掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/s0140-6736(24)02317-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Up to seven doses of coronavirus disease 2019 (COVID-19) mRNA vaccines (BNT162b2) were administered to Japanese healthcare workers, until February 2024. The monovalent Omicron XBB.1.5 vaccine (hereafter called XBB.1.5 vaccine) was used for dose 7. OBJECTIVE: Although the XBB.1.5 vaccine has been reported to induce a robust increase in neutralizing antibodies against the currently circulating Omicron variant BA.2.86, little is known about its serological effects in Japan, where the BNT162b2 mRNA vaccine is the most frequently administered in the world. STUDY DESIGN: Twenty-five recipients of the XBB.1.5 vaccine, categorized as seronegative (n = 18) or seropositive (n = 7) based on their recent history of COVID-19, were analyzed. Neutralizing antibody titers against Omicron subvariants, receptor binding domain (RBD) IgG levels, IgG subclass distribution, and T-cell responses were assessed. RESULTS: We found a significant increase in neutralizing antibody titers against XBB.1.5 and BA.2.86 variants following XBB.1.5 vaccination, particularly in seropositive individuals. No significant change in total RBD IgG levels was observed, indicating efficient induction of antibodies targeting regions outside the RBD by XBB.1.5 vaccination. IgG subclass analysis demonstrated no significant subclass switching after vaccination. T-cell responses against the virus were comparable between seropositive and seronegative groups. CONCLUSIONS: The study suggests that XBB.1.5 vaccination enhances humoral immunity against Omicron variants without significant IgG subclass switching. However, some individuals with low pre-vaccination IgG titers did not exhibit increased antibody levels post-vaccination, raising concerns about potential immune tolerance.

DOI： 10.1016/j.vaccine.2024.126452

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Observational studies have reported associations between primary aldosteronism (PA) and cardiovascular outcomes, including coronary artery diseases (CAD), congestive heart failure (CHF), and stroke. However, establishing causality remains a challenge due to the lack of randomized controlled trial data on this topic. We thus aimed to investigate the causal relationship between PA and the risk of developing CAD, CHF, and stroke. METHODS AND RESULTS: Cross-ancestry meta-analysis of genome-wide association studies combining East Asian and European ancestry (1560 PA cases and 742 139 controls) was conducted to identify single-nucleotide variants that are associated with PA. Then, using the identified genetic variants as instrumental variables, we conducted the 2-sample Mendelian randomization analysis to investigate the causal relationship between PA and incident CAD, CHF, and stroke among both East Asian and European ancestry. Summary association results were extracted from large genome-wide association studies consortia. Our cross-ancestry meta-analysis of East Asian and European populations identified 7 genetic loci significantly associated with the risk of PA, for which the genes nearest to the lead variants were CASZ1, WNT2B, HOTTIP, LSP1, TBX3, RXFP2, and NDP. Among the East Asian population, the pooled odds ratio estimates using these 7 genetic instruments of PA were 1.07 (95% CI, 1.03-1.11) for CAD, 1.10 (95% CI, 1.01-1.20) for CHF, and 1.13 (95% CI, 1.09-1.18) for stroke. The results were consistent among the European population. CONCLUSIONS: Our 2-sample Mendelian randomization study revealed that PA had increased risks of CAD, CHF, and stroke. These findings highlight that early and active screening of PA is critical to prevent future cardiovascular events.

DOI： 10.1161/JAHA.123.034180

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

It is expected but unknown whether machine-learning models can outperform regression models, such as a logistic regression (LR) model, especially when the number and types of predictor variables increase in electronic health records (EHRs). We aimed to compare the predictive performance of gradient-boosted decision tree (GBDT), random forest (RF), deep neural network (DNN), and LR with the least absolute shrinkage and selection operator (LR-LASSO) for unplanned readmission. We used EHRs of patients discharged alive from 38 hospitals in 2015-2017 for derivation and in 2018 for validation, including basic characteristics, diagnosis, surgery, procedure, and drug codes, and blood-test results. The outcome was 30-day unplanned readmission. We created six patterns of data tables having different numbers of binary variables (that ≥5% or ≥1% of patients or ≥10 patients had) with and without blood-test results. For each pattern of data tables, we used the derivation data to establish the machine-learning and LR models, and used the validation data to evaluate the performance of each model. The incidence of outcome was 6.8% (23,108/339,513 discharges) and 6.4% (7,507/118,074 discharges) in the derivation and validation datasets, respectively. For the first data table with the smallest number of variables (102 variables that ≥5% of patients had, without blood-test results), the c-statistic was highest for GBDT (0.740), followed by RF (0.734), LR-LASSO (0.720), and DNN (0.664). For the last data table with the largest number of variables (1543 variables that ≥10 patients had, including blood-test results), the c-statistic was highest for GBDT (0.764), followed by LR-LASSO (0.755), RF (0.751), and DNN (0.720), suggesting that the difference between GBDT and LR-LASSO was small and their 95% confidence intervals overlapped. In conclusion, GBDT generally outperformed LR-LASSO to predict unplanned readmission, but the difference of c-statistic became smaller as the number of variables was increased and blood-test results were used.

DOI： 10.1371/journal.pdig.0000578

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: Japan started the Diabetic Nephropathy Aggravation Prevention Program. Its early impact was assessed in this study. METHODS: This study used the Kokuho Database of patients with type 2 diabetes from program-implementing and non-implementing municipalities (fiscal years [FYs] 2015-2021). Implementing municipalities facilitated clinic visits and provided education to eligible patients. Average treatment effects on the treated in FYs 2016 and 2018 were evaluated using the inverse probability of treatment weighting. Comparison included intervened vs. non-intervened patients in program-implementing municipalities (Comparison A), intervened patients in program-implementing vs. eligible patients in non-implementing municipalities (Comparison B), and eligible patients in implementing and non-implementing municipalities (Comparison C). RESULTS: Overall, 89,611/89,685 patients from FY 2016/2018 were eligible. Among 68,125/68,170 patients in program-implementing municipalities, 1,470/1,819 were intervened. In Comparison A, the estimated effect of the program on ΔeGFR at 3 years were -0.4 (95 % confidence interval; -1.0, 0.2)/-0.4 (-0.9, 0.1) mL/min/1.73 m2 in FY 2016/2018. Comparisons B and C demonstrated similar tendency; distribution of %change in eGFR varied between municipalities. CONCLUSIONS: Early in the program, renal function did not improve in the intervened patients or program-implementing municipalities. Diverse eGFR changes across municipalities highlighted diverse intervention outcomes, emphasizing the need of program refinement.

DOI： 10.1016/j.diabres.2024.111804

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

DOI： 10.1007/s13340-024-00723-8

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その他リンク： https://link.springer.com/article/10.1007/s13340-024-00723-8/fulltext.html

記述言語：英語   掲載種別：研究論文（学術雑誌）  

In observational studies, identifying and adjusting for a sufficient set of confounders is crucial for accurately estimating the causal effect of the exposure on the outcome. Even in studies with large sample sizes, which typically benefit from small variances in estimates, there is a risk of producing estimates that are precisely inaccurate if the study suffers from systematic errors or biases, including confounding bias. To date, several approaches have been developed for selecting confounders. In this article, we first summarize the epidemiological and statistical approaches to identify a sufficient set of confounders. Particularly, we introduce the modified disjunctive cause criterion as one of the most useful approaches, which involves controlling for any pre-exposure covariate that affects the exposure, outcome, or both. It then excludes instrumental variables but includes proxies for the shared common cause of exposure and outcome. Statistical confounder selection is also useful when dealing with a large number of covariates, even in studies with small sample sizes. After introducing several approaches, we discuss some pitfalls and considerations in confounder selection, such as the adjustment for instrumental variables, intermediate variables, and baseline outcome variables. Lastly, as it is often difficult to comprehensively measure key confounders, we introduce two statistics, E-value and Robustness value, for assessing sensitivity to unmeasured confounders. Illustrated examples are provided using the National Health and Nutritional Examination Survey Epidemiologic Follow-up Study. Integrating these principles and approaches will enhance our understanding of confounder selection and facilitate better reporting and interpretation of future epidemiological studies.

DOI： 10.2188/jea.JE20240082

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

To ascertain the involvement of insulin receptors (IRs) in colorectal carcinogenesis, we investigated the association of height, body mass index (BMI), and physical activity with colorectal cancer (CRC) and two subtypes of CRC according to the expression level of IR. We utilized data from a large-scale, population-based prospective cohort study of 18,158 middle-aged and elderly subjects in Akita and Okinawa, Japan. In the statistical analysis, we used the Cox proportional hazards model and estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of CRC and its subtypes as defined by immunohistochemistry of IRβ, a transmembrane subunit of IR. In the IRβ-defined subtypes, height showed no apparent association with the risk of IRβ-positive CRC. In contrast, a multivariable HR of IRβ-positive CRC was 1.77 (95% CI = 1.04-3.03) with a BMI of ≥30.0 kg/m2 (i.e., obesity), compared to a BMI of <25.0 kg/m2. Further, an increase in physical activity was significantly associated with decreased risk of IRβ-positive CRC (multivariable HR per 5 METs-hour/day = 0.93, 95% CI = 0.88-0.99). Meanwhile, we found no significant association between any exposure and IRβ-negative CRC. Likewise, heterogeneity between the two subtypes of CRC was not statistically significant. These findings imply that obesity and physical activity exert promoting and suppressing effects on the development of CRC expressing IRs, respectively.

DOI： 10.1002/ijc.35075

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: The COVID-19 pandemic posed tremendous challenges for children. However, the long-term effects of the pandemic on various aspects of physical health at a national level remain unclear. METHODS: In this retrospective cohort study, we analysed data from nationwide health checkup records amongst children aged 7-15 years. The dataset comprised 3 544 146 records from 393 794 individuals who graduated from junior high school during fiscal years 2007 to 2022. Difference-in-differences (DID) analyses with multiple time periods were used to examine the impact of COVID-19 on physical health outcomes. RESULTS: Compared with the pre-pandemic period, the COVID-19 pandemic was associated with excess increases in obesity for boys and girls, persisting over the 3 years (+0.42%; [95% CI, 0.23-0.61]). Also, it was associated with excess increases in underweight (+0.28% [0.25-0.32]) and poor visual acuity amongst boys in the 3rd year (+1.80% [1.30-2.30]). There were excess reductions in dental caries (-1.48% [-2.01 to -0.95]), glucosuria (-0.55 [-0.88 to -0.23]) and hematuria (-0.43% [-0.73 to -0.13]) during the 3rd year of the pandemic. CONCLUSIONS: These findings underscore the multifaceted impact of the pandemic on various health indicators for school-aged children. This information could be valuable for public health policy and paediatric healthcare planning in the post-pandemic era.

DOI： 10.1111/ijpo.13126

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

In observational studies, instrumental variable (IV) methods are commonly applied when there are unmeasured covariates. In Mendelian randomization, constructing an allele score using many single nucleotide polymorphisms is often implemented; however, estimating biased causal effects by including some invalid IVs poses some risks. Invalid IVs are those IV candidates that are associated with unobserved variables. To solve this problem, we developed a novel strategy using negative control outcomes (NCOs) as auxiliary variables. Using NCOs, we are able to select only valid IVs and exclude invalid IVs without knowing which of the instruments are invalid. We also developed a new two-step estimation procedure and proved the semiparametric efficiency of our estimator. The performance of our proposed method was superior to some previous methods through simulations. Subsequently, we applied the proposed method to the UK Biobank dataset. Our results demonstrate that the use of an auxiliary variable, such as an NCO, enables the selection of valid IVs with assumptions different from those used in previous methods.

DOI： 10.1002/bimj.202300113

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: While past research suggested that living arrangements are associated with suicide death, no study has examined the impact of sustained living arrangements and the change in living arrangements. Also, previous survival analysis studies only reported a single hazard ratio (HR), whereas the actual HR may change over time. We aimed to address these limitations using causal inference approaches. METHODS: Multi-point data from a general Japanese population sample were used. Participants reported their living arrangements twice within a 5-year time interval. After that, suicide death, non-suicide death and all-cause mortality were evaluated over 14 years. We used inverse probability weighted pooled logistic regression and cumulative incidence curve, evaluating the association of time-varying living arrangements with suicide death. We also studied non-suicide death and all-cause mortality to contextualize the association. Missing data for covariates were handled using random forest imputation. RESULTS: A total of 86,749 participants were analysed, with a mean age (standard deviation) of 51.7 (7.90) at baseline. Of these, 306 died by suicide during the 14-year follow-up. Persistently living alone was associated with an increased risk of suicide death (risk difference [RD]: 1.1%, 95% confidence interval [CI]: 0.3-2.5%; risk ratio [RR]: 4.00, 95% CI: 1.83-7.41), non-suicide death (RD: 7.8%, 95% CI: 5.2-10.5%; RR: 1.56, 95% CI: 1.38-1.74) and all-cause mortality (RD: 8.7%, 95% CI: 6.2-11.3%; RR: 1.60, 95% CI: 1.42-1.79) at the end of the follow-up. The cumulative incidence curve showed that these associations were consistent throughout the follow-up. Across all types of mortality, the increased risk was smaller for those who started to live with someone and those who transitioned to living alone. The results remained robust in sensitivity analyses. CONCLUSIONS: Individuals who persistently live alone have an increased risk of suicide death as well as non-suicide death and all-cause mortality, whereas this impact is weaker for those who change their living arrangements.

DOI： 10.1017/S2045796024000325

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The mechanistic associations between obesity and risk of colorectal cancer (CRC) remain unclear. Here, using body mass index (BMI) as an obesity indicator, we decomposed the total effects of obesity on the risk of CRC into: (1) direct effects, which are possibly mediated by unmeasured or currently unknown factors; (2) indirect effects mediated by circulating leptin and adiponectin; and (3) indirect effects that are not mediated by circulating leptin and adiponectin but by hyperinsulinemia and chronic inflammation (assessed via circulating connecting peptide and C-reactive protein, respectively). METHODS: We adopted a causal mediation framework, using data from a large prospective cohort study of 44,271 Japanese men. RESULTS: BMI was not associated with the risk of CRC due to direct and indirect effects that were not mediated by circulating leptin and adiponectin. By contrast, individuals with BMIs of 25.0-27.4 kg/m2 (risk ratio, 1.29; 95% confidence interval, 0.98-1.69) and ≥27.5 kg/m2 (risk ratio, 1.28; 95% confidence interval, 0.98-1.68) had a higher risk of CRC due to indirect effects of circulating leptin and adiponectin. CONCLUSIONS: Our mediation analyses suggest that the association between BMI and CRC risk may be largely mediated by a pathway involving circulating leptin and adiponectin.

DOI： 10.2188/jea.JE20230148

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Instrumental variable (IV) methods are widely employed to estimate causal effects when concerns regarding unmeasured confounders. Although comparisons among several IV methods for binary outcomes exist, comprehensive evaluations are insufficient. Therefore, in this study, we aimed to conduct a simulation with some settings for a detailed comparison of these methods, focusing on scenarios where IVs are valid and under effect homogeneity with different instrument strengths. METHODS: We compared six IV methods under 32 simulation scenarios: two-stage least squares (2SLS), two-stage predictor substitutions (2SPS), two-stage residual inclusions (2SRI), limited information maximum likelihood (LIML), inverse-variance weighted methods with a linear outcome model (IVWLI), and inverse-variance weighted methods with a non-linear model (IVWLL). By comparing these methods, we examined three key estimates: the parameter estimates of the exposure variable, the causal risk ratio, and the causal risk differences. RESULTS: Based on the results, six IV methods could be classified into three groups: 2SLS and IVWLI, 2SRI and 2SPS, and LIML and IVWLL. The first pair showed a clear bias owing to outcome model misspecification. The second pair showed a relatively good performance when strong IVs are available; however, the estimates suffered from a significant bias when only weak IVs are used. The third pair produced relatively conservative results, although they were less affected by weak IV issues. CONCLUSIONS: The findings indicate that no panacea is available for the bias associated with IV methods. We suggest using multiple IV methods: one for primary analysis and another for sensitivity analysis.

DOI： 10.2188/jea.JE20230271

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Genetic epidemiological evidence for the kidney function traits in East Asian population including Japanese remain still relatively unclarified. Especially, the number of GWASs for kidney traits reported still remains limited, and the sample size of each independent study is relatively small. Given the genetic variability between ancestries/ethnicities, implementation of GWAS with sufficiently large sample sizes in specific population of Japanese is considered meaningful. METHODS: We conducted the GWAS meta-analyses of kidney traits by leveraging the GWAS summary data of the representative large genome cohort studies with about 200,000 Japanese participants (n = 202,406 for estimated glomerular filtration rate [eGFR] and n = 200,845 for serum creatinine [SCr]). RESULTS: In the present GWAS meta-analysis, we identified 110 loci with 169 variants significantly associated with eGFR (on chromosomes 1-13 and 15-22; p < 5×10-8), whereas we also identified 112 loci with 176 variants significantly associated with SCr (on chromosomes 1-22; p < 5×10-8), of which one locus (more than 1Mb distant from known loci) with one variant (CD36 rs146148222 on chromosome 7) for SCr was considered as the truly novel finding. CONCLUSIONS: The present GWAS meta-analysis of largest genome cohort studies in Japanese provided some original genomic loci associated with kidney function in Japanese, which may contribute to the possible development of personalized prevention of kidney diseases based on genomic information in the near future.

DOI： 10.2188/jea.JE20230281

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The Japan Diabetes Society and the Japan Cancer Association launched a joint committee and published their "First Joint Committee Report on Diabetes and Cancer" in 2013, compiling recommendations for physicians and health-care providers as well as for the general population. In 2016, the "Second Joint Committee Report on Diabetes and Cancer" summarized the current evidence on glycemic control and cancer risk in patients with diabetes. The current "Third Joint Committee Report on Diabetes and Cancer", for which the joint committee also enlisted the assistance of the Japanese Society of Clinical Oncology and the Japanese Society of Medical Oncology, reports on the results from the questionnaire survey, "Diabetes Management in Patients Receiving Cancer Therapy," which targeted oncologists responsible for cancer management and diabetologists in charge of glycemic control in cancer patients. The results of the current survey indicated that there is a general consensus among oncologists and diabetologists with regard to the need for guidelines on glycemic control goals, the relevance of glycemic control, and glycemic control during cancer therapy in cancer patients.

DOI： 10.1111/cas.15975

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

An East Asian-specific variant on aldehyde dehydrogenase 2 (ALDH2 rs671, G>A) is the major genetic determinant of alcohol consumption. We performed an rs671 genotype-stratified genome-wide association study meta-analysis of alcohol consumption in 175,672 Japanese individuals to explore gene-gene interactions with rs671 behind drinking behavior. The analysis identified three genome-wide significant loci (GCKR, KLB, and ADH1B) in wild-type homozygotes and six (GCKR, ADH1B, ALDH1B1, ALDH1A1, ALDH2, and GOT2) in heterozygotes, with five showing genome-wide significant interaction with rs671. Genetic correlation analyses revealed ancestry-specific genetic architecture in heterozygotes. Of the discovered loci, four (GCKR, ADH1B, ALDH1A1, and ALDH2) were suggested to interact with rs671 in the risk of esophageal cancer, a representative alcohol-related disease. Our results identify the genotype-specific genetic architecture of alcohol consumption and reveal its potential impact on alcohol-related disease risk.

DOI： 10.1126/sciadv.ade2780

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The optimal administration of inotrope after cardiac surgery is unknown. This study aimed to investigate the impact of postoperative inotrope on clinical outcomes in adult elective cardiac surgery patients. Data from the Blood Pressure and Relative Optimal Target after Heart Surgery in Epidemiologic Registry study were analyzed, employing propensity score considering the hospital of admission. The primary outcome was the length of hospital stay evaluated using quantile regression. Secondary outcomes were kidney injury progression, renal replacement therapy, atrial fibrillation, mortality, mechanical ventilation duration, and length of intensive care unit (ICU) stay. Among 870 patients from 14 ICUs in Japan, 535 received inotropes within 24 h of ICU admission, with usage rates ranging from 40 to 100% among facilities. After propensity score matching, 218 patients were included in each group. The inotrope group had a significantly longer hospital stay compared to the control group (16 days vs. 14 days; median difference 1.78 [95% confidence interval [CI] 0.31-3.24]; p = 0.018). However, no significant differences were observed in the secondary outcomes, except for mechanical ventilation duration. The results of the sensitivity analysis using a mixed-effects quantile regression analysis considering the hospital of admission for length of hospital stay in the original cohort were consistent with the results of the propensity analyses (median difference in days, 2.35 [95% CI, 0.35-4.36]; p = 0.022). The use of inotropes within 24 h of ICU admission in adult elective cardiac surgery patients was associated with an extended hospitalization period of approximately 2 days, without offering any prognostic benefit. Clinical trial registration: UMIN-CTR, https://www.umin.ac.jp/ctr/index-j.htm , UMIN000037074.

DOI： 10.1007/s00380-023-02349-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: We aimed to evaluate the validity of self-administered questionnaire surveys and face-to-face interview surveys for the detection of Helicobacter pylori eradication therapy. METHODS: Participants were a cohort, aged 40-74 years, living in three different locations of Japan, who took part in the baseline survey (2011-2012) of the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT). Five years after the baseline survey, a questionnaire and interview survey were independently conducted to determine the history of Helicobacter pylori eradication treatment over the 5-year period. Prescription of Helicobacter pylori eradication medications in national insurance claims data from the baseline survey to the 5-year survey was used as a reference standard. RESULTS: In total, 15,760 questionnaire surveys and 8,006 interview surveys were included in the analysis. There were 3,471 respondents to the questionnaire and 2,398 respondents to the interview who reported having received Helicobacter pylori eradication treatment within the past five years. Comparison of the questionnaire survey to national insurance claims data showed a sensitivity of 95.1% (2213/2328), specificity of 90.6% (12174/13432), positive predictive value of 63.8% (2213/3471), negative predictive value of 99.1% (12174/12289), and Cohen's Kappa value of 0.71. Respective values of the interview survey were 94.4% (1694/1795), 88.7% (5507/6211), 70.6% (1694/2398), 98.2% (5507/5608), and 0.74. CONCLUSION: Both the questionnaire and the interview showed high sensitivity, high specificity, and good agreement with the insurance claim prescriptions data. Some participants may have received eradication treatment without going through the public insurance claim database, resulting in a low positive predictive value.

DOI： 10.2188/jea.JE20230168

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記述言語：英語  

The Japan Diabetes Society (JDS) and the Japan Cancer Association (JCA) launched a joint committee and published their "First Joint Committee Report on Diabetes and Cancer" in 2013, compiling recommendations for physicians and healthcare providers as well as for the general population. In 2016, the "Second Joint Committee Report on Diabetes and Cancer" summarized the current evidence on glycemic control and cancer risk in patients with diabetes. The current "Third Joint Committee Report on Diabetes and Cancer", for which the joint committee also enlisted the assistance of the Japanese Society of Clinical Oncology (JSCO) and the Japanese Society of Medical Oncology (JSMO), reports on the results from the questionnaire survey, "Diabetes Management in Patients Receiving Cancer Therapy," which targeted oncologists responsible for cancer management and diabetologists in charge of glycemic control in cancer patients. The results of the current survey demonstrated that there is a general consensus among oncologists and diabetologists with regard to the need for guidelines on glycemic control goals, the relevance of glycemic control, and glycemic control during cancer therapy in cancer patients.

DOI： 10.1007/s13340-023-00672-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Antibody obtained by the coronavirus disease-19 (COVID-19) mRNA vaccine declines over time, and additional vaccinations are offered. It is not clear how repeated vaccination affects humoral immunity in uninfected individuals. We analyzed immunoglobulin G for spike protein (S-IgG) titers in COVID-19 uninfected and infected individuals vaccinated up to six times. The geometric mean S-IgG titers were 575.9 AU/mL and 369.0 AU/mL in those who received 6 and 5 doses less than 180 days after the last vaccination in uninfected subjects. In the 180-360 days after the last vaccination, the geometric mean S-IgG titers were 237.9 AU/mL and 128.6 AU/mL in the uninfected subjects who underwent five-dose and four-dose groups, respectively. Multivariate analysis showed that S-IgG titer increased 1.261-fold with each additional dose of mRNA vaccine. The S-IgG titers were 2.039-fold higher in the COVID-infected subjects compared to uninfected subjects. The positivity rate of nucleocapsid antibodies, suggesting a history of COVID-19, decreased 82% and 30% of COVID-infected cases after 180 and 360 days of infection, respectively. This result suggested that repeated vaccination with the COVID-19 mRNA vaccine may increase antibody titer in uninfected subjects.

DOI： 10.1080/21645515.2023.2278376

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記述言語：日本語   出版者・発行元：日本公衆衛生学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: To find an index of glycemic exposure that predicts retinopathy by a simple regression setting regardless of duration in type 1 diabetes which might be useful for the care of diabetes. MATERIALS AND METHODS: To exclude the possible disturbing effect of metabolic memory, we examined a subgroup of patients with glycohemoglobin A1c (A1C) data for the total period of type 1 diabetes selected from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications data. Three indices-(1) mean value of yearly A1C (mA1C), (2) sum of yearly A1C values (ƩA1C), and (3) sum of yearly A1C values above 6.5% (ƩexcessA1C)-were assessed as potential candidates. Development of retinopathy was defined by ≥ 3-steps' progression of retinopathy from baseline. RESULTS: The areas under the receiver operating characteristics curves of the indices for development of retinopathy at years 5, 9, and 13 after the onset of diabetes were the same: 0.8481, 0.8762, and 0.8213, respectively, indicating that each index was substantially capable of predicting development of retinopathy at each timepoint. Linear regression analyses showed that each index had significant and substantial linear relations to retinopathy at each timepoint: all P < 0.0001 for slopes; contribution rate R2 = 0.21 (year 5), 0.46 (year 9), and 0.48 (year 13) for each index. But only ƩexcessA1C index appeared to have similar linear relations to retinopathy at all three timepoints (interactions by timepoint: for slopes: P = 0.1393; for intercepts: P = 0.9366). CONCLUSION: ƩexcessA1C may have the potential to predict retinopathy by just one linear regression setting regardless of duration in type 1 diabetes.

DOI： 10.1007/s13340-023-00654-w

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Controlling avoidable causes of cancer may save cancer-related healthcare costs and indirect costs of premature deaths and productivity loss. This study aimed to estimate the economic burden of cancer attributable to major lifestyle and environmental risk factors in Japan in 2015. We evaluated the economic cost of cancer attributable to modifiable risk factors from a societal perspective. We obtained the direct medical costs for 2015 from the National Database of Health Insurance Claims and Specific Health Checkups of Japan, and estimated the indirect costs of premature mortality and of morbidity due to cancer using the relevant national surveys in Japan. Finally, we estimated the economic cost of cancer associated with lifestyle and environmental risk factors. The estimated cost of cancer attributable to lifestyle and environmental factors was 1,024,006 million Japanese yen (\) (8,460 million US dollars [$]) for both sexes, and \673,780 million ($5,566 million) in men and \350,226 million ($2,893 million) in women, using the average exchange rate in 2015 ($1 = \121.044). A total of \285,150 million ($2,356 million) was lost due to premature death in Japan in 2015. Indirect morbidity costs that could have been prevented were estimated to be \200,602 million ($1,657 million). Productivity loss was highest for stomach cancer in men (\28,735 million/$237 million) and cervical cancer in women (\24,448 million/$202 million). Preventing and controlling cancers caused by infections including Helicobacter pylori, human papillomavirus and tobacco smoking will not only be life-saving but may also be cost-saving in the long run.

DOI： 10.35772/ghm.2023.01001

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病インフォマティクス学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS/INTRODUCTION: To investigate whether the COVID-19 pandemic affected behavioral changes and glycemic control in patients with diabetes and to conduct a survey of telemedicine during the pandemic. MATERIALS AND METHODS: In this retrospective study, a total of 2,348 patients were included from 15 medical facilities. Patients were surveyed about their lifestyle changes and attitudes toward telemedicine. Hemoglobin A1c (HbA1c) levels were compared among before (from June 1 to August 31, 2019) and in the first (from June 1 to August 31, 2020) and in the second (from June 1 to August 31, 2021) year of the pandemic. A survey of physician attitudes toward telemedicine was also conducted. RESULTS: The HbA1c levels were comparable between 2019 (7.27 ± 0.97%), 2020 (7.28 ± 0.92%), and 2021 (7.25 ± 0.94%) without statistical difference between each of those 3 years. Prescriptions for diabetes medications increased during the period. The frequency of eating out was drastically reduced (51.7% in 2019; 30.1% in 2020), and physical activity decreased during the pandemic (48.1% in 2019; 41.4% in 2020; 43.3% in 2021). Both patients and physicians cited increased convenience and reduced risk of infection as their expectations for telemedicine, while the lack of physician-patient interaction and the impossibility of consultation and examination were cited as sources of concern. CONCLUSIONS: Our data suggest that glycemic control did not deteriorate during the COVID-19 pandemic with appropriate intensification of diabetes treatment in patients with diabetes who continued to attend specialized diabetes care facilities, and that patients and physicians shared the same expectations and concerns about telemedicine.

DOI： 10.1111/jdi.14027

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Renin suppression in primary aldosteronism indicates mineralocorticoid receptor activation via excessive aldosterone secretion, inducing renal damage. We investigated whether the reversal of renin suppression after the initiation of mineralocorticoid receptor antagonist therapy was associated with long-term renal outcomes in medically treated patients with primary aldosteronism. METHODS: This retrospective cohort study included 318 patients with primary aldosteronism treated with mineralocorticoid receptor antagonist between 2008 and 2020 at the Yokohama Rosai Hospital in Japan. The posttreatment renin status was defined as unsuppressed (ie, reversal of renin suppression) when individual plasma renin activity after the initiation of mineralocorticoid receptor antagonist (post-plasma renin activity) was ≥1.0 ng/(mL h); otherwise, it was defined as suppressed. We analyzed the association of posttreatment renin status with subsequent longitudinal estimated glomerular filtration rate changes using linear mixed-effects models for repeated measurements, adjusting for potential confounders. RESULTS: The posttreatment renin status of 119 patients was unsuppressed (median post-plasma renin activity, 1.7 ng/[mL h]) and that of 199 patients was suppressed (median post-PRA, 0.5 ng/[mL h]). Through the median follow-up period of 3.1 years, the decline in estimated glomerular filtration rate was milder among patients with the unsuppressed posttreatment renin (-0.46 [95% CI, -0.63 to -0.28] mL/min per 1.73 m2 per year) than those with suppressed posttreatment renin (-1.41 [95% CI, -1.56 to -1.27] mL/min per 1.73 m2 per year; difference, 0.96 [95% CI, 0.72-1.20] mL/min per 1.73 m2 per year). CONCLUSIONS: Our findings may highlight the importance of reversing renin suppression with optimal mineralocorticoid receptor antagonist titration in medically treated primary aldosteronism, which could mitigate adverse renal outcomes.

DOI： 10.1161/HYPERTENSIONAHA.123.21096

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS/INTRODUCTION: Non-attendance from regular medical care is a major problem in diabetes patients. This study aimed to examine the impact of a multifaceted lifestyle intervention by face-to-face approach (FFA) on non-attendance from regular medical care in comparison with that by telephone from the technical support center (TSC). MATERIALS AND METHODS: This was secondary analysis from a 1-year, prospective, cluster randomized, intervention study. Patients with type 2 diabetes, who were regularly visiting primary care physicians cluster-randomized into the control or intervention (TSC or FFA according to resource availability of the district medical associations) groups, were consecutively recruited. The primary end-point was non-attendance from regular medical care. The interaction between the type of intervention (TSC vs FFA) and behavioral change stage (pre- vs post-action stage) in diet and exercise for the dropout rate was assessed. RESULTS: Among the 1,915 participants (mean age 56 ± 6 years; 36% women) enrolled, 828, 564 and 264 patients belonged to the control, TSC and FFA groups, respectively. We found evidence suggestive of an interaction between the intervention type and behavioral change stage in diet (P = 0.042) and exercise (P = 0.038) after adjusting for covariates. The hazard ratios (95% confidence interval) of FFA to TSC were 0.21 (0.05-0.93) and 7.69 (0.50-117.78) in the pre-action and post-action stages for diet, respectively, whereas they were 0.20 (0.05-0.92) and 4.75 (0.29-73.70) in the pre-action and post-action stages for exercise. CONCLUSIONS: Among diabetes patients, the impact of multifaceted intervention on non-attendance from medical care might differ by the behavioral change stage.

DOI： 10.1111/jdi.14012

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Long-acting beta-agonists (LABAs), long-acting muscarinic antagonists (LAMAs), and inhaled corticosteroids (ICSs) are inhaled medications used to manage chronic obstructive pulmonary disease (COPD). When two classes of medications are required, a LAMA plus an ICS (LABA+ICS) were previously recommended within a single inhaler as the first-line treatment for managing stable COPD in people in high-risk categories. However, updated international guidance recommends a LAMA plus a LABA (LAMA+LABA). This systematic review is an update of a Cochrane Review first published in 2017. OBJECTIVES: To compare the benefits and harms of LAMA+LABA versus LABA+ICS for treatment of people with stable COPD. SEARCH METHODS: We performed an electronic search of the Cochrane Airways Group Specialised Register, ClinicalTrials.gov, and the World Health Organization Clinical Trials Search Portal, followed by handsearches. Two review authors screened the selected articles. The most recent search was run on 10 September 2022. SELECTION CRITERIA: We included parallel or cross-over randomised controlled trials of at least one month's duration, comparing LAMA+LABA and LABA+ICS for stable COPD. We included studies conducted in an outpatient setting and irrespective of blinding. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and evaluated risk of bias. We resolved any discrepancies through discussion. We analysed dichotomous data as odds ratios (ORs), and continuous data as mean differences (MDs), with 95% confidence intervals (CIs) using Review Manager 5. Primary outcomes were: participants with one or more exacerbations of COPD; serious adverse events; quality of life, as measured by the St. George's Respiratory Questionnaire (SGRQ) total score change from baseline; and trough forced expiratory volume in one second (FEV1). We used the GRADE framework to rate our certainty of the evidence in each meta-analysis as high, moderate, low or very low.  MAIN RESULTS: This review updates the first version of the review, published in 2017, and increases the number of included studies from 11 to 19 (22,354 participants). The median number of participants per study was 700. In each study, between 54% and 91% (median 70%) of participants were males. Study participants had an average age of 64 years and percentage predicted FEV1 of 51.5% (medians of study means). Included studies had a generally low risk of selection, performance, detection, attrition, and reporting biases. All but two studies were sponsored by pharmaceutical companies, which had varying levels of involvement in study design, conduct, and data analysis. Primary outcomes The odds of having an exacerbation were similar for LAMA+LABA compared with LABA+ICS (OR 0.91, 95% CI 0.78 to 1.06; I2 = 61%; 13 studies, 20,960 participants; moderate-certainty evidence). The odds of having a serious adverse event were also similar (OR 1.02, 95% CI 0.91 to 1.15; I2 = 20%; 18 studies, 23,183 participants; high-certainty evidence). Participants receiving LAMA+LABA had a similar improvement in quality of life, as measured by the SGRQ, to those receiving LABA+ICS (MD -0.57, 95% CI -1.36 to 0.21; I2 = 78%; 9 studies, 14,437 participants; moderate-certainty evidence) but showed a greater improvement in trough FEV1 (MD 0.07, 95% CI 0.05 to 0.08; I2 = 73%; 12 studies, 14,681 participants; moderate-certainty evidence).  Secondary outcomes LAMA+LABA decreased the odds of pneumonia compared with LABA+ICS from 5% to 3% (OR 0.61, 95% CI 0.52 to 0.72; I2 = 0%; 14 studies, 21,829 participants; high-certainty evidence) but increased the odds of all-cause death from 1% to 1.4% (OR 1.35, 95% CI 1.05 to 1.75; I2 = 0%; 15 studies, 21,510 participants; moderate-certainty evidence). The odds of achieving a minimal clinically important difference of four or more points on the SGRQ were similar between LAMA+LABA and LABA+ICS (OR 1.06, 95% CI 0.90 to 1.25; I2 = 77%; 4 studies, 13,614 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Combination LAMA+LABA therapy probably holds similar benefits to LABA+ICS for exacerbations and quality of life, as measured by the St George's Respiratory Questionnaire, for people with moderate to severe COPD, but offers a larger improvement in FEV1 and a slightly lower risk of pneumonia. There is little to no difference between LAMA+LABA and LAMA+ICS in the odds of having a serious adverse event. Whilst all-cause death may be lower with LABA+ICS, there was a very small number of events in the analysis, translating to a low absolute risk. Findings are based on moderate- to high-certainty evidence from heterogeneous trials with an observation period of less than one year. This review should be updated again in a few years.

DOI： 10.1002/14651858.CD012066.pub3

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN EPIDEMIOLOGICAL ASSOC  

Background: This study aimed to develop models to predict the 5-year incidence of T2DM in a Japanese population and validate them externally in an independent Japanese population.Methods: Data from 10,986 participants (aged 46-75 years) in the development cohort of the Japan Public Health Center-based Prospective Diabetes Study and 11,345 participants (aged 46-75 years) in the validation cohort of the Japan Epidemiology Collaboration on Occupational Health Study were used to develop and validate the risk scores in logistic regression models.Results: We considered non-invasive (sex, body mass index, family history of diabetes mellitus, and diastolic blood pressure) and invasive (glycated hemoglobin [HbA1c] and fasting plasma glucose [FPG]) predictors to predict the 5-year probability of incident diabetes. The area under the receiver operating characteristic curve was 0.643 for the non-invasive risk model, 0.786 for the invasive risk model with HbA1c but not FPG, and 0.845 for the invasive risk model with HbA1c and FPG. The optimism for the performance of all models was small by internal validation. In the internal-external cross-validation, these models tended to show similar discriminative ability across different areas. The discriminative ability of each model was confirmed using external validation datasets. The invasive risk model with only HbA1c was well-calibrated in the validation cohort.Conclusions: Our invasive risk models are expected to discriminate between high-and low-risk individuals with T2DM in a Japanese population.

DOI： 10.2188/jea.JE20220329

Web of Science

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Observational studies suggest that abnormal glucose metabolism and insulin resistance contribute to colorectal cancer; however, the causal association remains unknown, particularly in Asian populations. A two-sample Mendelian randomisation analysis was performed to determine the causal association between genetic variants associated with elevated fasting glucose, haemoglobin A1c (HbA1c), and fasting C-peptide and colorectal cancer risk. In the single nucleotide polymorphism (SNP)-exposure analysis, we meta-analysed study-level genome-wide associations of fasting glucose (~ 17,289 individuals), HbA1c (~ 52,802 individuals), and fasting C-peptide (1,666 individuals) levels from the Japanese Consortium of Genetic Epidemiology studies. The odds ratios of colorectal cancer were 1.01 (95% confidence interval [CI], 0.99-1.04, P = 0.34) for fasting glucose (per 1 mg/dL increment), 1.02 (95% CI, 0.60-1.73, P = 0.95) for HbA1c (per 1% increment), and 1.47 (95% CI, 0.97-2.24, P = 0.06) for fasting C-peptide (per 1 log increment). Sensitivity analyses, including Mendelian randomisation-Egger and weighted-median approaches, revealed no significant association between glycaemic characteristics and colorectal cancer (P > 0.20). In this study, genetically predicted glycaemic characteristics were not significantly related to colorectal cancer risk. The potential association between insulin resistance and colorectal cancer should be validated in further studies.

