Publications by authors named "Atsushi Goto"

235 Publications

No Healthcare Utilization and Death.

J Gen Intern Med 2021 Sep 29. Epub 2021 Sep 29.

Department of Epidemiology, UCLA Fielding School of Public Health, 650 Charles E. Young Dr. South, Los Angeles, CA, 90095, USA.

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.
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http://dx.doi.org/10.1007/s11606-021-07138-0DOI Listing
September 2021

Association between sugar and starch intakes and type 2 diabetes risk in middle-aged adults in a prospective cohort study.

Eur J Clin Nutr 2021 Sep 20. Epub 2021 Sep 20.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Chuo-ku, Tokyo, 104-0045, Japan.

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.
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http://dx.doi.org/10.1038/s41430-021-01005-1DOI Listing
September 2021

Epstein-Barr virus-associated gastric carcinoma diagnosed by EUS-guided fine needle biopsy (with video).

Endosc Ultrasound 2021 Sep 3. Epub 2021 Sep 3.

Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan.

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http://dx.doi.org/10.4103/EUS-D-21-00026DOI Listing
September 2021

Rapid detection of neutralizing antibodies to SARS-CoV-2 variants in post-vaccination sera.

J Mol Cell Biol 2021 Aug 27. Epub 2021 Aug 27.

Department of Microbiology, Yokohama City University School of Medicine, Yokohama, Japan.

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.
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http://dx.doi.org/10.1093/jmcb/mjab050DOI Listing
August 2021

Combined Use of Computed Tomography Enterography/Enteroclysis and Capsule Endoscopy Improves the Accuracy of Diagnosis of Small Bowel Bleeding.

Intern Med 2021 15;60(16):2545-2555. Epub 2021 Aug 15.

Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Japan.

Objective CT enterography/enteroclysis (CTE) is listed in the clinical practice guidelines as a method for diagnosing small bowel bleeding, as is capsule endoscopy (CE), but there are no real-world data yet available on CTE in Japan. This study aimed to investigate the diagnostic ability of CTE and long-term prognosis after CTE in Japan. Patients We conducted a retrospective cohort study of patients suspected of having small bowel bleeding who underwent both CTE and CE within 30 days between April 2008 and March 2019. The number of patients free from rebleeding for up to 24 months was thus determined. Results Seventy-one patients were extracted from the database. The 43 patients (60.6%) with a definite and suspicious source of bleeding in the small bowel were detected by CTE. When the 31 patients with a definite source of bleeding in the small bowel were analyzed, the sensitivity of CTE was 19/31 (61.3%) and that of CE was 24/31 (77.4%), thus indicating no significant difference (p=0.332). However, the sensitivity when CTE and CE were used in combination was 30/31 (96.8%), which was significantly higher than that of CE alone (p=0.0412). No rebleeding was observed in the CTE and CE negative group (p=0.0965). Conclusion The combined use of CTE and CE increased the detection rate of small bowel bleeding. Therefore, in patients with suspected tumor/polyp lesions, not only CE, but also CTE should be performed. This study provides the first real-world data on the diagnostic accuracy of CTE for small bowel bleeding in Japan.
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http://dx.doi.org/10.2169/internalmedicine.6785-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429301PMC
August 2021

Relation Between Body Mass Index and Dry Eye Disease: The Japan Public Health Center-Based Prospective Study for the Next Generation.

