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Comprehensive evidence about the burden of infectious diseases in the Western Pacific Region is scarce. We thus examined the disease burden of infectious diseases in Japan in terms of disability-adjusted life years (DALYs). We extracted national claims data from Japan's universal health insurance system to estimate the burden of disease for selected infections between 2015 and 2020 using DALYs. The mortality rate, disability duration and severity weight of each disease were estimated based on national data and literature reviews. Disease burden per 100,000 population was 1307.0 in 2015 and 972.1 in 2020 for bloodstream infections (BSI), 796.5 DALYs in 2015 and 498.9 DALYs in 2020 for pneumonia, 171.5 in 2015 and 149.4 in 2020 for meningitis and 11.6 in 2015 and 11.4 in 2020 for urinary tract infections (UTI). Only surgical site infections (SSI) showed a slightly increasing trend over the 5-year period, from 2.2 in 2015 to 2.8 in 2020. Our results showed that the disease burden of the five major infectious diseases was higher in Japan than in other countries. However, while the burden of SSI increased, the burden of pneumonia, meningitis, BSI and UTI gradually decreased year on year. The possible causes of the decreased morbidity should be examined in future work. [ABSTRACT FROM AUTHOR]

Aim: To examine the potential negative effects of the COVID‐19 pandemic on short‐term postoperative outcomes of emergency surgery for gastroduodenal perforation in Japan. Methods: A total of 7973 cases of gastroduodenal perforation from 2019 to 2021 were retrieved from the National Clinical Database (NCD), which includes >95% of surgical cases in Japan. Data were analyzed nationally and in subgroups for subjects in areas with high infection levels (HILs). Postoperative 30‐d mortality, surgical mortality, and complications (Clavien–Dindo (CD) grade ≥3) were examined. Months were considered to have significantly high or low mortality or complication rates, if the 95% confidence interval (CI) of the standardized mortality (morbidity) ratio (SMR) does not contain 1. Results: Nationally, data from 2019 vs 2020 and 2021 showed 30‐d mortality of 175 (6.7%) vs 398 (7.4%), surgical mortality of 250 (9.5%) vs 537 (10.1%), and complications (CD ≥3) of 558 (21.2%) vs 1163 (21.8%). Among these data, the only significantly high SMR was found for complications in July 2020 (1.36 [95% CI: 1.001–1.80]). In areas with HILs, data from 2019 vs 2020 and 2021 indicated 30‐d mortality of 91 (6.3%) vs 215 (7.3%), surgical mortality of 135 (9.4%) vs 294 (10.0%), and complications (CD ≥3) of 304 (21.1%) vs (23.1%). In these data, no month had a significantly high SMR. Conclusion: The COVID‐19 pandemic had few negative effects on outcomes after surgery for gastroduodenal perforation. These findings suggest that the emergency system for gastroduodenal perforation in Japan was generally maintained during the pandemic. [ABSTRACT FROM AUTHOR]

Background: In Japan, comprehensive cancer statistics are collected through cancer registries. However, data on urological cancers are rarely summarized or published in research papers. Methods: This retrospective study was performed using publicly available statistical data on urological cancers (prostate cancer [PCa], bladder cancer [BCa], and cancers of kidney and urinary tract [except urinary bladder]) in Japan, including a summary of the Ministry's mortality statistics, cancer incidence statistics from the Regional Cancer Registries through 2015, and the National Cancer Registry statistics from 2016. We examined the incidence and mortality rates of urological cancers stratified by age groups. Results: The number of new cases of PCa, BCa, and cancers of kidney and urinary tract (except urinary bladder) in 2019 was 94,748, 23,383, and 30,458, respectively, and the number of deaths in 2022 was 13,439, 9,598, and 9,795, respectively. The incidence and mortality rates of urological cancers have consistently increased. Since 2000, there has been a noteworthy increase in the mortality rate of urological cancers among individuals aged > 85 years. The incidence and mortality rates of BCa and cancers of kidney and urinary tract (except urinary bladder) were significantly higher in males than in females. Conclusions: Urological cancers in very elderly patients (> 85 years) will become increasingly important in the future. [ABSTRACT FROM AUTHOR]

Summary: Background and Aims: While filgotinib, an oral Janus kinase (JAK) 1 preferential inhibitor, is approved for moderately to severely active ulcerative colitis (UC), real‐world studies assessing its short‐ and long‐term efficacy and safety are limited. Methods: This is a multicenter, retrospective study of UC patients who started filgotinib between March 2022 and September 2023. The primary outcome was clinical remission, defined as a partial Mayo score ≤1 with a rectal bleeding score of 0, or Simple Clinical Colitis Activity Index (SCCAI) ≤2 with a blood‐in‐stool score of 0. Secondary outcomes included clinical response, corticosteroid‐free remission, and endoscopic improvement. Outcomes were assessed at 10, 26, and 58 weeks based on patients with available follow‐up. Adverse events were evaluated. Results: We identified 238 UC patients and 54% had prior exposure to biologics/JAK inhibitors. The median baseline partial Mayo score and SCCAI were 5 (IQR 3–6) and 4 (IQR 2–7). Clinical remission rates based on per‐protocol analysis at 10, 26, and 58 weeks were 47% (70/149), 55.8% (48/86), and 64.6% (31/48), respectively. At a median follow‐up of 28 weeks (IQR 10–54) with a discontinuation rate of 39%, the rates of clinical remission, clinical response, corticosteroid‐free remission, and endoscopic improvement were 39.9% (81/203), 54.7% (111/203), and 36.5% (74/203), and 43.5% (10/23), respectively. These rates were comparable between biologic/JAK inhibitor‐naïve and ‐experienced patients. While three patients (1.3%) developed herpes zoster infection, no cases of thrombosis or death were reported. Conclusions: Real‐world data demonstrate favourable clinical and safety outcomes of filgotinib for UC. [ABSTRACT FROM AUTHOR]

The age-standardized incidence of head trauma in 2016 was 369 per 100,000 people worldwide. The Western Pacific region, including Japan, had the highest incidence. This study aimed to extract ICD-10 code data for intracranial injury (S06) and external causes of morbidity and mortality (V01–Y89), analyze their characteristics and interrelationships, and contribute to these diseases' prevention, treatment, and prognosis. The number of deaths according to injury type and external cause type of intracranial injury published by the Japanese government was statistically analyzed using JoinPoint, and univariate distribution and multivariate correlation were conducted using JMP Software. From 1999–2021, there was a downward trend in the number of deaths because of intracranial injuries: mortality from intracranial injuries was higher among those aged ≥65 years. Conversely, mortality from intracranial injuries was lower among those aged ≤14 years. Among deaths from intracranial injury, mortality from diffuse brain injury and traumatic subdural hemorrhage was more common. Among deaths from external causes of intracranial injury, mortality from falls, transport accidents, and other unforeseen accidents was more common. Mortality because of intracranial injuries increased significantly during the 2011 Great East Japan Earthquake. For some age groups and sexes, there were significant inverse correlations of mortality with traumatic subdural hemorrhage and traumatic subarachnoid hemorrhage for transport accidents, intentional self-harm and assault, and diffuse brain injury and focal brain injury for falls. We believe that the data presented in this study will be useful for preventing and treating intracranial injuries and for developing administrative measures to reduce intracranial injuries. [ABSTRACT FROM AUTHOR]

