and their attribution to AC score increased with age. Antihistamines were the principal drug type for the ARS.

Objective: This analysis was conducted to investigate the cardiovascular (CV) safety outcomes from the MILAI II study. MILAI II was conducted to evaluate the long-term safety and efficacy of antimuscarinic add-on therapy to mirabegron over 52 weeks in patients with overactive bladder (OAB) symptoms., Methods: MILAI II consisted of a 2-week screening period (patients received mirabegron 50 mg once daily) plus a 52-week treatment period (patients were randomized to receive a combination of mirabegron 50 mg/d plus solifenacin 5 mg/d, propiverine 20 mg/d, imidafenacin 0.2 mg/d, or tolterodine 4 mg/d). CV safety was assessed using treatment-emergent adverse events (TEAEs), vital signs, and 12-lead electrocardiograms (ECGs). Vital signs and ECG data were evaluated for each patient using worst post-baseline values reported., Results: Of 647 patients, 570 (88.1%) were female with a mean age of 65 years. CV history at baseline and CV-related concomitant medication use throughout the study were balanced between groups. The incidences of overall and drug-related CV TEAEs were ≤8.1% and ≤6.2%, respectively, for all groups. The most common TEAEs were ECG T wave amplitude decreased, ECG QT prolonged, and ventricular extrasystoles. Overall, 36 TEAEs of interest related to the CV system that were possibly/probably related to treatment were reported with similar incidences for each group. For the worst post-baseline vital signs and ECGs, no relationships were noted in terms of either timing or treatment group., Conclusion: A favorable CV safety profile was observed following long-term combination treatment with mirabegron and an antimuscarinic in patients with OAB symptoms., (© 2019 The Authors. LUTS: Lower Urinary Tract Symptoms published by John Wiley & Sons Australia, Ltd.)

Objective To describe the clinical research support systems in Japanese board certification programs of internal medicine and to assess the relationship between these support systems and the scholarly activities of residents. Methods In 2018, a 26-item web questionnaire was mailed to 542 points of contact of hospitals listed as certified residency programs of internal medicine in order to obtain information about the presence of a research support system and scholarly activity from 2016. We used hospital characteristic data from the Japanese Diagnostic Procedure Combination database, a national inpatient database, and the annual report of the Japanese Society of Internal Medicine. Results A total of 228 hospitals (42%) responded to the survey. There were regular research lectures in 129 hospitals (57%), protected time (time to perform research during working hours) in 53 hospitals (23%), research consultations in 175 hospitals (77%), regular journal clubs in 213 hospitals (77%), regular research conferences in 151 hospitals (66%), data warehouses in 139 hospitals (61%), and financial research support from the hospital budget in 140 hospitals (61%). A multivariate analysis showed that none of the research support systems were related to the number of conference presentations. In contrast, protected time [odds ratio (OR) 3.66, 95% confidence interval (CI) 1.43-9.39] and regular research conferences (OR 2.20, 95% CI 1.14-4.23) were related to the presence of clinical research presentations in scientific conferences hosted by residents. Conclusion Protected time and regular research conferences were related to the scholarly activity of residents in Japanese teaching hospitals.

Objective: The aim of this study was to report the final 3-year results from a surveillance study evaluating the safety, efficacy, and persistence of mirabegron for treating overactive bladder (OAB) symptoms., Methods: Patients who had started mirabegron for the treatment of urinary urgency, daytime frequency, and urgency urinary incontinence symptoms associated with OAB were followed for 3 years. Adverse drug reactions (ADRs), residual urine volume measurements, OAB symptoms, Overactive Bladder Symptom Scores (OABSS), and treatment discontinuations were evaluated prospectively. Persistence was estimated using the Kaplan-Meier method., Results: Of the 1138 patients included in the study (mean ±SD age: 71.9 ± 11.0 years; 574 [50.4%] women), 97 (8.52%) experienced 109 ADRs, with the incidence of ADRs decreasing over time (<1 year: 1.34%-2.37%; ≥1-<2 years: 0.45%-1.60%; ≥2-<3 years: 0.29%-1.10%; 3-monthly interval data). No significant increases in residual urine volume were observed. The investigators considered mirabegron to be an effective treatment for 842 of 1082 (77.8%) patients. Significant decreases in OABSS were reported throughout (P < 0.001), and 321 (65.1%) patients achieved a minimal clinically important change (MCIC) in OABSS. Most patients who achieved an MCIC within ≤1 year continued to maintain an MCIC throughout the study. Treatment persistence rates after 1, 2, and 3 years of mirabegron treatment were 65.8%, 52.9%, and 46.7%, respectively., Conclusion: Over 3 years, mirabegron was well tolerated and no cumulative events or delayed ADRs were observed. Mirabegron was an effective treatment with early improvements in OABSS being maintained throughout the treatment period. High persistence was observed after the use of mirabegron., (© 2018 The Authors. LUTS: Lower Urinary Tract Symptoms published by John Wiley & Sons Australia, Ltd.)

