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Background: Interstitial lung disease/pneumonitis (ILD/pneumonitis) has been identified as a drug-related adverse event of special interest of trastuzumab deruxtecan (T-DXd), but there were a few reports of T-DXd-related ILD/pneumonitis in clinical practice. Methods: Between May 25, 2020 (the launch of T-DXd in Japan) and February 24, 2022, there were 287 physician-reported potential ILD/pneumonitis cases from the Japanese post-marketing all-case surveillance. By February 27, 2022, an independent adjudication committee assessed 138 cases and adjudicated 130 cases as T-DXd-related ILD/pneumonitis. The clinical features and imaging characteristics of these cases were evaluated. Results: The majority of adjudicated T-DXd-related ILD/pneumonitis cases were grade 1 or 2 (100/130, 76.9%). The most common radiological pattern types observed were organizing pneumonia patterns (63.1%), hypersensitivity pneumonitis patterns (16.9%), and diffuse alveolar damage (DAD) patterns (14.6%). Eleven cases (8.5%) from 130 resulted in death; the majority of these (8/11, 72.7%) had DAD patterns. The overall proportion of recovery (including the outcomes of recovered, recovered with sequelae, and recovering) was 76.9%, and the median time to recovery was 83.5 days (interquartile range: 42.25–143.75 days). Most cases (59/71, 83.1%) that were treated with corticosteroids were considered responsive to treatment. Conclusions: This is the first report to evaluate T-DXd-related ILD/pneumonitis cases in clinical practice. Our findings are consistent with previous reports and suggest that patients with DAD patterns have poor outcomes. Evaluation of a larger real-world dataset may further identify predictors of clinical outcome. [ABSTRACT FROM AUTHOR]

Objective: Cognitive decline is an important and well-documented health problem. The Mini-Cog, a simple cognitive function test, is recommended as a potential early cognitive screening tool. Kanagawa Prefecture, one of the largest prefectures in Japan, developed this self-testing application on a smartphone to enable a large number of residents to assess their cognitive function. This study aimed to verify the validity and reliability of the Mini-Cog. Results: Twenty men and 20 women aged 65–85 years were enrolled. Criterion-related validity of the method tested by professional staff was found to have an acceptable positive association. The test–retest reliability was lower than the clinically expected intraclass correlation coefficient value because of the inclusion of learning and order effects. If the Mini-Cog score of this application is low, the system is equipped with a function that advises the users on preventing cognitive decline, directing them to the appropriate services, and recommending visits to a medical institution. Therefore, the system can be used continuously as a tool for health behaviors and promotions. [ABSTRACT FROM AUTHOR]

Background: While community-wide interventions to promote physical activity have been encouraged in older adults, evidence of their effectiveness remains limited. We conducted a qualitative study among older adults participating in regular group exercise to understand their perceptions of the physical, mental, and social changes they underwent as a result of the physical activity.Methods: We conducted a qualitative study with purposeful sampling to explore the experiences of older adults who participated in regular group exercise as part of a community-wide physical activity intervention. Four focus group interviews were conducted between April and June of 2016 at community halls in Fujisawa City. The participants in the focus group interviews were 26 older adults with a mean age of 74.69 years (range: 66-86). The interviews were analysed using the constant comparative method in the grounded theory approach. We used qualitative research software NVivo10® to track the coding and manage the data.Results: The finding 'regular group exercise contributes to balanced health in older adults' emerged as an overarching theme with seven categories (regular group exercise, functional health, active mind, enjoyment, social connectedness, mutual support, and expanding communities). Although the participants perceived that they were aging physically and cognitively, the regular group exercise helped them to improve or maintain their functional health and enjoy their lives. They felt socially connected and experienced a sense of security in the community through caring for others and supporting each other. As the older adults began to seek value beyond individuals, they gradually expanded their communities beyond geographical and generational boundaries.Conclusions: The participants achieved balanced health in the physical, mental, and social domains through regular group exercise as part of a community-wide physical activity intervention and contributed to expanding communities through social connectedness and mutual support. Health promotion through physical activity is being increasingly emphasized. The study results can help to develop effective physical activity programs for older adults in the community. [ABSTRACT FROM AUTHOR]

