Virological characteristics of the SARS-CoV-2 Omicron BA.2 subvariants, including BA.4 and BA.5.

After the global spread of the SARS-CoV-2 Omicron BA.2, some BA.2 subvariants, including BA.2.9.1, BA.2.11, BA.2.12.1, BA.4, and BA.5, emerged in multiple countries. Our statistical analysis showed that the effective reproduction numbers of these BA.2 subvariants are greater than that of the original BA.2. Neutralization experiments revealed that the immunity induced by BA.1/2 infections is less effective against BA.4/5. Cell culture experiments showed that BA.2.12.1 and BA.4/5 replicate more efficiently in human alveolar epithelial cells than BA.2, and particularly, BA.4/5 is more fusogenic than BA.2. We further provided the structure of the BA.4/5 spike receptor-binding domain that binds to human ACE2 and considered how the substitutions in the BA.4/5 spike play roles in ACE2 binding and immune evasion. Moreover, experiments using hamsters suggested that BA.4/5 is more pathogenic than BA.2. Our multiscale investigations suggest that the risk of BA.2 subvariants, particularly BA.4/5, to global health is greater than that of original BA.2.

ORF3c is expressed in SARS-CoV-2-infected cells and inhibits innate sensing by targeting MAVS.

Most SARS-CoV-2 proteins are translated from subgenomic RNAs (sgRNAs). While the majority of these sgRNAs are monocistronic, some viral mRNAs encode more than one protein. One example is the ORF3a sgRNA that also encodes ORF3c, an enigmatic 41-amino-acid peptide. Here, we show that ORF3c is expressed in SARS-CoV-2-infected cells and suppresses RIG-I- and MDA5-mediated IFN-ß induction. ORF3c interacts with the signaling adaptor MAVS, induces its C-terminal cleavage, and inhibits the interaction of RIG-I with MAVS. The immunosuppressive activity of ORF3c is conserved among members of the subgenus sarbecovirus, including SARS-CoV and coronaviruses isolated from bats. Notably, however, the SARS-CoV-2 delta and kappa variants harbor premature stop codons in ORF3c, demonstrating that this reading frame is not essential for efficient viral replication in vivo and is likely compensated by other viral proteins. In agreement with this, disruption of ORF3c does not significantly affect SARS-CoV-2 replication in CaCo-2, CaLu-3, or Rhinolophus alcyone cells. In summary, we here identify ORF3c as an immune evasion factor of SARS-CoV-2 that suppresses innate sensing in infected cells.

Determination of the factors responsible for the tropism of SARS-CoV-2-related bat coronaviruses to Rhinolophus bat ACE2.

IMPORTANCE: The efficiency of infection receptor use is the first step in determining the species tropism of viruses. After the coronavirus disease 2019 pandemic, a number of SARS-CoV-2-related coronaviruses (SC2r-CoVs) were identified in Rhinolophus bats, and some of them can use human angiotensin converting enzyme 2 (ACE2) for the infection receptor without acquiring additional mutations. This means that the potential of certain SC2r-CoVs to cause spillover from bats to humans is "off-the-shelf." However, both SC2r-CoVs and Rhinolophus bat species are highly diversified, and the host tropism of SC2r-CoVs remains unclear. Here, we focus on two Laotian SC2r-CoVs, BANAL-20-236 and BANAL-20-52, and determine how the tropism of SC2r-CoVs to Rhinolophus bat ACE2 is determined at the amino acid resolution level.

Multiple mutations of SARS-CoV-2 Omicron BA.2 variant orchestrate its virological characteristics.

IMPORTANCE: Most studies investigating the characteristics of emerging SARS-CoV-2 variants have been focusing on mutations in the spike proteins that affect viral infectivity, fusogenicity, and pathogenicity. However, few studies have addressed how naturally occurring mutations in the non-spike regions of the SARS-CoV-2 genome impact virological properties. In this study, we proved that multiple SARS-CoV-2 Omicron BA.2 mutations, one in the spike protein and another downstream of the spike gene, orchestrally characterize this variant, shedding light on the importance of Omicron BA.2 mutations out of the spike protein.