The aim of this study was to conduct a cross-sectional survey of investigations related to the bone mineral density (BMD) of both non-metastatic prostate cancer (NMPC) patients who have not yet received androgen deprivation therapy (ADT) and patients receiving prolonged ADT in Japan. Japanese male patients with NMPC who received continuous ADT or who were planning to receive ADT were enrolled in this study. Lumbar spine and femoral neck BMD was measured using dual-energy X-ray absorptiometry (DEXA). To assess patient characteristics, we searched medical records and questionnaires to determine whether they had any factors that could possibly affect BMD. A total of 230 patients with a mean age of 76.6 ± 6.4 years were evaluated. Of these, 151 (65.7%) were receiving ADT, and 79 (34.4%) had not yet received ADT. The mean duration of ADT was 37.4 ± 30.7 months. DEXA showed that as the duration of ADT increased, lumbar spine and femoral neck BMD decreased gradually (p = 0.0005 and p = 0.0014, respectively). Stepwise regression analyses revealed that the duration of ADT was a significant variable of both lumbar spine and femoral neck BMD. Moreover, as the duration of ADT increased, the prevalence of osteoporosis increased statistically (p = 0.0002). This study showed that ADT negatively affected lumbar spine and femoral neck BMD. It also showed a progressive increase in the prevalence of osteoporosis in Japanese NMPC patients with ADT.

This report described the experience of active surveillance culture implemented in response to the identification of a single carbapenemase-producing Escherichia coli in a Japanese university hospital. It revealed a horizontal transmission event and an additional asymptomatic carrier of carbapenemase-producing Escherichia coli with unique drug susceptibility and resistance gene profiles. Early implementation of active surveillance culture as a part of multifaceted infection control measures appeared to be useful to control further transmission of carbapenemase-producing Escherichia coli even in the low endemic facility. Further investigations on the timing and usefulness of active surveillance culture in the control of carbapenemase-producing Enterobacteriaceae would be warranted., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objectives: To assess anticholinergic use, especially the use of antimuscarinics, in the elderly (aged ≥65 years) Japanese overactive bladder and non-overactive bladder populations., Methods: Patient records were sourced from a large, nationwide Japanese pharmacy claims database. Anticholinergic use on a random day in 2016 (index date) was investigated through the Anticholinergic Cognitive Burden scale (primary scale), the Anticholinergic Drug Scale, the Anticholinergic Risk Scale and Beers criteria. The prevalence of anticholinergic use and anticholinergic scores at the index date were summarized descriptively. The overactive bladder population was defined as patients who had at least one prescription record for any antimuscarinic (fesoterodine, imidafenacin, oxybutynin, propiverine, solifenacin or tolterodine) or the β3-adrenoreceptor agonist, mirabegron, within the 1-year pre-index period., Results: Among 1 216 126 outpatients, 35 138 (2.9%) were included in the overactive bladder group. In total, 112 (68.7%) of the anticholinergics listed in the scales were identified. In those who received any Anticholinergic Cognitive Burden scale-listed anticholinergic, the mean scores were higher in overactive bladder patients versus non-overactive bladder patients (3.2 ± 1.3 and 1.6 ± 1.1, respectively). Similarly, overactive bladder patients who received antimuscarinics had higher Anticholinergic Cognitive Burden scores (3.3 ± 1.2) than patients who received mirabegron only (1.7 ± 1.1). In 58.8% of the overactive bladder patients, ≥80% of the total Anticholinergic Cognitive Burden score was exclusively attributable to antimuscarinics., Conclusions: Anticholinergic use was higher in overactive bladder patients versus non-overactive bladder patients. This increased use was largely attributable to antimuscarinics. The alternative use of mirabegron could therefore be considered to reduce the burden experienced by patients in Japan., (© 2018 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Urological Association.)

