Difference between Keratinized- and Non-Keratinized-Originating Epithelium in the Process of Immune Escape of Oral Squamous Cell Carcinoma.

Immune checkpoint inhibitors (ICIs), including anti-programmed cell death 1 ligand 1 (PD-L1) antibodies, are significantly changing treatment strategies for human malignant diseases, including oral cancer. Cancer cells usually escape from the immune system and acquire proliferative capacity and invasive/metastatic potential. We have focused on the two immune checkpoints, PD-1/PD-L1 and CD47/SIRPα, in the tumor microenvironment of oral squamous cell carcinoma (OSCC), performed a retrospective analysis of the expression of seven immune-related factors (PD-L1, PD-1, CD4, CD8, CD47, CD56 and CD11c), and examined their correlation with clinicopathological status. As a result, there were no significant findings relating to seven immune-related factors and several clinicopathological statuses. However, the immune checkpoint-related factors (PD-1, PD-L1, CD47) were highly expressed in non-keratinized epithelium-originated tumors when compared to those in keratinized epithelium-originated tumors. It is of interest that immunoediting via immune checkpoint-related factors was facilitated in non-keratinized sites. Several researchers reported that the keratinization of oral mucosal epithelia affected the immune response, but our present finding is the first study to show a difference in tumor immunity in the originating epithelium of OSCC, keratinized or non-keratinized. Tumor immunity, an immune escape status of OSCC, might be different in the originating epithelium, keratinized or non-keratinized.

Development and usability of a hospital standardized ADL ratio (HSAR) for elderly patients with cerebral infarction: a retrospective observational study using administrative claim data from 2012 to 2019 in Japan.

BACKGROUND: Maintenance of activities of daily living (ADL) during acute hospitalization is an important treatment goal, especially for elderly inpatients with diseases that often leave disabilities, such as cerebral infarction. However, studies assessing risk-adjusted ADL changes are limited. In this study, we developed and calculated a hospital standardized ADL ratio (HSAR) using Japanese administrative claims data to measure the quality of hospitalization care for patients with cerebral infarction. METHODS: This study was designed as a retrospective observational study using the Japanese administrative claim data from 2012 to 2019. The data of all hospital admissions with a primary diagnosis of cerebral infarction (ICD-10, I63) were used. The HSAR was defined as the ratio of the observed number of ADL maintenance patients to the expected number of ADL maintenance patients multiplied by 100, and ratio of ADL maintenance patients was risk-adjusted using multivariable logistic regression analyses. The c-statistic was used to evaluate the predictive accuracy of the logistic models. Changes in HSARs in each consecutive period were assessed using Spearman's correlation coefficient. RESULTS: A total of 36,401 patients from 22 hospitals were included in this study. All variables used in the analyses were associated with ADL maintenance, and evaluations using the HSAR model showed predictive ability with c-statistics (area under the curve, 0.89; 95% confidence interval, 0.88-0.89). CONCLUSIONS: The findings indicated a need to support hospitals with a low HSAR because hospitals with high/low HSAR were likely to produce the same results in the subsequent periods. HSAR can be used as a new quality indicator of in-hospital care and may contribute to the assessment and improvement of the quality of care.

Cost of illness for colorectal cancer in Japan - a time trend and future projections (1996-2035) based on governmental statistics.

BACKGROUND: In Japan, the crude mortality rate of colorectal cancer is the second highest among men and highest among women by site. We aimed to calculate the social burden of colorectal cancer using the cost of illness (COI) method and identify the main factors that drove changes in the COI. METHODS: From 1996 to 2020, the COI was estimated by summing direct, morbidity, and mortality costs. In addition, the COI by 2035 was projected by fitting approximate curves obtained from historical data to health-related indicators by sex and age. Future projections of the number of patients by the stage of disease were also made to explore the factors that changed the COI. RESULTS: The number of deaths and incidence from colorectal cancer was expected to continue increasing due to population aging. However, the COI was projected to rise from 850.3 billion yen in 1996 to 1.451 trillion yen in 2020, and peaked at 1.478 trillion yen in 2023 before it declined. CONCLUSION: Although the increased number of deaths associated with population aging increased COI, it was expected that the COI would decrease around 2023 due to a decrease in the human capital value of the deceased. In addition, the mortality rate was expected to decrease in the future due to an increase in the percentage of early detection of colorectal cancer via widespread screening and advances in medical technology.

