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The objective of this study was to estimate the potential sediment yield distribution in Japan attributed to extreme-rainfall-induced slope failures in the future. For this purpose, a regression relationship between the slope failure probability and the subsequent sediment yield was developed by using sediment yield observations from 59 dams throughout Japan. The slope failure probability accounts for the effects of topography (as relief energy), geology and hydro- climate variations (hydraulic gradient changes due to extreme rainfall variations) and determines the potential slope failure occurrence with a 1-km resolution. The applicability of the developed relationship was then validated by comparing the simulated and observed sediment yields in another 43 dams. To incorporate the effects of a changing climate, extreme rainfall variations were estimated by using two climate change scenarios (the MRI-RCM20 Ver.2 model A2 scenario and the MIROC A1B scenario) for the future and by accounting for the slope failure probability through the effect of extreme rainfall on the hydraulic gradient. Finally, the developed slope failure hazard-sediment yield relationship was employed to estimate the potential sediment yield distribution under a changing climate in Japan. Time series analyses of annual sediment yields covering 15-20 years in 59 dams reveal that extreme sedimentation events have a high probability of occurring on average every 5-7 years. Therefore, the extreme-rainfall-induced slope failure probability with a five-year return period has a statistically robust relationship with specific sediment yield observations (with r² = 0.65). The verification demonstrated that the model is effective for use in simulating specific sediment yields with r² = 0.74. The results of the GCM scenarios suggest that the sediment yield issue will be critical in Japan in the future. When the spatially averaged sediment yield for all of Japan is considered, both scenarios produced an approximately 17-18% increase around the first half of the 21st century as compared to the present climate. For the second half of the century, the MIROC and MRI- RCM20 scenarios predict increased sediment yields of 22% and 14%, respectively, as compared to present climate estimations. On a regional scale, both scenarios identified several common areas prone to increased sediment yields in the future. Substantially higher specific sediment yield changes (over 1000m /km /year) were estimated for the Hokuriku, Kinki and Shikoku regions. Out of 105 river basins in Japan, 96 will have an increasing trend of sediment yield under a changing climate, according to the predictions. Among them, five river basins will experience an increase of more than 90% of the present sediment yield in the future. This study is therefore expected to guide decision-makers in identifying the basins that are prone to sedimentation hazard under a changing climate in order to prepare and implement appropriate mitigation measures to cope with the impacts. [ABSTRACT FROM AUTHOR]

Aims The study aimed to investigate early-stage atherosclerosis in patients with impaired fasting glucose compared with patients with impaired glucose tolerance. Methods Body mass index, systolic blood pressure, fasting plasma glucose, lipid variables, ankle-brachial pressure index and brachial-ankle pulse wave velocity were measured in 2842 subjects from Takasaki city located approximately 100 km north of Tokyo in Japan. The subjects were divided into the following five groups based on a 75-g oral glucose tolerance test: (i) normal fasting plasma glucose / normal glucose tolerance group, (ii) impaired fasting glucose group, (iii) impaired glucose tolerance group, (iv) combined glucose intolerance group and (v) diabetic glucose intolerance group. Results In comparison with fasting plasma glucose levels (r = 0.269,P < 0.0001), 2-h post-challenge glucose levels weremore closely correlated with pulse wave velocity values (r = 0.300, P < 0.0001). The groups with impaired glucose tolerance, combined glucose intolerance and diabetic glucose intolerance had significantly higher pulse wave velocity values compared with the groups with normal glucose tolerance and impaired fasting glucose. Multiple regression analyses showed an independent association of age, systolic blood pressures, total cholesterol, fasting and 2h plasma glucose with pulsewave velocityvalues. Furthermore, pulse wave velocitywas not significantly correlated with fasting plasma glucose, but was correlated with increased 2h plasma glucose. Conclusions Groupswith impaired glucose tolerance and combined glucose intolerance had significantly higher brachio-ankle pulse wave velocity values compared with the group with normal glucose tolerance. Although the group with impaired fasting glucose showed amarginal increase in pulse wave velocity values compared with the group with normal glucose tolerance, the difference was not significant. Thus impaired glucose tolerance, but not impaired fasting glucose, is a risk factor for early-stage atherosclerosis [ABSTRACT FROM AUTHOR]

Abstract: Dwarf bamboos (mainly Sasa species) form dense undergrowth in many forests in Japan and compete with overstory vegetation for soil resources. For a better understanding of the interaction between tree and undergrowth root for soil nutrients, we compared soil N availability, root biomass and its substrate quality in two Betula ermanii stands. In one stand, the aboveground part of undergrowth (Sasa kurilensis) had been removed for 5 years (SR) and in the other, the undergrowth was present (SP). The SR stand had significantly higher NO3-N levels in soil (1.7–5.5mgkg−1 at different soil depths) than the SP stand (1.2–1.7mgkg−1), which may affect the amount and substrate quality of fine root. Although the total (live+dead) of the root and rhizome (root–rh) mass did not differ between the two stands, the total production by these categories was about half in the SR stand than the SP stand. Further, the proportion of dead root–rh mass was about two times in the SR stand than the SP stand. In the investigated depth (to 30cm), the contribution of the C and N inputs to the total in the uppermost layer (0–10cm deep) was greater in the SR stand (56–59%) than the SP stand (38–42%). Total root–rh of S. kurilensis in the SP stand contributed to about 38–40% of the total C and N input, and in the SR stand the contribution was still about half that of the SP stand. Further, the acid-insoluble C:N ratio in very fine root and live fine root of B. ermanii was significantly less in the SR stand. The contribution of N content in very fine root to the total root–rh was much greater in the SR (45%) stand than the SP stand (36%). These results suggest that the remaining S. kurilensis detritus and the decreased N use by this species after its removal resulted in increased N availability for B. ermanii. Natural regeneration of tree species after simultaneous death of Sasa species, which is very common in Sasa-dominant forests in Japan, may in part, be facilitated by the presence of residues of the root–rh of Sasa species. [Copyright &y& Elsevier]

Twenty-seven patients received boron neutron capture therapy during craniotomy at our research reactor from 1991 to 1999. This is a form of intra-operative radiation therapy, which uses neutrons from a nuclear reactor. There are three additional major problems to anaesthetists: boron neutron capture therapy must be given beside the nuclear reactor, with no hospital facilities; neutrons cannot be shielded effectively by ordinary protectors; and neutrons are detrimental to metal devices and especially to electrical appliances. Boron neutron capture therapy has been adopted as an effective therapy for glioblastoma/astrocytoma, but special considerations are required for anaesthesia. [ABSTRACT FROM AUTHOR]

Summary Background Japanese cedar (Cryptomeria japonica ) pollen is a major cause of seasonal pollinosis, and more than 10% of Japanese people suffer from this allergic disorder. However, only two major pollen allergens, Cry j 1 and Cry j 2, have been identified and exclusively characterized. Objective The aim of this study was to explore and identify important Japanese cedar pollen allergens other than Cry j 1 or Cry j 2. Methods C. japonica cDNA library was immunoscreened by rabbit antiserum raised against a partially purified cedar pollen allergen fraction. An isolated cDNA clone was inserted into a glutathione S-transferase (GST)-tagged Escherichia coli expression vector to obtain recombinant GST fusion protein. Non-fusion recombinant protein was purified by glutathione Sepharose affinity chromatography in conjunction with factor Xa cleavage of the GST moiety. IgE-binding ability of the recombinant protein was then evaluated by western blot analysis and enzyme-linked immunosorbent assay (ELISA). Results The cDNA encodes 306 amino acids with significant sequence similarity to those of plant isoflavone reductase-like proteins, which include a recently identified birch pollen allergen Bet v 5. Western blot analysis demonstrated that recombinant protein was recognized by cedar pollinosis patient IgE. In contrast to Bet v 5 being reported as a minor allergen, the recombinant protein exhibited 76% IgE binding frequency (19/25) against pollinosis patients. Conclusion Here we identified the third member of Japanese cedar pollen allergen homologous to isoflavone reductase. Its high IgE-binding frequency implicates that the isoflavone reductase homologue might be an additional major pollen allergen in C. japonica . [ABSTRACT FROM AUTHOR]

Abstract: At Kyoto University Research Reactor Institute (KURRI), cyclotron-based epithermal neutron source was installed in December 2008, and the supplementary construction works have been performed. As of December 2010, the various irradiation characteristics important for BNCT were mostly evaluated. The whole body exposure during BNCT medical irradiation is one of the important characteristics. In this article, measurements of absorbed dose for thermal and fast neutrons and gamma-ray at ten positions corresponding to important organs are reported. [Copyright &y& Elsevier]

