Background: The COVID-19 pandemic has affected cancer care. The aim of this study was to clarify the trend of colorectal cancer (CRC) stage distribution in Japan during the COVID-19 pandemic.

Methods: In this retrospective study, we used an inpatient medical claims database established at approximately 400 acute care hospitals. From the database, we searched patients who were identified as having the main disease (using ICD-10codes [C18.0–C20]) between January 2018 and December 2020. A multivariate logistic regression analysis was used to determine the impact of the pandemic on CRC stage distribution each month, and the odds ratio (OR) for late-stage cancer was calculated.

Results: We analyzed 99,992 CRC patients. Logistic regression analysis, including the interaction term between increased late-stage CRC effect during the pandemic period and by each individual month, showed that the OR for late-stage CRC was highest in July during the pandemic, at 1.31 (95%CI: 1.13– 1.52) and also significantly higher in September at 1.16 (95%CI: 1.00– 1.35).

Conclusion: We investigated the trend of CRC stage distribution during the COVID-19 pandemic using a nationwide hospital-claims database in Japan, and found that the proportion of early-stage cancers tended to decrease temporarily after the state of emergency declaration due to the COVID-19 pandemic, but the effect was only temporary.

Background: Studies on the association between preserved ratio impaired spirometry (PRISm) and dementia are limited. Indeed, PRISm has often been overlooked or ignored as an index of lung function impairment. Therefore, we investigated the association of PRISm with the risk for the development of dementia in an older Japanese population.

Methods: A total of 1202 community-dwelling, older Japanese participants aged ≥65 years without dementia were followed up for a median of 5.0 years. Participants were categorized by spirometry as follows: normal spirometry (FEV₁/FVC ≥0.70 and FEV₁ ≥80% predicted), PRISm (≥0.70 and <80%), airflow limitation (AFL) Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 (<0.70 and ≥80%), and AFL GOLD 2 to 4 (<0.70 and <80%). Hazard ratios (HRs) and their 95% confidence intervals (CIs) were computed using a Cox proportional hazards model.

Results: During the follow-up period, 122 participants developed dementia. The age- and sex-adjusted incidences of dementia in the participants with normal spirometry, PRISm, AFL GOLD 1, and AFL GOLD 2 to 4 were 20.5, 37.0, 18.4, and 28.6 per 1000 person-years, respectively. Participants with PRISm had a higher risk of dementia (HR 2.04 [95%CI, 1.19-3.49]) than those with normal spirometry after adjusting for confounders. Moreover, both reduced FEV₁% predicted values and FVC% predicted values were associated with the risk for dementia.

Conclusion: PRISm was associated with an increased risk of dementia in a general older Japanese population.

Background: An association between birth weight and cardiovascular disease (CVD) in adulthood has been observed in many countries; however, only a few studies have been conducted in Asian populations.

Methods: We used data from the baseline survey (2011–2016) of the Japan Public Health Center-based Prospective Study for the Next Generation Cohort, which included 114,105 participants aged 40–74 years. Adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs) were calculated from the prevalence of present and past histories of CVD and other lifestyle-related diseases, including hypertension, diabetes, hyperlipidemia, and gout, by birth weight, using Poisson regression.

Results: The prevalence of CVD increased with lower birth weight, with the highest prevalence among those with birth weight under 1,500 grams (males 4.6%; females 1.7%) and the lowest one among those with birth weight at or over 4,000g (males 3.7%: females 0.8%). Among 88.653 participants (41,156 males and 47,497 females) with complete data on possible confounders, birth weight under 1,500g was associated with a higher prevalence of CVD (aPR 1.76 [95%CI 1.37-2.26]), hypertension (aPR 1.29 [95%CI 1.17–1.42]), and diabetes (aPR 1.53 [95%CI 1.26–1.86]) when a birth weight of 3,000–3,999 grams was used as the reference. Weaker associations were observed for birth weight of 1500–2499 grams and 2500–2999 grams, while no significant associations were observed for birth weight at or over 4000 g. The association between birth weight and the prevalence of hyperlipidemia was less profound, and no significant association was observed between birth weight and gout.

Conclusion: Lower birth weight was associated with a higher prevalence of CVD, hypertension, and diabetes in the Japanese population.

Background: We prospectively examined the association between total fat and fatty acid intake and type 2 diabetes (T2D) among Japanese adults.

Methods: This study was conducted using data from the Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC). A validated food frequency questionnaire evaluated the intake of total fat and fatty acids. Diabetes was assessed using self-reported data. Multivariable logistic regression analysis was performed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of incident T2D across quintiles of total fat and fatty acid intake after adjusting for potential confounders.

Results: A total of 19,088 non–diabetic participants (age range, 40–79 years) enrolled in the JACC between 1988 and 1990 were included in this study. During the five-year study period, 494 the participants developed T2D. The OR of T2D for the highest versus lowest quintiles was 0.58 (95% CI, 0.37–0.90) for total fat, 0.78 (95% CI, 0.51–1.20) for saturated fatty acid (SFA), 0.55 (95% CI, 0.35–0.86) for monounsaturated fatty acids (MUFA), 0.61 (95% CI, 0.39–0.96) for polyunsaturated fatty acids (PUFA), 0.64 (95% CI, 0.42–0.99) for n-3 PUFA, and 0.70 (95% CI, 0.45–1.09) for n-6 PUFA. Total fat and fatty acid (except SFA and n-6 PUFA) intake were inversely associated with T2D in men. Total fat and fatty acid intake were not associated with T2D in women.

Conclusion: Higher intakes of total fats, MUFA, PUFA, and n-3 PUFA were inversely associated with T2D among Japanese men.

Background: Currently, awareness about platelet count (PC) and its consequences for perinatal outcome have increased, but there is little reliable evidence on fecundability.

Methods: Based on the National Free Pre-conception Check-up Projects supported by the Chinese government, 5,524,886 couples met the inclusion criteria were included in this cohort study. Cox regression models were adopted to estimate fecundability ratios (FRs) and their 95% confidence intervals for pre-pregnancy PC quintiles. Restricted cubic splines were used to flexibly model and visualize the relationship of PC with FRs. Microsoft SQL server and R software were used for data management and analysis.

Results: The median of pre-pregnancy PC among women was 221.00×10⁹/L. The first (<177.00 ×10⁹/L) and second quintile (177.00-207.99 ×10⁹/L) of PC showed slightly increased fecundability (Q1: adjusted FR 1.05, 95% CI 1.04-1.06; Q2: adjusted FR 1.04, 95% CI 1.03-1.05), while higher quintals (Q4: 236.00-271.99 ×10⁹/L; Q5: ≥272.00 ×10⁹/L) were related to reduction of fecundability, when compared with the third quintile of PC (208.00-235.99 ×10⁹/L) (Q4: adjusted FR 0.96, 95% CI 0.95-0.97; Q5: adjusted FR 0.88, 95% CI 0.87-0.89). In the first quintiles (<177.00×10⁹/L), only 20.93% women had PC below 129.94×10⁹/L. An inverse-U shape association was consistently observed among women such that the lower PC of normal range (<118.03×10⁹/L) and higher PC (>223.06×10⁹/L) were associated with the risk of reduced female fecundability (P for non-linearity < 0.01).