Cost of illness in a super-aged society-comparison of breast, lung, and prostate cancer in Japan.

BACKGROUND: Aging increases the disease burden because of an increase in disease prevalence and mortality among older individuals. This could influence the perception of the social burden of different diseases and treatment prioritization within national healthcare services. Cancer is a disease with a high disease burden in Japan; however, the age-specific frequency and age-specific mortality rates differ according to site. In this study, we evaluated the relationship between the aging of the Japanese society and the disease burden by comparing the features of three cancers with different age-specific frequency rates in Japan. Furthermore, we made projections for the future to determine how the social burden of these cancers will change. METHODS: We calculated the social burden of breast, lung, and prostate cancers by adding the direct, morbidity, and mortality costs. Estimates were made using the cost of illness (COI) method. For future projections, approximate curves were fitted for mortality rate, number of hospital admissions per population, number of outpatient visits per population, and average length of hospital stay according to sex and age. RESULTS: The COI of breast, lung, and prostate cancers in 2017 was 903.7, 1,547.6, and 390.8 billion yen, respectively. Although the COI of breast and prostate cancers was projected to increase, that of lung cancer COI was expected to decrease. In 2017, the average age at death was 68.8, 76.8, and 80.7 years for breast, lung, and prostate cancers, respectively. CONCLUSIONS: Patients with breast cancer die earlier than those with other types of cancer. The COI of breast cancer ("young cancer") was projected to increase slightly because of an increase in mortality costs, whereas that of prostate cancer ("aged cancer") was projected to increase because of an increase in direct costs. The COI of lung cancer ("aging cancer") was expected to decrease in 2020, despite the increase in deaths, as the impact of the decrease in human capital value outweighed that of the increase in deaths. Our findings will help prioritize future policymaking, such as cancer control research grants.

Trends in the development process of clinical practice guidelines: a questionnaire survey for the guideline development groups in Japan.

BACKGROUND: Clinical practice guidelines (CPGs) are representative methods for promoting healthcare standardization and improving its quality. Previous studies on the CPG (published by 2006) development process in Japan reported that the involvement of experts and patients, efficient evidence collection and appraisal, and paucity of evidence on Japanese patients should be improved for the efficient CPG development. This study aimed to clarify the trends of CPG development process in Japan, focusing on the involvement of experts and patients, efficient evidence collection and appraisal, and paucity of Japanese evidence. METHODS: A cross-sectional questionnaire survey was conducted for CPG development groups to collect information on the development activities of the CPGs published from 2012 to 2019. These CPGs were identified from the Japanese guideline clearinghouse. The questionnaire included the questions on composing the group, securing funding sources, collecting and appraising the research evidence, and the difficulties in the CPG development process. The questionnaires were distributed to the chairpersons of the CPG development groups through postal mail from November 2020 to January 2021. Combining the data from the current survey with those of previous studies reporting the development process of CPGs published by 2011, we analyzed the trend in the CPG development process. RESULTS: Of the total 265 CPGs included in the analysis, 164 (response rate: 41.4%) were from the current survey and 101 (response rate: 44.5%) were from previous studies. Among these, 40 (15.1%) were published by 2005, 47 (17.7%) in 2006-2010, 77 (29.1%) in 2011-2015, and 101 (38.1%) in 2016-2019. The proportion of CPGs involving methodologists did not increase through the publication periods. The proportion of CPGs involving patients almost doubled from the first period (15.9%) to the fourth period (32.4%). The yield rates of the articles did not change through the publication periods. The difficulty in "Coping with the paucity of Japanese evidence" has been improving consistently (69.2% in the first period to 37.4% in the fourth period). CONCLUSIONS: Our results suggest the need for methodological improvement in the efficient collection and appraisal of evidence and in the system assigning experts to the CPG development groups.

Cross-cultural adaptation and validation of the Chinese version of the revised surveys on patient safety culture™ (SOPS®) hospital survey 2.0.