DOI： 10.1038/s41598-023-33966-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Oxford University Press (OUP)  

Abstract

Background

Loneliness is a global issue, and primary care physicians play an important role in assessing and intervening with loneliness. This study aimed to examine the association between having a usual source of care (USC) or a good quality of primary care, and loneliness.

Methods

This cross-sectional study was conducted in Japan in 2022. A total of 6,000 residents were randomly sampled from the general population, aged 20–74 years. The outcome was the total score of the University of California, Los Angeles (UCLA) 3-item loneliness scale. The exposure included USC and the Person-Centered Primary Care Measure (PCPCM), which assesses the quality of primary care. We conducted a linear regression analysis to adjust for age, sex, educational status, annual household income, self-rated health, living status (whether alone or not), and the existence of physical health problems.

Results

Of the 6,000 residents, 1,277 responded to the survey. The median score of the UCLA 3-item loneliness scale was 6.0 and the mean total score of the PCPCM was 2.62. Of the 1,277 individuals, 713 (55.8%) had USC. Having USC was significantly associated with lower scores on the UCLA 3-item loneliness scale; the coefficient was −0.34 (95% confidence interval (CI): −0.57 to −0.12). Also, the total PCPCM score was significantly associated with lower loneliness scores; the coefficient was −0.56 (P &amp;lt; 0.001, 95% CI: −0.78 to −0.35).

Conclusions

Having USC and a better quality primary care were associated with a lower loneliness score. The quality of primary care could be a factor to mitigate patient loneliness.

DOI： 10.1093/fampra/cmad049

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.2188/jea.JE20230078

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are extensively used in the treatment of non-small cell lung cancer (NSCLC); hence, equal access to them is important. Therefore, this study aimed to identify regional differences in the prescription of EGFR-TKIs and the factors contributing to these differences. In this ecological study, we collected data using the National Database Open Data and the National Cancer Registry. The standardized claim ratio (SCR) was used as an indicator of the number of EGFR-TKI prescriptions. Additionally, we examined the association between SCR and various factors to identify the factors associated with this difference. The average SCR for the top three provinces was 153.4, while the average for the bottom three provinces was 61.6. Multivariate analysis used for evaluating the association of SCR with variables revealed that the number of designated cancer hospitals and radiation therapies were independent factors associated with the SCR of EGFR-TKIs. There were significant regional differences in the prescriptions of EGFR-TKIs in Japan based on the number of coordinated designated cancer hospitals and the number of patients receiving radiotherapy alone. These findings emphasize the need to implement policies to increase the number of hospitals to reduce regional differences.

DOI： 10.1038/s41598-023-31856-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Accumulating evidence suggests that pneumonia mortality is lower for individuals with high body mass index (BMI) compared to normal BMI, but it remains unclear whether weight change during adulthood influences subsequent mortality due to pneumonia in Asian populations, who have a relatively lean body mass. This study aimed to examine the association of BMI and weight change over 5 years with the subsequent risk of pneumonia mortality in a Japanese population. METHODS: The present analysis included 79,564 Japan Public Health Center (JPHC)-based Prospective Study participants who completed a questionnaire between 1995 and 1998 were followed for death through 2016. BMI was categorized into four groups: underweight (<18.5 kg/m2), normal weight (BMI: 18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), and obese (BMI: ≥30.0 kg/m2). Weight change was defined as the difference of body weight between questionnaire surveys with a 5-year interval. Cox proportional hazards regression was used to estimate hazard ratios of baseline BMI and weight change for pneumonia mortality. RESULTS: During a median follow-up of 18.9 y, we identified 994 deaths from pneumonia. Compared with participants with normal weight, an elevated risk was observed among those who were underweight (hazard ratio = 2.29, 95% confidence interval [CI]: 1.83-2.87), whereas a decreased risk was found among those who were overweight (hazard ratio = 0.63, 95% CI: 0.53-0.75). Regarding weight change, the multivariable-adjusted hazard ratio (95% CI) of pneumonia mortality for a weight loss of 5 kg or more versus a weight change of less than 2.5 kg was 1.75 (1.46-2.10), whereas that for a weight gain of 5 kg or more was 1.59 (1.27-2.00). CONCLUSION: Underweight and greater weight change was associated with an increase in the risk of pneumonia mortality in Japanese adults.

DOI： 10.1038/s41366-023-01289-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

While higher circulating 25-hydroxyvitamin D concentrations have been reported to be associated with decreased risk of all-cause mortality, evidence on dietary vitamin D intake is limited and inconsistent. We investigated whether vitamin D intake is associated with all-cause and cause-specific mortality among Japanese adults. Participants were 42,992 men and 50,693 women who responded to the second survey of the Japan Public Health Center-based Prospective Study (1995-1998) and who were followed up for mortality through 2018. Dietary intake was ascertained using a validated food frequency questionnaire. Hazard ratios of deaths from the second survey to December 2018 were estimated using Cox proportional hazard regression analysis. During follow-up, we identified 22,630 deaths. Overall, the third and fourth quintiles, but not the highest quintile, of vitamin D intake were each associated with a significantly lower risk of all-cause mortality. In subgroups characterized by low sunlight exposure, risk of all-cause mortality decreased linearly with increasing vitamin D intake. The multivariable-adjusted hazard ratios (95% confidence intervals) of all-cause mortality for the highest versus lowest quintile of vitamin D intake were 0.87 (0.79-0.95) in women and 0.88 (0.79-0.97) in residents of higher latitude areas. Lower risk was also observed for all-cause mortality in participants with hypertension and for heart disease mortality in those with higher calcium intake. Higher vitamin D intake was associated with decreased risk of ischemic stroke and pneumonia mortality. Higher dietary vitamin D was associated with a lower risk of mortality among individuals with low sunlight exposure or hypertension. Individuals with potentially low vitamin D may benefit from increasing dietary vitamin D intake for the prevention of premature death.

DOI： 10.1007/s10654-023-00968-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The influence of sugar consumption on the risk of colorectal cancer (CRC) remains controversial. Prospective cohort studies focusing on total and specific types of sugar intake among the Asian population who have different patterns of sugar intake sources than American and European populations are scarce. We intended to examine the association of sugar intake with CRC risk among middle-aged adults in a Japanese large-scale population-based cohort study. The participants (42,405 men and 48,600 women) who were 45-74 years old and answered the questionnaire in 1995-1999 in the Japan Public Health Center-based Prospective Study were followed up until December 2013. Total sugars, total fructose, and specific types of sugar intake were estimated using a validated 147-item food frequency questionnaire and divided into quintiles (Q1-Q5). We used Cox proportional hazard regression models adjusted for potential confounders to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During the follow-up, 2118 CRC cases (1226 men and 892 women) were identified. We did not observe any clear association between all types of sugar intake and an increased risk of CRC. Analyses by tumor sites yielded a positive association of total sugar consumption with rectal cancer in women (1.75 [1.07-2.87] for Q1 vs. Q5; p linear trend  = 0.03), but no statistically significant trend was detected among men. Sugar intake was not associated with CRC risk in middle-aged Japanese adults. However, for rectal cancer, the probability of an increased risk among women with a higher total sugar intake cannot be excluded.

DOI： 10.1111/cas.15766

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: To assess dietary behaviours and related lifestyles according to the presence or absence of skipping breakfast. DESIGN: We analysed the cross-sectional data from a baseline survey of a large-scale population-based cohort study in Japan conducted in 2011-2016. Participants provided information on dietary behaviours and lifestyles through a self-administered questionnaire. Skipping breakfast was defined as not eating breakfast at least once a week and was classified according to the frequency of skipping breakfast as 1-2, 3-4 or ≥5 times/week. SETTING: Sixteen municipalities in seven prefectural areas across Japan under the Japan Public Health Centre-based prospective study for the Next Generation. PARTICIPANTS: 112 785 residents (51 952 males and 60 833 females) aged 40-74 years. RESULTS: After adjustment for age, socio-demographic status, drinking status and smoking status, individuals who skipped breakfast at least once a week, compared with those who ate breakfast every day, were more likely to have adverse dietary behaviours such as frequent eating out (multivariable OR = 2·08, 95 % CI (1·96, 2·21) in males and 2·15, 95 % CI (1·99, 2·33) in females), frequent eating instant foods (1·89, 95 % CI (1·77, 2·01) in males and 1·72, 95 % CI (1·56, 1·89) in females). They had late bedtime (1·85, 95 % CI (1·75, 1·95) in males and 1·98, 95 % CI (1·86, 2·11) in females) and living alone (2·37, 95 % CI (2·17, 2·58) in males and 2·02, 95 % CI (1·83, 2·21) in females), using the logistic regression model. CONCLUSIONS: Both adult males and females who skipped breakfast were likely to eat out, to have a dietary habit of eating instant foods and have lifestyles such as late bedtime and living alone than those who ate breakfast.

DOI： 10.1017/S1368980023000010

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The association between vitamin D and total and colorectal cancer risk was inconsistent in observational studies. We conducted Mendelian randomization approach in which the effect of confounding might be reduced. 110 single nucleotide polymorphisms (SNPs) associated with 25-hydroxyvitamin D concentrations were systematically selected according to the "GWAS Catalog" from all ethnic populations. For the SNP-vitamin D concentration association, 3978 individuals from two Japanese cohorts were included. Regarding SNP-total and colorectal cancer association, 4543 cancer cases and 14,224 controls and 7936 colorectal cancer cases and 38,042 controls, respectively were included from the Japanese Consortium of Genetic Epidemiology and other studies in Japan. There was no significant association between the genetically predicted plasma 25-hydroxyvitamin D concentration and total or colorectal cancer in any of the MR analyses. Odds ratios per doubling in vitamin D concentration were 0.83 (95% confidence interval [CI] 0.63-1.09) for total cancer and 1.00 (95% CI 0.80-1.24) for colorectal cancer in inverse variance weighted method, 0.83 (95% CI 0.57-1.19) for total cancer and 1.01 (95% CI 0.75-1.37) for colorectal cancer in MR-Egger method. Consistent with previous MR analyses among European ancestries, there was no significant association identified between 25-hydroxyvitamin D levels and total or colorectal cancer among Asians.

DOI： 10.1038/s41598-023-29596-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s13340-022-00605-x

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掲載種別：研究論文（学術雑誌）  

In observational studies, unmeasured covariates are an important problem. In the presence of some unmeasured covariates, some instrumental variable methods, such as the two-stage residual inclusion (2SRI) estimator or limited-information maximum likelihood (LIML) estimator, can still obtain an unbiased estimate for causal effects despite the existence of nonlinear models, such as logistic regression and probit models. However, not only a correct outcome model but also a correct treatment model needs to be specified. Therefore, it is important to identify the correct models. In this paper, we consider model selection procedures for 2SRI and LIML, and confirm their properties through simulation and real datasets. Specifically, we confirm the model selection procedures can detect the correct treatment and outcome models, and unbiased causal effects can be estimated. The model selection properties are confirmed through simulation datasets and GENEVA Diabetes Study datasets. From the simulation and data analysis results, we recommend that LIML with any model selection procedures is a good choice when there are binary outcomes and any concerns about unmeasured covariates.

DOI： 10.1007/s41237-022-00177-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: Despite extensive vaccination campaigns to combat the coronavirus disease (COVID-19) pandemic, variants of concern, particularly the Omicron variant (B.1.1.529 or BA.1), may escape the antibodies elicited by vaccination against SARS-CoV-2. Therefore, this study aimed to evaluate 50% neutralizing activity (NT50) against SARS-CoV-2 D614G, Delta, Omicron BA.1, and Omicron BA.2 and to develop prediction models to predict the risk of infection in a general population in Japan. METHODS: We used a random 10% of samples from 1,277 participants in a population-based cross-sectional survey conducted in January and February 2022 in Yokohama City, the most populous municipality in Japan. We measured NT50 against D614G as a reference and three variants (Delta, Omicron BA.1, and BA.2) and immunoglobulin G against SARS-CoV-2 spike protein (SP-IgG). RESULTS: Among 123 participants aged 20-74, 93% had received two doses of SARS-CoV-2 vaccine. The geometric means (95% confidence intervals) of NT50 were 65.5 (51.8-82.8) for D614G, 34.3 (27.1-43.4) for Delta, 14.9 (12.2-18.0) for Omicron BA.1, and 12.9 (11.3-14.7) for Omicron BA.2. The prediction model with SP-IgG titers for Omicron BA.1 performed better than the model for Omicron BA.2 (bias-corrected R 2 with bootstrapping: 0.721 vs. 0.588). The models also performed better for BA.1 than for BA.2 (R 2 = 0.850 vs. 0.150) in a validation study with 20 independent samples. CONCLUSION: In a general Japanese population with 93% of the population vaccinated with two doses of SARS-CoV-2 vaccine, neutralizing activity against Omicron BA.1 and BA.2 were substantially lower than those against D614G or the Delta variant. The prediction models for Omicron BA.1 and BA.2 showed moderate predictive ability and the model for BA.1 performed well in validation data.

DOI： 10.3389/fmicb.2023.1126527

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

DOI： 10.1111/jdi.13960

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/jdi.13960

記述言語：英語   掲載種別：研究論文（学術雑誌）  

INTRODUCTION: This study explored the psychological and situational factors affecting dropout from regular visits to diabetes care using data obtained from the Japan Diabetes Outcome Intervention Trial 2 (J-DOIT2) Large-scale Trial (LT). METHODS: A total of 2,031 patients with type 2 diabetes who participated in the J-DOIT2-LT were included in the analysis. Responses to a baseline questionnaire with 17 items asking about the experience of dropout from regular visits in diabetes care and its reasons were analyzed using principal component analysis, and factors related to dropout were extracted. Using Cox regression analysis, the association of these factors with the incidence of dropout was investigated. RESULTS: The mean age of the 2,031 patients was 56.4 ± 5.9 years and 742 (36.5%) were women. They were followed for a median of 392 days, and 125 patients dropped out from regular visits during the follow-up period. In the principal component analysis of the questionnaire, there were four latent factors with eigenvalues of >1.0, which were labeled as "negative perceptions for regular visits," "social pressure," "lack of perceived necessity," and "environmental obstacles" based on the retained items. The Cox regression analysis demonstrated that patients with high scores of "lack of perceived necessity" and "environmental obstacles" had a significantly increased risk of dropout from regular visits. CONCLUSIONS: The present study revealed psychological and situational factors related to dropout, which may be useful for detecting patients at high risk of dropout. Effective measures focusing on such patients to prevent dropouts should be investigated in future studies (The trial registration number: UMIN000002186, registered at the University Hospital Medical Information Network-Clinical Trials Registry).

DOI： 10.31662/jmaj.2022-0065

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Although studies have found an association between chronic kidney disease (CKD) and cancer incidence, the results are inconsistent. METHODS: This study included participants in the Japan Public Health Center-based Prospective Study who had data on serum creatinine measurements. We assessed the association between estimated glomerular filtration rate (eGFR) and the risk of total and site-specific cancer incidence using a systematic survey in Japan. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for participant demographics and lifestyle factors. RESULTS: A total of 21 978 participants who met the inclusion criteria were followed up for a mean period of 12.9 years, within which a total of 2997 incident cancer cases were reported. In the multivariable adjusted models, an eGFR of <45 ml/ml/min/1.73 m2 was not significantly associated with total cancer incidence (adjusted HR 1.22, 95% CI 0.94-1.60), compared to an eGFR of 60-89 ml/min/1.73 m2 (reference). The HR among those with eGFRs of ≥90 ml/min/1.73 m2 was 1.10 (95% CI 1.00-1.22). CONCLUSIONS: In this large prospective study, a low eGFR was not significantly associated with an increased risk of total cancer incidence in patients with CKD, which may be partly due to an underpowered sample size. This finding may be due to the many shared risk factors between CKD and cancer.

DOI： 10.1093/ndt/gfac288

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: A meta-analysis suggests a relationship between abnormal glucose metabolism and primary open-angle glaucoma (POAG); however, the causal association between them remains controversial. We therefore conducted a Mendelian randomization (MR) study to assess the causal association between genetically predicted glycemic traits and the risk of POAG. DESIGN: Two-sample MR design. METHODS: We examined the genetically predicted measures of fasting glucose, hemoglobin A1c (HbA1c), and fasting C-peptide, in relation to POAG. For the single nucleotide polymorphism (SNP)-exposure analyses, we meta-analyzed the study-level genome-wide associations of fasting glucose levels (n=17,289; n of SNPs=34), HbA1c (n=52,802; n of SNPs=43), and fasting C-peptide levels (n=1,666; n of SNPs=17) from the Japanese Consortium of Genetic Epidemiology studies. We used summary statistics from the BioBank Japan projects (n=3,980 POAG cases and 18,815 controls) for the SNP-outcome association. RESULTS: We observed no association of genetically predicted HbA1c and fasting C-peptide with POAG. The MR inverse-variance weighted (IVW) odds ratios (ORs) were 1.44 (95% confidence interval [CI], 0.78-2.65; P=0.25) for HbA1c (per 1 % increment) and 0.92 (95% CI, 0.56-1.53; P=0.76) for fasting C-peptide (per two-fold increment). A significant association between fasting glucose (per 10 mg/dL increment) and POAG was observed according to the MR IVW analysis (OR=1.48 [95% CI, 1.10-1.79, P=0.009]); however, sensitivity analyses, including MR-Egger and weighted-median methods, did not support this association (P>0.10). CONCLUSIONS: We did not provide strong evidence to support the association between genetically predicted glycemic traits and POAG in the Japanese population.

DOI： 10.1016/j.ajo.2022.09.004

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記述言語：英語  

DOI： 10.1007/s00520-022-07232-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The associations between blood lipids, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides, and low-density lipoprotein cholesterol (LDL-C), and colorectal cancer risk are controversial. We evaluated potential causal relationships between blood lipids and colorectal cancer risk. Using the baseline data from the Japanese Consortium of Genetic Epidemiology studies, we estimated the single-nucleotide polymorphism (SNP)-exposure associations (n=34,546 for TC, n=50,290 for HDL-C, n=51,307 for triglycerides, and n=30,305 for LDL-C). We also estimated the SNP-outcome associations in another Japanese dataset (n=7,936 colorectal cancer cases and n=38,042 controls). We conducted Mendelian randomization analyses for the association between each blood lipid type and the risk of colorectal cancer using an inverse variance-weighted method. The total variances explained by the selected SNPs in TC (68 SNPs), HDL-C (50 SNPs), log-transformed triglycerides (26 SNPs), and LDL-C (35 SNPs) were 7.0%, 10.0%, 6.2%, and 5.7%, respectively. The odds ratios for colorectal cancer were 1.15 (95% confidence interval 1.01-1.32) per 1 standard deviation (SD) (33.3 mg/dL) increase in TC, 1.11 (0.98-1.26) per 1 SD (15.4 mg/dL) increase in HDL-C, 1.06 (0.90-1.26) per 1 SD (0.5 log-mg/dL) increase in log-transformed triglycerides, and 1.17 (0.91-1.50) per 1 SD (29.6 mg/dL) increase in LDL-C. Sensitivity analyses consistently suggested the positive association between TC and colorectal cancer, whereas results of each lipid component were inconsistent. In conclusion, this large Mendelian randomization study of a Japanese population showed a potentially causal association between high TC and colorectal cancer risk, although the association between each lipid component and colorectal cancer remained inconclusive.

DOI： 10.1158/1940-6207.CAPR-22-0146

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

DOI： 10.11213/tonyobyo.65.419

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BMJ  

Objectives

Continuity of care is a core dimension of primary care, and better continuity is associated with better patient outcomes. Therefore, care fragmentation can be an indicator to assess the quality of primary care, especially in countries without formal gatekeeping system, such as Japan. Thus, this study aimed to describe care fragmentation among older adults in an ageing city in Japan.

Design

Cross-sectional study.

Setting

The most populated basic municipality in Japan.

Participants

Older adults aged 75 years and older.

Interventions

This study used a health claims database, including older adults who visited medical facilities at least four times a year in an urban city in Japan. The Fragmentation of Care Index (FCI) was used as an indicator of fragmentation. The FCI was developed from the Continuity of Care Index and is based on the total number of visits, different institutions visited and proportion of visits to each institution. We employed Tobit regression analysis to examine the association between the FCI and age, sex, type of insurance and most frequently visited facility.

Results

The total number of participants was 413 600. The median age of the study population was 81 years, and 41.6% were men. The study population visited an average of 3.42 clinics/hospitals, and the maximum number of visited institutions was 20. The proportion of patients with FCI &gt;0 was 85.0%, with a mean of 0.583. Multivariable analysis showed that patients receiving public assistance had a lower FCI compared with patients not receiving public assistance, with a coefficient of 0.137.

Conclusions

To our knowledge, this is the first study to demonstrate care fragmentation in Japan. Over 80% of the participants visited two or more medical facilities, and their mean FCI was 0.583. The FCI could be a basic indicator for assessing the quality of primary care.

DOI： 10.1136/bmjopen-2022-061921

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: The prevention of chemotherapy-induced nausea and vomiting (CINV), a common chemotherapy side effect, should be attempted by oncology nurses. Certified nurses could be certified nurse specialists in cancer nursing (CNSCNs), who have high-level graduate education, or certified nurses in cancer chemotherapy nursing (CNCCNs), who have short-term training. The relationship between these certifications and compliance with the CINV prevention guidelines has not been investigated. We aimed to evaluate the association between certified nurse staffing and prescription of prophylactic antiemetic drugs for chemotherapy patients with high emetic risk. METHODS: We used health service utilisation data for cancer patients diagnosed in 2016 from 474 hospitals nationwide in Japan and a list of certified nurses published by the Japanese Nurse Association. Patients receiving highly emetic chemotherapy were included. A multilevel mixed-effect logistic regression analysis was conducted to estimate the prescription of prophylactic antiemetic drugs associated with CNSCN and/or CNCCN staffing. RESULTS: Data of 46,306 patients were analysed. Overall, 68.4% and 94.0% of the patients received chemotherapy at hospitals with CNSCNs and CNCCNs, respectively. Small cell lung cancer, non-small cell lung cancer, breast cancer, and oesophageal cancer were positively associated with the prescription of recommended antiemetic drugs. CNSCNs was significantly associated with the prescription of prophylactic antiemetic drugs, while CNCCNs was positively but non-significantly associated with antiemetic prescriptions. CONCLUSION: This study is the first to demonstrate that CNSCN placement was significantly associated with prescribing antiemetic drugs recommended by clinical guidelines. Patients are likely to receive appropriate supportive care with the proper placement of CNSCNs.

DOI： 10.1007/s00520-022-07019-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: A dose-response and nonlinear association between fruit and vegetable intake and mortality has been reported in Europe and the United States, but little is known about this association in Asia. OBJECTIVES: This study aimed to evaluate the association of fruit and vegetable intake with all-cause, cancer, cardiovascular, and respiratory disease mortality in a Japanese cohort. METHODS: In the Japan Public Health Center-based prospective study, we included 94,658 participants (mean age; 56.4 ± 7.8 years, male; 46.0%) without cancer and cardiovascular disease at baseline. Information on fruit and vegetable intake was collected using a validated food frequency questionnaire. The Cox proportional-hazards model was used to estimate hazard ratios (HR) and 95% confidence intervals (CIs) of each quintile of fruit and vegetable intake, separately, in relation to all-cause and cause-specific mortality using the first quintile as a reference. Nonlinear associations were evaluated using a likelihood ratio test, comparing a linear model with a restricted cubic spline model. RESULTS: During a median of 20.9 follow-up years (interquartile range: 19.6-23.8), 23,687 all-cause deaths were documented. After adjusting for age, sex, and potential confounding factors, fruit and vegetable intake was nonlinearly and significantly associated with lower all-cause mortality, with the fourth and fifth quintiles having comparable HRs (fruit: fourth quintile, HR: 0.91; 95%CI: 0.87, 0.95, fifth quintile, HR: 0.92; 95%CI: 0.88, 0.96; P for nonlinearity < 0.001; vegetable: fourth quintile, HR: 0.92; 95%CI: 0.88, 0.97, fifth quintile, HR: 0.93; 95%CI: 0.89, 0.98; P for nonlinearity = 0.002). Fruit intake was significantly associated with lower cardiovascular mortality (HR in the fifth quintile: 0.91; 95%CI: 0.83, 0.99; P for nonlinearity = 0.01). CONCLUSIONS: In the Japanese population, higher intake of fruits and vegetables was nonlinearly associated with decreased all-cause mortality. These findings may contribute to the establishment of dietary recommendations for enhancing life expectancy in Asia.

DOI： 10.1093/jn/nxac136

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: This study determined the validity of claims-based definitions for identifying the incidence of total and site-specific cancers in a population-based cohort study. METHODS: Claims data were obtained for 21 946 participants aged 40-74 years enrolled in the Japan Public Health Center-based Prospective Study for the Next Generation. We defined total and site-specific cancer incidence using combinations of codes from claims data, including diagnosis and procedure codes for cancer therapy. Data from the cancer registry were used as the gold standard to evaluate validity. RESULTS: Among 21 946 participants, 454 total, 89 stomach, 67 colorectal, 51 lung, 39 breast and 99 prostate invasive cancer cases were newly diagnosed in the cancer registry. For invasive cancer, the sensitivity and specificity of the definition that combined codes for diagnosis and procedures for cancer therapy were 87.0% and 99.4% for total, 88.8% and 99.9% for stomach, 80.6% and 99.9% for colorectal, 86.3% and 99.9% for lung, 100% and 99.9% for breast and 91.9% and 99.9% for prostate cancer, respectively. Furthermore, for invasive and/or in situ cancer, the sensitivity and specificity of the definition were 84.5% and 99.5% for total, 66.7% and 99.9% for colorectal and 100% and 99.9% for breast cancer. CONCLUSIONS: Our findings suggest that claims-based definitions using diagnosis and procedure codes generally have high validity for total, stomach, lung, breast and prostate cancer incidence, but may underestimate colorectal cancer incidence.

DOI： 10.1002/pds.5494

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BackgroundRegular visits with healthcare professionals are important for preventing serious complications in patients with diabetes. The purpose of this retrospective cohort study was to clarify whether there was any suppression of physician visits among patients with diabetes during the spread of COVID-19, in Japan and to assess whether telemedicine contributed to continued visits.MethodsWe used the JMDC Claims database which contains the monthly claims reported from July 2018 to May 2020 and included 4595 (type 1) and 123,686 (type 2) patients with diabetes.Using a difference-in-differences analysis, we estimated the changes in the monthly numbers of physician visits or telemedicine per 100 patients in April and May 2020 compared with the same months in 2019.ResultsFor patients with type 1 diabetes, the estimates for total overall physician visits were -2.53 (95% CI, -4.63 to 0.44) in April and -8.80 (-10.85 to -6.74) in May; those for telemedicine visits were 0.71 (0.47 to 0.96) in April and 0.54 (0.32 to 0.76) in May. For patients with type 2 diabetes, the estimates for overall physician visits were -2.50 (-2.95 to -2.04) in April and -3.74 (-4.16 to -3.32) in May; those for telemedicine visits were 1.13 (1.07 to 1.20) in April and 0.73 (0.68 to 0.78) in May.ConclusionsThe COVID-19 pandemic was associated with suppression of physician visits and a slight increase in the utilisation of telemedicine among patients with diabetes during April and May 2020.

DOI： 10.2188/jea.JE20220032

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: Workplace demands, support, and relationships differ according to employment status (e.g., employment that is full-time, part-time, or self-employed) and may lead to unequal opportunities to keep diabetic appointments. We investigated the association between employment status and outpatient diabetic appointment non-attendance among working-age adults with type 2 diabetes. METHODS: This was a secondary analysis of a cluster-randomized trial (the Japan diabetes outcome intervention trial 2 large-scale trial). The analysis included 2010 trial participants (40-65 years old) with type 2 diabetes who were regularly followed by primary care physicians (PCPs). The outcome measure was the first non-attendance (defined as a failure to visit a PCP within 2 months of the original appointment) during the one-year follow-up. The association between baseline employment status and non-attendance was examined using Cox proportional hazard model in men and women. RESULTS: During the 1279 and 789 person-year follow-up periods, 90 men and 34 women, respectively, experienced their first appointment non-attendance. Among men, self-employed participants had a higher risk of non-attendance compared with full-time employees (adjusted HR, 1.84; 95% CI, 1.15, 2.95). The trial intervention (attendance promotion) was associated with a significantly reduced risk of non-attendance among self-employed participants (HR, 0.51; 95% CI, 0.26, 0.99). Among women, a significant association between employment status and non-attendance was not observed. CONCLUSIONS: Self-employed men with type 2 diabetes had a twofold increased risk of non-attendance than did full-time employees. Our study suggests that self-employed men with type 2 diabetes should be targeted for interventions promoting appointment adherence.

DOI： 10.1007/s00592-022-01869-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: The associations between the types/amounts of beverages consumed in daily life and measures of the glycemia status were investigated in a Japanese population-based cohort. Methods: Data from the baseline survey of the Japan Public Health Center-based Prospective Diabetes cohort were used. A cross-sectional analysis was performed in 3852 men and 6003 women who were evaluated under the fasting condition. The daily consumptions of coffee, green tea, oolong tea, black tea, soft drinks, fruit juices, or plain water were assessed using a self-reported questionnaire. Multivariable-adjusted linear regression analyses were performed using measures of the glycemia status (fasting plasma glucose (FPG) and glycated hemoglobin (HbA1c) ) as dependent variables and the types/amounts of beverages consumed as the independent variables, to calculate the differences according to the types/amounts of beverages consumed. Results: In the multivariable-adjusted models, coffee consumption of ≥240 mL/day was significantly associated with a change of the FPG level by -1.9 mg/dL in men (p = 0.013) and -1.4 mg/dL in women (p = 0.015), as compared to coffee consumption of 0 mL/day. No significant association of the FPG level was observed with any of the other types/amounts of beverages consumed. On the other hand, significant associations were found between the HbA1c levels and consumption of several types of beverages. Conclusions: High coffee consumption was associated with lower FPG levels in this Japanese population. Some unexpected associations of the HbA1c levels with the consumption of some types of beverages were observed, which need to be further investigated.

DOI： 10.1016/j.metop.2022.100185

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: Urbanization and ageing are worldwide issues for healthcare providers. In particular, older adults aged 90 years and older have increased cognitive impairment and lower daily functioning than younger adults. However, the healthcare use of the oldest old remains unclear. This study aimed to describe the healthcare use of the oldest old compared with younger older adults in a city using the ecology of medical care model. METHODS: We conducted a cross-sectional study. This study targeted all residents aged 75 years and older registered in a city in Japan for one year. We described healthcare use per 1000 inhabitants over a 1-month period and included: outpatient visits, emergency department visits, hospitalizations, home visits, home care services, and facility services. We also compared healthcare use among older adults aged 75-89 years and 90 years and older. RESULTS: We described the healthcare use of 454 366 (male/female: 186 177/268 189) older adults. The numbers of persons per 1000 residents who used healthcare resources at least once in 1 month (75-89 years/90 years and older) were: outpatient clinic visits, 622/570; hospital outpatient visits, 300/263; advanced treatment hospital outpatient visits, 16/6; emergency department visits, 10/27; hospitalizations, 45/96; advanced treatment hospital hospitalizations, 2/1; planned home visits, 36/228; urgent home visits, 6/38; home care services, 173/533; and facility services, 32/178. CONCLUSIONS: The results revealed that older adults over 90 years had more hospitalizations, emergency department visits and home visits, and used facility/home care services more compared with older adults aged 75-89 years. The results provide a useful benchmark for healthcare use estimation. Geriatr Gerontol Int 2022; 22: 483-489.

DOI： 10.1111/ggi.14387

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS/INTRODUCTION: Among colorectal cancer (CRC) patients, pre-existing diabetes is suggested to influence poor prognosis, but the impact on adjuvant chemotherapy implementation is largely unknown. We aimed to compare the implementation rate of adjuvant chemotherapy between CRC patients with and without pre-existing diabetes in a retrospective cohort study. MATERIALS AND METHODS: Colorectal cancer diagnosis information was obtained from the hospital-based cancer registry of patients with stage III CRC who underwent curative surgery in 2013 in Japan (n = 6,344). Health claims data were used to identify diabetes and chemotherapy. We examined the association between diabetes and the implementation rate of adjuvant chemotherapy using a generalized linear model adjusted for age, sex, updated Charlson Comorbidity Index, hospital type and prefecture. Furthermore, we applied a mediation analysis to examine the extent to which postoperative complications mediated the association. RESULTS: Of the 6,344 patients, 1,266 (20.0%) had diabetes. The mean ages were 68.2 and 71.3 years for patients without and with diabetes, respectively. Compared with those without diabetes, patients with diabetes were less likely to receive adjuvant chemotherapy (crude rate 58.9 and 49.8%; adjusted percentage point difference 4.6; 95% confidence interval 1.7-7.5). The difference was evident for patients aged <80 years, and larger for platinum-containing regimens than others. Mediation analysis showed that postoperative complications explained 9.1% of the inverse association between diabetes and adjuvant chemotherapy implementation. CONCLUSIONS: We observed that patients with stage III CRC and diabetes are less likely to receive adjuvant chemotherapy than those without diabetes, and postoperative complications might partially account for the association.

DOI： 10.1111/jdi.13837

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: We aimed to investigate the association between sugar or starch intake and the risk of type 2 diabetes (T2D) in middle-aged Japanese adults. SUBJECTS/METHODS: Participants comprised 27,797 men and 36,880 women aged 45-75 years with no history of diabetes and critical illness before the second survey in the Japan Public Health Center-based Prospective Study. We calculated sugar (total sugar, total fructose, and sugar subtypes) and starch intakes (% energy/d) using a validated 147-item food frequency questionnaire, to estimate the average dietary intake over the previous year. T2D onset was defined by validated self-reports. ORs adjusted for potential confounders were estimated using multiple logistic regression with categorical and cubic spline models. RESULTS: During the 5-year follow-up, 690 men and 500 women were identified with T2D. In women, the quartiles of total sugar or total fructose intakes were not significantly associated with T2D risk; however, the spline curves showed an increased risk at extremely high intake levels (ORs [95% CI]: 1.88 [1.07-3.31] at 30% energy/d for total sugar and 1.87 [1.10-3.16] at 14% energy/d for total fructose). Starch intake was positively associated with T2D risk among women in the categorical and spline models (ORs [95% CI]: 1.55 [1.13-2.12] at 50% energy/d). In men, sugar and starch intakes were not associated with T2D risk. CONCLUSIONS: In this large-scale population-based cohort study, starch intake was associated with an increased T2D risk in Japanese women. An increased risk with extremely high intake of total sugar or total fructose among women cannot be disregarded.

DOI： 10.1038/s41430-021-01005-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

To evaluate vaccine-induced humoral and cell-mediated immunity at 6 months after completion of two doses of BNT162b2 vaccination, immunoglobulin G against SARS-CoV-2 spike protein (SP IgG), 50% neutralizing antibody (NT50), and spot-forming cell (SFC) counts were evaluated by interferon-γ releasing ELISpot assay of 98 healthy subjects (median age, 43 years). The geometric mean titers of SP IgG and NT50 decreased from 95.2 (95% confidence interval (CI) 79.8-113.4) to 5.7 (95% CI 4.9-6.7) and from 680.4 (588.0-787.2) to 130.4 (95% CI 104.2-163.1), respectively, at 3 weeks and 6 months after the vaccination. SP IgG titer was negatively correlated with age and alcohol consumption. Spot-forming cell counts at 6 months did not correlate with age, gender, and other parameters of the patients. SP IgG, NT50, and SFC titers were elevated in the breakthrough infected subjects. Although the levels of vaccine-induced antibodies dramatically declined at 6 months after vaccination, a certain degree of cellular immunity was observed irrespective of the age.

DOI： 10.1016/j.vaccine.2022.03.057

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: It is often challenging to determine which variables need to be included in the g-computation algorithm under the time-varying setting. Conditioning on instrumental variables (IVs) is known to introduce greater bias when there is unmeasured confounding in the point-treatment settings, and this is also true for near-IVs which are weakly associated with the outcome not through the treatment. However, it is unknown whether adjusting for (near-)IVs amplifies bias in the g-computation algorithm estimators for time-varying treatments compared to the estimators ignoring such variables. We thus aimed to compare the magnitude of bias by adjusting for (near-)IVs across their different relationships with treatments in the time-varying settings. METHODS: After showing a case study of the association between the receipt of industry payments and physicians' opioid prescribing rate in the US, we demonstrated Monte Carlo simulation to investigate the extent to which the bias due to unmeasured confounders is amplified by adjusting for (near-)IV across several g-computation algorithms. RESULTS: In our simulation study, adjusting for a perfect IV of time-varying treatments in the g-computation algorithm increased bias due to unmeasured confounding, particularly when the IV had a strong relationship with the treatment. We also found the increase in bias even adjusting for near-IV when such variable had a very weak association with unmeasured confounders between the treatment and the outcome compared to its association with the time-varying treatments. Instead, this bias amplifying feature was not observed (i.e., bias due to unmeasured confounders decreased) by adjusting for near-IV when it had a stronger association with the unmeasured confounders (≥0.1 correlation coefficient in our multivariate normal setting). CONCLUSION: It would be recommended to avoid adjusting for perfect IV in the g-computation algorithm to obtain a less biased estimate of the time-varying treatment effect. On the other hand, it may be recommended to include near-IV in the algorithm unless their association with unmeasured confounders is very weak. These findings would help researchers to consider the magnitude of bias when adjusting for (near-)IVs and select variables in the g-computation algorithm for the time-varying setting when they are aware of the presence of unmeasured confounding.

DOI： 10.1186/s12874-022-01563-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The This study estimated the cancer burden attributable to modifiable factors in Japan in 2015 using the best available epidemiological evidence and a standard methodology. We selected the following factors for inclusion in the estimates, namely tobacco smoking (active smoking and secondhand smoking), alcohol drinking, excess bodyweight, physical inactivity, infectious agents (Helicobacter pylori, hepatitis C virus, hepatitis B virus, human papilloma virus, Epstein-Barr virus, and human T-cell leukemia virus type 1), dietary intake (highly salted food, fruit, vegetables, dietary fiber, red meat, processed meat), exogenous hormone use, never breastfeeding and air pollution, given that these were considered modifiable, in theory at least. We first estimated the population attributable fraction (PAF) of each cancer attributable to these factors using representative relative risks of Japanese and the prevalence of exposures in Japanese around 2005, in consideration of the 10-year interval between exposure and cancer outcomes. Using nationwide cancer incidence and mortality statistics, we then estimated the attributable cancer incidence and mortality in 2015. We finally obtained the PAF for site-specific and total cancers attributable to all modifiable risk factors using this formula, with statistical consideration of the effect of overlap between risk factors. The results showed that 35.9% of all cancer incidence (43.4% in men and 25.3% in women) and 41.0% of all cancer mortality (49.7% in men and 26.8% in women) would be considered preventable by avoidance of these exposures. Infections and active smoking followed by alcohol drinking were the greatest contributing factors to cancer in Japan in 2015.