The six Japanese species of the subgenus Dicranomyia (Erostrata) Savchenko, 1976 are revised. D. (E.) globithorax Osten Sacken, 1869 and D. (E.) tabashii (Alexander, 1934) are newly recorded from Japan. We elevate the two subspecies of D. globithorax to species rank based on distinct morphological differences. Three new species, D. (E.) reniformis sp. nov., D. (E.) submelas sp. nov., and D. (E.) yazuensis sp. nov. are described. The male genitalia of all Japanese species and female ovipositors of four of the six species are illustrated, and the habitus of adults are photographed. A key to the Japanese species of the subgenus is provided.

Two huge earthquakes struck Kumamoto, Japan, in April 2016, forcing residents to evacuate. Few studies have reported early-phase disease and injury trends among evacuees following major inland earthquakes. We evaluated the trends among evacuees who visited a medical clinic in a shelter located at the epicenter of the 2016 Kumamoto earthquakes. The clinic opened on April 15, the day after the foreshock, and closed 3 weeks later. We reviewed medical charts related to 929 outpatient visits and conducted descriptive analyses. The evacuees experienced mild injuries and common diseases. The types of diseases changed weekly. Elderly people needed medical support for longer than other age groups. Future earthquakes may be inevitable, but establishing arrangements for medical needs or making precautions for infectious diseases in shelters could reduce the effects of earthquake-related health problems.

Objectives: To evaluate persistence and adherence to mirabegron and antimuscarinics in Japan using data from two administrative databases., Methods: The present retrospective study evaluated insurance claims for employees and dependents aged ≤75 years, and pharmacy claims for outpatients. From October 2012 to September 2014, new users of mirabegron or five individual antimuscarinics indicated for overactive bladder in Japan (fesoterodine, imidafenacin, propiverine, solifenacin and tolterodine) were identified and followed for 1 year. Persistence with mirabegron and antimuscarinics were evaluated using Kaplan-Meier methods. Any associations between baseline characteristics (age, sex and previous medication use) and persistence were explored. Adherence was assessed using the medication possession ratio., Results: In total, 3970 and 16 648 patients were included from the insurance and pharmacy claims databases, respectively. Mirabegron treatment was associated with longer median persistence compared with antimuscarinics (insurance claims: 44 [95% confidence intervals 37-56] vs 21 [14-28] to 30 [30-33] days, pharmacy claims: 105 [96-113] vs 62 [56-77] to 84 [77-86] days). The results were consistent when patients were stratified by age, sex and previous medication. Persistence rate at 1 year was higher for mirabegron (insurance claims: 14.0% [11.5-16.8%] vs 5.4% [4.1-7.0%] to 9.1% [5.3-14.2%], pharmacy claims: 25.9% [24.6-27.3%] vs 16.3% [14.0-18.6%] to 21.3% [20.2-22.4%]). Compared with each antimuscarinic, a higher proportion of mirabegron-treated patients had medication possession ratios ≥0.8., Conclusions: This large nationwide Japanese study shows that persistence and adherence are greater with mirabegron compared with five antimuscarinics., (© 2017 The Japanese Urological Association.)

Background: Pancreatic fistula after pancreatoduodenectomy (PD) is associated with high mortality and morbidity. Trypsinogen activation and bacteria, although hypothesized to be interrelated etiopathogenetically, have not had their relationship and pathogenic mechanisms elucidated. This study investigated bacterial involvement in pancreatic juice activation perioperatively after PD at sites of pancreatic fistula formation., Methods: Fifty patients underwent PD; postoperative pancreatic fistulae were graded based on the International Study Group for Pancreatic Fistula grading criteria. Bacteria were isolated from cultures of drainage fluid. Digested peptides from trypsinogen and bacterial culture supernatants underwent sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) separation and mass spectrometric analysis. Zymography was used to detect the trypsinogen activator., Results: Pseudomonas aeruginosa and Enterobacter cloacae isolated from drainage fluid in patients with grades B and C pancreatic fistulae could cause trypsinogen activation. Trypsinogen activation by P. aeruginosa and E. cloacae were preventable by the use of a serine protease inhibitor in vitro. A protease in the supernatant from P. aeruginosa-positive cultures acted as the trypsinogen activator., Conclusions: Infection with P. aeruginosa perioperatively to PD entails secretion of a protease activator of trypsinogen to trypsin. Bacterial infection control in the perioperative PD period could be crucial to prevent development of pancreatic fistula., (© 2015 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: Treatment protocols (including those for thoracic surgery) tend to be customized for individual hospitals. Procedural standardization is required to improve surgical tasks and patient outcomes. This study aimed to evaluate the effects of an initiative to standardize surgical tasks for efficient and safe performance., Methods: Hospitals associated with the Division of Chest Surgery of the Kyoto Prefectural University of Medicine held joint meetings involving their thoracic surgeons and operating room nurses between February 2011 and November 2012 to standardize surgical tasks. Operation times and blood loss were compared before and after standardization., Results: The implementation rate of standardized surgical tasks was 97%. The pre-operative (from entry to the operating room until commencement of surgery) and post-operative (from conclusion of surgery until departure from the operating room) times were significantly decreased after the standardization. When compared according to operative group (all thoracic surgery, lung lobectomy, and partial lung resection), operation times were shorter for all three groups; in addition, the amount of blood loss was lower in all three groups after standardization. A post-standardization survey showed improved morale among the meeting participants., Conclusions: Interdisciplinary standardization of surgical tasks across institutions improved thoracic surgery tasks and surgical outcomes.