BACKGROUND: Surveys on Patient Safety Culture™ (SOPS®) Hospital Survey (HSOPS 1.0), developed by the U.S. Agency for Healthcare Research and Quality in 2004, has been widely adopted in the United States and internationally. An updated version, the SOPS Hospital Survey 2.0 (HSOPS 2.0), released in 2019, has not yet been applied in China. The aim of the present study was to translate HSOPS 2.0 into Chinese version with cross-cultural adaptations and test its psychometric properties. METHODS: A convenience sample was used. Hospital nurses (N = 1013) and a sub-set (n = 200) was invited for the re-test. A three-stage study was conducted. Firstly, the HSOPS 2.0 was translated by a panel. Secondly, the content validity was tested using the two-round Delphi method and cognitive interview. Next, the construct validity was tested by the confirmatory factor analysis and further demonstrated by the convergent validity, discriminant validity, and correlations with the outcome of patient safety. Thirdly, the reliability was tested by internal consistency reliability and re-test reliability. RESULTS: The "float or PRN" and "manager" words were deleted as considered unfitted for the Chinese health care system. The content validity index provided evidence of strong content validity (I-CVI = 0.84 ~ 1.00, S-CVI = 0.98). Confirmatory factor analysis revealed a good model fit (χ2/df = 4.05, RMSEA = 0.06, CFI = 0.94) and acceptable factor loadings (0.41 ~ 0.97). Convergent validity, and discriminant validity supported the factorial structure of the Chinese version of HSOPS 2.0. Further evidence for the construct validity was derived from correlations with the outcome of patient safety (r = 0.10 ~ 0.41). A good internal consistency (Cronbach's α = 0.68 ~ 0.93, McDonald's omega = 0.84 ~ 0.96) and test-retest reliability (ICC = 0.78 ~ 0.95) showed acceptable reliability. Additionally, Chinese nurses reported markedly lower scores for three dimensions, including "Response to Error", "Communication Openness", and "Reporting Patient Safety Events", when comparing the findings of this study with those from U.S. research utilizing the HSOPS 2.0. CONCLUSION: The Chinese version of HSOPS 2.0 demonstrated good validity and reliability in a Chinese sample of hospital nurses, which suggests that it can be used to measure nurse-perceived patient safety culture in future research and practice. Psychometric properties of the Chinese version of HSOPS 2.0 among other Chinese healthcare professionals remain to be confirmed.

Effectiveness of cetuximab as preemptive postsurgical therapy for oral squamous cell carcinoma patients with major risk: a single-center retrospective cohort study.

A retrospective cohort study was performed to investigate the effectiveness of preemptive postsurgical therapy with cetuximab for patients with a major risk of recurrence or metastasis after clinical complete resection of primary oral squamous cell carcinoma (OSCC). The study period was from 2007 to 2019 for patients treated at the Department of Oral and Maxillofacial Surgery, Dokkyo Medical University School of Medicine. OSCC patients with major risk (n = 88) in the follow-up period were divided into groups with no postsurgical treatment (NP group), with standard postsurgical treatment (SP group), and with postsurgical treatment including cetuximab (CP group), and prognosis were compared among those groups. The 5-year overall survival rate was significantly higher in patients who received postsurgical treatment with cetuximab (CP) compared to that in the other two groups ((CP vs. NP, p = 0.028; CP vs. SP, p = 0.042). Furthermore, we performed multivariate analysis to evaluate the effects of the main components of the treatment. Among CDDP, radiotherapy, and cetuximab, only cetuximab significantly contributed to improved survival by univariate analysis (crude HR:0.228, 95%CI:0.05-0.968, p = 0.045). cetuximab also showed the same tendency in multivariate analysis, although p value did not reach significant level (Adjusted HR: 0.233, 95%CI: 0.053-1.028, p = 0.054). The results suggest that the postsurgical treatment with cetuximab as a preemptive postsurgical therapy after complete surgical resection of a visible tumor is considerably effective for OSCC patients with major risk, in other words, invisible dormant metastasis.

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.