DOI： 10.35772/ghm.2021.01037

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記述言語：英語  

DOI： 10.2188/jea.JE20210459

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Levels of 50% neutralizing titer (NT50) reflect the a vaccine-induced humoral immunity after the vaccination against the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Measurements of NT50 are difficult to implement in large quantities. A high-throughput laboratory test is expected for determining the level of herd immunity against SARS-CoV-2. METHODS: We analyzed samples from 168 Japanese healthcare workers who had completed two doses of the BNT162b2 vaccine. We analyzed immunoglobulin G (IgG) index values against spike protein (SP) using automated chemiluminescent enzyme immunoassay system AIA-CL and analyzed the background factors affecting antibody titer. SP IgG index was compared with 50% neutralization titers. RESULTS: The median SP IgG index values of the subjects (mean age = 43 years; 75% female) were 0.1, 1.35, 60.80, and 97.35 before and at 2, 4, and 6 weeks after the first dose, respectively. At 4 and 6 weeks after the first dose, SP IgG titers were found to have positive correlation with NT50 titer (r = 0.7535 in 4 weeks; r = 0.4376 in 6 weeks). Proportions of the SP IgG index values against the Alpha, Beta, Gamma, and Delta variants compared with the original strain were 2.029, 0.544, 1.017, and 0.6096 respectively. Older age was associated with lower SP IgG titer index 6 weeks after the first dose. CONCLUSIONS: SP IgG index values were rised at 3 weeks after two doses of BNT162b2 vaccination and have positive correlation with NT50. SP IgG index values were lower in the older individuals and against Beta and Delta strain.

DOI： 10.1016/j.jiac.2021.11.021

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS/INTRODUCTION: To investigate the national trend in the prescription of first-line non-insulin antidiabetic agents and total medical costs (TMCs) after prescribing the drug in Japanese patients with type 2 diabetes. MATERIALS AND METHODS: Using the National Database of Health Insurance Claims and Specific Health Check-ups of Japan (NDB) covering almost the entire Japanese population, we calculated the proportion of each antidiabetic drug from 2014 to 2017 and determined the factors associated with drug selection. The TMCs in the first year after starting the drugs were calculated, and factors associated with the costs were also determined. RESULTS: Among 1,136,723 new users of antidiabetic agents, dipeptidyl peptidase-4 (DPP4) inhibitors were the most prescribed (65.1%), followed by biguanides (15.9%) and sodium-glucose co-transporter-2 (SGLT2) inhibitors (7.6%). SGLT2 inhibitor and biguanide use increased during 2014-2017 (2.2%-11.4% and 13.7%-17.2%, respectively), whereas the others decreased. Biguanides were not prescribed at all in 38.2% of non-Japan Diabetes Society-certified facilities. The TMCs were the lowest among those who started with biguanides. Fiscal year, age, sex, facility, number of beds, and comorbidities were associated with drug choice and TMCs. There were wide regional variations in the drug choice, but not in the TMCs. CONCLUSIONS: Unlike in the US/Europe, DPP4 inhibitor is the most prescribed first-line medication for type 2 diabetes in Japan, while there is a wide variation in the drug choice by facility-type and prefecture.

DOI： 10.1111/jdi.13636

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection elicits varying degrees of protective immunity conferred by neutralizing antibodies (nAbs). In this study, we report the persistence of nAb responses over 12 months after infection despite their decreasing trend noticed from 6 months. METHODS: The study included sera from 497 individuals who had been infected with SARS-CoV-2 between January and August 2020. Samples were collected at 6 and 12 months after onset. The titers of immunoglobulin (Ig)G to the viral nucleocapsid protein (NP) and receptor-binding domain (RBD) of the spike protein were measured by chemiluminescence enzyme immunoassay. The nAb titer was determined using lentivirus-based pseudovirus or authentic virus. RESULTS: Antibody titers of NP-IgG, RBD-IgG, and nAbs were higher in severe and moderate cases than in mild cases at 12 months after onset. Although the nAb levels were likely to confer adequate protection against wild-type viral infection, the neutralization activity to recently circulating variants in some of the mild cases (~30%) was undermined, implying the susceptibility to reinfection with the variants of concerns (VOCs). CONCLUSIONS: Coronavirus disease 2019 convalescent individuals have robust humoral immunity even at 12 months after infection albeit that the medical history and background of patients could affect the function and dynamics of antibody response to the VOCs.

DOI： 10.1093/ofid/ofab626

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Although childhood undervaccination among single mother families is a concern for child healthcare, their association is still under debate. This study aimed to investigate the association between maternal marital status and the risk of childhood undervaccination and determine the mediating effect of household income. METHODS: We utilised prospective birth cohort from the Japan Environment and Children's Study (JECS). Of 104,062 foetal records (children) from 97,413 mothers, 82,462 that included mothers recruited between 2011 and 2014, were analysed. Childhood undervaccination was defined as not having been vaccinated with at least one routine vaccine. A log-binomial regression analysis was used to estimate the risk ratio (RR) for the association between maternal marital status and the risk of childhood undervaccination. A causal mediation analysis was further performed to investigate the proportion of the association mediated by household income. RESULTS: Among 82,462 children, 3188 and 79,274 had unmarried and married mothers, respectively. Childhood undervaccination was observed in 1053 (33.0%) and 16,901 (21.3%) children of unmarried and married mothers, respectively. Maternal marital status was associated with a higher risk of childhood undervaccination (adjusted risk ratio [aRR], 1.34; 95% confidence interval [CI], 1.27 to 1.41). Compared with married and older mothers, both unmarried and older (aRR, 1.54; 95% CI, 1.35 to 1.77) and unmarried and younger (aRR, 1.66; 95% CI, 1.54 to 1.79) mothers were associated with a higher risk of childhood undervaccination. The causal mediation analysis showed that the proportion mediated by household income was 10.5% (95% CI, 9.9 to 11.0%). CONCLUSIONS: This nationwide, prospective, large-scale birth cohort study found that a household with a single mother was associated with an increased risk of childhood undervaccination, and 10% of this association was explained by household income. These findings underscore the importance of improving the social environment among single mother families, including not only poverty but also working conditions.

DOI： 10.1186/s12889-022-12511-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND AND AIM: Chronic hepatitis C virus (HCV) infection, long-term alcohol use, cigarette smoking, and obesity are the major risk factors for hepatocellular carcinoma (HCC) in the United States, but the disease risk varies substantially among individuals with these factors, suggesting host susceptibility to and gene-environment interactions in HCC. To address genetic susceptibility to HCC, we conducted a genome-wide association study (GWAS). METHODS: Two case-control studies on HCC were conducted in the United States. DNA samples were genotyped using the Illumian microarray chip with over 710 000 single nucleotide polymorphisms (SNPs). We compared these SNPs between 705 HCC cases and 1455 population controls for their associations with HCC and verified our findings in additional studies. RESULTS: In this GWAS, we found that two SNPs were associated with HCC at P < 5E-8 and six SNPs at P < 5E-6 after adjusting for age, sex, and the top three principal components (PCs). Five of the SNPs in chromosome 22q13.31, three in PNPLA3 (rs2281135, rs2896019, and rs4823173) and two in SAMM50 (rs3761472, rs3827385), were replicated in a small US case-control study and a cohort study in Singapore. The associations remained significant after adjusting for body mass index and HCV infection. Meta-analysis of multiple datasets indicated that these SNPs were significantly associated with HCC. CONCLUSIONS: SNPs in PNPLA3 and SAMM50 are known risk loci for nonalcoholic fatty liver disease (NAFLD) and are suspected to be associated with HCC. Our GWAS demonstrated the associations of these SNPs with HCC in a US population. Biological mechanisms underlying the relationship remain to be elucidated.

DOI： 10.1002/jgh3.12682

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: An inappropriately low frequency of healthcare utilization has been reported to be associated with poor control of chronic diseases, accelerating healthcare disparities. However, the evidence is limited regarding the association between no healthcare utilization and mortality. OBJECTIVES: To examine whether individuals without healthcare utilization have the increased risks of mortality among the US general population. DESIGN: Prospective cohort study PARTICIPANTS: Adults aged ≥ 20 years (n = 39,067) in the National Health and Nutrition Examination Survey (NHANES)1999-2014 linked to national mortality data through December 2015. MAIN MEASURES: The exposure was the number of visits to healthcare providers during the past year (healthcare utilization): none, 1-3 times (referent), 4-9 times, or ≥ 10 times. Cox hazard regression models were employed to estimate the adjusted hazard ratios (aHR) of all-cause, cardiovascular, and cancer mortality adjusting for socio-demographic characteristics and comorbidities. KEY RESULTS: During a median follow-up of 7.4 years, participants without visit over the past year showed higher risks of all-cause mortality (aHR [95% CI] = 1.16 [1.04-1.30]) and cardiovascular mortality (aHR [95% CI] = 1.62 [1.28-2.05]) than those who visited the office 1-3 times. We found no evidence of the association between no visit and cancer mortality. The association between no providers' office visit and all-cause mortality was stronger among males (aHR [95% CI] = 1.22 [1.06-1.40]) than females (aHR [95% CI] = 0.97 [0.79-1.19]; p-for-interaction = 0.01) and among uninsured individuals (aHR [95% CI] = 1.22 [0.98-1.51]) than insured individuals (aHR [95% CI] = 1.09 [0.95-1.25]; p-for-interaction = 0.04). CONCLUSION: No providers' office visit over a year was associated with increased risks of all-cause and cardiovascular mortality. Further investigations are warranted to identify the underlying reasons for the elevated mortality risks due to no healthcare utilization.

DOI： 10.1007/s11606-021-07138-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Evidence supporting the association of glycemic index (GI) and glycemic load (GL) with the risk of endometrial cancer is controversial and reports from Asia were limited. Therefore, we aimed to investigate the association in Japanese women. We evaluated 52 460 women in the Japan Public Health Center-based Prospective Study aged 45-74 years who responded to the 5-year follow-up survey. GI and GL were calculated from a validated food frequency questionnaire, and the participants were divided into three groups by GI and GL. The hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with the Cox proportional hazard model adjusted for potential confounding factors. As a result, within 15.5 years of follow-up, 166 new cases of endometrial cancer were identified. Compared with the lowest GI and GL tertile groups, the HR of the risk of endometrial cancer in the highest GI tertile group was 0.80 (95% CI, 0.53-1.20; Ptrend  = .33), and that of the highest GL tertile group was 0.79 (95% CI, 0.52-1.19; Ptrend  = .82). The results were unchanged after stratification by body mass index, coffee consumption, and history of diabetes. In conclusion, we did not find any significant association between GI and GL with the risk of endometrial cancer. Further research is required to clarify the association.

DOI： 10.1111/cas.14997

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Body mass index (BMI) is inversely associated with lung cancer risk, while residual confounding by smoking or weight change is controversial. Evidence on height and lung cancer is scarce. METHODS: We investigated the associations between anthropometrics, BMI, and height, and incidence of lung cancer among 92,098 study subjects (44,158 men and 47,940 women) in the Japan Public Health Center-based Prospective Study. Cox proportional hazards regression was performed with adjustment for potential confounders and by cancer subtypes and smoking status. Information on weight and height was self-reported at baseline, and validated using measured health check-up data. RESULTS: During follow-up between 1990 and 2013 (average, 19.1 years), a total of 2,152 lung cancer cases were newly diagnosed. In a multivariate regression model, lower BMI was positively associated with overall lung cancer risk [<19 kg/m2 HR = 1.48; 95% confidence interval (CI) = 1.18-1.85 and 19-22.9 kg/m2; HR = 1.19; 95% CI = 1.05-1.35; P trend = <0.001] in men. The risk estimate was also elevated for adenocarcinoma in the BMI <19 kg/m2 category and for squamous cell carcinoma among men in the 19-22.9 kg/m2 BMI category. An association was also observed between low BMI, weight decrease, and squamous cell carcinoma in women. No significant associations were observed for other weight categories, height, weight change and lung cancer, adenocarcinoma, squamous and small cell carcinoma. CONCLUSIONS: Our prospective study suggests that lower BMI may be associated with an increased risk of smoking-related lung cancer in Japan, irrespective of gender. IMPACT: This study highlights the association between lower BMI and the risk of lung cancer in men.

DOI： 10.1158/1055-9965.EPI-21-0195

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The uncontrolled spread of the COVID-19 pandemic has led to the emergence of different SARS-CoV-2 variants across the globe. The ongoing global vaccination strategy to curtail the COVID-19 juggernaut, is threatened by the rapidly spreading Variants of Concern (VOC) and other regional mutants, which are less responsive to neutralization by infection or vaccine derived antibodies. We have previously developed the hiVNT system which detects SARS-CoV-2 neutralizing antibodies in sera in less than three hours. In this study, we modify the hiVNT for rapid qualitative screening of neutralizing antibodies (nAb) to multiple VOC of SARS-CoV-2, and assess the neutralizing efficacy of the BNT162b2 mRNA vaccine on seven epidemiologically relevant SARS-CoV-2 variants. Here we show that the BNT162b2 mRNA vaccine can activate humoral immunity against the major SARS-CoV-2 mutants that are currently in circulation. Albeit a small sample size, we observed that one dose of vaccine was sufficient to elicit a protective humoral response in previously infected people. Using a panel of seven SARS-CoV-2 variants and a single prototype virus, our modified hiVNT would be useful for large-scale community wide testing to detect protective immunity that may confer vaccine/immune passport in the ongoing COVID-19 pandemic.

DOI： 10.1093/jmcb/mjab050

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: To investigate the relation between body mass index (BMI) and dry eye disease (DED). METHODS: We conducted a cross-sectional questionnaire-based survey in 85,264 Japanese men and women aged 40 to 74 years who participated in the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT Study). Dry eye disease was defined as the presence of severe symptoms or clinical diagnosis. A multivariable logistic regression model was used to estimate the odds ratios (ORs) of DED associated with BMI and their two-sided 95% confidence intervals (CIs). We adjusted for age, cohort area, visual display terminal time, smoking status, alcohol intake, education status, income status, as well as history of hormone replacement therapy for women. RESULTS: Prevalence of DED was 23.4% (n = 19,985; 6,289 men, 13,696 women). Higher BMI was correlated with a lower prevalence of DED in a dose-response fashion, with an adjusted OR of DED (95% CI) per 1 kg/m2 increment of BMI of 0.98 (95% CI: 0.97-0.99) for men and 0.97 (95% CI: 0.97-0.98) for women. CONCLUSIONS: This large population-based study showed an inverse relationship between BMI and prevalence of DED in a Japanese population. Underestimation of DED is warned, especially for participants with high BMI.

DOI： 10.1097/ICL.0000000000000814

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BackgroundValidation studies on diabetes definitions using nationwide healthcare databases are scarce. We evaluated the validity of diabetes definitions using disease codes and antidiabetic drug prescriptions in the Japanese Diagnosis Procedure Combination (DPC) data via medical chart review.MethodsWe randomly selected 500 records among 15,334 patients who participated in the Japan Public Health Center-Based Prospective Study for the Next Generation in Yokote City and who had visited a general hospital in Akita between October 2011 and August 2018. Of the 500 patients, 98 were linked to DPC data; however, only 72 had sufficient information in the medical chart. Gold standard confirmation was performed by board-certified diabetologists. DPC-based diabetes definitions were based on the International Classification of Diseases, 10th Revision codes, and antidiabetic prescriptions. Sensitivity, specificity, and the positive and negative predictive values (PPV and NPV, respectively) of DPC-based diabetes definitions were evaluated.ResultsOf 72 patients, 23 were diagnosed with diabetes by chart review; 19 had a diabetes code, and 13 had both a diabetes code and antidiabetic prescriptions. The sensitivity, specificity, PPV, and NPV were 89.5% (95% confidence interval: 66.9-98.7), 96.2% (87.0-99.5), 89.5% (66.9-98.7), and 96.2% (87.0-99.5), respectively, for (i) diabetes codes alone; 89.5% (66.9-98.7), 94.3% (84.3-98.8), 85.0% (62.1-96.8), and 96.2 (86.8-99.5) for (ii) diabetes codes and/or prescriptions; 68.4% (43.4-87.4), 100% (93.3-100), 100% (75.3-100), and 89.8% (79.2-96.2) for (iii) both diabetes codes and prescriptions.ConclusionsOur results suggest that DPC data can accurately identify diabetes among inpatients using (i) diabetes codes alone or (ii) diabetes codes and/or prescriptions.

DOI： 10.2188/jea.JE20210024

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To investigate whether and how unhealthy sleep habits (i.e., the frequency of difficulty falling or staying asleep, and the frequency of waking up tired) and the duration of sleep are related to the prevalence of dry eye disease (DED) in a general population. METHODS: This study included a total of 106,282 subjects aged 40-74 years who participated in a baseline survey of the Japan Public Health Center-based Prospective Study for the Next Generation. DED was defined as the presence of clinically diagnosed DED or severe symptoms. Multivariable-adjusted logistic regression models were used to assess the relationships of various components of sleep status with DED. RESULTS: Higher frequencies of having difficulty falling or staying asleep, and waking up tired were significantly related to increased DED in both sexes (Ptrend<0.001). Compared with those with 8 h/day of sleep, shorter sleepers had an increased prevalence of DED in both sexes, although DED was increased among men who slept ≥10 h/day. By comparing participants with the greatest vs. the least difficulty of falling asleep, the multivariable-adjusted odds ratios (95% confidence interval [CI]) were 2.23 (95% CI, 1.99-2.49) for men and 1.91 (95% CI, 1.76-2.07) for women. When analyzed separately, the magnitude of each relationship was stronger with severe DED symptoms than with clinically diagnosed DED. CONCLUSIONS: Sleep deprivation and poor sleep quality were significantly related to DED in a Japanese population.

DOI： 10.1016/j.jtos.2021.04.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1096/fj.202100317

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Evidence of the association between dietary fiber intake and gastric cancer (GC) risk from prospective studies is limited. We examined the association between dietary fiber intake and GC risk in a large prospective study. A total of 91 946 eligible Japanese aged 45 to 74 years (42 773 men and 49 173 women) participated in a population-based cohort study (Japan Public Health Center-based prospective study). From a validated food frequency questionnaire with 138 food items, total and food source-specific dietary fiber intake was calculated as exposure. The hazard ratio (HR) and the 95% confidence interval (CI) of GC incidence according to quintile of dietary fiber intake were examined after adjusting for confounding factors. In total, 2228 GC cases (1559 men and 669 women) were observed during the 15.0 years follow-up. Total dietary fiber intake was not associated with GC risk; however, a marginally increased risk trend because of high HR in the highest quintile of total fiber intake was found in women (HR [95% CI] in Q5 vs Q1: 0.95 [0.79-1.14], P for trend .30 in men, HR [95% CI] 1.25 [0.98-1.61], P for trend .05 in women). Stratification by tumor location did not change the results. A marginal but not significant inverse trend was observed regarding cereal fiber intake and GC risk in men. Total dietary fiber intake was not associated with GC risk. Further studies are warranted to confirm this association.

DOI： 10.1002/ijc.33450

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記述言語：日本語   出版者・発行元：(一社)日本糖尿病学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Helicobacter pylori (H. pylori) is an established causative factor of gastric cancer. Although the expansion of insurance coverage has led to an increase in the number of patients treated for H. pylori, the population impact of eradication treatment for H.pylori has been scarcely investigated. This study aimed to clarify the long-term responses of H. pylori antibody titer after eradication treatment using large scale cross-sectional data from the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT Study). METHODS: A total of 55,282 Japanese participants aged 40 to 74 years residing in 16 areas provided blood samples between 2011 and 2016. From these, treated (n=6,276) and untreated subjects who were seropositive for H. pylori or had serological atrophy (n= 22,420) formed the study population (n=28,696). Seropositivity was defined as an anti-H. pylori IgG titer of ≥10 U/mL. Antibody level was compared among subjects according to self-reported treatment history as untreated, and treated for less than one year (<1Y), one to five years (1-5Y), and more than six years ago (6Y+). RESULTS: Median serum antibody titer was 34.0 U/mL, 7.9 U/mL, 4.0 U/mL, and 2.9 U/mL for the Untreated, <1Y, 1-5Y, and 6Y+ groups, respectively. While those treated for H.pylori within the previous year had a 76.8% lower antibody titer compared to untreated subjects, approximately 41% of subjects were still seropositive. CONCLUSIONS: A significant reduction in H.pylori antibody titer occurs within one year after eradication treatment, but that a long period is needed to achieve complete negative conversion.

DOI： 10.2188/jea.JE20200618

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Although prevalence of low birth weight has increased in the last 3 decades in Japan, no studies in Japanese women have investigated whether birth weight is associated with the risk of pregnancy complications, such as pregnancy-induced hypertension (PIH) and gestational diabetes mellitus (GDM). METHODS: We used data from the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT), a population-based cohort study in Japan that launched in 2011. In the main analysis, we included 46,365 women who had been pregnant at least once, for whom information on birth weight and events during their pregnancy was obtained using a self-administered questionnaire. Women were divided into five categories according to their birth weight, and the relationship between birth weight and risk of PIH and GDM was examined using multilevel logistic regression analyses with place of residence as a random effect. RESULTS: Compared to women born with birth weight of 3,000-3,999 grams, the risk of PIH was significantly higher among women born <1,500 grams (adjusted odd ratio [aOR] 1.60; 95% confidence interval [CI], 1.17-2.21), 1,500-2,499 grams (aOR 1.16; 95% CI, 1.03-1.30), and 2,500-2,999 grams (aOR 1.13; 95% CI, 1.04-1.22). The risk of GDM was significantly higher among women born 1,500-2,499 grams (aOR 1.20; 95% CI, 1.02-1.42), albeit non-significant association among women in other birthweight categories. CONCLUSIONS: We observed an increased risk of PIH among women born with lower birth weight albeit non-significant increased risk of GDM among Japanese women.

DOI： 10.2188/jea.JE20200302

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The association between fish consumption and new-onset type 2 diabetes is inconsistent and differs according to geographical location. We examined the association between the total and types of fish consumption and type 2 diabetes using individual participant data from 28 prospective cohort studies from the Americas (6), Europe (15), the Western Pacific (6), and the Eastern Mediterranean (1) comprising 956,122 participants and 48,084 cases of incident type 2 diabetes. Incidence rate ratios (IRRs) for associations of total fish, shellfish, fatty, lean, fried, freshwater, and saltwater fish intake and type 2 diabetes were derived for each study, adjusting for a consistent set of confounders and combined across studies using random-effects meta-analysis. We stratified all analyses by sex due to observed interaction (p = 0.002) on the association between fish and type 2 diabetes. In women, for each 100 g/week higher intake the IRRs (95% CIs) of type 2 diabetes were 1.02 (1.01-1.03, I2 = 61%) for total fish, 1.04 (1.01-1.07, I2 = 46%) for fatty fish, and 1.02 (1.00-1.04, I2 = 33%) for lean fish. In men, all associations were null. In women, we observed variation by geographical location: IRRs for total fish were 1.03 (1.02-1.04, I2 = 0%) in the Americas and null in other regions. In conclusion, we found evidence of a neutral association between total fish intake and type 2 diabetes in men, but there was a modest positive association among women with heterogeneity across studies, which was partly explained by geographical location and types of fish intake. Future research should investigate the role of cooking methods, accompanying foods and environmental pollutants, but meanwhile, existing dietary regional, national, or international guidelines should continue to guide fish consumption within overall healthy dietary patterns.

DOI： 10.3390/nu13041223

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

PURPOSE: The aim of this study was to compare the impact of fermented and unfermented soy intake, based on the following soy-derived products: tofu, soymilk, natto, and miso, on the risk of liver cancer among Japanese adults. METHODS: 75,089 Participants of the Japan Public Health Center-based Prospective Study (JPHC Study) were followed from the time of the 5-year follow-up questionnaire until the end of 2012-2013. Subjects with available data on hepatitis B virus (HBV) and hepatitis C virus (HCV) infection status from blood samples (n = 14,016) and those who were anti-HCV antibody (anti-HCV) or hepatitis B virus antigen (HBsAg) positive (n = 1033) were also analyzed separately. Cox proportional hazard models were employed to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). RESULTS: During 1,145,453 person-years, 534 newly diagnosed cases of liver cancer were identified in the JPHC Study. For miso intake among men, the multivariate-adjusted highest versus lowest quartile HR was 0.65 (95% CI, 0.48-0.89); p for trend = 0.006. Results were similar in those who were anti-HCV or HBsAg positive, 0.24 (0.08-0.70); p for trend = 0.004 highest versus lowest tertile. For the sub-analysis among only participants with known hepatitis infection status and HCV and HBsAg adjustment, a similar association was observed. In the multivariate complete cohort analysis, among women, the highest intake of fried tofu was inversely associated with the risk of liver cancer, HR = 0.45 (0.26-0.80); p for trend = 0.014. CONCLUSIONS: We observed no association between total soy intake, fermented and unfermented, and risk of liver cancer, and only an inverse association between miso intake and liver cancer among men.

DOI： 10.1007/s00394-020-02335-9

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その他リンク： http://link.springer.com/article/10.1007/s00394-020-02335-9/fulltext.html

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Evidence is limited regarding the association between low-carbohydrate diet (LCD) score and mortality among Asians, a population that consumes a large amount of carbohydrates. OBJECTIVE: The present study examined the association between low-carbohydrate diet (LCD) score (based on percentage of energy as carbohydrate, fat, and protein) and the risk of total and cause-specific mortality among Asians. DESIGN: This study was a prospective cohort study in Japan with follow-up for a median of 16.9 years involving 43008 men and 50646 women aged 45-75 years. Association of LCD score, LCD score based on animal sources of protein and fat, and LCD score based on plant sources of protein and fat with risk of mortality was assessed using Cox proportional hazards model. RESULTS: A U-shaped association was observed between LCD score and total mortality: the multivariable-adjusted hazard ratios (HRs) (95% CI) of total mortality for lowest through highest scores were 1.00, 0.95 (0.91, 1.01), 0.93 (0.88, 0.98), 0.93 (0.88, 0.98), and 1.01 (0.95, 1.07) (P-non-linearity <0.01). A similar association was found for mortality from cardiovascular disease (CVD) and heart disease. LCD score based on carbohydrate, animal protein, and animal fat also showed a U-shaped association for total mortality (P-non-linearity <0.01). In contrast, LCD score based on carbohydrate, plant protein, and plant fat was linearly associated with lower total (HR, 0.89; 95% CI: 0.83, 0.94 for highest versus lowest quintile), CVD [0.82 (0.73, 0.92)], heart disease [0.83 (0.71, 0.98)], and cerebrovascular disease [0.75 (0.62, 0.91) mortality. CONCLUSIONS: Both LCD with high animal protein and fat and high-carbohydrate diet with low animal protein and fat were associated with higher risk of mortality. Meanwhile, LCD high in plant-based sources of protein and fat was associated with a lower risk of total and CVD mortality.

DOI： 10.1016/j.clnu.2020.09.022

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: The present study aimed to examine the association between adherence to the Japanese diet and the subsequent risk of all-cause and cause-specific mortality using a large-scale cohort from settings all over Japan. METHODS: We analyzed data from a cohort study of 92,969 Japanese adults aged 45-74 years, covering 11 public health center areas nationwide. We collected dietary information using a validated 147-item food frequency questionnaire. Adherence to the Japanese diet consisting of eight components (high intake of rice, miso soup, seaweeds, pickles, green and yellow vegetables, fish, and green tea; low intake of beef and pork) was assessed using 8-item Japanese Diet Index (JDI8) score, with scores ranging from 0 to 8. The Cox proportional hazards model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for all-cause and cause-specific mortality. RESULTS: During a median follow-up of 18.9 years, we documented 20,596 deaths. A higher JDI8 score was significantly associated with a lower risk for all-cause and cardiovascular disease (CVD) mortality. The multivariable-adjusted HR of all-cause and CVD mortality for the highest JDI8 score group (score of 6-8) versus the lowest JDI8 score group (score of 0-2) were 0.86 (95% CI 0.81-0.90, P trend < 0.001), and 0.89 (95% CI 0.80-0.99, P trend = 0.007), respectively. CONCLUSIONS: Adhering to the Japanese diet, as assessed by the JDI8, was associated with a decreased risk of all-cause and CVD mortality among adults living in multiple areas across Japan.

DOI： 10.1007/s00394-020-02330-0

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Traditional observational studies have reported a positive association between higher body mass index (BMI) and the risk of colorectal cancer (CRC). However, evidence from other approaches to pursue the causal relationship between BMI and CRC is sparse. A two-sample Mendelian randomization (MR) study was undertaken using 68 single nucleotide polymorphisms (SNPs) from the Japanese genome-wide association study (GWAS) and 654 SNPs from the GWAS catalogue for BMI as sets of instrumental variables. For the analysis of SNP-BMI associations, we undertook a meta-analysis with 36 303 participants in the Japanese Consortium of Genetic Epidemiology studies (J-CGE), comprising normal populations. For the analysis of SNP-CRC associations, we utilized 7636 CRC cases and 37 141 controls from five studies in Japan, and undertook a meta-analysis. Mendelian randomization analysis of inverse-variance weighted method indicated that a one-unit (kg/m2 ) increase in genetically predicted BMI was associated with an odds ratio of 1.13 (95% confidence interval, 1.06-1.20; P value <.001) for CRC using the set of 68 SNPs, and an odds ratio of 1.07 (1.03-1.11, 0.001) for CRC using the set of 654 SNPs. Sensitivity analyses robustly showed increased odds ratios for CRC for every one-unit increase in genetically predicted BMI. Our MR analyses strongly support the evidence that higher BMI influences the risk of CRC. Although Asians are generally leaner than Europeans and North Americans, avoiding higher BMI seems to be important for the prevention of CRC in Asian populations.

DOI： 10.1111/cas.14824

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Fruits and vegetables may induce greater satiety, reduce hunger, decrease energy intake, and modulate energy metabolism, thereby playing a role in weight loss. OBJECTIVE: To determine the associations between changes in fruit and vegetable consumption and weight change over a 5-year interval in Japanese adults. METHODS: This cohort study included 54,015 subjects (54.6% female, mean age 56.5 years) of the Japan Public Health Center-based Prospective Cohort Study who had no known history of major chronic diseases at baseline. Data on fruit and vegetable consumption were collected using a validated food frequency questionnaire. Body weight was self-reported. We used multivariable linear mixed-effects regression models to examine the associations between changes in fruit and vegetable consumption and change in body weight. RESULTS: On average, body weight decreased by 25 g [95% confidence interval (CI), 3, 47] for every 100 g/d increase in total vegetable consumption. Change in fruit consumption was nonlinearly associated with weight change. Fruit consumption was directly associated with weight change among subjects who increased consumption (70 g; 95% CI, 39, 101) but was not associated with weight change among subjects who reduced or did not change fruit consumption. These associations did not vary by sex, age, and body mass index (BMI) at baseline. The association with vegetables was restricted to yellow/red vegetables (- 74 g; 95% CI, - 129, - 18) and allium vegetables (- 129 g; 95% CI, - 231, - 28). Lower-fiber vegetables were inversely associated with weight change, whereas lower-fiber fruits or higher-energy fruits were directly associated with weight change beyond 0 g/d change in consumption. CONCLUSIONS: Change in vegetable consumption was inversely associated with weight change while fruit consumption was positively associated with weight change among subjects who increased consumption. The influence of fruits and vegetables on weight change may depend on the characteristics of the fruits and vegetables.

DOI： 10.1007/s00394-020-02236-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: This study compared working cancer survivors' self-rated health status (SRHS), physical functional capacity, depressive symptoms, and happiness to those of cancer-free workers. METHODS: A nationwide general population-based cross-sectional study on a sample of Japanese was conducted. Prevalence of deteriorated SRHS, restricted physical functional capacity, depressive symptoms, and perceived happiness were compared between working cancer survivors and cancer-free workers with multivariable logistic regression analysis adjusted for age and sociodemographic and health-related backgrounds. RESULTS: Of the 28,311 male and 26,068 female workers, 977 (3.5%) and 1267 (4.9%) were cancer survivors, respectively. Working cancer survivors reported deteriorated SRHS more frequently than cancer-free workers: 21.3% vs. 13.8%, multivariable-adjusted odds ratio (95% confidence interval), 1.64 (1.39-1.95) for men, 23.8% vs. 17.5%, 1.34 (1.16-1.54) for women. Restricted physical functional capacity was reported more frequently in working cancer survivors than cancer-free workers: 6.8% vs. 2.6%, 1.76 (1.34-2.32) for men, 4.9% vs. 2.0%, 2.06 (1.56-2.71) for women. No significant difference was found for depressive symptoms: 21.6% vs. 22.9% in men, 30.0% vs. 28.5% in women. Working cancer survivors felt happiness more frequently than cancer-free survivors in men (77.3% vs. 71.7%, 1.21 (1.01-1.45)) but not in women (76.1% vs. 74.9%). CONCLUSIONS: Working cancer survivors had worse SRHS and more restricted physical functional capacity than cancer-free workers. In men, working cancer survivors felt happiness more frequently than cancer-free workers. IMPLICATIONS FOR CANCER SURVIVORS: Continuous support to improve cancer survivors' SRHS and physical functional capacity would be necessary even while they are working.

DOI： 10.1007/s11764-020-00984-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Although preclinical studies suggest that fermented soy foods may have a protective effect against breast cancer, no prospective cohort studies have examined this association. OBJECTIVE: Our study examined the association between fermented and nonfermented soy food intake and breast cancer risk using a population-based prospective cohort study in Japan. METHODS: We included a total of 47,614 women aged 45-74 years in an analysis of the Japan Public Health Center-based Prospective Study (JPHC Study). A validated food frequency questionnaire (FFQ) was used for the assessment of dietary intake. Breast cancer incidence was analyzed by multivariate Cox proportional hazards regression models. RESULTS: During an average of 15.5 years of follow-up, 825 breast cancer cases were newly identified. We found no association of intake of soy foods with breast cancer risk, regardless of fermentation, with multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) for the highest quartiles of fermented and nonfermented soy food intake of 0.94 (0.67, 1.32) and 1.15 (0.85, 1.57) compared with the lowest quartile (p for trend = 0.305 and 0.393). Unlike nonfermented soy, higher intake of fermented soy foods was associated with a significant decrease in the risk of nonlocalized breast cancer. The HR and 95% CI in the highest compared to lowest intake category of fermented soy foods was 0.53 (0.28, 0.99) versus nonfermented soy foods 0.85 (0.51, 1.42) (p for trend = 0.026 and 0.797). CONCLUSIONS: Our analyses showed that fermented soy foods had no association with overall breast cancer but may be associated with decreased risk of nonlocalized breast cancer.

DOI： 10.1002/cam4.3677

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記述言語：日本語   出版者・発行元：(一社)日本疫学会  

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記述言語：日本語   出版者・発行元：(一社)日本疫学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objective: There is scarce evidence regarding the long-term persistence of neutralizing antibodies among coronavirus disease 2019 (COVID-19) survivors. This study determined neutralizing antibody titers (NT50) and antibodies against spike protein (SP) or nucleocapsid protein (NP) antigens approximately 6 months after the diagnosis of COVID-19. Methods: COVID-19 survivors in Japan were recruited. Serum samples and data related to patients' characteristics and COVID-19 history were collected. NT50 and titers of antibodies against NP and SP antigens were measured at 20-32 weeks after the first positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test results. Factors associated with NT50 were identified using the multivariable linear regression and the correlations among NT50 and titers of immunoglobulin G (IgG) and total immunoglobulins (Igs) against NP and SP were assessed by Spearman's correlation. Results: Among 376 participants (median [range] days after testing positive for SARS-CoV-2, 180 (147-224); median [range] years of age, 50 (20-78); 188 [50%] male), most tested positive for NT50 (n = 367, 98%), SP-IgG (n = 344, 91%), SP-total Ig (n = 369, 98%), NP-IgG (n = 314, 84%), and NP-total Ig (n = 365, 97%). Regression analysis indicated that higher BMI, fever, and the requirement of mechanical ventilation or extracorporeal membrane oxygenation were significantly associated with higher NT50. Anti-SP antibodies correlated moderately with NT50 (Spearman's correlation: 0.63 for SP IgG; 0.57 for SP-total Ig), while the correlation was weak for anti-NP antibodies (0.37 for NP IgG; 0.32 for NP-total Ig). Conclusions: Most COVID-19 survivors had sustained neutralizing antibodies and tested positive for SP-total Ig and NP-total Ig approximately 6 months after infection.

DOI： 10.3389/fmicb.2021.661187

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: It is unclear whether relatively low glycated haemoglobin (HbA1c) levels are beneficial or harmful for the long-term health outcomes among people without diabetes. We aimed to investigate the association between low HbA1c levels and mortality among the US general population. METHODS: This study includes a nationally representative sample of 39 453 US adults from the National Health and Nutrition Examination Surveys 1999-2014, linked to mortality data through 2015. We employed the parametric g-formula with pooled logistic regression models and the ensemble machine learning algorithms to estimate the time-varying risk of all-cause and cardiovascular mortality by HbA1c categories (low, 4.0 to <5.0%; mid-level, 5.0 to <5.7%; prediabetes, 5.7 to <6.5%; and diabetes, ≥6.5% or taking antidiabetic medication), adjusting for 72 potential confounders including demographic characteristics, lifestyle, biomarkers, comorbidities and medications. RESULTS: Over a median follow-up of 7.5 years, 5118 (13%) all-cause deaths, and 1116 (3%) cardiovascular deaths were observed. Logistic regression models and machine learning algorithms showed nearly identical predictive performance of death and risk estimates. Compared with mid-level HbA1c, low HbA1c was associated with a 30% (95% CI, 16 to 48) and a 12% (95% CI, 3 to 22) increased risk of all-cause mortality at 5 years and 10 years of follow-up, respectively. We found no evidence that low HbA1c levels were associated with cardiovascular mortality risk. The diabetes group, but not the prediabetes group, also showed an increased risk of all-cause mortality. CONCLUSIONS: Using the US national database and adjusting for an extensive set of potential confounders with flexible modelling, we found that adults with low HbA1c were at increased risk of all-cause mortality. Further evaluation and careful monitoring of low HbA1c levels need to be considered.

DOI： 10.1093/ije/dyaa263

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Confounding adjustment is important for observational studies to derive valid effect estimates for inference. Despite the theoretical advancement of confounding selection procedure, it is often challenging to distinguish between confounders and mediators due to the lack of information about the time-ordering and latency of each variable in the data. This is also the case for the studies of perfluoroalkyl substances (PFAS), a group of synthetic chemicals used in industry and consumer products that are persistent and have endocrine-disrupting properties on health outcomes. In this article, we used directed acyclic graphs to describe potential biases introduced by adjusting for or stratifying by the measure of obesity as an intermediate variable in PFAS exposure analyses. We compared results with or without adjusting for body mass index in two cross-sectional data analyses: (1) PFAS levels and maternal thyroid function during early pregnancy using the Danish National Birth Cohort and (2) PFAS levels and cardiovascular disease in adults using the National Health and Nutrition Examination Survey. In these examples, we showed that the potential heterogeneity observed in stratified analyses by overweight or obese status needs to be interpreted cautiously considering collider stratification bias. This article highlights the complexity of seemingly simple adjustment or stratification analyses, and the need for careful consideration of the confounding and/or mediating role of obesity in PFAS studies.

DOI： 10.3390/toxics8040125

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: To provide updated systematic and quantitative summary of the association between depression and the risk of CVD events among individuals with type 2 diabetes. We also aimed to examine the sensitivity of the association to uncontrolled confounding. METHODS: Data sources included Medline, Embase, and PsycInfo through September 2019. Two independent reviewers selected cohort studies that evaluated the association between depression and fatal or non-fatal CVD events among individuals with type 2 diabetes. Bias analysis was performed using the bias formula approach. RESULTS: Of 2527 citations screened, 17 eligible studies with a total of 1,033,131 participants were identified. Based on random-effects meta-analysis, depression was associated with higher risks of non-fatal CVD events (relative risk 1.35, 95% confidence interval [CI] 1.20 to 1.53) and fatal CVD event (relative risk 1.47, 95% CI 1.21 to 1.77). Bias analysis indicated that unmeasured confounders alone may not explain the observed association between depression and CVD events among individuals with type 2 diabetes. CONCLUSIONS: Depression was associated with a higher risk of non-fatal and fatal CVD events among individuals with type 2 diabetes. Our findings provide updated and robust evidence about the association between depression and CVD events among individuals with type 2 diabetes.