Aim: Some studies have reported a higher incidence of falls during winter with similar proportions of indoor and outdoor falls. We investigated the relationship between indoor temperature during winter and falls at home in the past year among community-dwelling older adults., Methods: This cross-sectional study enrolled 964 individuals of ≥65 years of age in Japan. Participants answered questions about falls (including trips) at home within the past year, and the living room temperature was measured for 2 weeks during winter. Participants were divided into those living in cold (mean temperature near the floor <12°C), slightly cold (12-17.9°C), and warm (≥18°C) houses. The association between indoor temperature (cold vs. slightly cold vs. warm houses) and falls at home in the past year was examined using a logistic regression analysis adjusted for potential confounding factors., Results: Valid data were obtained from 907 participants (mean age: 72.0±6.3 years), of whom 265,553, and 89 lived in cold, slightly cold, and warm houses, respectively. In the past year, falls occurred once in 325 (35.8%) participants and multiple times in 148 (16.3%) participants. In warm houses, the odds ratio of falling once and multiple times in the past year was 0.49 (p=0.032) and 0.34 (p=0.035), respectively, in comparison to cold houses., Conclusions: Living in cold houses may be associated with an increased risk of falling at home among older adults. Maintaining an appropriate indoor thermal environment during winter may reduce the risk of falling among individuals who spend most of their time at home.

Objective: This study aimed to determine the association between psychological distress and leisure-time exercise/socioeconomic status by age group, using data from a cohort study in Japan during the COVID-19 pandemic., Methods: This cross-sectional study was conducted among participants in the ME-BYO cohort, aged 20-85 years, living or working in Kanagawa, Japan. A questionnaire was disseminated to 1,573 participants (51.7% men) between December 2020 and March 2021. The questionnaire items included psychological distress (using the 6-item Kessler Psychological Distress Scale [K6]), leisure-time exercise, and socioeconomic status. Multivariate analyses were conducted using logistic regression analysis for each age group., Results: We found that 47.4% of 20-39-year-olds, 40.6% of 40-64-year-olds, and 28.3% of 65-85-year-olds experienced psychological distress (K6: ≥5 points). For those aged 20-39 years, leisure-time exercise (odds ratio [OR] (95% confidence interval) = 0.45 (0.28-0.73)) and higher annual household income [0.53 (0.32-0.90)] were associated with less psychological distress. For those aged 40-64 years, older age was associated with less psychological distress, while full-time work [1.98 (1.05-9.71)] was associated with more psychological distress. In the 65-85-year age group, higher education and higher annual income tended to be associated with less psychological distress. For those over 40 years of age, living with other(s) was associated with reduced psychological distress., Conclusion: In the general population of Japan, not engaging in leisure-time exercise and low income affect psychological distress among young adults. Further detailed studies are needed to consider overall physical activity, job type, and work style., Competing Interests: HI and NS are members of Hygeia Communication General Incorporated Association. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Saito, Nakamura, Watanabe, Ikegami, Shinmura, Sato, Miyagi and Narimatsu.)