Eye Contact Lens 2021 Aug;47(8):449-455

Department of Ophthalmology (R.Y., A.H., M.U., M.K., K. Yuki, K. Tsubota), Keio University School of Medicine, Tokyo, Japan; Epidemiology and Prevention Group (R.Y., N.S., A.H., T.S., T.Y., A.G., M. Inoue, M. Iwasaki, S.T.), Center for Public Health Sciences, National Cancer Center, Tokyo, Japan; Center for Education and Educational Research (T.K.), Faculty of Education, Ehime University, Matsuyama, Japan; Department of Public Health and Epidemiology (I.S.), Faculty of Medicine, Oita University, Oita, Japan; Department of Public Health (K.A., S.M.), Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; Department of Hygiene and Preventive Medicine (K. Tanno, K.S.), School of Medicine, Iwate Medical University, Iwate, Japan; Department of Public Health Medicine (K. Yamagishi, H.I.), Faculty of Medicine, and Health Services Research and Development Center, University of Tsukuba, Tsukuba, Japan; Ibaraki Western Medical Center (Kazumasa Yamagishi), Chikusei, Japan; Public Health (H.I.), Department of Social Medicine, Osaka University Graduate School of Medicine, Suita, Japan; and Department of Public Health (N.Y.), Kochi University Medical School, Kochi, Japan.

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.
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http://dx.doi.org/10.1097/ICL.0000000000000814DOI Listing
August 2021

Retrospective nationwide study on the trends in first-line antidiabetic medication for patients with type 2 diabetes in Japan.

J Diabetes Investig 2021 Jul 26. Epub 2021 Jul 26.

Department of Diabetes, Endocrinology and Metabolism, National Center for Global Health and Medicine, Tokyo, Japan.

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 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 inhibitors were the most prescribed (65.1%), followed by biguanides (15.9%) and sodium-glucose cotransporter 2 inhibitors (7.6%). Sodium-glucose cotransporter 2 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 USA and Europe, dipeptidyl peptidase-4 inhibitor is the most prescribed first-line medication for type 2 diabetes patients in Japan, while there is a wide variation in the drug choice by facility-type and prefecture.
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http://dx.doi.org/10.1111/jdi.13636DOI Listing
July 2021

Validation study on diabetes definitions using Japanese Diagnosis Procedure Combination data among hospitalized patients.

J Epidemiol 2021 Jul 17. Epub 2021 Jul 17.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center.

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.
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http://dx.doi.org/10.2188/jea.JE20210024DOI Listing
July 2021

Body Mass Index, Height, Weight Change, and Subsequent Lung Cancer Risk: The Japan Public Health Center-Based Prospective Study.

Cancer Epidemiol Biomarkers Prev 2021 Sep 25;30(9):1708-1716. Epub 2021 Jun 25.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tsukiji, Chuo-ku, Tokyo, Japan.

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/m HR = 1.48; 95% confidence interval (CI) = 1.18-1.85 and 19-22.9 kg/m; HR = 1.19; 95% CI = 1.05-1.35; = <0.001] in men. The risk estimate was also elevated for adenocarcinoma in the BMI <19 kg/m category and for squamous cell carcinoma among men in the 19-22.9 kg/m 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.
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http://dx.doi.org/10.1158/1055-9965.EPI-21-0195DOI Listing
September 2021

The 2020 FASEB virtual Catalyst Conference on Integrative Approach for Complex Diseases Prevention and Management and Beyond, December 16, 2020.

FASEB J 2021 07;35(7):e21500

Herbert Wertheim School of Public Health and Human Longevity, University of California, San Diego, CA, USA.

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http://dx.doi.org/10.1096/fj.202100317DOI Listing
July 2021

Dietary glycemic index, glycemic load, and endometrial cancer risk: The Japan Public Health Center-based Prospective Study.

Cancer Sci 2021 Sep 16;112(9):3682-3690. Epub 2021 Jul 16.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.

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; P  = .33), and that of the highest GL tertile group was 0.79 (95% CI, 0.52-1.19; P  = .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.
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http://dx.doi.org/10.1111/cas.14997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409411PMC
September 2021

Sustained Neutralizing Antibodies 6 Months Following Infection in 376 Japanese COVID-19 Survivors.

Front Microbiol 2021 7;12:661187. Epub 2021 May 7.

Department of Health Data Science, Yokohama City University Graduate School of Data Science, Yokohama, Japan.

