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In recent years, the population of sika deer in Japan has been increasing, causing animal damage. As for sika deer in the vicinity of the village of Yamanakako, Yamanashi Prefecture, although the total number of individuals is on a downward trend due to the controlled capture that has been conducted throughout the year since 2009, the number of individuals (population) that stay in the vicinity of residential areas (villa areas) has been increasing in recent years. Unmanned aerial vehicle (UAV) or drone has been proven as an effective tool in wildlife research. In particular, thermal images are useful for relatively large mammals such as deer. In this paper, the utility of drone remote sensing using RGB and thermal video is tested for controlled capture of sika deer as a case study in the village of Yamanakako. We develop a methodology to acquire data and to visually identify sika deer specifically for this mission. As a result, the drone remote sensing was considered successful completing within 1 hour and identifying 25 sika deer individuals. Thermal video format was effective to visually identify sika deer on site in terms of time savings, compared to RGB video or RGB/thermal still image format. To have flight area grided and hovering 3 seconds at the centre of a grid during the flight was essential both for visually identifying the number and location of sika deer and for sharing such information later with beaters and shooters using a map. [ABSTRACT FROM AUTHOR]

Predicting rainfall-induced landslides hinges on the quality of the rainfall product. Satellite rainfall estimates or rainfall reanalyses aid in studying landslide occurrences especially in ungauged areas, or in the absence of ground-based rainfall radars. Quality of these rainfall estimates is critical; hence, they are commonly crosschecked with their ground-based counterparts. Beyond their temporal precision compared to ground-based observations, we investigate whether these rainfall estimates are adequate for hindcasting landslides, which particularly requires accurate representation of spatial variability of rainfall. We developed a logistic regression model to hindcast rainfall-induced landslides in two sites in Japan. The model contains only a few topographic and geologic predictors to leave room for different rainfall products to improve the model as additional predictors. By changing the input rainfall product, we compared GPM IMERG and ERA5 rainfall estimates with ground radar–based rainfall data. Our findings emphasize that there is a lot of room for improvement of spatiotemporal prediction of landslides, as shown by a strong performance increase of the models with the benchmark radar data attaining 95% diagnostic performance accuracy. Yet, this improvement is not met by global rainfall products which still face challenges in reliably capturing spatiotemporal patterns of precipitation events. [ABSTRACT FROM AUTHOR]

The problem of uneven distribution of medical services and inequitable distribution of physicians is drawing much attention worldwide. Revealing how changes in the specialty training system in Japan have affected the distribution of doctors could help us understand this problem. In 2018, a new and standardized specialty training system was implemented by the Japanese Medical Specialty Board, which is recognized by the Ministry of Health, Labor and Welfare. The purpose of this study was to investigate how this new system has affected the geographical distribution of doctors commencing specialty training (trainees) and choice of specialty in Japan. Retrospective observational study. The change in the number of trainees between the control period (2012–2014) and 2018 was investigated, taking into account the prefecture and specialty selected. Population, the proportion of residents aged 65 years or older (aging rate), and the total number of overall doctors in each prefecture were considered as the background characteristics of each prefecture. We created a Lorenz curve and calculated the Gini coefficient for the distribution of trainees. In 2018, the number of trainees per 100,000 population increased to 6.6 nationwide compared with 5.5 during the control period. The number of trainees per 100,000 population in 2018 increased in prefectures with a large population of ≧ 2,000,000, a low aging rate (<27%), and a high doctor density (≧ 250 doctors per 100,000 population). The Gini coefficient showed an increase to 0.226 in 2018 compared with only 0.160 during the control period. After the implementation of the new training system, there was an increase in the number of doctors enrolling in specialty programs, and the specialties other than internal medicine and surgery have attracted more trainees. Inequality in the distribution of doctors between urban and rural prefectures worsened. This indicates the need to explore new ways of balancing distribution while maintaining optimal opportunities for specialist training. • In 2018, the Japanese Medical Specialty Board implemented a new and standardized physician specialty training system in Japan. • We investigated the change in the number of trainees between the control period (2012–2014) and 2018. • The total number of trainees and that per 100,000 population showed an increase in all specialties. • The Gini coefficient showed an increase to 0.226 in 2018 compared with only 0.160 during the control period. • Seeking ways of balancing trainees's unevenness while maintaining optimal opportunities for specialist training is needed. [ABSTRACT FROM AUTHOR]

The MRSA clinical practice guidelines, which include a recommended treatment for MRSA infections, could be considered important clinical practice guidelines for both clinicians and pharmaceutical companies in the area of infectious diseases. Surprisingly, some authors failed to accurately declare their financial conflicts of interest, and employees of anti-MRSA drug companies joined as the advisory authors of the MRSA clinical practice guidelines, suggesting significant negligence in the management of conflicts of interests. To the best of our knowledge no previous study has analysed the financial relationships of clinical practice guideline committee members of infectious diseases, and this study revealed for the first time that manufacturers of anti-MRSA drugs made large payments to Japanese MRSA clinical practice guidelines authors, totalling nearly €240 000. Hence, medical societies in Japan should carefully screen authors of clinical practice guidelines - including but not limited to the MRSA clinical practice guidelines - to improve their credibility among the general public. [Extracted from the article]

Reconciling the paths of extreme rainfall with those of typhoons remains difficult despite advanced forecasting techniques. We use complex networks defined by a nonlinear synchronization measure termed event synchronization to track extreme rainfall over the Japanese islands. Directed networks objectively record patterns of heavy rain brought by frontal storms and typhoons but mask out contributions of local convective storms. We propose a radial rank method to show that paths of extreme rainfall in the typhoon season (August-November, ASON) follow the overall southwest-northeast motion of typhoons and mean rainfall gradient of Japan. The associated eye-of-the-typhoon tracks deviate notably and may thus distort estimates of heavy typhoon rainfall. We mainly found that the lower spread of rainfall tracks in ASON may enable better hindcasting than for westerly-fed frontal storms in June and July. [ABSTRACT FROM AUTHOR]

Study Question: Are pregnancy and neonatal outcomes following letrozole use comparable with natural and HRT cycles in patients undergoing single frozen-thawed embryo transfer (FET)?Summary Answer: Letrozole use was significantly associated with higher rates of clinical pregnancy, clinical pregnancy with fetal heart beat and live birth, and with a lower rate of miscarriage, compared with natural and HRT cycles.What Is Known Already: Letrozole is the most commonly used aromatase inhibitor for mild ovarian stimulation in ART. However, the effect of letrozole on pregnancy and neonatal outcomes in FET are not well known.Study Design Size, Duration: A retrospective cohort study was conducted using data from the Japanese national ART registry between 2012 and 2013.Participants/materials Setting Methods: A total of 110 722 single FET cycles with letrozole (n = 2409), natural (n = 41 470) or HRT cycles (n = 66 843) were included. The main outcomes were the rates of clinical pregnancy, clinical pregnancy with fetal heart beat, miscarriage and live birth. Adjusted odds ratios and relative risks (RRs) were calculated using a generalized estimating equation adjusting for correlations within clinics.Main Results and the Role Of Chance: The rates of clinical pregnancy, clinical pregnancy with fetal heart beat, and live birth were significantly higher, while the rate of miscarriage was significantly lower in the letrozole group compared with the natural and HRT groups. In blastocyst stage transfers, the adjusted RRs for clinical pregnancy with fetal heart beat of letrozole compared with natural and HRT cycles were 1.48 (95% CI: 1.41-1.55) and 1.62 (95% CI: 1.54-1.70), respectively. Similarly, the adjusted RRs of letrozole for miscarriage compared with natural and HRT cycles were 0.91 (95% CI: 0.88-0.93) and 0.84 (95% CI: 0.82-0.87), respectively. Neonatal outcomes were mostly similar in letrozole, natural and HRT cycles.Limitations Reasons For Caution: Important limitations of this study included the lack of information concerning the reasons for selecting the specific FET method, parity, the number of previous ART failures, embryo quality and the dose and duration of letrozole intake.Wider Implications Of the Findings: These results suggest that letrozole use may improve clinical pregnancy, clinical pregnancy with fetal heart beat, and live births and reduce the risk of miscarriage in patients undergoing single FET cycles.Study Funding/competing Interest(s): No external funding was used for this study. There are no conflicts of interest.Trial Registration Number: Not applicable. [ABSTRACT FROM AUTHOR]