DOI： 10.1016/j.jdiacomp.2020.107710

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記述言語：英語  

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

DOI： 10.1038/s41598-020-70072-4

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記述言語：英語   出版者・発行元：(一社)日本癌学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

The well-known gene-environment interaction between alcohol consumption and aldehyde dehydrogenase 2 (ALDH2) genotype in upper aerodigestive tract cancer risk may improve our ability to identify high-risk subjects. Here, we developed and validated risk prediction models for this cancer in Japanese men and evaluated whether adding the gene-environment interaction to the model improved the predictive performance. We developed two case-cohort datasets in the Japan Public Health Center-based Prospective Study: one from subjects in the baseline survey for model development (108 cases and 4049 subcohort subjects) and the second from subjects in the 5-year follow-up survey for model validation (31 cases and 1527 subcohort subjects). We developed an environmental model including age, smoking status, and alcohol consumption, and a gene-environment interaction model including age, smoking status, and the combination of alcohol consumption and the ALDH2 genotype. We found a statistically significant gene-environment interaction for alcohol consumption and the ALDH2 genotype. The c-index for the gene-environment interaction model (0.71) was slightly higher than that for the environmental model (0.67). The values of integrated discrimination improvement and net reclassification improvement for the gene-environment interaction model were also slightly higher than those for the environmental model. Goodness-of-fit tests suggested that the models were well calibrated. Results from external model validation by the 5-year follow-up survey were consistent with those from the model development by the baseline survey. The addition of a gene-environment interaction to a lifestyle-based model might improve the performance to estimate the probability of developing upper aerodigestive tract cancer for Japanese men.

DOI： 10.1111/cas.14573

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Although intake of highly sugary foods is considered to be a potential risk factor for colorectal cancer through hyperinsulinemia, the association of sugar intake and colorectal adenoma, a precursor lesion to most colorectal cancer, is poorly understood, particularly in Asian populations. We undertook a cross-sectional study in a Japanese population to investigate the association between dietary sugar intake and the prevalence of colorectal adenoma. Study subjects were selected from participants who underwent magnifying colonoscopy with dye spraying as part of a cancer screening program and who responded to a self-administered questionnaire before the colonoscopy. A total of 738 cases with colorectal adenoma and 697 controls were enrolled. Dietary intakes of glucose, fructose, galactose, sucrose, maltose, lactose, and total sugars (sum of these six mono- or disaccharides) were calculated from a food frequency questionnaire, and divided into quartiles based on the distribution among controls. Odds ratios and 95% confidence intervals of colorectal adenoma were estimated using unconditional logistic regression models, with adjustment for potential confounding factors. Total sugar intake was not significantly associated with the prevalence of colorectal adenoma (odds ratio for the highest intake group compared to reference group = 1.18; 95% confidence interval, 0.81-1.73; P for trend = .34). Furthermore, no statistically significant positive associations were observed for any of the six mono- or disaccharides. Findings were similar on additional analyses by site, size, and number of adenomas. Our findings do not support an association between high sugar intake and increased odds ratios of colorectal adenoma.

DOI： 10.1111/cas.14596

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Soy is commonly consumed in east Asian countries and is suggested to reduce colorectal cancer (CRC) risk. However, results from epidemiologic studies are inconsistent, despite the anti-inflammatory and antiproliferative properties of soy isoflavones and soy protein. OBJECTIVE: We evaluated the association between soy isoflavones and soy protein and CRC risk using 4 prospective cohort studies from China and Japan. METHODS: Data were pooled from the Shanghai Women's Health Study (SWHS), Shanghai Men's Health Study (SMHS), Japan Public Health Center-based Prospective Study Cohort 1 (JPHC1), and Cohort 2 (JPHC2). Cox proportional hazards models estimated HRs and corresponding 95% CIs for the association of soy protein and isoflavone intake with CRC risk. The study included 205,060 individuals, among whom 2971 were diagnosed with incident CRC over an average follow-up of 12.7 y. RESULTS: No statistically significant associations with CRC risk were observed for soy protein or isoflavone intake. No association was observed among ever smokers consuming higher isoflavones (HRisoflavones: 0.83; 95% CI: 0.68, 1.00) and soy protein (HRsoy protein: 0.81; 95% CI: 0.39, 1.10). However, risk reductions were observed among premenopausal women with a body mass index [BMI (kg/m2)] <23.0 at baseline for higher isoflavone (HRisoflavones: 0.58, 95% CI: 0.34, 0.98). CONCLUSIONS: No evidence for an overall reduction in CRC risk by increasing soy food intake (i.e., protein or isoflavones) was observed. However, the association between soy and CRC risk may vary by BMI, smoking, and menopausal status among women. Future investigations are needed to further understand the biologic mechanisms observed.

DOI： 10.1093/jn/nxaa194

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.clnu.2020.09.022

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS/INTRODUCTION: The aim of the current study was to prospectively evaluate the association between passive smoking from a spouse and the risk of diabetes among never-smoking Japanese women. Passive smoking at a workplace (or public facilities) was assessed as a secondary measure. MATERIALS AND METHODS: In the Japan Public Health Center-based Prospective Study (baseline 1990 or 1993), we followed 25,391 never-smoking women aged 40-69 years and without diabetes. Passive smoking was defined as having a husband who was a self-reported smoker, and the exposure at a workplace (or public facilities) was self-reported by women. The development of diabetes was identified in questionnaires administered at the 5-year and 10-year surveys. A pooled logistic regression model was used to assess the association between passive smoking and the development of diabetes with adjustment for age and possible confounders. RESULTS: Compared with women whose husbands had never smoked, women whose husband smoked ≥40 cigarettes/day had significantly higher odds of developing diabetes in an age-adjusted model, but the association was attenuated in a multivariable model (odds ratio 1.34, 95% confidence interval 0.96-1.87). There was a dose-response trend between the number of cigarettes smoked by a husband and the odds of developing diabetes (P = 0.02). Women reporting daily passive smoking at a workplace (or public facilities) had higher odds of developing diabetes than women reporting no such exposure (odds ratio 1.23, 95% confidence interval 0.995-1.53). CONCLUSIONS: Our results indicated a higher risk of diabetes among never-smoking Japanese women with higher exposure to passive smoking from a spouse.

DOI： 10.1111/jdi.13259

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Cancer patients with diabetes experience a poorer prognosis, yet the population burden of this multimorbidity remains unknown. This study aimed to estimate the latest incidence and prevalence of cancer with diabetes mellitus in Japan. We used projection of cancer incidence and latest survival data from population-based cancer registries. The incidence of cancer associated with diabetes was estimated separately for patients with pre-existing diabetes and those without diabetes, and used to estimate the 5-year cancer prevalence for those with and without diabetes. The prevalence of pre-existing diabetes in cancer patients at any cancer site was estimated to be 20.7% (647,160 men and women). Among cancer sites, diabetes prevalence was high in patients with liver and pancreatic cancers in both sexes. In conclusion, our study shows a large burden of diabetes in cancer patients in Japan, which warrants further attention by health practitioners and policy-makers.

DOI： 10.1111/jdi.13231

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Family history (FH) of cancer is an important factor of increased risk of several cancers. Although the association between FH of cancer and concordant cancer risk has been reported in many previous epidemiological studies, no comprehensive prospective study with adjustment for lifestyle habits has evaluated the association of FH of cancer and concordant cancer risk. We investigated the association between FH of cancer and concordant cancer risk in a Japanese population-based prospective study, initiated in 1990 for cohort I and in 1993 for cohort II. We analyzed data on 103,707 eligible subjects without a history of cancer who responded to a self-administered questionnaire including FH of cancer at baseline. Study subjects were followed through 2012 and analyzed using multivariable-adjusted Cox proportional hazards regression models. During 1,802,581 person-years of follow-up, a total of 16,336 newly diagnosed cancers were identified. Any site (Hazard ratios = 1.11 (95% confidence interval = 1.07-1.15]), esophagus (2.11 [1.00-4.45]), stomach (1.36 [1.19-1.55]), liver (1.69 [1.10-2.61]), pancreas (2.63 [1.45-4.79]), lung (1.51 [1.14-2.00]), uterus (1.93 [1.06-3.51]) and bladder cancers (6.06 [2.49-14.74]) with FH of the concordant cancer were associated with an increased risk compared to those without FH. Our findings suggest that having FH of cancer is associated with an increased risk of several concordant cancer incidences in an Asian population. Enquiring about FH of several types of cancer may be important in identifying groups at high-risk of those cancers.

DOI： 10.1002/ijc.32724

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s13340-020-00439-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/jdi.13306

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Pancreatic cancer is the fourth leading cause of cancer-related deaths in Japan. To identify risk loci, we perform a meta-analysis of three genome-wide association studies comprising 2,039 pancreatic cancer patients and 32,592 controls in the Japanese population. Here, we identify 3 (13q12.2, 13q22.1, and 16p12.3) genome-wide significant loci (P < 5.0 × 10-8), of which 16p12.3 has not been reported in the Western population. The lead single nucleotide polymorphism (SNP) at 16p12.3 is rs78193826 (odds ratio = 1.46, 95% confidence interval = 1.29-1.66, P = 4.28 × 10-9), an Asian-specific, nonsynonymous glycoprotein 2 (GP2) gene variant. Associations between selected GP2 gene variants and pancreatic cancer are replicated in 10,822 additional cases and controls of East Asian origin. Functional analyses using cell lines provide supporting evidence of the effect of rs78193826 on KRAS activity. These findings suggest that GP2 gene variants are probably associated with pancreatic cancer susceptibility in populations of East Asian ancestry.

DOI： 10.1038/s41467-020-16711-w

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

AIM: To examine the association between body mass index (BMI) and mortality among middle-aged people with diabetes in Japan. METHODS: A total of 3032 men and 1615 women, aged 40-69 years, with diabetes were analyzed. Cox proportional hazards models, adjusted for potential confounding factors, were used to estimate mortality hazard ratios (HRs) across BMI categories at the baseline. RESULTS: There were 1761 deaths during a mean follow-up period of 18.5 years. Increased all-cause mortality was observed at both ends of the BMI distribution; compared with the reference BMI category (23.0-24.9 kg/m2), the HRs were 1.25 (95% confidence interval [CI], 0.9997-1.56) in the lowest (14.0-18.9 kg/m2) and 1.36 (95% CI, 1.06-1.74) in the highest (30.0-39.9 kg/m2) categories (P = 0.001). Similar all-cause mortality trends were observed after excluding deaths within 3 years of follow-up, as well as for men and men who had ever smoked. While a similar non-linear pattern was observed for cancer-specific mortality, heart disease-specific mortality was only increased in the highest BMI category (HR, 1.86; 95% CI, 1.06-3.25). CONCLUSION: This population-based prospective study demonstrated increased all-cause mortality at both ends of the BMI distribution among Japanese people with diabetes.

DOI： 10.1016/j.diabres.2020.108198

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Although the poor prognosis and increasing incidence of pancreatic cancer highlight the need for prevention strategies, few lifestyle risk factors for pancreatic cancer have yet been identified. Soybeans contain various bioactive compounds. However, the association between soy food intake and pancreatic cancer risk remains unknown. METHODS: The Japan Public Health Center-based Prospective Study is a cohort study conducted in a general Japanese population. To determine the association of soy food intake and pancreatic cancer incidence, we analyzed 90,185 participants who responded to a questionnaire on medical history and lifestyle factors, including dietary factors based on a food frequency questionnaire in 1995-1998, using Cox proportional hazards models. RESULTS: During a median follow-up of 16.9 years, 577 cases of pancreatic cancer were identified. In the multivariate-adjusted model, total soy food intake was statistically significantly associated with an increased risk of pancreatic cancer [HR for the highest vs. lowest intake quartile: 1.48; 95% confidence interval (CI), 1.15-1.92; Ptrend = 0.007]. Among soy foods, nonfermented soy food intake showed a statistically significant positive association with pancreatic cancer (HR, 1.41; 95% CI, 1.09-1.81; Ptrend = 0.008), whereas fermented soy food intake showed no association (HR, 0.96; 95% CI, 0.73-1.26; Ptrend = 0.982). CONCLUSIONS: Higher intake of soy foods, particularly nonfermented soy foods, might increase pancreatic cancer risk. IMPACT: This study is the first to report an association between the intake of various soy foods and pancreatic cancer risk. Further studies are required to confirm our findings.

DOI： 10.1158/1055-9965.EPI-19-1254

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Some Okinawan vegetables have been reported to have anti-diabetic activity; however, no prospective cohort study has clarified whether consumption of Okinawan vegetables is associated with a risk of type 2 diabetes. This study aimed to determine the association between consumption of Okinawan vegetables and risk of type 2 diabetes through a large-scale, population-based, prospective study in Japan. METHODS: We examined 10,732 participants (4,714 men and 6,018 women) aged 45-74 years who resided in Okinawa. Participants were asked to answer a 147-item food frequency questionnaire. We calculated the overall amount of Okinawan vegetables consumed and the amount of seven specific kinds of Okinawan vegetables consumed. The odds ratios (ORs) for self-reported type 2 diabetes during 5 years of follow-up were estimated via multivariate logistic regression analysis. RESULTS: During the 5-year period, 216 new cases (123 men and 93 women) of type 2 diabetes were reported. Comparing the highest tertile to the lowest tertile of intake, the overall amount of Okinawan vegetables consumed was not associated with risk of type 2 diabetes in men (OR 1.22; 95% confidence interval [CI], 0.74-2.01, P-trend = 0.53) or in women (OR 0.96; 95% CI, 0.57-1.62, P-trend = 0.89). The consumption of seven specific kinds of Okinawan vegetables was also not associated with the risk of type 2 diabetes. CONCLUSIONS: The consumption of total Okinawan vegetables was not associated with the risk of type 2 diabetes.

DOI： 10.2188/jea.JE20180262

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: An inverse association has been shown between dietary fiber intake and several noncommunicable diseases. However, evidence of this effect remains unclear in the Asian population. OBJECTIVE: We examined the association between dietary fiber intake and all-cause and cause-specific mortality, as well as the association between fiber intake from dietary sources and all-cause mortality. METHODS: We conducted a large-scale population-based cohort study (Japan Public Health Center-based prospective study). A validated questionnaire with 138 food items was completed by 92,924 participants (42,754 men and 50,170 women) aged 45-74 y. Dietary fiber intake was calculated and divided into quintiles. HR and 95% CI of total and cause-specific mortality were reported. RESULTS: During the mean follow-up of 16.8 y, 19,400 deaths were identified. In multivariable adjusted models, total, soluble, and insoluble fiber intakes were inversely associated with all-cause mortality. The HRs of total mortality in the highest quintile of total fiber intake compared with the lowest quintile were 0.77 (95% CI: 0.72, 0.82; Ptrend <0.0001) in men and 0.82 (95% CI: 0.76, 0.89; Ptrend <0.0001) in women. Increased quintiles of dietary fiber intake were significantly associated with decreased mortality due to total cardiovascular disease (CVD), respiratory disease, and injury in both men and women, whereas dietary fiber intake was inversely associated with cancer mortality in men but not women. Fiber from fruits, beans, and vegetables, but not from cereals, was inversely associated with total mortality. CONCLUSION: In this large-scale prospective study with a long follow-up period, dietary fiber was inversely associated with all-cause mortality. Since intakes of dietary fiber, mainly from fruits, vegetables, and beans were associated with lower all-cause mortality, these food sources may be good options for people aiming to consume more fiber.

DOI： 10.1093/ajcn/nqaa002

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Although occupational sitting time has been associated with adverse health outcomes and mortality, the association with cancer incidence remains unknown. This study investigated the association between occupational sitting time and risk of total and site-specific cancer in a Japanese population. We evaluated 33 307 participants aged 50-79 years who responded to a questionnaire in 2000-2003 in the Japan Public Health Center-based Prospective Study and were followed until 2013. Participants were grouped by sitting time at work. Hazard ratio (HR) and 95% confidence interval (CI) of cancer incidence were calculated with adjustment for potential confounders including moderate-to-vigorous physical activity. During 10.2 years of follow-up, 3807 newly diagnosed cases of cancer were identified. Occupational sitting time was marginally associated with total cancer, with multivariable HRs for the ≥7 h/d vs 1 to <3 h/d category of 1.12 (95% CI, 0.99-1.26; P for trend = .071) in men, but not women. Among findings for cancers at specific sites, long occupational sitting time was associated with increased risk of pancreas cancer, with multivariable HRs for the ≥7 h/d vs 1 to <3 h/d category of 2.25 (95% CI, 1.17-4.34; P for trend = .021) in men, and lung cancer, with multivariable HRs for the ≥7 h/d vs 1 to <3 h/d category of 2.80 (95% CI, 1.33-5.90; P for trend = .013) in women. Extended sitting time at work was associated with an increased risk of pancreas cancer in men and lung cancer in women.

DOI： 10.1111/cas.14304

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We aimed to assess whether a triple-faceted intervention program administered in the primary care setting could decrease the risk of insufficient adherence to primary care physician (PCP) appointments among this patient population. We conducted a cluster-randomized controlled study to assess the effects of a 1-year intervention. The primary outcome was insufficient adherence to regular PCP attendance for diabetes treatment, defined as failure to visit a PCP within 2 months of an original appointment date. The intervention consisted of mailing patient reminders of their PCP appointments, providing patients with health education aimed at lifestyle modification and benchmarking PCP procedures. Eleven municipal level district medical associations employing 192 PCPs were divided into two subregions for assignment to intervention and control clusters, with 971 and 1,265 patients assigned to the intervention and control groups, respectively. Primary outcome data were available for 2,200 patients. The intervention reduced insufficient adherence to regular PCP appointments by 63% (hazard ratio, 0.37; 95% confidence interval [CI], 0.23-0.58). In conclusion, a triple-faceted intervention program consisting of health education, appointment reminders, and physician benchmarking may decrease the risk of incomplete adherence to regular PCP appointments by diabetes patients.

DOI： 10.1038/s41598-020-59588-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Alcohol drinking is a risk factor for cancer. The degree of risk is increased in subjects showing the flushing response, which is due to aldehyde dehydrogenase 2 (ALDH2) polymorphism. The attributable risk of alcohol drinking for cancer in Japan has not been sufficiently investigated with consideration of flushing response. We followed 78,825 Japanese in JPHC study cohort II. The association between alcohol consumption and cancer incidence was assessed according to self-reported flushing response using Cox proportional hazards regression models. The population-attributable fraction (PAF) of cancer incidence was also estimated. During 1993-2013 (average follow-up, 16.8 years), 8486 incident cancers (included 4386 alcohol-related cancers) were reported. Half of men and 36% of women had flushing response. In men with flushing response, moderate or higher alcohol drinking increased the risk of alcohol-related cancers compared with non-drinkers (150-299 g/week, HR 1.63, 95% CI, 1.43-1.99; 300-449 g/week, HR 2.02 95% CI, 1.67-2.44; ≥450 g/week, HR 1.75, 95% CI, 1.39-2.21). When flushing response was considered in comparisons between non-drinkers and non-flushers, non-flushing heavy drinkers had a slightly higher PAF than flushers (all cancers: flushers, 2.0% and non-flushers, 2.2%; alcohol-related cancers: flushers, 3.8% and non-flushers, 5.8%). Although the risk of alcohol-related cancer in men with flushing response increased with increasing alcohol consumption, heavy drinkers were also at high risk regardless of flushing response. Considering the PAF of alcohol consumption on cancer, efforts to discourage heavy alcohol consumption to reduce the incidence of alcohol-related cancers appear warranted regardless of flushing response.

DOI： 10.1016/j.ypmed.2020.106026

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BackgroundShort and long sleep durations are associated with mortality outcomes. The association between sleep duration and mortality outcomes may differ according to sex and age.MethodsParticipants of the Japan Public Health Center-based prospective study (JPHC Study) were aged 40-69 years and had completed a detailed questionnaire on lifestyle factors. Sex- and age-stratified analyses on the association between habitual sleep duration and mortality from all-causes, cardiovascular diseases (CVD), cancer and other causes included 46,152 men and 53,708 women without a history of CVD or cancer. Cox proportional hazards regression models, adjusted for potential confounders, were used to determine hazard ratios and 95% confidence intervals.ResultsMean follow-up time was 19.9 years for men and 21.0 years for women. In the multivariable sex-stratified models, and compared with 7 hours, some categories of sleep durations ≥ 8 hours were positively associated with mortality from all-causes, CVD, and other causes in men and women.The sex- and age-stratified analyses did not reveal any major differences in the association between sleep duration and mortality outcomes in groups younger and older than 50 years of age. The only exception was the significant interaction between sleep duration and age in women for mortality from other causes.ConclusionsSleep durations ≥8 hours are associated with mortality outcomes in men and women. Age may be an effect modifier for the association between sleep duration and mortality from other causes in women.

DOI： 10.2188/jea.JE20190210

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Serologic testing of anti-Helicobacter pylori antibody, together with testing of pepsinogen I and II, is now widely used to stratify groups at high risk of gastric cancer in Japan. Those with a negative anti-H. pylori IgG titer, especially "high-negative" (3-<10 U/mL), are speculated to have higher risk of gastric cancer. We aimed to evaluate the association between a high-negative anti-H. pylori IgG titer and the long-term risk of gastric cancer in the Japan Public Health Center-based Prospective Study (JPHC Study) Cohort II. METHODS: The study population consisted of 19,106 Japanese men and women who were followed from 1993 to 2013. A Cox proportional hazards model was used to assess the risk of gastric cancer for plasma anti-H. pylori IgG titers, together with the severity of atrophic gastritis by pepsinogen I and II levels. A total of 595 cases of gastric cancer occurred during an average of 18 years of follow-up. RESULTS: Compared with those with a low-negative anti-H. pylori IgG titer (≤3 U/mL), subjects with a high-negative titer (3-<10 U/mL) showed a significantly elevated risk of gastric cancer [HR = 2.81; 95% confidence interval (CI) = 1.62-4.89]. Among those with a high-negative titer, risk increase was observed under moderate or severe atrophic gastritis (HR = 18.73; 95% CI = 8.83-39.70). CONCLUSIONS: Our results suggest that those with a high-negative anti-H. pylori IgG titer and moderate and severe atrophic gastritis are at increased long-term risk of gastric cancer. IMPACT: Development of moderate or severe atrophic gastritis in subjects with high-negative anti-H. pylori IgG titer is suggested to increase risk of gastric cancer.

DOI： 10.1158/1055-9965.EPI-19-0993

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: To investigate the association between several types of soy products and all cause and cause specific mortality. DESIGN: Population based cohort study. SETTING: Japan Public Health Centre-based Prospective Study, which includes 11 public health centre areas in Japan. PARTICIPANTS: 92 915 participants (42 750 men and 50 165 women) aged 45 to 74 years. EXPOSURES: Intake of total soy products, fermented soy products (natto and miso), non-fermented soy products, and tofu from a five year survey questionnaire. MAIN OUTCOME MEASURES: All cause and cause specific mortality (cancer, total cardiovascular disease, heart disease, cerebrovascular disease, respiratory disease, and injury) obtained from residential registries and death certificates. RESULTS: During 14.8 years of follow-up, 13 303 deaths were identified. In the multivariable adjusted models, intake of total soy products was not significantly associated with total mortality. Compared with the lowest fifth of total soy product intake, the hazard ratios in the highest fifth were 0.98 (95% confidence interval 0.91 to 1.06, Ptrend=0.43) in men and 0.98 (0.89 to 1.08, Ptrend=0.46) in women. Intake of fermented soy products was inversely associated with all cause mortality in both sexes (highest versus lowest fifth: 0.90 (0.83 to 0.97), Ptrend=0.05 in men, and 0.89 (0.80 to 0.98), Ptrend=0.01 in women). Natto showed significant and inverse associations with total cardiovascular disease related mortality in both sexes. CONCLUSIONS: In this study a higher intake of fermented soy was associated with a lower risk of mortality. A significant association between intake of total soy products and all cause mortality was not, however, observed. The findings should be interpreted with caution because the significant association of fermented soy products might be attenuated by unadjusted residual confounding.

DOI： 10.1136/bmj.m34

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Lifestyle and life-environment factors have undergone drastic changes in Japan over the last few decades. Further, many molecular epidemiologic studies have reported that genetic, epigenetic, and other biomarker information may be useful in predicting individual disease risk. METHODS: The Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT) was launched in 2011 to identify risk factors for lifestyle-related disease, elucidate factors that extend healthy life expectancy, and contribute toward personalized healthcare based on our more than 20 years' experience with the JPHC Study. From 2011 through 2016, a baseline survey was conducted at 16 municipalities in seven prefectures across the country. A self-administered questionnaire was distributed to all registered residents aged 40-74, which mainly asked about lifestyle factors, such as socio-demographic situation, personal medical history, smoking, alcohol and dietary habits. We obtained informed consent from each participant to participate in this long follow-up study of at least 20 years, including consent to the potential use of their residence registry, medical records, medical fee receipts, care insurance etc., and to the provision of biospecimens (blood and urine), including genomic analysis. RESULTS: As of December 31, 2016, we have established a population-based cohort of 115,385 persons (Response rate 44.1%), among whom 55,278 (47.9% of participants) have provided blood and urine samples. The participation rate was slightly higher among females and in the older age group. CONCLUSION: We have established a large-scale population-based cohort for next-generation epidemiological study in Japan.

DOI： 10.2188/jea.JE20180182

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: This population-based, cross-sectional study was performed to assess the influence of life-style modalities, including physical activity, sedentary behaviors, and visual display terminal (VDT) use, on the prevalence of dry eye disease (DED). METHODS: The study included a total of 102,582 participants aged 40-74 years, from the Japan Public Health Center-based Prospective Study for the Next Generation, a large nationwide prospective ongoing Japanese cohort study. Logistic regression analyses were used to investigate the relationship of total and leisure-time physical activity, duration of sedentary behaviors, and VDT use (hours/day) with DED. RESULTS: Among 47,346 men and 55,236 women, 25,234 (8315 males and 16,919 females) cases of DED were documented. Total physical activity was significantly related to decreased DED in both sexes; for the highest vs. lowest total physical activity quartiles, the multivariable-adjusted odds ratios (ORs) for DED were 0.90 (95% confidence interval [CI], 0.84-0.97; Ptrend<0.03) and 0.91 (95% CI, 0.86-0.95; Ptrend<0.001) for men and women, respectively. Conversely, prolonged sedentary behaviors and VDT use had significantly higher prevalence of DED in both sexes (Ptrend<0.001). Notably, the favorable effect of total physical activity on decreased DED in women was more prevalent with prolonged VDT use (≥2 h/day) (Pinteraction<0.01). In men, the duration of VDT use or sitting was a significant modifier of the inverse relationship between leisure-time physical activity and DED (Pinteraction<0.05). CONCLUSIONS: Physical inactivity, prolonged sedentary behaviors, and use of VDT were related to increased susceptibility to DED among middle-aged to older Japanese adults.

DOI： 10.1016/j.jtos.2019.09.007

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objectives: Serological tests for COVID-19 have been instrumental in studying the epidemiology of the disease. However, the performance of the currently available tests is plagued by the problem of variability. We have developed a high-throughput serological test capable of simultaneously detecting total immunoglobulins (Ig) and immunoglobulin G (IgG) against nucleocapsid protein (NP) and spike protein (SP) and report its performance in detecting COVID-19 in clinical samples. Methods: We designed and prepared reagents for measuring NP-IgG, NP-Total Ig, SP-IgG, and SP-Total Ig (using N-terminally truncated NP (ΔN-NP) or receptor-binding domain (RBD) antigen) dedicated automated chemiluminescent enzyme immunoassay analyzer AIA-CL1200. After determining the basal thresholds based on 17 sera obtained from confirmed COVID-19 patients and 600 negative sera, the clinical validity of the assay was evaluated using independent 202 positive samples and 1,000 negative samples from healthy donors. Results: All of the four test parameters showed 100% specificity individually (1,000/1,000; 95%CI, 99.63-100). The sensitivity of the assay increased proportionally to the elapsed time from symptoms onset, and all the tests achieved 100% sensitivity (153/153; 95%CI, 97.63-100) after 13 days from symptoms onset. NP-Total Ig was the earliest to attain maximal sensitivity among the other antibodies tested. Conclusion: Our newly developed serological testing exhibited 100% sensitivity and specificity after 13 days from symptoms onset. Hence, it could be used as a reliable method for accurate detection of COVID-19 patients and to evaluate seroprevalence and possibly for surrogate assessment of herd immunity.

DOI： 10.3389/fmicb.2020.628281

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Importance: Epidemiological evidence regarding the long-term effects of higher dietary protein intake on mortality outcomes in the general population is not clear. Objective: To evaluate the associations between animal and plant protein intake and all-cause and cause-specific mortality. Design, Setting, and Participants: This prospective cohort study included 70 696 participants in the Japan Public Health Center-based Prospective Cohort who were aged 45 to 74 years and had no history of cancer, cerebrovascular disease, or ischemic heart disease at study baseline. Data were collected from January 1, 1995, through December 31, 1999, with follow-up completed December 31, 2016, during which 12 381 total deaths were documented. Dietary intake information was collected through a validated food frequency questionnaire and used to estimate protein intake in all participants. Participants were grouped into quintile categories based on their protein intake, expressed as a percentage of total energy. Data were analyzed from July 18, 2017, through April 10, 2019. Main Outcomes and Measures: Hazard ratios (HRs) and 95% CIs for all-cause and cause-specific mortality were estimated using Cox proportional hazards regression models with adjustment for potential confounding factors. Results: Among the 70 696 participants, 32 201 (45.5%) were men (mean [SD] age, 55.6 [7.6] years) and 38 495 (54.5%) were women (mean [SD] age, 55.8 [7.7] years). Intake of animal protein showed no clear association with total or cause-specific mortality. In contrast, intake of plant protein was associated with lower total mortality, with multivariable-adjusted HRs of 0.89 (95% CI, 0.83-0.95) for quintile 2; 0.88 (95% CI, 0.82-0.95) for quintile 3; 0.84 (95% CI, 0.77-0.92) for quintile 4; and 0.87 (95% CI, 0.78-0.96) for quintile 5, with quintile 1 as the reference category (P = .01 for trend). For cause-specific mortality, this association with plant protein intake was evident for cardiovascular disease (CVD)-related mortality (HRs, 0.84 [95% CI, 0.73-0.96] to 0.70 [95% CI, 0.59-0.83]; P = .002 for trend). Isocaloric substitution of 3% energy from plant protein for red meat protein was associated with lower total (HR, 0.66; 95% CI, 0.55-0.80), cancer-related (HR, 0.61; 95% CI, 0.45-0.82), and CVD-related (HR, 0.58; 95% CI, 0.39-0.86) mortality; substitution for processed meat protein was associated with lower total (HR, 0.54; 95% CI, 0.38-0.75) and cancer-related (HR, 0.50; 95% CI, 0.30-0.85) mortality. Conclusions and Relevance: In this large prospective study, higher plant protein intake was associated with lower total and CVD-related mortality. Although animal protein intake was not associated with mortality outcomes, replacement of red meat protein or processed meat protein with plant protein was associated with lower total, cancer-related, and CVD-related mortality.

DOI： 10.1001/jamainternmed.2019.2806

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Although empirical data suggest a possible link between female reproductive events and risk of nonfatal accidents and suicidal behaviors, evidence to determine these effects on mortality is scarce. This study investigated the association between female reproductive factors and the risk of external causes of death among middle-aged Japanese women. We used a population-based cohort study consisting of 71 698 women residing in 11 public health center areas across Japan between 1990 and 1994. Multivariable-adjusted Cox proportional hazard regression models were used to estimate hazard ratios (HRs) of the risk of all external causes, suicide, and accidents according to female reproductive factors at the baseline survey. During 1 028 583 person-years of follow-up for 49 279 eligible subjects (average 20.9 years), we identified 328 deaths by all injuries. Among parous women, ever versus never breastfeeding [0.67 (95% CI: 0.49-0.92)] was associated with a decreased risk of all injuries. Risk of suicide was inversely associated with ever versus never parity [0.53 (95% CI: 0.32-0.88)]. A lower risk of death by accidents was seen in ever breastfeeding [0.63 (95% CI: 0.40-0.97)] compared to never breastfeeding. This study suggests that parity and breastfeeding are associated with reduced risk of death by all external causes, suicide and/or accidents among Japanese women.

DOI： 10.1038/s41598-019-50890-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Few studies have assessed associations of non-enzymatic antioxidant capacity (NEAC) in the overall diet with all-cause or specific mortality, and their results have been inconsistent. OBJECTIVES: The present study investigated the association between dietary NEAC and all-cause or cause-specific mortality. METHODS: The study was a large-scale population-based prospective cohort study in Japan consisting of 42,520 men and 50,207 women aged 44-76 y, who had no history of cancer, stroke, ischemic heart disease, or chronic liver disease. We evaluated FFQ-based dietary NEAC with use of published databases in which the NEACs of individual foods were analyzed by ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC) assays. Dietary NEAC was calculated by multiplying the estimated NEAC with the consumed amount and summing up those values for all foods, and was categorized in quartiles. We identified death and cause of death with use of residential registry and death certificates. HRs and 95% Cls for death from the second survey, which was conducted from April 1995 to December 2014 were estimated with Cox proportional hazards regression analysis. RESULTS: After 1,498,308 person-years of follow-up, 12,978 total deaths occurred. The multivariable-adjusted HRs (95% Cls) for all-cause mortality for the highest compared with the lowest quartile of FRAP and ORAC were 0.85 (0.80, 0.89) and 0.84 (0.79, 0.89), respectively. Dietary NEACs were inversely associated with mortality from cardiovascular disease (CVD), but not from cancer. The multivariable-adjusted HRs (95% Cls) for CVD for the highest compared with the lowest quartile of FRAP and ORAC were 0.83 (0.75, 0.92) and 0.79 (0.70, 0.89), respectively. CONCLUSIONS: Higher dietary NEACs from FRAP and ORAC were associated with lower risk of all-cause mortality and mortality from CVD in Japanese adults.

DOI： 10.1093/jn/nxz145

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We aimed to assess the association between cruciferous vegetable intake and colorectal cancer (CRC) development among Japanese adults aged between 45 and 74 years in the Japan Public Health Center-based Prospective Study. During 1 325 853 person-years of follow-up, 2612 CRC cases were identified. The association of cruciferous vegetable intake with CRC risk was assessed using a Cox proportional hazard regression model to compute hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for potential confounders. No significant association was observed between the highest cruciferous vegetable intake quartile (compared with the lowest) and CRC risk in men (multivariate HRs: 1.08; 95% CI: 0.91, 1.29) and women (multivariate HRs: 0.99; 95% CI: 0.80, 1.22) and its subsites. Women showed a marginal negative association between cruciferous vegetable intake and the risk of colon cancer (CC) after excluding participants who developed CC in the first 3 years of follow-up (P for trend = 0.08); a positive association was found with proximal CC in men. Cruciferous vegetable intake does not have a significant association with CRC risk in the Japanese general population.

DOI： 10.1097/CEJ.0000000000000491

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/ijc.32431

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記述言語：英語  

DOI： 10.1001/jamainternmed.2019.2806

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BackgroundFew studies examining the impact for women of employment status on health have considered domestic duties and responsibilities as well as household socioeconomic conditions. Moreover, to our knowledge, no studies have explored the influence of work-family conflict on the association between employment status and health. This research aimed to investigate the cross-sectional associations between employment status (regular employee, non-regular employee, or self-employed) with self-rated health among Japanese middle-aged working women.MethodsSelf-report data were obtained from 21,450 working women aged 40-59 years enrolled in the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT Study) in 2011-2016. Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for poor self-rated health ('poor' or 'not very good') by employment status. The sub-group analyses by household income and marital status as well as mediation analysis for work-family conflict were also conducted.ResultsAdjusted ORs for the poor self-rated health of non-regular employees and self-employed workers were 0.90 (95% CI, 0.83-0.98) and 0.84 (95% CI, 0.75-0.94), respectively, compared with regular employees. The identified association of non-regular employment was explained by work-family conflict. Subgroup analysis indicated no statistically significant modifying effects by household income and marital status.ConclusionAmong middle-aged working Japanese women, employment status was associated with self-rated health; non-regular employees and self-employed workers were less likely to report poor self-rated health, compared with regular employees. Lowered OR of poor self-rated health among non-regular employees may be explained by their reduced work-family conflict.

DOI： 10.2188/jea.JE20190005

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記述言語：英語  

PURPOSE: It is unclear whether habitual intake of soy or isoflavones induces long-term changes in the concentrations of blood lipids and glycaemia. We examined the associations of soy food and isoflavone consumption with changes in blood lipids and HbA1c concentrations over 5 years among Japanese adults. METHODS: This cohort study included 7252 subjects with no known history of major chronic disease at baseline. Soy intake was measured using a food frequency questionnaire; while the concentrations of serum lipids and HbA1c were measured using standard laboratory methods. We used multivariable linear mixed-effects models to examine the associations of changes in lipids and HbA1c concentrations with intakes of soy food and isoflavones. RESULTS: Among the participants, mean age was 61 years, 67% were females and median intakes of soy and isoflavones were 95.3 g/day and 47.4 mg/day, respectively. Soy food and isoflavone intakes were not associated with 5-year changes in blood lipids or HbA1c concentrations. However, stratified analyses showed inverse associations between fermented soy intake and serum lipids among obese/overweight subjects. In particular, intake of 20 g/day of natto was associated with a reduction of 1.4 (95% CI 0.3, 2.5) mg/dL in TC, 1.5 (95% CI 0.4, 2.6) mg/dL in non-high-density lipoprotein cholesterol, 1.0 (95% CI - 0.0, 2.0) mg/dL in low-density lipoprotein cholesterol and 4.0 (95% CI 0.6, 7.5) mg/dL in triglycerides. CONCLUSIONS: Overall, habitual consumption of soy or isoflavones was not associated with changes in serum lipids or HbA1c concentrations. The negative associations between intake of natto and changes in serum lipids among overweight/obese subjects deserve further investigation.

DOI： 10.1007/s00394-019-02057-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS/INTRODUCTION: The aim of the present study was to examine the associations of pregestational body mass index (BMI) and gestational weight change with birthweight for gestational age in Japanese mothers with gestational diabetes mellitus (GDM). MATERIALS AND METHODS: We retrospectively examined the clinical and laboratory characteristics of 101 mothers with GDM (pregestational BMI 24.7 ± 5.8 kg/m2 ; maternal age at delivery 34.7 ± 5.1 years; gestational age 38.5 ± 1.4 weeks) at a single center from January 2011 to December 2016. RESULTS: Gestational weight changes were 6.22 ± 5.39 kg, and infant birthweights were 2,987.3 ± 393.6 g. Multivariable analysis showed that, in all mothers, pregestational BMI and gestational weight change were positively associated with infant birthweight (P < 0.001 and P = 0.007, respectively). Pregestational BMI, but not gestational weight change, was positively associated with infant birthweight (P = 0.007) in 31 mothers with GDM who had pregestational BMI ≥25 kg/m2 ; in 68 mothers with GDM who had pregestational BMI 18.5-24.9 kg/m2 , only gestational weight gain was positively associated with infant birthweight (P = 0.039). Two mothers had pregestational BMI <18.5 kg/m2 . No statistically significant interactions of pregestational BMI with gestational weight change were found (P = 0.158). CONCLUSIONS: In mothers with GDM, pregestational BMI ≥25 kg/m2 and excessive gestational weight gain were significantly associated with increased infant birthweight. A prospective multicenter clinical study enrolling a larger number of mothers with GDM will be required to verify the effects of adequately controlling pregestational and gestational weights on infant birthweight for gestational age.

