Atsushi Goto

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Glycemic index (GI) and glycemic load (GL) are markers for postprandial glucose level. Since insulin, a hormone secreted to control hyperglycemia, is likely to promote the progression of tumor cells, the association between GI/GL and risk of colorectal cancer (CRC) has been researched for decades but still remains controversial. This study investigated the association between GI/GL and CRC risk, considering subtypes based on insulin receptor beta (IRβ) expression. In a large-scale, population-based prospective cohort study involving 18,537 Japanese participants, a total of 415 CRC cases were evaluated for IRβ expression using immunohistochemistry. GI and GL were calculated using a validated food frequency questionnaire. The Cox proportional hazards model was used to assess the hazard ratios (HRs) and 95% confidence intervals (CIs) of the risk of CRC and its specific subtypes. Additionally, we conducted sensitivity analyses to confirm the robustness of the results. No significant associations were observed between dietary GI, GL and overall CRC risk. Further, no significant associations were detected in IRβ-stratified analyses. The heterogeneities in the associations by IRβ status were also not statistically significant. (GI: p for heterogeneity 0.83 for men and 0.96 for women; GL: p for heterogeneity 0.84 for men and 0.60 for women) Sensitivity analyses yielded robust results. This study did not observe a significant association between GI/GL and overall CRC or IRβ-defined subtypes. These results, particularly those from the assessment of IRβ status, do not support a possible association between GI/GL and CRC development.

Japan has one of the highest dialysis prevalence rates worldwide, resulting in substantial economic and health burdens. Although obesity is a known risk factor for the decline of kidney function, the impact of being underweight remains unclear. This study aimed to investigate the relationship between body mass index (BMI), including underweight status, and kidney function decline using health check-up data. We conducted a retrospective cohort study involving Japanese individuals aged 40–74 years in Gunma Prefecture who underwent health checkups in fiscal years 2018 and 2020. The exposure was baseline BMI, which was classified into seven categories. The primary outcome was kidney function decline, defined as a ≥ 30% reduction in estimated glomerular filtration rate (eGFR) over a two-year period. Associations between BMI and kidney function decline were assessed using multivariable logistic regression analysis, adjusting for age, sex, smoking status, alcohol consumption, blood pressure, hemoglobin A1c, lipid profile, and baseline eGFR. A total of 64,970 individuals were included in the final analysis. A U-shaped association was observed between BMI and decline in kidney function. Compared to the reference group, those with obesity (BMI = 30.0–39.9 kg/m²; odds ratio [OR]: 2.05; 95% confidence interval [CI]: 1.31–3.19) and those underweight (BMI = 14.0–18.9 kg/m²; OR: 2.09; 95% CI: 1.43–3.04) had significantly increased risk. The U-shaped association between BMI and kidney function decline suggests that both obesity and underweight status are risk factors. Health guidance should target individuals in both categories to prevent chronic kidney disease.

To examine the causal effects of time-varying treatments on survival, structural nested cumulative survival time models (SNCSTMs) are flexible and theoretically promising semiparametric models characterized by causally interpretable parameters. One concern is the prerequisite for uniformly scheduled data collection and complete data for time-varying confounders. For example, in pharmacoepidemiological studies using medical information databases, laboratory test results can be missing due to unscheduled hospital visits or non-compliance with health checkups. Furthermore, missing mechanisms data may be non-ignorable and non-monotone, invalidating the typical missing-data methods that assume ignorable or monotone missing mechanisms. We propose a novel g-estimation method for SNCSTMs with non-ignorable, non-monotonic missing data for time-varying confounders. We augment the g-estimation functions using missing probability and imputation models, incorporating a user-defined selection function, which allows sensitivity analyses to evaluate the departure of missing data from ignorable mechanisms. Using a proper selection function, our estimator is doubly robust in the sense that it is consistent if either model for missing probability or imputation of missing data is correct at each time point and if either model for propensity score or conditional expectation of counterfactual counting processes is correct. Moreover, applying frequentist-type multiple imputation yields a closed-form solution for calculating the estimator, even if time-varying confounders are missing. A simulation study evaluated our proposed method’s finite sample performance and the estimator’s double robustness. We also conducted sensitivity analyses in a pharmacoepidemiological study using a Japanese medical claims database, assessing the risk of hypoglycemia in sulfonylurea-treated patients with incomplete hemoglobin A1c values.

Background: The Area Deprivation Index (ADI) is widely used to monitor health inequalities and often used as a proxy for individual socioeconomic status (SES). However, the extent to which it reflects individual SES remains unclear. This study aimed to establish evidence linking neighborhood-level ADI with individual SES indicators in Japan and examine whether similar patterns of association are observed across independent population-based cohorts.Methods: We analyzed baseline data from two population-based cohorts: the Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT) (baseline survey, 2011–2016; ages 40–74 years; N=100,024) and the Yokohama Health Study (YHS) (baseline survey, 2023; ages 30–69 years; N=8,860). ADI was ranked into quartiles (Q1: lowest, Q4: highest deprivation) based on the distribution across all postcodes in Japan and linked to each participant by residential area. Logistic regression models estimated associations between ADI quartile and low income (<1.53 million JPY) or limited education (≤9 or ≤12 years) by gender.Results: Higher ADI showed increasing trends of association with low income and ≤9 years of education in both cohorts and across genders, with p for trend <0.001 for all. In contrast, associations with ≤12 years of education were less consistent across cohorts and subgroups, with no significant trend observed among women in JPHC-NEXT (p for trend = 0.74).Conclusions: While the ADI consistently reflected income-related disadvantage across cohorts, its association with educational attainment varied across contexts. This should be carefully considered when using or interpreting ADI-based measures of health inequality in Japan.