Study Question: What are the effects of fertility education on knowledge, childbearing desires and anxiety?Summary Answer: Providing fertility information contributed to greater knowledge, but increased anxiety.What Is Known Already: Past studies have found that exposure to educational material improved fertility awareness and changed desires toward childbearing and its timing. Existing educational websites with evidence-based medical information provided in a non-judgmental manner have received favorable responses from reproductive-aged men and women.Study Design, Size, Duration: This three-armed (one intervention and two control groups), randomized controlled trial was conducted using online social research panels (SRPs) in Japan in January 2015.Participants/materials, Setting, Methods: A total of 1455 participants (726 men and 729 women) between 20 and 39 years of age who hoped to have (more) children in the future were block-randomized and exposed to one of three information brochures: fertility education (intervention group), intake of folic acid during pregnancy (control group 1) or governmental financial support for pregnancy and childbirth (control group 2). Fertility knowledge was measured with the Japanese version of the Cardiff Fertility Knowledge Scale (CFKS-J). Knowledge, child-number and child-timing desires, subjective anxiety (i.e. whether participants felt anxiety [primary outcome]), and scores on the State-Trait Anxiety Inventory were assessed immediately after exposure. Non-inferiority comparisons were performed on subjective anxiety with non-inferiority declared if the upper limit of the two-sided 95% confidence interval (CI) for risk difference did not exceed a margin of 0.15. This test for non-inferiority was only performed for subjective anxiety; all the other variables were tests of superiority.Main Results and the Role Of Chance: Posttest scores on the CFKS-J (mean, SD) were higher in the intervention group than that of the control groups: intervention versus Control 1 and versus Control 2: 52.8 (28.8) versus 40.9 (26.2) (P< 0.001) versus 45.1 (27.1) (P = 0.003) among men and 64.6 (26.0) versus 50.8 (26.9) (P< 0.001) versus 53.0 (26.4) (P< 0.001) among women.The percentage of participants who felt subjective anxiety after exposure to the intervention brochure was significantly higher than that of the control groups: intervention versus Control 1 and versus Control 2: 32.6 versus 17.8% (risk difference [RD] = 0.149, 95% CI: 0.073-0.225) versus 14.5% (RD = 0.182, 95% CI: 0.108-0.256) among men, and 50.2 versus 26.3% (RD = 0.239, 95% CI: 0.155-0.322) versus 14.0% (RD = 0.362, 95% CI: 0.286-0.439) among women. Non-inferiority of the intervention was inconclusive (i.e. the CI included 0.15) among men whereas inferiority was declared among women. The incidence of anxiety was higher in the intervention group than that of the control groups especially among men aged 30 and older and among women aged 25 and older. No difference existed in childbearing desires between groups after exposure.Limitations, Reasons For Caution: The possibility of selection bias associated with the use of SRPs (higher socioeconomic status and education) and volunteer bias toward those more interested in fertility may limit the generalizability of these findings.Wider Implications Of the Findings: In addition to education targeting a younger generation, psychological approaches are needed to alleviate possible anxiety caused by fertility information.Study Funding/competing Interests: This study was funded by National Center for Child Health and Development, Seiiku Medical Study Grant (24-6), the Daiwa Foundation Small Grants and Grant-in-Aid for JSPS Fellows (26-1591). No competing interest declared.Trial Registration Number: UMIN Clinical Trials Registry. Trial registration number, 000016168.Trial Registration Date: 13 January 2015.Date Of First Patient's Enrolment: 15 January 2015. [ABSTRACT FROM AUTHOR]

Summary: Combined treatment with alendronate and eldecalcitol was found to be more effective in reducing the bone turnover markers and increasing bone mineral density than alendronate treatment with vitamin D3 and calcium supplementation in the osteoporotic patients. Introduction: We compared the clinical efficacy and safety of combined treatment with alendronate plus eldecalcitol (ALN + ELD) with those of treatment with ALN plus vitamin D and calcium (ALN + VitD). Methods: Osteoporotic 219 patients were randomly assigned to the ALN + ELD, or the ALN + VitD group. Primary endpoint was the inter-group differences in lumbar spine BMD (L-BMD) at patient's last visit. Secondary endpoints included the differences in BMD at other sites and the bone turnover marker (BTM) levels. Results: L-BMD, total hip BMD and femoral neck (FN-BMD) increased from baseline by 7.30, 2.41, and 2.70 % in the ALN + ELD group, and by 6.52, 2.27, and 1.18 % in the ALN + VitD group, respectively. Inter-group differences of the L-BMD and total hip BMD values were not significant. The increase of the FN-BMD was larger in the ALN + ELD group than the ALN + VitD group. Reductions of the BTMs were greater in the ALN + ELD group than the ALN + VitD group. Interaction of the percent increase of the L-BMD with the baseline values of the BTMs was observed in the ALN + VitD group only. The increases of the FN-BMD in patients with lower baseline values of type-I-collagen C-telopeptide (sCTX) and serum 25(OH) D levels <20 ng/mL were significantly larger in the ALN + ELD group than the other group. Conclusion: Combination treatment of ALN plus ELD was more effective in reducing the BTMs and increasing the FN-BMD than ALN treatment with vitamin D3 and calcium. [ABSTRACT FROM AUTHOR]

We produced a preliminary high-resolution probable hourly precipitation (mm h-1) and probable Soil Water Index (SWI) for a 50-yr recurrence interval over the Japanese archipelago from 5-km grid-cell Radar/Raingauge-Analyzed Precipitation (R/A) with a 26-yr time series (1988-2013). To date, the selection and applicability of a probability density function such as the Gumbel distribution (GUM) or the generalized extreme value distribution (GEV) has been investigated mainly from a statistical perspective, whereas this study examines them from the viewpoint of disaster prevention. Results show detailed spatial patterns of the probable hourly precipitation and SWI in Japan with ranges of 17.0-158.0 (±1.1-51.1) mm h-1 and 82.1-638.6 (±3.7-93.0), respectively, by spatial resolution of 5-km grid-cell. The probable hourly precipitation by GUM is less than that of GEV with a shape parameter of less than 0.0. Our results demonstrate that R/A-based probable hourly precipitation and SWI by GUM, which has robust estimation, is appropriate for landslide hazard assessment. There results revealed the potential and limitation of estimating the probable precipitation from the R/A dataset. Further study should verify the R/A dataset and the probable precipitations with accumulation of R/A. [ABSTRACT FROM AUTHOR]

To cite this article: Ohta K, Bousquet P-J, Aizawa H, Akiyama K, Adachi M, Ichinose M, Ebisawa M, Tamura G, Nagai A, Nishima S, Fukuda T, Morikawa A, Okamoto Y, Kohno Y, Saito H, Takenaka H, Grouse L, Bousquet J. Prevalence and impact of rhinitis in asthma: SACRA, a cross-sectional nation-wide study in Japan. Allergy 2011; 66: 1287-1295. Abstract Background: Asthma and rhinitis are common co-morbidities everywhere in the world but nation-wide studies assessing rhinitis in asthmatics using questionnaires based on guidelines are not available. Objective: To assess the prevalence, classification, and severity of rhinitis using the Allergic Rhinitis and its Impact on Asthma (ARIA) criteria in Japanese patients with diagnosed and treated asthma. Methods: The study was performed from March to August 2009. Patients in physicians' waiting rooms, or physicians themselves, filled out questionnaires on rhinitis and asthma based on ARIA and Global Initiative for Asthma (GINA) diagnostic guides. The patients answered questions on the severity of the diseases and a Visual Analog Scale. Their physicians made the diagnosis of rhinitis. Results: In this study, 1910 physicians enrolled 29 518 asthmatics; 15 051 (51.0%) questionnaires were administered by physician, and 26 680 (90.4%) patients were evaluable. Self- and physician-administered questionnaires gave similar results. Rhinitis was diagnosed in 68.5% of patients with self-administered questionnaires and 66.2% with physician-administered questionnaires. In this study, 994 (7.6%) patients with self-administered and 561 (5.2%) patients with physician-administered questionnaires indicated rhinitis symptoms on the questionnaires without a physician's diagnosis of rhinitis. Most patients with the physician's diagnosis of rhinitis had moderate/severe rhinitis. Asthma control was significantly impaired in patients with a physician's diagnosis of rhinitis for all GINA clinical criteria except exacerbations. There were significantly more patients with uncontrolled asthma as defined by GINA in those with a physician's diagnosis of rhinitis (25.4% and 29.7%) by comparison with those without rhinitis (18.0% and 22.8%). Conclusion: Rhinitis is common in asthma and impairs asthma control. [ABSTRACT FROM AUTHOR]

Objective The level of serum urate is generally elevated in postmenopausal individuals. In addition to estrogen, other menopause-related factors may also affect uric acid metabolism in postmenopausal females. Accordingly, we investigated factors related to increased serum urate levels in addition to lack of estrogen. Subjects and methods We studied 448 females who participated in an annual health check-up. None were being treated for gout, hyperuricemia, or diabetes mellitus, and no subjects had a history of hysterectomy and had never used estrogens or progestins. Body mass index (BMI), homeostasis model of insulin resistance (HOMA-R), and ethanol ingestion were investigated in all subjects, while information regarding menopause status was also obtained. Results Serum urate levels rose from the age of 46 to 60 years in the subjects. Multivariate regression analysis showed that BMI, HOMA-R, ethanol ingestion and menopause were independently associated with serum urate level. In addition, BMI and HOMA-R were higher in postmenopausal, as compared to premenopausal, subjects. Conclusion Our results suggest that menopause-related insulin resistance, obesity and ethanol ingestion as well as menopause may contribute to an increase in level of serum urate in postmenopausal Japanese women. [ABSTRACT FROM AUTHOR]

