研究者詳細 - 杉山　大典

論文 - 杉山　大典

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The association between sleep parameters and sarcopenia in Japanese community-dwelling older adults

Shibuki T., Iida M., Harada S., Kato S., Kuwabara K., Hirata A., Sata M., Matsumoto M., Osawa Y., Okamura T., Sugiyama D., Takebayashi T.

Archives of Gerontology and Geriatrics （Archives of Gerontology and Geriatrics） 109 2023年06月

ISSN 01674943

Purpose: This study aimed to examine the association between sleep duration and quality and sarcopenia, assessed by factors such as low muscle mass (LMM), low muscle strength (LMS), and low physical performance (LPP) among older community-dwellers in Japan. Methods: In this cross-sectional study, a total of 2,069 (men, 902; women, 1,167) participants aged 65 to 80 years were included. Sarcopenia and each low physical function were defined using the definitions of the Asian Working Groups of Sarcopenia 2019. Sleep duration was stratified into three categories: short sleep (<6 h), normal sleep (6-8 h), and long sleep (>8 h). Sleep quality was classified into two groups based on 8-item Athens Insomnia Scale score: insomnia (≥6), and non-insomnia (<6). We analyzed the association between sleep parameters and sarcopenia, including low physical functions, by logistic regression analysis. Results: Compared to normal sleepers, long sleepers had a positive association with sarcopenia (odds ratio [OR] 2.11, 95% confidence interval [CI] 1.25-3.58). In particular, long sleep was strongly associated with LMS (OR 1.77, 95%CI 1.07-2.94) and LPP (OR 1.90, 95%CI 1.25-2.88). On the other hand, poor sleep quality was not associated with sarcopenia in long sleepers, but in normal sleepers. Conclusions: Long sleep was associated with sarcopenia, including LMS and LPP. However, in long sleepers, insomnia was not associated with sarcopenia or any of its components.

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Tsuji M., Fukahori H., Sugiyama D., Doorenbos A., Nasu K., Mashida Y., Ogawara H.

PLoS ONE （PLoS ONE） 18 （ 5 May ） 2023年05月

Globally, residents of long-term care facilities (LTCFs) often experience adverse events (AEs) and corresponding lawsuits that result in suffering among the residents, their families, and the facilities. Hence, we conducted a study to clarify the factors related to the facilities’ liabilities for damages for the AEs that occur at LTCFs in Japan. We analyzed 1,495 AE reports from LTCFs in one Japanese city. A binomial logistic regression analysis was conducted to identify factors associated with liability for damages. The independent variables were classified as: residents, organizations, and social factors. In total, 14% of AEs resulted in the facility being liable for damages. The predictors of liability for damages were as follows: for the resident factors, the increased need for care had an adjusted odds ratio (AOR) of 2.00 and care levels of 2–3; and AOR of 2.48 and care levels of 4–5. The types of injuries, such as bruises, wounds, and fractures, had AORs of 3.16, 2.62, and 2.50, respectively. Regarding the organization factors, the AE time, such as noon or evening, had an AOR of 1.85. If the AE occurred indoors, the AOR was 2.78, and if it occurred during staff care, the AOR was 2.11. For any follow-ups requiring consultation with a doctor, the AOR was 4.70, and for hospitalization, the AOR was 1.76. Regarding the type of LTCF providing medical care in addition to residential care, the AOR was 4.39. Regarding the social factors, the reports filed before 2017 had an AOR of 0.58. The results of the organization factors suggest that liability tends to arise in situations where the residents and their family expect high quality care. Therefore, it is imperative to strengthen organizational factors in such situations to avoid AEs and the resulting liability for damages.

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Fatty liver index predicts the development of hypertension in a Japanese general population with and without dysglycemia

Wu D., Hirata A., Hirata T., Imai Y., Kuwabara K., Funamoto M., Sugiyama D., Okamura T.