Background: The effects of hypnotics use on the risk of adverse pregnancy outcomes across pregnancy trimesters are underexplored.Methods: From the data of the Japan Environment and Children’s Study (JECS), we constructed cohorts of women registered between January 2011 and March 2014 who delivered a liveborn singleton child. Exposure to hypnotics during the first (Period 1) and second/third (Period 2) trimesters was assessed in interviews. We identified the outcomes, preterm birth, low birth weight, and major congenital malformations, based on medical record transcripts. For each exposure period and pregnancy outcome, we estimated the risk differences (RDs) and risk ratios (RRs) using modified least-squares and modified Poisson models, respectively, adjusting for the mother’s age, body mass index, lifestyle factors, comorbidities, and other medication use.Results: A total of 91,370 and 80,089 women were included for Periods 1 and 2, respectively. For Period 2, an increased risk of preterm birth (RD: 0.0748, 95% confidence interval [CI] 0.0175—0.132; RR 2.57 95%CI 1.42—4.65) and low birth weight (RD 0.0661 95%CI 0.00204—0.130; RR 1.77 95%CI 1.10—2.85) were observed among exposed compared with unexposed individuals. These risks were not observed for Period 1. The risk of major congenital malformations was not increased for both Periods 1 and 2.Conclusion: Hypnotic medication in late-stage pregnancy may increase the risks of preterm birth and low birth weight, although caution is warranted because of possible confounding by indication. The elevation of the risk of the usage of hypnotics at any stage of pregnancy on major malformations was not observed.

Background: Rapid and high-throughput diagnostic methods are essential for controlling the spread of infectious diseases, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Lateral flow immunoassay (LFIA) strips provide a cost-effective and user-friendly platform for point-of-care testing. However, the sensitivity of conventional LFIA kits is often limited by the performance of their detection probes. This study reports a highly sensitive LFIA strip for detecting the SARS-CoV-2 nucleocapsid (NP) protein using platinum-decorated poly(2-vinylpyridine) nanoparticles (Pt-P2VPs) as probes. Methods: Monoclonal antibodies against SARS-CoV-2 NP were conjugated with Pt-P2VPs and incorporated into LFIA strips. The test line was coated with anti–SARS-CoV-2 NP monoclonal antibody, and the control line with goat anti-mouse IgG. Recombinant proteins, viral strains, and nasopharyngeal swab specimens from patients were used to evaluate assay performance, with reverse transcription polymerase chain reaction (RT-PCR) as the reference standard. Diagnostic accuracy was assessed using nonparametric statistical tests. Results: Pt-P2VP-based LFIA strips enabled sensitive detection of recombinant NP and inactivated SARS-CoV-2, with minimal cross-reactivity. In 200 clinical specimens (100 PCR-negative and 100 PCR-positive), the assay achieved 74% sensitivity and 100% specificity, with strong correlation to viral RNA load. Compared with conventional LFIA kits, Pt-P2VP strips demonstrated superior sensitivity at lower viral loads. Conclusions: Pt-P2VPs represent a promising probe material for enhancing LFIA performance and may facilitate the development of rapid, sensitive, and scalable immunoassays for infectious disease diagnostics in biomedical applications.

Objectives To estimate uptake of the 75 g oral glucose tolerance test (OGTT) at 6–12 weeks postpartum among women with gestational diabetes mellitus (GDM) in Japan, and to explore the demographic and clinical characteristics associated with screening uptake. Design Retrospective cohort study using administrative claims data. Setting Data from a nationwide employees’ health insurance claims database (Japan Medical Data Center; JMDC) during the fiscal years 2012–2020 were assessed. Participants 2282 women with GDM in the JMDC claims database (April 2012–January 2021), ascertained using the International Classification of Diseases 10th revision (ICD-10) codes cross-validated with a high-risk GDM management fee. Primary and secondary outcome measures Primary outcome: completion of a 75 g OGTT at 6–12 weeks postpartum. Secondary outcomes: completion of a 75 g OGTT at 4–12 weeks postpartum and cumulative completion up to 1 year postpartum. Results We included 2282 women in the analysis. The overall screening rate was 28.7% (654/2282) from 2012 to 2020. Even in 2020, the year with the highest reported screening rate, it remained low at 33.2% (181/546). After expanding the range to include 4 weeks to ≤1 year postpartum, the cumulative screening rate reached 64.9% by 1 year postpartum. The screening rate was lower when childbirth and GDM were managed at different facilities than when both were managed within the same facility. Conclusions We report suboptimal screening rates for women with a GDM history in Japan. This study highlights the need for continuous monitoring and the development of effective strategies for early screening and intervention in this high-risk group. These strategies should include system-level improvements in screening methods and enhance patient awareness through antenatal education prior to delivery.