Objective: Assessing retention rate and risk factor for drug discontinuation is important for drug evaluation. We examined a 3-year retention rate and the risk factor for discontinuation due to insufficient efficacy (IE) and adverse events (AE) in Japanese patients with rheumatoid arthritis (RA) who are receiving etanercept (ETN)., Methods: Data were collected from 588 patients treated with ETN as a first biologic from the Tsurumai Biologics Communication Registry. Baseline characteristics for the incidence of both IE and AE were analyzed using the Cox proportional-hazards regression model. Patients were divided into groups based on age and concomitant methotrexate (MTX). Drug retention rates were calculated using the Kaplan-Meier method and compared among groups using the log-rank test., Results: ETN monotherapy without concomitant MTX [MTX(-)] was significantly related to a higher incidence of discontinuation due to IE [hazard ratio (HR) = 2.226, 95% CI 1.363-3.634]. Older age and MTX(-) were significantly related to a higher incidence of discontinuation due to AE [HR = 1.040, 1.746, 95% CI 1.020-1.060, 1.103-2.763, respectively]. The MTX(-)/≥ 65 years group had the lowest retention rate (p < 0.001). The discontinuation rate due to IE was lower in the MTX(+)/< 65 years group compared to < 65 years/MTX(-), ≥ 65 years/MTX(-) group (p = 0.006, p < 0.001, respectively). The discontinuation rate due to AE was highest in the MTX(-)/≥ 65 years group (p < 0.001)., Conclusion: Our findings suggest that the risk of discontinuation due to IE was high in the patients who did not use concomitant MTX and that the risk of discontinuation due to AE was high in elderly patients who did not use concomitant MTX.

Objectives: The purpose of this study was to examine the treatment retention and efficacy of abatacept, the first member of a new class of biologic agents, in Japanese rheumatoid arthritis (RA) patients during clinical practice., Methods: A retrospective multicenter study was conducted with patients who underwent abatacept therapy for 24 weeks (n = 143)., Results: Patients at baseline had a mean age of 63.5 years, a mean disease duration of 11.3 years, and a mean disease activity score in 28 joints (DAS28) of 4.5. Overall retention of abatacept treatment was 83.2 % at 24 weeks, when 46.2 % of patients achieved DAS28-defined low disease activity (LDA; DAS28 <3.2) and 26.6 % achieved DAS28-defined remission (DAS28 <2.6). LDA was achieved in a significantly higher proportion of patients without prior biologics therapy compared to those with prior biologics (60.9 vs. 34.2 %, p = 0.001). There was no significant difference between patients with or without concomitant methotrexate (MTX) therapy (45.2 vs. 47.5 %)., Conclusions: Abatacept therapy appears to be highly effective and well tolerated during clinical treatment of RA. Abatacept was particularly effective in patients with no history of biologics use, and did not appear to be dependent on concomitant MTX therapy.

Objective: This study investigated the feasibility and outcomes of the illness management and recovery program in Japan., Methods: Thirty-five patients with schizophrenia were recruited. Participants were assigned (not randomly) to the intervention and wait-list comparison groups. Symptom severity, functioning, activation level in self-management, quality of life, satisfaction, self-efficacy in community living, and satisfaction with services were measured before and after the intervention., Results: Over two years 25 patients completed the intervention (some after being wait-listed). In the pre-post comparison, they showed significant improvement in symptoms and functioning, self-reported activation in self-management, quality of life, satisfaction, and self-efficacy in community living. Compared with the ten participants in a wait-list comparison group, the eight participants in the first intervention group showed an increased quality of life in social functioning, satisfaction in living, and self-efficacy for social relationships in community living., Conclusions: Findings suggest that the program is effective for participants with severe mental illness in Japan.

