[A framework for promoting and evaluating "Kayoi-no-ba" initiatives according to the Plan-Do-Check-Action cycle: The ACT-RECIPE framework].

Objective　In 2019, the Ministry of Health, Labour and Welfare emphasized the importance of promoting "Kayoi-no-ba" (or "places to go") initiatives according to the Plan-Do-Check-Action (PDCA) cycle. However, it proposed no specific promotion measures or standardized evaluation frameworks. This study is intended to propose a framework for local government officials to promote and evaluate "Kayoi-no-ba" initiatives according to the PDCA cycle.Methods　The working group (WG) conducted a narrative review of research and extracted evaluation models and indicators that could be used to create the framework. The co-researcher review committee discussed a draft framework prepared by the WG, and the WG revised it based on the discussion; this process was repeated four times. Using the completed framework, we calculated the score of the "Kayoi-no-ba" initiatives in 50 Tokyo municipalities and conducted regional correlation analyses on the relationship between the score of the "Kayoi-no-ba" initiatives in 50 Tokyo municipalities and the number of "Kayoi-no-ba" per 1,000 older persons.Results　The completed framework (named "ACT-RECIPE" by rearranging the underlined characters below) comprised the following six evaluation phases: (1) Comprehension: understanding the key lessons around disability and frailty prevention, and the necessity for "Kayoi-no-ba"; (2) Research and Planning: clarifying the current status of "Kayoi-no-ba," the strengths of the community, and the issues to be addressed through a community assessment, and developing a plan to resolve the issues; (3) Team Building and Collaboration: building a team by collaborating with organizations to solve problems; (4) Implementation: implementing the initiatives necessary to solve problems; (5) Evaluation: verifying changes in output and outcome indicators from the initiatives; and (6) Adjustment and Improvement: re-examining plans, teams, content, and goals based on the evaluation results. In these six phases, we designated 10 core items and accompanying subitems. The median score rate of the ACT-RECIPE framework in 50 municipalities was 75% for "Comprehension," 61% for "Research and Planning," 69% for "Team Building and Collaboration," 64% for "Implementation," 31% for "Evaluation," and 56% for "Adjustment and Improvement," and the mean ACT-RECIPE score rate was 57%. A significant positive correlation (rs=0.43, P=0.002) was observed between the ACT-RECIPE mean score rate and the number of "Kayoi-no-ba" per 1,000 older persons.Conclusion　We proposed the ACT-RECIPE as a framework for promoting and evaluating "Kayoi-no-ba" initiatives according to the PDCA cycle. We hope that this framework will lead to further progress in "Kayoi-no-ba" initiatives and facilitate evaluation of their effectiveness according to the PDCA cycle.

Association between choices of transportation means and instrumental activities of daily living: observational cohort study of community-dwelling older adults.

INTRODUCTION: The association between the physical health of older people and the frequency of going out has been reported, and in recent years, local governments have developed transportation support programs for older people. Although previous studies show an association between the frequency of going out and functional health status, little has been reported on the impact of the choice of means of transport on instrumental activities of daily living (IADL). OBJECTIVE: To evaluate the association between choice of transportation means and the risk of decline in IADL among older adults. METHODS: We conducted an observational, population (community-dwelling)-based cohort study using data from the Resident Health Status Survey, and longitudinal panel data at 2-time points in 2016 and 2019. In addition, we combined this panel data and a database on people who were certified as requiring long-term care to identify participants' IADL. The propensity score matching method was used to classify the respondents into two groups, "active means of transportation" and "passive means of transportation," and determine the risk of a decline in means-tested independence after 3 years. RESULTS: Active means were used by 6,280 (76.2%) and passive means were used by 1,865 (22.6%). 999 (12.1%) individuals declined in IADL in 2019. The results of the comparison by balancing the attributes of "active means of transportation" and "passive means of transportation," with propensity score matching, showed that "passive means of transportation" were more likely to be "active" than "passive means of transportation," and "active" was more likely to be "passive" The risk of IADL decline was significantly higher than that of "active means of transportation" with an RR of 1.93 (95% CI: 1.62-2.30). CONCLUSION: Passive means of transportation in older adults could be a possible risk for decreasing IADL 3 years later. Increasing the number of opportunities and places in the community for older adults to use active means of transportation may be effective in encouraging socially independent living among older adults.

[Relationship between volunteer group participation and depressive symptoms in older Japanese: A 3-year JAGES longitudinal study using propensity score matching].