Impact of Imprinted Immunity Induced by mRNA Vaccination in an Experimental Animal Model.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants has led to concerns that ancestral SARS-CoV-2-based vaccines may not be effective against newly emerging Omicron subvariants. The concept of "imprinted immunity" suggests that individuals vaccinated with ancestral virus-based vaccines may not develop effective immunity against newly emerging Omicron subvariants, such as BQ.1.1 and XBB.1. In this study, we investigated this possibility using hamsters. Although natural infection induced effective antiviral immunity, breakthrough infections in hamsters with BQ.1.1 and XBB.1 Omicron subvariants after receiving the 3-dose mRNA-lipid nanoparticle vaccine resulted in only faintly induced humoral immunity, supporting the possibility of imprinted immunity.

Identification and characterization of the genome of a papillomavirus from skin lesions of four-toed hedgehogs (Atelerix albiventris).

The present study describes the clinical and pathological characteristics of skin lesions in two four-toed hedgehogs (Atelerix albiventris). We performed inverse PCR to identify the genome of papillomavirus (PV) in the skin lesions and subsequently sequenced the full genome of the virus, which was tentatively named Atelerix albiventris papillomavirus 1 (AalbPV1). The overall sequences of the viral genomes of both four-toed hedgehogs were identical. This study first identified the presence of a novel PV in Japanese four-toed hedgehogs and provided genetic information about this virus.

Successful laparoscopic management of acute abdominal pain due to spontaneous rupture of subserosal vessels overlying a uterine fibroid: a case report and surgical video.

BACKGROUND: Acute abdomen comprises several emergencies. Hemoperitoneum associated with uterine fibroids, which can present as acute abdominal pain, is rare and difficult to diagnose. Especially, spontaneous hemorrhage from the rupture of the superficial vessels overlying a uterine fibroid is extremely rare, and its diagnosis and management have not been established. CASE PRESENTATION: We report a case of a 55-year-old woman who presented at our hospital with acute abdomen. After performing a computed tomography scan, we conducted a laparoscopic examination and diagnosed hemoperitoneum of ambiguous origin. We treated the patient surgically, performing a laparoscopic myomectomy to remove the origin of the hemorrhage. The patient recovered well. CONCLUSIONS: We report a case of hemoperitoneum of ambiguous origin that was diagnosed laparoscopically and treated by laparoscopic myomectomy to remove the origin of the hemorrhage. Surgeons should rapidly diagnose and manage acute abdominal pain in women with a history of uterine fibroids to prevent severe morbidity or even mortality. Therefore, laparoscopic surgery is recommended in patients with stable hemodynamics.

Cost of illness of liver diseases in Japan.

INTRODUCTION AND OBJECTIVES: Liver disease is characterized by the progression from hepatitis to cirrhosis, followed by liver cancer, i.e., a disease with a higher mortality rate as the disease progresses. To estimate the cost of illness (COI) of liver diseases, including viral hepatitis, cirrhosis, and liver cancer, and to determine the overall effect of expensive but effective direct-acting antivirals on the COI of liver diseases. PATIENTS OR MATERIALS AND METHODS: Using a COI method from available government statistics data, we estimated the economic burden at 3-year intervals from 2002 to 2017. RESULTS: The total COI of liver diseases was 1402 billion JPY in 2017. The COI of viral hepatitis, cirrhosis, and liver cancer showed a downward trend. Conversely, other liver diseases, including alcoholic liver disease and nonalcoholic steatohepatitis (NASH), showed an upward trend. The COI of hepatitis C continued to decline despite a sharp increase in drug unit prices between 2014 and 2017. CONCLUSIONS: The COI of liver diseases in Japan has been decreasing for the past 15 years. In the future, a further reduction in patients with hepatitis C is expected, and even if the incidence of NASH and alcoholic liver disease increases, that of cirrhosis and liver cancer will likely continue to decrease.