Hypertension Research （Hypertension Research） 46 （ 4 ） 879 - 886 2023年04月

ISSN 09169636

Fatty liver has been suggested to be associated with the development of hypertension. However, whether this association is related to glycemia has not been elucidated. Therefore, we investigated whether the fatty liver index (FLI) predicts the development of hypertension among individuals with and without dysglycemia in a general Japanese population. A total of 3114 participants (1036 males and 2078 females) without hypertension who underwent a Specific Health Checkup in the fiscal year 2013 were followed up until 2018. The participants were divided into six groups based on FLI tertiles (low, moderate, or high) and whether they had dysglycemia. We estimated the hazard ratios (HRs) of each group by sex using the Cox proportional hazard model. Models were adjusted for age, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, smoking, and alcohol consumption and further adjusted for systolic blood pressure (SBP). During the mean follow-up period of 2.8 years, 160 of the 3114 participants developed hypertension. Using the low FLI group with normoglycemia as a reference, the HR for incident hypertension was increased in the high FLI group with and without dysglycemia in both sexes after adjusting for confounders, except SBP (HR [95% confidence interval]: male: 1.52 (1.06–2.17) in normoglycemia and 2.05 (1.43–2.92) in dysglycemia, and female: 1.86 (1.43–2.42) in normoglycemia and 2.98 (2.19–4.07) in dysglycemia). Furthermore, in females, this association was observed after adjusting for SBP. We concluded that FLI was independently associated with an increased risk of incident hypertension in individuals with and without dysglycemia. [Figure not available: see fulltext.].

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Impact of hypertension and diabetes on the onset of chronic kidney disease in a general Japanese population

Kaneyama A., Hirata A., Hirata T., Imai Y., Kuwabara K., Funamoto M., Sugiyama D., Okamura T.

Hypertension Research （Hypertension Research） 46 （ 2 ） 311 - 320 2023年02月

ISSN 09169636

Hypertension (HT) and diabetes mellitus (DM) are both major risk factors for chronic kidney disease (CKD); however, few studies have examined the impacts of the combination of HT and DM on CKD development in general populations. We aimed to explore whether HT or DM contributes more to CKD development in a Japanese community. A total of 5823 individuals without a history of CKD who underwent specific health checkups in fiscal year 2013 were monitored until the end of March 2018. Participants were categorized as having neither HT nor DM (none group), either HT or DM, and both (HT + DM). We calculated the hazard ratios (HRs) for developing CKD in each category using Cox proportional hazards models after adjusting for age, dyslipidemia, smoking, and alcohol drinking and with the none group as the reference. We also estimated the population attributable fraction (PAF) for CKD development in populations with either HT or DM or both. During a mean follow-up of 3.0 years, 759 individuals developed CKD, with HRs of 1.56 with a 95% confidence interval (CI) [1.33, 1.83], 1.22 with a 95% CI [0.86, 1.75], and 2.83 with a 95% CI [2.22, 3.63] for the HT only, DM only and HT + DM categories, respectively. Sex-specific analysis showed similar findings. The PAFs for CKD (14.1% and 17.2% for men and women, respectively) were the highest among participants with HT only. We concluded that in this Japanese community, HT contributed more than DM to CKD development; hence, managing hypertension is important to prevent CKD as well as diabetes.

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Association between visceral fat accumulation and decline in the estimated glomerular filtration rate based on cystatin C in the Japanese urban population: the KOBE study

Tanabe A., Hirata A., Kuwabara K., Kubo S., Higashiyama A., Hirata T., Sugiyama D., Nishida Y., Kubota Y., Kadota A., Nishikawa T., Miyamatsu N., Miyamoto Y., Okamura T.

Endocrine journal （Endocrine journal） 70 （ 1 ） 97 - 106 2023年01月

Although metabolic syndrome, including visceral fat accumulation, causes kidney and cardiovascular diseases, the impact of visceral fat accumulation on mild decreased renal function remains unclear. This study examines the association between visceral fat area (VFA) measured by bioimpedance methods and the estimated glomerular filtration rate based on serum cystatin C (eGFRcys) in the Japanese urban population. This community-based cross-sectional study enrolled 952 individuals (287 men, 665 women) who participated in the second follow-up survey of the Kobe Orthopedic and Biomedical Epidemiological (KOBE) study. We compared the multivariate-adjusted means of eGFRcys among VFA quartile groups by gender using the analysis of covariance. Models were adjusted for age, high blood pressure, hypercholesterolemia, glucose intolerance, smoking, and alcohol use, and further adjusted for body mass index (BMI). The highest VFA quartile group had lower eGFRcys than the lowest VFA quartile group after adjusted for cardiometabolic risk factors, except for BMI (93.1 [95% confidence interval (CI), 90.1-96.2] vs. 82.1 [95% CI, 79.1-85.0] in men and 95.8 [95% CI, 94.1-97.5] vs. 89.4 [95% CI, 87.8-90.9] in women). Moreover, further adjustment for BMI revealed a similar result in men (93.5 [95% CI, 89.8-97.2] vs. 81.6 [95% CI, 77.9-85.3]), while no significant association was found in women. This study suggests a significant association between increased VFA levels and lower eGFRcys levels independent of cardiometabolic risk factors, such as glucose intolerance and hypercholesterolemia in men and women, as well as independent of BMI in men.