Objective: To clarify the infection control measures required in the event of a new infectious disease outbreak, we conducted a questionnaire survey on the infection control measures implemented against coronavirus disease 2019 (COVID-19)., Methods: An invitation to participate in this survey was sent to the heads of 2689 facilities affiliated with the members of the Japanese Society for Infection Prevention and Control in February 2023, requesting responses to the online survey using Google Forms by March 2023., Results: Six hundred and forty-five facilities, including 20 clinics and 625 hospitals, participated in the survey. This survey revealed that various infection control measures were implemented, including universal masking in the non-COVID-19 ward (96.5 %), screening tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on scheduled admission (89.0 %), SARS-CoV-2 tests (98.7 %), and isolation in private rooms (76.5 %) for inpatients with fever. However, nosocomial infections and clusters of COVID-19 occurred in 94.4 % and 90.9 % of cases during the investigation period, respectively. One of the reasons for these results is that healthcare personnel (HCP) and patients were common index cases of nosocomial infections, and the most common cause of clusters was the work of symptomatic HCPs. These results suggest that HCPs should understand that they can be index cases or spreaders. On the other hand, the most common support from external facilities was healthcare centers, followed by physicians or nurses from other hospitals., Conclusion: In response to the emergence of infections, it is important to consider implementing infection control measures for HCPs and patients., Competing Interests: Declaration of Competing interest None., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Objectives: The aim of this article is to update evidence on the efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) and provide information to the taskforce for the 2024 update of the Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis (RA)., Methods: We searched various databases for randomised controlled trials on RA published until June 2022, with no language restriction. For each of the 15 clinical questions, two independent reviewers screened the articles, evaluated the core outcomes, and performed meta-analyses., Results: Subcutaneous injection of methotrexate (MTX) showed similar efficacy to oral MTX in MTX-naïve RA patients. Ozoralizumab combined with MTX improved drug efficacy compared to the placebo in RA patients with inadequate response (IR) to conventional synthetic DMARD (csDMARD). Rituximab with and without concomitant csDMARDs showed similar efficacy to other biological DMARDs (bDMARDs) in bDMARD-IR RA patients. Combined Janus kinase inhibitors and MTX achieved similar clinical responses and equal safety during a 4-year period compared to tumour necrosis factor inhibitors in MTX-IR RA patients. Biosimilars showed efficacy equivalent to that of the original bDMARDs in csDMARD-IR and bDMARD-IR RA patients., Conclusions: This systematic review provides latest evidence for the 2024 update of the Japan College of Rheumatology clinical practice guidelines for RA management., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Background: The simplified Pulmonary Embolism Severity Index (sPESI) score could help identify low-risk patients with pulmonary embolism for home treatment. However, the application of the sPESI score and selection for home treatment have not been fully evaluated in the direct oral anticoagulants era., Methods and Results: The COMMAND VTE (Contemporary Management and Outcomes in Patients With Venous Thromboembolism) Registry-2 is a multicenter registry enrolling consecutive patients with acute symptomatic venous thromboembolism. The current study population consists of 2496 patients with hemodynamically stable pulmonary embolism (2100 patients [84%] treated with direct oral anticoagulants), who were divided into 2 groups: sPESI scores of 0 and ≥1. We investigated the 30-day mortality, home treatment prevalence, and factors predisposing to home treatment using the Kaplan-Meier method and logistic regression model. Patients with an sPESI score of 0 accounted for 612 (25%) patients, and only 17% among 532 patients with out-of-hospital pulmonary embolism were treated at home. The cumulative 30-day mortality was lower in patients with an sPESI score of 0 than the score of ≥1 (0% and 4.8%, log-rank P <0.001). There was no patient with 30-day mortality with an sPESI score of 0. Independent factors for home treatment among out-of-hospital pulmonary embolism patients with an sPESI score of 0 were no transient risk factors for venous thromboembolism, no cardiac biomarker elevation, and direct oral anticoagulants use in the acute phase., Conclusions: The 30-day mortality rate was notably low in an sPESI score of 0. Nevertheless, only a minority of patients with an sPESI score of 0 were treated at home between 2015 and 2020 after the introduction of direct oral anticoagulants for venous thromboembolismin Japan.

Aims: In recent years, there has been remarkable development in machine learning (ML) models, showing a trend towards high prediction performance. ML models with high prediction performance often become structurally complex and are frequently perceived as black boxes, hindering intuitive interpretation of the prediction results. We aimed to develop ML models with high prediction performance, interpretability, and superior risk stratification to predict in-hospital mortality and worsening heart failure (WHF) in patients with acute heart failure (AHF)., Methods and Results: Based on the Kyoto Congestive Heart Failure registry, which enrolled 4056 patients with AHF, we developed prediction models for in-hospital mortality and WHF using information obtained on the first day of admission (demographics, physical examination, blood test results, etc.). After excluding 16 patients who died on the first or second day of admission, the original dataset (n = 4040) was split 4:1 into training (n = 3232) and test datasets (n = 808). Based on the training dataset, we developed three types of prediction models: (i) the classification and regression trees (CART) model; (ii) the random forest (RF) model; and (iii) the extreme gradient boosting (XGBoost) model. The performance of each model was evaluated using the test dataset, based on metrics including sensitivity, specificity, area under the receiver operating characteristic curve (AUC), Brier score, and calibration slope. For the complex structure of the XGBoost model, we performed SHapley Additive exPlanations (SHAP) analysis, classifying patients into interpretable clusters. In the original dataset, the proportion of females was 44.8% (1809/4040), and the average age was 77.9 ± 12.0. The in-hospital mortality rate was 6.3% (255/4040) and the WHF rate was 22.3% (900/4040) in the total study population. In the in-hospital mortality prediction, the AUC for the XGBoost model was 0.816 [95% confidence interval (CI): 0.815-0.818], surpassing the AUC values for the CART model (0.683, 95% CI: 0.680-0.685) and the RF model (0.755, 95% CI: 0.753-0.757). Similarly, in the WHF prediction, the AUC for the XGBoost model was 0.766 (95% CI: 0.765-0.768), outperforming the AUC values for the CART model (0.688, 95% CI: 0.686-0.689) and the RF model (0.713, 95% CI: 0.711-0.714). In the XGBoost model, interpretable clusters were formed, and the rates of in-hospital mortality and WHF were similar among each cluster in both the training and test datasets., Conclusions: The XGBoost models with SHAP analysis provide high prediction performance, interpretability, and reproducible risk stratification for in-hospital mortality and WHF for patients with AHF., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Data on the incidence, timing, and severity of myocardial damage after anthracycline-based chemotherapy (AC) in Japanese patients with breast cancer are limited., Method: We evaluated cancer therapy-related cardiac dysfunction (CTRCD) in Japanese women with breast cancer (n = 51) after the first AC according to the definitions of the 2022 European Society of Cardiology onco-cardiology guideline, including assessment of high-sensitivity troponin I (TnI) and B-type natriuretic peptide (BNP) levels., Results: CTRCD was detected in 67 % of the patients (3.9 %, 7.8 %, 9.8 %, 43 %, 37 %, 22 %, 20 %, and 9.8 % of patients at 1 week and 1, 2, 3, 6, 9, 12, and 15 months post-AC, respectively) without significant left ventricular ejection fraction reduction (<50 %) and heart failure. Elevated TnI levels (>26 pg/mL) were found in 43 % of patients, and elevated BNP levels (≥35 pg/mL) were observed in 22 % of patients during the follow-up period., Conclusions: Approximately two-thirds of the Japanese patients in this study experienced CTRCD, which was frequently observed at 3 or 6 months post-AC. However, all patients with CTRCD were diagnosed with mild asymptomatic CTRCD. Although, these patients were diagnosed with mild asymptomatic CTRCD, careful long-term follow-up will be required., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Time off work after traumatic hand injury not only affects individuals but also has socioeconomic repercussions, becoming a serious problem from the viewpoint of labor shortages. In depopulated rural areas, the impact of labor shortages due to time off work is more serious than in urban areas; however, few studies have examined return to original work in rural areas. The purpose of this study was to investigate the patient demographics at the time of hand injury that affect return to original work in a rural area of Japan., Methods: We retrospectively examined 246 patients with traumatic hand and/or forearm injuries who were working at the time of injury, and who underwent surgical operations and postoperative rehabilitation in a level II hospital in a rural agricultural area. We examined patients' initial demographic data, including gender, age, occupation (white or blue collar), employment status (self-employed, full-time, or part-time workers), complications other than hand injury, workers' compensation, dominant hand injury, and injury severity as determined using the modified Hand Injury Severity Score. Multivariate logistic regression analysis examined the association between initial patient demographics and return to original work within 150 days after injury., Results: In total, 186 patients (76 %) were able to return to original work within 150 days. A multivariate logistic regression analysis showed that three explanatory variables (i.e., severity of injury, complications other than hand injury, and female gender) significantly compromised return to original work., Conclusions: In the treatment of traumatic hand injury, intensive support should be provided for return to original work for patients who are expected to have difficulty returning to work quickly. In addition, labor shortages can be mitigated by sharing information with the workplace about patients' prospects of return to original work., (Copyright © 2023 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Using a nationwide multicenter prospective registry in Japan's data, we calculated prognostic and predictive scores, including the Out-of-Hospital Cardiac Arrest (OHCA); Cardiac Arrest Hospital Prognosis (CAHP); Nonshockable rhythm, Unwitnessed arrest, Long no-flow or Long low-flow period, blood PH < 7.2, Lactate > 7.0 mmol/L, End-stage chronic kidney disease on dialysis, Age ≥ 85 years, Still resuscitation, and Extracardiac cause (NULL-PLEASE); revised post-Cardiac Arrest Syndrome for Therapeutic hypothermia (rCAST); and MIRACLE2 scores, for adult patients with cardiac arrest. The MIRACLE2 score was validated with the modified MIRACLE2 score, which excludes information of pupillary reflexes. Each score was calculated only for the cases with no missing data for the variables used. These scores' accuracies were compared using neurological outcomes 30 days after out-of-hospital cardiac arrest (OOHCA). Patients with a cerebral performance category scale of 1 or 2 were designated as having favorable neurological outcomes. Each score's discrimination ability was evaluated by the receiver operating characteristic curve's area under the curve (AUC). To assess in detail in areas of high specificity and high sensitivity, which are areas of interest to clinicians, partial AUCs were also used. The analysis included 11,924 hospitalized adult patients. The AUCs of the OHCA, MIRACLE2, CAHP, rCAST, and NULL-PLEASE scores for favorable neurological outcomes were 0.713, 0.727, 0.785, 0.761, and 0.831, respectively. The CAHP and NULL-PLEASE scores were significantly more accurate than the rest. Accuracies did not differ significantly between the CAHP and NULL-PLEASE scores. The NULL-PLEASE score was significantly better at discriminating favorable neurological prognoses at 30 days in patients with OOHCA compared to other scoring systems., (© 2024. The Author(s).)