The following review focuses on how the study of anatomy in Japan has evolved throughout the centuries; specifically, we investigate anatomical knowledge during the primitive, ancient, feudal, and early modern periods of Japanese history. Early vague and mythical anatomical concepts derived from China prevailed for many centuries in Japan. Kajiwara wrote one of the earliest anatomical works in 1302. As a science, anatomy was the first basic science to be established in Japan, beginning simplistically during the 1600s and flourishing more recently with the onset of Meiji Restoration. As a result, Japan has produced several of the most influential anatomists of the 20th century, including Buntaro Adachi, who added detail to our knowledge of the vascular system and its variations; and Sunao Tawara, who discovered the atrioventricular node. Herein, we discuss the ways in which Japan has added to and promoted the anatomical sciences.

Background: The incidence of suicide has increased markedly in Japan since 1998. As psychological autopsy is not generally accepted in Japan, surveys of suicide attempts, an established risk factor of suicide, are highly regarded. We have carried out this study to gain insight into the psychiatric aspects of those attempting suicide in Japan., Methods: Three hundred and twenty consecutive cases of attempted suicide who were admitted to an urban emergency department were interviewed, with the focus on psychosocial background and DSM-IV diagnosis. Moreover, they were divided into two groups according to the method of attempted suicide in terms of lethality, and the two groups were compared., Results: Ninety-five percent of patients received a psychiatric diagnosis: 81% of subjects met the criteria for an axis I disorder. The most frequent diagnosis was mood disorder. The mean age was higher and living alone more common in the high-lethality group. Middle-aged men tended to have a higher prevalence of mood disorders., Conclusion: This is the first large-scale study of cases of attempted suicide since the dramatic increase in suicides began in Japan. The identification and introduction of treatments for psychiatric disorders at emergency departments has been indicated to be important in suicide prevention.

Objective: Neuroleptic malignant syndrome (NMS) is one of the most serious adverse reactions to antipsychotic medications. We accumulated data on Japanese NMS patients and, in a study designed to examine the effects of drug metabolism on the occurrence of NMS, tested the possibility of association between NMS and CYP2D6 polymorphisms., Methods: We studied 53 patients who had experienced NMS and 112 healthy individuals. We determined what drugs the patients with NMS had been given and retrospectively identified candidates for drugs causing NMS. We screened the prevalence of CYP2D6 genotypes using polymerase chain reaction and restriction fragment length polymorphism analyses., Results: The prevalence of *5 alleles in the group of all patients with NMS was higher than that in the controls, though this difference was not statistically significant (10.4% vs. 5.4%; P = 0.107; odds ratio (OR) 2.05; 95% confidence interval (CI) 0.87-4.80). No association was found between the frequency of *10 alleles and the occurrence of NMS. We found *4 and duplicated alleles in only one patient each among the patients with NMS. A total of 29 patients appeared to have developed NMS as a result of having taking CYP2D6 substrates. The prevalence of *5 alleles in these 29 patient was significantly higher than that in the controls (15.5% vs. 5.4%; P = 0.020; OR 3.25; 95% CI 1.30-8.13)., Conclusion: Our findings suggest that the CYP2D6*5 allele is likely to affect vulnerability to development of NMS.

Although foscarnet is a promising alternative for the treatment of cytomegalovirus (CMV) infection, its toxicity can be significant in patients with advanced age. We retrospectively reviewed medical records of 123 patients (median age of 55; range, 17-79) who received reduced-intensity cord blood transplantation (RI-CBT). Patients preemptively received reduced-dose foscarnet 30 mg/kg twice daily when CMV antigenemia exceeded 10/50,000. Sixty-three patients developed CMV antigenemia on a median of day 34, and 29 received foscarnet preemptively. The median level of CMV antigenemia at the initiation of foscarnet was 30. Median duration of foscarnet administration was 24 days. Adverse effects included electrolyte abnormalities (n=19), renal impairment (n=13), and skin eruption requiring discontinuation of foscarnet (n=1). Preemptive therapy of foscarnet was completed in 18 patients. Seven patients died during foscarnet use without developing CMV disease. The remaining 3 developed CMV enterocolitis 5, 14, and 17 days after initiation of foscarnet. All of them were successfully treated with ganciclovir or foscarnet. Reduced dose of foscarnet is beneficial to control CMV reactivation following RI-CBT; however, it has considerable toxicities in RI-CBT recipients with advanced age. Further studies are warranted to minimize toxicities and identify optimal dosages.