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 (NT) and antibodies against spike protein (SP) or nucleocapsid protein (NP) antigens approximately 6 months after the diagnosis of COVID-19. COVID-19 survivors in Japan were recruited. Serum samples and data related to patients' characteristics and COVID-19 history were collected. NT 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 NT were identified using the multivariable linear regression and the correlations among NT and titers of immunoglobulin G (IgG) and total immunoglobulins (Igs) against NP and SP were assessed by Spearman's correlation. 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 NT ( = 367, 98%), SP-IgG ( = 344, 91%), SP-total Ig ( = 369, 98%), NP-IgG ( = 314, 84%), and NP-total Ig ( = 365, 97%). Regression analysis indicated that higher BMI, fever, and the requirement of mechanical ventilation or extracorporeal membrane oxygenation were significantly associated with higher NT. Anti-SP antibodies correlated moderately with NT (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). Most COVID-19 survivors had sustained neutralizing antibodies and tested positive for SP-total Ig and NP-total Ig approximately 6 months after infection.
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http://dx.doi.org/10.3389/fmicb.2021.661187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137897PMC
May 2021

Polymer Coupling via Hetero-Disulfide Exchange and Its Applications to Rewritable Polymer Brushes.

ACS Appl Mater Interfaces 2021 May 13;13(20):24183-24193. Epub 2021 May 13.

Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, 637371 Singapore.

An iodide-terminated polymer (Polymer-I) is converted to a thiol-terminated polymer (Polymer-SH) using HSCHCHSH in a remarkably short time (10 min). Polymer-SH is further converted to a pyridyl disulfide-terminated polymer (Polymer-SS-Py). The hetero-coupling of Polymer-SH and Polymer-SS-Py is successfully achieved to quantitatively generate a polymer disulfide (Polymer-SS-Polymer). Exploiting this efficient hetero-coupling technique, Polymer-SH is attached (grafted) on a Py-SS-immobilized surface to generate a polymer brush via a disulfide (-SS-) linkage (writing process). The -SS- linkage is cleaved by the treatment with dithiothreitol (DTT) to detach the polymer from the surface (erasing process). Subsequently, another Polymer-SH is attached on the surface to generate another polymer brush (rewriting process). Thus, a writable, erasable, and rewritable polymer brush surface is achieved. Hydrophilic, hydrophobic, and super-hydrophobic polymers (Polymer-SH) are attached on the surface, tailoring the surface wettability in the writing-erasing-rewriting cycles. Polymer-SH is also attached on a chain-end Py-SS-functionalized polymer brush surface, generating a rewritable block copolymer brush surface. A patterned block copolymer brush surface is also obtained using photo-irradiation and a photo-mask in the erasing process. The metal-free synthetic procedure, accessibility to patterned brushes, and switchable surface properties via the writing-erasing-rewriting process are attractive features of the present approach.
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http://dx.doi.org/10.1021/acsami.1c07195DOI Listing
May 2021

Heterogeneity of Associations between Total and Types of Fish Intake and the Incidence of Type 2 Diabetes: Federated Meta-Analysis of 28 Prospective Studies Including 956,122 Participants.

Nutrients 2021 Apr 7;13(4). Epub 2021 Apr 7.

Postgraduate Program in Epidemiology Faculdade de Medicina, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 90040-060, Brazil.

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 ( = 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, = 61%) for total fish, 1.04 (1.01-1.07, = 46%) for fatty fish, and 1.02 (1.00-1.04, = 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, = 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.
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http://dx.doi.org/10.3390/nu13041223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068031PMC
April 2021

Long-term response of Helicobacter pylori antibody titer after eradication treatment in middle-aged Japanese: JPHC-NEXT Study.

J Epidemiol 2021 Apr 28. Epub 2021 Apr 28.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center.

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.
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http://dx.doi.org/10.2188/jea.JE20200618DOI Listing
April 2021

Association Between Birth Weight and Risk of Pregnancy-Induced Hypertension and Gestational Diabetes in Japanese Women: JPHC-NEXT Study.

J Epidemiol 2021 Apr 13. Epub 2021 Apr 13.

Epidemiology and Prevention Group, Center for Public Health and Sciences, National Cancer Center.