DOI： 10.1111/jdi.12989

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Usual sleep duration has substantial heritability and is associated with various physical and psychiatric conditions as well as mortality. However, for its genetic locus, only PAX8 and VRK2 have been replicated in previous genome-wide association studies (GWAS). We conducted a GWAS meta-analysis of self-reported usual sleep duration using three population-based cohorts totaling 31 230 Japanese individuals. A genome-wide significant locus was identified at 12q24 (p-value < 5.0 × 10-8). Subsequently, a functional variant in the ALDH2 locus, rs671, was replicated in an independent sample of 5140 Japanese individuals (p-value = 0.004). The association signal, however, disappeared after adjusting for alcohol consumption, indicating the possibility that the rs671 genotype modifies sleep duration via alcohol consumption. This hypothesis explained a modest genetic correlation observed between sleep duration and alcohol consumption (rG = 0.23). A Mendelian randomization analysis using rs671 and other variants as instrumental variables confirmed this by showing a causal effect of alcohol consumption, but not of coffee consumption on sleep duration. Another genome-wide significant locus was identified at 5q33 after adjusting for drinking frequency. However, this locus was not replicated, nor was the PAX8 and VRK2. Our study has confirmed that a functional ALDH2 variant, rs671, most strongly influences on usual sleep duration possibly via alcohol consumption in the Japanese population, and presumably in East Asian populations. This highlights the importance of considering the involvement of alcohol consumption in future GWAS of usual sleep duration, even in non-East Asian populations, where rs671 is monomorphic.

DOI： 10.1093/sleep/zsz046

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記述言語：英語  

DOI： 10.1111/pcn.12905

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DOI： 10.1111/jdi.13077

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Oxidative stress and chronic inflammation are potential pathogenic factors of pancreatic cancer. Although fruits and vegetables are abundant in antioxidants and anti-inflammatory constituents, the reported associations between fruit and vegetable intake and pancreatic cancer risk have been inconsistent. Here, we investigated the association between fruit and vegetable intake and pancreatic cancer risk as part of the Japan Public Health Center-based Prospective Study. The analysis included 90,185 participants who responded to a medical and lifestyle questionnaire during 1995-1998. Associations between fruit and vegetable intake and pancreatic cancer risk were evaluated with Cox proportional hazards models. Additional analyses were stratified by smoking status and body mass index. During follow-up (median duration, 16.9 years), 577 participants were diagnosed with pancreatic cancer. In multivariate-adjusted models, pancreatic cancer risk was inversely associated with total fruit intake (highest vs. lowest intake quartile; hazard ratio [HR]: 0.74, 95% confidence interval [CI]: 0.57-0.95, p-trend: 0.116) and positively associated with total vegetable intake (HR: 1.30, 95% CI: 1.01-1.66, p-trend: 0.151). For total fruit intake, the inverse association with pancreatic cancer risk was more apparent in never smokers (HR: 0.67, 95% CI: 0.47-0.97, p-trend: 0.034). For total vegetable intake, the positive association was statistically significant in ever smokers (HR: 1.49, 95% CI: 1.01-2.19, p-trend: 0.043) and statistically nonsignificant in never smokers. In summary, total fruit intake and total vegetable intake had inverse and positive associations, respectively, with pancreatic cancer risk. Vegetable intake may correlate with increased risk partly because of the influence of smoking on vegetable intake.

DOI： 10.1002/ijc.31894

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: To investigate whether social support and social trust are associated with DED. METHODS: Cross-sectional data from the Japan Public Health Center-Based Prospective Study for the Next Generation (JPHC-NEXT) were used. Subjects are 96,227 Japanese men and women aged 40 to 74. Data from respondents included information on DED, social support and social trust. DED was defined as the presence of clinically diagnosed DED or severe symptoms. Social support was measured by emotional support and tangible support. Social trust was measured by level of general trust in others. Multiple logistic regression analysis was conducted to assess the association of social determinants for DED. RESULTS: Individuals with high levels of social support and social trust were less likely to have severe symptoms of DED and clinically diagnosed DED (P for trend < 0.001 in both cases). Those with the highest levels of social support and social trust were least likely to have DED (odds ratios [OR] = 0.64 [0.61-0.67], 95% confidence interval [CI] = 0.63 [0.60-0.67] for severe symptoms of DED; OR = 0.88 [0.83-0.93] and 0.85 [0.80-0.91] for clinically diagnosed DED). CONCLUSIONS: High levels of social support and social trust were associated with a lower prevalence of DED.

DOI： 10.1016/j.jtos.2019.01.005

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Although a possible role of reproductive factors in lymphomagenesis has been hypothesized, results of epidemiological studies have been inconsistent. Here, we investigated the association between reproductive factors and the risk of lymphoid neoplasm and its subgroups. We used data from a large-scale, population-based prospective study in a Japanese cohort with 42 691 eligible women aged 40-69 years from 1990 to 1994. During a mean follow up of 18.7 years, we identified 176 cases of lymphoid neoplasm and 90 of non-Hodgkin lymphoma (NHL). A multivariable-adjusted Cox proportional hazards regression model was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for the risk of lymphoid neoplasms and its subgroups according to self-reported reproductive factors. Parous women had an increased risk of lymphoid neoplasm compared with nulliparous women (HR = 2.51, 95% CI, 1.03-6.13). An increased risk of lymphoid neoplasms was found in women with later onset of menarche (≤13 years old; reference: 14-15; HR = 1.75, 95% CI = 1.10-2.79: ≥16; HR = 1.93, 95% CI = 1.17-3.19: P-trend: 0.01) and a shorter menstrual cycle (28-29 days; reference: ≤27; HR = 1.60, 95% CI = 1.05-2.43, P-trend = 0.81). No association was observed between lymphoid neoplasms and other reproductive factors, including age at first birth, breastfeeding, type of menopause, or exogenous hormone use. Our study suggests that ever parity, late age at menarche and a short menstrual cycle length may be associated with the development of lymphoid neoplasms. The inconsistency seen in epidemiological research to date warrants further investigation.

DOI： 10.1111/cas.13962

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Risk factors for hypertension consist of lifestyle and genetic factors. Family history and twin studies have yielded heritability estimates of BP in the range of 34-67%. The most recent paper of BP GWAS has explained about 20% of the population variation of BP. An overestimation of heritability may have occurred in twin studies due to violations of shared environment assumptions, poor phenotyping practices in control cohorts, failure to account for epistasis, gene-gene and gene-environment interactions, and other non-genetic sources of phenotype modulation that are suspected to lead to underestimations of heritability in GWAS. The recommendations of hypertension guidelines in major countries consist of the following elements: weight reduction, a healthy diet, dietary sodium reduction, increasing physical activity, quitting smoking, and moderate alcohol consumption. The hypertension guidelines are mostly the same for each country or region, beyond race and culture. In this review, we summarize gene-environmental interactions associated with hypertension by describing lifestyle modifications according to the hypertension guidelines. In the era of precision medicine, clinicians who are responsible for hypertension management should consider the gene-environment interactions along with the appropriate lifestyle components toward the prevention and treatment of hypertension. We briefly reviewed the interaction of genetic and environmental factors along the constituent elements of hypertension guidelines, but a sufficient amount of evidence has not yet accumulated, and the results of genetic factors often differed in each study.

DOI： 10.1186/s12199-019-0771-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

We evaluated the validity and reproducibility of estimated sugar intakes using a food frequency questionnaire (FFQ) among middle-aged Japanese adults in the Japan Public Health Centre-Based Prospective (JPHC) study. In subsamples of the JPHC study (Cohorts I and II in multiple areas), we computed Spearman's correlations of FFQ results with urine sugar concentrations and dietary records (DR) for validity; we evaluated correlations between two FFQs for reproducibility. During 1994⁻1998, participants (Cohort I: n = 27 [men], n = 45 [women]) provided two (spring and fall) 24-h urine samples and completed 7-consecutive-day DR per season (I: n = 99, n = 113; II: n = 168, n = 171) and two FFQs (147 food items) at yearly intervals (I: n = 101, n = 108; II: n = 143, n = 146). Sugar intakes from FFQ were correlated with urinary sugar (de-attenuated correlations: 0.40; 95%CI: 0.19, 0.58). After adjustment for sociodemographic and lifestyle variables, correlations between FFQ and DR for men and women were 0.57 (0.42, 0.69) and 0.41 (0.24, 0.55) (I) and 0.56 (0.44, 0.65) and 0.34 (0.20, 0.47) (II), respectively. Correlations between FFQs for men and women were 0.63 (0.49, 0.73) and 0.55 (0.41, 0.67) (I) and 0.66 (0.55, 0.74) and 0.63 (0.52, 0.72) (II). In conclusion, our study showed moderate FFQ validity and reproducibility for sugar intake evaluation.

DOI： 10.3390/nu11030554

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/s41416-019-0392-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/ijc.32310

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

To elucidate the individual impacts of insulin and blood glucose on cancer risk, we investigated the association of plasma C-peptide, a surrogated marker of insulin and glycated albumin (GA), a more stable marker of blood glucose, with all-site and site-specific cancer risk by mutually accounting for their confounding effects. The study was prospectively conducted with nearly 4,000 cancer cases arising in our population-based cohort of 33,736 subjects who answered the baseline questionnaire and supplied blood samples. After exclusion of subjects with apparent DM, analysis was done in 3,036 cancer cases and 3,667 subcohort subjects. Among men and women combined, highest levels of C-peptide were statistically significantly associated with an increased risk of all-site [Hazard ratio (HR): 1.21; 95% confidence interval: 1.02-1.42], colon [1.73; 1.20-2.47], liver [3.23; 1.76-5.91], kidney, renal pelvis and ureter cancers [2.47; 1.07-5.69], compared to the respective lowest levels, after adjustment for GA levels. Among these C-peptide-related cancers, colon and liver cancers also showed an increased risk associated with elevated GA levels independently of C-peptide levels. The corresponding HRs for colon and liver cancers compared to the highest and lowest GA levels were 1.43 [1.02-2.00] and 2.02 [1.15-3.55], respectively. Effect modification by gender was only evident for the association between C-peptide and colon cancer (p for interaction = 0.04). Higher insulin levels, independently of higher blood glucose levels, may be relevant to DM-related carcinogenesis for several cancer sites. Examination of circulating insulin levels is a plausible option in evaluating cancer risk even in individuals who have not developed DM.

DOI： 10.1002/ijc.31847

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1093/sleep/zsz046

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

[This corrects the article DOI: 10.1007/s13340-018-0345-3.].

DOI： 10.1007/s13340-018-0385-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/liv.14030

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.3390/nu11010048

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND & AIMS: A marker is needed to identify individuals at risk for pancreatic cancer. Increases in branched-chain amino acids (BCAAs) have been associated with pancreatic cancer. We performed a prospective case-control study to study the association between plasma BCAA levels and risk of pancreatic cancer in a large cohort. METHODS: We conducted a nested case-control study selected from 30,239 eligible participants 40-69 years old within the Japan Public Health Center-based prospective study. Over 16.4 years, 170 newly diagnosed pancreatic cancer cases were identified. Each case was matched to 2 controls by age, gender, geographic area, and fasting time at blood collection. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for pancreatic cancer were calculated using conditional logistic regression models with adjustment for potential confounding factors. RESULTS: Increased plasma BCAA levels at baseline were associated with an increased risk of pancreatic cancer. Compared with the lowest quartile of BCAA levels, the OR in the highest quartile was 2.43 (95% CI 1.21-4.90), and the OR per 1 SD increase in BCAA levels was 1.32 (95% CI 1.05-1.67). The association was especially strong for cases with blood samples collected at least 10 years before cancer diagnosis (OR per SD 1.60, 95% CI 1.10-2.32) compared with those detected less than 10 years before diagnosis (OR per SD 1.16, 95% CI 0.86-1.57). CONCLUSIONS: In an analysis of data from the Japan Public Health Center-based prospective study, we found an association between increased plasma BCAA level and increased risk of pancreatic cancer-particularly when the increase in BCAAs was observed at least 10 years before diagnosis. These findings add to the growing body of evidence for the association between BCAA levels and pancreatic cancer risk.

DOI： 10.1053/j.gastro.2018.07.033

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/s0140-6736(18)32281-5

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/jdi.12947

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その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/jdi.12947

記述言語：英語   掲載種別：研究論文（学術雑誌）  

PURPOSE: We investigated the association between reproductive history and mortality from all and major causes among Japanese women. METHODS: A large-scale population-based cohort study in Japan included 40,149 eligible women aged 40-69 years in 1990-1994. A total of 4788 deaths were reported during follow-up (average 20.9 years). A Cox proportional hazards regression model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CI) for all-cause and major causes of mortality, adjusting for potential confounders. RESULTS: Inverse associations with all-cause mortality were found in parous women (0.74 [0.67-0.82]), women with two or three births compared with a single birth (2 births: 0.88 [0.78-0.99]; 3 births: 0.83 [0.74-0.94]), parous women who breastfed (0.81 [0.75-0.87]), women who were older at menopause (0.88 [0.80-0.97]; p-trend: <0.01), and women who had a longer fertility span (0.85 [0.76-0.95]; p-trend: <0.01). A positive association was seen between all-cause mortality and later age at first birth (≥30 years) than early childbearing (≤22 years). CONCLUSIONS: Our study suggests that parous, two or three births, breastfeeding, late age at menopause, and longer reproductive span are associated with lower risk of all-cause of mortality.

DOI： 10.1016/j.annepidem.2018.06.001

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/s41431-018-0251-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：John Wiley and Sons Inc.  

Background: Low circulating levels of sex hormone-binding globulin (SHBG) have been shown to be a direct and strong risk factor for type 2 diabetes, cardiovascular diseases, and hormone-dependent cancers, although the relationship between various aspects of dietary carbohydrates and SHBG levels remains unexplored in population studies. Methods: Among postmenopausal women with available SHBG measurements at baseline (n = 11 159) in the Women's Health Initiative, a comprehensive assessment was conducted of total dietary carbohydrates, glycemic load (GL), glycemic index (GI), fiber, sugar, and various carbohydrate-abundant foods in relation to circulating SHBG levels using multiple linear regressions adjusting for potential covariates. Linear trend was tested across quartiles of dietary variables. Benjamini and Hochberg's procedure was used to calculate the false discovery rate for multiple comparisons. Results: Higher dietary GL and GI (both based on total and available carbohydrates) and a higher intake of sugar and sugar-sweetened beverages were associated with lower circulating SHBG concentrations (all P trend &lt
0.05
Q -values = 0.04,0.01, 0.07, 0.10, 0.01, and &lt
0.0001, respectively). In contrast, women with a greater intake of dietary fiber tended to have elevated SHBG levels (P trend = 0.01, Q -value = 0.04). There was no significant association between total carbohydrates or other carbohydrate-abundant foods and SHBG concentrations. Conclusions: The findings suggest that low GL or GI diets with low sugar and high fiber content may be associated with higher serum SHBG concentrations among postmenopausal women. Future studies investigating whether lower GL or GI diets increase SHBG concentrations are warranted.

DOI： 10.1111/1753-0407.12550

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：John Wiley and Sons Inc.  

Background: Sex hormones are implicated in the development of diabetes. However, whether genetic variations in sex hormone pathways (SHPs) contribute to the risk of type 2 diabetes mellitus (T2DM) remains to be determined. This study investigated associations between genetic variations in all candidate genes in SHPs and T2DM risk among a cohort of women participating in the Women’s Health Initiative (WHI). Methods: Single nucleotide polymorphisms (SNPs) located within 30 kb upstream and downstream of SHP genes were comprehensively examined in 8180 African American, 3498 Hispanic American, and 3147 European American women in the WHI. In addition, whether significant SNPs would be replicated in independent populations was examined. Results: After adjusting for age, region, and ancestry estimates and correcting for multiple testing, seven SNPs were significantly associated with the risk of T2DM among Hispanic American women were identified in the progesterone receptor (PGR) gene, with rs948516 showing the greatest significance (odds ratio 0.67
95% confidence interval 0.57–0.78
P = 8.8 × 10−7
false discovery rate, Q = 7.8 × 10−4). These findings were not replicated in other ethnic groups in the WHI or in sex-combined analyses in replication studies. Conclusion: Significant signals were identified implicating the PGR gene in T2DM development in Hispanic American women in the WHI, which are consistent with genome-wide association studies findings linking PGR to glucose homeostasis. Nevertheless, the PGR SNPs–T2DM association was not statistically significant in other ethnic populations. Further studies, especially sex-specific analyses, are needed to confirm the findings and clarify the role of SHPs in T2DM.

DOI： 10.1111/1753-0407.12648

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Blackwell Publishing  

DOI： 10.1111/jdi.12810

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Blackwell Publishing Ltd  

Aims: To assess the predictive ability of a genetic risk score for the incidence of Type 2 diabetes in a general Japanese population. Methods: This prospective case–control study, nested within a Japan Public Health Centre-based prospective study, included 466 participants with incident Type 2 diabetes over a 5-year period (cases) and 1361 control participants, as well as 1463 participants with existing diabetes and 1463 control participants. Eleven susceptibility single nucleotide polymorphisms, identified through genome-wide association studies and replicated in Japanese populations, were analysed. Results: Most single nucleotide polymorphism loci showed directionally consistent associations with diabetes. From the combined samples, one single nucleotide polymorphism (rs2206734 at CDKAL1) reached a genome-wide significance level (odds ratio 1.28, 95% CI 1.18–1.40
P = 1.8 × 10–8). Three single nucleotide polymorphisms (rs2206734 in CDKAL1, rs2383208 in CDKN2A/B, and rs2237892 in KCNQ1) were nominally significantly associated with incident diabetes. Compared with the lowest quintile of the total number of risk alleles, the highest quintile had a higher odds of incident diabetes (odds ratio 2.34, 95% CI 1.59–3.46) after adjusting for conventional risk factors such as age, sex and BMI. The addition to the conventional risk factor-based model of a genetic risk score using the 11 single nucleotide polymorphisms significantly improved predictive performance
the c-statistic increased by 0.021, net reclassification improved by 6.2%, and integrated discrimination improved by 0.003. Conclusions: Our prospective findings suggest that the addition of a genetic risk score may provide modest but significant incremental predictive performance beyond that of the conventional risk factor-based model without biochemical markers.

DOI： 10.1111/dme.13602

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

Discovery of a high-risk group for pancreatic cancer is important for prevention of pancreatic cancer. The present study was conducted as a nested case-control study including 170 pancreatic cancer cases and 340 matched controls of our population-based cohort study involving 30 239 subjects who answered a baseline questionnaire and supplied blood samples. Twelve targeted metabolites were quantitatively analyzed by gas chromatography/tandem mass spectrometry. Odds ratios (OR) and their corresponding 95% confidence intervals (CI) were calculated using conditional logistic regression models. Statistically significant P-value was defined as P < .05. Increasing 1,5-anhydro-d-glucitol (1,5-AG) levels were associated with a decreasing trend in pancreatic cancer risk (OR of quartile 4 [Q4], 0.50; 95% CI, 0.27-0.93; P = .02). Increasing methionine levels were also associated with an increasing trend of pancreatic cancer risk (OR of Q4, 1.79; 95% CI, 0.94-3.40: P = .03). Additional adjustment for potential confounders attenuated the observed associations of 1,5-AG and methionine (P for trend = .06 and .07, respectively). Comparing subjects diagnosed in the first 0-6 years, higher levels of 1,5-AG, asparagine, tyrosine and uric acid showed a decreasing trend for pancreatic cancer risk (P for trend = .04, .04, .04 and .02, respectively), even after adjustment for potential confounders. We found that the 12 target metabolites were not associated with pancreatic cancer risk. However, metabolic changes in the subjects diagnosed in the first 0-6 years showed a similar tendency to our previous reports. These results might suggest that these metabolites are useful for early detection but not for prediction of pancreatic cancer.

DOI： 10.1111/cas.13573

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DOI： 10.1111/jdi.12853

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley-Liss Inc.  

Although coffee and green tea are suggested to reduce the risk of some types of cancers, only a few epidemiological studies have investigated their effect on the risk of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Here, we investigated the association of coffee and green tea consumption and the risk of AML and MDS in a large-scale population-based cohort study in Japan. A total of 95,807 Japanese subjects (45,937 men and 49,870 women
age 40–69 years at baseline) were followed to the end of 2012, for an average of 18 years. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association between coffee and green tea consumption at baseline and the risk of AML and MDS were assessed using a Cox proportional hazards model with adjustment for potential confounders. During 1,751.956 person-years, we identified 85 AML cases and 70 MDS cases. Our findings showed no significant association between coffee consumption and the risk of AML, or between green tea consumption and the risk of AML or MDS. In contrast, we observed a decreasing dose-response relationship between coffee consumption and the risk of MDS among men (almost none: reference, 1–4 times/week: HR = 0.83, 95% CI: 0.43–1.62
≥1cups/day: HR = 0.47, 0.22–0.99, p for trend = 0.049). Stratified analysis by smoking status suggested that the observed relative risk for AML and MDS of coffee drinkers relative to non-coffee drinkers might be due to residual confounding by smoking. These findings deserve further investigation in future studies.

DOI： 10.1002/ijc.31135

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: To evaluate the association between pre-diagnostic circulating vitamin D concentration and the subsequent risk of overall and site specific cancer in a large cohort study. DESIGN: Nested case-cohort study within the Japan Public Health Center-based Prospective Study cohort. SETTING: Nine public health centre areas across Japan. PARTICIPANTS: 3301 incident cases of cancer and 4044 randomly selected subcohort participants. EXPOSURE: Plasma concentration of 25-hydroxyvitamin D measured by enzyme immunoassay. Participants were divided into quarters based on the sex and season specific distribution of 25-hydroxyvitamin D among subcohorts. Weighted Cox proportional hazard models were used to calculate the multivariable adjusted hazard ratios for overall and site specific cancer across categories of 25-hydroxyvitamin D concentration, with the lowest quarter as the reference. MAIN OUTCOME MEASURE: Incidence of overall or site specific cancer. RESULTS: Plasma 25-hydroxyvitamin D concentration was inversely associated with the risk of total cancer, with multivariable adjusted hazard ratios for the second to fourth quarters compared with the lowest quarter of 0.81 (95% confidence interval 0.70 to 0.94), 0.75 (0.65 to 0.87), and 0.78 (0.67 to 0.91), respectively (P for trend=0.001). Among the findings for cancers at specific sites, an inverse association was found for liver cancer, with corresponding hazard ratios of 0.70 (0.44 to 1.13), 0.65 (0.40 to 1.06), and 0.45 (0.26 to 0.79) (P for trend=0.006). A sensitivity analysis showed that alternately removing cases of cancer at one specific site from total cancer cases did not substantially change the overall hazard ratios. CONCLUSIONS: In this large prospective study, higher vitamin D concentration was associated with lower risk of total cancer. These findings support the hypothesis that vitamin D has protective effects against cancers at many sites.

DOI： 10.1136/bmj.k671

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1177/1359105317718057

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DOI： 10.1016/j.diabres.2018.02.034

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1111/cas.13573

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Tokyo  

DOI： 10.1007/s13340-018-0345-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Previous studies have consistently reported an association between circulating levels of branched-chain amino acids (BCAAs) or adipokines and insulin resistance; however, the association between BCAA and adipokine levels remains to be clarified. In this cross-sectional study involving 678 participants (435 men) without diabetes, plasma BCAA (valine, leucine, and isoleucine), adipokine (total and high molecular weight [HMW] adiponectin, leptin, and tumor necrosis factor-α [TNF-α]) concentrations, and an updated homeostasis model assessment of insulin resistance (HOMA2-IR) were measured. The association between the concentrations of total BCAAs and adipokines was adjusted for confounding factors, including body mass index. For the lowest and highest BCAA quartiles, the adjusted geometric mean levels of HMW adiponectin were, respectively, 1.51 and 0.91 μg/mL, in men (P for trend < 0.0001); 3.61 and 2.29 μg/mL, in women (P = 0.0005). The corresponding geometric mean levels for leptin were 1681 and 2620 pg/mL, in men (P = 0.003), and 4270 and 6510 pg/mL, in women (P = 0.003). Those for HOMA2-IR were 0.89 and 1.11, in men (P < 0.0001), and 0.79 and 0.96, in women (P < 0.0001); no significant association was found with TNF-α. These results suggest significant associations between BCAA concentrations and those for adiponectin, leptin and HOMA2-IR in individuals without diabetes.

DOI： 10.1038/s41598-018-19388-w

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/S0140-6736(18)31891-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Public Library of Science  

Adult height is determined by both genetic characteristics and environmental factors in early life. Although previous studies have suggested that adult height is associated with risk of mortality, comprehensive associations between height and all-cause and cause-specific mortality in the Japanese population are unclear. We aimed to evaluate the associations between adult height and all-cause and cause-specific mortality among Japanese men and women in a prospective cohort study. We investigated 107,794 participants (50,755 men and 57,039 women) aged 40 to 69 years who responded to the baseline questionnaire in the Japan Public Health Center-based Prospective Study. Participants were classified by quartile of adult height obtained from a self-reported questionnaire in men (&lt
160cm, 160-163cm, 164-167cm, 168cm) and women (&lt
149cm, 149-151cm, 152-155cm, 156cm). Hazard ratios (HR) and 95% confidence intervals (CI) for mortality from all-cause, cancer, heart disease, cerebrovascular disease, respiratory disease, and other cause mortality were calculated using Cox proportional hazards models. During follow-up, 12,320 men and 7,030 women died. Taller adult height was associated with decreased risk for mortality from cerebrovascular disease (HR&lt
160cm vs.168cm (95% CI) = 0.83 (0.69–0.99)
HRfor 5-cm increment (95% CI) = 0.95 (0.90–0.99)) and respiratory disease (HR&lt
160cm vs.168cm (95% CI) = 0.84 (0.69–1.03)
Rfor 5-cmincrement (95% CI) = 0.92 (0.87–0.97)), but was also associated with increased risk for overall cancer mortality (HR&lt
160cm vs.168cm (95% CI) = 1.17 (1.07–1.28)
HRfor -mincrement (95% CI) = 1.04 (1.01–1.07)) in men. Taller adult height was also associated with decreased risk for mortality from cerebrovascular disease (HR&lt
149cm vs. 156cm (95% CI) = 0.84 (0.66–1.05)
HRfor 5-cmincrement (95% CI) = 0.92 (0.86–0.99)) in women. Our results confirmed that adult height is associated with cause-specific mortality in a Japanese population.

DOI： 10.1371/journal.pone.0197164

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Churchill Livingstone  

Background &amp
aims: Cruciferous vegetables contain isothiocyanates, which effectively reduce inflammation and oxidative stress related to chronic diseases, inhibit the bioactivation of procarcinogens, and enhance the excretion of carcinogens. However, at present, no large cohort studies have investigated the effect of cruciferous vegetable on mortality. We aimed to examine the association between cruciferous vegetable intake and all-cause mortality, namely cancer, heart disease, cerebrovascular disease, and injuries, in a large cohort study conducted between 1990 and 1993, in Japan. Methods: The analysis included 88,184 participants (age: 45–74 years) with no history of cancer, myocardial infarction, and stroke. Participants were tracked for a median of 16.9 years, during which 15,349 deaths were occurred. The association between cruciferous vegetable intake and risk of all-cause and cause-specific mortality was determined by Cox proportional hazard regression analysis to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs), after adjustment for potential confounding factors. Results: An inverse association was found between cruciferous vegetable intake and total mortality in both gender. HRs (95% CI) for all-cause mortality in the highest compared to the lowest quintile were 0.86 (0.80, 0.93) for men (P = 0.0002 for trend) and 0.89 (0.81, 0.98) for women (P = 0.03 for trend). Cruciferous vegetable intake was associated with lower cancer mortality in men, as well as with heart disease-, cerebrovascular disease-, and injury-related mortality in women. Conclusions: This prospective study suggests that a higher cruciferous vegetables intake is associated with reduced risk of all-cause mortality.

DOI： 10.1016/j.clnu.2018.04.012

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記述言語：英語   出版者・発行元：ELSEVIER SCIENCE INC  

Cigarette smoking is the leading avoidable cause of disease burden. Observational studies have suggested an association between smoking and risk of type 2 diabetes mellitus (T2DM). We conducted a meta-analysis of prospective observational studies to investigate the association of smoking status, smoking intensity, and smoking cessation with the risk of T2DM in Japan, where the prevalence of smoking has been decreasing but remains high. We systematically searched MEDLINE and the Ichushi database to December 2015 and identified 22 eligible articles, representing 343,573 subjects and 16,383 patients with T2DM. We estimated pooled relative risks (RRs) using a random-effects model and conducted subgroup analyses by participant and study characteristics. Compared with nonsmoking, the pooled RR of T2DM was 1.38 (95% confidence interval [CI], 1.28-1.49) for current smoking (19 studies) and 1.19 (95% CI, 1.09-1.31) for former smoking (15 studies). These associations persisted in all subgroup and sensitivity analyses. We found a linear dose-response relationship between cigarette consumption and T2DM risk; the risk of T2DM increased by 16% for each increment of 10 cigarettes smoked per day. The risk of T2DM remained high among those who quit during the preceding 5 years but decreased steadily with increasing duration of cessation, reaching a risk level comparable to that of never smokers after 10 years of smoking cessation. We estimated that 18.8% of T2DM cases in men and 5.4% of T2DM cases in women were attributable to smoking. The present findings suggest that cigarette smoking is associated with an increased risk of T2DM, so tobacco control programs to reduce smoking could have a substantial effect to decrease the burden of T2DM in Japan. (C) 2017 The Authors. Publishing services by Elsevier B.V.

DOI： 10.1016/j.je.2016.12.017

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

The association between alcohol consumption and bladder cancer risk has been insufficiently investigated in East Asian populations, who frequently have the inactive enzyme for metabolizing acetaldehyde. Given that acetaldehyde associated with alcohol consumption is assessed as a carcinogen, consideration of differences in acetaldehyde exposure would aid accuracy in assessing the bladder cancer risk associated with alcohol consumption. Here, we conducted a population-based cohort study in Japan to examine this association, including information on the flushing response as a surrogate marker of the capacity of acetaldehyde metabolism. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using multivariate Cox proportional hazard models. During follow up from 1990 through 2012 for the 95,915 subjects (45,649 men and 50,266 women, aged 40-69 years), 354 men and 110 women were newly diagnosed with bladder cancer. No significant association between alcohol consumption and bladder cancer risk was observed in the overall analysis. Among male flushers, HRs were 1.04 (95% CI 0.70-1.54), 1.67 (1.16-2.42), 1.02 (0.62-1.67) and 0.63 (0.33-1.20) for alcohol consumption of 1-150, 151-300, 301-450, &gt;450 g/week of pure ethanol compared with non-drinkers and occasional drinkers, respectively, indicating an inverted U-shaped association between alcohol consumption and bladder cancer risk. In contrast, no significant association was identified among male non-flushers. The marginally significant interaction between alcohol consumption and the flushing response (p for interaction=0.083) may support our hypothesis that acetaldehyde derived from alcohol consumption is associated with bladder cancer risk. A prospective study considering polymorphisms of genes involved in acetaldehyde metabolism is warranted.

DOI： 10.1002/ijc.31028

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

Background: The influence of body mass index (BMI) change during adulthood on the development of oesophageal squamouscell carcinoma (ESCC) is unknown.
Methods: Based on the Japan Public Health Center-based Prospective Study, we enrolled 103 238 participants from 1990 to 1994. Anthropometric data at age 20 years, baseline, and 5-and/or 10-year follow-up surveys were collected by questionnaire. The effect of BMI change between age 20 years and baseline on ESCC risk was estimated by Cox proportional hazards regression models. The updated BMI was taken into account by fitting a simple linear regression model for each individual, where the slope was incorporated into regressions as a time-varying variable.
Results: After excluding the first 5 years of observation, we identified 342 newly diagnosed ESCC cases. An increase in BMI during adulthood was linked with a decreased risk of ESCC development, with each 1% increase per 5 years corresponding to a 15% decrease in ESCC risk (95% confidence interval 9-21%). Identical estimates were obtained from time-dependent models. The importance of BMI change was not modified by gender, smoking, or alcohol drinking but confined to participants assessed as non-overweight at baseline.
Conclusions: An increase in BMI during adulthood is associated with a lower risk of developing ESCC among non-overweight subjects.

DOI： 10.1038/bjc.2017.332

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

Platinum regimens still play a key role in chemotherapy for incurable non-small cell lung cancer (NSCLC). Although guidelines list many platina regimens, the best regimens have not yet clarified. Electronic searches were carried out during November 26th-28th, 2016. We included individually randomized trials comparing two or more platinum regimes for incurable chemo-naive NSCLC published in English full papers. The platinum doublets should be either Cisplatin (CDDP), Carboplatin (CBDCA), or Nedaplatin (CDGP) plus one of the third-generation agents. The platinum triplet should be the doublet plus bevacizumab (BEV). The data were independently extracted and cross-checked by two investigators. We did not observed heterogeneity (whole network level Q = 28.9, df = 34, P = 0.717) among 59 pairwise comparisons from 45 studies with 16141 cases for the primary outcome, hazard ratio for overall survival (HRos). Using CBDCA + Paclitaxel (PTX) + BEV as a common comparator, CDGP + Docetaxel (DTX) (HRos = 0.98, 95% CI: 0.75-1.29, P = 0.884), CDDP + Tegafur gimeracil oteracil (S1) (HRos = 1.23, 95% CI: 0.96-1.57, P = 0.099), CBDCA + S1 (HRos = 1.23, 95% CI: 0.99-1.53, P = 0.062), and CDGP + Gemcitabine (GEM) (HRos = 1.24, 95% CI: 0.71-2.17, P = 0.45) did not have significantly poorer HRos. We suggest that these regimens as acceptable first-choice regimens.

DOI： 10.1038/s41598-017-13724-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

Evidence regarding stress as a risk factor for cancer onset is inconsistent. In this study, based on the Japan Public Health Center-based Prospective Study, we enrolled 101,708 participants aged 40-69 years from 1990-1994. The self-reported perceived stress level was collected at baseline and updated through 5-year follow-up. The association between perceived stress and cancer risk was measured by Cox proportional hazards regression model, adjusted for all known confounders. During follow-up (mean = 17.8 years), we identified 17,161 cancer cases. We found no association between baseline perceived stress level and cancer incidence. However, by taking account of the dynamic changes in perceived stress, time-varying analyses revealed a slightly (4-6%) increased overall cancer risk for subjects under elevated perceived stress levels compared to the 'low stress level' group. Analyses concerning long-term perceived stress level showed that individuals with constantly high perceived stress level had an 11% (95% confidence interval 1-22%) excess risk for cancer compared to subjects with persistently low stress levels. This association was confined to men (20% excess risk), and was particularly strong among smokers, alcohol drinkers, obese subjects, and subjects without family history of cancer. Therefore, we concluded high perceived stress level might contribute to excess overall cancer incidence among men.

DOI： 10.1038/s41598-017-13362-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ASSOC CANCER RESEARCH  

We previously developed and validated a risk prediction model for colorectal cancer in Japanese men using modifiable risk factors. To further improve risk prediction, we evaluated the degree of improvement obtained by adding a genetic risk score (GRS) using genome-wide association study (GWAS)-identified risk variants to our validated model. We examined the association between 36 risk variants identified by GWAS and colorectal cancer risk using a weighted Cox proportional hazards model in a nested case-control study within the Japan Public Health Center-based Prospective Study. GRS was constructed using six variants associated with risk in this study of the 36 tested. We assessed three models: a nongenetic model that included the same variables used in our previously validated model; a genetic model that used GRS; and an inclusive model, which included both. The c-statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were calculated by the 5-fold cross-validation method. We estimated 10-year absolute risks for developing colorectal cancer. A statistically significant association was observed between the weighted GRS and colorectal cancer risk. The mean c-statistic for the inclusive model (0.66) was slightly greater than that for the nongenetic model (0.60). Similarly, the mean IDI and NRI showed improvement when comparing the nongenetic and inclusive models. These models for colorectal cancer were well calibrated. The addition of GRS using GWAS-identified risk variants to our validated model for Japanese men improved the prediction of colorectal cancer risk. (C) 2017 AACR.

DOI： 10.1158/1940-6207.CAPR-17-0141

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

Background: Although birth weight is considered as a fetal determinant of the development of adultonset diabetes mellitus (DM), its public health importance relative to adult body mass index (BMI) remains unclear. We aimed to examine the association between adult-onset DM and birth weight in relation to adult BMI.
Methods: We conducted a self-administered questionnaire as a baseline survey of the Japanese Nurses' Health Study cohort between 2001 and 2007. Exclusion criteria were applied to the volunteer sample of 49,927 female nurses (age &lt; 30 years or unknown, current pregnancy, development of DM before the age of 30 years, unknown core variables), and data from 26,949 female nurses aged 30 years or older were used. The association between history of DM diagnosis and birth weight was analyzed using logistic regression.
Results: A linear inverse association was observed between birth weight and DM, after adjustment for age, BMI, and parental history of DM. The odds ratio for developing DM per 100 g increase in birth weight was 0.93 (95% confidence interval [CI], 0.90-0.96). The association was unchanged when birth weight was converted to percentile for gestational age. In the BMI-stratified analysis, the odds ratio for DM in the &lt; 2500 g birth weight group reached 4.75 (95% CI, 1.22-18.44, compared to the reference 3000-3499 g group) among women with normal low BMI (18.5-20.9).
Conclusions: Birth weight and its percentile for gestational age were associated with adult-onset DM. Attention should be paid to the risk of DM among women born with low weight, even when their current BMI is normal. (C) 2017 The Authors. Publishing services by Elsevier B.V. on behalf of The Japan Epidemiological Association.

DOI： 10.1016/j.je.2016.08.016

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：NATURE PUBLISHING GROUP  

Handgrip strength is useful for the diagnosis of sarcopenia. We examined the associations of handgrip strength with all-cause mortality, cardiovascular events, and hospitalization in patients with type 2 diabetes. From April 2013 to December 2015, we conducted a retrospective cohort study to examine patients with type 2 diabetes whose handgrip strength was measured at our hospital. All patients were followed up until May 2016. A total of 1,282 patients (63.8 +/- 13.9 years) were enrolled and followed up for 2.36 +/- 0.73 years. During the follow-up period, 20 patients (1.6%) died, 14 (1.1%) experienced cardiovascular events, and 556 (43.4%) were admitted to our hospital for any diseases. Multiple regression analyses revealed that handgrip strength was favorably associated with abdominal obesity and renal function. Moreover, Cox proportional hazard analyses with adjustment for potential confounding variables revealed that handgrip strength was significantly associated with occurrence of CVD events and hospitalization in all subjects. In addition, handgrip strength was significantly associated with mortality and hospitalization in men and with hospitalization in women. Handgrip strength could be a prognostic indicator for health as well as a diagnostic marker of skeletal muscle mass loss in Japanese patients with type 2 diabetes.