Background: There have been limited data on the changes in clinical outcomes after the introduction of direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) in real clinical practice. We evaluated the changes in management strategies and long-term outcomes from the warfarin era to the DOAC era., Methods and Results: We compared the 2 series of multicenter COMMAND VTE (Contemporary Management and Outcomes in Patients With Venous Thromboembolism) registries in Japan enrolling consecutive patients with acute symptomatic VTE: Registry 1: 3027 patients in the warfarin era (2010-2014) and Registry 2: 5197 patients in the DOAC era (2015-2020). The prevalence of DOAC use increased more in Registry 2 than in the Registry 1 (Registry 1: 2.6% versus Registry 2: 79%, P <0.001). The cumulative 5-year incidence of recurrent VTE was significantly lower in Registry 2 than in Registry 1 (10.5% versus 9.5%, P =0.02), and the risk reduction of recurrent VTE in Registry 2 remained significant even after adjusting the confounders (hazard ratio [HR], 0.78 [95% CI, 0.65-0.93]; P =0.005). The cumulative 5-year incidence of major bleeding was not significantly different between the 2 registries (12.1% versus 13.7%, P =0.26), and the risk of major bleeding between the 2 registries was not significantly different even after adjusting the confounders (HR, 1.04 [95% CI, 0.89-1.21]; P =0.63)., Conclusions: Along with the shift from warfarin to DOACs, there was a lower risk of recurrent VTE in the DOAC era than in the warfarin era, whereas there was no apparent change in the risk of major bleeding, which might still be an unmet need even in the DOAC era.

The Tsuruoka Metabolomics Cohort Study (TMCS) is an ongoing population-based cohort study being conducted in the rural area of Yamagata Prefecture, Japan. This study aimed to enhance the precision prevention of multi-factorial, complex diseases, including non-communicable and aging-associated diseases, by improving risk stratification and prediction measures. At baseline, 11,002 participants aged 35-74 years were recruited in Tsuruoka City, Yamagata Prefecture, Japan, between 2012 and 2015, with an ongoing follow-up survey. Participants underwent various measurements, examinations, tests, and questionnaires on their health, lifestyle, and social factors. This study uses an integrative approach with deep molecular profiling to identify potential biomarkers linked to phenotypes that underpin disease pathophysiology and provide better mechanistic insights into social health determinants. The TMCS incorporates multi-omics data, including genetic and metabolomic analyses of 10,933 participants, and comprehensive data collection ranging from physical, psychological, behavioral, and social to biological data. The metabolome is used as a phenotypic probe because it is sensitive to changes in physiological and external conditions. The TMCS focuses on collecting outcomes for cardiovascular disease, cancer incidence and mortality, disability and functional decline due to aging and disease sequelae, and the variation in health status within the body represented by omics analysis that lies between exposure and disease. It contains several sub-studies on aging, heated tobacco products, and women's health. This study is notable for its robust design, high participation rate (89%), and long-term repeated surveys. Moreover, it contributes to precision prevention in Japan and East Asia as a well-established multi-omics platform.

Statins were reported to have a potential effect of primary prevention of venous thromboembolism (VTE), although that of secondary prevention remains uncertain. To investigate the association between statins use and recurrent VTE in the current era. The COMMAND VTE Registry-2 is a multicenter registry enrolling 5,197 consecutive VTE patients among 31 centers in Japan between January 2015 and August 2020. We divided the entire cohort into 2 groups according to statins use at the time of discharge; the statins (N = 865) and no statins groups (N = 4332). The statins group was older (72.9 vs. 66.7 years, P < 0.001), and less often had active cancer (22.0% vs. 30.4%, P < 0.001). The cumulative incidence of discontinuation of anticoagulation was significantly lower in the statins group (60.3% vs. 52.6%, Log-rank P < 0.001). The cumulative 5-year incidence of recurrent VTE was significantly lower in the statins group (6.8% vs. 10.1%, Log-rank P = 0.01). Even after adjusting for the confounders, the lower risk of the statins group relative to the no statins group remained significant for recurrent VTE (HR 0.65, 95% CI 0.45-0.91, P = 0.01). The cumulative 5-year incidence of major bleeding was significantly lower in the statins group (12.2% vs. 14.1%, Log-rank P = 0.04), although, after adjusting for the confounders, the risk of the statins group relative to the no statins group turned to be insignificant (HR 0.77, 95% CI 0.59-1.00, P = 0.054). In this large real-world VTE registry, statins use was significantly associated with a lower risk for the recurrent VTE in the current era., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Treatment with regorafenib, which inhibits vascular endothelial growth factor (VEGF) receptor, frequently results in hand-foot skin reaction (HFSR), requiring treatment discontinuation or dose reduction. In our prospective study of regorafenib on patients with metastatic colorectal cancer, 17% of patients developed grade 3 HFSR. Herein, we retrospectively examined genetic polymorphisms associated with regorafenib-induced severe HFSR., Methods: To identify associated polymorphisms, exploratory whole-exome sequencing focusing on factors related to VEGF-mediated signaling pathways was first performed in seven patients each, with grade 3 HFSR and without HFSR. The identified HFSR-associated polymorphisms were analyzed in all the 40 patients., Results: The genotype frequency of rs3025009 G/A or A/A in the gene encoding VEGF-A (VEGFA) in patients with ≥ grade 2 HFSR was significantly higher than in other patients (P = 0.0257, Pc = 0.0771 [Bonferroni correction]). The frequency of C-C motif of chemokine ligand 4-like 2 (CCL4L2) rs3744596 A/T or T/T in patients with grade 3 HFSR was significantly lower than in others (P = 0.00894, Pc = 0.0268). The combination of the risk genotypes VEGFA rs3025009 G/A or A/A and CCL4L2 rs3744596 A/A was significantly associated with a higher incidence of grade 3 (P = 0.000614, Pc = 0.00246) and a longer median progression-free survival (P = 0.0234) than others., Conclusions: These VEGF-related polymorphisms were found to be associated with HFSR and the survival benefits of regorafenib treatment., Trial Registration Number and Date: UMIN000013939, registered on May 12, 2014, when 6 months after the approval by the Institutional Review Board of Showa University., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Catheter ablation (CA) for atrial fibrillation (AF) in patients on hemodialysis (HD) is reported to have a high risk of late recurrence (LR). However, the relationship between early recurrence (ER) within a 90-day blanking period after CA in AF patients and LR in HD patients remains unclear., Methods and results: Of the 5,010 patients in the Kansai Plus Atrial Fibrillation Registry, 5,009 were included in the present study. Of these patients, 4,942 were not on HD (non-HD group) and 67 were on HD (HD group). HD was an independent risk factor for LR after the initial CA (adjusted hazard ratio 1.6; 95% confidence interval 1.1-2.2; P=0.01). In patients with ER, the rate of sinus rhythm maintenance at 3 years after the initial CA was significantly lower in the HD than non-HD group (11.4% vs. 35.4%, respectively; log-rank P=0.004). However, in patients without ER, there was no significant difference in the rate of sinus rhythm maintenance at 3 years between the HD and non-HD groups (67.7% vs. 74.5%, respectively; log-rank P=0.62)., Conclusions: ER in HD patients was a strong risk factor for LR. However, even HD patients could expect a good outcome without ER after the initial CA.