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.
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http://dx.doi.org/10.2188/jea.JE20200302DOI Listing
April 2021

Relationship between unhealthy sleep status and dry eye symptoms in a Japanese population: The JPHC-NEXT study.

Ocul Surf 2021 07 18;21:306-312. Epub 2021 Apr 18.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.

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 (P<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.
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http://dx.doi.org/10.1016/j.jtos.2021.04.001DOI Listing
July 2021

High-Temperature Pulsed-Field-Gradient Li-NMR Measurements of LiCO over 700 K.

Anal Sci 2021 Oct 12;37(10):1477-1479. Epub 2021 Mar 12.

National Institute for Materials Science.

Understanding the transport property of Li ions is crucial for improving the performance of Li-ion batteries. To investigate the ion diffusion at high temperatures, we constructed a high-temperature pulsed-field-gradient (PFG) nuclear magnetic resonance (NMR) probe capable of measurements at temperatures >700 K. The accuracy of the sample temperature was confirmed via Br NMR measurements of KBr. Li PFG-NMR measurements of LiCO were performed at temperatures up to 724 K using the probe. The apparent diffusion coefficient of Li ions in LiCO was obtained experimentally.
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http://dx.doi.org/10.2116/analsci.21A001DOI Listing
October 2021

Use of portable partitions with high-efficiency particulate air filters in the endoscopy unit.

Endosc Int Open 2021 Feb 3;9(2):E278-E279. Epub 2021 Feb 3.

Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan.

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http://dx.doi.org/10.1055/a-1322-2761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857964PMC
February 2021

Development of an Automated Chemiluminescence Assay System for Quantitative Measurement of Multiple Anti-SARS-CoV-2 Antibodies.

Front Microbiol 2020 15;11:628281. Epub 2021 Jan 15.

Department of Microbiology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

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.
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http://dx.doi.org/10.3389/fmicb.2020.628281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7843449PMC
January 2021

Body mass index and colorectal cancer risk: A Mendelian randomization study.

Cancer Sci 2021 Apr 25;112(4):1579-1588. Epub 2021 Feb 25.

Department of Integrative Genomics, Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan.

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/m ) 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.
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http://dx.doi.org/10.1111/cas.14824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019210PMC
April 2021

Synthesis of vinyl iodide chain-end polymers organocatalyzed chain-end transformation.

Chem Commun (Camb) 2021 Feb;57(9):1105-1108

Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, 637371, Singapore.

In the presence of alkynes (CH[triple bond, length as m-dash]C-R2), iodide chain-end polymers (Polymer-I) were successfully transformed to vinyl iodide chain-end polymers (polymer-CH[double bond, length as m-dash]CR2-I) in a single step via organocatalysis. This reaction is completely metal-free and easy to carry out without using special reagents or special conditions. The polymers encompassing polyacrylates and polymethacrylate, and additional functionalities (e.g., OH and CF3) were also incorporated into the R2 moiety. The obtained Polymer-CH[double bond, length as m-dash]CR2-I further served as a useful precursor for copper-catalyzed cross-coupling reactions with various thiols (R3-SH) to yield vinyl sulfide chain-end polymers (polymer-CH[double bond, length as m-dash]CR2-SR3) with various R3 moieties. Interestingly, under selected conditions, this organocatalysis also offered block-like copolymers containing a conjugated oligo-alkyne segment and a non-conjugated polyacrylate segment. Exploiting the unique structure, the block-like copolymer was used as an efficient dispersant of carbon nanotubes.
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http://dx.doi.org/10.1039/d0cc07987aDOI Listing
February 2021

Working cancer survivors' physical and mental characteristics compared to cancer-free workers in Japan: a nationwide general population-based study.

J Cancer Surviv 2021 Dec 12;15(6):912-921. Epub 2021 Jan 12.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Tokyo, Japan.

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.
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http://dx.doi.org/10.1007/s11764-020-00984-7DOI Listing
December 2021

The Confounder-Mediator Dilemma: Should We Control for Obesity to Estimate the Effect of Perfluoroalkyl Substances on Health Outcomes?