Conclusion: PC is associated with female fecundability. Further classification of PC levels may deepen our understanding of the early warnings and significance of female fecundability.

Background: Improving diets requires an awareness of the need to limit foods for which excessive consumption is a health problem. Since there are limited reports on the link between this awareness and mortality risk, we examined the association between awareness of limiting food intake (energy, fat, and sweets) and all-cause mortality in a Japanese cohort study.

Methods: Participants comprised 58,772 residents (27,294 men; 31,478 women) aged 35–69 years who completed baseline surveys of the Japan Multi-Institutional Collaborative Cohort Study from 2004 to 2014. Hazard ratios (HRs) for all-cause mortality and 95% confidence intervals (CIs) were estimated by sex using a Cox proportional hazard model, with adjustment for related factors. Mediation analysis with fat intake as a mediator was also conducted.

Results: The mean follow-up period was 11 years and 2,516 people died. Estimated energy and fat intakes according to the Food Frequency Questionnaire were lower in those with awareness of limiting food intake than in those without this awareness. Women with awareness of limiting fat intake showed a significant decrease in mortality risk (HR=0.73; 95% CI, 0.55 to 0.94). Mediation analysis revealed that this association was due to the direct effect of the awareness of limiting fat intake and that the total effect was not mediated by actual fat intake. Awareness of limiting energy or sweets intake was not related to mortality risk reduction.

Conclusion: Awareness of limiting food intake had a limited effect on reducing all-cause mortality risk.

Background: Heated tobacco products (HTPs) have gained global popularity, but their health risks remain unclear. Therefore, the current study aimed to identify plasma metabolites associated with smoking and HTP use in a large Japanese population to improve health risk assessment.

Methods: Metabolomics data from 9,922 baseline participants of the Tsuruoka Metabolomics Cohort Study (TMCS) were analyzed to determine the association between smoking habits and plasma metabolites. Moreover, alterations in smoking-related metabolites among HTP users were examined based on data obtained from 3,334 participants involved from April 2018 to June 2019 in a follow-up survey.

Results: Our study revealed that cigarette smokers had metabolomics profiles distinct from never smokers, with 22 polar metabolites identified as candidate biomarkers for smoking. These biomarker profiles of HTP users were closer to those of cigarette smokers than those of never smokers. The concentration of glutamate was higher in cigarette smokers, and biomarkers involved in glutamate metabolism were also associated with cigarette smoking and HTP use. Network pathway analysis showed that smoking was associated with the glutamate pathway, which could lead to endothelial dysfunction and atherosclerosis of the vessels.

Conclusions: Our study showed that the glutamate pathway is affected by habitual smoking. These changes in the glutamate pathway may partly explain the mechanism by which cigarette smoking causes cardiovascular disease. HTP use was also associated with glutamate metabolism, indicating that HTP use may contribute to the development of cardiovascular disease through mechanisms similar to those in cigarette use.

Background: In regions with a high prevalence of peanut allergy (PA), there is a consensus that the introduction of peanuts in early infancy is preventive against the development of PA. However, few studies have investigated whether the introduction of peanuts to infants is associated with PA in regions with a low prevalence of PA, including Japan.

Methods: We used data from 74,240 mother–child pairs who participated in the Japan Environment and Children’s Study, a prospective birth cohort recruited between January 2011 and March 2014. A logistic regression model was used to analyze the association between infantile peanut introduction and PA at the age of 4 years with non-infantile peanut introduction as the reference group, adjusted for potential confounders.

Results: The percentage of infantile peanut introduction was 4.9% (n=3294) and 286 (0.4%) participants had allergic symptoms to peanuts at 4 years of age. Of all participants, 129 (0.2%) had PA at 4 years of age, which was defined as allergic symptoms and sensitization to peanuts. Those with infantile peanut introduction had a lower prevalence of PA than those without infantile peanut introduction, although this did not reach statistical significance (adjusted odds ratio: 0.53, 95% confidence interval, 0.17–1.68). Sensitivity analysis using IgE-mediated symptoms caused by peanuts as the outcome showed a similar result in relation to infantile peanut introduction.

Conclusions: In countries with a low prevalence of PA, the effect of infantile peanut introduction on PA prevention was unclear.

Background: We aimed to assess whether the United States-developed Claims-based Frailty Index (CFI) can be implemented in Japanese older adults using claims data.

Methods: We used the monthly claims data and certification of long-term care (LTC) insurance data of residents from 12 municipalities from April 2014 to March 2019. The 12 months from first recording was defined as the “baseline period,” and the time thereafter as the “follow-up period”. Participants aged ≥65 years were included, and those with no certified LTC insurance or who died at baseline were excluded. New certification of LTC insurance and all-cause mortality during the follow-up period were defined as outcome events. CFI categorization consisted of three steps including: 1) using 12 months deficit-accumulation approach that assigned different weights to each of the 52 items; 2) the accumulated score to derive the CFI; and 3) categorizing the CFI as “robust” (<0.15), “prefrail” (0.15–0.24), and “frail” (≥0.25). Kaplan–Meier survival curves and Cox proportional hazard models were used to determine the association between CFI and outcomes. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated.

Results: There were 519,941 participants in total. After adjusting for covariates, the severe CFI category had a high risk of certification of LTC insurance (prefrail: HR 1.33; 95% CI, 1.27–1.39 and frail: HR 1.60; 95% CI, 1.53–1.68) and all-cause mortality (prefrail: HR 1.44; 95% CI, 1.29–1.60 and frail: HR 1.84; 95% CI, 1.66–2.05).

Conclusion: This study suggests that CFI can be implemented in Japanese claims data to predict the certification of LTC insurance and mortality.

Background: This study aimed to develop models to predict the 5-year incidence of type 2 diabetes mellitus (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.

Conclusion: Our invasive risk models are expected to discriminate between high- and low-risk individuals with T2DM in a Japanese population.

Background: Although fat mass index (FMI) and fat-free mass index (FFMI) affect lung function, FMI and FFMI are not independent of each other, since FMI and FFMI were calculated as fat mass and fat-free mass divided by height squared, respectively. We aimed to examine the association of combined FMI and FFMI with lung function.

Methods: In this cross-sectional study, lung function was evaluated using forced expiratory volume at 1 s (FEV₁) and forced vital capacity (FVC) measured using spirometry. Both FMI and FFMI were classified into sex-specific quartiles (16 groups). Analysis of covariance was used to assess the associations of combined FMI and FFMI with lung function. The trend test was conducted by stratifying the FMI and FFMI, scoring the categories from 1–4 (lowest–highest), and entering the number as a continuous term in the regression model.

Results: This study included 3,736 men and 8,821 women aged ≥20 years living in Miyagi Prefecture, Japan. The mean FEV₁ was 3.0 (standard deviation [SD], 0.7) L for men and 2.3 (SD, 0.5) L for women. The mean FVC was 3.8 (SD, 0.7) L for men and 2.8 (SD, 0.5) L for women. FMI was inversely associated with lung function among all FFMI subgroups in both sexes. Conversely, FFMI was positively associated with lung function in all FMI subgroups in both sexes.

Conclusion: Higher FMI was associated with lower lung function independent of FFMI; higher FFMI was associated with higher lung function independent of FMI. Reducing FMI and maintaining FFMI might be important for respiratory health.