Purpose: To clarify the influence of surgical volume on the mortality and morbidity of gastrointestinal perforation in children in Japan. Methods: We collected data on pediatric patients with gastrointestinal perforation between 2017 and 2019, from the National Clinical Database. The surgical volumes of various institutions were classified into three groups: low (average number of surgeries for gastrointestinal perforation/year < 1), medium (≥ 1, < 6), and high (≥ 6). The observed-to-expected (o/e) ratios of 30-day mortality and morbidity were calculated for each group using an existing risk model. Results: Among 1641 patients (median age, 0.0 years), the 30-day mortality and morbidity rates were 5.2% and 37.7%, respectively. The 30-day mortality rates in the low-, medium-, and high-volume institutions were 4.9%, 5.3%, and 5.1% (p = 0.94), and the 30-day morbidity rates in the three groups were 26.8%, 39.7%, and 37.7% (p < 0.01), respectively. The o/e ratios of 30-day mortality were 1.05 (95% confidence interval [CI] 0.83–1.26), 1.08 (95% CI 1.01–1.15), and 1.02 (95% CI 0.91–1.13), and those of 30-day morbidity were 1.72 (95% CI 0.93–2.51), 1.03 (95% CI 0.79–1.28), and 0.95 (95% CI 0.56–1.33), respectively. Conclusion: Surgical volume does not have significant impact on the outcomes of pediatric gastrointestinal perforation in Japan. [ABSTRACT FROM AUTHOR]

Candidemia, linked to high mortality rates, requires prompt antifungal therapy for better outcomes. Treatment is structured as an action bundle, which is beneficial when followed closely. However, the Japanese action bundle lacks detailed guidance on severe complications like endocarditis or ocular issues. To address this, we adjusted the action bundle and assessed outcomes with and without AFT intervention. We strengthened protocols for blood cultures and organ assessments, and the AFT contacted the primary physician when yeast-like fungi were detected in the patient's blood culture bottles. Analyzing 204 candidemia cases from 2008–2021, we observed increased adherence and reduced mortality post-AFT intervention. Ophthalmology consultations rose significantly, but many patients had only one visit, suggesting inadequate follow-up. If endophthalmitis is diagnosed, a change in the treatment approach may be necessary. There is a possibility that abnormal ocular findings will be detected during subsequent visits, which highlights the need for improvement in ophthalmology follow-up rates as a future challenge for our AFT activities. [ABSTRACT FROM AUTHOR]

Aim: We explored institutional factors in Japan associated with lower operative mortality and failure‐to‐rescue (FTR) rates for eight major gastrointestinal procedures. Methods: A 22‐item online questionnaire was sent to 2119 institutional departments (IDs) to examine the association between institutional factors and operative mortality and FTR rates. IDs were classified according to the number of annual surgeries, board certification status, and locality. In addition, the top 20% and bottom 20% of IDs were identified based on FTR rates and matched with the results of the questionnaire survey. Factors associated with operative mortality were selected by multivariate analysis. Results: Of the 1083 IDs that responded to the questionnaire, 568 (213 382 patients) were included in the analysis. Operative morbidity, operative mortality, and FTR rates in the top 20% and bottom 20% of IDs were 13.1% and 8.4% (p < 0.001), 0.52% and 4.3% (p < 0.001), and 4.0% and 51.2% (p < 0.001), respectively. Based on the patients' background characteristics, the top 20% of IDs handled more advanced cases. No significant difference in locality was seen between better or worse hospital FTR rates, but fewer esophagectomies, hepatectomies, and pancreatoduodenectomies were performed in depopulated areas. Six items were found to be associated with operative mortality by multivariate logistic analysis. Only 50 (8.8%) IDs met all five factors related to better FTR rates. Conclusions: The present findings indicate that several hospital factors surrounding surgical treatment, characterized by abundant human resources, are closely related to better postoperative recovery from severe complications. [ABSTRACT FROM AUTHOR]

Background: In the global aging, the coronavirus disease 2019 (COVID-19) pandemic may have affected the place of death (PoD) in Japan, where hospital deaths have dominated for decades. We analyzed the PoD trends before and during the COVID-19 pandemic in Japan. Methods: This nationwide observational study used vital statistics based on death certificates from Japan between 1951 and 2021. The proportion of PoD; deaths at home, hospitals, and nursing homes; and annual percentage change (APC) were estimated using joinpoint regression analysis. Analyses were stratified by age groups and causes of death. Results: After 2019, home deaths exhibited upward trends, while hospital death turned into downward trends. By age, no significant trend change was seen in the 0–19 age group, while hospital deaths decreased in the 20–64 age group in 2019. The trend change in home death in the ≥65 age group significantly increased since 2019 with an APC of 12.3% (95% confidence interval [CI]: 9.0 to 15.7), while their hospital death trends decreased by −4.0% (95% CI: −4.9 to −3.1) in 2019−2021. By cause of death, home death due to cancer and the old age increased since 2019 with an APC of 29.3% (95% CI: 25.4 to 33.2) and 8.8% (95% CI: 5.5 to 12.2), respectively. Conclusion: PoD has shifted from hospital to home during the COVID-19 pandemic in Japan. The majority of whom were older population with cancer or old age. [ABSTRACT FROM AUTHOR]

This paper constructs a theoretical framework for multi-population mortality modeling via generalized linear models and Lévy stochastic perturbations driven by a common Brownian motion and idiosyncratic factors to capture the mortality shocks. By having Lévy stochastic perturbations, our model admits various jump types, which is increasingly important for capturing mortality shocks such as pandemics, particularly when they affect various populations differently. At the same time, the proposed model allows a novel dependence structure of multiple populations, which is essential when it comes to the development of multi-population or joint-life products in the context of mortality shocks. In our empirical investigations, the mortality experiences of male and female lives in the UK and Japan are used. Compared with pure Poisson-generalized linear models, the proposed multi-population model shows superiority in predicting future mortality rates. [ABSTRACT FROM AUTHOR]

This study aimed to clarify the relationship between maternal mortality and advanced maternal age in Japan and to provide useful information for future perinatal management. Maternal death rates by age group were investigated for all maternal deaths in Japan for an 11-year period, from 2010 to 2021. Maternal deaths among those aged ≥ 40 years were examined in detail to determine the cause, and the number of deaths by cause was calculated. The causes of onset of the most common causes of death were also investigated. The maternal mortality rates were 0.8 (95% confidence interval [CI] 0.3–4.7) for < 20 years, 2.6 (95% CI 1.7–3.8) for 20–24 years, 2.9 (95% CI 2.3–3.6) for 25–29 years, 3.9 (95% CI 3.3–4.5) for 30–34 years, 6.8 (95% CI 5.9–7.9) for 35–39 years, and 11.2 (95% CI 8.8–14.3) for ≥ 40 years of age. Patients who were ≥ 40 years of age had a significantly higher mortality rate compared to that in other age groups. Hemorrhagic stroke was the most common cause of death in patients aged ≥ 40 years (15/65 [23%]), and preeclampsia (8/15 [54%]) was the most common cause of hemorrhagic stroke. Maternal mortality is significantly higher in older than in younger pregnant women in Japan, with hemorrhagic stroke being the most common cause of maternal death among women > 40 years of age. More than half of hemorrhagic strokes are associated with hypertension disorder of pregnancy. These facts should be considered by women who become pregnant at an advanced age and by healthcare providers involved in their perinatal care. [ABSTRACT FROM AUTHOR]

We encountered 34 Clostridioides difficile (C. difficile) infection (CDI) cases among Thoroughbred horses in Japan from 2010 to 2021. Among them, 79.4% (27/34) either died or were euthanised. The risk factors associated with CDI and mortality among Japanese Thoroughbred horses remain unclear. We used genetic methods to examine C. difficile strains and their relationships with prognosis. Twenty-two (64.7%) cases were hospitalised at the onset of colitis. Outcomes were balanced for hospitalisation rates at the onset of colitis. The mortality rates of cases treated with metronidazole (65.0%) were significantly lower than untreated cases (100%). The predominant genotype of C. difficile isolate was polymerase chain reaction ribotype (RT) 078, isolated from 12 cases (35.3%), followed by RT014 (six cases, 17.6%). Binary toxin (C. difficile transferase [CDT])-positive strains, including all RT078 strains, were isolated from 16 horses. Mortality rates in RT078 strain (75.0%) or CDT-positive strain (83.3%) cases were comparable to that in cases of other types. Sufficient infection control is needed to prevent CDI in Thoroughbred horses. A timely and prompt CDI diagnosis leading to metronidazole treatment would improve CDI outcomes. [ABSTRACT FROM AUTHOR]