In this study, we aimed to use the loss of happy life expectancy (LHpLE), an indicator that enables risk assessment considering wellbeing, to compare the risks of environmental carcinogenic chemicals in Japan. First, we surveyed Japanese people to determine their emotional happiness by age and sex and evaluated whether cancer incidence reduced emotional happiness. Questionnaires were administered to a general population panel and a panel of patients with cancer in 2022, recruiting a predetermined number of responses of 5000 and 850, respectively. Second, using the survey data, LHpLE was calculated for radon, arsenic, and fine particulate matter (aerodynamic diameter <2.5 μm; PM 2.5 ) and compared to psychological distress, considering increased mortality and decreased emotional happiness due to these risks. We discovered no significant decrease in emotional happiness due to cancer incidence and no significant associations between emotional happiness and cancer type, history, or stage. LHpLE was calculated to be 6.4 × 10 -3 years for radon, 2.6 × 10 -3 years for arsenic, 1.1 × 10 -2 years (2012 exposure) and 8.6 × 10 -4 years (2020 exposure) for PM 2.5 , and 9.7 × 10 -1 years for psychological distress. The fraction of losses caused by these carcinogenic chemicals to HpLE exceeded 10 -5 , suggesting that risk reduction for these chemicals is important in environmental policies. The LHpLE indicator allows for comparing different types of risks, such as environmental chemicals and psychological distress. This is the first study to compare chemical risks using the LHpLE indicator., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: To assess the association between plasma amyloid β (Aβ) 42/40, phosphorylated tau (p-τ)181, glial fibrillary acidic protein (GFAP), or neurofilament light chain (NfL) and the risk of dementia and to determine whether these plasma biomarkers could improve the ability to predict incident dementia in a general older population., Methods: A total of 1346 Japanese community-dwelling individuals aged ≥65 years without dementia were followed prospectively for 5.0 years. Plasma biomarkers were quantified using a Simoa HD-X analyzer. A Cox proportional hazards model was used to estimate the hazard ratios of each plasma biomarker level for the risk of dementia., Results: During the follow-up, 151 participants developed dementia, of whom 108 had Alzheimer disease (AD) and 43 non-Alzheimer dementia (non-AD). Lower plasma Aβ42/40 levels and higher plasma p-τ181 levels were significantly associated with developing AD but not non-AD, whereas significant associations were observed between higher plasma levels of GFAP and NfL and risk of both AD and non-AD (all P for trend <0.05). In addition, adding these four plasma biomarkers into a model consisting of the total score of the dementia risk model significantly improved the predictive ability for incident dementia., Conclusion: Our findings suggest that plasma Aβ42/40 and p-τ181 are specific markers of AD, and plasma GFAP and NfL are potential biomarkers for all-cause dementia in the general Japanese older population. In addition, the measurement of these plasma biomarkers may be a useful and relatively low-invasive procedure for identifying individuals at high risk for developing dementia in clinical practice., (© 2024 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Objectives: Patient safety events (PSEs) have detrimental consequences for patients and healthcare staff, highlighting the importance of prevention. Although evidence shows that nurse staffing affects PSEs, the role of an appropriate nursing care delivery system remains unclear. The current study aimed to investigate whether nursing care delivery systems could prevent PSEs., Methods: This retrospective study was conducted in Japan. The study examined the collaborative 4:2 nursing care delivery system in which 2 nurses are assigned to care for 4 patients, collaborating to perform tasks, and provide care. The cohort receiving care from a collaborative 4:2 nursing care delivery system was labeled the postintervention, whereas the cohort receiving care from a conventional individualized system, in which one nurse provides care for 2 patients, was labeled the preintervention. The primary outcome was the occurrence of PSEs., Results: The preintervention and postintervention comprised 561 and 401 patients, respectively, with the latter consisting of a younger and more critically ill population. The number of PSEs per 1000 patient-days was not significantly different between the 2 groups (10.3 [95% confidence interval, 7.1-13.5] versus 6.0 [95% confidence interval, 3.2-8.9], P = 0.058). Multiple logistic regression analysis showed that the collaborative 4:2 nursing care delivery system was significantly associated with PSEs (adjusted odds ratio, 0.53; 95% confidence interval, 0.29-0.95; P = 0.037)., Conclusions: These findings suggest that in an emergency intensive care unit, a collaborative nursing care delivery system was associated with a decrease in PSEs., Competing Interests: Conflicts of Interest and Source of Funding: None., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Since June 2020, boron neutron capture therapy (BNCT) has been a health care service covered by health insurance in Japan to treat locally advanced or recurrent unresectable head and neck cancers. Therefore, we aimed to assess the clinical outcomes of BNCT as a health insurance treatment and explore its role among the standard treatment modalities for head and neck cancers., Materials and Methods: We retrospectively analyzed data from patients who were treated using BNCT at Kansai BNCT Medical Center, Osaka Medical and Pharmaceutical University, between June 2020 and May 2022. We assessed objective response rates based on the Response Evaluation Criteria in Solid Tumors version 1.1, and adverse events based on the Common Terminology Criteria for Adverse Events, version 5.0. Additionally, we conducted a survival analysis and explored the factors that contributed to the treatment results., Results: Sixty-nine patients (72 treatments) were included in the study, with a median observation period of 15 months. The objective response rate was 80.5%, and the 1-year locoregional control, progression-free survival, and overall survival rates were 57.1% (95% confidence interval [CI]: 43.9%-68.3%), 42.2% (95% CI: 30.1%-53.8%), and 75.4% (95% CI: 62.5%-84.5%), respectively. Locoregional control was significantly longer in patients with earlier TNM staging and no history of chemotherapy., Conclusions: BNCT may be an effective treatment option for locally advanced or recurrent unresectable head and neck cancers with no other definitive therapies. If definitive surgery or radiation therapy are not feasible, BNCT should be considered at early disease stages., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: The purpose of the study is to assess if daily use of hypnotics increases mortality, aspiration pneumonia and hip fracture among relatively healthy individuals aged 75 years or older who lead independent lives in the community., Method and Patients: Of the adults aged 75 years or older residing in Hokkaido prefecture of Japan (n = 705,538), those who did not meet several exclusion criteria were eligible for generating propensity score-matched cohorts (n = 214,723). Exclusion criteria included co-prescribed medications acting on the central nervous system, diagnoses of malignant neoplasm, dementia, depression, etc. We compared 33,095 participants who were prescribed hypnotics for daily use (hypnotic group) with a propensity score-matched cohort without a prescription (control group). Participants were followed for more than 42 months., Results: During the 42-month follow-up period, the incidence of the three outcome measures in the hypnotics group was significantly higher than that in the control group (aspiration pneumonia p < 0.001, hip fracture p = 0.007, and all-cause mortality p < 0.001). Sensitivity analyses utilizing inverse probability weighting demonstrated hazard ratios of 1.083 [1.023-1.146] for mortality, 1.117 [1.014-1.230] for aspiration pneumonia, and 1.720 [1.559-1.897] for hip fracture. Meanwhile, the attribute risk differences were 2.7, 1.5, and 1.0 per 1000 patient-years, respectively., Conclusions: Although daily use of hypnotics increased the risk of three events, their attribute risk differences were fewer than 3.0 per 1000 patient-years. The results will help provide guidance on whether it is reasonable to prescribe hypnotics to geriatric population aged 75 or older leading independent lives in the community., Clinical Trial Registration: UMIN-CTR UMIN000048398., (© 2024 John Wiley & Sons Ltd.)