Background: The novel coronavirus disease 2019 (COVID-19) pandemic may have reduced opportunities for engaging in physical activity (PA) and increased sedentary behavior (SB) among workers. However, most previous studies used self-reported assessments. This study aimed to examine the changes in accelerometer-measured PA and SB from before to after COVID-19 outbreak among Japanese workers.

Methods: This 1-year longitudinal study used data from the annual health check-ups of workers who lived in the Tokyo metropolitan area. Baseline and follow-up data were collected from June to November of 2019 and June to November of 2020, respectively. Participants were asked to wear the accelerometer on their hip during awake hours for at least 10 days in both the surveys. Before the analysis, considering the difference in wearing time, time spent in PA and SB were converted to the percentage of wearing time. To investigate the changes in PA or SB from before to during COVID-19 outbreak, paired t-tests were performed.

Results: Of the 757 eligible participants, 536 were included in the analysis (70.8%). Participants’ mean age was 53.3 years, 69.6% were female, and most were full-time employees. Time spent in PA decreased, regardless of weekdays or weekends, although changes on the weekends were not significant. Conversely, time spent in SB increased on both weekdays and weekends in 2020. These changes corresponded to approximately 10 minutes per day decrease in PA and increase in SB.

Conclusion: Objectively measured PA decreased and SB increased by approximately 10 minutes per day after the COVID-19 outbreak among Japanese workers.

Background: Although the effectiveness of BNT162b2 messenger RNA vaccines against the Omicron variant has been reported in several countries, data are limited in children living in Asian countries. Therefore, this study aimed to estimate the effectiveness of the pediatric primary two-dose monovalent mRNA vaccine series in preventing symptomatic novel coronavirus disease 2019 (COVID-19) in Japan.

Methods: We conducted a test-negative case-control study (262 test-positive cases and 259 test-negative controls) in patients aged 5–11 years who presented with COVID-19-like symptoms during the Omicron BA.2- and BA.5-predominant periods. Vaccination status, demographic data, underlying medical conditions, lifestyle, personal protective health behaviors, living environment, and PCR test results were obtained using parent-administered questionnaires and clinical records. Vaccine effectiveness (VE) against symptomatic COVID-19 was calculated using a multivariate logistic regression analysis.

Results: Of the test-positive cases and test-negative controls, 9.2% (n = 24) and 12.7% (n = 33) received two vaccine doses, respectively. Having siblings and a BA.5-dominant period were significantly associated with symptomatic COVID-19. After adjusting for age, siblings, study period, and duration after the last vaccination, the overall VE of two-dose vaccination was 50.0% (95% confidence interval [CI], 5–74%). VE was 72% (95% CI, 24–89%) within 3 months after the two-dose vaccination, while it decreased to 24% (95% CI, −80% to 68%) after 3 months.

Conclusion: Two BNT162b messenger RNA vaccine doses provided moderate protection against symptomatic COVID-19 during the Omicron variant period. A time-dependent decrease in VE was noted after the second dose; thus, a booster dose 3 months after the second dose is warranted.

Background: Symptoms after novel coronavirus disease 2019 (COVID-19) recovery by severe acute respiratory syndrome coronavirus 2 strains are unspecified.

Methods: This self-administered questionnaire-based study was conducted to investigate symptoms after COVID-19 recovery at one of the main hospitals for COVID-19 treatment in Hiroshima, Japan, from September 2020 to March 2022 for patients who visited follow-up consultations after COVID-19. Study subjects were divided into four groups (Wild-type, Alpha, Delta, and Omicron periods) according to COVID-19 onset date. Hierarchical cluster analysis was performed to determine symptom clusters and investigate risk factors for each symptom cluster using multivariate analysis.

Results: Among 385 patients who enrolled in this study, 249 patients had any persistent symptoms at a median of 23.5 (interquartile range, 20–31) days after COVID-19 onset. Among patients with any persistent symptoms, symptom clusters including olfactory or taste disorders, respiratory symptoms, and cardiac symptoms were found. Respiratory symptoms were more frequent among patients infected in the Omicron period compared to the Wild-type period (adjusted odds ratio [AOR] 3.13; 95% confidence interval [CI], 1.31–7.48). Compared to patients who recovered from mild COVID-19, patients who needed oxygen or ventilation support suffered fewer post-COVID-19 respiratory symptoms (AOR 0.46; 95% CI, 0.22–0.97) but more post-COVID-19 cardiac symptoms among them (AOR 2.67; 95% CI, 1.26–5.65). Olfactory or taste disorders were fewer among patients infected in the Omicron period compared to the Wild-type period (AOR 0.14; 95% CI, 0.04–0.46).

Conclusion: This study revealed that symptoms after COVID-19 may vary depending on the infected strain.

Introduction

The Covid-19 pandemic has significantly impacted end-of-life decisions for cancer patients in Japan, with disparities existing between preferred and actual care settings. Our study investigates the potential shifts in cancer death locations during the pandemic and if there were excess cancer deaths.

Methods

Utilizing national mortality data from the Ministry of Health, Labour, and Welfare from January 2012 to February 2023, we identified cancer deaths using ICD-10 codes. We assessed death locations, including medical institutions, nursing facilities, and homes. The Farrington algorithm was employed to estimate expected death counts, and the differences between observed and expected counts were denoted as excess deaths.

Results

From January 2018 to February 2023, there was consistently increase in the weekly observed cancer deaths. The presence of a definitive excess during the pandemic period remains uncertain. The percentage of deaths in medical institutions declined from 83.3% to 70.1% , while home deaths increased from 12.1% to 22.9%. Between April 2020 and February 2023, deaths in medical institutions frequently fell below the 95% prediction lower limit. Home deaths consistently exceeded the 95% prediction upper limit, with significant excess deaths reported annually.

Conclusion

Our study found a shift in cancer death locations from medical institutions to homes in Japan during the COVID-19 pandemic. Our study did not confirm an overall increase in cancer deaths during this period. As with global trends, the profound shift from hospitals to homes in Japan calls for a comprehensive exploration to grasp the pandemic's multifaceted impact on end-of-life cancer care decisions.

Background: The Guangzhou Nutrition and Health Study (GNHS) aims to assess the determinants of metabolic disease in nutritional aspects, as well as other environmental and genetic factors, and explore possible biomarkers and mechanisms with multi-omics integration.

Methods: The population-based sample of adults in Guangzhou, China (baseline: 40-83 years old; n = 5118) was followed up about every 3 years. All will be tracked via on-site follow-up and health information systems. We assessed detailed information on lifestyle factors, physical activities, dietary assessments, psychological health, cognitive function, body measurements, and muscle function. Instrument tests included dual-energy X-ray absorptiometry scanning, carotid artery and liver ultrasonography evaluations, vascular endothelial function evaluation, upper-abdomen and brain magnetic resonance imaging, and 14-d real-time continuous glucose monitoring tests. We also measured multi-omics, including host genome-wide genotyping, serum metabolome and proteome, gut microbiome (16S rRNA sequencing, metagenome, and internal transcribed spacer 2 sequencing), and fecal metabolome and proteome.