Objective: Social stigma related to coronavirus disease (COVID-19), i. e., COVID-19 stigma, forms a burden on people socially, economically, and mentally. This study assessed COVID-19 stigma using a scale to identify a population likely to exhibit higher prejudice against COVID-19 itself as well as those infected with COVID-19., Methods: We adapted and modified the Cancer Stigma Scale to assess COVID-19 stigma and used it as the baseline survey of a cohort study in Japan. The questionnaire was disseminated to 1,573 participants (51.7% men) between December 2020 and March 2021. The questionnaire items included the infection status of individuals close to the respondent and their preventive behaviors related to COVID-19, quality of life (QOL; using the EuroQoL 5-Dimension 5-Level [EQ-5D-5L]), and psychological distress (using the 6-item Kessler Psychological Distress Scale [K6]). Exploratory and confirmatory factor analyses were performed to validate the COVID-19 stigma scale, and we further used the structural equation modeling (SEM) to assess the relationship with QOL and psychological distress., Results: COVID-19 stigma was calculated for the 257 (16.3%) participants who responded to the questionnaire. The mean age (standard deviation) was 54.5 (14.4) years, and 50.2% were men. Factor analysis revealed a five-factor model: Awkwardness (feeling uncomfortable being with a person infected before), Severity (fear of not being able to return to normal after infection), Avoidance (attitude of avoiding infected persons), Policy Opposition (expecting more public funding investment), and Personal Responsibility (believing that infected persons themselves are responsible for their infection). Participants > 70 years had the highest scores among other age groups considering all factors except for Policy Opposition. Standardized coefficients in SEM for COVID-19 stigma (latent variable) was highest for Severity (beta = 0.86). Regression coefficients of COVID-19 stigma on K6 and QOL were 0.21 (95% confidence interval [CI] 0.074-0.342) and -0.159 (95% CI -0.295-0.022), respectively., Conclusion: People aged ≥ 70 years are more likely to exhibit COVID-19 stigma. Additionally, the results indicate that COVID-19 stigma impacts QOL and psychological distress., Competing Interests: Authors HI and NS are members of Hygeia Communication General Incorporated Association. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sawaguchi, Nakamura, Watanabe, Tsuno, Ikegami, Shinmura, Saito and Narimatsu.)

Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge 1-5 . Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target., (© 2022. The Author(s).)

Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection., (© 2022. The Author(s).)

Background and Objectives: The incidence of coronavirus disease 2019 (COVID-19) has increased in Wakayama, Japan, due to the spread of the highly infectious B.1.1.7 variant. Before this event, the medical systems were almost unaffected. We aimed to assess the clinical characteristics of patients hospitalized with COVID-19 and the risk factors for therapeutic intervention of remdesivir during the fourth pandemic period in Wakayama, Japan. Materials and Methods: This single-center retrospective study enrolled 185 patients with mild to moderate COVID-19 hospitalized in our hospital without intensive care between 14 March and 31 May 2021. Results: In this period, 125 (67.6%) of the 185 patients had the B.1.1.7 variant. Sixty-three patients (34.1%) required remdesivir treatment. Age upon admission and length of hospitalization were significantly different between remdesivir treatment and careful observation groups (mean (standard deviation); 59.6 (14.7) versus 45.3 (20.6) years; p < 0.001 and median (interquartile range); 10 (9-12) versus 9 (8-10) years; p < 0.001). One patient was transferred to another hospital because of disease progression. At hospital admission, age ≥60 years (odds ratio (OR) 6.90, p < 0.001), a previous history of diabetes mellitus (OR 20.9, p = 0.002), B.1.1.7 variant (OR 5.30; p = 0.005), lower respiratory symptoms (OR 3.13, p = 0.011), headache (OR 3.82, p = 0.011), and fever ≥37.5 °C (OR 4.55, p = 0.001) were independent risk factors to require remdesivir treatment during the admission. Conclusions: Many patients with mild to moderate COVID-19 required the therapeutic intervention of remdesivir during the fourth pandemic period in Wakayama, Japan. From the clinical data obtained at admission, these risk factors could contribute to a prediction regarding the requirement of remdesivir treatment in cases of mild to moderate COVID-19.