In recent years, the association between neuroinflammatory markers and dementia, especially Alzheimer's disease (AD), has attracted much attention. However, the evidence for the relationship between serum-hs-CRP and dementia including AD are inconsistent. Therefore, the relationships of serum high-sensitivity CRP (hs-CRP) with dementia including AD and with regions of interest of brain MRI were investigated. A total of 11,957 community residents aged 65 years or older were recruited in eight sites in Japan (JPSC-AD Study). After applying exclusion criteria, 10,085 participants who underwent blood tests and health-related examinations were analyzed. Then, serum hs-CRP levels were classified according to clinical cutoff values, and odds ratios for the presence of all-cause dementia and its subtypes were calculated for each serum hs-CRP level. In addition, the association between serum hs-CRP and brain volume regions of interest was also examined using analysis of covariance with data from 8614 individuals in the same cohort who underwent brain MRI. After multivariable adjustment, the odds ratios (ORs) for all-cause dementia were 1.04 (95% confidence interval [CI] 0.76-1.43), 1.68 (95%CI 1.08-2.61), and 1.51 (95%CI 1.08-2.11) for 1.0-1.9 mg/L, 2.0-2.9 mg/L, and ≥ 3.0 mg/L, respectively, compared to < 1.0 mg/L, and those for AD were 0.72 (95%CI 0.48-1.08), 1.76 (95%CI 1.08-2.89), and 1.61 (95%CI 1.11-2.35), for 1.0-1.9 mg/L, 2.0-2.9 mg/L, and ≥ 3.0 mg/L, respectively, compared to < 1.0 mg/L. Multivariable-adjusted ORs for all-cause dementia and for AD prevalence increased significantly with increasing serum hs-CRP levels (p for trend < 0.001 and p = 0.001, respectively). In addition, the multivariable-adjusted temporal cortex volume/estimated total intracranial volume ratio decreased significantly with increasing serum hs-CRP levels (< 1.0 mg/L 4.28%, 1.0-1.9 mg/L 4.27%, 2.0-2.9 mg/L 4.29%, ≥ 3.0 mg/L 4.21%; p for trend = 0.004). This study's results suggest that elevated serum hs-CRP levels are associated with greater risk of presence of dementia, especially AD, and of temporal cortex atrophy in a community-dwelling Japanese older population., (© 2024. The Author(s).)

Objectives: This study validated the Japanese version of the Attention-Deficit/Hyperactivity Disorder-Rating Scale-5 (ADHD-RS-5) and the Disruptive Behavior Disorders Rating Scale. We extended the ADHD-RS-5 by adding the oppositional defiant disorder and conduct disorder subscales to compare the two rating scales psychometrically., Methods: We examined the internal consistency, test-retest reliability, construct validity and criterion validity of the two rating scales in 135 Japanese outpatients aged 6-18 years., Results: The internal consistency and test-retest reliability were good for all the subscales of the two rating scales except for the conduct disorder subscale of the ADHD-RS-5 extended. Good construct validity was revealed by expected correlational patterns between subscales from the two rating scales and the Children Behavior Checklist. The criterion validity was good for all the subscales of the two rating scales rated by parents, while teacher-ratings revealed substantially lower predictive ability for all the subscales. Agreement between parent- and teacher-ratings of the two rating scales was generally moderate and using predictive ratings alone of both ratings showed the best predictive ability among the integration methods examined., Conclusion: The two rating scales have sound psychometric properties and will aid in screening and severity assessment of externalizing disorders in Japanese clinical settings., (© 2024 The Authors. International Journal of Methods in Psychiatric Research published by John Wiley & Sons Ltd.)

A moment magnitude (Mw) 7.5 earthquake (the Global IDentifire (GLIDE) number: # Q-2024-000001-JPN) struck the Noto Peninsula of Ishikawa Prefecture on 1 January 2024 at 16:10 (Japan Standard Time). The reversed fault, 150 km in length and subducting beneath the peninsula, resulted in maximum seismic intensity 7 shaking, triggered the tsunami, destroyed over 43 thousand buildings, and disrupted roads and lifelines. The disaster claimed 236 deaths, including 15 indirect disaster deaths as of Jan. 28, 2024. There were Disaster Base Hospitals (DBHs) in the region, which survived structurally but suffered from impaired functions and the surge of medical needs of affected people. The disaster medical system of Japan immediately responded and coordinated the hundreds of emergency medical teams (EMTs), i.e., the Japan Disaster Medical Assistance Team (DMAT), from all over the country. Tohoku University Hospital, which had the experience of the 2011 Great East Japan Earthquake (GEJE), joined the coordinated response, dispatching a chain of DMATs, which helped the medical and public health coordination in Wajima City. The medical and public health needs included injuries, non-communicable diseases, infectious diseases, mental health issues, and maternal and child health issues, which were similar in the affected communities in GEJE. Although the actual damage far exceeded expectations, the structural retrofitting and business continuity plans of DBHs and the coordinated response of the national disaster medical system enhanced the effectiveness of medical and public health response.

Background: Studies have shown that decreased gait speed is associated with impaired cognitive function. However, whether this association is equivalent across ages or genders in the older population remains unclear. Thus, we examined the association between mild cognitive impairment (MCI) and gait speed emphasising the influence of age and gender., Methods: Overall, 8233 Japanese participants aged ≥65 years were enrolled in this cross-sectional study between 2016 and 2018. After stratification by gender and age group, the participants' gait speeds were divided into quintiles, and the difference in MCI prevalence at each gait speed quintile was calculated. Logistic regression analyses were performed to assess the odds of MCI for each quintile and to assess the influence of age and gender., Results: Males had a consistently higher prevalence of MCI than females. The odds of MCI were increased as gait speed decreased. Logistic regression analyses revealed that in the multivariable-adjusted model 2, the odds ratios (95% confidence interval; CI) for MCI were 2.02 (1.47-2.76) for females and 1.75 (1.29-2.38) for males in the slowest gait speed quintiles compared to the fastest quintile. In the stratified analyses, only males showed an age-dependent increase in the associations between gait speed and MCI, while females exhibited comparable associations across age groups., Conclusions: Reduced gait speed was associated with increased odds of MCI, and this association may vary according to gender and age. Therefore, gait speed could serve as a valuable screening tool for MCI, with gender- and age-dependent clinical implications., (© 2023 The Authors. Psychogeriatrics published by John Wiley & Sons Australia, Ltd on behalf of Japanese Psychogeriatric Society.)

To reduce microplastic (MP) discharge into the aquatic environment, it is necessary to properly identify its sources and amounts. Here, specific MP sources, i.e., personal care products (PCPs), fibers from clothes, and tire-wear particles (TWPs) were focused, and MP generations from these sources in the Tokyo Bay watershed, Japan, were estimated based on statistical data on production and reported emission factors of the MP sources and executing considering uncertainty on the data. Potential annual MP emission into Tokyo Bay was estimated to be 10.2 ± 1.6, 38 ± 22, and 1500-1800 tons for PCPs, fibers, and TWPs, respectively. Emissions into Tokyo Bay by assuming MP density and diameter was estimated. For fiber, the fraction to potential emission was estimated at 1.0-2.8 %. This study contributes to determining potential discharge pathways. This will assist in the application of appropriate measures to reduce MP discharge into water bodies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Coronary debulking devices are essential in obtaining optimal results in percutaneous coronary intervention (PCI) for severely calcified lesions. However, since the introduction of these devices in Japan, the presence of full-time cardiovascular surgeons in their own facilities has been an essential condition (on-site surgical back-up) as the facility criteria for their use. The criteria were revised in April 2020, making their implementation possible at our hospital. Between May 2020 and January 2022, we administered PCIs using rotational atherectomy (RA) for 33 lesions in 28 patients and orbital atherectomy system (OAS) for 36 lesions in 27 patients. The most preferred strategy in our hospital is OAS via the distal radial approach using a 6Fr Glide sheath or RA via the femoral approach using a 7Fr sheath. The percentages of usable imaging modality as an initial device without lesion modification were 57.1 and 66.7% in the RA and OAS groups, respectively. In the RA procedure, 1.5- and 2.0-mm Rota burrs were more frequently adopted for the initial and second sessions, respectively. In the OAS procedure, the debulking was always initiated at a low speed. Nineteen of the 27 patients underwent additional high-speed debulking. Pre-procedural quantitative coronary angiographic analysis revealed that the minimal lumen diameter was significantly smaller in the RA than in the OAS group. Debulking procedures were successful in all patients excluding two instances of procedure-related complications in the RA group, one of which was coronary perforation safely treated via covered stent deployment without any resulting hemodynamic instability. Our early experience with coronary debulking devices with off-site surgical back-up clearly reveals the safety and feasibility of this procedure in a newcomer facility., (© 2022. The Author(s) under exclusive licence to Japanese Association of Cardiovascular Intervention and Therapeutics.)

In 2019, several aquarium-reared fish died at a sea life park in Japan. Necropsy revealed micronodules on the spleen in the dotted gizzard shad (Konosirus punctatus). Seven of 16 fish exhibited microscopic multifocal granulomas associated with acid-fast bacilli in the spleen, kidney, liver, alimentary tract, mesentery, gills, and/or heart. Bacterial cultures yielded isolates from the dotted gizzard shad and a Japanese sardine (Sardinops melanostictus). Microbiological and molecular biological examinations revealed the isolates as Mycobacterium pseudoshottsii. To our knowledge, this is the first isolation of M. pseudoshottsii from aquarium-reared fish.