DOI： 10.1038/s41598-017-07438-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：MASSACHUSETTS MEDICAL SOC  

BACKGROUNDAlthough the rising pandemic of obesity has received major attention in many countries, the effects of this attention on trends and the disease burden of obesity remain uncertain.METHODSWe analyzed data from 68.5 million persons to assess the trends in the prevalence of overweight and obesity among children and adults between 1980 and 2015. Using the Global Burden of Disease study data and methods, we also quantified the burden of disease related to high body-mass index (BMI), according to age, sex, cause, and BMI in 195 countries between 1990 and 2015.RESULTSIn 2015, a total of 107.7 million children and 603.7 million adults were obese. Since 1980, the prevalence of obesity has doubled in more than 70 countries and has continuously increased in most other countries. Although the prevalence of obesity among children has been lower than that among adults, the rate of increase in childhood obesity in many countries has been greater than the rate of increase in adult obesity. High BMI accounted for 4.0 million deaths globally, nearly 40% of which occurred in persons who were not obese. More than two thirds of deaths related to high BMI were due to cardiovascular disease. The disease burden related to high BMI has increased since 1990; however, the rate of this increase has been attenuated owing to decreases in underlying rates of death from cardiovascular disease.CONCLUSIONSThe rapid increase in the prevalence and disease burden of elevated BMI highlights the need for continued focus on surveillance of BMI and identification, implementation, and evaluation of evidence-based interventions to address this problem. (Funded by the Bill and Melinda Gates Foundation.)

DOI： 10.1056/NEJMoa1614362

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER MEDICAL ASSOC  

IMPORTANCE Comprehensive and timely monitoring of disease burden in all age groups, including children and adolescents, is essential for improving population health.OBJECTIVE To quantify and describe levels and trends of mortality and nonfatal health outcomes among children and adolescents from 1990 to 2015 to provide a framework for policy discussion.EVIDENCE REVIEW Cause-specific mortality and nonfatal health outcomes were analyzed for 195 countries and territories by age group, sex, and year from 1990 to 2015 using standardized approaches for data processing and statistical modeling, with subsequent analysis of the findings to describe levels and trends across geography and time among children and adolescents 19 years or younger. A composite indicator of income, education, and fertility was developed (Socio-demographic Index [SDI]) for each geographic unit and year, which evaluates the historical association between SDI and health loss.FINDINGS Global child and adolescent mortality decreased from 14.18 million (95% uncertainty interval [UI], 14.09 million to 14.28 million) deaths in 1990 to 7.26 million (95% UI, 7.14 million to 7.39 million) deaths in 2015, but progress has been unevenly distributed. Countries with a lower SDI had a larger proportion of mortality burden (75%) in 2015 than was the case in 1990 (61%). Most deaths in 2015 occurred in South Asia and sub-Saharan Africa. Global trends were driven by reductions in mortality owing to infectious, nutritional, and neonatal disorders, which in the aggregate led to a relative increase in the importance of noncommunicable diseases and injuries in explaining global disease burden. The absolute burden of disability in children and adolescents increased 4.3%(95% UI, 3.1%-5.6%) from 1990 to 2015, with much of the increase owing to population growth and improved survival for children and adolescents to older ages. Other than infectious conditions, many top causes of disability are associated with long-term sequelae of conditions present at birth (eg, neonatal disorders, congenital birth defects, and hemoglobinopathies) and complications of a variety of infections and nutritional deficiencies. Anemia, developmental intellectual disability, hearing loss, epilepsy, and vision loss are important contributors to childhood disability that can arise from multiple causes. Maternal and reproductive health remains a key cause of disease burden in adolescent females, especially in lower-SDI countries. In low-SDI countries, mortality is the primary driver of health loss for children and adolescents, whereas disability predominates in higher-SDI locations; the specific pattern of epidemiological transition varies across diseases and injuries.CONCLUSIONS AND RELEVANCE Consistent international attention and investment have led to sustained improvements in causes of health loss among children and adolescents in many countries, although progress has been uneven. The persistence of infectious diseases in some countries, coupled with ongoing epidemiologic transition to injuries and noncommunicable diseases, require all countries to carefully evaluate and implement appropriate strategies to maximize the health of their children and adolescents and for the international community to carefully consider which elements of child and adolescent health should be monitored.

DOI： 10.1001/jamapediatrics.2017.0250

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

We aimed to examine prevalence, patient characteristics, etiology, and clinical outcomes of hospitalized patients who had hypoglycemia without a diagnosis of diabetes mellitus, using a Japanese nationwide database.
This was a retrospective observational study using a national database of acute-care inpatients in Japan. Nondiabetic patients aged &gt;= 15 years who were hospitalized for hypoglycemia were eligible. We estimated the annual numbers of hospitalized cases in Japan. We also investigated the patient characteristics, and risk factors of in-hospital mortality.
We identified 8684 eligible patients out of 22.7 million discharge records between July 2008 and March 2013. The average age was 70.0 years and the average body mass index (BMI) was 19.9kg/m(2). Most frequently recorded underlying diseases were malignancies, cerebrovascular diseases, pneumonia, renal failure, and heart failure. The estimated annual numbers of hospitalizations because of hypoglycemia in nondiabetic patients were 5000 to 7000. In-hospital mortality was 14.9%, and predictive factors for poor survival included older age, community hospital, low BMI, coma at admission, urgent admission, renal failure, heart failure, pneumonia, sepsis, chronic liver diseases, and malignancies.
Patients without diabetes mellitus but with hypoglycemia had multiple comorbidities and high in-hospital mortality. Clinicians should carefully investigate the etiology of hypoglycemia in nondiabetic patients, and treat the underlying diseases.

DOI： 10.1097/MD.0000000000007271

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER IRELAND LTD  

Aims: To clarify the associations between plasma adiponectin levels and ADIPOQ variants with type 2 diabetes incidence in a general Japanese population.
Methods: We conducted a case-control study nested within the Japan Public Health Center-based Prospective Study. We measured plasma adiponectin levels and genotyped +45T &gt; G (rs2241766) and +276 G &gt; T (rs1501299) in the ADIPOQ gene among 417 incident diabetes cases and 1197 control subjects matched by age, sex, and area.
Results: After potential confounding factor adjustment, the multivariable-adjusted diabetes odds ratios (ORs) were 0.59 (95% confidence interval [CI]: 0.51-0.68) and 0.68 (95% CI: 0.60-0.78) per 1 standard deviation increment in the log-transformed levels of total- and high-molecular-weight (HMW) adiponectin levels, respectively. However, the ADIPOQ variants were not significantly associated with plasma adiponectin levels (for total adiponectin, +45 P = 0.15 and +276 P = 0.08) and diabetes risk (+45 P = 0.70 and +276 P = 0.72) under the additive genetic model.
Conclusions: Our prospective findings suggest that both total and HMW adiponectin levels are strongly and inversely associated with diabetes risk after adjustment for potential confounding factors; however, the ADIPOQ variants +45 and +276 are not associated with adiponectin levels and diabetes risk in the general Japanese population. (C) 2017 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

DOI： 10.1016/j.diabres.2017.03.020

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

Few studies have examined the association between smoking behavior (especially quitters) at the time of diagnosis and mortality among cancer patients. Our objective was to examine the benefits of quitting on all-cause mortality among cancer patients. 30,658 eligible cancer patients diagnosed between 1985 and 2009, identified by a hospital-based cancer registry in Japan, were followed up for up to 10 years. We evaluated smoking behavior at cancer diagnosis (especially recent quitters vs. current smokers) in association with all-cause mortality using Cox-proportional hazards models and covariates-adjusted survival curves. Risk of death was estimated to be reduced by 11% in recent quitters compared with current smokers. According to adjusted survival curves, median survival time was 8.25 years for recent quitters versus 7.18 years for current smokers, indicating an absolute difference of 1.07 year for a median survivor. Similarly, never and former smokers had 18% and 16% lower risk of death with 1.90 years and 1.77 years gained, respectively, compared with current smokers. In addition to former and never smokers, recent quitters showed consistently higher survival rates than current smokers during the 10-year calendar period after diagnosis among cancer patients. Because recent quitters may be similar to patients who stop smoking shortly after cancer diagnosis in terms of smoking duration, the latter may be able to decrease their risk of death, suggesting that smoking cessation could be part of cancer care.

DOI： 10.1002/ijc.30601

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Public Library of Science  

To examine associations between work-family conflict and self-rated health among Japanese workers and to determine whether the associations differed by household income. Data was derived from the Japan Public Health Center-based Prospective Study for the Next Generation in Saku area in 2011-2012 (7,663 men and 7,070 women). Multivariate odds ratios (ORs) and 95% confidence intervals (CIs) for poor self-rated health by work- family conflict consisting of two dimensions (work-to-family and family-to-work conflicts) were calculated by gender and household income. Multivariate ORs of high work-to-family and family-to-work conflicts for poor self-rated health were 2.46 (95% CI
2.04-2.97) for men and 3.54 (95% CI
2.92-4.30) for women, with reference to the low work-to-family and family-to-work conflicts (p-value for gender interaction = 0.02). Subgroup analysis indicated that health effects of work-family conflict were likely to be more evident in the low income group only among women. Work-family conflict was associated with poor self-rated health among middle-aged Japanese men and women
its health impact was relatively stronger among women, and particularly economically disadvantaged women. Copyright:

DOI： 10.1371/journal.pone.0169903

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記述言語：英語   出版者・発行元：WILEY  

Background
Three classes of inhaler medications are used to manage chronic obstructive pulmonary disease (COPD): long-acting beta-agonists (LABA), long-acting muscarinic antagonists (LAMA), and inhaled corticosteroids (ICS). When two classes of medications are required, LAMA plus LABA (LAMA+LABA) and LABA plus ICS (LABA+ICS) are often selected because these combinations can be administered via a single medication device. The previous Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidance recommended LABA+ICS as the first-line treatment for managing stable COPD in high-risk people of categories C and D. However, the updated GOLD 2017 guidance recommends LAMA+LABA over LABA+ICS.
Objectives
To compare the benefits and harms of LAMA+LABA versus LABA+ICS for treatment of people with stable COPD.
Search methods
We performed an electronic search of the Cochrane Airways Group Specialised Register (2 February 2016), ClinicalTrials.gov (4 June 2016), and the World Health Organization Clinical Trials Search Portal (4 June 2016), followed by a handsearch (5 June 2016). Two review authors screened and scrutinised the selected articles.
Selection criteria
We included individual randomised controlled trials, parallel-group trials, and cross-over trials comparing LAMA+LABA and LABA+ICS for stable COPD. The minimum accepted trial duration was one month and trials should have been conducted in an outpatient setting.
Data collection and analysis
Two review authors independently extracted data and evaluated risk of bias. We resolved any discrepancies through discussion. We analysed dichotomous data as odds ratios (OR), and continuous data as mean differences (MD), with 95% confidence interval (CI) using Review Manager 5. Exacerbations were measured by counting the number of people experiencing one or more exacerbation.
Main results
We included 11 studies comprising 9839 participants in our quantitative analysis. Most studies included people with moderate to severe COPD, without recent exacerbations. One pharmaceutical sponsored trial that included only people with recent exacerbations was the largest study and accounted for 37% of participants. All but one study were sponsored by pharmaceutical companies, thus we rated them as having a high risk of 'other bias'. The unsponsored study was at high risk of performance and detection bias, and possible selective reporting.
Five studies recruited GOLD Category B participants, one study recruited Category D participants, two studies recruited Category A/B participants, and three studies recruited participants regardless of category. Follow-up ranged from 6 to 52 weeks.
Compared to the LABA+ICS arm, the results for the pooled primary outcomes for the LAMA+LABA arm were as follows: exacerbations, OR 0.82 (95% CI 0.70 to 0.96, P = 0.01, I-2 = 17%, low quality evidence); serious adverse events (SAE), OR 0.91 (95% CI 0.79 to 1.05, P = 0.18, I-2 = 0, moderate quality evidence); St. George's Respiratory Questionnaire (SGRQ) total score change from the baseline, MD -1.22 (95% CI -2.52 to 0.07, P = 0.06, I-2 = 71%, low quality evidence); and trough forced expiratory volume in one second (FEV1) change from the baseline, MD 0.08 L (95% CI 0.06 to 0.09, P &lt; 0.0001, I-2 = 50%, moderate quality evidence). Compared to the LABA+ICS arm, the results for the pooled secondary outcomes for the LAMA+LABA arm were as follows: pneumonia, OR 0.57 (95% CI 0.42 to 0.79, P = 0.0006, I-2 = 0%, low quality evidence); all-cause death, OR 1.01 (95% CI 0.61 to 1.67, P = 0.88, I-2 = 0%, low quality evidence); and SGRQ total score change from the baseline of 4 points or greater (the minimal clinically important difference for the SGRQ is 4 points), OR 1.25 (95% CI 1.09 to 1.44, P = 0.002, I-2 = 0%, moderate quality evidence).
Authors' conclusions
For the treatment of COPD, LAMA+LABA has fewer exacerbations, a larger improvement of FEV1, a lower risk of pneumonia, and more frequent improvement in quality of life as measured by an increase over 4 units or more of the SGRQ. These data were supported by low or moderate quality evidence generated from mainly participants with moderate to severe COPD in heterogeneous trials with an observation period of less than one year. Our findings support the recently updated GOLD guidance.

DOI： 10.1002/14651858.CD012066.pub2

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

Background In transitioning from the Millennium Development Goal to the Sustainable Development Goal era, it is imperative to comprehensively assess progress toward reducing maternal mortality to identify areas of success, remaining challenges, and frame policy discussions. We aimed to quantify maternal mortality throughout the world by underlying cause and age from 1990 to 2015.
Methods We estimated maternal mortality at the global, regional, and national levels from 1990 to 2015 for ages 10-54 years by systematically compiling and processing all available data sources from 186 of 195 countries and territories, 11 of which were analysed at the subnational level. We quantified eight underlying causes of maternal death and four timing categories, improving estimation methods since GBD 2013 for adult all-cause mortality, HIV-related maternal mortality, and late maternal death. Secondary analyses then allowed systematic examination of drivers of trends, including the relation between maternal mortality and coverage of specific reproductive health-care services as well as assessment of observed versus expected maternal mortality as a function of Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility.
Findings Only ten countries achieved MDG 5, but 122 of 195 countries have already met SDG 3.1. Geographical disparities widened between 1990 and 2015 and, in 2015, 24 countries still had a maternal mortality ratio greater than 400. The proportion of all maternal deaths occurring in the bottom two SDI quintiles, where haemorrhage is the dominant cause of maternal death, increased from roughly 68% in 1990 to more than 80% in 2015. The middle SDI quintile improved the most from 1990 to 2015, but also has the most complicated causal profile. Maternal mortality in the highest SDI quintile is mostly due to other direct maternal disorders, indirect maternal disorders, and abortion, ectopic pregnancy, and/or miscarriage. Historical patterns suggest achievement of SDG 3.1 will require 91% coverage of one antenatal care visit, 78% of four antenatal care visits, 81% of in-facility delivery, and 87% of skilled birth attendance.
Interpretation Several challenges to improving reproductive health lie ahead in the SDG era. Countries should establish or renew systems for collection and timely dissemination of health data; expand coverage and improve quality of family planning services, including access to contraception and safe abortion to address high adolescent fertility; invest in improving health system capacity, including coverage of routine reproductive health care and of more advanced obstetric care-including EmOC; adapt health systems and data collection systems to monitor and reverse the increase in indirect, other direct, and late maternal deaths, especially in high SDI locations; and examine their own performance with respect to their SDI level, using that information to formulate strategies to improve performance and ensure optimum reproductive health of their population.

DOI： 10.1016/S0140-6736(16)31470-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

Background Healthy life expectancy (HALE) and disability-adjusted life-years (DALYs) provide summary measures of health across geographies and time that can inform assessments of epidemiological patterns and health system performance, help to prioritise investments in research and development, and monitor progress toward the Sustainable Development Goals (SDGs). We aimed to provide updated HALE and DALYs for geographies worldwide and evaluate how disease burden changes with development.Methods We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015) for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2015. We calculated DALYs by summing years of life lost (YLLs) and years of life lived with disability (YLDs) for each geography, age group, sex, and year. We estimated HALE using the Sullivan method, which draws from age-specific death rates and YLDs per capita. We then assessed how observed levels of DALYs and HALE differed from expected trends calculated with the Socio-demographic Index (SDI), a composite indicator constructed from measures of income per capita, average years of schooling, and total fertility rate.Findings Total global DALYs remained largely unchanged from 1990 to 2015, with decreases in communicable, neonatal, maternal, and nutritional (Group 1) disease DALYs off set by increased DALYs due to non-communicable diseases (NCDs). Much of this epidemiological transition was caused by changes in population growth and ageing, but it was accelerated by widespread improvements in SDI that also correlated strongly with the increasing importance of NCDs. Both total DALYs and age-standardised DALY rates due to most Group 1 causes significantly decreased by 2015, and although total burden climbed for the majority of NCDs, age-standardised DALY rates due to NCDs declined. Nonetheless, age-standardised DALY rates due to several high-burden NCDs (including osteoarthritis, drug use disorders, depression, diabetes, congenital birth defects, and skin, oral, and sense organ diseases) either increased or remained unchanged, leading to increases in their relative ranking in many geographies. From 2005 to 2015, HALE at birth increased by an average of 2.9 years (95% uncertainty interval 2.9-3.0) for men and 3.5 years (3.4-3.7) for women, while HALE at age 65 years improved by 0.85 years (0.78-0.92) and 1.2 years (1.1-1.3), respectively. Rising SDI was associated with consistently higher HALE and a somewhat smaller proportion of life spent with functional health loss; however, rising SDI was related to increases in total disability. Many countries and territories in central America and eastern sub-Saharan Africa had increasingly lower rates of disease burden than expected given their SDI. At the same time, a subset of geographies recorded a growing gap between observed and expected levels of DALYs, a trend driven mainly by rising burden due to war, interpersonal violence, and various NCDs.Interpretation Health is improving globally, but this means more populations are spending more time with functional health loss, an absolute expansion of morbidity. The proportion of life spent in ill health decreases somewhat with increasing SDI, a relative compression of morbidity, which supports continued efforts to elevate personal income, improve education, and limit fertility. Our analysis of DALYs and HALE and their relationship to SDI represents a robust framework on which to benchmark geography-specific health performance and SDG progress. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform financial and research investments, prevention efforts, health policies, and health system improvement initiatives for all countries along the development continuum. Copyright (C) The Author(s). Published by Elsevier Ltd.

DOI： 10.1016/S0140-6736(16)31460-X

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

Background Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures.Methods We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER).Findings Globally, life expectancy from birth increased from 61.7 years (95% uncertainty interval 61.4-61.9) in 1980 to 71.8 years (71.5-72.2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11.3 years (3.7-17.4), to 62.6 years (56.5-70.2). Total deaths increased by 4.1% (2.6-5.6) from 2005 to 2015, rising to 55.8 million (54.9 million to 56.6 million) in 2015, but age-standardised death rates fell by 17.0% (15.8-18.1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14.1% (12.6-16.0) to 39.8 million (39.2 million to 40.5 million) in 2015, whereas age-standardised rates decreased by 13.1% (11.9-14.3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42.1%, 39.1-44.6), malaria (43.1%, 34.7-51.8), neonatal preterm birth complications (29.8%, 24.8-34.9), and maternal disorders (29.1%, 19.3-37.1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death.Interpretation At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems. Copyright (C) The Author(s). Published by Elsevier Ltd.

DOI： 10.1016/S0140-6736(16)31012-1

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

Background Non-fatal outcomes of disease and injury increasingly detract from the ability of the world's population to live in full health, a trend largely attributable to an epidemiological transition in many countries from causes affecting children, to non-communicable diseases (NCDs) more common in adults. For the Global Burden of Diseases, Injuries, and Risk Factors Study 2015 (GBD 2015), we estimated the incidence, prevalence, and years lived with disability for diseases and injuries at the global, regional, and national scale over the period of 1990 to 2015.Methods We estimated incidence and prevalence by age, sex, cause, year, and geography with a wide range of updated and standardised analytical procedures. Improvements from GBD 2013 included the addition of new data sources, updates to literature reviews for 85 causes, and the identification and inclusion of additional studies published up to November, 2015, to expand the database used for estimation of non-fatal outcomes to 60 900 unique data sources. Prevalence and incidence by cause and sequelae were determined with DisMod-MR 2.1, an improved version of the DisMod-MR Bayesian meta-regression tool first developed for GBD 2010 and GBD 2013. For some causes, we used alternative modelling strategies where the complexity of the disease was not suited to DisMod-MR 2.1 or where incidence and prevalence needed to be determined from other data. For GBD 2015 we created a summary indicator that combines measures of income per capita, educational attainment, and fertility (the Socio-demographic Index [SDI]) and used it to compare observed patterns of health loss to the expected pattern for countries or locations with similar SDI scores.Findings We generated 9.3 billion estimates from the various combinations of prevalence, incidence, and YLDs for causes, sequelae, and impairments by age, sex, geography, and year. In 2015, two causes had acute incidences in excess of 1 billion: upper respiratory infections (17.2 billion, 95% uncertainty interval [UI] 15.4-19.2 billion) and diarrhoeal diseases (2.39 billion, 2.30-2.50 billion). Eight causes of chronic disease and injury each affected more than 10% of the world's population in 2015: permanent caries, tension-type headache, iron-deficiency anaemia, age-related and other hearing loss, migraine, genital herpes, refraction and accommodation disorders, and ascariasis. The impairment that affected the greatest number of people in 2015 was anaemia, with 2.36 billion (2.35-2.37 billion) individuals affected. The second and third leading impairments by number of individuals affected were hearing loss and vision loss, respectively. Between 2005 and 2015, there was little change in the leading causes of years lived with disability (YLDs) on a global basis. NCDs accounted for 18 of the leading 20 causes of age-standardised YLDs on a global scale. Where rates were decreasing, the rate of decrease for YLDs was slower than that of years of life lost (YLLs) for nearly every cause included in our analysis. For low SDI geographies, Group 1 causes typically accounted for 20-30% of total disability, largely attributable to nutritional deficiencies, malaria, neglected tropical diseases, HIV/AIDS, and tuberculosis. Lower back and neck pain was the leading global cause of disability in 2015 in most countries. The leading cause was sense organ disorders in 22 countries in Asia and Africa and one in central Latin America; diabetes in four countries in Oceania; HIV/AIDS in three southern sub-Saharan African countries; collective violence and legal intervention in two north African and Middle Eastern countries; iron-deficiency anaemia in Somalia and Venezuela; depression in Uganda; onchoceriasis in Liberia; and other neglected tropical diseases in the Democratic Republic of the Congo.Interpretation Ageing of the world's population is increasing the number of people living with sequelae of diseases and injuries. Shifts in the epidemiological profile driven by socioeconomic change also contribute to the continued increase in years lived with disability (YLDs) as well as the rate of increase in YLDs. Despite limitations imposed by gaps in data availability and the variable quality of the data available, the standardised and comprehensive approach of the GBD study provides opportunities to examine broad trends, compare those trends between countries or subnational geographies, benchmark against locations at similar stages of development, and gauge the strength or weakness of the estimates available. Copyright (C) The Author(s). Published by Elsevier Ltd.

DOI： 10.1016/s0140-6736(16)31678-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context.Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors-the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI).Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57.8% (95% CI 56.6-58.8) of global deaths and 41.2% (39.8-42.8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211.8 million [192.7 million to 231.1 million] global DALYs), smoking (148.6 million [134.2 million to 163.1 million]), high fasting plasma glucose (143.1 million [125.1 million to 163.5 million]), high BMI (120.1 million [83.8 million to 158.4 million]), childhood undernutrition (113.3 million [103.9 million to 123.4 million]), ambient particulate matter (103.1 million [90.8 million to 115.1 million]), high total cholesterol (88.7 million [74.6 million to 105.7 million]), household air pollution (85.6 million [66.7 million to 106.1 million]), alcohol use (85.0 million [77.2 million to 93.0 million]), and diets high in sodium (83.0 million [49.3 million to 127.5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa.Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Copyright (C) The Author(s). Published by Elsevier Ltd.

DOI： 10.1016/S0140-6736(16)31679-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER INC  

Background Timely assessment of the burden of HIV/AIDS is essential for policy setting and programme evaluation. In this report from the Global Burden of Disease Study 2015 (GBD 2015), we provide national estimates of levels and trends of HIV/AIDS incidence, prevalence, coverage of antiretroviral therapy (ART), and mortality for 195 countries and territories from 1980 to 2015.Methods For countries without high-quality vital registration data, we estimated prevalence and incidence with data from antenatal care clinics and population-based seroprevalence surveys, and with assumptions by age and sex on initial CD4 distribution at infection, CD4 progression rates (probability of progression from higher to lower CD4 cell-count category), on and off antiretroviral therapy (ART) mortality, and mortality from all other causes. Our estimation strategy links the GBD 2015 assessment of all-cause mortality and estimation of incidence and prevalence so that for each draw from the uncertainty distribution all assumptions used in each step are internally consistent. We estimated incidence, prevalence, and death with GBD versions of the Estimation and Projection Package (EPP) and Spectrum software originally developed by the Joint United Nations Programme on HIV/AIDS (UNAIDS). We used an open-source version of EPP and recoded Spectrum for speed, and used updated assumptions from systematic reviews of the literature and GBD demographic data. For countries with high-quality vital registration data, we developed the cohort incidence bias adjustment model to estimate HIV incidence and prevalence largely from the number of deaths caused by HIV recorded in cause-of-death statistics. We corrected these statistics for garbage coding and HIV misclassification.Findings Global HIV incidence reached its peak in 1997, at 3.3 million new infections (95% uncertainty interval [UI] 3.1-3.4 million). Annual incidence has stayed relatively constant at about 2.6 million per year (range 2.5-2.8 million) since 2005, after a period of fast decline between 1997 and 2005. The number of people living with HIV/AIDS has been steadily increasing and reached 38.8 million (95% UI 37.6-40.4 million) in 2015. At the same time, HIV/AIDS mortality has been declining at a steady pace, from a peak of 1.8 million deaths (95% UI 1.7-1.9 million) in 2005, to 1.2 million deaths (1.1-1.3 million) in 2015. We recorded substantial heterogeneity in the levels and trends of HIV/AIDS across countries. Although many countries have experienced decreases in HIV/AIDS mortality and in annual new infections, other countries have had slowdowns or increases in rates of change in annual new infections.Interpretation Scale-up of ART and prevention of mother-to-child transmission has been one of the great successes of global health in the past two decades. However, in the past decade, progress in reducing new infections has been slow, development assistance for health devoted to HIV has stagnated, and resources for health in low-income countries have grown slowly. Achievement of the new ambitious goals for HIV enshrined in Sustainable Development Goal 3 and the 90-90-90 UNAIDS targets will be challenging, and will need continued efforts from governments and international agencies in the next 15 years to end AIDS by 2030. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license

DOI： 10.1016/S2352-3018(16)30087-X

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Blackwell Publishing Ltd  

Aims: To evaluate the effect of multifaceted interventions using the Achievable Benchmark of Care (ABC) method for improving the technical quality of diabetes care in primary care settings. Methods: We conducted a 1-year cluster randomized controlled trial in 22 regions divided into an intervention group (IG) or control group (CG). Physicians in the IG received a monthly report of their care quality, with the top 10% quality of diabetes care scores for all physicians being the achievable benchmark. The change in quality-of-care scores between the IG and CG during follow-up was analysed using a generalized linear model considering clustering. Results: A total of 2199 patients were included. Their mean (sd) age was 56.5 ± 5.9 years and the mean (sd) HbA1c level was 56.4 ± 13.3 mmol/mol (7.4 ± 1.2%). The quality-of-care score in the CG changed from 50.2%-point at baseline to 51%-point at 12 months, whereas the IG score changed from 49.9%-point to 69.6%-point, with statistically significant differences between the two groups during follow-up [the effect of intervention was 19.0%-point (95% confidence interval 16.7%- to 21.3%-point
P &lt
0.001)]. Conclusions: Multifaceted intervention, measuring quality-of-care indicators and providing feedback regarding the quality of diabetes care to physicians with ABC, was effective for improving the technical quality of care in patients with Type 2 diabetes in primary care settings. (Trial Registration: umin.ac.jp/ctr as UMIN000002186)

DOI： 10.1111/dme.12949

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER SOC NUTRITION-ASN  

Background: Diet-induced metabolic acidosis has been linked to cardiometabolic abnormalities in Westerners, but the evidence on this issue is scarce in Asians.
Objective: The present study prospectively examined the association between dietary acid load and type 2 diabetes (T2D) in Japanese adults.
Methods: Study participants were 27,809 men and 36,851 women, aged 45-75 y, who completed a dietary questionnaire of the second survey of the Japan Public Health Center based Prospective Study and had no previous history of T2D. Dietary intake was assessed by using a validated 147-item food-frequency questionnaire. Potential renal acid load (PRAL) and net endogenous acid production (NEAP) scores were derived from the nutrient intake. A multilevel logistic regression model was used to estimate ORs and 95% Cis of self-reported, physician-diagnosed T2D over 5 y, with adjustment for potential confounding variables.
Results: A total of 1191 cases of newly diagnosed T2D were reported. PRAL score was positively associated with T2D in men; the multivariable-adjusted ORs (95% CIs) for the lowest through the highest quartiles of PRAL were 1.00, 1.09 (0.87, 1.36), 1.10 (0.88, 1.37), and 1.25 (1.01, 1.55) (P-trend = 0.047). Further adjustment for dietary intake strengthened the association. NEAP score was not associated with the risk of T2D (P-trend = 0.20). In stratified analyses, the positive association between PRAL and T2D was confined to younger men (age &lt;50 y; P-trend = 0.046). There was no association between dietary acid load score and T2D in women.
Conclusion: A high dietary acid load score is associated with an increased risk of T2D in Japanese men.

DOI： 10.3945/jn.115.225177

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN EPIDEMIOLOGICAL ASSOC  

Background: The association between time spent walking and risk of diabetes was investigated in a Japanese population-based cohort.
Methods: Data from the Japan Public Health Center-based Prospective Diabetes cohort were analyzed. The surveys of diabetes were performed at baseline and at the 5-year follow-up. Time spent walking per day was assessed using a self-reported questionnaire (&lt;30 minutes, 30 minutes to &lt;1 hour, 1 to &lt;2 hours, or &gt;= 2 hours). A cross-sectional analysis was performed among 26 488 adults in the baseline survey. Logistic regression was used to examine the association between time spent walking and the presence of unrecognized diabetes. We then performed a longitudinal analysis that was restricted to 11 101 non-diabetic adults who participated in both the baseline and 5-year surveys. The association between time spent walking and the incidence of diabetes during the 5 years was examined.
Results: In the cross-sectional analysis, 1058 participants had unrecognized diabetes. Those with time spent walking of &lt;30 minutes per day had increased odds of having diabetes in relation to those with time spent walking of &gt;= 2 hours (adjusted odds ratio [OR] 1.23; 95% CI, 1.02-1.48). In the longitudinal analysis, 612 participants developed diabetes during the 5 years of follow-up. However, a significant association between time spent walking and the incidence of diabetes was not observed.
Conclusions: Increased risk of diabetes was implied in those with time spent walking of &lt;30 minutes per day, although the longitudinal analysis failed to show a significant result.

DOI： 10.2188/jea.JE20150059

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Previous studies have reported associations between diabetes and cancer risk. However, specific association of hemoglobin A1c (HbA1c) levels with cancer risk remains inconclusive. We followed 29,629 individuals (11,336 men; 18,293 women) aged 46-80 years who participated in the Japan Public Health Center-based prospective study who had HbA1c measurements available and were cancer-free at baseline. Cancer incidence was assessed by systemic surveys. We estimated hazard ratios (HRs) for cancer risk with adjustment for age sex, geographic area, body mass index, smoking status, physical activity, alcohol, coffee, vegetable and total energy consumption, and history of cardiovascular disease. After a median follow-up of 8.5 years, 1,955 individuals had developed cancer. Higher HbA1c levels within both the non-diabetic and diabetic ranges in individuals without known diabetes were associated with overall cancer risk. Compared with individuals without known diabetes and HbA1c levels of 5.0-5.4%, the HRs for all cancers were 1.27 (95% confidence interval, 1.07-1.52); 1.01 (0.90-1.14); 1.28 (1.09-1.49); and 1.43 (1.14-1.80) for individuals without known diabetes and HbA1c levels &lt;5.0%, 5.5-5.9%, 6.0-6.4%, and &gt;= 6.5%, respectively, and 1.23 (1.02-1.47) for individuals with known diabetes. The lowest HbA1c group had the highest risk of liver cancer, and HbA1c levels were linearly associated with the risk of all cancers after excluding liver cancer (P for linear trend, 0.004). In conclusion, our findings corroborate the notion that glycemic control in individuals with high HbA1c levels may be important not only to prevent diabetes but also to prevent cancer.

DOI： 10.1002/ijc.29917

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Diabetes mellitus constitutes a major disease burden globally, and the prevalence of diabetes continues to increase worldwide. We aimed to estimate the burden of cancer associated with type 2 diabetes mellitus in Japan between 2010 and 2030. In this study, we estimated the population attributable fraction of cancer risk associated with type 2 diabetes in 2010 and 2030 using the prevalence estimates of type 2 diabetes in Japan from 1990 to 2030, summary hazard ratios of diabetes and cancer risk from a pooled analysis of eight large-scale Japanese cohort studies, observed incidence / mortality of cancer in 2010 and predicted incidence / mortality for 2030 derived from the age-period-cohort model. Our results showed that between 2010 and 2030, the total numbers of cancer incidence and mortality were predicted to increase by 38.9% and 10.5% in adults aged above 20 years, respectively. In the number of excess incident cancer cases associated with type 2 diabetes, an increase of 26.5% in men and 53.2% in women is expected between 2010 and 2030. The age-specific analysis showed that the population attributable fraction of cancer will increase in adults aged &gt;60 years over time, but will not change in adults aged 20-59 years. In conclusion, this study suggests a modest but steady increase in cancers associated with type 2 diabetes.

DOI： 10.1111/cas.12902

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記述言語：英語   出版者・発行元：AMER MEDICAL ASSOC  

IMPORTANCE The literature focuses on mortality among children younger than 5 years. Comparable information on nonfatal health outcomes among these children and the fatal and nonfatal burden of diseases and injuries among older children and adolescents is scarce.OBJECTIVE To determine levels and trends in the fatal and nonfatal burden of diseases and injuries among younger children (aged < 5 years), older children (aged 5-9 years), and adolescents (aged 10-19 years) between 1990 and 2013 in 188 countries from the Global Burden of Disease (GBD) 2013 study.EVIDENCE REVIEW Data from vital registration, verbal autopsy studies, maternal and child death surveillance, and other sources covering 14 244 site-years (ie, years of cause of death data by geography) from 1980 through 2013 were used to estimate cause-specific mortality. Data from 35 620 epidemiological sources were used to estimate the prevalence of the diseases and sequelae in the GBD 2013 study. Cause-specific mortality for most causes was estimated using the Cause of Death Ensemble Model strategy. For some infectious diseases (eg, HIV infection/AIDS, measles, hepatitis B) where the disease process is complex or the cause of death data were insufficient or unavailable, we used natural history models. For most nonfatal health outcomes, DisMod-MR 2.0, a Bayesian metaregression tool, was used to meta-analyze the epidemiological data to generate prevalence estimates.FINDINGS Of the 7.7 (95% uncertainty interval [UI], 7.4-8.1) million deaths among children and adolescents globally in 2013, 6.28 million occurred among younger children, 0.48 million among older children, and 0.97 million among adolescents. In 2013, the leading causes of death were lower respiratory tract infections among younger children (905 059 deaths; 95% UI, 810304-998 125), diarrheal diseases among older children (38 325 deaths; 95% UI, 30 365-47 678), and road injuries among adolescents (115 186 deaths; 95% UI, 105 185-124 870). Iron deficiency anemia was the leading cause of years lived with disability among children and adolescents, affecting 619 (95% UI, 618-621) million in 2013. Large between-country variations exist in mortality from leading causes among children and adolescents. Countries with rapid declines in all-cause mortality between 1990 and 2013 also experienced large declines in most leading causes of death, whereas countries with the slowest declines had stagnant or increasing trends in the leading causes of death. In 2013, Nigeria had a 12% global share of deaths from lower respiratory tract infections and a 38% global share of deaths from malaria. India had 33% of the world's deaths from neonatal encephalopathy. Half of the world's diarrheal deaths among children and adolescents occurred in just 5 countries: India, Democratic Republic of the Congo, Pakistan, Nigeria, and Ethiopia.CONCLUSIONS AND RELEVANCE Understanding the levels and trends of the leading causes of death and disability among children and adolescents is critical to guide investment and inform policies. Monitoring these trends over time is also key to understanding where interventions are having an impact. Proven interventions exist to prevent or treat the leading causes of unnecessary death and disability among children and adolescents. The findings presented here show that these are underused and give guidance to policy makers in countries where more attention is needed.

DOI： 10.1001/jamapediatrics.2015.4276

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

The Japan Diabetes Society/Japanese Cancer Association Joint Committee on Diabetes and Cancer published its first report in July 2013 on the epidemiological assessment of the associations of diabetes with cancer risk/prognosis, the common risk factors for diabetes and cancer, and cancer risk associated with diabetes treatment. The Joint Committee continued its work to assess the role of glycemic control in the development of cancer in patients with diabetes. This review shows that high-quality evidence examining the association between glycemic control and cancer risk is lacking. In 2014, the Japan Diabetes Society (JDS) and the Japanese Cancer Association (JCA) restarted the JDS/JCA Joint Committee on Diabetes and Cancer, which published the second committee report in Japanese [1]. This is the English version of that report. This article has been jointly published in Diabetology International (doi:) and Cancer Science by the Japan Diabetes Society and the Japanese Cancer Association. Members of the JDS/JCA Joint Committee on Diabetes and Cancer. JDS: Mitsuhiko Noda, Kohjiro Ueki, Masato Kasuga, Naoko Tajima, and Ken Ohashi; Editorial collaborators: Atsushi Goto and Hiroshi Noto; JCA: Ryuichi Sakai, Shoichiro Tsugane, Nobuyuki Hamajima, Kazuo Tajima, Kohzoh Imai, and Hitoshi Nakagama.

DOI： 10.1111/cas.12889

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BMJ PUBLISHING GROUP  

OBJECTIVE
To examine the association between adherence to the Japanese Food Guide Spinning Top and total and cause specific mortality.
DESIGN
Large scale population based prospective cohort study in Japan with follow-up for a median of 15 years.
SETTING
11 public health centre areas across Japan.
PARTICIPANTS
36 624 men and 42 970 women aged 45-75 who had no history of cancer, stroke, ischaemic heart disease, or chronic liver disease.
MAIN OUTCOME MEASURES
Deaths and causes of death identified with the residential registry and death certificates.
RESULTS
Higher scores on the food guide (better adherence) were associated with lower total mortality; the multivariable adjusted hazard ratios (95% confidence interval) of total mortality for the lowest through highest scores were 1.00, 0.92 (0.87 to 0.97), 0.88 (0.83 to 0.93), and 0.85 (0.79 to 0.91) (P&lt; 0.001 for trend) and the multivariable adjusted hazard ratio associated with a 10 point increase in food guide scores was 0.93 (0.91 to 0.95; P&lt; 0.001 for trend). This score was inversely associated with mortality from cardiovascular disease (hazard ratio associated with a 10 point increase 0.93, 0.89 to 0.98; P= 0.005 for trend) and particularly from cerebrovascular disease (0.89, 0.82 to 0.95; P= 0.002 for trend). There was some evidence, though not significant, of an inverse association for cancer mortality (0.96, 0.93 to 1.00; P= 0.053 for trend).
CONCLUSION
Closer adherence to Japanese dietary guidelines was associated with a lower risk of total mortality and mortality from cardiovascular disease, particularly from cerebrovascular disease, in Japanese adults.