Relationship of patient safety culture with factors influencing working environment such as working hours, the number of night shifts, and the number of days off among healthcare workers in Japan: a cross-sectional study.

BACKGROUND: Patient safety culture is defined as a product of individual and group values, attitudes, perceptions, competencies, and patterns of behavior that determine the commitment to, and the style and proficiency of, an organization's health and safety management. Factors influencing healthcare workers' working environment such as working hours, the number of night shifts, and the number of days off may be associated with patient safety culture, and the association pattern may differ by profession. This study aimed to examine the relationship between patient safety culture and working environment. METHODS: Questionnaire surveys were conducted in 2015 and 2016. The first survey was conducted in hospitals in Japan to investigate their patient safety management system and activities and intention to participate in the second survey. The second survey was conducted in 40 hospitals; 100 healthcare workers from each hospital answered a questionnaire that was the Japanese version of the Hospital Survey on Patient Safety Culture for measuring patient safety culture. The relationship of patient safety culture with working hours in a week, the number of night shifts in a month, and the number of days off in a month was analyzed. RESULTS: Response rates for the first and second surveys were 22.4% (731/3270) and 94.2% (3768/4000), respectively. Long working hours, numerous night shifts, and few days off were associated with low patient safety culture. Despite adjusting the working hours, the number of event reports increased with an increase in the number of night shifts. Physicians worked longer and had fewer days off than nurses. However, physicians had fewer composites of patient safety culture score related to working hours, the number of night shifts, and the number of days off than nurses. CONCLUSIONS: This study suggested a possibility of improving the patient safety culture by managing the working environment of healthcare workers. High number of night shifts may lead to high number of event reports. Working hours, the number of night shifts, and the number of days off may differently influence patient safety culture in physicians and nurses.

Capturing the trends in hospital standardized mortality ratios for pneumonia: a retrospective observational study in Japan (2010 to 2018).

BACKGROUND: Pneumonia has a high human toll and a substantial economic burden in developed countries like Japan, where the crude mortality rate was 77.7 per 100,000 people in 2017. As this trend is going to continue with increasing number of the elderly multi-morbid population in Japan; monitoring performance over time is a social need to alleviate the disease burden. The study objective was to determine the characteristics of hospital standardized mortality ratios (HSMRs) for pneumonia in Japan from 2010 to 2018 to describe this trend. METHODS: Data of the DPC (Diagnostic Procedures Combination) database were used, which is an administrative claims and discharge summary database for acute care in-patients in Japan. HSMRs were calculated using the actual and expected numbers of in-hospital deaths, the latter of which was calculated using logistic regression model, with a number of explanatory variables, e.g., age, sex, urgency of admission, mode of transportation, patient volume per month in each hospital, A-DROP score, and Charlson comorbidity index (CCI). We constructed two HSMR models: a single-year model, which included hospitals with > 10 in-patients per month and, a 9-year model, which included those hospitals with complete 9-year data. Predictive accuracy of the logistic models was assessed using c-index (area under receiver operating curve). RESULTS: Total 230,372 patients were included for the analysis over the 9-year study period. Calculated HSMRs showed wide variation among hospitals. The proportion of hospitals with HSMR less than 100 increased from 36.4% in 2010 to 60.6% in 2018. Both models showed good predictive ability with a c-statistic of 0.762 for the 9-year model, and no less than 0.717 for the single-year model. CONCLUSION: This study denoted that HSMRs of pneumonia can be calculated using DPC data in Japan and revealed significant variations among hospitals with comparable case-mixes. Therefore, HSMR can be used as yet another measure to help improve quality of care over time if other indicators are examined in parallel and to get a clear picture of where hospitals excel and lack.

The structure of the quality of clinical practice guidelines with the items and overall assessment in AGREE II: a regression analysis.