Objectives　In this study, we aim to clarify the optimal threshold for the frequency of volunteer group participation among older people aged 65 years and above, which is expected to prevent the risk of developing depression.Methods　We utilized longitudinal data from 2013 to 2016, collated by the Japan Gerontological Evaluation Study for people aged ≥65 years living in 24 municipalities and not certified as requiring long-term care. In addition, those who were not depressed in 2013 (≥5 points on the Geriatric Depression Scale-15) were followed up for 3 years and classified according to the frequency of participation in the volunteer group in 2013 (≥once per year, ≥once per month, ≥once per week). The odds ratio (OR) of being newly depressed in 2016 was determined using the propensity score matching method and t-test.Results　The frequency of volunteer group participation for 9,722 (25.0%), 6,026 (15.5%), and 2,735 (7.0%) older individuals was≥once per year, once per month, and once per week, respectively. A comparison of the balanced attributes of the volunteer group participation with those of the non-participation group using propensity scores revealed that the risk of developing depressive symptoms was significantly lower in the former compared with the latter for the frequency of ≥once per month and OR of 0.82 (95% confidence interval: 0.72, 0.93). The ORs were 0.92 (0.83, 1.02) and 0.82 (0.68, 1.00) for the ≥once per year and once per week groups, respectively.Conclusion　Older people's participation in a volunteer group ≥once per month was effective in reducing the risk of developing depressive symptoms after 3 years. This suggests that increasing the opportunities and community places where older people can be involved as volunteers even once a month may be employed as an effective measure to prevent depression.

Community-Level Participation in Volunteer Groups and Individual Depressive Symptoms in Japanese Older People: A Three-Year Longitudinal Multilevel Analysis Using JAGES Data.

BACKGROUND: The current study aimed to investigate the contextual effect of volunteer group participation on subsequent depressive symptoms in older people. METHODS: We analyzed the longitudinal data of 37,552 people aged 65 years and older in 24 municipalities surveyed in the Japan Gerontological Evaluation Study. Volunteer group participation of older people was assessed in 2013 by one question and depressive symptoms were assessed by the Geriatric Depression Scale 15 in 2016. To investigate a contextual effect, we aggregated individual-level volunteer group participation by each residence area as a community-level independent variable. We conducted a two-level multilevel Poisson regression analysis using the Random Intercepts and Fixed Slopes Model. RESULTS: The average proportion of community-level volunteer group participation was 10.6%. The results of the Poisson regression analysis showed that community-level volunteer group participation reduced the risk for the onset of depressive symptoms by 13% with a 10 percentage point increase in participation, after adjusting for sex, age, population density, total annual sunshine hours and annual rainfall (incident rate ratio, 0.87; 95% confidence interval, 0.78-0.98). CONCLUSIONS: Older people living in areas with higher volunteer group participation had a lower risk of developing depressive symptoms regardless of whether or not they participated in a volunteer group.

Effects of Reablement on the Independence of Community-Dwelling Older Adults with Mild Disability: A Randomized Controlled Trial.

We aimed to assess the efficacy of a reablement program in improving the independence from long-term care services of older adults with mild disability. This parallel, two-arm, randomized controlled, superiority trial was conducted in Neyagawa, a local government area in Osaka, Japan. Eligible participants were community-dwelling individuals aged ≥65 years certified as support-required level. They were assigned in a 1:1 ratio to receive either a community-based, multicomponent, multidisciplinary, individualized goal-directed, and time-limited intervention (the CoMMIT program) plus standard care or standard care alone. The primary outcome was independence, that is, the nonuse of long-term care services during the three-month follow-up period. The study was terminated early due to slow enrollment. A total of 375 participants were enrolled and randomized to either the intervention (n = 190) or control (n = 185) group. The proportions of independence were 11.1% and 3.8% in the intervention and control groups, respectively (absolute difference: 7.3; 95% confidence interval: 2.0-12.5). There was no difference in the risk of serious adverse events between the groups. The CoMMIT program plus standard care was found superior to standard care alone in enhancing the independence from long-term care services of older adults with mild disability.

Carney complex: a case with thyroid follicular adenoma without a PRKAR1A mutation.

BACKGROUND: Carney complex (CNC) is a very rare disease. Although thyroid lesions are included in the diagnostic criteria for CNC, they are an infrequent occurrence. CASE PRESENTATION: The patient was a 69-year-old woman who had undergone the removal of a left atrial myxoma 10 years earlier, at the age of 59. At the time of the operation, thyroid ultrasonography (US) revealed multiple hypoechoic nodules. Thyroid scintigraphy revealed an increased uptake of 99mTc in these lesions, which was consistent with toxic multinodular goiter, and she was diagnosed with CNC. Genetic studies showed no mutation in the PRKAR1A (protein kinase A regulatory subunit 1-α) gene. From then on, she received annual brain magnetic resonance imaging (MRI), abdominal computed tomography (CT), and thyroid US examinations. Her follicular thyroid nodules gradually increased in number and size. Although aspiration cytology samples from the thyroid nodules diagnosed them as class III, thyroid cancer could not be ruled out. The patient underwent a partial thyroidectomy, and the pathological diagnosis was multiple follicular adenomas. CONCLUSION: Careful and frequent evaluation of the thyroid gland should be required for CNC patients due to the potential for carcinoma to develop in the context of a variety of follicular thyroid lesions.