DOI： 10.1136/bmj.i1209

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1136/bmj.i1209

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Background-It remains unclear whether severe hypoglycemia is associated with cardiovascular disease (CVD) in Asian populations with type 2 diabetes (T2D). Furthermore, no study in Japan, where the prescription patterns differ from those in other countries, has examined this association.
Methods and Results-We retrospectively included 58 223 patients (18-74 years old) with T2D. First, we examined the potential predictors of severe hypoglycemia. Then, we investigated the association between severe hypoglycemia and CVD risk. Finally, we performed an updated systematic review and meta-analysis to incorporate our findings and recently published studies into the previous systematic review and meta-analysis. During 134 597 person-years from cumulative observation periods, 128 persons experienced severe hypoglycemia and 550 developed CVD events. In a multivariate Cox proportional hazard model, severe hypoglycemia was strongly and positively associated with the risk of CVD (multivariate-adjusted adjusted hazard ratio, 3.39; 95% CI, 1.25-9.18). In a propensity score-matched cohort that had similar baseline characteristics for patients with severe hypoglycemia and those without, severe hypoglycemia was more strongly associated with the risk of CVD. An updated systematic review and meta-analysis that included 10 studies found that severe hypoglycemia was associated with an approximate to 2-fold increased risk of CVD (pooled relative risk, 1.91; 95% CI, 1.69-2.15).
Conclusions-Our results suggest that severe hypoglycemia is strongly associated with an increased risk of CVD in Japanese patients with T2D, further supporting the notion that avoiding severe hypoglycemia may be important in preventing CVD in this patient population.

DOI： 10.1161/JAHA.115.002875

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記述言語：日本語   出版者・発行元：一般社団法人 日本糖尿病学会  

日本糖尿病学会と日本癌学会による合同委員会は，糖尿病と癌罹患リスクや予後などに関する検討を行い2013年7月に委員会報告を出版したが，その後も委員会を開催して糖尿病患者における血糖管理と癌罹患リスクについての検討を行った．本レビューはその報告であり，糖尿病患者における血糖管理と癌罹患リスクに関して，現時点で質の高いエビデンスが存在しないことを明らかにしている．

DOI： 10.11213/tonyobyo.59.174

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その他リンク： http://search.jamas.or.jp/link/ui/2016229976

記述言語：英語   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

Diabetes mellitus, especially type 2 diabetes, has been a major concern among health issues for Japanese policy requiring serious address. In this regard, the increasing number of people with diabetes in Japan over the past few decades has been regarded as a fundamental and evident problem. We herein clarify that the crude diabetes prevalence is likely to have increased mainly as a result of changes in the population distribution, namely, aging of the general population in Japan. We also predict the future trend for the number of people with diabetes according to available concrete evidence in this review.

DOI： 10.2169/internalmedicine.55.6475

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. FINDINGS: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks. FUNDING: Bill & Melinda Gates Foundation.

DOI： 10.1016/S0140-6736(15)00128-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：SPRINGER  

Background Glycated hemoglobin (HbA1c) and glycated albumin (GA) are frequently used as glycemic control markers. However, these markers are influenced by alterations in hemoglobin and albumin metabolism. Thus, conditions such as anemia, chronic renal failure, hypersplenism, chronic liver diseases, hyperthyroidism, hypoalbuminemia, and pregnancy need to be considered when interpreting HbA1c or GA values. Using data from patients with normal albumin and hemoglobin metabolism, we previously established a linear regression equation describing the GA value versus the HbA1c value to calculate an extrapolated HbA1c (eHbA1c) value for the accurate evaluation of glycemic control. In this study, we investigated the difference between the measured HbA1c and the eHbA1c values for patients with various conditions.
MethodsData sets for a total of 2461 occasions were obtained from 731 patients whose HbA1c and GA values were simultaneously measured. We excluded patients with missing data or changeable HbA1c levels, and patients who had received transfusions or steroids within the previous 3 months. Finally, we included 44 patients with chronic renal failure (CRF), 10 patients who were undergoing hemodialysis (HD), 7 patients with hematological malignancies and a hemoglobin level of less than 10 g/dL (HM), and 12 patients with chronic liver diseases (CLD).
ResultsIn all the groups, the eHbA1c values were significantly higher than the measured HbA1c values. The median difference was 0.75 % (95 % CI 0.40-1.10 %, P for the difference is &lt; 0.001) in the CRF group, 0.80 % (95 % CI 0.30-1.65 %, P for the difference is 0.041) in the HD group, 0.90 % (95 % CI 0.90-1.30 %, P for the difference is 0.028) in the HM group, and 0.85 % (95 % CI 0.40-1.50 %, P for the difference is 0.009) in the CLD group.
ConclusionsWe found that the measured HbA1c values were lower than the eHbA1c values in each of the groups.

DOI： 10.1007/s10157-015-1110-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

Background The Global Burden of Disease Study 2013 (GBD 2013) aims to bring together all available epidemiological data using a coherent measurement framework, standardised estimation methods, and transparent data sources to enable comparisons of health loss over time and across causes, age-sex groups, and countries. The GBD can be used to generate summary measures such as disability-adjusted life-years (DALYs) and healthy life expectancy (HALE) that make possible comparative assessments of broad epidemiological patterns across countries and time. These summary measures can also be used to quantify the component of variation in epidemiology that is related to sociodemographic development.Methods We used the published GBD 2013 data for age-specific mortality, years of life lost due to premature mortality (YLLs), and years lived with disability (YLDs) to calculate DALYs and HALE for 1990, 1995, 2000, 2005, 2010, and 2013 for 188 countries. We calculated HALE using the Sullivan method; 95% uncertainty intervals (UIs) represent uncertainty in age-specific death rates and YLDs per person for each country, age, sex, and year. We estimated DALYs for 306 causes for each country as the sum of YLLs and YLDs; 95% UIs represent uncertainty in YLL and YLD rates. We quantified patterns of the epidemiological transition with a composite indicator of sociodemographic status, which we constructed from income per person, average years of schooling after age 15 years, and the total fertility rate and mean age of the population. We applied hierarchical regression to DALY rates by cause across countries to decompose variance related to the sociodemographic status variable, country, and time.Findings Worldwide, from 1990 to 2013, life expectancy at birth rose by 6.2 years (95% UI 5.6-6.6), from 65.3 years (65.0-65.6) in 1990 to 71.5 years (71.0-71.9) in 2013, HALE at birth rose by 5.4 years (4.9-5.8), from 56.9 years (54.5-59.1) to 62.3 years (59.7-64.8), total DALYs fell by 3.6% (0.3-7.4), and age-standardised DALY rates per 100 000 people fell by 26.7% (24.6-29.1). For communicable, maternal, neonatal, and nutritional disorders, global DALY numbers, crude rates, and age-standardised rates have all declined between 1990 and 2013, whereas for non-communicable diseases, global DALYs have been increasing, DALY rates have remained nearly constant, and age-standardised DALY rates declined during the same period. From 2005 to 2013, the number of DALYs increased for most specific non-communicable diseases, including cardiovascular diseases and neoplasms, in addition to dengue, food-borne trematodes, and leishmaniasis; DALYs decreased for nearly all other causes. By 2013, the five leading causes of DALYs were ischaemic heart disease, lower respiratory infections, cerebrovascular disease, low back and neck pain, and road injuries. Sociodemographic status explained more than 50% of the variance between countries and over time for diarrhoea, lower respiratory infections, and other common infectious diseases; maternal disorders; neonatal disorders; nutritional deficiencies; other communicable, maternal, neonatal, and nutritional diseases; musculoskeletal disorders; and other non-communicable diseases. However, sociodemographic status explained less than 10% of the variance in DALY rates for cardiovascular diseases; chronic respiratory diseases; cirrhosis; diabetes, urogenital, blood, and endocrine diseases; unintentional injuries; and self-harm and interpersonal violence. Predictably, increased sociodemographic status was associated with a shift in burden from YLLs to YLDs, driven by declines in YLLs and increases in YLDs from musculoskeletal disorders, neurological disorders, and mental and substance use disorders. In most country-specific estimates, the increase in life expectancy was greater than that in HALE. Leading causes of DALYs are highly variable across countries.Interpretation Global health is improving. Population growth and ageing have driven up numbers of DALYs, but crude rates have remained relatively constant, showing that progress in health does not mean fewer demands on health systems. The notion of an epidemiological transition-in which increasing sociodemographic status brings structured change in disease burden-is useful, but there is tremendous variation in burden of disease that is not associated with sociodemographic status. This further underscores the need for country-specific assessments of DALYs and HALE to appropriately inform health policy decisions and attendant actions.

DOI： 10.1016/S0140-6736(15)61340-X

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer-Verlag Tokyo  

DOI： 10.1007/s13340-015-0206-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Aims/IntroductionTo provide age- and sex-specific trends, age-standardized trends, and projections of diabetes prevalence through the year 2030 in the Japanese adult population.
Materials and MethodsIn the present meta-regression analysis, we included 161,087 adults from six studies and nine national health surveys carried out between 1988 and 2011 in Japan. We assessed the prevalence of diabetes using a recorded history of diabetes or, for the population of individuals without known diabetes, either a glycated hemoglobin level of 6.5% (48mmol/mol) or the 1999 World Health Organization criteria (i.e., a fasting plasma glucose level of 126mg/dL and/or 2-h glucose level of 200mg/dL in the 75-g oral glucose tolerance test).
ResultsFor both sexes, prevalence appeared to remain unchanged over the years in all age categories except for men aged 70years or older, in whom a significant increase in prevalence with time was observed. Age-standardized diabetes prevalence estimates based on the Japanese population of the corresponding year showed marked increasing trends: diabetes prevalence was 6.1% among women (95% confidence interval [CI] 5.5-6.7), 9.9% (95% CI 9.2-10.6) among men, and 7.9% (95% CI 7.5-8.4) among the total population in 2010, and was expected to rise by 2030 to 6.7% (95% CI 5.2-9.2), 13.1% (95% CI 10.9-16.7) and 9.8% (95% CI 8.5-12.0), respectively. In contrast, the age-standardized diabetes prevalence using a fixed population appeared to remain unchanged.
ConclusionsThis large-scale meta-regression analysis shows that a substantial increase in diabetes prevalence is expected in Japan during the next few decades, mainly as a result of the aging of the adult population.

DOI： 10.1111/jdi.12333

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

We aimed to elucidate the epidemiology, patient demographics, and clinical outcomes of hospitalization for hypoglycemia in diabetic patients using a Japanese large-scale database.
We conducted a retrospective study using a national inpatient database of acute care hospitals in Japan. Diabetic patients ages &gt;= 15 years with hypoglycemia as a main diagnosis for hospitalization were eligible. We estimated the annual number of hospitalizations in Japan and compared the annual admission rate by age and treatment groups. We also analyzed the association between patient characteristics and in-hospital mortality.
Among 22.7 million discharge records from July 2008 and March 2013, a total of 25,071 patients were eligible. The mean age was 73.4 years, and the mean body mass index (BMI) was 22.3 kg/m(2). The estimated annual hospitalization for hypoglycemia in Japan was similar to 20,000. Annual admission rates for hypoglycemia per 1000 diabetic patients and 1000 diabetic patients receiving insulin or oral hypoglycemic agents were 2.1 and 4.1, respectively. Patients 70 years old were at a higher risk of hospitalization. In-hospital mortality was 3.8%, and risk factors associated with poor survival were male sex, older age, lower bed capacity, community hospital, low BMI, coma at admission, and higher Charlson Comorbidity Index.
To prevent severe hypoglycemia that leads to death and complications, individualized and careful glycemic control are important, especially in very old or young patients and in those with comorbid conditions or low BMI.

DOI： 10.1097/MD.0000000000001029

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：LIPPINCOTT WILLIAMS & WILKINS  

High hemoglobin A(1c) (HbA(1c)) levels are strongly associated with an increased risk of cardiovascular disease (CVD) in people with and without diabetes. However, information regarding the relationship between low HbA(1c) levels and the risk of CVD among people without known diabetes is limited. The aim of this large-scale, prospective, population-based cohort study was to clarify the association between HbA(1c) levels and CVD risk among people without known diabetes.
We followed-up 10,980 men and 18,079 women (46-80 years old and free of CVD and cancer at baseline) in the Japan Public Health Center-based Prospective Study. Using Cox models, we estimated the hazard ratios for CVD risk with adjustments for age, sex, geographic areas, body mass index, smoking status, sports and physical exercise, alcohol intake, systolic blood pressure, non-high-density lipoprotein cholesterol, and high-density lipoprotein cholesterol.
During the median follow-up of 9.4 years, 935 CVD events (770 strokes and 165 coronary heart diseases) occurred. We observed a nonlinear association between HbA(1c) levels and CVD risk in participants without known diabetes. Compared with HbA(1c) levels of 5.0 to 5.4% (31-36 mmol/mol), the hazard ratios for CVD in participants without known diabetes were 1.50 (95% confidence interval: 1.151.95), 1.01 (0.85-1.20), 1.04 (0.82-1.32), and 1.77 (1.32-2.38) for HbA(1c) levels of &lt; 5.0% (&lt; 31 mmol/mol), 5.5 to 5.9% (37-41 mmol/mol), 6.0 to 6.4% (42-47 mmol/mol), and &gt;= 6.5% (&gt;= 48 mmol/mol), respectively (P value for nonlinear trend: &lt; 0.001). In addition, the hazard ratio for CVD was 1.81 (1.43-2.29) in patients with known diabetes compared with participants with HbA(1c) levels of 5.0 to 5.4% and without known diabetes. This nonlinear relation persisted after excluding people with kidney dysfunction, liver dysfunction, anemia, body mass index &lt;18.5 kg/m(2), or early events within 3 years of followup (P value for nonlinear trend: &lt; 0.01 for all tests).
In conclusion, both low and high levels of HbA(1c) were associated with a higher risk of CVD in a Japanese general population without known diabetes.

DOI： 10.1097/MD.0000000000000785

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY  

To date, the association between diabetes mellitus (DM) and gastric cancer has been controversial, including the underlying mechanism. We investigated the association between plasma diabetic biomarkers (insulin, C-peptide, and blood glucose) and gastric cancer risk. In addition, homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of -cell function (HOMA-) were calculated. A total of 36,745 subjects aged 40-69 years in the Japan Public Health Center-based prospective study (JPHC) who returned the baseline questionnaire and provided blood samples were followed from 1990 to 2004. In the present analysis, 477 cases and 477 matched controls were used. The odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) for developing gastric cancer were calculated using conditional logistic regression models. Plasma insulin was positively associated with increased risk of gastric cancer; compared to tertile 1, ORs were 1.69 (95% CI=1.11-2.59) and 2.01 (1.19-3.38) for tertiles 2 and 3, respectively (p for trend=0.009). In men, C-peptide was also positively associated with a significant risk; corresponding ORs were 1.42 (0.85-2.38) and 1.91 (1.03-3.54), respectively (p for trend=0.04). These findings were confirmed for blood samples from the fasting group (8 hr after a meal). Higher HOMA-IR was also associated with increased risk, whereas no association was observed for blood glucose. Our findings suggest that Japanese population with higher insulin and C-peptide levels derived from insulin resistance have an elevated risk of gastric cancer.
What's new? The idea that diabetes mellitus may play a role in some instances of gastric carcinogenesis is intriguing but controversial. Here, a positive association was identified for gastric cancer risk and plasma insulin levels, based on investigation of plasma biomarkers in a Japanese study population. The association was evident for measures of homeostasis model assessment of insulin resistance (HOMA-IR). By contrast, no association was found for blood glucose levels. The results suggest that hyperinsulinemia derived from insulin resistance, rather than hyperglycemia, is important in gastric carcinogenesis.

DOI： 10.1002/ijc.29098

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

Objective
Evidence is sparse and contradictory regarding the association between low-carbohydrate diet score and type 2 diabetes risk, and no prospective study examined the association among Asians, who consume greater amount of carbohydrate. We prospectively investigated the association of low-carbohydrate diet score with type 2 diabetes risk.
Methods
Participants were 27,799 men and 36,875 women aged 45-75 years who participated in the second survey of the Japan Public Health Center-Based Prospective Study and who had no history of diabetes. Dietary intake was ascertained by using a validated food-frequency questionnaire, and low-carbohydrate diet score was calculated from total carbohydrate, fat, and protein intake. The scores for high animal protein and fat or for high plant protein and fat were also calculated. Odds ratios of self-reported, physician-diagnosed type 2 diabetes over 5-year were estimated by using logistic regression.
Results
During the 5-year period, 1191 new cases of type 2 diabetes were self-reported. Low-carbohydrate diet score for high total protein and fat was significantly associated with a decreased risk of type 2 diabetes in women (P for trend &lt; 0.001); the multivariable-adjusted odds ratio of type 2 diabetes for the highest quintile of the score were 0.63 (95% confidence interval 0.46-0.84), compared with those for the lowest quintile. Additional adjustment for dietary glycemic load attenuated the association (odds ratio 0.75, 95% confidence interval 0.45-1.25). When the score separated for animal and for plant protein and fat, the score for high animal protein and fat was inversely associated with type 2 diabetes in women, whereas the score for high plant protein and fat was not associated in both men and women.
Discussion
Low-carbohydrate diet was associated with decreased risk of type 2 diabetes in Japanese women and this association may be partly attributable to high intake of white rice. The association for animal-based and plant-based low-carbohydrate diet warrants further investigation.

DOI： 10.1371/journal.pone.0118377

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記述言語：英語  

OBJECTIVE: We aimed to examine factors associated with untreated diabetes in a nationally representative sample of the Japanese population. RESEARCH DESIGN AND METHODS: We pooled data from the Japanese National Health and Nutrition Survey from 2005 to 2009 (n = 20,496). Individuals aged 20 years and older were included in the analysis. We classified participants as having diabetes if they had HbA1c levels ≥6.5% (≥48 mmol/mol). People with diabetes who self-reported that they were not currently receiving diabetic treatment were considered to be untreated. We conducted a multinomial logistic regression analysis to determine factors associated with untreated diabetes relative to non-diabetic individuals. RESULTS: Of 20,496 participants who were included in the analysis, untreated diabetes was present in 748 (3.6%). Among participants with untreated diabetes, 48.3% were previously diagnosed with diabetes, and 46.5% had HbA1c levels ≥7.0% (≥53 mmol/mol). Participants with untreated diabetes were significantly more likely than non-diabetic participants to be male, older, and currently smoking, have lower HDL cholesterol levels and higher BMI, non-HDL cholesterol levels, and systolic blood pressure. CONCLUSIONS: A substantial proportion of people in Japan with untreated diabetes have poor glycemic control. Targeting relevant factors for untreated diabetes in screening programs may be effective to enhance the treatment and control of diabetes.

DOI： 10.1371/journal.pone.0118749

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掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/S0140-6736(14)61682-2

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BMJ PUBLISHING GROUP  

Objective: To examine the association between diabetes and premature death for Japanese general people.
Design: Prospective cohort study.
Setting: The Japan Public Health Center-based prospective study (JPHC study), data collected between 1990 and 2010.
Population: A total of 46 017 men and 53 567 women, aged 40-69 years at the beginning of baseline survey.
Main outcome measures: Overall and cause specific mortality. Cox proportional hazards models were used to calculate the HRs of all cause and cause specific mortality associated with diabetes.
Results: The median follow-up period was 17.8 years. During the follow-up period, 8223 men and 4640 women have died. Diabetes was associated with increased risk of death (856 men and 345 women; HR 1.60, (95% CI 1.49 to 1.71) for men and 1.98 (95% CI 1.77 to 2.21) for women). As for the cause of death, diabetes was associated with increased risk of death by circulatory diseases (HR 1.76 (95% CI 1.53 to 2.02) for men and 2.49 (95% CI 2.06 to 3.01) for women) while its association with the risk of cancer death was moderate (HR 1.25 (95% CI 1.11 to 1.42) for men and 1.04 (95% CI 0.82 to 1.32) for women). Diabetes was also associated with increased risk of death for 'non-cancer, non-circulatory system disease' (HR 1.91 (95% CI 1.71 to 2.14) for men and 2.67 (95% CI 2.25 to 3.17) for women).
Conclusions: Diabetes was associated with increased risk of death, especially the risk of death by circulatory diseases.

DOI： 10.1136/bmjopen-2015-007736

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN EPIDEMIOLOGICAL ASSOC  

Background: The present study examined the prevalence of diabetes in Japan during the late 1990s and early 2000s using the Japan Public Health Center-based Prospective Diabetes cohort. We also investigated the distributions of HbA1c values in noncompliant diabetic participants in the cohort.
Methods: A total of 28 183 registered inhabitants aged 46-75 years from 10 public health center areas were included in the initial survey. The 5-year follow-up survey included 20 129 participants. The prevalence of diabetes was estimated using both a self-reported questionnaire and laboratory measurements. Among the participants who reported the presence of diabetes on the questionnaire (self-reported diabetes), the distributions of HbA1c values were described according to their treatment status.
Results: The age-standardized prevalence of diabetes in 55- to 74-year-old adults was 8.2% at the initial survey and 10.6% at the 5-year follow-up. At the initial survey, among participants with self-reported diabetes, the mean HbA1c values in the participants who had never and who had previously received diabetes treatment were 7.01% (standard deviation [SD] 1.56%) and 6.56% (SD 1.46%), respectively. Approximately 15% of the participants who had self-reported diabetes but had never received diabetes treatment had an HbA1c &gt;= 8.4%.
Conclusions: The prevalence of diabetes increased in the JPHC cohort between the late 1990s and early 2000s. A certain proportion of participants who were aware of their diabetes but were not currently receiving treatment had poor diabetic control. Efforts to promote continuous medical attendance for diabetes care may be necessary.

DOI： 10.2188/jea.JE20130196

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記述言語：英語   出版者・発行元：ELSEVIER IRELAND LTD  

DOI： 10.1186/1758-5996-6-110

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CAMBRIDGE UNIV PRESS  

Limited and inconsistent associations between cholesterol and egg consumption and type 2 diabetes risk have been observed in Western countries. In the present study, the association of dietary cholesterol and egg intakes with type 2 diabetes risk was examined prospectively. The study subjects comprised 27 248 men and 36 218 women aged 45-75 years who participated in the second survey of the Japan Public Health Center-based Prospective Study and had no histories of type 2 diabetes or other serious diseases. Dietary cholesterol and egg intakes were estimated using a validated 147-item FFQ. The OR of self-reported, physician-diagnosed type 2 diabetes over 5 years were estimated using multiple logistic regression. A total of 1165 newly diagnosed cases of type 2 diabetes were self-reported. Although dietary cholesterol intake was not associated with type 2 diabetes risk in men, it was found to be associated with a 23% lower odds of type 2 diabetes risk in women in the highest quartile of intake, albeit not statistically significant, compared with those in the lowest quartile (P-trend = 0.08). Such risk reduction was somewhat greater among postmenopausal women; the multivariable-adjusted OR for the highest quartile of cholesterol intake compared with the lowest quartile was 0.68 (95% CI 0.49, 0.94; P-trend = 0.04). No association between egg intake and type 2 diabetes risk was found in either men or women. In conclusion, higher intake of cholesterol or eggs may not be associated with an increased risk of type 2 diabetes in Japanese populations. The observed association between decreased type 2 diabetes risk and higher dietary cholesterol intake in postmenopausal women warrants further investigation. British Journal of Nutrition

DOI： 10.1017/S000711451400258X

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

Background: Glucagon-like peptide-1 (GLP-1) receptor agonists can maintain good glycemic control in some diabetic. Here we compared the clinical characteristics and parameters reflecting glucose metabolism at the time of the initiation of GLP-1 receptor agonist therapy between patients who responded well to therapy and those who did not.
Methods: The records of 43 patients with type 2 diabetes who started receiving GLP-1 receptor agonist therapy during hospitalization were retrospectively reviewed. Glucagon stimulation tests were performed, and patients were started on liraglutide or exenatide therapy. Preprandial blood glucose levels were measured on days 2 and 3 of GLP-1 receptor agonist therapy. We used the Cox proportional hazard model to compare clinical parameters between responders (HbA1c level &lt;8% at more than 3 months after the initiation of treatment) and non-responders (HbA1c level &gt;= 8% at more than 3 months after the initiation of treatment or a switch to insulin therapy at any time).
Results: Twenty-six of the 43 patients were classified as non-responders. At baseline, mean HbA1c levels were 9.9% among responders and 9.7% among non-responders. Compared with treatment with only diet or metformin, the hazard ratio [HR] for non-response was 5.3 (95% confidence interval [CI]: 1.16-24.6, P = 0.03) for insulin therapy and 5.0 (95% CI: 1.13-22.16, P = 0.03) for sulfonylurea therapy. Compared with the lowest tertile, the HRs for non-response in the highest tertile were 3.1 (95% CI: 1.04-8.97, P = 0.04) for the mean preprandial blood glucose level on days 2 and 3 and 3.4 (95% CI: 1.05-11.01, P = 0.04) for the body mass index. The response was not significantly associated with the duration of diabetes or the glucagon stimulation test results. A receiver operating curve analysis showed that the mean preprandial blood glucose level had the highest area under the curve value (=0.72) for the prediction of non-responders.
Conclusions: In patients with poorly controlled diabetes, the response to GLP-1 receptor agonist therapy was significantly associated with the treatment used before the initiation of therapy, the body mass index, and the mean preprandial blood glucose level during the 2 days after the initiation of therapy.

DOI： 10.1186/1758-5996-6-110

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

Background Remarkable financial and political efforts have been focused on the reduction of child mortality during the past few decades. Timely measurements of levels and trends in under-5 mortality are important to assess progress towards the Millennium Development Goal 4 (MDG 4) target of reduction of child mortality by two thirds from 1990 to 2015, and to identify models of success.Methods We generated updated estimates of child mortality in early neonatal (age 0-6 days), late neonatal (7-28 days), postneonatal (29-364 days), childhood (1-4 years), and under-5 (0-4 years) age groups for 188 countries from 1970 to 2013, with more than 29 000 survey, census, vital registration, and sample registration datapoints. We used Gaussian process regression with adjustments for bias and non-sampling error to synthesise the data for under-5 mortality for each country, and a separate model to estimate mortality for more detailed age groups. We used explanatory mixed effects regression models to assess the association between under-5 mortality and income per person, maternal education, HIV child death rates, secular shifts, and other factors. To quantify the contribution of these different factors and birth numbers to the change in numbers of deaths in under-5 age groups from 1990 to 2013, we used Shapley decomposition. We used estimated rates of change between 2000 and 2013 to construct under-5 mortality rate scenarios out to 2030.Findings We estimated that 6.3 million (95% UI 6.0-6.6) children under-5 died in 2013, a 64% reduction from 17.6 million (17.1-18.1) in 1970. In 2013, child mortality rates ranged from 152.5 per 1000 livebirths (130.6-177.4) in Guinea-Bissau to 2.3 (1.8-2.9) per 1000 in Singapore. The annualised rates of change from 1990 to 2013 ranged from 6.8% to 0.1%. 99 of 188 countries, including 43 of 48 countries in sub-Saharan Africa, had faster decreases in child mortality during 2000-13 than during 1990-2000. In 2013, neonatal deaths accounted for 41.6% of under-5 deaths compared with 37.4% in 1990. Compared with 1990, in 2013, rising numbers of births, especially in sub-Saharan Africa, led to 1.4 million more child deaths, and rising income per person and maternal education led to 0.9 million and 2.2 million fewer deaths, respectively. Changes in secular trends led to 4.2 million fewer deaths. Unexplained factors accounted for only -1% of the change in child deaths. In 30 developing countries, decreases since 2000 have been faster than predicted attributable to income, education, and secular shift alone.Interpretation Only 27 developing countries are expected to achieve MDG 4. Decreases since 2000 in under-5 mortality rates are accelerating in many developing countries, especially in sub-Saharan Africa. The Millennium Declaration and increased development assistance for health might have been a factor in faster decreases in some developing countries. Without further accelerated progress, many countries in west and central Africa will still have high levels of under-5 mortality in 2030.

DOI： 10.1016/S0140-6736(14)60497-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

Background The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration.Methods To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010-13) of incidence, drug resistance, and coverage of insecticide-treated bednets.Findings Globally in 2013, there were 1.8 million new HIV infections (95% uncertainty interval 1.7 million to 2.1 million), 29.2 million prevalent HIV cases (28.1 to 31.7), and 1.3 million HIV deaths (1.3 to 1.5). At the peak of the epidemic in 2005, HIV caused 1.7 million deaths (1.6 million to 1.9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19.1 million life-years (16.6 million to 21.5 million) have been saved, 70.3% (65.4 to 76.1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7.5 million (7.4 million to 7.7 million), prevalence was 11.9 million (11.6 million to 12.2 million), and number of deaths was 1.4 million (1.3 million to 1.5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7.1 million (6.9 million to 7.3 million), prevalence was 11.2 million (10.8 million to 11.6 million), and number of deaths was 1.3 million (1.2 million to 1.4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64.0% of cases (63.6 to 64.3) and 64.7% of deaths (60.8 to 70.3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1.2 million deaths (1.1 million to 1.4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31.5% (15.7 to 44.1). Outside of Africa, malaria mortality has been steadily decreasing since 1990.Interpretation Our estimates of the number of people living with HIV are 18.7% smaller than UNAIDS's estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action.

DOI： 10.1016/S0140-6736(14)60844-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

Background The fifth Millennium Development Goal (MDG 5) established the goal of a 75% reduction in the maternal mortality ratio (MMR; number of maternal deaths per 100 000 livebirths) between 1990 and 2015. We aimed to measure levels and track trends in maternal mortality, the key causes contributing to maternal death, and timing of maternal death with respect to delivery.Methods We used robust statistical methods including the Cause of Death Ensemble model (CODEm) to analyse a database of data for 7065 site-years and estimate the number of maternal deaths from all causes in 188 countries between 1990 and 2013. We estimated the number of pregnancy-related deaths caused by HIV on the basis of a systematic review of the relative risk of dying during pregnancy for HIV-positive women compared with HIV-negative women. We also estimated the fraction of these deaths aggravated by pregnancy on the basis of a systematic review. To estimate the numbers of maternal deaths due to nine different causes, we identified 61 sources from a systematic review and 943 site-years of vital registration data. We also did a systematic review of reports about the timing of maternal death, identifying 142 sources to use in our analysis. We developed estimates for each country for 1990-2013 using Bayesian meta-regression. We estimated 95% uncertainty intervals (UIs) for all values.Findings 292 982 (95% UI 261017-327792) maternal deaths occurred in 2013, compared with 376 034 (343483-407574) in 1990. The global annual rate of change in the MMR was -0.3% (-1.1 to 0.6) from 1990 to 2003, and -2.7% (-3.9 to -1.5) from 2003 to 2013, with evidence of continued acceleration. MMRs reduced consistently in south, east, and southeast Asia between 1990 and 2013, but maternal deaths increased in much of sub-Saharan Africa during the 1990s. 2070 (1290-2866) maternal deaths were related to HIV in 2013, 0.4% (-0.2-0.6) of the global total. MMR was highest in the oldest age groups in both 1990 and 2013. In 2013, most deaths occurred intrapartum or postpartum. Causes varied by region and between 1990 and 2013. We recorded substantial variation in the MMR by country in 2013, from 956.8 (685.1-1262.8) in South Sudan to 2.4 (1.6-3.6) in Iceland.Interpretation Global rates of change suggest that only 16 countries will achieve the MDG 5 target by 2015. Accelerated reductions since the Millennium Declaration in 2000 coincide with increased development assistance for maternal, newborn, and child health. Setting of targets and associated interventions for after 2015 will need careful consideration of regions that are making slow progress, such as west and central Africa.

DOI： 10.1016/S0140-6736(14)60696-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ELSEVIER SCIENCE INC  

Background In 2010, overweight and obesity were estimated to cause 3.4 million deaths, 3.9% of years of life lost, and 3.8% of disability-adjusted life-years (DALYs) worldwide. The rise in obesity has led to widespread calls for regular monitoring of changes in overweight and obesity prevalence in all populations. Comparable, up-to-date information about levels and trends is essential to quantify population health effects and to prompt decision makers to prioritise action. We estimate the global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013.
Methods We systematically identified surveys, reports, and published studies (n = 1769) that included data for height and weight, both through physical measurements and self-reports. We used mixed effects linear regression to correct for bias in self-reports. We obtained data for prevalence of obesity and overweight by age, sex, country, and year (n = 19 244) with a spatiotemporal Gaussian process regression model to estimate prevalence with 95% uncertainty intervals (UIs).
Findings Worldwide, the proportion of adults with a body-mass index (BMI) of 25 kg/m(2) or greater increased between 1980 and 2013 from 28.8% (95% UI 28.4-29.3) to 36.9% (36.3-37.4) in men, and from 29.8% (29.3-30.2) to 38.0% (37.5-38.5) in women. Prevalence has increased substantially in children and adolescents in developed countries; 23.8% (22.9-24.7) of boys and 22.6% (21.7-23.6) of girls were overweight or obese in 2013. The prevalence of overweight and obesity has also increased in children and adolescents in developing countries, from 8.1% (7.7-86) to 12.9% (12.3-13.5) in 2013 for boys and from 8.4% (8.1-8.8) to 13.4% (13.0-13.9) in girls. In adults, estimated prevalence of obesity exceeded 50% in men in Tonga and in women in Kuwait, Kiribati, Federated States of Micronesia, Libya, Qatar, Tonga, and Samoa. Since 2006, the increase in adult obesity in developed countries has slowed down.
Interpretation Because of the established health risks and substantial increases in prevalence, obesity has become a major global health challenge. Not only is obesity increasing, but no national success stories have been reported in the past 33 years. Urgent global action and leadership is needed to help countries to more effectively intervene.
Funding Bill & Melinda Gates Foundation.

DOI： 10.1016/S0140-6736(14)60460-8

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN ENDOCRINE SOC  

Glycated hemoglobin (HbA1c) and glycated albumin (GA) are frequently used as glycemic control markers. These markers are influenced by either altered hemoglobin metabolism or albumin metabolism. We investigated the correlation between HbA1c and GA by collecting only data that had not been affected by the turnover of either HbA1c or GA and proposed a novel equation for accurately estimating the extrapolated HbA1c (eHbA1c) value based on the GA value. Data sets for a total of 2461 occasions were obtained from 731 patients (including non-diabetes patients) whose HbA1c and GA values were simultaneously measured. Data sets obtained from patients undergoing hemodialysis, patients with hematological malignancies, pregnancy, chronic liver diseases, hyperthyroidism, steroid treatment or a blood transfusion during the past 3 months, or patients without albumin, hemoglobin, eGFR, or urinary protein measurements and data sets with an eGFR of less than 30 mL/min/1.73 m(2), a hemoglobin level of less than 10 mg/dL, an albumin level of below 3.0 g/mL, or a urinary protein level of 3+ were excluded. Finally, we selected 284 data sets. We then analyzed these data sets, performed a scatter plot to examine the correlation between HbA1c and GA, and established an equation describing the resulting correlation. Based on all the data points, the resulting equation was HbA1c = 0.216 x GA + 2.978 [R-2 = 0.5882, P &lt; 0.001].

DOI： 10.1507/endocrj.EJ13-0450

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Objective: To evaluate the association between adiponectin complexes (high-molecular-weight [HMW], middle-molecular-weight [MMW], and low-molecular-weight [LMW] adiponectin) and diabetes.
Design and Methods: We conducted a case-control study, based on a cohort in Saku, Japan. Among 2565 participants, 300 participants with diabetes and 300 matched controls (430 men and 170 women) were analyzed.
Results: After adjusting for age, physical activity, hypertension, family history, alcohol use, smoking, and menopausal status, total, HMW, and LMW, but not MMW adiponectin levels were inversely associated with diabetes: total adiponectin, odds ratio comparing the highest with the lowest quartiles, 0.46 (95% confidence interval, 0.25-0.82; P for trend = 0.046); HMW, 0.40 (95%CI, 0.22-0.72; P = 0.046); MMW, 1.04 (95%CI, 0.60-1.77; P = 0.81); and LMW, 0.51 (95%CI, 0.29-0.89; P = 0.01). The associations between total and HMW adiponectin and diabetes attenuated after adjustment for BMI (P = 0.15 and 0.13, respectively), but LMW remained (P = 0.04). When stratified by sex, LMW adiponectin levels were associated with diabetes in men only. None of the associations were significant after adjustment for HOMA-IR.
Conclusions: Decreased LMW, total, and HMW adiponectin levels are associated with diabetes. These associations may be secondary to adiposity or insulin resistance.

DOI： 10.1002/oby.20553

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ASSOC CLINICAL CHEMISTRY  

BACKGROUND: Circulating concentrations of sex hormone-binding globulin (SHBG) have been associated with cardiovascular diseases, type 2 diabetes, metabolic syndrome, and hormone-dependent cancers; however, correlates of SHBG concentrations are not well understood.
METHODS: We comprehensively investigated correlates of SHBG concentrations among 13 547 women who participated in the Women's Health Initiative and who had SHBG measurements. We estimated study-and ethnicity-specific associations of age, reproductive history, usage of exogenous estrogen, body mass index (BMI), and lifestyle factors such as physical activity, smoking, alcohol consumption, coffee intake, and dietary factors with SHBG concentrations. These estimates were pooled using random-effects models. We also examined potential nonlinear associations using spline analyses.
RESULTS: There was no significant ethnic difference in the age-adjusted mean concentrations of SHBG. Age, exogenous estrogen use, physical activity, and regular coffee intake were positively associated with SHBG concentrations, whereas BMI was inversely associated with SHBG concentrations after adjustment for potential confounding factors. Similar patterns were observed among both ever users and never users of exogenous estrogen. The spline analysis indicated nonlinear relations of regular intake of coffee, age, and BMI with SHBG concentrations. Two or more cups/day of regular coffee consumption and age of 60 years or older were associated with higher SHBG concentrations; the inverse BMI-SHBG relation was especially strong among women whose BMI was below 30.
CONCLUSIONS: In this large sample of postmenopausal women, age, exogenous estrogen use, physical activity, regular coffee intake, and BMI were significant correlates of SHBG concentrations, presenting potential targets for interventions. (C) 2013 American Association for Clinical Chemistry

DOI： 10.1373/clinchem.2013.207217

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Background: Although dietary patterns have been linked to depression, a frequently observed precondition for suicide, no study has yet examined the association between dietary patterns and suicide risk. Aims: To prospectively investigate the association between dietary patterns and death from suicide. Method: Participants were 40 752 men and 48 285 women who took part in the second survey of the Japan Public Health Centerbased Prospective Study (1995-1998). Dietary patterns were derived from principal component analysis of the consumption of 134 food and beverage items ascertained by a food frequency questionnaire. Hazard ratios of suicide from the fourth year of follow-up to December 2005 were calculated. Results: Among both men and women, a 'prudent' dietary pattern characterised by a high intake of vegetables, fruits, potatoes, soy products, mushrooms, seaweed and fish was associated with a decreased risk of suicide. The multivariable-adjusted hazard ratio of suicide for the highest v. lowest quartiles of the dietary pattern score was 0.46 (95% CI 0.28-0.75) (P for trend, 0.005). Other dietary patterns (Westernised and traditional Japanese) were not associated with suicide risk. Conclusions: Our findings suggest that a prudent dietary pattern may be associated with a decreased risk of death from suicide.