The purpose of this survey was to examine the status of radiotherapy in Japan based on the cases registered in the Japanese Radiation Oncology Database (JROD), from 2015 to 2021, and to provide basic data to help improve the usefulness of the JROD in the future. The study population consisted of patients who underwent radiotherapy between 2014 and 2020 and did not opt out of the study. The survey item data analyzed in this study were entered into the database at each radiotherapy institution by referring to medical records from the preceding year. Our results show that the number of registered radiotherapy institutions and cases increased by ~50% in 2019 compared to those in 2015 (to 113 institutions and 60 575 cases, respectively). Among the survey item categories, the registration rate was lowest for prognostic information (13.9% on average over the 7-year period). In terms of the Japanese Society for Radiation Oncology disease site, the breast; lung, trachea and mediastinum and urogenital sites accounted for >50% of the total cases. The average survival and mortality rates over the 7-year study period were 67.4 and 17.4%, respectively. The X-ray radiotherapy completion rate exceeded 90% for all years and across all disease categories. 192Ir-based brachytherapy and 223Ra-based radionuclide therapy accounted for an average of 61.9 and 44.6%, respectively, of all corresponding cases over the 7-year period. In conclusion, this survey enables us to infer the actual status of radiotherapy in Japan based on the analysis of relevant nationwide data. [ABSTRACT FROM AUTHOR]

This study aimed to test Marshall's third hypothesis--that information about the death penalty hardly affects the attitude of death penalty supporters on retribution grounds--utilizing a non-American sample. Four pre-registered experiments were conducted, involving Japanese participants randomly selected fromsample pools of retributivists and non-retributivists, based on their reasons for supporting the death penalty. One group received information exposure, while the other was under control conditions. Participants read about deterrence (Study 1) or false convictions (Study 2-4). Except for the results of Study 4, retributivists and non-retributivists were equally affected or unaffected by information. Marshall's third hypothesis is therefore not supported. Retributivists strongly favored the death penalty; higher empathy toward criminals was associated with less pro-death penalty attitudes. Additionally, there were differences in the influence of information. These results suggest the need for a new approach to researching the relationship between public attitudes and information on the death penalty. [ABSTRACT FROM AUTHOR]

Encapsulating peritoneal sclerosis (EPS), a condition with a high mortality rate, is a serious complication of peritoneal dialysis (PD). In Japan, EPS became a central issue in the clinical setting during the mid-90s and the beginning of this century. However, following the introduction of biocompatible neutral PD solutions containing lower levels of glucose degradation products, the incidence and clinical severity of EPS has been greatly lessened. During the past three decades, the etiology of EPS has been elucidated by findings obtained by peritoneal biopsy, laparoscopy, and surgical intervention. Accumulating findings suggest the need for a paradigm change on the nature of EPS pathophysiology; notably, EPS appears not to reflect peritoneal sclerosis per se, but rather the formation of a neo-membrane as a biological reaction to peritoneal injury. This narrative review looks back on the history of EPS in Japan, and discusses EPS pathophysiology, the impact of neutral PD solution on peritoneal protection, and a future novel diagnostic approach, ultra-fine endoscope, for the identification of patients at high risk of EPS. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic had a low impact on Japan in 2020, but the size of the epidemic increased considerably there in 2021. This study made a statistical analysis of life expectancy changes up to the end of 2021 in Japan. Objective: We aimed to estimate changes in life expectancy from 2019 to 2021 associated with the COVID-19 pandemic. To do so, we decomposed the life expectancy changes from 2020-2021 into age-specific and cause of death-specific contributions. Methods: We used the absolute number of deaths by age and prefecture in Japan to calculate life expectancy from 2019-21 at both national and prefectural levels, and also examined the correlation between life expectancy gap and annual number of COVID-19 cases, total person-days spent in intensive care, and documented deaths due to COVID-19. We used the Arriaga decomposition method to decompose national life expectancy changes from 2020 to 2021 into age and cause of death components. Results: From 2019-2020, Japan's national level life expectancy across the entire population was extended by 0.24 years. From 2020-2021, it shortened by 0.15 years. The life expectancy shortened more among women (0.15 years) than men (0.12 years). There was significant heterogeneity in life expectancy changes from 2020-2021 by prefecture. It ranged from the maximum shortening of 0.57 years in Tottori prefecture to the maximum extension of 0.23 years in Fukui. The regression analysis revealed the negative correlation between the life expectancy change and burden of COVID-19 at prefectural level. The decomposition of life expectancy changes at birth from 2020-2021 showed that losses in life expectancy were largely attributable to the mortality of the population over 70 years old. Changes in life expectancy among infants and working-age adults mostly contributed to lengthening overall life expectancy. Among leading major causes of death, deaths due to neoplastic tumor and cardiovascular diseases contributed to shortening life expectancy, whereas respiratory diseases did not. Conclusion: The decades-long increasing trend in life expectancy was suspended by the COVID-19 pandemic. However, life expectancy changes from 2019-2020 and 2020-2021 were small in Japan. This may be attributable to the small epidemiological impact of COVID-19 during this time period, but nonetheless, the negative impact of COVID-19 on life expectancy was indicated in the present study. The chance of death accelerated in older people in 2021, but a smaller number of deaths than usual among infants and working age adults contributed to extended life expectancy, and the change in the cause of death structure under the COVID-19 pandemic also significantly contributed to shortening life expectancy. [ABSTRACT FROM AUTHOR]

Pedestrian deaths account for the highest percentage of fatality caused by traffic accidents in Japan. Increasing pedestrian safety is a key objective for reducing such deaths. For pedestrian fatality caused by vehicles at low speed, turning the vehicle toward the right was the most common behavior under left-hand traffic. Autonomous emergency braking (AEB) systems for pedestrian safety have great potential to mitigate pedestrian injuries and fatalities in traffic accidents. However, pedestrian-AEB systems, especially for vehicles turning right, are still under development. This study identified the characteristics of dangerous traffic scenarios between vehicles turning right and pedestrians, focusing on two directions of pedestrian crossing: from the left to the right side (Left-Pedestrian) and from the right to the left side (Right-Pedestrian). The ego vehicle recorded near-miss incidents using a drive recorder. The results revealed that the Left-Pedestrian and Right-Pedestrian scenarios had different features for both the width of roads going to and through the intersection and the average of the travel speeds of the ego vehicles. They had similar characteristics in terms of the presence of other vehicle categories, but differences in the relationship of numbers and/or travel directions of other vehicles. The findings of this study will contribute to the development and evaluation of safety systems for preventing collisions between right-turning vehicles and pedestrians at intersections. [ABSTRACT FROM AUTHOR]

COVID-19 has brought a great challenge to the medical system. A key scientific question is how to make a balance between home quarantine and staying in the hospital. To this end, we propose a game-based susceptible-exposed-asymptomatic -symptomatic- hospitalized-recovery-dead model to reveal such a situation. In this new framework, time-varying cure rate and mortality are employed and a parameter m is introduced to regulate the probability that individuals are willing to go to the hospital. Through extensive simulations, we find that (1) for low transmission rates (β < 0.2), the high value of m (the willingness to stay in the hospital) indicates the full use of medical resources, and thus the pandemic can be easily contained; (2) for high transmission rates (β > 0.2), large values of m lead to breakdown of the healthcare system, which will further increase the cumulative number of confirmed cases and death cases. Finally, we conduct the empirical analysis using the data from Japan and other typical countries to illustrate the proposed model and to test how our model explains reality. [ABSTRACT FROM AUTHOR]