Background: Vitamin K antagonist (VKA) remains an essential option for venous thromboembolism (VTE), although direct oral anticoagulants have become available. However, there is a paucity of data on the optimal intensity and quality of control for VKA in Japanese., Methods: The COMMAND VTE Registry is a multicenter registry enrolling consecutive 3027 patients with acute symptomatic VTE among 29 centers in Japan. The current study population consisted of 1938 patients who received VKA with prothrombin time-international normalized ratio (PT-INR) measurement >5 times. The primary outcome measure was a composite of symptomatic VTE recurrence or major bleeding at 1 year. The presumed optimal quality of VKA therapy was defined as the combination of PT-INR range and time in therapeutic range (TTR) with the numerically lowest event rate., Results: The group with TTR ≥70 % based on PT-INR range ≥1.5 and <2.0 showed the lowest cumulative incidence rate. The cumulative 1-year incidence and the adjusted risk for the primary outcome measure were significantly lower in the optimal quality group than in the non-optimal quality group (5.2 % vs. 11.7 %, p = 0.001, and HR 0.49, 95%CI 0.28-0.81). Similarly, the cumulative 1-year incidences of a recurrent VTE, major bleeding, and all-cause death were significantly lower in the optimal quality group (recurrent VTE: 2.5 % vs. 6.0 %, p = 0.02; major bleeding: 2.8 % vs. 7.0 %, p = 0.008; and all-cause death: 2.8 % vs. 12.6 %, p < 0.0001). The lower risk of the optimal quality group relative to non-optimal quality group for the clinical outcomes was consistent regardless of the etiology of VTE (active cancer, transient risk factor, and unprovoked)., Conclusions: The current VTE registry showed the optimal intensity of VKA therapy was target PT-INR range ≥1.5 and <2.0, which could support the current Japanese guideline recommendation, and the good quality of control for VKA therapy of TTR ≥70 % was independently associated with better outcomes., Competing Interests: Declaration of competing interest Dr. Yamashita received lecture fees from Daiichi-Sankyo, Bristol-Myers Squibb, Pfizer, and Bayer Healthcare. Dr. Morimoto received lecture fees from Mitsubishi Tanabe Pharma and Pfizer Japan and consultant fees from Asahi Kasei, Bristol-Myers Squibb, and Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: To determine normal corneal eccentricity in a rural Japanese population and to examine factors associated with eccentricity value., Methods: This used data from the Locomotive Syndrome and Health Outcome in Aizu Cohort Study (LOHAS) project between 2009 and 2012. Residents of Minamiaizu and Tadami in Fukushima, Japan, who were aged 40 years or over, were invited for a comprehensive eye examination. For 1371 patients with no history of internal eye surgery, corneal eccentricity was measured using a Pentacam., Results: Of 1371 people recruited to the study, 1215 (1215 eyes) met the inclusion criteria. The overall mean eccentricity was 0.46 (SD = 0.18; range, -0.85 to 0.88). Corneal eccentricity was significantly associated with age, spherical equivalent, pupil diameter, anterior chamber angle, anterior chamber volume, and central corneal thickness, but not with gender or body mass index., Conclusions: In this study, the normal cornea in this Japanese population was prolate. Corneal eccentricity was likely to decrease with increasing age. Also, spherical equivalent and other anterior segment parameters had an influence on corneal eccentricity. Corneal eccentricity measurements might be helpful in the diagnosis of corneal diseases and in calculations for intraocular lens implantation and corneal refractive surgery.

There is a paucity of data on anticoagulation strategies and clinical outcomes after bleeding events for venous thromboembolism (VTE). In a multicenter Japanese registry enrolling 3027 patients with acute symptomatic VTE, after excluding 430 patients with thrombolysis and 207 patients without anticoagulation therapy, the current study population consisted of 2390 patients, who were divided into patients with major bleeding, clinically relevant non-major (CRNM) bleeding and no bleeding during anticoagulation therapy. All-cause death at 90 days after the bleeding events was evaluated as the primary outcome. There were 189 patients with major bleeding, 147 patients with CRNM bleeding, and 2054 patients without bleeding. Among 189 patients with major bleeding, 142 patients (75%) discontinued anticoagulants, of whom patients with temporary discontinuation and those with permanent discontinuation accounted for 63 patients (44%) and 79 patients (56%), and 58 patients (30.7%) died within 90 days after the bleeding events. The multivariable logistic regression model among patients with bleeding events revealed that active cancer and bleeding events within 90 days after VTE diagnosis were independently associated with 90-day mortality after the bleeding events (active cancer: OR 5.05, 95%CI 2.82-9.05; bleeding events within 90 days after VTE diagnosis: OR 2.23, 95%CI 1.25-3.96). In this practice-based large registry, anticoagulants were frequently discontinued in patients who experienced major bleeding events during anticoagulation therapy and nearly half of them restarted anticoagulants with mortality rate of approximately 30% within 90 days after the bleeding events, and active cancer was the most prevalent cause of death.Clinical trial registration COMMAND VTE Registry: http://www.umin.ac.jp/ctr/index.htm . Unique identifier: UMIN000021132., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Although previous studies have investigated age and gender effects on striatal subregional dopamine transporter (DaT) binding, these studies were mostly based on a conventional regions of interest-based analysis. Here, we investigated age and gender effects on striatal DaT binding at the voxel level, using a multicenter database of [( 123 )I] N-omega-fluoropropyl-2beta-carbomethoxy-3beta-{4-iodophenyl}nortropane ([( 123 )I] FP-CIT)-single photon emission computed tomography (SPECT) scans in 256 healthy Japanese adults., Methods: We used the Southampton method to calculate the specific binding ratios (SBRs) of each subject's striatum and then converted the [ 123 I] FP-CIT SPECT images to quantitative SBRs images. To investigate the effects of age and gender effects on striatal DaT binding, we performed a voxel-based analysis using statistical parametric mapping. Gender differences were also compared between young to middle-aged subjects and elderly subjects (age threshold: 60 years)., Results: When all subjects were explored as a group, DaT binding throughout the striatum decreased with advancing age. Among all subjects, the females showed higher DaT binding in the bilateral caudate compared to the males. In the young to middle-aged subjects, the females showed higher DaT binding throughout the striatum (with a slight caudate predominance) versus the males. In the elderly, there were no gender differences in striatal DaT binding., Conclusion: Our findings of striatal subregional age- and gender-related differences may provide useful information to construct a more detailed DaT database in healthy Japanese subjects., (© 2022. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

Background: Helicopter Emergency Medical Services (HEMS) has been in operation in Japan since 2001, allowing patients almost anywhere in the nation to receive on-scene emergency treatment from physicians. However, there is insufficient literature on the characteristics of the patients who use Japanese HEMS. Thus, this study aimed to investigate the overall characteristics of patients receiving HEMS care within a single prefecture in Japan., Methods: We retrospectively analyzed the data of 5163 patients-in Tochigi Prefecture-who received HEMS care from 2012 to 2019. Descriptive statistics were used to analyze the following aspects of care: diagnosis, severity, background characteristics, geographical and environmental variables, immediate pre-hospital intervention, transportation type, and short-term clinical outcomes., Results: Among 7370 HEMS requests received during the study period, treatment was provided to 5163 patients (1.8 cases per day; 3489 men [67.6%]). Nearly 55% (n = 2856) of patients were aged above 60 years. Age peaks were observed at 0-9 years and 60-69 years. The median distance from the base hospital to the site was 26.7 km. The age-standardized rate of HEMS treatment was 30.3 patients per 100,000 people. Cases of trauma and cardiovascular diseases were the most common (65.3%). Most individuals aged 0-9 years and 60-69 years had neurological disease (seizures accounted for 80.5% of this group) and cardiovascular disease, respectively. The number of patients was similar across all four seasons. After immediate pre-hospital intervention, 81.6% of patients receiving HEMS care were transferred by the helicopter ambulance (53.4% and 28.2% to the base hospital and to other hospitals, respectively). Overall, 56.6% of patients receiving HEMS care were transferred to the base hospital, and the short-term recovery rate was above 75%. Intravenous drip and oxygen administration were the most common pre-hospital interventions (93.1% and 72.7%, respectively)., Conclusions: This study is the first to describe the overall characteristics of HEMS patients using comprehensive data of all HEMS patients in one prefecture in Japan. Further research using both local- and national-level data is needed to accelerate the understanding of the benefits of HEMS., (© 2022. The Author(s).)