Background: Phase IV clinical trials in Western countries have reported that combined therapy with pirfenidone and nintedanib for idiopathic pulmonary fibrosis (IPF) has a manageable safety profile. However, data on the long-term safety and tolerability of this combination treatment in the real-world setting in Japan are limited., Methods: The retrospective data of 46 patients with IPF who received combination therapy with pirfenidone and nintedanib were obtained from 16 institutes in Japan. Adverse events and adverse drug reactions (ADRs) were reported through a retrospective review of medical records., Results: Nintedanib and pirfenidone were added to preceding treatment with antifibrotic drugs in 32 (69.6%) and 13 (28.3%) patients, respectively. In one patient (2.1%), the two drugs were concurrently initiated. The mean duration of monotherapy before initiating the combination was 26.3 months. In 26 of 38 patients (68.4%), the Gender-Age-Physiology index stage was II or III. Thirty-three patients (71.7%) had some ADRs, and 14 patients (30.4%) permanently discontinued either drug or both drugs owing to the development of ADRs during the observation period (mean: 59 weeks). The percentage of grade III or IV IPF according to the Japanese Respiratory Society severity classification was higher in patients who permanently discontinued either drug or both drugs than in those who continued both drugs (90.9% [10/11; 3 undetermined grade] vs. 61.1% [11/18; 1 undetermined grade]). Decreased appetite (18/46, 39.1%) and diarrhea (16/46, 34.8%) were frequently observed ADRs. Two patients (4.3%) had serious ADRs (liver toxicity and pneumothorax)., Conclusions: Real-world data imply that combination therapy with pirfenidone and nintedanib for IPF has a manageable safety/tolerability profile., Competing Interests: Conflict of Interest Shu Hisata, Kensuke Kataoka, Yoshinobu Saito, and Motoyasu Kato received honoraria from Nippon Boehringer Ingelheim Co., Ltd.; Masashi Bando, Sakae Homma, and Takashi Ogura received honoraria from Nippon Boehringer Ingelheim Co., Ltd. and Shionogi & Co., Ltd.; Yasuhiko Nishioka received honoraria, donations, and research funding from Nippon Boehringer Ingelheim Co., Ltd.; Kazuhiro Yatera received honoraria from Nippon Boehringer Ingelheim Co., Ltd., and donations from Shionogi & Co., Ltd. and Nippon Boehringer Ingelheim Co., Ltd.; Hiroshi Mukae received honoraria, donations, and research funding from Nippon Boehringer Ingelheim Co., Ltd. and Shionogi & Co., Ltd.; Shinyu Izumi, Susumu Sakamoto, Kizuku Watanabe, Yasuo Shimizu, Hiromichi Hara, Yuko Waseda, Yoshinori Tanino, Seishu Hashimoto, and Naohiko Inase have no conflicts of interest to declare., (Copyright © 2021 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Nivolumab can cause interstitial lung disease (ILD), which may be fatal; however, mortality risk factors have not been identified. This postmarketing study evaluated the poor prognostic factors of ILD in nivolumab-treated patients with non-small cell lung cancer (NSCLC) in Japan. Clinical and chest imaging findings for each ILD case were assessed by an expert central review committee, and prognosis was evaluated by radiographic findings, including the presence/absence of peritumoral ground-glass opacity (peritumoral-GGO). Poor prognostic factors were identified by univariate and multivariate Cox regression analysis. Of the 238 patients with nivolumab-induced ILD, 37 died. The main radiographic patterns of ILD were cryptogenic organizing pneumonia/chronic eosinophilic pneumonia-like (53.4%), faint infiltration pattern/acute hypersensitivity pneumonia-like (20.2%), diffuse alveolar damage (DAD)-like (10.9%), and nonspecific interstitial pneumonia-like (6.3%). The main poor prognostic factors identified were DAD-like pattern (highest hazard ratio: 10.72), ≤60 days from the start of nivolumab treatment to the onset of ILD, pleural effusion before treatment, lesion distribution contralateral or bilateral to the tumor, and abnormal change in C-reactive protein (CRP) levels. Of