Background The mortality rates of coronavirus disease 2019 (COVID-19) have been changed across the epidemiological waves. The aim was to investigate the differences in mortality rates of COVID-19 patients in Japan across the 6 epidemiological waves stratified by age group and Coronavirus Clinical Characterisation Consortium (4C) mortality score risk group. Methods A total of 56 986 COVID-19 patients in the COVID-19 Registry Japan from 2 March 2020 to 1 February 2022 were enrolled. These patients were categorized into 4 risk groups based on their 4C mortality score. Mortality rates of each risk group were calculated separately for different age groups: 18–64, 65–74, 75–89, and ≥90 years. In addition, mortality rates across the wave periods were calculated separately in 2 age groups: <75 and ≥75 years. All calculated mortality rates were compared with reported data from the United Kingdom (UK) during the early epidemic. Results The mortality rates of patients in Japan were significantly lower than in the UK across the board, with the exception of patients aged ≥90 years at very high risk. The mortality rates of patients aged ≥75 years at very high risk in the fourth and fifth wave periods showed no significant differences from those in the UK, whereas those in the sixth wave period were significantly lower in all age groups and in all risk groups. Conclusions The present analysis showed that COVID-19 patients had a lower mortality rate in the most recent sixth wave period, even among patients ≥75 years old at very high risk. [ABSTRACT FROM AUTHOR]

Purpose: Serious group A streptococcal (GAS) infections and toxic shock syndrome (TSS) are rare conditions, but their rapid progression often results in death. The purpose of the present study was to clarify recent trend after the coronavirus disease (COVID-19) pandemic of GAS infection in Japan. Materials and Methods: Maternal death statistics were analyzed by the Japan Maternal Death Exploratory Committee. Results: Maternal deaths due to GAS–TSS accounted for 4.2% (n = 22) of all maternal deaths in Japan (n = 525) in the last 12 years. GAS–TSS remains one of the leading causes of maternal death after obstetric hemorrhage and hypertensive disorder. However, no maternal deaths due to GAS–TSS have been reported since the COVID-19 pandemic in Japan after the last death occurred in February 2020. Conclusions: The major change during this period was that most Japanese people wore facemasks at all times and did frequent disinfection. It is considered that the reduction in the incidence of GAS infections itself reduced the number of serious GAS-related maternal deaths. Wearing facemasks and frequent disinfection during pregnancy might to be recommended to prevent various infectious diseases including serious GAS infection, even after the COVID-19 pandemic era. [ABSTRACT FROM AUTHOR]

The objective of the present study was to investigate the associations between major diseases (clinical mastitis, peracute mastitis, metabolic disorders, peripartum disorders) and four parameters related to productivity (305-day milk yield, number of days open, culling rate, death rate) on a large dairy farm in a temperate zone with approximately 2500 Holstein cows. Data were collected from 2014 to 2018 and involved 9663 calving records for 4256 cows. We found negative effects of clinical mastitis, peracute mastitis, metabolic disorders, and peripartum disorders on the productivity of cows. Clinical-mastitis-suffered cows with multiple diseases had more days open compared with those with clinical mastitis alone and the healthy group, and they had a higher death rate than the healthy group, whereas there was no difference in death rate between the clinical mastitis only and healthy groups. Cows suffering from peracute mastitis, metabolic disorders, and peripartum disorders with either single or multiple diseases exhibited reduced productivity compared with the healthy group. Our findings clearly show that major diseases of cows in a temperate zone have severely negative effects on their productivity. [ABSTRACT FROM AUTHOR]

We draw the attention of readers and governments to the death rate from coronavirus disease 2019 in Japan, continuing as a fraction of that experienced by many other developed nations. We think this is due to the activity of the powerful, protective lactoperoxidase system (LPO) which prevents serious airborne infections. The LPO system requires iodine, which is liberally provided by the typical Japanese diet but lacking in many others. One might consider the Japanese experience an incredibly large, open‐label study exhibiting the preventative power of a high‐iodine diet. We predict this favourable trend will continue for Japan because deadly variants of the severe, acute respiratory syndrome coronavirus 2 will be with us, forever. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to clarify the prognostic factors for patients with esophageal squamous cell carcinoma (ESCC) invading into the muscularis mucosa (pT1a‐MM) or submucosa (pT1b‐SM) after endoscopic submucosal dissection (ESD). Methods: This retrospective study enrolled such patients at 21 institutions in Japan between 2006 and 2017. We evaluated 15 factors, including pathological risk categories for ESCC‐specific mortality, six non‐cancer‐related indices, and treatment strategies. Results: In the analysis of 593 patients, the 5‐year overall and disease‐specific survival rates were 83.0% and 97.6%, respectively. In a multivariate Cox analysis, male sex (hazard ratio [HR] 3.56), Charlson comorbidity index (CCI) ≥3 (HR 2.53), ages of 75–79 (HR 1.61) and ≥80 years (HR 2.04), prognostic nutrition index (PNI) <45 (HR 1.69), and pathological intermediate‐risk (HR 1.63) and high‐risk (HR 1.89) were prognostic factors. Subsequently, we developed a clinical risk classification for non‐ESCC‐related mortality based on the number of prognostic factors (age ≥75 years, male sex, CCI ≥3, PNI <45): low‐risk, 0; intermediate‐risk, 1–2; and high‐risk, 3–4. The 5‐year non‐ESCC‐related mortality rates for patients without additional treatment were 0.0%, 10.2%, and 45.8% in the low‐, intermediate‐, and high‐risk groups, respectively. Meanwhile, the 5‐year ESCC‐specific mortality rates for the pathological low‐, intermediate‐, and high‐risk groups were 0.3%, 5.3%, and 18.2%, respectively. Conclusions: We clarified prognostic factors for patients with pT1a‐MM/pT1b‐SM ESCC after ESD. The combined assessment of non‐ESCC‐ and ESCC‐related mortalities by the two risk classifications might help clinicians in deciding treatment strategies for such patients. [ABSTRACT FROM AUTHOR]

Taylor's law is a widely observed empirical pattern that relates the variances to the means of population densities. We present four extensions of the classical Taylor's law (TL): (1) a cubic extension of the linear TL describes the mean–variance relationship of human mortality at subnational levels well; (2) in a time series, long‐run variance measures not only variance but also autocovariance, and it is a more suitable measure than variance alone to capture temporal/spatial correlation; (3) an extension of the classical equally weighted spatial variance takes account of synchrony and proximity; (4) robust linear regression estimators of TL parameters reduce vulnerability to outliers. Applying the proposed methods to age‐specific Japanese subnational death rates from 1975 to 2018, we study temporal and spatial variations, compare different coefficient estimators, and interpret the implications. We apply a clustering algorithm to the estimated TL coefficients and find that cluster memberships are strongly related to prefectural gross domestic product. The time series of spatial TL coefficients has a decreasing trend that confirms the narrowing gap between rural and urban mortality in Japan. [ABSTRACT FROM AUTHOR]

Purpose: The underreporting of suicides has been a serious global concern among scholars and policymakers. Several studies have sought to detect the prevalence of underreporting by examining whether suicide mortality rates are negatively correlated with those due to unknown intent or causes. This study adds to the literature by examining the potential underreporting of suicides in Japan, where suicide rates have greatly declined in the recent years. Methods: We compiled subnational data from 47 prefectures between 1995 and 2016, obtained from Vital Statistics of Japan. We examined whether (1) mortality rates due to unknown intent or causes increased as suicide rates decreased; and (2) major socioeconomic causes of suicide (unemployment and divorce rates) had any relationship with the deaths due to unknown intent or causes. Results: Our analysis indicates that mortality rates due to unknown intent or causes were uncorrelated with suicide rates and the above socioeconomic indicators. Conclusions: In Japan, the frequency of suicides has no systematic relationship with deaths due to unknown intent or causes, suggesting the accuracy of suicide statistics. [ABSTRACT FROM AUTHOR]