The study reported herein was initiated to examine dietary tin intake (Sn-D) in Japan to elucidate the possible effects of consumption of canned food (including beverages) on Sn-D, and to compare the intake among regions and between the two sexes in reference to the current provisional tolerable weekly intake and intake in other countries. Urinary tin levels (Sn-U) were also studied. Duplicate diet samples (24 h) together with records of food intake were collected in 1999-2004 from 111 adult residents in four areas of Japan. After exclusion of incomplete samples, 95 valid samples were subjected to determination of tin by inductively coupled plasma mass spectrometry (ICP-MS) after acid digestion. Among the 95 cases, 37 women additionally provided urine samples. Distribution of Sn-D was markedly skewed. Median Sn-D was 5.6 µg day-1 for total subjects, which was about one-tenth of the values previously reported for the Japanese population; the difference was most probably attributable to the difference in the methods of determination. Consumption of canned foods led to a substantial increase in Sn-D. Thus, the median Sn-D for canned food consumers of 35.7 µg day-1, was eight-fold higher than the median Sn-D for non-consumers of 4.5 µg day-1. Sn-U (as corrected for creatinine concentration) distributed log-normally with a geometric mean of 2.0 µg (g cr)-1. No effect of canned food consumption was evident on Sn-U. When compared internationally, Sn-D for the Japanese population was substantially lower than Sn-D for populations in other industrialized countries. [ABSTRACT FROM AUTHOR]

Objectives:To evaluate the dietary fiber (DF) intake pattern among the Japanese general population.Design:We performed a dietary survey among the general population in northern Japan to evaluate the intake patterns. DF intake was calculated by substituting the DF content of each food in the Dietary Fiber Table for the intake of each food from this dietary survey.Subjects:Five hundred and seventy-seven subjects participated in the study, 198 men and 379 women.Results:In subjects with higher DF intakes the origins of the DF that were from all food groups, but with the notable exception of rice. The contribution of the seaweed group was of particular interest. From multiple regression analysis, as for food group, seaweeds showed the highest positive correlation with DF intake in both genders, followed by vegetables, pulses, fruits. On the other hand, rice showed the negative correlation with DF intake in both genders. As for life factor, body mass index showed the negative correlation with DF intake in women.Conclusion:Seaweed, a typical Japanese food, was most related to the increase in DF intake for the Japanese general population, whereas rice, the Japanese staple, had a small influence on decreased DF intake.European Journal of Clinical Nutrition (2007) 61, 99–103. doi:10.1038/sj.ejcn.1602505; published online 2 August 2006 [ABSTRACT FROM AUTHOR]

Docetaxel plus cisplatin and docetaxel plus irinotecan are active and well-tolerated chemotherapy regimens for advanced non-small-cell lung cancer (NSCLC). A randomised phase II study compared their efficacy and toxicity in 108 patients with stage IIIb/IV NSCLC, who were randomised to receive docetaxel 60 mg m(-2) and cisplatin 80 mg m(-2) on day 1 (DC; n=51), or docetaxel 60 mg m(-2) on day 8 and irinotecan 60 mg m(-2) on day 1 and 8 (DI; n=57) every 3 weeks. Response rates were 37% for DC and 32% for DI patients. Median survival times and 1- and 2-year survival rates were 50 weeks (95% confidence interval: 34-78 weeks), 47 and 25% for DC, and 46 weeks (95% confidence interval: 37-54 weeks), 40 and 18% for DI, respectively. The progression-free survival time was 20 weeks (95% confidence interval: 14-25 weeks) with DC and 18 (95% confidence interval: 12-22 weeks) with DI. Significantly more DI than DC patients had grade 4 leucopenia and neutropenia (P<0.01); more DC patients had grade >/=2 thrombocytopenia (P<0.01). Nausea and vomiting was more pronounced with DC (P<0.01); diarrhoea was more common with DI (P=0.01). Three treatment-related deaths occurred in DC patients. In conclusion, although the DI and DC regimens had different toxicity profiles, there was no significant difference in survival. [ABSTRACT FROM AUTHOR]

Purpose : To assess the relationship between the lower extremity muscle forces and risk of falls among the elderly who were using day-care services in the long-term care insurance system. Method : The study population comprised 96 women aged 69 - 91 years. At baseline, we assessed ADL, functional capacity, isometric muscle forces of knee extension and ankle dorsiflexion obtained with a hand-held dynamometer. After 1 year, we asked subjects about falls during the follow up period. Results : In univariate analysis, only the knee extensor strength ( p = 0.003) and ankle dorsiflexor strength ( p = 0.02) differed significantly according to the fall status. After adjustment for age using multinomial logistic regression analysis, the weak quadriceps group was 7.50 times more likely than the strong group to fall once ( p = 0.02), and 5.00 times more likely to fall twice or more ( p = 0.02). The weakest ankle dorsiflexor group was 5.09 times more likely than the strongest group to fall twice or more ( p = 0.05). Conclusions : Our results indicated that the forces of knee extensor and ankle dorsiflexor were strongly associated with falls among day-care users. Physiotherapy should focus on the lower-extremity muscle strength to prevent falls and deterioration of physical ability among elderly persons who are partially dependent and need support. [ABSTRACT FROM AUTHOR]

Examines the effect of high-activity antiretroviral therapy (HAART) on hepatitis C, hepatitis G, and TT virus in multiply coinfected HIV-positive patients with hemophilia in Japan. Changes in CD4 cell counts, alanine aminotransferase levels and serum concentrations; Association of viral concentrations; Restoration of immune status.

Background: TT virus (TTV), a novel DNA virus, was originally thought to be transmitted by transfusion. However, nonparenteral transmission is recently suspected to be a major mode of transmission. To investigate the possibility of reinfection with TTV in multiply transfused patients and to evaluate the significance of transfusion transmission of TTV in patients with hemophilia, serial changes in TTV genotype were investigated in three groups.Study Design and Methods: Serial changes in TTV genotype were investigated in 16 multiply transfused patients with hemophilia, 16 age-matched patients with chronic hepatitis C, and 16 age-matched healthy subjects.Results: Mixed infection with multiple TTV genotypes was common in all groups. However, changes in TTV genotype were frequent in patients with hemophilia (15/16; 93.8%) but rare in patients with chronic hepatitis C and in healthy subjects (each group: 1/16; 6.3%).Conclusion: Changes in TTV genotype were frequently observed in multiply transfused patients with hemophilia but not in patients with chronic hepatitis or in healthy subjects without risk of transfusion transmission. This difference may suggest that exposure to TTV or even reinfection occurs frequently in patients with hemophilia, which could be evidence of transfusion transmission of TTV in this population. [ABSTRACT FROM AUTHOR]

Abstract The human Rad51 gene, HsRAD51, is a homolog of RecA of Escherichia coli and functions in recombination and DNA repair. BRCA1 and BRCA2 proteins form a complex with Rad51, and these genes are thought to participate in a common DNA damage response pathway associated with the activation of homologous recombination and double-strand break repair. Additionally, we have shown that the pattern of northern blot analysis of the Rad51 gene is closely similar to those of the BRCA1 and BRCA2 genes. It is therefore possible that alterations of the Rad51 gene may be involved in the development of hereditary breast cancer. To investigate this possibility, we screened Japanese patients with hereditary breast cancer for Rad51 mutations and found a single alteration in exon 6. This was determined to be present in the germline in two patients with bilateral breast cancer, one with synchronous bilateral breast cancer and the other with synchronous bilateral multiple breast cancer. In both patients, blood DNAs showed a G-to-A transition in the second nucleotide of codon 150, which results in the substitution of glutamine for arginine. As this alteration was not present in any patients with breast or colon cancer examined, we assume that this missense alteration is likely to be a disease-causing mutation. [ABSTRACT FROM AUTHOR]

We carried out human leukocyte antigen (HLA)-A, B, Cw, DR and DQ serological typing and HLA-DQA1, DQB1, DRB1 and DPB1 genetic typing for 46 Japanese haemophilia A patients, including 20 who had developed an antibody to factor VIII. It appears that anti FVIII inhibitor formation is associated with the major histocompatibility complex in Japanese haemophilia A patients. Absence of HLA-A24 is a principal risk factor for inhibitor formation in Japanese haemophilia A patients. As supplemental risk factors, HLA-DR4.1, DQ4 and DQA1*0301=2 are positively associated with patients exhibiting inhibitor compared with normal subjects. This and previous studies show that the association between HLA antigens and the formation of inhibitor depends on race. Data of HLA typing may be useful for the recognition of groups at high risk for the possible formation of inhibitor among Japanese haemophilia A patients. [ABSTRACT FROM AUTHOR]