Identification of Binding Proteins for TSC22D1 Family Proteins Using Mass Spectrometry.

TSC-22 (TGF-ß stimulated clone-22) has been reported to induce differentiation, growth inhibition, and apoptosis in various cells. TSC-22 is a member of a family in which many proteins are produced from four different family genes. TSC-22 (corresponding to TSC22D1-2) is composed of 144 amino acids translated from a short variant mRNA of the TSC22D1 gene. In this study, we attempted to determine the intracellular localizations of the TSC22D1 family proteins (TSC22D1-1, TSC-22 (TSC22D1-2), and TSC22(86) (TSC22D1-3)) and identify the binding proteins for TSC22D1 family proteins by mass spectrometry. We determined that TSC22D1-1 was mostly localized in the nucleus, TSC-22 (TSC22D1-2) was localized in the cytoplasm, mainly in the mitochondria and translocated from the cytoplasm to the nucleus after DNA damage, and TSC22(86) (TSC22D1-3) was localized in both the cytoplasm and nucleus. We identified multiple candidates of binding proteins for TSC22D1 family proteins in in vitro pull-down assays and in vivo binding assays. Histone H1 bound to TSC-22 (TSC22D1-2) or TSC22(86) (TSC22D1-3) in the nucleus. Guanine nucleotide-binding protein-like 3 (GNL3), which is also known as nucleostemin, bound to TSC-22 (TSC22D1-2) in the nucleus. Further investigation of the interaction of the candidate binding proteins with TSC22D1 family proteins would clarify the biological roles of TSC22D1 family proteins in several cell systems.

Morphometric and histomorphometric evaluations of high-purity macro/microporous beta-tricalcium phosphate in maxillary sinus floor elevation: preliminary results on a retrospective, multi-center, observational study.

BACKGROUND: The present study examined the effectiveness of high-purity macro/microporous beta-tricalcium phosphate (HPMM ß-TCP) as a bone grafting material for maxillary sinus floor elevation by morphometric, histopathological, and histomorphometric evaluations. METHODS: Ten unilateral maxillary sinus floor elevation procedures using 100% HPMM ß-TCP were performed in 10 patients. Morphometric evaluation was carried out by computed tomography (CT) imaging immediately after augmentation and prior to dental implant placement 7 months later. Histopathological and histomorphometric evaluations were carried out by bone biopsy retrieval at the time of dental implant placement 7 months after sinus floor elevation. RESULTS: All 10 sinus floor elevations were successful. Morphometric evaluation by CT showed that the vertical height and volume gained by sinus floor elevation decreased 7 months after surgery. Histopathological evaluation of bone biopsy retrieval specimens showed no signs of inflammation at the newly formed bone area and the native alveolar bone area. New bone formation was observed at the cranial side from the native alveolar bone. The newly formed bone had a trabecular structure and was in intimate contact with the HPMM ß-TCP material. Histomorphometric evaluation of bone biopsy retrieval specimens showed an average new bone volume of 33.97% ± 2.79% and an average residual HPMM ß-TCP volume of 15.81% ± 4.52%. CONCLUSIONS: In this study, HPMM ß-TCP showed osteoconductive properties for vertical augmentation of the atrophied maxilla by means of a maxillary sinus floor elevation procedure allowing subsequent dental implant placement after a 7-month healing period.

Clinical characteristics, treatment methods and prognoses of patients with oral squamous cell carcinoma in Japanese population: a single institution retrospective cohort study.