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Determinants of double product: a cross-sectional study of urban residents in Japan

Nakagoshi N., Kubo S., Nishida Y., Kuwabara K., Hirata A., Sata M., Higashiyama A., Kubota Y., Hirata T., Tatsumi Y., Kawamura K., Miyazaki J., Miyamatsu N., Sugiyama D., Miyamoto Y., Okamura T.

Environmental Health and Preventive Medicine （Environmental Health and Preventive Medicine） 28 （ 1 ） 2023年

ISSN 1342078X

Background: The current study aimed to investigate the determinants of high double product (DP) by evaluating the association between resting DP, which is calculated as systolic blood pressure (SBP) multiplied by heart rate (HR), and blood test results and lifestyle factors. Methods: This research included 973 participants in the baseline survey of the KOBE study, which included a cohort of urban residents. The possible DP determinants were identified by examining the association between lifestyle factors and laboratory findings and DP by analyzing covariance adjusted for sex and age. Logistic regression analysis was performed with high DP (SBP © HR ² 9145 mmHg beats/min or quintile according to sex) as outcome and DP determinants as independent variables. Results: Age, hematocrit, and gamma-glutamyl transferase (log) level were positively associated with a high DP in both men and women. In addition, a high DP was positively associated with Homeostatic Model Assessment for Insulin Resistance score in women alone. Meanwhile, the amount of exercise was negatively associated with a high DP in men alone. Conclusions: High DP values at rest were associated with insulin resistance, gamma-glutamyl transferase, and the amount of exercise in participants without underlying disease.

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Impact of Resting Heart Rate on Cardiovascular Mortality According to Serum Albumin Levels in a 24-year Follow-up Study on a General Japanese Population: NIPPON DATA80

Liu Y., Hirata A., Okamura T., Sugiyama D., Hirata T., Kadota A., Kondo K., Ohkubo T., Miura K., Okayama A., Ueshima H.

Journal of Epidemiology （Journal of Epidemiology） 33 （ 5 ） 227 - 235 2023年

ISSN 09175040

Background: Elevated resting heart rate (RHR) is associated with an increased risk of cardiovascular disease (CVD) and all-cause mortality. However, the findings of cohort studies differed. Thus, the impact of RHR on CVD mortality might be different according to the background of the population. Therefore, we examined the relationship of RHR and CVD mortality according to serum albumin (ALB) levels in a Japanese general population. Methods: In total, 8,363 individuals without a history of CVD were followed for 24.0 years. The participants were divided into four groups according to the quartiles of RHR (Q1–Q4), and they were further classified into the high and low ALB groups based on a median value of 44 g/L. We estimated the multivariable-adjusted hazard ratios (HRs) of CVD mortality in each RHR group based on ALB levels, and the interaction between RHR and ALB groups on CVD mortality was evaluated. Results: We found no significant association between RHR and CVD mortality. However, the Q4 of RHR was significantly associated with an increased risk for CVD mortality (HR 1.27; 95% confidence interval [CI], 1.02–1.57) in participants with a low ALB level. Meanwhile, the Q4 of RHR was significantly correlated with a decreased risk for CVD morality in those with a high ALB level (HR 0.61; 95% CI, 0.47–0.79) after adjusting for covariates. A significant interaction between RHR and ALB for CVD mortality was shown (P < 0.001). Conclusion: The impact of RHR on CVD mortality differed according to ALB levels in a general Japanese population.

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Japanese version of the Patient-rated elbow evaluation score correlates with physician-rated Japanese orthopaedic association-Japan elbow society elbow function score

Sato K., Ishigaki D., Iwabu S., Okazaki M., Koh S., Soejima O., Funakoshi T., Moriya K., Suzuki T., Ozasa Y., Sugiyama D.

Journal of Orthopaedic Science （Journal of Orthopaedic Science） 2023年

ISSN 09492658

Background: The association between Patient-Rated Elbow Evaluation: Japanese version (PREE-J) and Japanese Orthopaedic Association-Japan Elbow Society Elbow Function score (JOA-JES score) is unclear. This study evaluated the association between PREE-J and JOA-JES scores. Methods: The patients with elbow disorders were divided into two groups: Group A (conservative treatment, n = 97) and Group B (surgical treatment, n = 156). The patients were also divided into four disease subgroups according to the JOA-JES classification (rheumatoid arthritis, trauma, sports, and epicondylitis groups), and the association between PREE-J and JOA-JES scores in each disease category was examined. In group B, associations between PREE-J and JOA-JES scores were examined pre-and postoperatively. Results: In group A, there were significant associations between PREE-J and JOA-JES scores. In group B, a strong association between preoperative PREE-J and JOA-JES scores was observed in all disease categories. There was also a significant association between postoperative PREE-J and JOA-JES scores. Additionally, group B showed significant postoperative improvements in PREE-J and JOA-JES scores. Conclusions: The PREE-J score correlates well with the JOA-JES score and reflects treatment response before and after treatment.