Summary. We studied the prevalence of the hepatitis C virus (HCV), human immunodeficiency virus (HIV) and GB virus C or hepatitis G virus (GBV-C/HGV), and characteristics of infections in Japanese haemophilia patients. Haemophilia patients were highly infected with HCV (88.2%) because of frequent use of unheated blood concentrates. Analysis for HCV genotypes revealed characteristics of HCV infection in haemophilia patients. Japanese haemophilia patients were highly infected with rare genotypes in Japan: genotype 1a (26.5%), genotype 3 (14.5%) and genotype 4 (2.4%). HIV infection was observed in 32.3% of haemophilia patients. HCV quasispecies (clones) and direct sequencing were investigated in patients with a single HCV genotype in the hypervariable region 1 of HCV, which resulted in a high degree of diversity. This indicates that even a single genotype of HCV might have multiple origins. GBV-C/HGV infection was noted in 20.9% of Japanese haemophilia patients. Over 40 haemophilia patients with chronic hepatitis C have been treated with interferon alpha for 6 months at total doses of 480–720 million units. About 38% showed clearance of HCV RNA from serum. Six patients with HIV infection were included in the study and they did not show eradication of HCV from the serum. This might derive from that they had high serum HCV RNA titers and genotype 1a or 1b. Histologic assessment was performed in 36 haemophilia patients with HCV. No case showed a histologically normal liver. Hepatic fibrosis in the biopsy specimens was classified into five stages of fibrosis and compared with serum hepatic fibrosis markers. Serum hyaluronic acid mostly correlated with hepatic fibrosis (γ= 0.78, P < 0.0001) followed by type IV collagen (γ= 0.38, P < 0.05). This suggests that estimation of serum fibrosis markers might be substituted for liver biopsy in haemophilia patients. [ABSTRACT FROM AUTHOR]

The article presents a retrospective study of patients with moderate to severe atopic dermatitis (AD) who were treated and followed up in the Division of Allergy, National Center for Child Health and Development in Tokyo, Japan. It aims to investigate whether proactive treatment, the long-term, low-dose intermittent application of anti-inflammatory agents to previously affected skin together with daily application of emollients, changes serum immunoglobulin (Ig) E levels.

Background Primary analysis of the phase III study WJTOG 3405 demonstrated superiority of progression-free survival (PFS) for gefitinib (G) in patients treated with the epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) gefitinib compared with cisplatin plus docetaxel (CD) as the first-line treatment of stage IIIB/IV or postoperative recurrent EGFR mutation-positive non-small-cell lung cancer. This report presents final overall survival (OS) data. Patients and methods Patients were randomized between G (250 mg/day orally) and cisplatin (80 mg/m2 intravenously) plus docetaxel (60 mg/m2 i.v.), administered every 21 days for three to six cycles. After the exclusion of 5 patients, 172 patients (86 in each group, modified intention-to-treat population) were included in the survival analysis. OS was re-evaluated using updated data (data cutoff, 30 September 2013; median follow-up time 59.1 months). The Kaplan–Meier method and the log-rank test were used for analysis, and hazard ratios (HRs) for death were calculated using the Cox proportional hazards model. Results OS events in the G group and CD group were 68 (79.1%) out of 86 and 59 (68.6%) out of 86, respectively. Median survival time for G and CD were 34.9 and 37.3 months, respectively, with an HR of 1.252 [95% confidence interval (CI): 0.883–1.775, P  = 0.2070]. Multivariate analysis identified postoperative recurrence and stage IIIB/IV disease as independent prognostic factors, with an HR of 0.459 (95% CI: 0.312–0.673, P  <   0.001). Median survival time (postoperative recurrence versus stage IIIB/IV disease) were 44.5 and 27.5 months in the G group and 45.5 and 32.8 months in the CD group, respectively. Conclusion G did not show OS benefits over CD as the first-line treatment. OS of patients with postoperative recurrence was better than that of stage IIIB/IV disease, even though both groups had metastatic disease. This study was registered with UMIN (University Hospital Medical Information Network in Japan), number 000000539. [ABSTRACT FROM AUTHOR]

Seven brands of commercial milk and related products that are available in the Japanese market were investigated. Quantitative descriptive analysis was used to describe 12 sensory properties of the samples, and the position of each sample was displayed by principal component analysis. The sensory descriptors of the samples were correlated with various analytical data by partial least squares regression analysis. Aroma descriptors were correlated with the headspace gas chromatography-mass spectrometry profile. Descriptors of flavor, mouthfeel, and aftertaste were correlated with the results of the physicochemical analysis. Many of the volatile compounds that contributed to aroma attributes, according to the partial least squares loading plot, were in agreement with the influence of volatile compounds shown by previous studies. Lactulose and furosine, as indicators of heating, and viscosity were parameters that influenced flavor, mouthfeel, and aftertaste. In addition, overall aftertaste was significantly related to fat content. [ABSTRACT FROM AUTHOR]

Objective　To decrease cancer mortality by implementing cancer screening programs, rigorous quality control measures that utilize standardized indicators are imperative. In Japan, although each municipality performing cancer screening programs implements quality control for their programs using the checklist authorized by the Ministry of Health, Labour and Welfare, compliance with all the items listed is not possible because calculating sensitivity and specificity using cancer registry data is difficult under these circumstances. This report elucidates the methodology for calculating indicators, including sensitivity and specificity, by delineating the parameters of false-negative cases within population-based cancer screening programs in Japan. Furthermore, the inherent challenges associated with ensuring the quality control of cancer screening procedures are expounded upon in this report.Method　Data from the Prefectural Cancer Registry of Japan and cancer screening records compiled by municipalities were used to differentiate true-positive, true-negative, false-positive, and false-negative cases based on the combination of screening test outcomes and subsequent cancer incidence.Results　A false-negative case was defined as an examinee who received a cancer diagnosis within one year after undergoing the screening test, notwithstanding the negative judgment of the cancer screening decision. The duration for judgment of true-positive, true-negative, and false-negative cases was also extended to one year. Cancer identification after cancer screening was ascertained using data from the Prefectural Cancer Registry, ensuring uniform categorization of the four cases. Subsequently, sensitivity and specificity values were calculated for municipalities conducting cancer screening programs.Conclusion　Sensitivity and specificity are indispensable metrics for the inherent quality control of cancer screening because these parameters directly assess the efficacy of screening tests. The anticipated increase in the number of municipalities engaged in comprehensive quality control of cancer screening in Japan is poised to enhance the efficiency of cancer control policies. This augmentation will be accomplished through the meticulous utilization of the sensitivity and specificity values elucidated in the present report. The forthcoming challenges involve the proliferation of medical institutes reporting their adherence to the checklist stipulated by the National Cancer Center of Japan and the widespread dissemination of fundamental knowledge pertaining to cancer screening.

Aims/introduction: The time course of chronic kidney disease in young-onset type 2 diabetes mellitus remains unclear. We compared the trajectories of proteinuria and estimated glomerular filtration rate (eGFR) decline between young-onset (aged ≤40 years) and late-onset (aged >40 years) type 2 diabetes mellitus in a Japanese multicenter cohort., Materials and Methods: Participants without diabetic kidney disease were divided into two groups according to age at diagnosis: young- and late-onset. The primary endpoint was eGFR <60 mL/min/1.73 m 2 , proteinuria or both. Multivariable Cox proportional hazards were calculated to estimate incidence., Results: Among 626 participants with type 2 diabetes mellitus, 78 (12.4%) had young-onset and 548 (87.6%) had late-onset diabetes. The incidence of eGFR <60 mL/min/1.73 m 2 was lower (16.7% vs 33.5%, P = 0.003), but that of proteinuria was higher (46.2% vs 28.9%, P = 0.002) in the young-onset type 2 diabetes mellitus group. The Kaplan-Meyer curve showed that young-onset type 2 diabetes mellitus was associated with a decreased hazard ratio (HR) for eGFR <60 mL/min/1.73 m 2 and an increased HR for proteinuria compared with late-onset type 2 diabetes mellitus. In the multivariate Cox analysis, young-onset type 2 diabetes mellitus increased the HR (95% confidence interval) of proteinuria (1.53, 95% confidence interval 1.03-2.26), but did not change the eGFR <60 mL/min/1.73 m 2 HR., Conclusions: Young-onset type 2 diabetes mellitus has a lower HR of eGFR <60 mL/min/1.73 m 2 and an increased HR of proteinuria compared with late-onset type 2 diabetes mellitus, indicating that young-onset type 2 diabetes mellitus has a different time course for the development of proteinuria and subsequent eGFR decline., (© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background/Objectives: Refeeding syndrome (RFS) is recognized as a potentially fatal metabolic disturbance, particularly concerning for non-critically ill patients who do not receive frequent electrolyte assessments. Assessing the risk of developing RFS and implementing preventive strategies is essential in these cases. We investigated the proportion of risk and its association with prognosis in a high-dependency unit (HDU). Method: This observational study was conducted in a tertiary care hospital's HDU in Japan. We consecutively enrolled all patients who had been admitted urgently to the HDU and hospitalized for three days or more. We evaluated the National Institute for Health and Clinical Excellence (NICE) RFS risk factors at admission and classified patients into four groups based on the modified NICE criteria. The primary outcome was 30-day in-hospital mortality. The secondary outcome was a composite of 30-day in-hospital mortality and transfer to the intensive care unit, or discharge to locations other than home. Using logistic regression, we assessed the association between the four risk groups and outcomes, using the no-risk group as a reference. Results: A total of 955 patients were analyzed, of which 33.1%, 26.7%, 37.8%, and 2.4% were classified into the no-risk, low-risk, high-risk, and very high-risk groups, respectively. The 30-day in-hospital mortality was 4.4%, 5.5%, 5.0%, and 21.7%, respectively (Log-rank trend test: p = 0.047). In multivariable logistic regression, adjusting for sepsis, comorbidities, and age, only the very high-risk group was associated with 30-day in-hospital mortality (odds ratio: 5.54, 95% confidence interval: 1.73-17.79) A similar association was observed for the secondary outcomes. Conclusions: For patients admitted urgently to the HDU, there may be an opportunity to improve outcomes for very high-risk patients through preventive strategies.