the 37 deaths due to ILD, 17 had DAD-like radiographic pattern, three had peritumoral-GGO, and five had a change in radiographic pattern from non-DAD at the onset to DAD-like. Patients with NSCLC who develop ILD during nivolumab treatment should be managed carefully if they have poor prognostic factors such as DAD-like radiographic pattern, onset of ILD ≤60 days from nivolumab initiation, pleural effusion before nivolumab treatment, lesion distribution contralateral or bilateral to the tumor, and abnormal changes in CRP levels., (© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Nivolumab, a human monoclonal antibody against programmed death-1, is approved for the treatment of non-small cell lung cancer (NSCLC). Although nivolumab is generally well tolerated, it can cause interstitial lung disease (ILD), a rare but potentially fatal immune-related adverse event. Currently, there are limited data available on the treatment of nivolumab-induced ILD and its outcome. This retrospective cohort study based on a post-marketing study described the treatment of nivolumab-induced ILD and its outcome in NSCLC patients in Japan through the assessment of clinical and chest imaging findings by an expert central review committee. Treatment details for patients who experienced a relapse of ILD were also analyzed. Of the 238 patients identified as having nivolumab-induced ILD, 37 patients died of ILD. Corticosteroids were used in 207 (87.0%) patients. Of those, 172 (83.1%) patients responded well and survived and 35 (16.9%) died (most died during corticosteroid treatment). A total of nine patients experienced a relapse; at the time of relapse, four patients were taking nivolumab. Of those who were receiving corticosteroids at the time of relapse, three of four patients were taking low doses or had nearly completed dose tapering. All patients (except one, whose treatment was unknown) received corticosteroids for the treatment of relapse, but one patient died. Patients with NSCLC who experience nivolumab-induced ILD are treated effectively with corticosteroids, and providing extra care when ceasing or reducing the corticosteroid dose may prevent relapse of ILD., (© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Introduction: Using real-world Japanese postmarketing data, we characterized interstitial lung disease (ILD) development during the second- or later-line osimertinib treatment for EGFR mutation-positive NSCLC. Retrospective radiologic image evaluation of patients developing ILD was also performed., Methods: Patients who had ILD events reported as an adverse drug reaction by their physicians and who were assessed as having developed ILD as assessed by an ILD expert committee in Japan were included., Results: Among 3578 patients, 252 ILD events were reported in 245 patients (6.8%) by their attending physicians. The median (range) time to the first onset of ILD after osimertinib treatment initiation was 63.0 (5-410) days, and 29 patients with a fatal outcome were reported. The ILD expert committee assessed 231 of 3578 patients (6.5%) as having ILD. A previous history of nivolumab therapy (adjusted OR: 2.84; 95% confidence interval: 1.98-4.07) and a history or concurrence of ILD (3.51; 2.10-5.87) were identified as factors potentially associated with ILD onset during osimertinib treatment. In patients who had received a previous nivolumab treatment, the number and proportion of patients developing ILD were highest for patients who discontinued nivolumab treatment within the first month before initiating osimertinib; trends for decreasing incidence and proportion were observed, with an increasing duration between the end of nivolumab treatment and the initiation of osimertinib treatment., Conclusions: The frequency of ILD was consistent with the known osimertinib safety profile in the Japanese population. A history or concurrence of ILD and history of previous nivolumab therapy are factors potentially associated with ILD onset during osimertinib treatment., (Copyright © 2020. Published by Elsevier Inc.)