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Effect of Chronic Kidney Disease or Anemia or Both on Cardiovascular Mortality in a 25-Year Follow-Up Study of Japanese General Population (From NIPPON DATA90)

Kubo K., Okamura T., Sugiyama D., Hisamatsu T., Hirata A., Kadota A., Kondo K., Hirata T., Higashiyama A., Hayakawa T., Miyamoto Y., Okayama A., Miura K., Ueshima H.

American Journal of Cardiology （American Journal of Cardiology） 184 1 - 6 2022年12月

ISSN 00029149

The relation between chronic kidney disease (CKD) and cardiovascular disease (CVD) in the general population is well elucidated. In patients with CKD, anemia is associated with adverse outcomes. However, the effects of CKD and anemia on CVD in the general population remains poorly explored, especially in Asian populations. This study aimed to investigate the effect of CKD and/or anemia on CVD mortality in a long-term cohort study involving Japanese community dwellers. We assessed 7,339 participants (aged ≥30 years) with no CVD history. These participants were divided into 4 categories according to their CKD (estimated glomerular filtration rate <60 or urine protein >1+ by dipstick qualitative test) and/or anemia (hemoglobin: <13 g/100 ml [men], <12 g/100 ml [women]) statuses. For each category, we calculated the hazard ratios (HRs) of CVD mortality by using the Cox proportional hazards model after adjusting for age, body mass index, hypertension, diabetes, dyslipidemia, smoking, and alcohol drinking. Within 25 years of follow-up, 637 participants died because of CVD. The HRs of CVD in patients with CKD only, anemia only, and both were 1.27, 1.59, and 2.60 (95% confidence intervals [CI] 1.06 to 1.53, 1.34 to 1.90, and 1.80 to 3.76) in men and 1.42, 1.08, and 2.00 (95% CI 1.19 to 1.69, 0.99 to 1.18, and 1.54 to 2.60) in women, respectively. In conclusion, CKD with anemia is associated with an increased risk for CVD mortality in a general population in Japan.

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Real-Time Survey of Vaccine Safety of the mRNA-1273 SARS-CoV-2 Vaccine in Workplace Vaccination at Keio University

Okumura K., Hara A., Inada I., Sugiyama D., Hoshino T., Yakoh T., Yokoyama H., Urushihara H.

Vaccines （Vaccines） 10 （ 9 ） 2022年09月

The mRNA-1273 Moderna COVID-19 vaccine was introduced to combat the COVID-19 global pandemic in 2020. Although the safety of the vaccine has been investigated worldwide, real-world safety data is scarce in Japan. An online, real-time survey of adverse events following immunization (AEFIs) with mRNA-1273 was conducted in the setting of a workplace vaccination program at the School of Pharmacy, Keio University from 26 June 2021, to 11 June 2022. Participants were requested to take four surveys during a seven-day follow-up period after each of the first, second, and third booster doses. The maximum number of responses, from 301 respondents, was obtained on day 0 (vaccination date) for the first dose. 98% of respondents reported local and systemic AEFIs for the second dose on day 1. No noticeable difference in local reactions was seen among the three doses. Females reported more AEFIs than males, and the young group (18–29 years) reported a higher rate than the middle age group (≥30 years) after the first dose. Age and gender differences in rates decreased at the second and third doses. This survey confirmed that the safety profile of mRNA-1273 in a real-world setting was similar to that derived from the clinical trials, and that the agent was well-tolerated.

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An Accelerated Failure Time Cure Model with Shifted Gamma Frailty and Its Application to Epidemiological Research

Aida H., Hayashi K., Takeuchi A., Sugiyama D., Okamura T.