BACKGROUND: The Appraisal of Guidelines for Research & Evaluation (AGREE) II has been widely used to evaluate the quality of clinical practice guidelines (CPGs). While the relationship between the overall assessment of CPGs and scores of six domains were reported in previous studies, the relationship between items constituting these domains and the overall assessment has not been analyzed. This study aims to investigate the relationship between the score of each item and the overall assessment and identify items that could influence the overall assessment. METHODS: All Japanese CPGs developed using the evidence-based medicine method and published from 2011 to 2015 were used. They were independently evaluated by three appraisers using AGREE II. The evaluation results were analyzed using regression analysis to evaluate the influence of 6 domains and 23 items on the overall assessment. RESULTS: A total of 206 CPGs were obtained. All domains and all items except one were significantly correlated to the overall assessment. Regression analysis revealed that Domain 3 (Rigour of Development), Domain 4 (Clarity of Presentation), Domain 5 (Applicability), and Domain 6 (Editorial Independence) had influence on the overall assessment. Additionally, four items of AGREE II, clear selection of evidence (Item 8), specific/unambiguous recommendations (Item 15), advice/tools for implementing recommendations (Item 19), and conflicts of interest (Item 22), significantly influenced the overall assessment and explained 72.1% of the variance. CONCLUSIONS: These four items may highlight the areas for improvement in developing CPGs.

Trends in hospital standardized mortality ratios for stroke in Japan between 2012 and 2016: a retrospective observational study.

OBJECTIVE: Stroke is one of the leading causes of death and disability, and imposes a major healthcare burden. The aim of this study was to determine the characteristics of hospital standardized mortality ratios (HSMRs) for stroke in Japan for the year 2012-16 to describe the trend. DESIGN: Retrospective observational study. SETTING: Data from the Japanese administrative database. PARTICIPANTS: All hospital admissions for stroke were identified from diagnostic procedures combination (DPC) database from 2012 to 2016. MAIN OUTCOME MEASURES: HSMR was calculated using the actual number of in-hospital deaths and expected deaths. To obtain the expected death number, a logistic regression model was developed to get the coefficient with a number of explanatory variables. Predictive accuracy of the logistic models was assessed using c-index and calibration was evaluated using the Hosmer-Lemeshow test. RESULTS: A total of 63 084 patients admitted for stroke from January 2012 to December 2016 were analyzed. HSMRs showed declining tendency over these 5 years, suggesting stroke-related mortality has been improving. While the HSMRs varied from year to year, a wide variation was also seen among the different hospitals in Japan. The proportion of hospitals with HSMR less than 100 increased from 41.0% in 2012 to 59.0% in 2016. CONCLUSION: This study demonstrated that HSMR can be calculated using DPC data and found wide variation in HSMR of stroke among hospitals in Japan and enabled us to image the trend. By examining these trends, facilities, authorities and provinces can initiate designs that will ultimately lead to an upgraded healthcare delivery system.

Comprehensive cost of illness of dementia in Japan: a time trend analysis based on Japanese official statistics.

OBJECTIVE: To analyze the chronological change in social burden of dementia in Japan for policy implications of appropriate resource allocation and quality improvement. DESIGN: National, population-based, observational study from 2002 to 2014. SETTING: Seven nationwide data sets from Japanese official statistics. METHOD: Comprehensive Cost of Illness method. MAIN OUTCOME MEASURES: The outcome variables included healthcare services, nursing care services, informal care (unpaid care offered by family and relatives), mortality cost and morbidity cost. RESULTS: The number of patients with dementia increased 2.50 times from 0.42 million in 2002 to 1.05 million in 2014. While the number of patients living in homes and communities increased by 3.22 times that of patients living in nursing care facilities increased by 1.42 times. The total social burden increased 2.06-2.27 times from JPY 1.84-2.42 to 3.79-5.51 trillion (JPY 1 trillion = US$ 100 billion). Regarding the total burden, the proportion of informal care provided increased from 36.6-51.9% to 37.7-57.2%. Furthermore, the proportion of primary caretakers aged ≥70 years increased from 27.6% to 37.6%. CONCLUSIONS: Owing to the promotion of 'Deinstitutionalization' (shift of nursing care site from in-facilities to in-home and in-community), 'Elderly care by the elderly,' and 'Earlier diagnosis of dementia,' the average cost per patient reduced by 0.82-0.91 times from JPY 4.37-5.77 to 3.60-5.24 million. Therefore, the management of informal care in a manner that does not exceed the acceptable limit of the patients' caretakers, while maintaining patient safety and quality of care, is imperative.