Hepatitis E virus derived from different sources exhibits different behaviour in virus inactivation and/or removal studies with plasma derivatives.

Hepatitis E virus (HEV) causes viral hepatitis, and is considered a risk factor for blood products. Although some HEV inactivation/removal studies have been reported, detailed investigations of different manufacturing steps as heat treatment, partitioning during cold ethanol fractionation, low pH treatment, and virus filtration have yet to be reported for plasma-derived medicinal products. In this study, human serum- and swine faeces-derived HEVs, with and without detergent treatment, were used. The kinetic patterns of inactivation, log reduction value, or partitioning during the process were evaluated. In addition, the mouse encephalomyocarditis virus (EMCV) and canine and porcine parvoviruses (CPV/PPV) were also evaluated as model viruses for HEV. Small pore size (19 or 15 nm) virus filtration demonstrated effective removal of HEV. Middle pore size (35 nm) virus filtration and 60 °C liquid heating demonstrated moderate inactivation/removal. Ethanol fractionation steps demonstrated limited removal of HEV. Unpurified HEV exhibited different properties than the detergent-treated HEV, and both forms displayed differences when compared with EMCV, CPV, and PPV. Limited or no inactivation of HEV was observed during low pH treatment. Untreated plasma-derived HEV from humans showed different properties compared to that of HEV treated with detergent or derived from swine faeces. Therefore, HEV spike preparation requires more attention.

Mode of swine hepatitis E virus infection and replication in primary human hepatocytes.

The aim of this study was to investigate the infection and replication of swine-derived hepatitis E virus (HEV) in primary cultured human hepatocytes (PHCs). Hepatocytes were cultured from the resected normal livers of patients with metastatic tumours. These cultured hepatocytes were infected with swine-derived genotype 3 or 4 HEV. Viral replication was monitored using reverse transcriptase-quantitative PCR. The amount of HEV RNA increased in the culture media and cells following infection. Immunofluorescence staining implied that the spread of HEV infection in hepatocytes was attributed mainly to cell-to-cell transmission via the cell membrane. The sequences of the inoculated and propagated HEV were determined to examine whether sequence variation occurred during infection. Sequence analysis showed that there were no differences between inoculated and propagated HEV, demonstrating that in vitro infection and replication of swine HEV in PHCs occurred without sequence variation.

Prion removal by nanofiltration under different experimental conditions.

Manufacturing processes used in the production of biopharmaceutical or biological products should be evaluated for their ability to remove potential contaminants, including TSE agents. In the present study, we have evaluated scrapie prion protein (PrP Sc) removal in the presence of different starting materials, using virus removal filters of different pore sizes. Following 75 nm filtration, PrP Sc was detected in the filtrate by Western blot (WB) analysis when a "super-sonicated" microsomal fraction derived from hamster adapted scrapie strain 263K (263K MF) was used as the spike material. In contrast, no PrP Sc was detected when an untreated 263K MF was used. By using spike materials prepared in a manner designed to optimize the particle size distribution within the preparation, only 15 nm filtration was shown to remove PrP Sc to below the limits of detection of the WB assays used under all the experimental conditions. However, infectious PrP Sc was recovered following 15 nm filtration under one experimental condition. The results obtained suggest that the nature of the spike preparation is an important factor in evaluating the ability of filters to remove prions, and that procedures designed to minimize the particle size distribution of the prion spike, such as the "super-sonication" or detergent treatments described herein, should be used for the preparation of the spike materials.

FR-167653, a selective p38 MAPK inhibitor, exerts salutary effect on liver cirrhosis through downregulation of Runx2.