Results: The baseline surveys were conducted from 2008 to 2015. Now, we have completed 3 waves. The 3rd and 4th follow-ups have started but have yet to end. A total of 5118 participants aged 40-83 took part in the study. The median age at baseline was approximately 59.0 years and the proportion of female participants was about 69.4%. Among all the participants, 3628 (71%) completed at least one on-site follow-up with a median duration of 9.48 years.

Conclusion: The cohort will provide data that have been influential in establishing the role of nutrition in metabolic diseases with multi-omics.

Background: In Japan, older drivers have been encouraged to surrender their driving licenses for traffic safety despite the potential adverse social and health outcomes of driving cessation. We reconsidered such policies and social pressure by comparing the risk of at-fault motor vehicle collisions (MVCs) across the age groups of drivers.

Methods: Using the national data of police-reported MVCs that occurred between 2016 and 2020, we examined the number of at-fault MVCs per licensed driver (MVC rate) and the number of fatally and non-fatally injured persons per at-fault MVC by the sex and age groups of at-fault drivers.

Results: The MVC rate of older drivers was higher than that of middle-aged drivers but lower than that of young drivers. The number of injured persons among the collided counterparts (collided car occupants, motorcyclists, bicyclists, and pedestrians) per MVC caused by older drivers was not greater than that by drivers in other age groups. In fatal MVCs caused by older drivers, drivers themselves or their passengers tend to be killed rather than their collided counterparts. Overall, the results were mostly consistent between male and female drivers.

Conclusions: The risk of at-fault MVCs increased with the advancing age of drivers after middle age; however, this risk among older drivers did not exceed that among young drivers, without posing a high risk of injuries to their collided counterparts.

Background: In Japan, sentinel surveillance is used to monitor the trend of infectious gastroenteritis. Another method of pathogen surveillance, wastewater-based epidemiology, has been used recently because it can help to monitor infectious disease without relying on patient data. Here, we aimed to determine the viral trends reflected in the number of reported patients and number of gastroenteritis virus-positive samples. We focused on gastroenteritis viruses present in wastewater and investigated the usefulness of wastewater surveillance for the surveillance of infectious gastroenteritis.

Methods: Real-time polymerase chain reaction was used for viral gene detection in wastewater. The number of reported patients per pediatric sentinel site and number of viral genome copies were compared for correlation potential. The number of gastroenteritis virus-positive samples reported by National Epidemiological Surveillance of Infectious Disease (NESID) and the status of gastroenteritis viruses detected in wastewater were also evaluated.

Results: Genes of norovirus genotype I, norovirus genotype II, sapovirus, astrovirus, rotavirus group A, and rotavirus group C were detected in wastewater samples. Viruses were detected in wastewater during periods when no gastroenteritis virus-positive samples were reported to NESID.

Conclusion: Norovirus genotype II and other gastroenteritis viruses were detected in wastewater even during periods when no gastroenteritis virus-positive samples were found. Therefore, surveillance using wastewater can complement sentinel surveillance and is an effective tool for the surveillance of infectious gastroenteritis.

Background: Glomerular hyperfiltration has been reported to be associated with adverse renal outcomes in the general population. It is not known whether drinking pattern is associated with the risk of glomerular hyperfiltration in healthy individuals.

Methods: We prospectively followed middle-aged 8,640 Japanese men with normal renal function, no proteinuria, no diabetes, and no use of antihypertensive medications at entry. Data on alcohol consumption were gathered by questionnaire. Glomerular hyperfiltration was defined as estimated glomerular filtration rate (eGFR) ≥117 mL/min/1.73 m², which was the upper 2.5th percentile value of eGFR in the entire cohort.

Results: During 46,186 person-years of follow-up, 330 men developed glomerular hyperfiltration. In a multivariate model, for men who consumed alcohol on 1–3 days per week, alcohol consumption of ≥69.1 g ethanol/drinking day was significantly associated with the risk of glomerular hyperfiltration (hazard ratio [HR] 2.37; 95% confidence interval [CI], 1.18–4.74) compared with non-drinkers. For those who consumed alcohol on 4–7 days per week, higher alcohol consumption per drinking day was associated with a higher risk of glomerular hyperfiltration: the HRs for alcohol consumption of 46.1–69.0, and ≥69.1 g ethanol/drinking day were 1.55 (95% CI, 1.01–2.38), and 1.78 (95% CI, 1.02–3.12), respectively.

Conclusion: For high drinking frequency per week, more alcohol intake per drinking day was associated with an increased risk of glomerular hyperfiltration, while for low drinking frequency per week, only very high alcohol intake per drinking day was associated with an increased risk of glomerular hyperfiltration in middle-aged Japanese men.

Background: For therapeutic efficacy, molnupiravir and nirmatrelvir-ritonavir must be started to treat patients within 5 days of disease onset to treat patients with novel coronavirus disease 2019 (COVID-19). However, some patients spend more than 5 days from disease onset before reporting to the Public Health Office. This study aimed to clarify the characteristics of patients with reporting delay.

Methods: This study included data from 12,399 patients with COVID-19 who reported to the Public Health Office from March 3^rd, 2021 to June 30^th, 2021. Patients were stratified into “linked” (n = 7,814) and “unlinked” (n = 4,585) cases depending on whether they were linked to other patients. A long reporting delay was defined as the difference between the onset and reporting dates of 5 days or more. Univariate and multivariate analyses were performed using log-binomial regression to identify factors related to long reporting delay, and prevalence ratios with corresponding 95% confidence intervals were calculated.

Results: The proportion of long reporting delay was 24.4% (1,904/7,814) and 29.3% (1,344/4,585) in linked and unlinked cases, respectively. Risks of long reporting delay among linked cases were living alone and onset on the day with a higher 7-day daily average confirmed cases or onset on weekends; whereas, risks for unlinked cases were age over 65 years, without occupation, and living alone.

Conclusion: Our results suggest the necessity to establish a Public Health Office system that is less susceptible to the rapid increase in the number of patients, promotes educational activities for people with fewer social connections, and improves access to health care.

Background: Little is known about the trends of imported infectious diseases among travelers to non-endemic countries during the novel coronavirus disease 2019 (COVID-19) pandemic. This article aimed to describe those among travelers to Japan.

Methods: This is a descriptive study based on national surveillance data. Imported infectious disease cases were defined as those with a reported overseas source of infection among 15 diseases pre-selected based on the probability and impact of importation. The number of notified cases from April 2016 to March 2021 were described by disease and time of diagnosis. The relative ratio and absolute difference in case counts—both by number and per arrival—were calculated by disease comparing those from the pandemic period (April 2020–March 2021) to the pre-pandemic period (April 2016–March 2020).

Results: A total of 3,524 imported infectious disease cases were diagnosed during the study period, including 3,439 cases before and 85 cases during the pandemic. The proportionate distribution of diseases changed but notification counts of all 15 diseases decreased during the pandemic. Accounting for arrivals, however, seven diseases showed a two-fold or greater increase, with a notable absolute increase per million arrivals for amebiasis (60.1; 95% confidence interval [CI], 41.5–78.7), malaria (21.7; 95% CI, 10.5–33.0), and typhoid fever (9.3; 95% CI, 1.9–16.8).

Conclusion: The epidemiology of imported infectious diseases changed during the pandemic. While the number of imported infectious disease cases decreased, the number of cases per arrivals increased considerably both in relative and absolute terms for several diseases of public health and clinical importance.