Introduction: The introduction of new drugs often leads to aggressive promotion and potential financial conflicts of interest, which may bias treatment decisions and potentially harm patients. The breast cancer therapeutics market is rapidly evolving globally, and Japan is no exception. This study aimed to analyze trends in pharmaceutical payments to breast cancer specialists in Japan from 2016 to 2019, focusing on company-level data, relationships with new drug introductions, and individual specialist payment patterns., Methods: This retrospective study examined financial relationships between pharmaceutical companies and breast cancer specialists in Japan from 2016 to 2019. The analysis focused on certified specialists as of May 2023 and used payment data from 93 pharmaceutical companies for activities such as lecturing, writing, and consulting. First, a company-level analysis examined total payments, categories, and trends for all companies and the top 10 individually; second, a specialist-level analysis looked at payment amounts amount and counts. The Gini index was employed to assess the concentration of payments among specialists., Results: Total payments reached USD 13,329,911, growing at 10.1% annually, with 81.4% allocated to lecturing engagements. The top 10 companies, led by Chugai Pharmaceutical, Eisai, and AstraZeneca, accounted for 89.5% of all payments. Companies like Pfizer Japan and Eli Lilly Japan saw notable increases following the introduction of new drugs such as palbociclib and abemaciclib. Payment distribution was highly skewed, with an average of $7,692 per specialist but a median of only $2,884. A Gini index of 0.994 further confirmed that a small group of specialists received a disproportionately large share of the payments., Conclusion: From 2016 to 2019, pharmaceutical payments to Japanese breast cancer specialists increased significantly, coinciding with new drug introductions. The concentration of payments among a select group of specialists raises concerns about potential influences on clinical decision-making and guideline recommendations., Competing Interests: Dr. Ozaki received personal fees from Medical Network Systems, Kyowa Kirin Inc., Becton, Dickinson and Company, Pfizer Inc, and Taiho Pharmaceutical Co., Ltd., outside the scope of the submitted work. Hiroaki Saito received personal fees from Taiho Pharmaceutical Co. Ltd. outside the scope of the submitted work. Tetsuya Tanimoto received personal fees from Medical Network Systems and Bionics Co. Ltd., outside the scope of the submitted work. All remaining authors have nothing to disclose. Regarding non-financial conflicts of interest among the study authors, Dr. Ozaki is engaged in ongoing research examining financial and non-financial conflicts of interest among healthcare professionals and pharmaceutical companies in Japan and other countries., (Copyright: © 2024 Kaneda et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Helicobacter pylori (HP) infection, a risk factor for gastric cancer, is prevalent in Japan. Consequently, some municipalities across Japan are implementing HP screening and treatment programs for adolescents. However, little is known about parents' attitudes and awareness regarding HP screening for their children. This study aimed to elucidate parental perspectives on HP screening for their children and identify the factors influencing these attitudes., Methods: This study focused on the parents of first-year junior high school students in Yokosuka City, Kanagawa Prefecture, where an HP screening and treatment program had been implemented for adolescents. The survey questionnaire was distributed among parents in all 23 public junior high schools in Yokosuka City., Results: Among the 618 respondents, 86.4% supported HP screening for their children. Regression analysis identified sufficient knowledge about HP (adjusted odds ratio (aOR) = 5.80; 95% confidence interval (CI), 2.10-16.03) and being in their 40s (aOR = 2.25; 95% CI, 1.35-3.77) as significant factors influencing supportive attitudes. For parents favoring the screening, common reasons included perceiving it as a promising opportunity (53.2%) and considering the test necessary (44.0%). In contrast, those who opposed screening frequently cited it as unnecessary (66.7%) or believed that their children did not have HP., Conclusions: A significant proportion of parents in Yokosuka City, Japan, demonstrated a good understanding of HP and expressed a high level of interest in HP screening for their children. Further investigation of parents' attitudes is essential for the effective implementation of adolescent HP screening programs., (© 2024. The Author(s).)

Background: Prevotella bacteria are associated with inherent diseases of the oral cavity, such as periodontal disease, and systemic diseases. Oral frailty (OF) has been associated with nursing necessity and death. However, the relationship between OF and oral microbiota has not been fully clarified., Objective: This cross-sectional study investigated the association between OF and Prevotella percentage in the oral microbiota of community-dwelling older adults., Methods: Oral bacteria species from saliva were identified in 208 community-dwelling older individuals aged ≥60 years in Japan. The proportion of Prevotella in the oral microbiota was classified into three tertile groups, and its relationship with each test item for OF (number of remaining teeth, masticatory performance, oral diadochokinesis, tongue pressure, difficulties eating tough foods, difficulties swallowing tea or soup, number of applicable OF judgement items, and existence of OF) was examined using ordinal logistic regression analysis., Results: The Prevotella proportions were classified into lower, middle and upper groups, comprising 70, 69 and 69 participants, respectively. The three groups showed a significant relationship between the number of remaining teeth (odds ratio [OR]: 0.946, 95% confidence interval [CI]: 0.915-0.977), masticatory performance (OR: 0.897, 95% CI: 0.844-0.953), number of applicable OF judgement items (OR: 1.477, 95% CI: 1.14-1.915), and existence of OF (OR: 4.194, 95% CI: 1.519-11.576)., Conclusion: The proportion of Prevotella in oral microbiota was high in individuals with OF. Among the older adults, the type of oral microbiota and systemic diseases may be related to the examination and management of oral function decline., (© 2024 John Wiley & Sons Ltd.)