Liver cirrhosis remains a difficult-to-treat disease with a substantial morbidity and mortality rate. There is an emerging body of data purporting a pivotal role of the activated p38 mitogen-activated protein kinase (MAPK) in the process of cirrhosis. Several anticirrhotic agents have been developed over the past few years, and most of them exert their effects by indirectly inhibiting the p38 pathway. Effect of a selective p38 inhibitor is yet to be reported. In this study, we evaluated the salutary effect of FR-167653 (FR), a selective p38 inhibitor, in a carbon tetrachloride (CCl(4))-induced rat cirrhotic model. Twenty rats were assigned into four groups: Sham, olive oil only; Control, CCl(4) in olive oil; FR50, FR 50 mg/kg/day and CCl(4); and FR100, FR 100 mg/kg/day and CCl(4). FR dose-dependently inhibited activation of p38 and had an ameliorating effect on cirrhosis formation. Significant dose-dependent reduction in alpha-smooth muscle actin immunostaining and hydroxyproline content of the liver was noticed in the FR-treated rats. Also densitometric analysis showed a significant reduction in azan-stained area in the FR-treated rats. These fibrotic changes were observed in the myofibroblasts including the hepatic stellate cells and portal fibroblasts. mRNA expression of runt-related protein 2 (Runx2), a profibrogenic transcription factor, was significantly low in FR-treated livers, indicating that Runx2 might be a key downstream regulator of the p38 pathway. A similar reduction in expression of Smad4 and tissue inhibitor of metalloproteinase-1 was noticed in the FR-treated rats. In conclusion, FR treatment exerted a significant beneficial effect in a CCl(4)-induced rat cirrhotic model. The ameliorating effect of FR could be partially attributable to an inhibition of the Smad4/p38/Runx2 axis in the cirrhotic liver.

Appraisal of a revised lymph node classification system for esophageal squamous cell cancer.

BACKGROUND: Node-positive patients with esophageal carcinoma constitute a heterogeneous population with a variable prognosis, which the current staging system insufficiently addresses. To that end, 863 patients with a curative resection for esophageal squamous cell carcinoma were analyzed to evaluate a useful and simple nodal classification system. METHODS: Along with standard conventional clinicopathologic factors, data for metastatic lymph node (MLN) number, metastatic to examined LN ratio (MLN ratio), and MLN size were evaluated. The greatest microscopic dimension of the metastatic tumor inside the largest MLN (MLN size) was measured on histopathologic slides. Patients with MLNs were classified into n1 (< 9 mm) and n2 (> or = 9 mm) groups, according to size of MLNs (n-stage). RESULTS: The paratracheal LNs most frequently contained the largest MLN and among them the right recurrent laryngeal LNs were the most common site (81.8%). Patients were stratified into significant groups by all the nodal criteria. In multivariable analysis, MLN size n-stage and MLN ratio N-stage were the best independent predictors for disease-free and overall survival, respectively. In the disease-free survival, MLN ratio N-stage subcategories were divided into prognostic groups according to the n-stage. A combined nodal staging strategy combining the n-stage and N-stage had the strongest prognostic value and was used for the tumor-node-metastasis classification with distinct separation of patients into prognostic groups. CONCLUSIONS: Results of this study indicate that the MLN size may serve as an accurate metric to classify node-positive patients and a combination of the MLN ratio and size may have synergism in classifying node-positive patients into prognostically homogenous groups.

Surgical treatment of superficial esophageal cancer.

OBJECTIVE: The worldwide incidence of superficial esophageal cancer (SEC) is increasing. The aim of this study is to review the systematic surgical outcomes of esophagectomy for SEC. DATA SOURCES: Only manuscripts written in English and written between 1980 and 2003 were selected from MEDLINE. The keywords consisting of superficial esophageal cancer, early esophageal cancer, and early stage or superficial stage or stage I in esophageal cancer were searched. STUDY SELECTION: There were no exclusion criteria for published information relevant to the topics. The most representative articles were selected when there were several articles from the same institution. Case reports were excluded. DATA EXTRACTIONS: Thirty-two manuscripts were finally collected from MEDLINE and eight articles were also added from reference lists of the pertinent literatures. In evaluating the statistical analysis of the complications of the reported literature, collective method was used. DATA SYNTHESIS: The collected information was organized. CONCLUSIONS: The conclusions drawn from those articles showed that the overall prevalence of SEC accounted around 10% and increased to 25% in the 2000s. The overall incidence of lymph node metastasis of SEC was about 25% and its incidences in mucosal and submucosal cancer were 5 and 35%, respectively. The percentage of the cases of squamous cell carcinoma (SCC) vs adenocarcinoma (AC) widely varied depending on the geographic locations reported; most SCC cases were from the Asian countries and most AC cases were from the European countries. Clinical significance of multimodal treatment for SEC has dramatically developed in the recent era and could provide various potential therapeutic options for SEC. These concepts make it possible to individualize surgical management of SEC as part of various multimodal treatments. The operative approaches for SEC varied from minimally invasive thoracoscopic esophagectomy, limited transabdominal distal esophagectomy, conventional transthoracic esophagectomy, transhiatal esophagectomy without thoracotomy, en bloc esophagectomy, and to extended esophagectomy with a complete three-field lymph node dissection. A 5-year overall survival rate of SEC after esophagectomy was good (46 to 83%) to excellent (71 and 100%) for mucosal SEC, but far from satisfactory (33 and 78%) for submucosal SEC. Early diagnosis, development of multimodal treatment, standardization of the surgical procedure including routine lymph node dissection, and improved perioperative management of patients have led to a better survival for patients with SEC.