Background: Whether smoking is associated with worse quality of life (QoL) or not is relatively controversial. Current study is to investigate relationship between smoking and subjective QoL in a long cohort study.

Methods: NIPPON DATA 90 project collected 8383 community residents in 300 randomly selected areas as baseline data in 1990, and 4 follow-up QOL surveys and mortality statistics were performed. We conducted multinomial logistic regression analysis to compare past smoker and current smoker to never smoker, of which impaired QOL and mortality as outcomes.

Results: In 4 follow-ups, QOL data was collected from 2035, 2252, 2522 and 3280 participants, in 1995, 2000, 2005, 2012, respectively. In 1995 follow-up, current smoking at baseline was not associated with worse QOL. In 2000 and 2005 follow-up, smoking is significantly associated with worse QOL, OR = 2.11[95%CI: 1.33, 3.36, P<0.01], OR = 2.29[95%CI:1.38, 3.80, P < 0.001], respectively. In 2012 follow-up, smoking is not associated with QOL. Sensitivity analysis didn’t change the result significantly.

Conclusions: In this study we found that baseline smoking is associated worse QOL in long-follow-up.

Background: We evaluated the effectiveness of the BNT162b2 vaccine against infection, symptomatic infection, and hospitalization in older people during the Delta-predominant period (July 1 to September 30, 2021).

Methods: We performed a population-based cohort study in an older adult population aged ≥65 years using data from the Vaccine Effectiveness, Networking, and Universal Safety Study conducted from January 1, 2019, to September 30, 2021, in Japan. We matched BNT162b2 vaccinated and unvaccinated individuals in a 1:1 ratio on the date of vaccination of the vaccinated individual. We evaluated the effectiveness of the vaccine against infection, symptomatic infection, and COVID-19-related hospitalization by comparing the vaccinated and unvaccinated groups. We estimated the risk ratio and risk difference using the Kaplan–Meier method with inverse probability weighting. The vaccine effectiveness was calculated as (1 − risk ratio) × 100%.

Results: The study included 203,574 matched pairs aged ≥65 years. At 7 days after the second dose, the vaccine effectiveness (95% confidence interval) of BNT162b2 against infection, symptomatic infection, and hospitalization was 78.1% (65.2 to 87.8%), 79.1% (64.6 to 88.9%), and 93.5% (83.7 to 100%), respectively.

Conclusions: BNT162b2 was highly effective against infection, symptomatic infection, and hospitalization in Japan's older adult population aged ≥65 years during the Delta-predominant period.

Background: Per the biopsychosocial model, pain, especially chronic low back pain, which often presents with nonspecific pain, requires a comprehensive approach involving social factors. However, the association of social factors, including social isolation and loneliness, with this condition remains unclear. This study examined the cross-sectional association of social isolation and loneliness with chronic low back pain among older adults.

Methods: We recruited functionally independent older adults through a mail survey in 2019 from the Japan Gerontological Evaluation Study (JAGES). Chronic low back pain was defined as low back pain lasting more than three months. Social isolation was identified based on face-to-face and non-face-to-face interactions (“not isolated,” “isolated tendency,” and “isolated”). Loneliness was assessed using the UCLA Loneliness Scale (“not lonely,” “lonely tendency,” and “lonely”).

Results: Consequently, 21,463 participants were analyzed (mean age: 74.4 years; 51.5% females); 12.6% reported chronic low back pain. Multivariable Poisson regression analysis revealed that loneliness was significantly associated with the likelihood of chronic low back pain; compared with “not lonely”, the prevalence ratio (PR) was 1.14 (95% confidence interval [CI]: 1.05–1.25) for “lonely tendency” and 1.40 (1.27–1.54) for “lonely.” Social isolation was not associated; compared with “not isolated,” the PR (95% CI) was 0.96 (0.88–1.05) for “isolated tendency” and 0.99 (0.89–1.10) for “isolated.” A positive multiplicative interaction between social isolation and loneliness for chronic low back pain was found.

Conclusions: Lonelier individuals were more likely to experience chronic low back pain, and those with loneliness and social isolation were synergistically more likely for this condition.

Background: The association between the frequency of going outdoors and the risk of poor oral health has been reported in several studies; however, the findings have been inconclusive.

Methods: We conducted a 3-year longitudinal study of 19,972 Japanese adults aged ≥65 years who reported no poor oral condition at baseline in 2013. The respondents rated their frequency of going outdoors in three categories (≤1, 2–3, or ≥4 times/week), and the oral conditions reported in 2016 included tooth loss, chewing difficulty, swallowing difficulty, dry mouth, and composite outcomes. The associations between the frequency of going outdoors and the risk of poor oral health were examined as relative risk ratios (RRs) and 95% confidence intervals (CIs) using multivariable Poisson regression, while mediation analysis was performed to investigate indirect effects.

Results: During the follow-up, 32.5% of participants developed poor oral health. In the mediation analysis, indirect effects were observed through low instrumental activities of daily living, depressive symptoms, little social network diversity, and underweight. Compared to going outdoors ≥4 times/week, the multivariable RRs of composite poor oral health conditions were 1.12 (95% CI, 1.05–1.20) for 2–3 times/week and 1.22 (95% CI, 1.07–1.39) for ≤1 time/week (P-trend < 0.001). Similar associations were observed for tooth loss, chewing difficulty, and swallowing difficulty; the corresponding RRs were 1.07 (95% CI, 0.97–1.19) and 1.36 (95% CI, 1.13–1.64) (P-trend = 0.002), 1.18 (95% CI, 1.06–1.32) and 1.30 (95% CI, 1.05–1.60) (P-trend < 0.001), and 1.15 (95% CI, 1.01–1.31) and 1.38 (95% CI, 1.08–1.77) (P-trend = 0.002), respectively.

Conclusion: The frequency of going outdoors was inversely associated with the risk of poor oral health through several modifiable risk factors in the older population.

Background: Many epidemiological studies have investigated dietary intake of antioxidant vitamins in relation to prostate cancer risk in Western countries, but the results are inconsistent. However, few studies have reported this relationship in Asian countries.

Methods: We investigated the association between intake of vitamins, including lycopene, α-carotene, β-carotene, vitamin C, vitamin E, with prostate cancer risk in the Japan Public Health Center-based Prospective (JPHC) study. 40,720 men without history of cancer finished the food frequency questionnaire (FFQ) and were included in the study. Hazard ratios (HRs) and 95% confidence intervals (CIs) of prostate cancer risk were calculated according to the quintiles of energy-adjusted intake of vitamins using Cox models.

Results: After an average of 15.2 years (617,599 person-years in total) of follow-up, 1,386 cases of prostate cancer were identified, including 944 localized cases and 340 advanced cases. No associations were observed in consumption of antioxidant vitamins, including α-carotene, β-carotene, vitamin C, and vitamin E, and prostate cancer risk. Although higher lycopene intake was associated with increased risk of prostate cancer (highest vs lowest quintile, HR 1.24; 95% CI, 1.04–1.47; P for trend = 0.01), there was a null association of lycopene intake with risk of prostate cancer detected by subjective symptoms (HR 1.12; 95% CI, 0.79–1.58; P for trend = 0.11).

Conclusion: Our study suggested no association between antioxidant intake of vitamins and prostate cancer risk.