We aimed to define the burden and clinical features of invasive group B streptococcus (GBS) disease in infants younger than 1 year in Japan, to explore transmission route of late-onset disease (LOD), and to identify risk factors associated with recurrent GBS disease. We conducted a retrospective, questionnaire-based nationwide surveillance study between 2016 and 2020. A total of 875 GBS cases were identified, including 186 early-onset disease, 628 LOD, and 61 ultra-late-onset disease. Case fatality rate in each age category was 6.5%, 3.0%, and 3.3%, respectively. Patients with meningitis had neurodevelopmental sequelae in 21.5% (64/297). Annual incidence in infants younger than 1 year and in LOD significantly increased from 0.28 to 0.45/1000 livebirths (p = 0.021) and from 0.19 to 0.29/1000 livebirths (p = 0.046), respectively. Maternal colonization status at the LOD diagnosis was available for 148 mothers, of whom 21/58 (36.2%) had positive rectovaginal swabs and 42/117 (36.2%) had GBS in breastmilk culture. These two sites are potentially infectious routes in LOD. The four leading disease-causing serotypes III, Ia, Ib, and V represented 95% of the available serotypes. Thirty-one recurrent cases were identified, accounting for 3.7% of total patients. A multivariate regression analysis showed that prematurity (p = 0.029) and antepartum maternal GBS colonization (p = 0.032) were significantly associated with risk for the recurrence. Our findings indicated that GBS disease burden still remains with considerable mortality and morbidity in Japan, and provided important information for developing better strategies for the prevention of GBS disease, including maternal vaccination. [ABSTRACT FROM AUTHOR]

The effects of insecticides on arrhenotokous and thelytokous types in adult females of onion thrips, Thrips tabaci Lindeman, collected from a total of 13 sites of Welsh onions, cabbages, and onions in Kyoto Prefecture, Japan, in 2016 and 2017 were evaluated. Susceptibility to the tested insecticides varied among the reproductive types, populations, and years. Among the 14 insecticides tested on female adults in arrhenotokous type using the kidney bean leaf dipping method, spinetoram, spinosad, avermectin, cyantraniliprole, fluxametamide, and flometoquin were the most toxic. In addition, cypermethrin, imidacloprid, spinetoram, spinosad, avermectin, cyantraniliprole, fluxametamide, and flometoquin caused a high mortality rate in female adults in thelytokous type. Overall, the mortality rate in thelytokous type was higher than that in arrhenotokous type. [ABSTRACT FROM AUTHOR]

This article investigates the trends in injury rates and causes of fatalities in the Japanese mining industry. Accident data were collected from the Japan Statistics Yearbooks released by the Bureau of the Prime Minister. These data were analyzed to estimate the injury rates and accident causes in the Japanese mining industry. In Japan, the median injury, severe injury and fatality rates were 129.25, 5.44 and 2.99/1000 workers, respectively. A collapsing roof in an underground mine was the principal cause of fatal accidents, accounting for a median value of 21/1000 worker deaths during the entire period under study. In comparison with the accident experience of the USA and the Democratic Republic of Congo, countries with substantial mining industries, the median values of the fatality rates were 0.58 and 0.28/1000 workers, respectively. We conclude that Japanese mineworkers were most exposed to the risk of accidents during the prewar era. [ABSTRACT FROM AUTHOR]

We assessed the impact of the pediatric 13-valent pneumococcal conjugate vaccine (PCV13) on pneumococcal meningitis in adults in Japan in 2014–2018 by comparing epidemiological characteristics of adults with invasive pneumococcal disease with (n = 222) and without (n = 1258) meningitis. The annual incidence of pneumococcal meningitis in 2016–2018 was 0.20–0.26 cases/100,000 population. Age (p < 0.001) and case fatality rate (p = 0.003) were significantly lower in patients with meningitis than in those without meningitis. The odds of developing meningitis were higher in asplenic/hyposplenic or splenectomized patients (adjusted odds ratio [aOR] 2.29, 95% CI 1.27–4.14), for serotypes 10A (aOR 3.26, 95% CI 2.10–5.06) or 23A (aOR 3.91, 95% CI 2.47–6.19), but lower for those aged ≥ 65 years (aOR 0.59, 95% CI 0.44–0.81). PCV13 had an indirect effect on nonmeningitis, but its impact on meningitis was limited because of an increase in non-PCV13 serotypes. Of meningitis isolates, 78 (35.1%) and 3 (1.4%) were penicillin G- or ceftriaxone-resistant, respectively. We also confirmed an association of the pbp1bA641C mutation with meningitis (aOR 2.92, 95% CI 1.51–5.65). [ABSTRACT FROM AUTHOR]

Pulmonary oxalosis can be fatal, and Aspergillus tubingensis is commonly resistant to azoles in Japan. We report a case of bronchopulmonary oxalosis caused by A. tubingensis in a non-neutropenic patient who was successfully treated with voriconazole monotherapy. The susceptibility of the isolates to voriconazole and the effective elimination of contagious necrotic tissue by expectoration seemed to be two major factors contributing to the patient's survival. According to the literature review, pulmonary oxalosis is associated with a high mortality rate over a short term. An exploration of detailed information about the genomic characteristics and drug susceptibility of Aspergillus isolates is important for the development of treatment strategies for this life-threatening disease. [ABSTRACT FROM AUTHOR]

Candida auris was first isolated in Japan in 2009. It has since been reported in more than 25 countries worldwide. This species, which can cause invasive infections with high mortality rates, is difficult to identify with traditional biochemical methods. C. auris can be transmitted among hospitalized patients by colonizing the skin. Resistance to fluconazole and amphotericin B is common in this species, and resistance to echinocandins, which are preferred in the treatment in some countries, is seen to develop. Studies have shown that resistance to antifungals is acquired, not intrinsic, and primary resistance mechanisms against echinocandins and azoles have been identified. This species is difficult to control because of its multidrug resistance, even the emergence of pan-resistant strains, misidentification with conventional methods in clinical microbiology laboratories, and long-term persistence in the hospital environment. In order to prevent infections with infection control measures, advanced laboratory methods that allow accurate diagnosis is needed. In addition, new antifungal agents should be researched and included in practice in order to ensure success in treatment. In this short review, current information about the epidemiology, infections, microbiological features and laboratory diagnosis of C. auris is mentioned. [ABSTRACT FROM AUTHOR]

Objects: Although anti‐thrombotic use is recognized as a risk factor for upper gastrointestinal bleeding (UGIB), there has been no clear evidence that it worsens the outcomes after the bleeding. The aim of this study is to investigate the effects of anti‐thrombotic agents on in‐hospital mortality following UGIB. Methods: Information on clinical parameters, including usage of anti‐thrombotic agents, was retrospectively collected from consecutive patients with UGIB at 12 high‐volume centers in Japan between 2011 and 2018. The all‐cause in‐hospital mortality rate was evaluated according to the usage of anti‐thrombotic agents. Results: Clinical data were collected from 2205 patients with endoscopically confirmed UGIB. Six hundred and forty‐five (29.3%) patients used anti‐thrombotic agents. The all‐cause in‐hospital mortality rate was 5.7% (125 deaths). After excluding 29 cases in which death occurred due to end‐stage malignancy, 96 deaths (bleeding‐related, n = 22 ; non‐bleeding‐related, n = 74) were considered "preventable." Overall, the "preventable" mortality rate in anti‐thrombotic users was significantly higher than that in non‐users (6.0% vs. 3.7%, P < 0.05). However, the "preventable" mortality of anti‐thrombotic users showed a marked improvement over time; although the rate in users remained significantly higher than that in non‐users until 2015 (7.3% vs. 4.2%, P < 0.05), after 2016, the difference was no longer statistically significant (4.8% vs. 3.5%). Conclusions: Although the usage of anti‐thrombotic agents worsened the outcomes after UGIB, the situation has recently been improving. We speculate that the recent revision of the Japanese guidelines on the management of anti‐thrombotic treatment after UGIB may have partly contributed to improving the survival of users of anti‐thrombotic agents. [ABSTRACT FROM AUTHOR]