Aims: This study aimed to investigate the prevalence, clinical characteristics, and prognostic value of bendopnea in older patients hospitalized for heart failure., Methods and Results: This post hoc analysis was performed using two prospective, multicentre, observational studies: the FRAGILE-HF (main cohort) and SONIC-HF (validation cohort) cohorts. Patients were categorized based on the presence of bendopnea, which was evaluated before discharge. The primary endpoint was 2-year all-cause mortality after discharge. Among the 1243 patients (median age, 81 years; 57.2% male) in the FRAGILE-HF cohort and 225 (median age, 79 years; 58.2% men) in the SONIC-HF cohort, bendopnea was observed in 31 (2.5%) and 10 (4.4%) patients, respectively. Over a 2-year follow-up period, all-cause death occurred in 20.8 and 21.9% of the patients in the FRAGILE-HF and SONIC-HF cohorts, respectively. Kaplan-Meier survival curves demonstrated significantly higher mortality rates in patients with bendopnea than in those without bendopnea in the FRAGILE-HF (log-rank P = 0.006) and SONIC-HF cohorts (log-rank P = 0.014). Cox proportional hazard analysis identified bendopnea as an independent prognostic factor for all-cause mortality in both the FRAGILE-HF [hazard ratio (HR) 2.11, 95% confidence interval (CI) 1.18-3.78, P = 0.012] and SONIC-HF cohorts (HR 4.20, 95% CI 1.63-10.79, P = 0.003), even after adjusting for conventional risk factors., Conclusion: Bendopnea was observed in a relatively small proportion of older patients hospitalized for heart failure before discharge. However, its presence was significantly associated with an increased risk of all-cause mortality., Competing Interests: Conflict of interest: Y.M. received an honorarium from Otsuka Pharmaceutical Co., Novartis Pharma K.K., Bayer Inc., and AstraZeneca and research grants from Pfizer Japan Inc., Otsuka Pharmaceutical Co., EN Otsuka Pharmaceutical Co., Ltd, and Nippon Boehringer Ingelheim Co., Ltd. T.K. (Takatoshi Kasai) was affiliated with a department sponsored by Philips Respironics, ResMed, Teijin Home Healthcare, and Fukuda Denshi. N.K. is affiliated with a department funded by Paramount Bed Ltd., and receives research grants from EchoNous Inc. and AMI Inc. and honorarium from Novartis Pharama, Otsuka Pharma, Boehringer Ingelheim, and Elli Lilly. K.K. received funding outside the submitted work from Eiken Chemical Co., Ltd and SoftBank Corp., Ltd. The other authors have no conflicts of interest to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Patients undergoing hemodialysis are particularly vulnerable to severe outcomes of SARS-CoV-2 infection, with mortality rates higher than that of the general population. Vaccination reduces the risk of adverse outcomes, with booster doses being particularly beneficial. However, limited data are available on the effectiveness of subsequent vaccinations or their effect on increasing antibody levels. This single-center study aimed to investigate changes in SARS-CoV-2 IgG antibody titers following the fourth vaccination among 28 patients undergoing hemodialysis. Blood tests were conducted at various intervals post-vaccination, with a focus on identifying factors associated with antibody levels. The IgG antibody levels rapidly increased by Day 7 post-vaccination, with a median time to peak of 11 days. Antibody titers tended to be higher in male patients than in female patients. This study sheds light on the immune response to the fourth vaccination in patients undergoing hemodialysis. As this study included a small sample size, with a short observation period, further research is warranted to comprehensively understand the effectiveness of vaccination and the benefits of additional doses of vaccine., Competing Interests: Author YK was employed by company Medical and Biological Laboratories Co., Ltd. MT received a grant from Pfizer Health Research Foundation for research not associated with this work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Watanabe, Sawano, Saito, Ozaki, Wakui, Zhao, Yamamoto, Kobashi, Kawamura, Sugiyama, Nakayama, Kaneko, Shimmura and Tsubokura.)

Malnutrition is reportedly associated with adverse clinical outcomes in various populations. However, associations between nutritional status and adverse outcomes in patients with hypertension have not been sufficiently elucidated. We therefore aimed to investigate the impact of nutritional status as evaluated by the Geriatric Nutritional Risk Index (GNRI) on adverse outcomes in patients with hypertension. We conducted a retrospective cohort study of 1588 hypertensive patients enrolled in the Fukushima Cohort Study. Participants were categorized into tertiles (T1-T3) according to GNRI at baseline. The primary endpoint of the present study was a kidney event, defined as a combination of a 50% decline in eGFR from baseline and end-stage kidney disease requiring kidney replacement therapy. Associations between GNRI and kidney events were assessed using Kaplan-Meier curves and multivariate Cox regression analyses. Median age was 64 years, 55% were men, median eGFR was 63.1 mL/min/1.73 m 2 , and median GNRI was 101.3. The lower GNRI group (T1) showed an increased incidence of kidney events in the Kaplan-Meier curve analysis. Compared to the highest GNRI group (T3), lower GNRI carried a higher risk of kidney events for both T2 (hazard ratio [HR] 1.38, 95% confidence interval [CI] 0.71-2.68) and T1 (HR 3.59, 95%CI 1.96-6.63). Similar relationships were observed for risks of all-cause death and cardiovascular events. Lower GNRI was associated with kidney events, all-cause death, and cardiovascular events in patients with hypertension. Nutritional status as evaluated by GNRI could offer a simple and useful predictor of adverse outcomes in this population., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Introduction: Vaccination has been implemented as a useful measure to combat the COVID-19 pandemic. However, there is a tendency for individuals to avoid vaccination due to the possibility of adverse events, making it important to investigate the relationship between COVID-19 vaccines and their adverse events. This study explored longitudinal adverse event patterns and factors that influence adverse events following the second to fourth doses of the COVID-19 vaccine through a latent class analysis., Methods: Participants were recruited from the Fukushima Prefecture and included individuals who had completed four doses of the COVID-19 mRNA vaccine. This study utilized data from questionnaire surveys and blood collection conducted between September 2021 and November 2022. In the questionnaire, factors such as sex, age, medical history, medication, type of vaccine administered, and adverse events following vaccination were recorded. Additionally, in the blood data, serological tests [IgG(S)] and cellular immune responses (T-spot) were measured. Descriptive statistics, latent class analysis, multivariable logistic regression, and multiple regression analyses were performed to identify the longitudinal adverse event patterns and influencing factors. By analyzing adverse events over time, we identified two distinct groups: those less prone to experiencing adverse events (Group 1) and those more susceptible (Group 2) to latent class analysis., Results: A total of 1,175 participants were included after excluding those without any adverse events. The median age of the participants in Group 1 was 70 years, and in Group 2 it was 51 years. The proportion of female participants was 298 in Group 1 and 353 in Group 2. Patients in Group 2 were significantly younger ( p  < 0.001) and more likely to be female ( p  < 0.001) than those in Group 1. Furthermore, the median IgG(S) value after the fourth vaccination was 3,233 AU/mL in Group 1 and 4,059.39 AU/mL in Group 2. The median T-spot value was 15.4 in Group 1 and 28.5 in Group 2. Group 2 showed significantly higher IgG(S) and T-spot values after the fourth vaccination ( p  < 0.001)., Discussion: Our findings suggest that factors other than age, particularly sex and a history of allergies, significantly influence the likelihood of experiencing adverse events. Groups categorized by latent class analysis for longitudinal adverse events are expected to be valuable for optimizing vaccination strategies and formulating public health measures., Competing Interests: YKa was hired by Medical & Biological Laboratories Co. (MBL, Tokyo, Japan). MBL imported the test materials used in the study. YKa participated in the testing process; however, he did not engage in the research design and analysis. YKo and MTs received a grant from the Pfizer Health Research Foundation for research that was not associated with this study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Yamamoto, Kobashi, Kawamura, Nishikawa, Saito, Oguro, Zhao, Takita, Sawano, Ozaki, Abe, Ito, Kaneko, Nakayama, Wakui, Kodama and Tsubokura.)

Background: The fast-growing migrant population in Japan and globally poses challenges in mental healthcare, yet research addressing migrants' mental health treatment engagement remains limited., Objective: This study examined language proficiency, demographic and clinical characteristics as predictors of early treatment discontinuation among migrants., Methods: Electronic health record data from 196 adult migrants, identified from 14 511 patients who received mental health outpatient treatment during 2016 and 2019 at three central hospitals in the Tokyo-Yokohama metropolitan region of Japan, were used. We conducted multivariable regression models to identify predictors of early discontinuation within 3 months., Findings: The study cohort (65% women, age range: 18-90 years, from 29 countries or regions) included 23% non-Japanese speakers. Japanese and non-Japanese speakers had similar discontinuation rates (26% vs 22%). Multivariable models revealed younger age (OR=0.97; 95% CI: 0.95, 0.99; p=0.016) and those with a primary diagnosis other than a schizophrenia spectrum disorder (OR=3.99; 95% CI: 1.36, 11.77; p=0.012) or a neurotic, stress-related and somatoform disorder (OR=2.79; 95% CI: 1.14, 6.84; p=0.025) had higher odds of early discontinuation. These effects were more pronounced among the Japanese speakers with significant language-by-age and language-by-diagnoses interactions., Conclusion: Younger age and having a primary diagnosis other than a schizophrenia spectrum disorder or a neurotic, stress-related and somatoform disorder increased vulnerability for discontinuing mental health treatment early in Japanese-speaking migrants but not for migrants with limited Japanese proficiency., Clinical Implications: Understanding language needs within a context of mental health treatment should go beyond assumed or observed fluency. Unmet language needs might increase vulnerability for treatment disengagement among migrants. Targeted clinical efforts are crucial for enhancing early treatment engagement and informing health practices in Japan and countries with growing migrant populations., Competing Interests: Competing interests: Tsoh, Takubo, Fukui, Uchino, Katagiri, and Nemoto belong to the Department of Psychiatry and Implementation Science, Toho University Faculty of Medicine, which is funded by Nippon Life Insurance Company. All authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. Published by BMJ.)

Objective: Evacuation, owing to a disaster, impacts various aspects of an individual's life, including health status. This study aimed to determine the prevalence of obesity among residents of Katsurao Village, Fukushima Prefecture, after the evacuation order due to the Fukushima nuclear disaster in 2011 was lifted in 2016 and to compare the prevalence of obesity by place of residence (inside or outside the village)., Methods: The number of examinees, sex, age, place of residence, body mass index (BMI), exercise habits, smoking habits, drinking habits, and dietary status were extracted from the results of health checkups since 2016. We compared the BMI of the indigenes of Katsurao Village by place of residence (inside or outside the village) over time., Results: Although 7 years have passed since 2016, ~70% of the registered residents of Katsurao Village still live outside the village. The obesity rates have consistently been higher among people living outside the village compared to those inside, and the place of residence was the only factor significantly associated with obesity., Conclusion: The findings of this study suggest early intervention is necessary to prevent health risks associated with disaster evacuation if the evacuation period is prolonged., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ito, Takita, Moriyama, Amir, Furuyama, Saito, Abe, Yamamoto, Sato, Zhao and Tsubokura.)