Cost of illness of non-alcoholic liver cirrhosis in Japan: A time trend analysis and future projections.

AIM: Liver cirrhosis is a preneoplastic condition to hepatocellular carcinoma that is an important worldwide public health concern, and its economic burden has been estimated in some countries. The objective of this study was to estimate and predict the cost of illness (COI) associated with non-alcoholic liver cirrhosis in Japan. METHODS: Using a COI method on available data from government statistics, we estimated the economic burden in 3-year intervals from 1996 to 2014. We then predicted the COI in 3-year intervals from 2017 to 2029 using fixed and variable model estimations. With fixed model estimation, only the estimated future population was used as a variable. Variable model estimation considered the time trends of health-related indicators throughout the past 18 years. RESULTS: The estimated COI of non-alcoholic liver cirrhosis was ¥208.1bn in 2014. The COI of non-alcoholic liver cirrhosis had a downward trend from 1996 to 2014. The predicted future COI of non-alcoholic liver cirrhosis was ¥144.3-210.5bn, ¥106.0-213.8bn, ¥88.6-213.4bn, ¥76.7-215.5bn, and ¥66.4-214.3bn in 2017, 2020, 2023, 2026, and 2029, respectively. CONCLUSIONS: The results of this study suggest that the COI of non-alcoholic liver cirrhosis in Japan has steadily decreased and will continue to decrease. Treatment of patients with hepatitis C virus infection with newly introduced technologies has high therapeutic effectiveness, which will affect the future prevalence of non-alcoholic liver cirrhosis. When interpreting the results of long-term estimation, it should be noted that the results of this study were based on present conditions.

Effects of the concentration of digestive surgical operations in regional Japan.

PURPOSE: The purpose of this study was to investigate the relationship between the concentration of digestive system surgery and outcomes at a regional level in Japan, using time-series data. METHODS: We used nationwide data from 2008 to 2013, and analyzed the ten most common surgical procedures. The unit of analysis was secondary medical areas (SMAs), which cover several municipalities and provide medical services for common diseases. The concentration of surgery in these areas was measured using the Herfindahl-Hirschman Index (HHI) and the relationship between the concentration of surgery and length of stay in hospital (LOS) was analyzed, in accordance with surgical difficulty. RESULTS: There was a downward trend in both the HHI and LOS from 2008 to 2013. SMAs showing an upward trend in the HHI (increased concentration) were associated with a greater reduction in LOS than those showing a downward trend for eight surgical procedures. For three easy surgical procedures, increased concentration of surgery was significantly associated with a reduction in LOS. After adjustment for trends in the aging population and the surgical volume in 2008, an increasing concentration for three easy surgical procedures was significantly related to a reduction in the LOS. CONCLUSION: Concentrating relatively easy surgical procedures at a regional level may be associated with a reduction in LOS.

Cost of illness of the prostate cancer in Japan--a time-trend analysis and future projections.