• Patients with COVID-19 were recruited from more than 70 institutes in Japan. • Japan experienced 3 waves of COVID-19 during the first year of the pandemic. • The case fatality rate of 3.2% was relatively low. • The data will be used for a genome-wide association study. The coronavirus disease (COVID-19) pandemic is having a devastating effect worldwide. Host genome differences between populations may influence the severity of COVID-19. The Japan COVID-19 Task Force is conducting host genome analysis of hospitalized patients with COVID-19 from more than 70 institutions nationwide in Japan. This report describes the clinical characteristics of patients enrolled to date. The median (interquartile range) age of the 1674 patients included in the analysis was 59 (45–71) years, and more than half of the patients (66.2%) were male. Less than half of the patients (41.2%) had severe disease. The case fatality rate was 3.2%. Since this is a hospital-based study, the number of severe cases was relatively high, but the case fatality rate was relatively low, when compared to that of other countries. In the future, we will continue to enroll patients and conduct genome analyses of patients with COVID-19. [ABSTRACT FROM AUTHOR]

To determine differences in clinical characteristics of patients with bacteremia caused by Corynebacterium striatum, C. jeikeium, and other species of Corynebacterium, we retrospectively reviewed medical records of patients in Japan who had Corynebacterium bacteremia during January 2014–May 2020. Of the 115 records evaluated, 60 (52%) were cases of true bacteremia and 55 (48%) were cases of contamination. Proportions of true bacteremia cases caused by C. striatum (70%) and by C. jeikeium (71%) were significantly higher than those caused by other species of Corynebacterium (9%). These 2 organisms were commonly detected in blood cultures of patients with hematologic malignancies and neutropenia. The mortality rates at 90 days were 34% (C. striatum), 30% (C. jeikeium), and 0 (other species). Given the high mortality rates, assessing true bacteremia when C. striatum or C. jeikeium is detected in blood cultures, especially in patients with hematologic malignancy, is warranted. [ABSTRACT FROM AUTHOR]

Purpose: The association between advanced age and postoperative morbidity and mortality after major gastroenterological surgeries remains unclear. This study aimed to assess the association between old age and the short-term postoperative outcomes of gastroenterological surgeries. Methods: We evaluated 327,642 patients who underwent any of the seven major gastroenterological surgeries—esophagectomy, total gastrectomy, distal gastrectomy, right hemicolectomy, low anterior resection, hepatectomy, and pancreatoduodenectomy—and were registered with the Japanese national surgical registry between January 2011 and December 2013. Perioperative characteristics, frequency/nature of postoperative morbidities, and postoperative mortality were compared according to age at the time of surgery. Results: Overall, 18% (59,182/327,642) of the entire cohort were aged ≥ 80 years. The overall mortality rates in the entire cohort and in those aged ≥ 80 years were 1.7% and 3.3%, respectively. The postoperative mortality increased with increasing age for all procedures, with the trend persisting even after adjusting for various confounding factors. The incidence of postoperative pneumonia increased with increasing age, and with all procedures, except esophagectomy, subjects aged ≥ 80 years had a markedly higher risk of developing postoperative pneumonia than those aged < 60 years. Conclusion: Advanced age is associated with significantly worse short-term outcomes in older patients undergoing gastroenterological surgeries. However, we could not identify any distinct cutoff age beyond which major gastroenterological surgery could be considered as being contraindicated. The mortality risk should be carefully considered before recommending major gastroenterological surgeries for older patients. [ABSTRACT FROM AUTHOR]

Background: As lung transplantation (LTX) is a valuable treatment procedure for end-stage pulmonary disease, delayed referral to a transplant center should be avoided. We aimed to conduct a single-center analysis of the survival time after listing for LTX and waitlist mortality in each disease category in a Japanese population.Methods: We included patients listed for LTX at Tohoku University Hospital from January 2007 to December 2020 who were followed up until March 2021. Pulmonary disease was categorized into the Obstructive, Vascular, Suppurative, Fibrosis, and Allogeneic groups. Risk factors for waitlist mortality were assessed using a Cox proportional hazards model. The Kaplan-Meier method was used to model time to death.Results: We included 269 LTX candidates. Of those, 100, 72, and 97 patients were transplanted, waiting, and dead, respectively. The median time to LTX and time to death were 796 days (interquartile range [IQR] 579-1056) and 323 days (IQR 129-528), respectively. The Fibrosis group showed the highest mortality (50.9%; p < .001), followed by the Allogeneic (35.0%), Suppurative (33.3%), Vascular (32.1%), and Obstructive (13.1%) groups. The Fibrosis group showed a remarkable risk for waitlist mortality (hazard ratio 3.32, 95% CI 2.11-4.85).Conclusions: In Japan, the waiting time is extremely long and candidates with Fibrosis have high mortality. There is a need to document outcomes based on the underlying disease for listed LTX candidates to help determine the optimal timing for listing patients based on the estimated local waiting time. [ABSTRACT FROM AUTHOR]

Within no definite diuretic protocol for acute heart failure (AHF) patients and its variation in regional clinical guidelines, the latest national guidelines in Japan commends use of tolvaptan in diuretic-resistant patients. This study aimed to examine trends in tolvaptan usage and associated outcomes of AHF patients requiring hospitalization. Between April, 2018 and October, 2019, 1343 consecutive AHF patients (median 78 [69–85] year-old) were enrolled in a prospective, multicenter registry in Japan. Trends over time in tolvaptan usage, along with the severity of heart failure status based on the Get With The Guideline-Heart Failure [GWTG-HF] risk score, and in-hospital outcomes were investigated. During the study period, tolvaptan usage has increased from 13.0 to 28.7% over time (p for trend = 0.07), and 49.4% started tolvaptan within 3 days after admission. The GWTG-HF risk score in the tolvaptan group has significantly decreased over time, while that in the non-tolvaptan group has unchanged. There were no differences in the in-hospital mortality rate between the patients with and without tolvaptan (6.7% vs. 5.8%). After revision of the Japanese clinical practice guidelines for AHF in March 2018, tolvaptan usage for AHF patients has steadily increased. However, in-hospital outcomes including mortality do not seem to be affected. [ABSTRACT FROM AUTHOR]

Background and Aim: The current prevalence of hepatitis C virus infection and hepatitis C virus‐associated mortality in Japan falls short of the World Health Organization goal of viral hepatitis elimination by 2030. We aimed to evaluate the trends in hepatitis C virus‐associated mortality in Japan. Methods: This nationwide observational study used the Japanese Vital Statistics from 1998 to 2017 and included all Japanese hepatitis C virus‐associated deaths (84 936) of adults aged ≥ 40 years. We calculated the crude and age‐standardized mortality rates per 100 000 persons by age and sex. Joinpoint regression analysis was used to identify significant changing points in trends and to estimate the annual percentage changes and the average annual percentage changes for the entire study period. Results: The crude mortality rate per 100 000 persons (annual death number) increased from 5.5 (3548) in 1998 to 7.0 (4843) in 2005 and decreased to 4.0 (3095) in 2017. By 2017, the crude mortality rates per 100 000 persons among men and women had dropped to 3.6 and 4.3, respectively. The age‐standardized mortality rate was higher in women than in men. The average annual percentage change was −3.8% (95% confidence interval: −5.0 to −2.5). The declining trend was more rapid in men (−4.5%, 95% confidence interval: −5.3 to −3.6) than in women (−2.7%, 95% confidence interval: −3.8 to −1.6). Conclusions: Trends in hepatitis C virus‐associated mortality rates have declined in an accelerating manner in Japan, especially among men. [ABSTRACT FROM AUTHOR]