Regulatory authorities must balance ensuring evidence of efficacy and safety of new drugs. Various regulatory pathways, such as the accelerated approval program in the United States (US), allow authorities to quickly approve drugs for severely ill patients by granting market authorization based on surrogate end points and pending confirmatory trials. In this cross-sectional study, we considered 23 indications of cancer drugs that received accelerated approval by the US Food and Drug Administration (FDA) but were subsequently withdrawn as of April 2023. Our investigation extended to assessing the regulatory status of these accelerated approvals in the European Union (EU) and Japan, examining relevant regulatory documents and identifying factors contributing to the withdrawal in the United States. Comparing regions, we found that for 52% (12/23) and 30% (7/23) of withdrawn accelerated approvals in the United States, sponsors had also sought marketing authorization from the European Medicines Agency (EMA) and Japan's Pharmaceuticals and Medical Devices Agency (PMDA), respectively. As of the April 30, 2023 study cutoff date, 83% (10/12) of drug-indication pairs remained approved by the EMA, while the PMDA retained 100% (7/7). For these indications, the time from FDA withdrawal until the study cutoff date ranged from 0.23 years to 11.45 years for EMA approvals (median: 1.28 years) and 1.10 years to 11.45 years for PMDA approvals (median: 3.22 years). These findings highlight substantial regulatory discrepancies concerning cancer drugs with unconfirmed benefits. Addressing these discrepancies may involve requiring pharmaceutical companies to confirm clinical benefits using more robust end points and fostering international harmonization in regulators' assessment., (© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

It is crucial to anticipate nuclear emergency scenarios and implement effective measures. Japan's climate and topography make it vulnerable to natural disasters; thus, it is necessary to address compounding and cascading disaster scenarios involving the simultaneous occurrence of natural and nuclear disasters. On 1 January 2024, an earthquake hit the Noto region of Ishikawa Prefecture, resulting in damage to the area around the Shika Nuclear Power Plant, located 90 km from the epicenter. This earthquake revealed that, in the event of a complex disaster, it is possible that residents living within 30 km of the Shika Nuclear Power Plant will be completely unprepared for a nuclear disaster. In the event of a complex disaster, it is crucial to implement appropriate countermeasures while balancing responses to both nuclear and natural disasters and optimizing radiation disaster prevention measures., (Creative Commons Attribution license.)

Background: Social factors encompass a broad spectrum of nonmedical factors, including objective (social isolation [SI]) and perceived (loneliness) conditions. Although social factors have attracted considerable research attention, information regarding their impact on patients with heart failure is scarce. We aimed to investigate the prognostic impact of objective SI and loneliness in older patients with heart failure., Methods and Results: This study was conducted using the FRAGILE-HF (Prevalence and Prognostic Value of Physical and Social Frailty in Geriatric Patients Hospitalized for Heart Failure; derivation cohort) and Kitasato cohorts (validation cohort), which included hospitalized patients with heart failure aged ≥65 years. Objective SI and loneliness were defined using the Japanese version of Lubben Social Network Scale-6 and diagnosed when the total score for objective and perceived questions on the Lubben Social Network Scale-6 was below the median in the FRAGILE-HF. The primary outcome was 1-year death. Overall, 1232 and 405 patients in the FRAGILE-HF and Kitasato cohorts, respectively, were analyzed. Objective SI and loneliness were observed in 57.8% and 51.4% of patients in the FRAGILE-HF and 55.4% and 46.2% of those in the Kitasato cohort, respectively. During the 1-year follow-up, 149 and 31 patients died in the FRAGILE-HF and Kitasato cohorts, respectively. Cox proportional hazard analysis revealed that objective SI, but not loneliness, was significantly associated with 1-year death after adjustment for conventional risk factors in the FRAGILE-HF. These findings were consistent with the validation cohort., Conclusions: Objective SI assessed using the Lubben Social Network Scale-6 may be a prognostic indicator in older patients with heart failure. Given the lack of established SI assessment methods in this population, further research is required to refine such methods.

Background: Although frailty is strongly associated with mortality in patients with heart failure (HF), the risk of which specific cause of death is associated with being complicated with frailty is unclear. We aimed to clarify the association between multidomain frailty and the causes of death in elderly patients hospitalized with HF., Methods: We analyzed data from the FRAGILE-HF cohort, where patients aged 65 years and older, hospitalized with HF, were prospectively registered between 2016 and 2018 in 15 Japanese hospitals before discharge and followed up for 2 years. All patients were assessed for physical, social, and cognitive dysfunction, and categorized into 3 groups based on their number of frailty domains (FDs, 0-1, 2, and 3). Kaplan-Meier survival analysis was used to evaluate the association between the number of FDs and all-cause mortality, whereas Fine-Gray competing risk regression analysis was used for assessing the impact on cause-specific mortality., Results: We analyzed 1181 patients with HF (81 years old in median, 57.4% were male), 530 (44.9%), 437 (37.0%), and 214 (18.1%) of whom were categorized into the FD 0 to 1, FD 2, and FD 3 groups, respectively. During the 2-year follow-up, 240 deaths were observed (99 HF deaths, 34 cardiovascular deaths, and 107 noncardiovascular deaths), and an increase in the number of FD was significantly associated with mortality (Log-rank: P <0.001). The Fine-Gray competing risk analysis adjusted for age and sex showed that FDs 2 (subdistribution hazard ratio, 1.77 [95% CI, 1.11-2.81]) and 3 (2.78, [95% CI, 1.69-4.59]) groups were associated with higher incidence of noncardiovascular death but not with HF and other cardiovascular deaths., Conclusions: Although multidomain frailty is strongly associated with mortality in older patients with HF, it is mostly attributable to noncardiovascular death and not cardiovascular death, including HF death., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: UMIN000023929., Competing Interests: Disclosures Dr Matsue received an honorarium from Otsuka Pharmaceutical Co., Novartis Pharma K.K., Bayer Inc., and AstraZeneca and research grants from Pfizer Japan, Inc, Otsuka Pharmaceutical Co, EN Otsuka Pharmaceutical Co., Ltd., and Nippon Boehringer Ingelheim Co., Ltd. Nobuyuki Kagiyama received grants from Philips, Asahi KASEI Corporation, Toho Holdings Co. Ltd, Inter Reha Co. Ltd, EchoNous, Inc., and AMI, Inc. Outside of the submitted work. Dr Kamiya received grants and honorarium from Eiken Chemical Co., Ltd. and a research grant from SoftBnk Corp. Dr Kasai is affiliated with a department sponsored by Philips Respironics, ResMed, Teijin Home Healthcare, and Fukuda Denshi. The other authors declare no conflicts.

Purpose To evaluate the impact of an artificial intelligence (AI) assistant for lung cancer screening on multinational clinical workflows. Materials and Methods An AI assistant for lung cancer screening was evaluated on two retrospective randomized multireader multicase studies where 627 (141 cancer-positive cases) low-dose chest CT cases were each read twice (with and without AI assistance) by experienced thoracic radiologists (six U.S.-based or six Japan-based radiologists), resulting in a total of 7524 interpretations. Positive cases were defined as those within 2 years before a pathology-confirmed lung cancer diagnosis. Negative cases were defined as those without any subsequent cancer diagnosis for at least 2 years and were enriched for a spectrum of diverse nodules. The studies measured the readers' level of suspicion (on a 0-100 scale), country-specific screening system scoring categories, and management recommendations. Evaluation metrics included the area under the receiver operating characteristic curve (AUC) for level of suspicion and sensitivity and specificity of recall recommendations. Results With AI assistance, the radiologists' AUC increased by 0.023 (0.70 to 0.72; P = .02) for the U.S. study and by 0.023 (0.93 to 0.96; P = .18) for the Japan study. Scoring system specificity for actionable findings increased 5.5% (57% to 63%; P < .001) for the U.S. study and 6.7% (23% to 30%; P < .001) for the Japan study. There was no evidence of a difference in corresponding sensitivity between unassisted and AI-assisted reads for the U.S. (67.3% to 67.5%; P = .88) and Japan (98% to 100%; P > .99) studies. Corresponding stand-alone AI AUC system performance was 0.75 (95% CI: 0.70, 0.81) and 0.88 (95% CI: 0.78, 0.97) for the U.S.- and Japan-based datasets, respectively. Conclusion The concurrent AI interface improved lung cancer screening specificity in both U.S.- and Japan-based reader studies, meriting further study in additional international screening environments. Keywords: Assistive Artificial Intelligence, Lung Cancer Screening, CT Supplemental material is available for this article. Published under a CC BY 4.0 license.