Japan has one of the highest suicide rates in the world. Suicides numbered 32,863 in 1998 and have exceeded 30,000 in every subsequent year. Education of those involved in general and psychosocial patient care can contribute greatly to suicide prevention. The authors administered a brief knowledge and attitude assessment questionnaire concerning suicide to students in their first, third, and fifth years at a Japanese medical school. Participants numbered 160 (94 men with a mean age of 21.8 years, SD = 3.01, and 66 women with a mean age of 21.2 years, SD = 2.64); 59 first year, 52 third year, and 49 in their fifth year. The questionnaire consists of eight multiple-choice questions asking knowledge of suicide and one open-ended question asking attitude. In the knowledge part, only about half of the items were answered correctly (mean score was 4.21, SD = 1.28). A significant difference was observed in prevalence of attitudes as categorical variables between student years (P = 0.001). Sympathetic comments increased along with student years, while critical comments decreased. Given the frequent and interventional opportunities of primary-care medical contacts, poor understanding of suicide from the medical viewpoint was of concern. Moreover, judgmental attitudes were common, especially in earlier school years. Better informed, more understanding physicians and other health professionals could contribute greatly to prevention.

Background: At present in Japan, there are neither reports on antibiotic prophylaxis regardless of underlying diseases nor precise guidelines on prophylactic antibiotics in orthopedic surgery. Therefore, the preventive effect of antimicrobial agents on surgical site infection (SSI) after clean orthopedic surgery was studied to control the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in our ward and to reduce SSI caused by MRSA., Methods: Regardless of the type of operation or underlying disease, a regimen of prophylaxis that is of shorter duration than before was conducted in 419 patients admitted to our orthopedic ward (one ward) and who underwent clean orthopedic surgery between 2001 and 2002., Results: The annual usage of beta-lactam antibiotics in the ward decreased by 960.9 g, the isolation rate of MRSA in the ward decreased to 50% (the lowest isolation rate in the past 4 years), and SSIs caused by MRSA were found in 3 of 419 (0.71%) patients in one year compared with 6 of 470 (1.28%) during the previous year. Comparison of two antibiotics revealed that SSI caused by MRSA did not occur in any of the 187 patients receiving sulbactam/ampicillin as prophylaxis but did occur in 1.29% (3/232) patients receiving cefazolin. Concerning all SSIs caused by any organisms, they occurred in 0.53% of patients receiving sulbactam/ampicillin and in 2.16% of patients receiving cefazolin. The difference in the SSI rates between the two groups was not statistically significant., Conclusions: Although there is statistically no significant difference in the incidence of SSI caused by MRSA, we were able to decrease the isolation rates of MRSA and prevent MRSA from spreading owing to the reduced antibiotic usage in this study. Sulbactam/ampicillin can be recommended, as well as cefazolin, for antibiotic prophylaxis in clean orthopedic surgery.

A genetic predisposition to the development of neuroleptic malignant syndrome (NMS) has been suggested by clinical studies. Although the molecular basis of NMS is unclear, a dopaminergic blockade mechanism has been considered the main cause. We therefore investigated the association between NMS and three functional polymorphisms of the dopamine D(2) receptor (DRD(2)) gene: TaqI A, -141C Ins/Del, and Ser311Cys. Subjects included 32 Japanese patients, previously diagnosed with NMS, and 132 schizophrenic patients treated with neuroleptics without occurrence of NMS. Polymerase chain reaction and restriction fragment length polymorphism analyses were performed to determine each genotype. We found significant differences in genotypic and allelic frequencies of the -141C Ins/Del polymorphism between patients with and without NMS. The -141C Del allele was significantly more frequent in the NMS group (23.4 vs 11.7%, P=0.026). Similarly, the proportion of -141C Del allele carriers was significantly higher in the NMS group (40.6 vs 20.5%, P=0.022). No significant differences between the two groups were seen for allelic and genotypic frequencies of the TaqI A and Ser311Cys polymorphisms. This result suggests that the -141C Ins/Del polymorphism is likely to predispose toward the development of NMS, probably together with other unidentified factors.