Background: In the context of worldwide public health, it is very important to promote physical activity among the older people. This study explored the roles and attitudes of senior leaders in promoting group-based exercise in their local communities, specifically to determine the level and extent to which to elderly participation was encouraged., Methods: This study conducted semi-structured face-to-face in-depth interviews and employed a subsequent thematic analysis. Participants included 10 club leaders and five sub-leaders who were working at senior clubs in Fujisawa-city, Kanagawa, Japan, from July to September 2018., Results: Four themes emerged from the interview responses, including "unwavering attitude/conviction in relation to the vision," "leaders must set an example," "a search for balance in delegating responsibilities to members," and "creating and fostering culture and environment of mutual help." Further, each participant outlined several aims, including "achieving healthy longevity for the entire local community," "having older people promote healthy activities among the older people," and "creating a pro-health town.", Conclusions: Findings indicate that policymakers, public health workers, and healthcare providers should recognize the pivotal roles that senior group leaders play in promoting healthy activities for the older people. These efforts should be strongly considered when developing policies and strategies designed to promote overall healthy longevity from a general community perspective.

Objective: Adverse drug reactions (ADRs) during real-world osimertinib use were investigated in Japan., Methods: Patients with epidermal growth factor receptor (EGFR) T790M-positive non-small cell lung cancer treated with second-line or later oral osimertinib per the Japanese package insert (80 mg once daily) were included. Data were collected between 28 March 2016 and 31 August 2018., Results: The median observation period in the safety analysis population (n = 3578) was 343.0 days. ADRs (defined as adverse events whose causality to osimertinib could not be denied by the attending physicians or manufacturer) were reported in 58.1% (2079/3578) of patients. ADRs of interstitial lung disease events were reported in 6.8% (245/3578; Grade ≥ 3, 2.9% [104/3578]) of patients, of whom 29 (11.8%) died (0.8% of patients overall). ADRs of QT interval prolonged, liver disorder and haematotoxicity were reported in 1.3% (45/3578; Grade ≥ 3, 0.1% [5/3578]), 5.9% (212/3578; Grade ≥ 3, 1.0% [35/3578]) and 11.4% (409/3578; Grade ≥ 3, 2.9% [104/3578]) of patients, respectively. In the efficacy analysis population (n = 3563), 119 (3.3%) patients had complete responses, 2373 (66.6%) had partial responses and 598 (16.8%) had stable disease. The objective response rate was 69.9%; disease control rate was 86.7%; and median progression-free survival (PFS) was 12.3 months. At 6 and 12 months, PFS rates were 77.4% (95% confidence interval [CI], 75.9-78.9) and 53.2% (95% CI, 51.3-55.1) and overall survival rates were 88.3% (95% CI, 87.2-89.4) and 75.4% (95% CI, 73.8-77.0), respectively., Conclusions: These data support the currently established benefit-risk assessment of osimertinib in this patient population., (© The Author(s) 2020. Published by Oxford University Press.)

Very few community intervention studies that promote physical activity (PA) using guidelines and its dissemination and implementation have been conducted. Consequently, we evaluated the effectiveness of a community-wide intervention (CWI) of PA with adults based on the Japanese guidelines for promoting PA. This was a non-randomized controlled trial, with four administrative districts in Fujisawa city assigned to the intervention group and nine to the control group. The CWI, conducted from 2013 to 2015, comprised information dissemination, education, and community support. The primary outcome was change in PA participation. Secondary outcomes were CWI awareness and PA guideline knowledge. Outcomes were assessed using questionnaires distributed to two independent, random samples of 3000 community-based adults (aged ≥20years). Two separate samples-1230 adults at baseline and 1393 at the two-year follow-up-responded to the survey. The median time spent in PA did not differ between intervention and control groups after adjusting for potential confounders (adjusted difference between groups=-0.02min/day [95% confidence interval (CI): -0.11, 0.10]). However, intervention group participants were more aware of the CWI (33.8%) than were control group participants (25.2%) at the two-year follow-up (odds ratio=1.44 [95% CI: 1.06, 1.95]). A significant difference was also observed in participants' PA guideline knowledge (adjusted difference between groups=0.82% [95% CI: 0.33, 1.31]). Although significant differences in awareness and knowledge were observed between groups, this CWI did not change PA levels over two years. Future studies should investigate the long-term effects of CWIs beyond two years., Trial Registration Number: UMIN-CTR UMIN000018389., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Recent studies have suggested the importance of the neighborhood environment in determining the specific type of physical activity. However, few studies on this topic have been undertaken in Japan. This study examined the association of three types of physical activity and their associations with individual and neighborhood environmental factors among middle-aged and elderly Japanese. Participants were 2,449 adults aged 40-69 living in Fujisawa city who had undergone health checkups and responded to our survey by mail. Individual factors, the International Physical Activity Questionnaire (long form), and its environmental module acted as inputs to the study. The adjusted odds ratios (ORs) of high levels of moderate-to-vigorous intensity leisure-time physical activity (LTPA), walking for active recreation, and transportation were calculated in relation to individual and neighborhood environmental factors through multiple logistic regression models. Not working and good self-rated health were significantly associated with a higher level of each physical activity outcome. According to the adjusted ORs, higher educational attainment, higher economic status, good access to exercise facilities, and owning motor vehicles were associated with longer LTPA time. However, different sets of factors were associated with longer walking times for recreation and transportation. The results suggest that diverse individual and neighborhood environmental characteristics are associated with different physical activity outcomes. Therefore, customizing environments to become activity-friendly is necessary to increase physical activity effectively among middle-aged and elderly Japanese.