BACKGROUND: The majority of patients with prostate cancer (International Classification of Diseases, 10th edition, code C61) are elderly. With Japan's rapidly society aging, both the prevalence and mortality of prostate cancer are expected to increase in the future. The objective of this study was to estimate and predict the cost of illness (COI) associated with prostate cancer in Japan. METHODS: Using a COI method based on available data from government office statistics, we estimated the COI for 2002, 2005, 2008, and 2011. We then predicted the COI for 2014, 2017, and 2020 using fixed model estimation and variable model estimation. With fixed model estimation, only estimated future population was used as a variable. Variable model estimation considered the time trend of health-related indicators in the past 15 years. We derived the COI from the sum of direct and indirect costs (morbidity and mortality). RESULTS: We found the predicted future COI of prostate cancer to be 354.7-378.3 billion yen in 2014, 370.8-421.0 billion yen in 2017, and 385.3-474.1 billion yen in 2020. Regardless of the estimation model, we found that COI would increase compared with the baseline year 2011 (307.3 billion yen). The direct costs for inpatient and outpatient treatment, laboratory tests, and drugs accounted for 60-75% of the COI of prostate cancer. CONCLUSIONS: The results of this study suggest that the COI of prostate cancer in Japan has steadily increased and is expected to rise in the future. Direct costs comprised the largest proportion of the COI and are anticipated to continue expanding; this will result in increased burden on public funds in Japan, where a universal public insurance system operates. These trends differ from those with other forms of cancer.

Characteristics of unit-level patient safety culture in hospitals in Japan: a cross-sectional study.

BACKGROUND: Patient safety culture (PSC) has an important role in determining safety and quality in healthcare. Currently, little is known about the status of unit-level PSC in hospitals in Japan. To develop appropriate strategies, characteristics of unit-level PSC should be investigated. Work units may be classified according to the characteristics of PSC, and common problems and appropriate strategies may be identified for each work unit category. This study aimed to clarify the characteristics of unit-level PSC in hospitals in Japan. METHODS: In 2012, a cross-sectional study was conducted at 18 hospitals in Japan. The Hospital Survey on Patient Safety Culture questionnaire, developed by the United States Agency for Healthcare Research and Quality, was distributed to all healthcare workers (n =12,076). Percent positive scores for 12 PSC sub-dimensions were calculated for each unit, and cluster analysis was used to categorise the units according to the percent positive scores. A generalised linear mixed model (GLMM) was used to analyse the results of the cluster analysis, and odds ratios (ORs) for categorisation as high-PSC units were calculated for each unit type. RESULTS: A total of 9,124 respondents (75.6%) completed the questionnaire, and valid data from 8,700 respondents (72.0%) were analysed. There were 440 units in the 18 hospitals. According to the percent positive scores for the 12 sub-dimensions, the 440 units were classified into 2 clusters: high-PSC units (n =184) and low-PSC units (n =256). Percent positive scores for all PSC sub-dimensions for high-PSC units were significantly higher than those for low-PSC units. The GLMM revealed that the combined unit type of 'Obstetrics and gynaecology ward, perinatal ward or neonatal intensive care unit' was significantly more likely to be categorised as high-PSC units (OR =9.7), and 'Long-term care ward' (OR =0.2), 'Rehabilitation unit' (OR =0.2) and 'Administration unit' (OR =0.3) were significantly less likely to be categorised as high-PSC units. CONCLUSIONS: Our study findings demonstrate that PSC varies considerably among different unit types in hospitals in Japan. Factors contributing to low PSC should be identified and possible measures for improving PSC should be developed and initiated.

Virological characteristics of a SARS-CoV-2-related bat coronavirus, BANAL-20-236.