Healthcare (Switzerland) （Healthcare (Switzerland)） 10 （ 8 ） 2022年08月

Survival analysis is a set of methods for statistical inference concerning the time until the occurrence of an event. One of the main objectives of survival analysis is to evaluate the effects of different covariates on event time. Although the proportional hazards model is widely used in survival analysis, it assumes that the ratio of the hazard functions is constant over time. This assumption is likely to be violated in practice, leading to erroneous inferences and inappropriate conclusions. The accelerated failure time model is an alternative to the proportional hazards model that does not require such a strong assumption. Moreover, it is sometimes plausible to consider the existence of cured patients or long-term survivors. The survival regression models in such contexts are referred to as cure models. In this study, we consider the accelerated failure time cure model with frailty for uncured patients. Frailty is a latent random variable representing patients’ characteristics that cannot be described by observed covariates. This enables us to flexibly account for individual heterogeneities. Our proposed model assumes a shifted gamma distribution for frailty to represent uncured patients’ heterogeneities. We construct an estimation algorithm for the proposed model, and evaluate its performance via numerical simulations. Furthermore, as an application of the proposed model, we use a real dataset, Specific Health Checkups, concerning the onset of hypertension. Results from a model comparison suggest that the proposed model is superior to existing alternatives.

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Influence of the COVID-19 pandemic on regular clinic visits and medication prescriptions among people with diabetes: Retrospective cohort analysis of health care claims

Maeda T., Nishi T., Harada M., Tanno K., Nishiya N., Asayama K., Okuda N., Sugiyama D., Yatsuya H., Okayama A., Arima H.

Medicine (United States) （Medicine (United States)） 101 （ 29 ） 2022年07月

ISSN 00257974

The aim of this study was to investigate the effect of the COVID-19 pandemic on regular clinic visits among people with diabetes and to elucidate the factors related to visit patterns among these patients during the pandemic. This was a longitudinal study using anonymized insurance claims data from the Joint Health Insurance Society in Tokyo from October 2017 to September 2020. First, we identified patients with diabetes who were fully enrolled in the health plan from fiscal year 2017 until September 2020 and who were regularly receiving glucose-lowering medications (every 1-3 months) from October 2017 to September 2018. We divided follow-up into the pre-pandemic period (October 2018 to March 2020) and the pandemic period (April 2020 to September 2020). A multilevel logistic regression model was used to determine the risks of delayed clinic visits/medication prescriptions (i.e., >3 months after a previous visit/prescription) during the pandemic period. We identified 1118 study participants. The number of delayed clinic visits/medication prescriptions during the pre-pandemic and pandemic periods was 188/3354 (5.6%) and 125/1118 (11.2%), respectively. There was a significant increase in delayed clinic visits during the pandemic (adjusted odds ratio 3.68 (95% confidence interval 2.24 to 6.04, P <.001), even after controlling for confounding factors. We also found a significant interaction between sex and delayed visits; women had significantly fewer clinic visits during the COVID-19 pandemic than men. We clarified the relationship of the COVID-19 pandemic with delays in regular clinic visits and medication prescriptions among people with diabetes. The response to the COVID-19 pandemic differed between men and women.

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Disparities in co-payments for influenza vaccine among the elderly, during the COVID-19 pandemic in Japan

Ando T., Maruyama T., Tamai A., Murakami T., Kido Y., Ishida T., Taya H., Haruta J., Sugiyama D., Fujishima S.

Journal of Infection and Chemotherapy （Journal of Infection and Chemotherapy） 28 （ 7 ） 896 - 901 2022年07月

ISSN 1341321X

Introduction: Seasonal influenza vaccination for the elderly is highly recommended during the COVID-19 pandemic. In Japan, the amount of subsidy for influenza differs among municipalities. Thus, we investigated the amount of and variation in subsidy for influenza vaccination for the elderly in 2020. Methods: This was an ecological study of 1,922 municipalities in Japan. The amount of subsidy for influenza vaccines for the elderly in each municipality was surveyed through websites or via telephone. Geographic and financial data for municipalities and prefectures were obtained from the open data. The amount of co-payment for the influenza vaccine and the geographical and financial status of each municipality were compared, according to the aging rate. Univariate logistic regression analysis was performed to explore factors related to the free influenza vaccine. Results: Municipalities with higher aging rates tended to have higher median co-payments for vaccines in 2020. (0 yen vs 1000 yen, p < 0.001) In addition, they tended to have worse financial conditions and lower per capita incomes. A similar trend was observed in the analysis by prefecture, i.e., a higher influenza mortality rate in prefectures with a higher aging rate. Despite having lower incomes, municipalities and prefectures with higher aging populations had higher mortality rates from influenza and higher co-payments for influenza vaccination. Conclusions: In Japan, there is a disparity among elderly people; areas with an aging population have higher co-payments for influenza vaccines despite lower incomes, suggesting that the government needs to implement corrective measures to reduce this disparity.

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Accumulated unhealthy behaviours and insomnia in Japanese dwellers with and without cardiovascular risk factors: A cross-sectional study

Kato S., Harada S., Iida M., Kuwabara K., Sugiyama D., Takeuchi A., Sata M., Matsumoto M., Kurihara A., Hirata A., Okamura T., Takebayashi T.