DOI： 10.1192/bjp.bp.112.114793

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

Background: Japanese diets contain a relatively high amount of carbohydrates, and its high dietary glycemic index and glycemic load may raise the risk of diabetes in the Japanese population. The current study evaluated the associations between the dietary glycemic index, glycemic load, and the risk of type 2 diabetes in a population based cohort in Japan.
Methods: We observed 27,769 men and 36,864 women (45-75 y) who participated in the second survey of the Japan Public Health Center-based Prospective Study. The dietary glycemic index and glycemic load were estimated using a food-frequency questionnaire. The development of diabetes was reported in a questionnaire administered five years later, and the associations were analyzed using logistic regression after controlling for age, area, total energy intake, smoking status, family history of diabetes, physical activity, hypertension, BMI, alcohol intake, magnesium, calcium, dietary fiber and coffee intake, and occupation.
Results: The dietary glycemic load was positively associated with the risk of diabetes among women: the multivariable-adjusted odds ratio comparing the highest vs. the lowest quartile was 1.52 (95% CI, 1.13-2.04; P-trend = 0.01). The association was implied to be stronger among women with BMI &lt; 25 than the women with BMI &gt;= 25. The dietary glycemic index was positively associated with the risk of diabetes among men with a high intake of total fat: the multivariable-adjusted odds ratio comparing the highest vs. the lowest quartile was 1.46 (95% CI, 0.94-2.28; P-trend = 0.04). Among women with a high total fat intake, those in the first and second quartiles of the dietary glycemic index had a significant reduced risk of diabetes, compared with those in the first quartile who had a lower total fat level (multivariable-adjusted odds ratio = 0.59 with 95% CI, 0.37-0.94, and odds ratio = 0.63 with 95% CI, 0.40-0.998 respectively).
Conclusions: The population-based cohort study in Japan indicated that diets with a high dietary glycemic load increase the risk of type 2 diabetes among women. Total fat intake may modify the association between the dietary glycemic index and the risk of type 2 diabetes among men and women.

DOI： 10.1186/1475-2891-12-165

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PUBLIC LIBRARY SCIENCE  

Objective: The aim of the present study was to test a hypothesis that a history of having a macrosomic infant (&gt;= 4000g) is associated with the risk of diabetes.
Methods: Data on the Japan Public Health Center-based Prospective diabetes cohort were analyzed, which is a population-based cohort study on diabetes. The survey of diabetes was performed at baseline and at the 5-year follow-up. A history of having a macrosomic infant was assessed using a self-administered questionnaire. A cross-sectional analysis was performed among 12,153 women who participated in the 5-year survey of the cohort. Logistic regression was used to examine the relationship between a history of having a macrosomic infant and the presence of diabetes. A longitudinal analysis was also conducted among 7,300 women without diabetes who participated in the baseline survey. Logistic regression was used to investigate the relationship between a history of having a macrosomic infant and the incidence of diabetes between the baseline survey and the 5-year survey.
Results: In the cross-sectional analysis, parous women with a positive history were more likely to have diabetes in relation to parous women without (OR = 1.44, 95% CI = 1.13-1.83). The longitudinal analysis showed a modest but non-significant increased risk of developing diabetes among women with a positive history (OR = 1.24, 95% CI = 0.80-1.94).
Conclusions: An increased risk of diabetes was implied among women with a history of having a macrosomic infant although the longitudinal analysis showed a non-significant increased risk.

DOI： 10.1371/journal.pone.0084542

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：CAMBRIDGE UNIV PRESS  

The relationship between different types of meat intake and the risk of type 2 diabetes remains unclear. We prospectively examined the association between total meat, total red meat, unprocessed red meat, processed meat and poultry intake and the incidence of type 2 diabetes. Subjects were 27 425 men and 36 424 women aged 45-75 years who participated in the second survey of the Japan Public Health Center-based Prospective Study, and had no history of type 2 diabetes, cancer, stroke, IHD, chronic liver disease or kidney disease. Meat intake was estimated using a validated 147-item FFQ. OR of self-reported, physician-diagnosed type 2 diabetes over 5 years were estimated using a multiple logistic regression. A total of 1178 newly diagnosed cases of type 2 diabetes were self-reported. Intakes of total meat and total red meat were associated with the increased risk of type 2 diabetes in men but not in women. The multivariate-adjusted OR for the highest quartile compared with the lowest quartile of total meat and total red meat intake were 1.36 (95% CI 1.07, 1.73; P for trend 0.006) and 1.48 (95% CI 1.15, 1.90; P for trend 0.003) for men, respectively, and 0.82 (95% CI 0.62, 1.09; P for trend = 0.14) and 0.77 (95% CI 0.57, 1.02; P for trend = 0.08) for women, respectively. Intakes of processed red meat and poultry were not associated with the increased risk of diabetes in either men or women. In conclusion, elevated intake of red meat is associated with the increased risk of type 2 diabetes in Japanese men but not in women.

DOI： 10.1017/S0007114513001128

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

Aims/IntroductionRecently, the prevalence of lifestyle-related disease has increased, and its associated medical costs have become considerable. Although walking is thought to prevent lifestyle-related disease, few studies have evaluated its effect on medical costs in Japanese subjects. We aimed at evaluating the effect of walking on medical costs by simulation mainly focusing on diabetes in the Japanese population.
Materials and MethodsA Markov model focusing on diabetes was constructed. As complications of diabetes, dialysis', ischemic heart disease' and stroke' were included. The model has four states: non-diabetes', diabetes', dialysis' and dead', and ischemic heart disease' and stroke' were included as events that occurred in each state. The effect of walking was included as changing the rate of transition and incident rates of events.
ResultsAfter 10years, the numbers of subjects with diabetes were 4.3 and 7.3% lower for daily increase of 3,000 and 5,000 steps, respectively. The numbers of cases of ischemic heart disease and stroke also decreased. Lower medical costs were also seen according to the daily increase in steps. In 10years, the total medical costs were 5.2 and 8.4% lower for 3,000 and 5,000 steps increase, respectively. The cost reduction associated with a daily increase of 3,000 steps walked was calculated as yen0.00146 for each step.
ConclusionsWalking is one of the most common and accessible forms of exercises. The present results suggested that walking reduced the medical costs associated with lifestyle-related disease, which will have a large impact on health policy.

DOI： 10.1111/jdi.12114

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記述言語：英語   出版者・発行元：PUBLIC LIBRARY SCIENCE  

Background: The definition of incident type 2 diabetes varies across studies; hence, the actual incidence of type 2 diabetes in Japan is unclear. Here, we reviewed the various definitions of incident type 2 diabetes used in previous epidemiologic studies and estimated the diabetes incidence rate in Japan.
Methods: We searched for related literature in the MEDLINE, EMBASE, and Ichushi databases through September 2012. Two reviewers selected studies that evaluated incident type 2 diabetes in the Japanese population.
Results: From 1824 relevant articles, we included 33 studies with 386,803 participants. The follow-up period ranged from 2.3 to 14 years and the studies were initiated between 1980 and 2003. The random-effects model indicated that the pooled incidence rate of diabetes was 8.8 (95% confidence interval, 7.4-10.4) per 1000 person-years. We observed a high degree of heterogeneity in the results (I-2 = 99.2%; p &lt; 0.001), with incidence rates ranging from 2.3 to 52.6 per 1000 person-years. Three studies based their definition of incident type 2 diabetes on self-reports only, 10 on laboratory data only, and 20 on self-reports and laboratory data. Compared with studies defining diabetes using laboratory data (n = 30; pooled incidence rate = 9.6; 95% confidence interval = 8.3-11.1), studies based on self-reports alone tended to show a lower incidence rate (n = 3; pooled incidence rate = 4.0; 95% confidence interval = 3.2-5.0; p for interaction &lt; 0.001). However, stratified analyses could not entirely explain the heterogeneity in the results.
Conclusions: Our systematic review and meta-analysis indicated the presence of a high degree of heterogeneity, which suggests that there is a considerable amount of uncertainty regarding the incidence of type 2 diabetes in Japan. They also suggested that laboratory data may be important for the accurate estimation of the incidence of type 2 diabetes.

DOI： 10.1371/journal.pone.0074699

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Dove Medical Press Ltd.  

Aims: Insulin resistance and the progressive loss of β-cell function are components of the fundamental pathophysiology of type II diabetes. A recent experimental study suggested that calcium channel blockers (CCBs) might inhibit β-cell apoptosis, enhance β-cell function, and prevent diabetes. The present meta-analysis examined the clinical effect of CCBs on the incidence of diabetes. Methods: MEDLINE, EMBASE, ISI Web of Science, the Cochrane Library, and ClinicalTrials.gov were each searched for relevant articles published up to March 11, 2013. Randomized controlled trials (RCTs) with a follow-up period of at least 1-year were included. Identified articles were systematically reviewed, and those with pertinent data were selected for inclusion in a meta-analysis. Results: We included ten RCTs in a meta-analysis. Of the 108,118 people with hypertension and no pre-existing diabetes, 7,073 (6.5%) cases of type II diabetes were reported. CCBs were associated with a higher incidence of diabetes than angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs
pooled risk ratios [95% confidence intervals]: 1.23 [1.01-1.51] and 1.27 [1.14-1.42], respectively) and a lower incidence compared with β blockers or diuretics (0.83 [0.73-0.94] and 0.82 [0.69-0.98], respectively). The overall risk of diabetes among subjects taking CCBs was not significant (0.99 [0.85-1.15]). Conclusion: The use of CCBs was not significantly associated with incident diabetes compared to other antihypertensive agents: the association with diabetes was lowest for ACEIs and ARBs, followed by CCBs, β blockers, and diuretics. Although CCBs can be safely used in hypertensive patients, it would be premature to advocate CCBs for the prevention or treatment of diabetes. © 2013 Noto et al, publisher and licensee Dove Medical Press Ltd.

DOI： 10.2147/DMSO.S49767

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN EPIDEMIOLOGICAL ASSOC  

Background: Diabetes is an important risk factor for cardiovascular disease, certain types of cancer, and death, and self-reports are one of the most convenient methods for ascertaining diabetes status. We evaluated the validity of diabetes self-reports among Japanese who participated in a health checkup.
Methods: Self-reported diabetes was cross-sectionally compared with confirmed diabetes among 2535 participants aged 28 to 85 years in the Saku cohort study. Confirmed diabetes was defined as the presence of at least 1 of the following: fasting plasma glucose (FPG) level of 126 mg/dL or higher, 2-hour post-load glucose (2-hPG) level of 200 mg/dL or higher after a 75-gram oral glucose tolerance test, glycated hemoglobin (HbA1c) level of 6.5% or higher, or treatment with hypoglycemic medication(s).
Results: Of the 251 participants with self-reported diabetes, 121 were taking hypoglycemic medication(s) and an additional 69 were classified as having diabetes. Of the 2284 participants who did not self-report diabetes, 80 were classified as having diabetes. These data yielded a sensitivity of 70.4%, a specificity of 97.3%, a positive predictive value of 75.7%, and a negative predictive value of 96.5%. The frequency of participants with undiagnosed diabetes was 3.0%. Of these, 64.2% had FPG within the normal range and were diagnosed by 2-hPG and/or HbA1c.
Conclusions: Our findings provide additional support for the use of self-reported diabetes as a measure of diabetes in epidemiologic studies performed in similar settings in Japan if biomarker-based diagnosis is difficult.

DOI： 10.2188/jea.JE20120221

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BMJ PUBLISHING GROUP  

Objectives To provide a systematic and quantitative summary of the association between severe hypoglycaemia and risk of cardiovascular disease in people with type 2 diabetes and to examine the sensitivity of the association to possible uncontrolled confounding by unmeasured comorbid severe illness using a bias analysis.
Design Meta-analysis of observational studies.
Data sources Medline, Embase, the Cochrane Library, and Web of Science databases were searched to February 2013, without any language restrictions.
Eligibility criteria Two independent reviewers selected cohort studies that evaluated the association of severe hypoglycaemia with cardiovascular events in people with type 2 diabetes; we excluded studies from acute hospital settings. We extracted descriptive and quantitative data.
Results Of 3443 citations screened, six eligible studies with 903 510 participants were identified. In the conventional random effects meta-analysis, severe hypoglycaemia was strongly associated with a higher risk of cardiovascular disease (relative risk 2.05, 95% confidence interval 1.74 to 2.42; P&lt;0.001). The excess fraction of cardiovascular disease incidence that was attributable to severe hypoglycaemia (the population attributable fraction) was 1.56% (95% confidence interval 1.32% to 1.81%; P&lt;0.001). Although moderate heterogeneity across the studies was suggested (I-2=73.1%; P=0.002 for heterogeneity), most subgroups showed similar results in stratified analyses. The bias analysis indicated that comorbid severe illness alone may not explain the association between hypoglycaemia and cardiovascular disease; to explain this association, comorbid severe illness would have had to be extremely strongly associated with both severe hypoglycaemia and cardiovascular disease.
Conclusion Our findings suggest that severe hypoglycaemia is associated with a higher risk of cardiovascular disease; they also support the notion that avoiding severe hypoglycaemia may be important to prevent cardiovascular disease in people with type 2 diabetes.

DOI： 10.1136/bmj.f4533

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DOI： 10.1136/bmj.f4533

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：WILEY-BLACKWELL  

In recent years, diabetes has been shown to be associated with cancer risk, and this has led to a joint committee being formed, enlisting experts from the Japan Diabetes Society and the Japanese Cancer Association to address this issue. Epidemiological data in Japan provides evidence to demonstrate that diabetes is associated with increased risk for cancers, especially colorectal, liver, and pancreatic cancers. The mechanisms through which diabetes is assumed to promote oncogenesis include insulin resistance and associated hyperinsulinemia, hyperglycemia, and inflammation. Common risk factors for type 2 diabetes and cancer include aging, male sex, obesity, physical inactivity, inappropriate diet (excessive red/processed meat intake, inadequate vegetable/fruit/dietary fiber intake), excessive alcohol drinking, and smoking. Given that inappropriate diet/exercise, smoking and excessive alcohol drinking are common risk factors for diabetes and cancer, diet/exercise therapy, smoking cessation and alcohol moderation may be associated with decreased risk for cancer in diabetic patients. There is as yet limited evidence as to whether any particular antidiabetic agents may influence cancer risk.

DOI： 10.1111/cas.12203

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

In recent years, diabetes has been shown to be associated with cancer risk, and this has led to a joint committee being formed, enlisting experts from the Japan Diabetes Society and the Japanese Cancer Association to address this issue. Epidemiological data in Japan provides evidence to demonstrate that diabetes is associated with increased risk for cancers, especially colorectal, liver, and pancreatic cancers. The mechanisms through which diabetes is assumed to promote oncogenesis include insulin resistance and associated hyperinsulinemia, hyperglycemia, and inflammation. Common risk factors for type 2 diabetes and cancer include aging, male sex, obesity, physical inactivity, inappropriate diet (excessive red/processed meat intake, inadequate vegetable/fruit/dietary fiber intake), excessive alcohol drinking, and smoking. Given that inappropriate diet/exercise, smoking and excessive alcohol drinking are common risk factors for diabetes and cancer, diet/exercise therapy, smoking cessation and alcohol moderation may be associated with decreased risk for cancer in diabetic patients. There is as yet limited evidence as to whether any particular antidiabetic agents may influence cancer risk. © 2013 The Japanese Cancer Association and the Japan Diabetes Society.

DOI： 10.1111/cas.12203

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記述言語：英語  

A growing body of evidence from observational studies and meta-analyses of the data suggest that diabetes mellitus is associated with an increased risk of cancer. Meta-analyses have shown that diabetes increases the risks of total cancer, and of site-specific cancers of the breast, endometrium, bladder, liver, colorectum and pancreas, and that it decreases the risk of prostate cancer. Insulin resistance and secondary hyperinsulinemia is the most frequently proposed hypothesis, and hyperglycemia itself might promote carcinogenesis. In addition to several facets of lifestyle including obesity, smoking and lack of exercise, treatment for diabetes might affect the risk of cancer. For instance, metformin, an insulin sensitizer, reportedly has a potential anticancer effect. In light of the exploding global epidemic of diabetes, even a modest increase in the cancer risk will translate into a substantial socioeconomic burden. The current insights underscore the need for clinical attention and better-designed studies of the complex interactions between diabetes and cancer. © 2013 Asian Association for the Study of Diabetes and Wiley Publishing Asia Pty Ltd.

DOI： 10.1111/jdi.12068

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1371/journal.pone.0057964

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Vegetable and fruit intake has been associated with a reduced risk of cancer and CVD, but its relationship to the risk of type 2 diabetes remains unclear. We prospectively examined the association between vegetable and fruit intake and the incidence of type 2 diabetes. Subjects were 21Â 269 men and 27Â 168 women aged 45-75 years who participated in the second survey of the Japan Public Health Center-based Prospective Study and had no history of type 2 diabetes or other serious diseases. Intake of vegetables and fruit was estimated using a validated 147-item FFQ. The OR of self-reported, physician-diagnosed type 2 diabetes over 5 years was estimated using multiple logistic regression. A total of 896 newly diagnosed cases of type 2 diabetes were self-reported. Intake of vegetables and fruit combined or fruit only was not associated with a lower risk of type 2 diabetes. However, there was an approximately 20Â %, albeit not statistically significant, risk reduction associated with vegetables (men only), green leafy vegetables (men and women) and cruciferous vegetables (men only). Such risk reduction was somewhat greater among obese or smoking men than non-obese or non-smoking men. In conclusion, although a small beneficial effect of vegetables, especially green leafy and cruciferous vegetables, cannot be excluded, vegetable and fruit intake may not be appreciably associated with the risk of type 2 diabetes for Japanese adults. © 2012 The Authors.

DOI： 10.1017/S0007114512001705

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記述言語：英語   出版者・発行元：PUBLIC LIBRARY SCIENCE  

Objective: Low-carbohydrate diets and their combination with high-protein diets have been gaining widespread popularity to control weight. In addition to weight loss, they may have favorable short-term effects on the risk factors of cardiovascular disease (CVD). Our objective was to elucidate their long-term effects on mortality and CVD incidence.
Data sources: MEDLINE, EMBASE, ISI Web of Science, Cochrane Library, and ClinicalTrials.gov for relevant articles published as of September 2012. Cohort studies of at least one year's follow-up period were included.
Review methods: Identified articles were systematically reviewed and those with pertinent data were selected for meta-analysis. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) for all-cause mortality, CVD mortality and CVD incidence were calculated using the random-effects model with inverse-variance weighting.
Results: We included 17 studies for a systematic review, followed by a meta-analysis using pertinent data. Of the 272,216 people in 4 cohort studies using the low-carbohydrate score, 15,981 (5.9%) cases of death from all-cause were reported. The risk of all-cause mortality among those with high low-carbohydrate score was significantly elevated: the pooled RR (95% CI) was 1.31 (1.07-1.59). A total of 3,214 (1.3%) cases of CVD death among 249,272 subjects in 3 cohort studies and 5,081 (2.3%) incident CVD cases among 220,691 people in different 4 cohort studies were reported. The risks of CVD mortality and incidence were not statistically increased: the pooled RRs (95% CIs) were 1.10 (0.98-1.24) and 0.98 (0.78-1.24), respectively. Analyses using low-carbohydrate/high-protein score yielded similar results.
Conclusion: Low-carbohydrate diets were associated with a significantly higher risk of all-cause mortality and they were not significantly associated with a risk of CVD mortality and incidence. However, this analysis is based on limited observational studies and large-scale trials on the complex interactions between low-carbohydrate diets and long-term outcomes are needed.

DOI： 10.1371/journal.pone.0055030

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

A 73-year-old Japanese man developed chronic intractable itching due to prurigo nodularis. High-dose glucocorticoid ointment failed, and the treatment resulted in poor glycemic control. Repeated scratching caused hematogenous bacterial dissemination via cutaneous injuries, resulting in the formation of iliopsoas and spinal epidural abscesses that required long-term antibiotic treatment. Pregabalin was administered to treat the pruritus, and a considerable improvement was observed. A reduction in the dose and intensity of the topical corticosteroids improved the patient's glycemic control, resulting in the complete resolution of the abscesses. Pregabalin significantly improved the patient's pruritus and decreased the risk of infection. © 2013 The Japanese Society of Internal Medicine.

DOI： 10.2169/internalmedicine.52.0060

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER ASSOC CLINICAL CHEMISTRY  

BACKGROUND: Recent prospective studies have shown a strong inverse association between sex hormone binding globulin (SHBG) concentrations and risk of clinical diabetes in white individuals. However, it remains unclear whether this relationship extends to other racial/ethnic populations.
METHODS: We evaluated the association between baseline concentrations of SHBG and clinical diabetes risk in the Women's Health Initiative Observational Study. Over a median follow-up of 5.9 years, we identified 642 postmenopausal women who developed clinical diabetes (380 blacks, 157 Hispanics, 105 Asians) and 1286 matched controls (777 blacks, 307 Hispanics, 202 Asians).
RESULTS: Higher concentrations of SHBG at baseline were associated with a significantly lower risk of clinical diabetes [relative risk (RR), 0.15; 95% CI, 0.09-0.26 for highest vs lowest quartile of SHBG, adjusted for BMI and known diabetes risk factors]. The associations remained consistent within ethnic groups [RR, 0.19 (95% CI, 0.10-0.38) for blacks; RR, 0.17 (95% CI, 0.05-0.57) for Hispanics; and 0.13 (95% CI, 0.03-0.48) for Asians]. Adjustment for potential confounders, such as total testosterone (RR, 0.11; 95% CI, 0.07-0.19) or HOMA-IR (RR, 0.26; 95% CI, 0.14-0.48) did not alter the RR substantially. In addition, SHBG concentrations were significantly associated with risk of clinical diabetes across categories of hormone therapy use (never users: RRper (SD) = 0.42, 95% CI, 0.34-0.51; past users: RRper (SD) = 0.53;, 95% CI, 0.37-0.77; current users: RRper (SD) = 0.57; 95% CI, 0.46-0.69; P-interaction = 0.10).
CONCLUSIONS: In this prospective study of postmenopausal women, we observed a robust, inverse relationship between serum concentrations of SHBG and risk of clinical diabetes in American blacks, Hispanics, and Asians/Pacific Islanders. These associations appeared to be independent of sex hormone concentrations, adiposity, or insulin resistance. (C) 2012 American Association for Clinical Chemistry

DOI： 10.1373/clinchem.2012.193086

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

Background: Sex hormone-binding globulin (SHBG) levels and sex hormones have been implicated in the pathogenesis of type 2 diabetes and cardiovascular diseases. As fatty liver has been suggested to be a major determinant of SHBG levels, we examined whether the associations of SHBG and testosterone with diabetes were independent of fatty liver.
Methods: We conducted a case-control study that included 300 diabetes cases (215 men and 85 women) and 300 matched controls from the Saku cohort study. Diabetes was defined by either fasting plasma glucose levels &gt;= 126 mg/dL, 2-h post-load glucose levels &gt;= 200 mg/dL after a 75 g oral glucose tolerance test, or diabetes diagnosed by physicians. We fitted conditional logistic regression models to examine the associations between SHBG and total testosterone levels with diabetes by sex. To evaluate the impact of fatty liver, we used the fatty liver index (FLI), a validated measure derived from serum triglyceride levels, body mass index (BMI), waist circumference, and gamma-glutamyltransferase levels.
Results: After adjusting for age, family history of diabetes, smoking, physical activity, BMI, and FLI, SHBG levels were inversely associated with diabetes among women (odds ratio [OR] comparing the highest with the lowest quartiles, 0.13 [95% confidence interval {CI}, 0.02-0.96]), but not among men. Similar patterns were observed in a subgroup analysis restricted to postmenopausal women"(OR, 0.12 [95% CI, 0.01-1.17]). In contrast, testosterone levels were inversely associated with diabetes among men (OR, 0.45 [95% CI, 0.23-0.89]), but not among women.
Conclusions: Our findings suggest that SHBG in women and testosterone in men may be inversely associated with diabetes.

DOI： 10.1186/1475-2840-11-130

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：BIOMED CENTRAL LTD  

Background: Dietary glycemic index or load is thought to play an important role in glucose metabolism. However, few studies have investigated the relation between glycemic index (GI) or load (GL) and glycemia in Asian populations. In this cross-sectional analysis of a randomized controlled trial, the Saku Control Obesity Program, we examined the relation between the baseline GI or GL and glycemia (HbA1c and fasting plasma glucose [FPG] levels), insulin resistance (HOMA-IR), beta-cell function (HOMA-beta), and other metabolic risk factors (lipid levels, diastolic and systolic blood pressure, and adiposity measures).
Methods: The participants were 227 obese Japanese women and men. We used multiple linear regression models and logistic regression models to adjust for potential confounding factors such as age, sex, visceral fat area, total energy intake, and physical activity levels.
Results: After adjustments for potential confounding factors, GI was not associated with HbA1c, but GL was positively associated with HbA1c. For increasing quartiles of GI, the adjusted mean HbA1c were 6.3%, 6.7%, 6.4%, and 6.4% (P for trend = 0.991). For increasing quartiles of GL, the adjusted mean HbA1c were 6.2%, 6.2%, 6.6%, and 6.5% (P for trend = 0.044). In addition, among participants with HbA1c &gt;= 7.0%, 20 out of 28 (71%) had a high GL (&gt;= median); the adjusted odds ratio for HbA1c &gt;= 7.0% among participants with higher GL was 3.1 (95% confidence interval [CI] = 1.2 to 8.1) compared to the participants with a lower GL (&lt;median). Further, among 16 participants with FPG &gt;= 150 mg/dL, 13 participants (81.3%) had a higher GL; the adjusted odds ratio for FPG &gt;= 150 mg/dL among participants with a higher GL was 8.5 (95% confidence interval = 1.7 to 43.4) compared to those with a lower GL. In contrast, GI and GL were not associated with metabolic risk factors other than glycemia.
Conclusions: Our findings suggest that participants with poor glycemic control tend to have a higher GL in an obese Japanese population.

DOI： 10.1186/1743-7075-9-79

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記述言語：日本語   出版者・発行元：THE JAPAN DIABETES SOCIETY  

DOI： 10.11213/tonyobyo.55.591

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その他リンク： https://jlc.jst.go.jp/DN/JALC/10008614123?from=CiNii

記述言語：英語   出版者・発行元：PUBLIC LIBRARY SCIENCE  

Background: A growing body of evidence has suggested that metformin potentially reduces the risk of cancer. Our objective was to enhance the precision of estimates of the effect of metformin on the risk of any-site and site-specific cancers in patients with diabetes.
Methods/Principal Findings: We performed a search of MEDLINE, EMBASE, ISI Web of Science, Cochrane Library, and ClinicalTrials.gov for pertinent articles published as of October 12, 2011, and included them in a systematic review and meta-analysis. We calculated pooled risk ratios (RRs) for overall cancer mortality and cancer incidence. Of the 21,195 diabetic patients reported in 6 studies (4 cohort studies, 2 RCTs), 991 (4.5%) cases of death from cancer were reported. A total of 11,117 (5.3%) cases of incident cancer at any site were reported among 210,892 patients in 10 studies (2 RCTs, 6 cohort studies, 2 case-control studies). The risks of cancer among metformin users were significantly lower than those among non-metformin users: the pooled RRs (95% confidence interval) were 0.66 (0.49-0.88) for cancer mortality, 0.67 (0.53-0.85) for all-cancer incidence, 0.68 (0.53-0.88) for colorectal cancer (n = 6), 0.20 (0.07-0.59) for hepatocellular cancer (n = 4), 0.67 (0.45-0.99) for lung cancer (n = 3).
Conclusion/Significance: The use of metformin in diabetic patients was associated with significantly lower risks of cancer mortality and incidence. However, this analysis is mainly based on observational studies and our findings underscore the more need for long-term RCTs to confirm this potential benefit for individuals with diabetes.

DOI： 10.1371/journal.pone.0033411

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

A 34-year-old Japanese woman presented at our institution weighing 182.7 kg, 148.2 cm tall, and with a body mass index of 83.2 kg/m(2). She had been overweight since childhood, but no abnormality was found to explain her obesity. Treatments, including mazindol, bofu-tsusho-san, dietary restriction, and BioEnterics Intragastric Balloon, did not result in improvement of her obesity. Finally, we performed sleeve gastrectomy, and she has maintained her weight within 130-140 kg without rebounding for 2 and a half years. We followed the clinical changes before and after the operation. This case provides potentially interesting information regarding operative treatment for morbid obesity in Japanese.

DOI： 10.2169/internalmedicine.51.7010

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s12149-011-0522-y

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：AMER DIABETES ASSOC  

OBJECTIVE-Coffee consumption has been inversely associated with type 2 diabetes risk, but its mechanisms are largely unknown. We aimed to examine whether plasma levels of sex hormones and sex hormone-binding globulin (SHBG) may account for the inverse association between coffee consumption and type 2 diabetes risk.
RESEARCH DESIGN AND METHODS-We conducted a case-control study nested in the prospective Women's Health Study (WHS). During a median follow-up of 10 years, 359 postmenopausal women with newly diagnosed type 2 diabetes were matched with 359 control subjects by age, race, duration of follow-up, and time of blood draw.
RESULTS-Caffeinated coffee was positively associated with SHBG but not with sex hormones. Multivariable-adjusted geometric mean levels of SHBG were 26.6 nmol/l among women consuming &gt;= 4 cups/day of caffeinated coffee and 23.0 nmol/l among nondrinkers (P for trend = 0.01). In contrast, neither decaffeinated coffee nor tea was associated with SHBG or sex hormones. The multivariable-adjusted odds ratio (OR) of type 2 diabetes for women consuming &gt;= 4 cups/day of caffeinated coffee compared with nondrinkers was 0.47 (95% CI 0.23-0.94; P for trend = 0.047). The association was largely attenuated after further adjusting for SHBG (OR 0.71 [95% CI 0.31-1.61]; P for trend = 0.47). In addition, carriers of rs6259 minor allele and noncarriers of rs6257 minor allele of SHBG gene consuming &gt;= 2 cups/day of caffeinated coffee had lower risk of type 2 diabetes in directions corresponding to their associated SHBG.
CONCLUSIONS-Our findings suggest that SHBG may account for the inverse association between coffee consumption and type 2 diabetes risk among postmenopausal women. Diabetes 60: 269-275, 2011

DOI： 10.2337/db10-1193

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN ENDOCRINE SOC  

Since there is increasing evidence that postprandial hyperglycemia is a risk factor for the development of macrovascular complications, it is important to predict postprandial hyperglycemia in the early stages of glucose intolerance, and routine medical checkups provide a good opportunity to do so. The aim of this study was to evaluate the usability of 1,5-anhydroglucitol (1,5-AG) in routine medical checkups. The subjects were 77 Japanese men who participated in a routine medical checkup. First, we performed 75 g oral glucose tolerance tests (OGTTs), and examined the changes in glucose and 1,5-AG levels measured at 0, 30, 60, 90, 120, and 180 minutes (min). 1,5-AG levels did not significantly change until 90 min after the glucose load. Second, a linear regression analysis showed an inverse correlation between the 2-hour post-challenge glucose (2h-PG) and baseline 1,5-AG levels during the OGTT (P = 0.001, r(2) = 0.13), and the correlation was still significant after adjustment for age (2h-PG = 170 + 0.83 x (age in years) - 3.23 x (1,5-AG), P = 0.002, adjusted r(2) = 0.12). Finally, to investigate the test characteristics of I,5-AG levels as a predictor of a 2h-PG level &gt;= 200 mg/dL, we plotted a receiver operating characteristic (ROC) curve. The area under the ROC curve was 0.78, and the maximal sum of sensitivity and specificity (78% and 72%, respectively) was obtained at a 1,5-AG cutoff level of &lt; 14.2 mu g/mL. We conclude that 1,5-AG values may provide an ancillary predictor of 2h-PG of 75 g OGTTs in routine medical checkups.

DOI： 10.1507/endocrj.K10E-224

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：ENDOCRINE SOC  

Context: Various autoimmune diseases, especially autoimmune thyroid disease, are known to occur in HIV-infected patients on highly active antiretroviral therapy (HAART). However, no reports have described the development of autoimmune diabetes during HAART.
Objective: Our objective was to investigate the clinical course of the development of autoantibodies and diabetes during HAART.
Patients and Methods: Based on their high antiislet autoantibody titers and requirement for insulin therapy, we diagnosed three HIV-infected patients with autoimmune diabetes. To clarify the relationship between the development of an autoimmune reaction against pancreatic beta-cells and recovery of CD4(+) T lymphocyte (CD4) counts, we retrospectively assayed stored samples of the patients&apos; plasma for antiglutamic acid decarboxylase antibody (GAD-Ab).
Results: No GAD-Ab was detected in the plasma samples of any of the three patients prior to HAART, and their CD4 counts were below 20 cells/mu l at their nadir. The GAD-Ab tests became positive from 6 to 38 months after the start of HAART, and their conversion to positive followed a dramatic increase in the patients&apos; CD4 count. Two patients developed diabetes after testing positive for GAD-Ab. Although one patient had mild diabetes prior to testing positive for GAD-Ab, the rapid worsening of glycemic control and introduction of insulin therapy almost coincided with the detection of GAD-Ab. The high magnitude of the CD4 increase during HAART and the timing of the detection of autoantibody were similar to the magnitude and timing reported in HAART-associated autoimmune thyroid disease.
Conclusions: Autoimmune diabetes develops in some HIV-infected patients after immune restoration during HAART. (J Clin Endocrinol Metab 95: 4056-4060, 2010)

DOI： 10.1210/jc.2010-0055

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN ENDOCRINE SOC  

Insulin therapy represents the most effective and reliable means of achieving satisfactory glycemic control. However, few studies have evaluated the predictors of future insulin use. The purpose of this study was to investigate the predictors of future insulin use in type 2 diabetic patients. In this study, we conducted a chart review of 158 Japanese type 2 diabetic patients admitted to our hospital for stringent glycemic control. Of the 158 subjects, 92 satisfied the inclusion criteria for this study. We assessed the associations between baseline BM I, fasting plasma glucose levels (FPG) and serum and urinary C-peptide levels (sCPR and uCPR), and insulin usage at 6 months after discharge. We also computed the area under the curve (AUC) in receiver operating characteristic (ROC) curve for each predictor to predict the future insulin use. After adjustment for gender, age, and BMI, the multivariable odds ratios (ORs) for future insulin use in the highest tertile as compared with lowest tertile were 0.12 for BMI (95% confidence interval [CI], 0.03-0.52), 17.0 for FPG (95% CI, 3.27-88.7), 0.12 for sCPR (95% CI, 0.02-0.71), and 0.03 for uCPR (95% CI, 0.00-0.24). Prediction analyses showed that the AUCs for BMI, FPG, sCPR, and uCPR were 0.73, 0.76, 0.74, and 0.78, respectively, which suggests that the predictive abilities of these predictors do not differ substantially. In conclusion, this study suggests that BMI, FPG, sCPR, and uCPR are strong predictors of the future insulin use in type 2 diabetic patients.

DOI： 10.1507/endocrj.K09E-279

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

A 55-year-old Japanese man was admitted to our hospital with severe weakness. Without measurement of serum electrolyte concentrations, diuretic therapy for hypertension was started 2 weeks prior to admission. Laboratory findings showed profound hypokalemia (1.4 mEq/L), and extreme elevation of the serum creatinine phosphokinase levels (15,760 IU/L), suggesting that the patient had hypokalemic paralysis and hypokalemia-induced rhabdomyolysis. Further evaluations, including adrenal venous sampling strongly suggested that he had primary aldosteronism. He was treated successfully by laparoscopic adrenalectomy. This case provides an important lesson that serum electrolyte concentrations should be measured in hypertensive patients before the administration of antihypertensive agents.

DOI： 10.2169/internalmedicine.48.1444

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記述言語：英語   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

DOI： 10.2169/internalmedicine.47.0897

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Type 1 diabetes mellitus is classified as either autoimmune or idiopathic. Fulminant type 1 diabetes was originally reported as a subtype of idiopathic type 1 diabetes. Though involvement of viral infections has been suggested as a triggering mechanism, its pathogenesis remains unknown. Here, we present a case of fulminant type 1 diabetes associated with significant elevation of mumps titers, A 56-year-old Japanese man had suffered from nausea and generalized fatigue for two days before being transferred to our hospital in a confused state. Findings on admission revealed a high blood glucose level, near-normal HbA1c level, metabolic acidosis, and increased urinary ketone levels. Serum tests for islet-associated autoantibodies were negative. The serum, urinary C-peptide levels and the result of glucagon test indicated severe impairment of insulin secretion. These results were compatible with the diagnosis of fulminant type 1 diabetes. Also, he was suspected as having mumps infection on the basis of serological testing. These findings suggest that fulminant type 1 diabetes developed after mumps virus infection in our case. To the best of our knowledge, no other report has indicated an association between a recent mumps infection and the onset of fulminant type 1 diabetes. This case suggests an association between fulminant type 1 diabetes and mumps virus infection.

DOI： 10.1507/endocrj.K07E-126

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記述言語：英語   出版者・発行元：JAPAN SOC INTERNAL MEDICINE  

DOI： 10.2169/internalmedicine.46.0361

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記述言語：日本語   出版者・発行元：日本体質医学会  

JPHCスタディ(The Japan Public Health Center-based prospective Study)(多目的コホート研究)は、地域住民を対象とした前向きコホート研究である。JPHCスタディにおける糖尿病研究(JPHC Diabetes Study)もその中で行われ、糖尿病の有病率や発症率を明らかにするとともに、主として前向きコホート研究のスキームにより、糖尿病の実態を、生活習慣との関係や、心血管疾患や発がんに対するリスクとしての視点からもHbA1cなどとの関係を含めて分析することを目的としている。近年では、ゲノム情報などとの統合を図ることにより、糖尿病の遺伝素因との関係の探索にも着手している。本稿では、JPHCスタディからの最近の成果である、糖尿病感受性遺伝子多型による2型糖尿病発症の予測能について、また、糖尿病とがんとの関連について述べるとともに、遺伝素因と体質、疾患発症との関係について考察した。すなわち、JPHCスタディにおいても、遺伝子多型情報が糖尿病発症リスクに関与することが確認されたが、従来の糖尿病発症予測因子に遺伝子多型情報を追加することによる予測能の向上はわずかであった。また、糖尿病とがん全体および部位ごとのがんリスクとの関連について、メンデルランダム化解析によってハザード比を推定したところ、今回の遺伝学的なアプローチによる検討では、日本人集団において、2型糖尿病自体ががんに直接関連するという強い遺伝学的エビデンスは得られなかった。以上のように、2型糖尿病の遺伝形質の多くはライフスタイルへの影響を介して発現している可能性が考えられた。(著者抄録)

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記述言語：日本語   出版者・発行元：医歯薬出版(株)  

2016年の国民健康・栄養調査では、糖尿病が強く疑われる人は約1,000万人と推定され、性・年齢階級別の解析では、高齢者における糖尿病有病率が高いことが報告されており、超高齢社会のわが国において、今後も糖尿病患者数が増加することが予想される。糖尿病患者では、合併症を併発すると死亡リスクが高くなると報告されているものの、糖尿病患者の平均余命を推計した研究は少ない。朝日生命成人病研究所附属医院において実施した研究では、糖尿病患者の40歳における平均余命は男性で39.2年、女性で43.6年と推計された。日本全体の傾向と同様に、社会環境、生活習慣や医療技術の進歩により、糖尿病患者の予後が改善している可能性を示唆している。(著者抄録)

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