Background: Acute pulmonary embolism (PE) is a life-threatening in-hospital complication. Recently, several studies have reported the clinical characteristics of PE among Japanese patients using the diagnostic procedure combination (DPC)/per diem payment system database. However, the validity of PE identification algorithms for Japanese administrative data is not yet clear. The purpose of this study was to evaluate the validity of using DPC data to identify acute PE inpatients.

Methods: The reference standard was symptomatic/asymptomatic PE patients included in the COntemporary ManageMent AND outcomes in patients with Venous ThromboEmbolism (COMMAND VTE) registry, which is a cohort study of acute symptomatic venous thromboembolism (VTE) patients in Japan. The validation cohort included all patients discharged from the six hospitals included in both the registry and DPC database. The identification algorithms comprised diagnosis, anticoagulation therapy, thrombolysis therapy, and inferior vena cava filter placement. Each algorithm’s sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were estimated.

Results: A total of 43.4% of the validation cohort was female, with a mean age of 67.3 years. The diagnosis-based algorithm showed a sensitivity of 90.2% (222/246; 95% confidence interval [CI], 85.8–93.6%), a specificity of 99.8% (228,485/229,027; 95% CI, 99.7–99.8%), a PPV of 29.1% (222/764; 95% CI, 25.9–32.4%) and an NPV of 99.9% (228,485/229,509; 95% CI, 99.9–99.9%) for identifying symptomatic/asymptomatic PE. Additionally, 94.6% (159/168; 95% CI, 90.1–97.5%) of symptomatic PE patients were identified using the diagnosis-based algorithm.

Conclusion: The diagnosis-based algorithm may be a relatively sensitive method for identifying acute PE inpatients in the Japanese DPC database.

Background: Disaster survivors experience deterioration in lifestyles and an increase in constipation. After the Great East Japan Earthquake in 2011, some survivors were evacuated for a long term, even after moving to temporary housing and public reconstruction housing. However, annual changes in constipation and the association between lifestyles and constipation among the survivors are still unknown.

Methods: Overall, 9,234 survivors aged 18 years or older participated in this 9-year follow-up survey after the disaster. Information about the prevalence of constipation and lifestyle factors (diet, physical activity, and mental health) was collected using a self-reported questionnaire. Their dietary intake was categorized into the following two dietary patterns: prudent (fish and shellfish, soybean products, vegetables, fruits, and dairy products) and meat (meat and eggs). Odds ratios for constipation according to lifestyle factors were calculated using a generalized linear mixed model.

Results: In women, the prevalence of constipation was the highest at baseline (8.7%) and remained around 5% afterward. In both men and women, older age, poor mental health, and poor physical activity were significantly associated with higher odds ratios of constipation. Moreover, a lower frequency of meals and a lower prudent dietary score were significantly associated with women’s constipation.

Conclusion: The prevalence of constipation was the highest at baseline and remained around 5% in women. Lifestyle factors, such as poor mental health, physical inactivity, and low frequency of meals were associated with constipation. Our findings suggest continuous support for the survivors with constipation for medium- to long-term after disasters.

Background: Ambient particulate matter is classified as a human Class 1 carcinogen, and recent studies found a positive relationship between fine particulate matter (PM_2.5) and liver cancer. Nevertheless, little is known about which specific metal constituent contributes to the development of liver cancer.

Objective: To evaluate the association of long-term exposure to metal constituents in PM_2.5 with the risk of liver cancer using a Taiwanese cohort study.

Methods: A total of 13,511 Taiwanese participants were recruited from the REVEAL-HBV in 1991–1992. Participants’ long-term exposure to eight metal constituents (Ba, Cu, Mn, Sb, Zn, Pb, Ni, and Cd) in PM_2.5 was based on ambient measurement in 2002–2006 followed by a land-use regression model for spatial interpolation. We ascertained newly developed liver cancer (ie, hepatocellular carcinoma [HCC]) through data linkage with the Taiwan Cancer Registry and national health death certification in 1991–2014. A Cox proportional hazards model was utilized to assess the association between exposure to PM_2.5 metal component and HCC.

Results: We identified 322 newly developed HCC with a median follow-up of 23.1 years. Long-term exposure to PM_2.5 Cu was positively associated with a risk of liver cancer. The adjusted hazard ratio (HR) was 1.13 (95% confidence interval [CI], 1.02–1.25; P = 0.023) with one unit increment on Cu normalized by PM_2.5 mass concentration in the logarithmic scale. The PM_2.5 Cu-HCC association remained statistically significant with adjustment for co-exposures to other metal constituents in PM_2.5.

Conclusion: Our findings suggest PM_2.5 containing Cu may attribute to the association of PM_2.5 exposure with liver cancer.

Background: The present genome-wide association study (GWAS) aimed to reveal the genetic loci associated with folate metabolites as well as to detect related gene-environment interactions in Japanese.

Methods: We conducted the GWAS of plasma homocysteine (Hcy), folic acid (FA), and vitamin B₁₂ (VB₁₂) levels in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study participants who joined from 2005 to 2012, and also estimated gene-environment interactions. In the replication phase, we used data from the Yakumo Study conducted in 2009. In the discovery phase, data of 2,263 participants from four independent study sites of the J-MICC Study were analyzed. In the replication phase, data of 573 participants from the Yakumo Study were analyzed.

Results: For Hcy, MTHFR locus on chr 1, NOX4 on chr 11, CHMP1A on chr 16, and DPEP1 on chr 16 reached genome-wide significance (P < 5×10^-8). MTHFR also associated with FA, and FUT2 on chr 19 associated with VB₁₂. We investigated gene-environment interactions in both studies and found significant interactions between MTHFR C677T and ever drinking, current drinking, and physical activity > 33% on Hcy (β = 0.039, 0.038 and -0.054, P = 0.018, 0.021 and < 0.001, respectively) and the interaction of MTHFR C677T with ever drinking on FA (β = 0.033, P = 0.048).

Conclusions: The present GWAS revealed the folate metabolism-associated genetic loci and gene-environment interactions with drinking and physical activity in Japanese, suggesting the possibility of future personalized CVD prevention.

In an aging society, it is important to visualize the conditions of people living with diseases or disabilities, such as frailty and sarcopenia, and determine the environmental and genetic factors underlying such conditions. Atherosclerosis and arterial stiffness are key conditions between these factors and noncommunicable diseases. In 2014, we launched a population-based prospective open-cohort study, the Nagasaki Islands Study (NaIS), which was conducted in Goto City, located in the remote islands of Nagasaki Prefecture, Japan, mostly involving middle-aged and older residents. We conducted our own health checkups along with the annual standardized checkups organized by the municipality; recruited study participants; and started to follow-up with them for vital status (death), migration, and occurrence of diseases such as myocardial infarction, stroke, fracture, and human T-cell leukemia virus type 1 (HTLV-1) -associated uveitis. Our checkups were conducted as baseline surveys in different areas of Goto City during the fiscal years 2014–2016, secondary surveys during 2017–2019, and tertiary surveys since 2021, consisting of medical interviews, physical examinations, blood and urine tests, body composition measurements, osteoporosis screening, arterial stiffness measurements, carotid ultrasonography, and dental examination. A total of 4,957 residents participated in either the baseline or secondary surveys and were followed-up; and 3,594 and 3,364 residents (aged 27–96 and 28–98 years) participated in the baseline and secondary surveys, respectively. In conclusion, the NaIS has been undertaken to reveal the influence of aging and risk factors of noncommunicable diseases and disabilities, with an aim to contribute towards better healthcare in the future.