Risk factors for death from invasive pneumococcal disease (IPD) have not been clearly established in patients aged under 65 years. We aimed to evaluate contributions of host and bacterial factors to the risk of death from IPD in patients aged under 65 years in Japan. In this prospective, observational, multicenter cohort study, patients with IPD (n = 581) aged 6–64 years were enrolled between 2010 and 2017. We investigated the role of host and bacterial factors in 28-day mortality. The mortality rate increased from 3.4% to 6.2% in patients aged 6–44 years to 15.5%–19.5% in those aged 45–64 years. Multivariable analysis identified the following risk factors for mortality: age 45–64 years (hazard ratio [HR], 3.4; 95% confidence interval [CI], 1.6–6.8, p = 0.001), bacteremia with unknown focus (HR, 2.0; 95% CI, 1.1–3.7, p = 0.024), meningitis (HR, 2.1; 95% CI, 1.1–4.0, p = 0.019), underlying multiple non-immunocompromising conditions (HR, 2.6; 95% CI, 1.1–7.4, p = 0.023), and immunocompromising conditions related to malignancy (HR, 2.4; 95% CI, 1.0–5.2, p = 0.039). Pneumococcal serotype was not associated with poor outcomes. Host factors, including age of 45–64 years and underlying multiple non-immunocompromising conditions, are important for the prognosis of IPD. Our results will contribute to the development of targeted pneumococcal vaccination strategies in Japan. [ABSTRACT FROM AUTHOR]

Two European phase III trials comparing D1 and D2 demonstrated that D2 did not improve the overall survival and was associated with a high mortality related to splenectomy. However, a long-term follow-up study showed that the gastric cancer-related death rate was significantly higher in D1 than D2. Based on these findings, the standard surgery in Europe became D2 without pancreatico-splenectomy to prevent mortality. In contrast, the JCOG9501 phase III comparing D2 and D2 plus para-aortic nodal dissection did not showed a survival efficacy of extended lymphadenectomy, but the mortality rate was quite low in both surgeries. Subsequently, the JCOG0110 phase III study comparing D2 and spleen-preserving D2 for upper gastric cancer not invading the greater curvature clearly showed the non-inferiority of spleen preservation. Thus, spleen-preserving D2 was made the standard surgery for these tumors in Japan. However, splenectomy is often selected for complete dissection of the splenic-hilar nodes, a frequent metastatic site for upper gastric tumors invading the greater curvature. Recently, an approach involving splenic hilar nodal dissection without splenectomy has been developed. [ABSTRACT FROM AUTHOR]

Detailed, long-term datasets on the life histories of long-lived species such as great apes are necessary to understand their survival patterns but are relatively rare. Such information requires prolonged and consistent record-keeping over many generations, so for chimpanzees (Pan troglodytes), this equates to many decades of input. As life history variables can be altered by differences in environmental influences (whether natural or artificial), there is substantial value to being able to compare across populations. Here, we present the first comparative analysis of life history data for two ex situ chimpanzee populations residing in North America (1975–2020; n = 730) and Japan (1980–2020; n = 660). Overall, survival patterns were similar between regions, and the median life expectancy from birth is estimated at 35.7 (95% CI = [32.4–40.0]) years for females and 30.1 (27.3–34.3) years for males across both populations. Females who survive to their first birthday are estimated to survive 42.4 (40.0–46.3) years and males 35.5 (32.6–38.0) years. We found that birth type (wild-born or captive-born) did not influence survival patterns in either population, but there were differential effects of sex on longevity. In the America population, males had higher mortality rates than females, whereas in the Japan population we found no differences between the sexes. First year mortality did not differ between populations for males (18–20%), but for females it was lower in America (15%) compared to Japan (25%). Survival patterns of chimpanzees in the present study will be useful for future investigation into potential causes of regional differences and cross-species comparisons. [ABSTRACT FROM AUTHOR]

Purpose: A sudden unexpected death has significant negative impacts on patients, family caregivers, and medical staff in hospice/palliative care. This study aimed to clarify the incidence and associated factors of sudden unexpected death according to four definitions in advanced cancer patients. Methods: We performed a prospective cohort study in 23 inpatient hospices/palliative care units in Japan. Advanced cancer patients aged ≥18 years who were admitted to inpatient hospices/palliative care units were included. The incidence and associated factors of sudden unexpected death were evaluated in all enrolled patients according to four definitions: (a) rapid decline death, defined as a sudden death preceded by functional decline over 1–2 days; (b) surprise death, defined if the primary responsible palliative care physician answered "yes" to the question, "Were you surprised by the timing of the death?"; (c) unexpected death, defined as a death that occurred earlier than the physicians had anticipated; and (d) performance status (PS)‐defined sudden death, defined as a death that occurred within 1 week of functional status assessment with an Australia‐modified Karnofsky PS ≥50. Results: Among 1896 patients, the incidence of rapid decline death was the highest (30‐day cumulative incidence: 16.8%, 95% CI: 14.8–19.0%), followed by surprise death (9.6%, 8.1–11.4%), unexpected death (9.0%, 7.5–10.8%), and PS‐defined sudden death (6.4%, 5.2–8.0%). Male sex, liver metastasis, dyspnea, malignant skin lesion, and fluid retention were significantly associated with the occurrence of sudden unexpected death. Conclusion: Sudden unexpected death is not uncommon even in inpatient hospices/palliative care units, with range of 6.4–16.8% according to the different definitions. [ABSTRACT FROM AUTHOR]

Background Vadadustat is an investigational, oral hypoxia-inducible factor prolyl hydroxylase inhibitor in development in Japan for the treatment of chronic kidney disease (CKD)-induced anemia. Methods Two Phase 2, multicenter, double-blind, placebo-controlled studies randomized Japanese patients with nondialysis-dependent (NDD, n  = 51) or dialysis-dependent (DD, n  = 60) CKD-induced anemia to once-daily vadadustat (150, 300 or 600 mg) or placebo. A 6-week, fixed-dose primary efficacy period was followed by a 10-week vadadustat dose adjustment/maintenance period. The primary endpoint was the mean change in hemoglobin (Hb) level from pretreatment to Week 6. Results Statistically significant (P < 0.01) dose-dependent increases in mean Hb values were observed at Week 6 in all vadadustat groups versus placebo [placebo and vadadustat 150, 300 and 600 mg: −0.47, 0.43, 1.13 and 1.62 (NDD-CKD) and −1.48, −0.28, 0.08 and 0.41 (DD-CKD), respectively]. By Week 16, 91% (NDD-CKD) and 71% (DD-CKD) of vadadustat-treated participants achieved target Hb levels (10.0–12.0 g/dL) and significant dose-dependent changes in iron utilization and mobilization biomarkers were observed with vadadustat. During the primary efficacy period, the incidence of treatment-emergent adverse events (AEs) with placebo and vadadustat 150, 300 and 600 mg was 36, 33, 58 and 54% (NDD-CKD) and 40, 53, 73 and 40% (DD-CKD), respectively. The most common AEs during the primary efficacy period were nausea and hypertension (NDD-CKD) and diarrhea, nasopharyngitis and shunt stenosis (DD-CKD). Of 23 serious AEs in 18 patients, 1 was deemed related (hepatic function abnormal); no deaths were reported. Conclusions The efficacy and safety results from these studies support the development of vadadustat for the treatment of anemia in patients with CKD. [ABSTRACT FROM AUTHOR]