BACKGROUND: Although several SARS-CoV-2-related coronaviruses (SC2r-CoVs) were discovered in bats and pangolins, the differences in virological characteristics between SARS-CoV-2 and SC2r-CoVs remain poorly understood. Recently, BANAL-20-236 (B236) was isolated from a rectal swab of Malayan horseshoe bat and was found to lack a furin cleavage site (FCS) in the spike (S) protein. The comparison of its virological characteristics with FCS-deleted SARS-CoV-2 (SC2ΔFCS) has not been conducted yet. METHODS: We prepared human induced pluripotent stem cell (iPSC)-derived airway and lung epithelial cells and colon organoids as human organ-relevant models. B236, SARS-CoV-2, and artificially generated SC2ΔFCS were used for viral experiments. To investigate the pathogenicity of B236 in vivo, we conducted intranasal infection experiments in hamsters. FINDINGS: In human iPSC-derived airway epithelial cells, the growth of B236 was significantly lower than that of the SC2ΔFCS. A fusion assay showed that the B236 and SC2ΔFCS S proteins were less fusogenic than the SARS-CoV-2 S protein. The infection experiment in hamsters showed that B236 was less pathogenic than SARS-CoV-2 and even SC2ΔFCS. Interestingly, in human colon organoids, the growth of B236 was significantly greater than that of SARS-CoV-2. INTERPRETATION: Compared to SARS-CoV-2, we demonstrated that B236 exhibited a tropism toward intestinal cells rather than respiratory cells. Our results are consistent with a previous report showing that B236 is enterotropic in macaques. Altogether, our report strengthens the assumption that SC2r-CoVs in horseshoe bats replicate primarily in the intestinal tissues rather than respiratory tissues. FUNDING: This study was supported in part by AMED ASPIRE (JP23jf0126002, to Keita Matsuno, Kazuo Takayama, and Kei Sato); AMED SCARDA Japan Initiative for World-leading Vaccine Research and Development Centers "UTOPIA" (JP223fa627001, to Kei Sato), AMED SCARDA Program on R&D of new generation vaccine including new modality application (JP223fa727002, to Kei Sato); AMED SCARDA Hokkaido University Institute for Vaccine Research and Development (HU-IVReD) (JP223fa627005h0001, to Takasuke Fukuhara, and Keita Matsuno); AMED Research Program on Emerging and Re-emerging Infectious Diseases (JP21fk0108574, to Hesham Nasser; JP21fk0108493, to Takasuke Fukuhara; JP22fk0108617 to Takasuke Fukuhara; JP22fk0108146, to Kei Sato; JP21fk0108494 to G2P-Japan Consortium, Keita Matsuno, Shinya Tanaka, Terumasa Ikeda, Takasuke Fukuhara, and Kei Sato; JP21fk0108425, to Kazuo Takayama and Kei Sato; JP21fk0108432, to Kazuo Takayama, Takasuke Fukuhara and Kei Sato; JP22fk0108534, Terumasa Ikeda, and Kei Sato; JP22fk0108511, to Yuki Yamamoto, Terumasa Ikeda, Keita Matsuno, Shinya Tanaka, Kazuo Takayama, Takasuke Fukuhara, and Kei Sato; JP22fk0108506, to Kazuo Takayama and Kei Sato); AMED Research Program on HIV/AIDS (JP22fk0410055, to Terumasa Ikeda; and JP22fk0410039, to Kei Sato); AMED Japan Program for Infectious Diseases Research and Infrastructure (JP22wm0125008 to Keita Matsuno); AMED CREST (JP21gm1610005, to Kazuo Takayama; JP22gm1610008, to Takasuke Fukuhara; JST PRESTO (JPMJPR22R1, to Jumpei Ito); JST CREST (JPMJCR20H4, to Kei Sato); JSPS KAKENHI Fund for the Promotion of Joint International Research (International Leading Research) (JP23K20041, to G2P-Japan Consortium, Keita Matsuno, Takasuke Fukuhara and Kei Sato); JST SPRING (JPMJSP2108 to Shigeru Fujita); JSPS KAKENHI Grant-in-Aid for Scientific Research C (22K07103, to Terumasa Ikeda); JSPS KAKENHI Grant-in-Aid for Scientific Research B (21H02736, to Takasuke Fukuhara); JSPS KAKENHI Grant-in-Aid for Early-Career Scientists (22K16375, to Hesham Nasser; 20K15767, to Jumpei Ito); JSPS Core-to-Core Program (A. Advanced Research Networks) (JPJSCCA20190008, to Kei Sato); JSPS Research Fellow DC2 (22J11578, to Keiya Uriu); JSPS Research Fellow DC1 (23KJ0710, to Yusuke Kosugi); JSPS Leading Initiative for Excellent Young Researchers (LEADER) (to Terumasa Ikeda); World-leading Innovative and Smart Education (WISE) Program 1801 from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) (to Naganori Nao); Ministry of Health, Labour and Welfare (MHLW) under grant 23HA2010 (to Naganori Nao and Keita Matsuno); The Cooperative Research Program (Joint Usage/Research Center program) of Institute for Life and Medical Sciences, Kyoto University (to Kei Sato); International Joint Research Project of the Institute of Medical Science, the University of Tokyo (to Terumasa Ikeda and Takasuke Fukuhara); The Tokyo Biochemical Research Foundation (to Kei Sato); Takeda Science Foundation (to Terumasa Ikeda and Takasuke Fukuhara); Mochida Memorial Foundation for Medical and Pharmaceutical Research (to Terumasa Ikeda); The Naito Foundation (to Terumasa Ikeda); Hokuto Foundation for Bioscience (to Tomokazu Tamura); Hirose Foundation (to Tomokazu Tamura); and Mitsubishi Foundation (to Kei Sato).