Toxics 2020 Dec 20;8(4). Epub 2020 Dec 20.

Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT 06510, USA.

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.
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http://dx.doi.org/10.3390/toxics8040125DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766757PMC
December 2020

Low HbA1c levels and all-cause or cardiovascular mortality among people without diabetes: the US National Health and Nutrition Examination Survey 1999-2015.

Int J Epidemiol 2021 08;50(4):1373-1383

Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA, USA.

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.
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http://dx.doi.org/10.1093/ije/dyaa263DOI Listing
August 2021

Dietary fiber intake and risk of gastric cancer: The Japan Public Health Center-based prospective study.

Int J Cancer 2021 06 30;148(11):2664-2673. Epub 2020 Dec 30.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Centre, Tokyo, Japan.

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.
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http://dx.doi.org/10.1002/ijc.33450DOI Listing
June 2021

Fermented and nonfermented soy foods and the risk of breast cancer in a Japanese population-based cohort study.

Cancer Med 2021 01 19;10(2):757-771. Epub 2020 Dec 19.

Epidemiology and Prevention Group, Center for Public Health Sciences, National Cancer Center, Chuo-ku, Japan.

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.
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http://dx.doi.org/10.1002/cam4.3677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877355PMC
January 2021

Primary Gastric Follicular Lymphoma Presenting as a Submucosal Tumor.

ACG Case Rep J 2020 Nov 19;7(11):e00478. Epub 2020 Nov 19.

Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.

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http://dx.doi.org/10.14309/crj.0000000000000478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683048PMC
November 2020

Author Correction: A cluster-randomized trial of the effectiveness of a triple-faceted intervention promoting adherence to primary care physician visits by diabetes patients: J-DOIT2 large-scale trial (J-DOIT2-LT).

Sci Rep 2020 Oct 19;10(1):18005. Epub 2020 Oct 19.

First Department of Internal Medicine, Faculty of Medicine, Toyama University, Sugitani, Toyama, Toyama, 2630, Japan.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-020-70072-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573588PMC
October 2020

Exploration of the characteristics of chronotypes in upper gastrointestinal tract diseases: a multicenter study in Japan.

Chronobiol Int 2021 04 15;38(4):534-542. Epub 2020 Oct 15.

Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Japan.

Characteristics of the chronotypes of patients with gastrointestinal disease are unknown. We evaluated chronotypes of patients with upper gastrointestinal diseases with the Munich ChronoType Questionnaire (MCTQ). A total of 2027 subjects from 29 institutions in Japan who had undergone esophagogastroduodenoscopy were asked to answer the MCTQ. The subjects' chronotypes were divided into three groups (early, intermediate, and late chronotype) using the sleep-corrected mid-point of sleep on free days (MSF) values. According to their endoscopic diagnosis and abdominal symptoms, the subjects were divided into the reflux esophagitis (RE) group, gastroduodenal ulcer (GDU) group, upper gastrointestinal carcinoma (CA) group, functional dyspepsia (FD) group, non-FD group, and control group. In total, 1128 subjects were eligible for the analysis. The MSF (average ± standard deviation, clock hours, h) of each disease group was as follows: control group: 02.51 ± 1.22, non-FD group: 02.69 ± 1.14, FD group: 02.91 ± 1.19, RE group: 02.58 ± 1.05, GDU group: 02.47 ± 1.31, and CA group: 02.11 ± 1.08 h. Compared to the control group, the rate of late chronotype of the FD group significantly increased to 33.3%, whereas that of early chronotype of the CA group significantly increased to 38.3% ( = .0177 and 0.0036, respectively). In both the FD and CA groups, chronotype was the independent factor related to the diseases. The adjusted odds ratio of late chronotype to early chronotype was 3.01 [95% CI, 1.23-7.35] in the FD group and 0.44 [95% CI, 0.23-0.85] in the CA group. In conclusion, late chronotype was common in patients with FD, and early chronotype was common in patients with upper gastrointestinal carcinoma.
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http://dx.doi.org/10.1080/07420528.2020.1830791DOI Listing
April 2021
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