BMJ Open （BMJ Open） 12 （ 4 ） 2022年04月

Objectives To date, the association between accumulated unhealthy behaviours and insomnia in individuals stratified according to the presence or absence of major cardiovascular risk factors is unclear. This study aimed to examine the effect of accumulated unhealthy behaviours on insomnia in Japanese dwellers. Design Cross-sectional study. Setting Baseline data between April 2012 and March 2015. Participants Our study used cross-sectional data among Japanese aged 35-74 years in a rural community (N=9565), the attendees of annual municipal or work site health check-up programmes. Main outcome measures Insomnia was assessed by Athens Insomnia Scale, which was set at 6 points and greater; other scales were given. Participants were categorised into three groups by their number of unhealthy behaviours (no exercise habit, smoking, alcohol drinking, skipping breakfast and obesity): 0-1, 2-3, 4 or more. The association between accumulated unhealthy behaviours and insomnia was estimated by logistic regression analysis. Further analysis was done after stratification of cardiovascular risk factors assessed by anthropometrics and clinical biochemistry measurements. Results The overall prevalence of insomnia was 13.3% for men and 19.3% for women. Men with unhealthy behaviour factors were more likely to have insomnia after adjusting for potential confounders, compared with the least unhealthy group (trend p=0.013). Women with four or more unhealthy behaviour factors were more likely to have insomnia, compared with the lowest groups (OR 1.175, 95% CI 1.077 to 1.282). Insomnia has an association with the unhealthy behaviours among men without cardiovascular risk factors (lowest groups: OR 1.133, 95% CI 1.037 to 1.238, trend p=0.026). Women without hypertension were more likely to have suspected insomnia, compared with the lowest group (OR 1.215, 95% CI 1.101 to 1.341). Conclusion The results showed accumulated unhealthy behaviours were associated with increased risk of insomnia in Japanese dwellers. For healthy population without cardiovascular risk factors, unhealthy behaviours should be considered as background conditions for insomnia.

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Changes in Smoking Habits and Behaviors Following the Introduction and Spread of Heated Tobacco Products in Japan and Its Effect on FEV<inf>1</inf> Decline: A Longitudinal Cohort Study

Harada S., Sata M., Matsumoto M., Iida M., Takeuchi A., Kato S., Hirata A., Kuwabara K., Shibuki T., Ishibashi Y., Sugiyama D., Okamura T., Takebayashi T.

Journal of Epidemiology （Journal of Epidemiology） 32 （ 4 ） 180 - 187 2022年04月

ISSN 09175040

Background: Heated tobacco product (HTP) use in Japan has rapidly increased. Despite this rapid spread, little is known about the health effects of HTP use. We conducted a longitudinal cohort study to investigate the change in smoking habits following the spread of HTP use and its effect on forced expiratory volume in 1 second (FEV1) decline. Methods: Participants consisted of a resident population (n = 2,612; mean age, 67.7 years) with FEV1 measurement in 2012–2014 and 2018–2019, and a worksite population (n = 722; mean age 49.3 years) without FEV1 data. Participants were categorized as combustible cigarette-only smokers, HTP-only users, dual users, past smokers, and never smokers. The association between smoking group and the change in smoking consumption over a mean 5.6 years was examined. Differences in annual FEV1 change between smoking groups were examined in the resident population. Results: Prevalence of HTP-only and dual users in 2018–2019 was 0.8% and 0.6% in the resident population, and 5.0% and 1.9% in the worksite population, respectively. The overall number of tobacco products smoked=used increased in dual users compared to baseline, but not in others. Annual FEV1 decline in dual users tended to be greater than that in cigarette-only smokers (16; 95% confidence interval, −34 to 2 mL=year after full adjustment). Participants switching to HTP-only use 1.7 years before had a similar FEV1 decline as cigarette-only smokers. Conclusions: HTP use, including dual use, is prevalent even in a rural region of Japan. Dual users appear to smoke=use tobacco products more and have a greater FEV1 decline. Tobacco policy should consider dual use as high-risk.

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The association of high Vancomycin trough concentration with acute kidney injury during combination therapy of Piperacillin/Tazobactam and Vancomycin

Saito S., Sugimoto T., Takenaka K., Goto H., Kumahara A., Watanabe R., Sugiyama D., Yasutomo Y., Takatsuki K.