Objective: To determine the characteristics associated with mortality in patients with culture-positive pulmonary tuberculosis (PTB) in Airin, Osaka City, Japan. Methods: The characteristics of patients with culture-positive PTB registered between 2015 and 2018 in Airin, Osaka City, Japan, were compared between those who died of all causes before or during treatment and those who completed treatment. Results: Of the 241 culture-positive PTB patients eligible for this study, 170 completed treatment, with negative sputum culture tests, and 62 died. The all-cause case fatality rate was 26.7% (62/232). Multivariate analysis showed that mortality was associated with age =70 years, having a positive sputum smear, a body mass index of <18.5 and serious comorbidities such as cancer and heart and renal disease. Detection of tuberculosis (TB) by screening or in an outpatient department (OPD) for other diseases was inversely associated with mortality. Discussion: Detection of PTB by chest X-ray screening and during regular visits to OPDs for other diseases was associated with non-fatal TB and might contribute to early case finding. Therefore, current active TB case finding and health education on regular visits to physicians for other diseases should be strengthened further for the urban poor population of Osaka City, Japan. [ABSTRACT FROM AUTHOR]

Background: The human leukocyte antigen (HLA) haplotype of the recipient in hematopoietic stem cell transplantation (HSCT) is a key factor in its success or failure. We analyzed the relationship between HLA haplotype frequency and associated clinical factors in HSCT patients. Methods: Patients who underwent allogeneic HSCT between 2000 and 2019 at our institution were enrolled in this study. The HSCT composition was 77 bone marrow transplantations (BMT), 38 peripheral blood stem cell transplantations (PBSCT), and 36 cord blood transplantations (CBT). Patients were classified into three groups according to their donor HLA haplotype frequency in the Japan Population: group A, top 1-10 haplotypes; group B, top 11-100 haplotypes; and group C, haplotype 101-. We then compared various items including clinical biomarkers with the HLA haplotype frequency. Results: A significant negative correlation was identified between older persons and length of survival. There are also significant correlations between survival and levels of immunoglobulin G, D-dimer, and C-reactive protein, as well as the platelet-large cell ratio before transplantation. A total of 96, 30, and 25 patients were classified into groups A, B, and C, respectively. The HSCT match rate was significantly higher in group A patients than in those of groups B and C. In contrast, the death rate, D-dimer level, and length of time for engraftment were significantly higher in group B and C patients than in those of group A. Conclusion: An assessment of transplant-related complications is important in improving the performance of HSCT. The present data suggest that a special therapeutic strategy is necessary for HSCT using low-frequency HLA haplotypes. [ABSTRACT FROM AUTHOR]

Tens of thousands of cases of invasive meningococcal diseases (IMD) with thousands of deaths are reported annually worldwide; however, only approximately 40 cases occur each year in Japan. Therefore, the majority of medical technologists in Japan have never performed or prepared for analyses of the causative agent, Neisseria meningitidis. Since IMD outbreaks have been reported at mass gathering events, the risk of IMD will increase in Japan in 2021 because of the Olympics. In the present study, we developed a new simple gel-based duplex PCR method that may be employed by the majority Japanese clinical laboratories. It is simple to perform and time- and cost-effectively identifies encapsulated and unencapsulated N. meningitidis by detecting the encapsulated N. meningitidis -specific ctrB and N. meningitidis -specific ggt genes. We consider this simple and cost-effective identification method to compensate for the lack of experience and resource-poor conditions in most Japanese laboratories in which N. meningitidis has rarely been examined. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C virus is the leading cause of liver cirrhosis and hepatocellular carcinoma in Japan. We aimed to examine the long-term (> 20 years) mortality and hepatocellular carcinoma rates and associated risk factors in 1412 Japanese patients with decompensated hepatitis C virus-related cirrhosis (Child-Pugh B or C).Methods: Cumulative survival and hepatocellular carcinoma rates were determined using Kaplan-Meier analysis. Independent risk factors were identified by multivariate analysis. A two-tailed P-value of < 0.05 was considered significant.Results: The patients were followed up for a median of 2 years (range 0.5-24.2 years). In total, 62.3%, 41.7%, 4.7%, and 68.3% of the patients had a history of hepatocellular carcinoma, ascites, hepatic encephalopathy, and esophageal varices, respectively. The 1-, 5-, 10-, and 20-year cumulative overall survival rates in the total cohort was 74.9%, 29.0%, 9.1%, and 1.4%, respectively. The 1-, 3-, 5-, and 10-year cumulative survival rates for patients without hepatocellular carcinoma were 93.1%, 54.4%, 18.2%, and 4.0%, respectively, and the corresponding cumulative post-decompensation hepatocellular carcinoma rates were 14.0%, 31.6%, 46.1%, and 66.2%, respectively. The independent risk factors for mortality were older age, Child-Pugh C cirrhosis, the presence of hepatocellular carcinoma, low estimated glomerular filtration rate, low serum sodium level, low platelet count, and high γ-glutamyl transferase and α-fetoprotein levels for all patients and older age, Child-Pugh C cirrhosis, and low estimated glomerular filtration rate for patients without hepatocellular carcinoma. Overall, 1035 patients (73.3%) died; the causes of death were liver failure with/without hepatocellular carcinoma, pneumonia, sepsis, cardiovascular disease, and non-hepatocellular carcinoma malignancies. The corresponding morality rates per person-year were 133.4, 59.9, 10.9, 10.6, 9.0, and 5.2, respectively.Conclusions: Among Japanese patients with decompensated hepatitis C virus-related cirrhosis, hepatocellular carcinoma is associated with poor prognosis. Our results highlight the importance of managing liver-related events, including hepatocellular carcinoma, in these patients. [ABSTRACT FROM AUTHOR]

Purpose: Improving the safety of general wards is a key to reducing serious adverse events in the postoperative period. We investigated the characteristics, treatment, and outcomes of postoperative patients managed by a rapid response system (RRS) in Japan to improve postoperative management. Methods: This retrospective study analyzed cases requiring RRS intervention that were included in the In-Hospital Emergency Registry in Japan. We analyzed data reported by 34 Japanese hospitals between January 2014 and March 2018, mainly focusing on postoperative patients for whom the RRS was activated within 7 days of surgery. Non-postoperative patients, for whom the RRS was activated in all other settings, were used for comparison as necessary. Results: There were 609 (12.7%) postoperative patients among the total patients in the registry. The major criteria were staff concerns (30.2%) and low oxygen saturation (29.7%). Hypotension, tachycardia, and inability to contact physicians were observed as triggers significantly more frequently in postoperative patients when compared with non-postoperative patients. Among RRS activations within 7 days of surgery, 68.9% of activations occurred within postoperative day 3. The ordering of tests (46.8%) and fluid bolus (34.6%) were major interventions that were performed significantly more frequently in postoperative patients when compared with non-postoperative patients. The rate of RRS activations resulting in ICU care was 32.8%. The mortality rate at 1 month was 16.2%. Conclusion: Approximately, 70% of the RRS activations occurred within postoperative day 3. Circulatory problems were a more frequent cause of RRS activation in the postoperative group than in the non-postoperative group. [ABSTRACT FROM AUTHOR]

Severe fever with thrombocytopenia syndrome (SFTS) has a high fatality rate and is caused by SFTS virus (SFTSV). Currently, SFTS is endemic to some areas in western Japan, and wild animals are considered to play important roles in the circulation of SFTSV in the environment. Previous retrospective surveys using samples mainly obtained between 2006 and 2015 revealed serological evidence of SFTSV infection in wild animals; however, seroprevalence before 2006 remains unclear. In this study, we investigated the presence of anti‐SFTSV antibodies in a total of 521 serum samples from nine wild animal species collected from 11 prefectures in central and eastern Japan between 1980 and 2000. All samples yielded negative results for antibodies to SFTSV, suggesting that there had been few or no SFTSV infections before 2000 in the sampled areas. [ABSTRACT FROM AUTHOR]