Background: Administering premixed drugs in commodity packets was first reported in Asia in 2015, but there continues to be a dearth of related population-based data. This study aimed at examining (1) the prevalence of drug packet use in the population and (2) the sociodemographic profiles, particularly gender distribution, of drug packet users.

Methods: Data were derived from a survey of 18,626 Taiwanese civilians, aged 12-64 years, using stratified, multi-stage, random sampling in 2018. Participants anonymously completed a computer-assisted self-interview on tablet computers which covered the use and problematic use of illicit drugs/inhalants, prescription drugs and other psychoactive substances, among others.

Results: Approximately 1.46% of respondents had a lifetime use of illicit drugs, with drugs in commodity packets (0.18%) being ranked the fifth-most commonly used illicit drugs, higher than nitrous oxide (0.14%) and heroin (0.09%). Ten formats of drug packets were endorsed by users. Approximately 81.6% of persons with drug packet use had a lifetime use of other illicit drugs. The correlates of the use of drugs in commodity packets were similar to those of the exclusive use of other drugs except that there was a lack of gender differences in the use of drugs in commodity packets but not in the exclusive use of other drugs.

Conclusion: Drugs in commodity packets have become a common way of administering illicit drugs in the population in Taiwan, and there were no gender differences among users. Our findings have implications for more efficient drug testing and culturally appropriate intervention for drug packet use.

Background: Associations of major risk factors for stroke with total and each type of stroke as well as subtypes of ischemic stroke and their population attributable fractions had not been examined comprehensively.

Methods: Participants of the Japan Public Health Center-based prospective (JPHC) Study Cohort II without histories of cardiovascular disease and cancer (n=14,797) were followed from 1993 through 2012. Associations of current smoking, hypertension, diabetes, overweight (body mass index ≥ 25 kg/m²), non-high-density lipoprotein cholesterol (non-HDLC) categories, low HDLC (< 40 mg/dL), urine protein, and history of arrhythmia were examined in a mutually-adjusted Cox regression model that included age and sex. Population attributable fraction (PAF) was estimated using the hazard ratios and the prevalence of risk factors among cases.

Results: Subjects with hypertension were 1.63 to 1.84 times more likely to develop any type of stroke. Diabetes, low HDLC, current smoking, overweight, urine protein, and arrhythmia were associated with risk of overall and ischemic stroke. Hypertension and urine protein were associated with risk of intracerebral hemorrhage while current smoking, hypertension, and low non-HDLC were associated with subarachnoid hemorrhage. Hypertension alone accounted for more than a quarter of stroke incidence, followed by current smoking and diabetes. High non-HDLC, current smoking, low HDLC, and overweight contributed mostly to large-artery occlusive stroke. Arrhythmia explained 13.2% of embolic stroke. Combined PAFs of all the modifiable risk factors for total, ischemic and large-artery occlusive strokes were 36.7 and 44.5% and 61.5%, respectively.

Conclusion: Although there are differences according to the subtypes, hypertension could be regarded as the most crucial target for preventing strokes in Japan.

Background: We aimed to clarify whether differences in food group intake according to household income have changed over the last decade in Japanese people aged 20 years or older.

Methods: This cross-sectional study was based on the 2010, 2014, and 2018 National Health and Nutrition Surveys in Japan. Food intake was assessed using a 1-day semi-weighed household dietary record. The participants were categorized into three groups based on their income. The mean of each food intake according to the income group was estimated by adjusting for age, occupation, and number of participants from the same household. The significance of the interaction terms between income and survey year was evaluated to assess the change in income-related differences in food intake over time.

Results: Cereal intake was lower in the middle- and the highest-income groups than in the lowest-income group, regardless of sex, and the interaction between income and year was nonsignificant for cereal intake. In the former two surveys, vegetable intake was higher among the highest-income women, while in the 2018 survey, the vegetable intake decreased in the women in the middle- and the highest-income groups. The interaction between income and year was significant for vegetable intake among the women. For other foods, the differences in intake among the income groups did not significantly change over time.

Conclusion: The tendency for lower cereal intake in the higher-income groups was consistent over time in both the sexes, and the tendency for higher vegetable intake in the highest income women disappeared over time.

Background: While tall stature has been linked to an increase in the risk of colorectal cancer (CRC), its association with cancer in the colorectum and its subsites remains unclear among Asians.

Methods: We conducted a pooled analysis of 10 population-based cohort studies among adults in Japan. Each study estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC incidence associated with adult height were estimated using Cox proportional hazards regression with adjustment of the same set of covariates were then pooled to estimate summary HRs incidence using random-effect models.

Results: We identified 9,470 CRC incidences among 390,063 participants during 5,672,930 person-years of follow-up. Men and women with tall stature had a higher risk of CRC and colon cancer. HRs for CRC, colon cancer, and distal colon cancer for the highest versus lowest height categories were 1.23 (95% CI, 1.07–1.40), 1.22 (95% CI, 1.09–1.36), and 1.27 (95% CI, 1.08–1.49), respectively, in men and 1.21 (95% CI, 1.09–1.35), 1.23 (95% CI, 1.08–1.40), and 1.35 (95% CI, 1.003–1.81), respectively, in women. The association with proximal colon cancer and rectal cancer was less evident in both sexes.

Conclusion: This pooled analysis confirms the link between tall stature and a higher risk of CRC and colon cancer (especially distal colon) among the Japanese and adds evidence to support the use of adult height to identify those at a higher risk of CRC.

Introduction: The burden of epilepsy is thought to be high but is difficult to measure. Very few studies in Japan have attempted to estimate prevalence and incidence rates of epilepsy in Japan.

Methods: This retrospective cohort study used commercially collected nationwide insurance claims data from a cohort of 10 million persons between 2012 and 2019 among those aged 0 to 74 years. Using the claims data, cases were identified, and incidence and prevalence rates were estimated.

Results: A total of 9,864,278 persons were included. The average age was 34.5 (standard deviation, 18.5) years. A total of 77,312 persons were diagnosed with epilepsy over the 8-year observation period, with a prevalence rate of 6.0 per 1,000 persons with almost no difference by gender. The highest rates were seen among those aged 70–74 years; prevalence rates tended to rise with calendar year (5.4/1,000 in 2012 and 6.0/1,000 in 2019). The incidence rate of epilepsy was 72.1 per 100,000 person-years with slightly higher rates seen among females. Incidence rates were highest at ages less than 12 months (199.8/100,000 person-years), followed by the eldest age group (70–74 years, 179.4/100,000 person-years).

Conclusion: Understanding the magnitude of disease burden is the basis of determining health policies. In this study, the prevalence and incidence of epilepsy in Japan was shown based on the analysis results of a large-scale general population insurance claims data covering all over Japan.

Background: This study aimed to examine the association between risk of brain tumors and radiofrequency (RF) exposure from mobile phones among young people in Korea and Japan.