Saw palmetto berry extract (SPE) is the most commonly consumed supplement by men with benign prostatic hyperplasia (BPH). The oral administration of SPE was previously shown to significantly attenuate urodynamic symptoms in the hyperactive bladders of female rats by increasing bladder capacity and prolonging the micturition interval. The amelioration of urodynamic symptoms by SPE may be partly attributed to its binding to muscarinic receptors in the urinary bladder and its inhibition of vanilloid receptors on afferent nerves. Therefore, SPE may be pharmacologically effective at mitigating lower urinary tract symptoms (LUTS) in women. The efficacy and safety of a 12-week treatment with SPE in adult women with urinary symptoms were examined herein. The daytime frequency score in the core lower urinary symptom score (CLSS) questionnaire was significantly lower in women with LUTS treated with SPE for 12 weeks than in the placebo group. A subgroup analysis revealed that SPE alleviated the symptoms of daytime frequency (CLSS Q1) and nocturia (CLSS Q2) in a subset of subjects with a CLSS Q5 score of 1 or higher. The daytime frequency of urination in overactive bladder symptom score (OABSS) Q1 was also significantly improved by the SPE treatment. In conclusion, the present study is the first to demonstrate the potential of SPE to mitigate LUTS in adult women.

Purpose: Uncorrected refractive error (URE) is the leading cause of vision impairment and the second leading cause of blindness. It is a major public health challenge worldwide. However, the current status of URE in Japan is unclear., Study Design: Cross-sectional study., Methods: In 2012, a population-based cross-sectional study was conducted among community dwellers aged 40 years and older who received health check-ups in Minamiaizu and Tadami, Fukushima Prefecture, Japan. URE was considered when the presenting visual acuity in the better-seeing eye was < 0.5 and when visual acuity improved more than 1 line with refractive correction in the better-seeing eye. We estimated the age-specific prevalence of URE, and calculated the p-value for trend to examine the linear pattern of the association of the prevalence of URE and age., Results: This analysis included 2952 participants. The mean age (standard deviation [SD]) of the study population was 69.10(9.67) years and 57.79% were women. The overall prevalence of URE was 10.90% (95% CI, 9.77-12.05%). Prevalence by age category was 5.00% (95% CI, 2.03-10.03%), 6.09% (95% CI, 3.59-9.58%), 7.02% (95% CI, 5.49-8.81%), 11.96% (95% CI, 10.15-13.97%), and 22.39% (95% CI, 18.41-26.78%) for 40-49 years, 50-59 years, 60-69 years, 70-79 years, and 80 years or older, respectively (p-for trend, < 0.001)., Conclusions: The prevalence of URE was 10.9% and exceeded 20%, especially in individuals older than 80 years. Given the correlation between increasing incidence of URE and increase in age, public health intervention to promote awareness of URE is important, especially for the older population., (© 2022. Japanese Ophthalmological Society.)

Background: The use of heated tobacco products (HTP) has increased exponentially in Japan since 2016; however, their effects on health remain a major concern., Methods: Tsuruoka Metabolome Cohort Study participants ( n = 11,002) were grouped on the basis of their smoking habits as never smokers (NS), past smokers (PS), combustible tobacco smokers (CS), and HTP users for <2 years. Peripheral blood mononuclear cells were collected from 52 participants per group matched to HTP users using propensity scores, and DNA and RNA were purified from the samples. DNA methylation (DNAm) analysis of the 17 smoking-associated DNAm biomarker genes (such as AHRR , F2RL3 , LRRN3 , and GPR15 ), as well as whole transcriptome analysis, was performed., Results: Ten of the 17 genes were significantly hypomethylated in CS and HTP users compared with NS, among which AHRR , F2RL3 , and RARA showed intermediate characteristics between CS and NS; nonetheless, AHRR expression was significantly higher in CS than in the other three groups. Conversely, LRRN3 and GPR15 were more hypomethylated in HTP users than in NS, and GPR15 expression was markedly upregulated in all the groups when compared with that in NS., Conclusions: HTP users (switched from CS <2 years) display abnormal DNAm and transcriptome profiles, albeit to a lesser extent than the CS. However, because the molecular genetic effects of long-term HTP use are still unknown, long-term molecular epidemiologic studies are needed., Impact: This study provides new insights into the molecular genetic effects on DNAm and transcriptome profiles in HTP users who switched from CS., (©2021 The Authors; Published by the American Association for Cancer Research.)

The aim of this study was to determine the proportion of near-miss dispensing errors in hospital pharmacies in Japan. A prospective multi-center observational study was conducted between December 2018 and March 2019. The primary objective was to determine the proportion of near-miss dispensing errors in hospital pharmacy departments. The secondary objective was to determine the predictive factors for near-miss dispensing errors using multiple logistic regression analysis. The study was approved by the ethical committee at The Institute of Medical Sciences, University of Tokyo, Japan. A multi-center prospective observational study was conducted in 20 hospitals comprising 8862 beds. Across the 20 hospitals, we assessed data from 553 pharmacists and 53039 prescriptions. A near-miss dispensing error proportion of 0.87% (n = 461) was observed in the study. We found predictive factors for dispensing errors in day-time shifts: a higher number of drugs in a prescription, higher number of quantified drugs, such as liquid or powder formula, in a prescription, and higher number of topical agents in a prescription; but we did not observe for career experience level for clinical pharmacists. For night-time and weekend shifts, we observed a negative correlation of near-miss dispensing errors with clinical pharmacist experience level. We found an overall incidence of near-miss dispensing errors of 0.87%. Predictive factors for errors in night-time and weekend shifts was inexperienced pharmacists. We recommended that pharmacy managers should consider education or improved work flow to avoid near-miss dispensing errors by younger pharmacists, especially those working night or weekend shifts.

Abstract: To assess the relationship between retinal vein occlusion (RVO) and the incidence of cardiovascular (CV) events.This was a single-institution, retrospective cohort study. We enrolled 57 patients diagnosed with RVO between January 2012 and December 2019, and 125 non-RVO patients who had undergone cataract surgery by a single surgeon between January and April 2012. We compared the relative risk and incidence rate ratio of CV events between the 2 groups. In addition, survival analysis was performed to calculate the hazard ratio (HR) using the Cox proportional hazards model. RVO, age, sex, blood pressure, body mass index, presence of diabetes, blood sample data, and smoking were considered confounders.The mean observation period (± standard deviation) for the RVO and non-RVO groups was 2.68 ± 2.04 and 2.81 ± 2.70 years, respectively. Seven CV events were observed in the RVO group and 2 in the non-RVO group. Relative risk and incidence rate ratio were 7.68 (95% confidence interval [CI]: 1.65-35.8) and 8.07 (95% CI: 1.54-79.6), respectively. Multivariate analysis revealed that the RVO group had a high HR for CV events (HR: 16.13 [95% CI: 2.29-113.74]) and older age (HR: 1.26 [95% CI: 1.06-1.49]).RVO can predict future CV events, especially in the elderly population. Fundus observations should be shared between ophthalmologists and internists to prevent future CV events., Competing Interests: The authors have no funding and conflicts of interest to disclose. Data Availability: The derived data supporting the findings of this study are available from the corresponding author (KO) on request., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Antimicrobial resistance is a major health concern. A primary cause is the inappropriate use of antimicrobials, particularly by patients with upper respiratory tract infection. However, baseline information for antibiotic use for common cold before being applied the National Action Plan on Antimicrobial Resistance in Japan is lacking. Here, we analyzed the inappropriate use of antibiotics in the working-age workers. We used large claims data from an annual health check-up for at least 5 consecutive years. Among 201,223 participants, we included 18,659 working-age workers who were diagnosed with common cold at a clinic/hospital. We calculated the proportion of patients with common cold who were prescribed antibiotics and analyzed predictive factors associated with antibiotics prescription. Antibiotics were prescribed to 49.2% (n = 9180) of patients diagnosed with common cold. In the logistic regression analysis, the group taking antibiotics was predominantly younger, male, without chronic diseases, and diagnosed at a small hospital/clinic (where the number of beds was 0-19). Cephems accounted for the highest proportion of prescribed antibiotics, with 40-45% of patients being prescribed antibiotics. Our data may be applied to prioritize resources such as medical staff-intervention or education of working-age people without chronic diseases who visit clinics for common cold to avoid the potential inappropriate use of antibiotics and prevent antimicrobial resistance acceleration., (© 2021. The Author(s).)