Objective: As first-line treatment for stage IV or recurrent non-small cell lung cancer, combination immunotherapy with nivolumab and ipilimumab, with or without chemotherapy, had demonstrated survival benefits over chemotherapy; however, data on Japanese patients are limited., Methods: LIGHT-NING was a multicenter, observational study and retrospectively collected data. In this interim analysis, we analyzed patients who received combination immunotherapy between 27 November 2020 and 31 August 2021 for the treatment status, safety objectives (treatment-related adverse events and immune-related adverse events incidences), and effectiveness objectives (objective response rate and progression-free survival) to determine the characteristics and early safety information., Results: We analyzed 353 patients, with a median follow-up of 7.1 (interquartile range, 5.0-9.7) months. Overall, 60.1 and 39.9% received nivolumab plus ipilimumab with and without chemotherapy, respectively. In these cohorts, the median age was 67 and 72 years; 10.8 and 35.5% were aged ≥75 years; 80.2 and 79.4% were male; 5.2 and 13.5% had a performance score ≥ 2; 32.1 and 27.0% developed grade 3-4 immune-related adverse events; treatment-related deaths were observed in 6 (2.8%) and 5 (3.5%) patients, respectively. Grade 3-4 immune-related adverse event incidence was the highest within the first month of treatment in both cohorts, although the immune-related adverse event risk persisted throughout. No new safety signals were observed at this interim analysis. The median progression-free survival was 6.0 (95% confidence interval, 5.2-7.6) and 5.8 (4.3-7.0) months in nivolumab plus ipilimumab with and without chemotherapy cohorts, respectively., Conclusions: LIGHT-NING offers valuable insights into combination immunotherapy for untreated patients with stage IV or recurrent non-small cell lung cancer in Japanese real-world settings., (© The Author(s) 2024. Published by Oxford University Press.)

Horsehair worms (Nematomorpha: Gordioidea) are endoparasites of terrestrial arthropods, of which two species, Chordodes japonensis and C. formosanus, may have been historically confused due to their morphological similarity. In this study, we conducted field surveys and laboratory parasite inoculation experiments to clarify the characteristics and differences in host range and specificity between the two species. The field surveys revealed that the host ranges of the two species are markedly different. C. formosanus parasitized diverse mantids, while C. japonensis infected only species in the genus Tenodera, as predicted in previous studies. However, the two species had one mantid host, T. angustipennis in common. Parasite inoculation experiments using three species of mantids, revealed parasitism in each of the host-parasite combinations same as in the field study. These results suggest that the observed differences in host patterns are due to physiological factors between the host and parasite. Furthermore, cross-testing conducted on the shared host T. angustipennis showed that the two species coexisted within the same host in some cases, suggesting that the competitive exclusivity of the two species is low. This study also presents a tentative list of host ranges for the two species, comparing and integrating information from this and previous studies. However, the possibility remains that the host ranges of both species may be more diverse., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier B.V.)

Introduction: It remains unclear whether increased perirenal fat (PRF) accumulation is equally related to renal involvement in patients with and without diabetes mellitus (DM). We evaluated the association between PRF volume (PRFV) and low glomerular filtration rate (GFR) and proteinuria in people with or without type 2 diabetes mellitus (T2DM)., Research Design and Methods: We performed a cross-sectional analysis of 473 individuals without T2DM (non-DM, n=202) and with T2DM (DM, n=271). PRFV (cm 3 ), obtained from non-contrast CT, was indexed as PRF index (PRFV/body surface area, cm 3 /m 2 ). Multivariate-adjusted models were used to determine the ORs of PRFV and PRFV index for detecting estimated GFR (eGFR) decrease of <60 mL/min/1.73 m 2 proteinuria onset, or both., Results: Although body mass index (BMI), visceral fat area, and waist circumference were comparable between the non-DM and DM groups, kidney volume, PRFV, and PRFV index were higher in individuals with T2DM than in those without T2DM. In the multivariate analysis, after adjusting for age, sex, BMI, hypertension, smoking history, and visceral fat area ≥100 cm 2 , the cut-off values of PRFV index were associated with an eGFR<60 in individuals with DM (OR 6.01, 95% CI 2.20 to 16.4, p<0.001) but not in those without DM., Conclusions: PRFV is associated with low eGFR in patients with T2DM but not in those without T2DM. This suggests that PRF accumulation is more closely related to the onset and progression of diabetic kidney disease (DKD) than non-DKD. Clarifying the mechanisms through which PRF influences DKD development could pave the way for novel prevention and treatment strategies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Despite being one of the world's largest pharmaceutical markets, interactions between Japanese physicians and pharmaceutical companies often remain opaque. Importantly, potential conflicts of interest associated with these interactions can compromise patient care and increase costs. We conducted an online survey of Japanese physicians to elucidate perspectives on pharmaceutical company promotional activities and how these influence physician prescribing patterns. Anticipating that physicians might downplay their reliance on, or the value of, pharmaceutical company-provided information, the survey incorporated a direct questioning method and an unmatched count technique (UCT) to identify hidden perceptions on factors likely to influence prescribing. Overall, 1080 eligible physicians participated. Of these, 105 (9.7%) self-identified as hospital directors or managers. Surprisingly, nearly twice as many participants responding to direct questioning (18.9%) versus those responding to the UCT (10.1%) asserted that information provided by pharmaceutical companies was important when prescribing medicine. Hospital directors or managers (adjusted odds ratio [adjOR] 2.56, 95% confidence interval [95% CI]: 1.00-6.54, reference = physician without title) and frequent interactions with pharmaceutical sales representatives (adjOR 5.96, 95% CI: 1.88-18.9, reference = rare interaction) significantly valued the information from sales representatives and sponsored lectures when considering prescribing decisions. Additionally, 77.1% of respondents believed that sales representatives provide fair, neutral, or relatively honest and unbiased information about their products. Few Japanese physicians acknowledged the influence of industry-provided information on prescribing patterns. Our study uniquely applies two distinct question formats, providing a novel approach to understanding the depth of physician-industry relationships and the effectiveness of various survey methodologies., (© 2024 John Wiley & Sons Ltd.)

The medical situation during disasters often differs from that at usual times. Disasters can lead to significant mortality that can be difficult to monitor. The types of disaster-related deaths are largely unknown. In this study, we conducted a survey to categorize the disaster-related deaths caused by a radiation disaster. A total of 520 people living in Minamisoma City, Fukushima Prefecture, at the time of the Fukushima Daiichi Nuclear Power Plant accident, who were certified to have died due to disaster-related causes were surveyed. We divided the participants into those who were at home at the time of the earthquake and those who were in hospitals or facilities when the disaster struck and conducted a hierarchical cluster analysis of the two groups. Disaster-related deaths could be divided into seven groups for those who were at home at the time of the disaster and five groups for those who were in hospitals or facilities at the time of the disaster. Each group showed different characteristics, such as "the group with disabilities," "the group receiving care," and "the group with depression," and it became evident that not only uniform post-disaster support, but support tailored to the characteristics of each group is necessary., (© 2024. The Author(s).)

Objectives: Despite the recent increase in infertility and perinatal complications, preconception care is not commonly available in Japan. Working women are considered to have the greatest need for preconception care, as increasingly they marry and have children later in life. This study aimed to assess the feasibility and effectiveness of preconception check-ups in the workplace., Methods: We provided 51 female employees aged 18-39 years with free preconception check-ups, including additional blood tests and an online medical questionnaire, during mandatory health check-ups at their workplace. A doctor provided online counseling based on the check-up results. We assessed fertility knowledge using the Cardiff Fertility Knowledge Scale (CFKS-J) and childbearing desire pre- and postintervention., Results: Preconception check-ups revealed various potential risk factors for future pregnancies, including underweight (12%), obesity (20%), Chlamydia trachomatis IgG antibody positivity (22%), low rubella IgG antibody levels (47%), iron deficiency (12%), and 25-hydroxyvitamin D levels <30 ng/mL (98%). Postintervention, the participants reported high satisfaction with the check-ups and significantly advanced their reproductive plans (P = .008). Furthermore, 95% of the participants indicated an intention to seek medical attention or make lifestyle changes. The postintervention CFKS-J score (mean [SD]) was higher than the preintervention score (71.7 [19.3] vs 63.0 [22.0]; P = .006)., Conclusions: We developed a preconception check-up package that can be integrated into workplace health examinations, complemented by tailored counseling. This novel check-up package is a feasible and effective approach for improving preconception health and fertility awareness., (© The Author(s) [2024]. Published by Oxford University Press on behalf of Journal of Occupational Health.)