Practical Laboratory Medicine （Practical Laboratory Medicine） 29 2022年03月

Background: Co-administration of Piperacillin/Tazobactam (PIPC/TAZ) and Vancomycin (VCM) as an antibiotic therapy for severe infectious diseases increases the risk of nephrotoxicity. We retrospectively investigated the utility of monitoring VCM trough concentration in early stage of developing acute kidney injury (AKI) on this combination therapy. Methods: We enrolled all infectious disease patients who were managed with concurrent PIPC/TAZ and VCM. The record of dosage and the administration interval of each antibiotic and its clinical parameters, as well as the VCM trough concentrations, blood culture for bacteria, and serum creatinine values, were collected. VCM trough concentration was measured during the initial 48–72 h of VCM administration. Nephrotoxicity was evaluated as the degree of AKI. Results: A total of 47 patients fulfilling the criteria were registered, and AKI developed in 10 patients. There was no statistical difference between the AKI and non-AKI groups with regard to age, height, weight, basal creatinine level, body surface area, body mass index, PIPC/TAZ dose, VCM dose, gender, artificial management, and death within around 30 days. The VCM trough level was increased significantly in the AKI group (mean [standard deviation {SD}]: 25.9 [7.8] μg/mL) compared to that in the non-AKI group (mean [SD]: 15.7 [6.9] μg/mL) (p = 0.003). During the clinical course, renal function returned to normal levels in three out of four AKI stage 2 patients, whereas only partial recovery was achieved in all AKI stage 3 patients. Conclusions: A high VCM trough concentration may have an influence on the occurrence of AKI during combination therapy of PIPC/TAZ and VCM. Careful monitoring of VCM trough concentration will be required to prevent AKI progression.

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Metabolic profiling of charged metabolites in association with menopausal status in Japanese community-dwelling midlife women: Tsuruoka Metabolomic Cohort Study

Watanabe K., Iida M., Harada S., Kato S., Kuwabara K., Kurihara A., Takeuchi A., Sugiyama D., Okamura T., Suzuki A., Amano K., Hirayama A., Sugimoto M., Soga T., Tomita M., Kobayashi Y., Banno K., Aoki D., Takebayashi T.

Maturitas （Maturitas） 155 54 - 62 2022年01月

ISSN 03785122

Background: Emerging evidence has shown that charged metabolites, such as amino acids, may play an important role in the pathogenesis of various metabolic disorders, many of which women in the postmenopausal period are at high risk of developing. This study examined the metabolic profile of middle-aged Japanese women to investigate alterations in charged metabolites induced by menopausal transition. Methods: The participants were 1193 female residents aged 40–60 at the baseline survey of the Tsuruoka Metabolomics Cohort Study. We investigated the cross-sectional association of menopausal status with 94 metabolomic biomarkers assayed in fasting plasma samples via capillary electrophoresis time-of-flight mass spectrometry using linear regression analysis. Results: Among the participants, 529 were premenopausal, 132 were in menopausal transition (MT), and 532 were postmenopausal. Significant differences were found in age, blood pressure, glucose and lipid levels, and smoking and drinking habits among the three groups. The concentrations of 5 metabolites in the MT group and 15 metabolites in the postmenopausal group were significantly higher than those in the premenopausal group after adjusting for confounding factors. When classified into pathways, these metabolites were related to the tricarboxylic cycle, urea cycle, and homocysteine metabolism, some of which are linked to arteriosclerosis. Conclusion: Multiple charged metabolites were associated with women's menopausal status, showing a gradual increase as women shifted from pre-, to peri-, to postmenopause. These findings might reflect the early changes behind the increased risk of dyslipidemia, diabetes, cardiovascular disease, and osteoporosis in later life.

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Physique at Birth and Cardiovascular Disease Risk Factors in Japanese Urban Residents: the KOBE Study

Umemoto K., Kubo S., Nishida Y., Higashiyama A., Kawamura K., Kubota Y., Hirata T., Hirata A., Sata M., Kuwabara K., Miyazaki J., Kadota A., Iida M., Sugiyama D., Miyamatsu N., Miyamoto Y., Okamura T.

Journal of Atherosclerosis and Thrombosis （Journal of Atherosclerosis and Thrombosis） 29 （ 2 ） 188 - 199 2022年

ISSN 13403478

Aim: This study investigated the relationship between birth physique and cardiovascular risk factors in Japanese urban residents aged 40 years and more. Methods: A self-administered questionnaire on birth physique was performed among 624 individuals (165 men and 459 women) who participated in the KOBE study. We examined whether self-reported birth physique and available recorded birth weights matched for 72 participants. Then the association between birth physique and risk factors for all participants was examined by gender. Body size at birth in the questionnaire (large, medium, small) was set as an exposure and laboratory values from the baseline survey (2010-2011) were used as outcomes. Results: Mean (standard deviation) recorded birth weight of 72 participants was 3665 (318), 3051 (300), and 2653 (199) g, in the large, medium, and small group, respectively. In the analysis for all participants, odds ratio for having both hypertension and impaired glucose tolerance were significantly higher in the small versus large birth weight group, which was 7.42 (95% CI 1.75–31.50) for men and 4.44 (95% CI 1.14–17.30) for women after adjusting for age, body mass index, smoking/alcohol/exercise habits, and menstrual status in women. Similar results were observed in participants with recorded birth weight. Conclusions: The present study indicates that individuals with small physique at birth might be at higher risk for hypertension and impaired glucose tolerance in middle age compared to those with large birth weight.