Background: As population aging progresses, volunteers in health field are expected to play a key role in health promotion and disease prevention, which may improve community residents' health and well-being and at the same time help slow the growth of healthcare cost. The objective of this study is to examine the effects of self-oriented motives and altruistic motives as explanatory factors for Japanese Community Health Workers (CHWs)' desire to continue their service. Unraveling the relative effects of these two types of motivation on CHW retention may lead to policy and practical implications for recruiting, training, and supporting CHWs in Japan. Haddad (2007) observed that citizens in Japan generally have a sense of governmental and individual responsibility for dealing with social problems. Applying these insights to CHWs, we hypothesize that altruistic motives have more potent influence on volunteers' willingness to continue to serve than self-oriented motives., Methods: Three cities in Shiga prefecture, Japan agreed to participate in the study. Anonymous, self-administered questionnaire was mailed to all CHWs who work in the three communities. The survey data were collected in March and April, 2013. A total of 417 questionnaires were mailed to CHWs, of which 346 were completed and returned (response rate 83.0%). Nine questionnaires missing response to the question concerning willingness to continue serving were removed from the analysis. The final analysis used 337 questionnaires (effective response rate 80.8%)., Results: One hundred ninety-nine (59.1%) of the respondents answered the question about willingness to continue CHW affirmatively, and 138 (40.9%) negatively. Controlling for other relevant factors, those with self-oriented motives in serving as CHWs were more likely to state they are willing to continue to serve (OR:1.54, confidence interval 1.00-2.37) than those without such motives. Those with altruistic motives were also more likely to say they want to continue their service (OR 1.56, confidence interval 1.08-2.27) than those without such motives. Contrary to our hypothesis, the two motives, altruistic and self-oriented, were shown to have nearly equal degree of influence on respondents' willingness to continue serving as CHWs., Conclusion: One practical implication of the research is that learning more about the twin motives, self-oriented and altruistic, of volunteers and tailoring the content of CHW training by municipal health professionals to address those motives may be beneficial., Competing Interests: The authors have declared that no competing interests exist.

Oarfish (Regalecus russelii Cuvier) are mesopelagic fish with little known about their life history. Oarfish live in deep water, making it difficult for researchers to collect specimens; thus, records of their parasitic helminths are limited. Two plerocercoids were found for the first time in an oarfish stranded on the coast of Akita Prefecture, Japan. These plerocercoids were identified as Clistobothrium sp. RR-1 using morphological and molecular analyses. It was revealed that oarfish represent one of the intermediate hosts of the genus Clistobothrium, and large sharks are the definitive hosts for these parasites.

The objective of this study was to administer commonly used tools, the Center for Epidemiological Studies Depression Scale (CES-D) and the Hospital Anxiety and Depression Scale - Depression subscale (HADS-D), to screen for depressive symptoms in patients with nontuberculous mycobacterial pulmonary disease (NTM-PD). In addition, we sought to identify whether differences existed in the prevalence of depressive symptoms as assessed by CES-D and HADS-D, and by various predictors of depression. The presence of depressive symptoms in 95 patients with NTM-PD was assessed using the CES-D and HADS-D. Data regarding age, body mass index, pulmonary function, dyspnea, cough, and exercise capacity were obtained to examine their independent contribution as predictors of depressive symptoms. The prevalence of depressive symptoms was 37.9% based on CES-D and 26.3% based on HADS-D. The prevalence of depressive symptoms based on CES-D and HADS-D revealed significant differences between the two instruments. Analysis suggested that the presence of cough is a significant predictor of depressive symptoms as assessed by both CES-D and HADS-D. Countermeasures are necessary because some patients with NTM-PD disease have depressive symptoms. It is possible that assessment of the prevalence of depressive symptoms differs in accordance with the screening tool used.

In Japan, reports on the association of individual characteristics, and geographical distance and time with clinical outcomes for neurological emergencies involving helicopter emergency medical services (HEMS) are scarce. Using Tochigi HEMS data (2010-2018), we assessed the characteristics of 1,170 emergency neurological patients (e.g., stroke, neurotrauma, and seizure) at the base hospital, which covered 58% of all HEMS patients in the prefecture. After initial treatment in the emergency room, emergency physicians confirmed the clinical outcomes of each patient compared to those at the incident sites (recovery/non-recovery). We calculated the geographic distance from the base hospital to each incident site, and estimated and adjusted odds ratios (aOR) and 95% confidence intervals (CI) for non-recovery against distance. The mean distance between the incident site and base hospital was 22.0 ± 11.7 km, and 77.4% of patients recovered following initial treatment. Two peak age groups were observed among emergency neurological diseases, including seizures in patients who were aged < 5 years and stroke and neurotrauma in patients who were aged 70-80 years. The percentages of stroke, traumatic head and brain injury, and seizure were 35.8%, 29.2%, and 22.8%, respectively. The incidence of stroke (aOR = 11.8, 95% CI 6.86-20.3) and neurotrauma (aOR = 4.86, 95% CI 2.78-8.51) independently predicted a poor prognosis. However, no significant association was observed with the distance from the base hospital. Therefore, in the Tochigi prefecture, geographical disparities may not affect the short-term prognosis of patients with neurological emergencies who were transported by HEMS.

Purpose: To investigate the prevalence and factors associated with uncorrected presbyopia among rural community dwellers in Japan., Study Design: A population-based cross-sectional study was conducted in 2011 among community dwellers aged 40-74 years who received specific health checkups in Minamiaizu and Tadami, Fukushima Prefecture, Japan., Methods: Uncorrected presbyopia was considered as when the distance-corrected visual acuity in the better eye was ≥0.5 and the near-presenting visual acuity in the better eye was <0.4, regardless of distance refractive status. Multiple logistic regression analysis was employed to calculate the odds ratios (ORs) for uncorrected presbyopia and to adjust for possible confounders., Results: A total of 2054 individuals participated in the specific health checkups. In the 1156 individuals (response rate: 56.28%) analyzed in the study, the mean (SD) age was 63.0 (8.7) years, the percentage of women was higher (57.87%), and the prevalence of uncorrected presbyopia was 26.38% (95% CI 23.86%-29.03%). Multivariate analysis revealed that the factors associated with uncorrected presbyopia were older age (adjusted OR: 1.054 [95% CI: 1.034-1.075]), female sex (adjusted OR: 1.388 [95% CI: 1.006-1.915]), and distance-presenting vision impairment (adjusted OR: 2.651 [95% CI: 1.697-4.143])., Conclusion: Approximately one-quarter of the participants in this study from a rural population of Japan did not have adequate near vision. It is recommended that a public health intervention should be enacted to correct presbyopia, especially in the older age group, women, and those with uncorrected refractive errors., (© 2021. Japanese Ophthalmological Society.)

To assess the safety of cosmetic contact lenses and to identify other factors of contact lens (CL)-related complications for Japanese females. A web-based, cross-sectional, observational survey of complications related to CL use was performed. The frequencies of complications were compared between transparent and cosmetic CLs. Besides lens pigmentation, age, replacement schedule, total experience, daily wear time, location of purchase, stacking of CLs, CL exchange with friends, compliance to hygiene procedure, replacement of CLs at intervals longer than recommended, and CL wear overnight were considered as risk factors. Logistic regression analyses were performed to calculate the odds ratios. A total of 3803 Japanese females were analyzed. The frequency of adverse events was 33.4% (95%CI 31.3-35.4%) and 35.7% (95%CI 33.5-38.0%) for transparent and cosmetic CLs, respectively. In a multivariate model, statistically significant factors associated with complications included the following: quarterly schedule lenses, replacement at intervals longer than recommended, compliance to hygiene procedure, overnight wearing, purchase at physical shops and on the internet, and longer daily wearing time. Most of the risk-increasing behaviors are preventable. The role of public health ophthalmology is to increase awareness and to improve CL use behaviors., (© 2021. The Author(s).)

Tangier disease is a genetic disorder characterized by an absence or extremely low level of high-density lipoprotein (HDL)-cholesterol (HDL-C). It is caused by a dysfunctional mutation of the ATP-binding cassette transporter A1 (ABCA1) gene, the mandatory gene for generation of HDL particles from cellular cholesterol and phospholipids, and it appears in an autosomal recessive hereditary profile. To date, 35 cases have been reported in Japan and 109 cases outside Japan. With dysfunctional mutations in both alleles (homozygotes or compound heterozygotes), the HDL-C level is mostly less than 5 mg/dL and there is 10 mg/dL or less of apolipoprotein A-I (apoA-I), the major protein component of HDL. In patients with Tangier disease, major physical findings are orange-colored pharyngeal tonsils, hepatosplenomegaly, corneal opacity, lymphadenopathy, and peripheral neuropathy. Although patients tend to have decreased low-density lipoprotein (LDL)-cholesterol (LDL-C) levels, premature coronary artery disease is frequently observed. No specific curative treatment is currently available, so early identification of patients and preventing atherosclerosis development are crucial. Management of risk factors other than low HDL-C is also important, such as LDL-C levels, hypertension and smoking. Additionally, treatment for glucose intolerance might be required because impaired insulin secretion from pancreatic beta cells has occasionally been reported.