BACKGROUND: The status of oral cancer therapy in elderly patients in Japan, where ageing is rapidly progressing, may serve as a model for other countries with similar demographics. There is controversy over what kind of treatment should be applied and how aggressively it should be applied to very elderly patients who have exceeded the average life expectancy. Given that 85 years is approximately the overall Japanese life expectancy at birth, we considered a threshold of 85 years and hypothesized that the prognosis of oral squamous cell carcinoma (SCC) patients aged ≥85 years was not inferior to that of those < 85 years. The aim of the present study was to investigate the clinical characteristics, treatment methods, and prognoses of Japanese oral SCC patients aged ≥85 years. METHODS: A retrospective cohort study was performed. The data of patients with primary oral SCC (n = 358) from 2005 to 2018 in our institute were extracted from electronic medical records. A total of 358 patients with oral SCC were divided into two groups (≥85 years group [n = 26] and < 85 years group [n = 332]) based on the age threshold of 85 years at the first visit. Kaplan-Meier survival analyses and Cox proportional hazard models were used to analyse overall survival (OS) and hazard ratios (HRs) according to age group, treatment, and TNM classification. RESULTS: There was no difference in the 5-year OS rate between the ≥85 years and < 85 years groups (80.8% vs. 82.2%, P = 0.359). This finding was the same in the operative (94.7% vs. 85.8%, P = 0.556) and non-operative (42.9% vs. 33.2%, P = 0.762) groups, indicating that age did not affect prognosis. Mortality was lower in the operative group than in the non-operative group (adjusted HR: 0.276, 95% CI: 0.156-0.489, P < 0.001), suggesting that surgery is a superior method. However, non-surgical treatment was selected at a higher rate in the ≥85 years group (26.9% vs. 11.1%, P = 0.028). CONCLUSIONS: This study suggests the prognosis of ≥85-year-old patients was not inferior to that of < 85-year-old patients. We recommend that surgery as the first choice treatment for ≥85-year-old patients with oral SCC who can tolerate surgery should be performed.

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.

Paclitaxel Potentiates the Anticancer Effect of Cetuximab by Enhancing Antibody-Dependent Cellular Cytotoxicity on Oral Squamous Cell Carcinoma Cells In Vitro.

Administration of cetuximab (C-mab) in combination with paclitaxel (PTX) has been used for patients with head and neck squamous cell carcinoma (SCC) clinically. In this study, we attempted to clarify the molecular mechanisms of the enhancing anticancer effect of C-mab combined with PTX on oral SCC cells in vitro. We used two oral SCC cells (HSC4, OSC19) and A431 cells. PTX alone inhibited cell growth in all cells in a concentration-dependent manner. C-mab alone inhibited the growth of A431 and OSC19 cells at low concentrations, but inhibited the growth of HSC4 cells very weakly, even at high concentrations. A combined effect of the two drugs was moderate on A431 cells, but slight on HSC4 and OSC19 cells. A low concentration of PTX enhanced the antibody-dependent cellular cytotoxicity (ADCC) induced by C-mab in all of the cells tested. PTX slightly enhanced the anticancer effect of C-mab in this ADCC model on A431 and HSC4 cells, and markedly enhanced the anticancer effect of C-mab on OSC19 cells. These results indicated that PTX potentiated the anticancer effect of C-mab through enhancing the ADCC in oral SCC cells.

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.

Determination of the origin of oral squamous cell carcinoma by microarray analysis: Squamous epithelium or minor salivary gland?

More than 90% of oral cancers are histopathologically squamous cell carcinomas (SCCs). According to clinical behavior and histopathological features, we hypothesize that oral SCC can originate from either oral squamous epithelium or minor salivary glands. Here, we examined whether some oral SCCs originate from minor salivary glands, and investigated whether these tumors show particularly aggressive biological behavior. The mRNA expression profiles of samples obtained from six patients with oral floor SCC (five men, one woman; mean age, 62.7 years) were analyzed using a microarray containing 32,878 probes. The six samples were divided into two groups by clustering of expression levels of 845 probes differentially expressed in normal oral squamous epithelium and normal salivary glands. The expression profile in four cases was similar to that of normal oral squamous epithelium, and in two cases was similar to that of normal salivary glands. Furthermore, we identified nine genes that reveal the origin of the oral SCC. Subsequently, we examined the expression levels of these nine marker genes by reverse transcriptase-polymerase chain reaction to determine the origin of 66 oral SCCs. Twelve of the 66 oral SCCs were considered to originate from minor salivary glands, and these tumors showed high metastatic potential (p = 0.044, Chi-square test). Furthermore, SCC derived from minor salivary glands showed a poor event-free survival rate (p = 0.017, Kaplan-Meier analysis). In conclusion, determination of the origin of oral SCC is helpful in planning treatment for patients with oral SCC.

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.