Kingella species including K. kingae are non-motile coccobacilli or short straight rods, and their normal habitats appear to be the upper respiratory and oropharyngeal tracts of humans. In recent years, K. kingae strains have been increasingly recognized as common causes of invasive infections in children at the age of less than 4 years. In Japan, however, invasive K. kingae infections including osteomyelitis have rarely been described. We incidentally encountered isolation of a K. kingae strain from intraoperatively obtained specimens from a previously healthy 44-month-old boy. He first consulted a nearby medical facility and a suspected diagnosis of osteomyelitis was made, after which the patient was then transferred to our Nagano Children's hospital. There was evidence of inflammation in his right calcaneus and toe walking was noted. He was treated with surgical drainage. An isolate grown on sheep blood agar with positive oxidase and negative catalase was biochemically characterized with the ID-Test HN20 (Nissui Pharmaceutical Co., Ltd., Tokyo, Japan) kit system together with genetic examinations involving sequencing the 16S rRNA gene, and the infection was finally identified as K. kingae. The patient was successfully treated with cefotiam (CTM) for the first 7 days followed by the administration of trimethoprim-sulfamethoxazole (ST) for an additional 2 months. The K. kingae isolate was confirmed as a sure causative pathogen by observing that the serum showed high agglutinin titers against the isolate. Accumulation of the case reports in Japan with the isolation of this species is essential for clarifying invasive infections due to K. kingae. Our case report is a noteworthy and useful piece of information.

This report presents the cases of three patients with fatal pneumonia that was highly suspected to be Pneumocystis pneumonia (PCP) based on serological diagnosis. Their chest radiographs showed bilateral pneumonia and each had presented with severe respiratory failure requiring mechanical ventilation when they arrived at the hospital. Although bronchoscopical sampling could not be performed, their chest computed tomography imaging and a marked elevation of serum KL-6 and β-D-glucan levels were characteristic of Pneumocystis pneumonia. All three were found to have been treated with temozolomide after surgery for malignant glioma. Temozolomide can cause Pneumocystis pneumonia. The three patients did not receive prophylactic medication against Pneumocystis pneumonia during treatment with temozolomide, and their histories suggested that all had delayed seeking treatment. It may be difficult to diagnose Pneumocystis pneumonia because the symptoms are not specific for Pneumocystis pneumonia and they tend to be similar to those of common respiratory infectious diseases. Therefore, patients who receive temozolomide therapy have the potential to develop fatal pneumonia and should be carefully observed. The patients should also be adequately informed about Pneumocystis pneumonia, and prophylaxis against Pneumocystis pneumonia should be considered proactively before treatment with temozolomide is initiated.