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Relationship Between Non-fasting Triglycerides and Cardiovascular Disease Mortality in a 20-year Follow-up Study of a Japanese General Population: NIPPON DATA90

Hirata A., Okamura T., Hirata T., Sugiyama D., Ohkubo T., Okuda N., Kita Y., Hayakawa T., Kadota A., Kondo K., Miura K., Okayama A., Ueshima H.

Journal of Epidemiology （Journal of Epidemiology） 32 （ 7 ） 303 - 313 2022年

ISSN 09175040

Background: Non-fasting triglycerides (TG) are considered a better predictor of cardiovascular disease (CVD) than fasting TG. However, the effect of non-fasting TG on fatal CVD events remains unclear. In the present study, we aimed to explore the relationship between non-fasting TG and CVD mortality in a Japanese general population. Methods: A total of 6,831 participants without a history of CVD, in which those who had a blood sampling over 8 hours or more after a meal were excluded, were followed for 18.0 years. We divided participants into seven groups according to non-fasting TG levels: ≤59 mg=dL, 60–89 mg=dL, 90–119 mg=dL, 120–149 mg=dL, 150–179 mg=dL, 180–209 mg=dL, and ≥210 mg=dL, and estimated the multivariable-adjusted hazard ratios (HRs) of each TG group for CVD mortality after adjusting for potential confounders, including high density lipoprotein cholesterol. Additionally, we performed analysis stratified by age <65 and ≥65 years. Results: During the follow-up period, 433 deaths due to CVD were detected. Compared with a non-fasting TG of 150–179 mg=dL, non-fasting TG ≥210 mg=dL was significantly associated with increased risk for CVD mortality (HR 1.56: 95% CI, 1.01–2.41). Additionally, lower levels of non-fasting TG were also significantly associated with increased risk for fatal CVD. In participants aged ≥65 years, lower levels of non-fasting TG had a stronger impact on increased risk for CVD mortality, while higher levels of non-fasting TG had a stronger impact in those aged <65 years. Conclusion: In a general Japanese population, we observed a U-shaped association between non-fasting TG and fatal CVD events.

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Bone Marrow Infiltration Is a Distinctive Risk Factor for Rituximab Infusion-Related Reactions in CD20-Positive B-Cell Non-Hodgkin Lymphoma

Ohata S., Takenaka K., Sugiyama D., Sugimoto T.

Advances in Hematology （Advances in Hematology） 2022 2022年

ISSN 16879104

Background. Bone marrow infiltration of lymphoma cells is a candidate risk factor for infusion-related reactions (IRRs) in patients with CD20-positive B-cell non-Hodgkin lymphoma (B-NHL). However, despite with the lack of sufficient data, the effect of bone marrow infiltration of B-NHL cells on the incidence rate of grade 2 or higher IRRs with the administration of rituximab has been retrospectively studied in this paper. Methods. Patients with CD20-positive B-NHL who received the rituximab induction therapy for the first time were enrolled in this study. To evaluate the bone marrow infiltration of B-NHL cells, May-Giemsa stain of bone marrow films and flow cytometry examination of bone marrow aspiration samples were performed. IRR grade was determined using the IRR criteria in the Common Terminology Criteria for Adverse Events version 4.0. Results. A total of 127 patients were eligible for this study. Grade 2 or higher IRRs were observed in 43 (34%) patients. In univariate analysis, use of glucocorticoid before rituximab infusion was a strong risk-avoiding factor for grade 2 or higher IRRs. Advanced stage of disease (Ann Arbor: stages III and IV) or bone marrow infiltration of B-NHL cells revealed the risk factors, regardless of glucocorticoid premedication. Using multivariate analysis, bone marrow infiltration was found to be an independent risk factor for patients without prior glucocorticoid use. Conclusion. Bone marrow infiltration of B-NHL cells is a risk factor for grade 2 or higher IRRs at the first rituximab induction therapy without glucocorticoid premedication.

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