Cost of illness of the stomach cancer in Japan - a time trend and future projections.

BACKGROUND: Stomach cancer is one of the leading causes of cancer deaths in Japan. The objectives of this study were to estimate and project the economic burden associated with stomach cancer in Japan, and to identify the key factors that drive the economic burden of stomach cancer. METHODS: We calculated Cost of illness (COI) of 1996, 2002, 2008, 2014 and 2020 by using government office statistics and the COI method. We calculated direct cost and indirect cost (morbidity cost and mortality cost), and estimated the COI by summing them up. RESULTS: The number of deaths remained at approximately 50,000 in 1996-2008. COI was in downward trend from 1,293.5 billion yen in 1996 to 1,114.2 billion yen in 2008. Morbidity cost was 85.6 billion yen and 54.0 billion yen, mortality cost was 972.3 billion yen and 806.4 billion yen, and mortality cost per person was 19.4 million yen and 16.1 million yen in 1996 and 2008, respectively. Decrease of mortality cost that accounted for a large part of the COI (72.4% in 2008) was the major contributing factor. COI is predicted to decrease if the trend of health related indicators continues (442.8-1,056.1 billion yen depending on the model in 2020). Mortality cost per person is also predicted to decrease (9.5-12.5 million yen depending on the model in 2020). CONCLUSIONS: If the trend of health related indicators continues, it is estimated that COI of stomach cancer would decrease. "Aging", "change of the healthcare providing system" and "new medical technology" are considered as contributing factors of COI.

The characteristics of patient safety culture in Japan, Taiwan and the United States.

BACKGROUND: Quality and safety issues are receiving growing attention. Patient safety culture (PSC) plays an important role in patient safety. The characteristics of PSC in various countries, each with a different set of values, have not been determined sufficiently. The aim of this study is to investigate the characteristics of PSC in Japan, Taiwan and the U.S. METHODS: A cross-sectional survey was conducted in Japan and Taiwan using the Hospital Survey on PSC (HSOPS) questionnaire developed by the U.S. Agency for Healthcare Research and Quality (AHRQ). Data from Japan and Taiwan were also compared with the U.S. "2010 HSOPS Comparative Database" provided by AHRQ. RESULTS: Valid response rates in Japan, Taiwan and the U.S. were 66.5% (6,963/10,466), 85.7% (10,019/11,692) and 35.2% (291,341/827,424), respectively. The proportion of respondents with some experience of event reporting during the past 12 months was highest in Japan. In general, U.S. healthcare workers were likely to evaluate their PSC higher than that in Japan or Taiwan. The attitude of continuous improvement in Japan and event reporting of near misses in Taiwan were rated as low. In the U.S., staffing was rated as high. CONCLUSIONS: The results suggest that PSC varies among different countries, and the cultural setting of each country should be given special consideration in the development of effective intervention plans to improve PSC. Additional investigations with improved methodology and a common protocol are required to accurately compare PSCs among countries.