Methods: This case-control study of brain tumors in young people was conducted in Korea and Japan under the framework of the international MOBI-Kids study. We included 118 patients diagnosed with brain tumors between 2011 and 2015 and 236 matched appendicitis controls aged 10–24 years. Information on mobile phone use was collected through face-to-face interviews. A detailed RF exposure algorithm, based on the MOBI-Kids algorithm and modified to account for the specificities of Japanese and Korean phones and networks, was used to calculate the odds ratios (ORs) for total cumulative specific energy using conditional logistic regression.

Results: The adjusted ORs in the highest tertile of cumulative call time at 1 year before the reference date were 1.61 (95% confidence interval [CI], 0.72-3.60) for all brain tumors and 0.70 (95% CI, 0.16-3.03) for gliomas, with no indication of a trend with exposure. The ORs for glioma specifically, were below 1 in the lowest exposure category.

Conclusions: This study provided no evidence of a causal association between mobile phone use and risk of brain tumors as a whole or glioma specifically. Further research will be required to evaluate the impact of newer technologies of communication in the future.

Background: Despite the widespread practice of Japanese traditional Kampo medicine, the characteristics of patients receiving various Kampo formulations have not been documented in detail. We applied a machine learning model to a health insurance claims database to identify the factors associated with the use of Kampo formulations.

Methods: A 10% sample of enrollees of the JMDC Claims Database in 2018 and 2019 was used to create the training and testing sets, respectively. Logistic regression analyses with lasso regularization were performed in the training set to construct models with prescriptions of 10 commonly used Kampo formulations in 1 year as the dependent variable and data of the preceding year as independent variables. Models were applied to the testing set to calculate the C-statistics. Additionally, the performance of simplified scores using 10 or 5 variables were evaluated.

Results: There were 338,924 and 399,174 enrollees in the training and testing sets, respectively. The commonly prescribed Kampo formulations included kakkonto, bakumondoto, and shoseityuto. Based on the lasso models, the C-statistics ranged from 0.643 (maoto) to 0.888 (tokishakuyakusan). The models identified both the common determinants of different Kampo formulations and the specific characteristics associated with particular Kampo formulations. The simplified scores were slightly inferior to full models.

Conclusion: Lasso regression models showed good performance for explaining various Kampo prescriptions from claims data. The models identified the characteristics associated with Kampo formulation use.

Background: Although many observational studies have demonstrated significant relationships between obesity and cardiometabolic traits, the causality of these relationships in East Asians remains to be elucidated.

Methods: We conducted individual-level Mendelian randomization (MR) analyses targeting 14,083 participants in the Japan Multi-Institutional Collaborative Cohort Study and two-sample MR analyses using summary statistics based on genome-wide association study data from 173,430 Japanese. Using 83 body mass index (BMI)-related loci, genetic risk scores (GRS) for BMI were calculated, and the effects of BMI on cardiometabolic traits were examined for individual-level MR analyses using the two-stage least squares estimator method. The β-coefficients and standard errors for the per-allele association of each single-nucleotide polymorphism as well as all outcomes, or odds ratios with 95% confidence intervals were calculated in the two-sample MR analyses.

Results: In individual-level MR analyses, the GRS of BMI was not significantly associated with any cardiometabolic traits. In two-sample MR analyses, higher BMI was associated with increased risks of higher blood pressure, triglycerides, and uric acid, as well as lower high-density-lipoprotein cholesterol and eGFR. The associations of BMI with type 2 diabetes in two-sample MR analyses were inconsistent using different methods, including the directions.

Conclusion: The results of this study suggest that, even among the Japanese, an East Asian population with low levels of obesity, higher BMI could be causally associated with the development of a variety of cardiometabolic traits. Causality in those associations should be clarified in future studies with larger populations, especially those of BMI with type 2 diabetes.

Background: Psychological stress can cause various mental and physical health problems. The previous results on stress and oral health are inconsistent, possibly because of the narrow stress measurements. We aimed to examine the association between a broader range of stressful life events and oral health among workers.

Methods: This cross-sectional study analyzed anonymous individual data from a national survey in Japan. Data on stressful life events, oral health problems which are one or more of tooth pain, gum swelling/bleeding, and difficulty chewing, and covariates were obtained using a self-reported questionnaire. Covariates used included gender, age group, and disease under treatment. Logistic regression analysis was used to estimate the association between stressful life events and oral health problems. We then estimated the causal treatment effects of stress using the augmented inverse-probability weighting (AIPW) method.

Results: Among the 274,881 subjects, 152,850 men (55.6%) and 122,031 women (44.4%) with a mean age of 47.0 (standard deviation, 14.4) years, 4.0% reported oral health problems, with a prevalence of 2.1% among those without any stress. The prevalence increased with stress score, reaching 15.4% for those with the maximum stress score. The adjusted odds ratio of this group compared to those without any stress was 9.2 (95% confidence interval [CI], 8.2–10.3). The estimated prevalence of oral health problems by the AIPW analysis was 2.2% (95% CI, 2.1–2.3%) for those without any stress and 14.4% (95% CI, 12.1–16.7%) for those with the maximum stress scores.

Conclusion: There was a clear dose-response association between stressful life events and oral health problems.

Background: Diabetes and prediabetes have been linked with morbidity or mortality from cardiovascular disease, cancer, or other physical disorders among working-age populations, but less is known about outcomes directly related to labor loss (eg, long-term sickness absence [LTSA] or pre-retirement death due to physical disorders).

This prospective study aimed to examine the association of diabetes and prediabetes with the risk of a composite outcome of LTSA and pre-retirement death due to physical disorders. The present study also examined the associations of severe outcomes (LTSA or death) due to specific physical disorders or injuries/external causes in relation to diabetes and prediabetes.

Methods: Data were derived from the Japan Epidemiology Collaboration on Occupational Health study. A total of 60,519 workers from 12 companies were followed for 8 years. Diabetes and prediabetes were defined based on the American Diabetes Association criteria. A Cox proportional hazards regression model was used to examine the association between diabetes/prediabetes and severe outcomes due to physical disorders or injuries/external causes.

Results: The adjusted hazard ratios of severe outcomes due to all physical disorders were 1.22 (95% confidence interval [CI], 1.02–1.45) and 2.32 (95% CI, 2.04–2.64) for prediabetes and diabetes, respectively. In cause-specific analyses, an increased risk was observed for severe outcomes due to cancers, cardiovascular diseases, diseases of the musculoskeletal system, and injuries/external causes in relation to either or both diabetes and prediabetes.

Conclusion: Diabetes and prediabetes were associated with an increased risk of severe outcomes due to physical disorders or injuries/external causes among Japanese workers.

Background: The logistic regression analysis proposed by Schouten et al (Stat Med. 1993;12:1733–1745) has been a standard method in current statistical analysis of case-cohort studies, and it enables effective estimation of risk ratios from selected subsamples, with adjustment of potential confounding factors. Schouten et al (1993) also proposed the standard error estimate of the risk ratio estimator can be calculated using the robust variance estimator, and this method has been widely adopted.

Methods and Results: The robust variance estimator does not account for the duplications of case and subcohort samples and generally has certain bias (ie, inaccurate confidence intervals and P-values are possibly obtained). To address the invalid statistical inference problem, we provide an alternative bootstrap-based valid variance estimator. Through simulation studies, the bootstrap method consistently provided more precise confidence intervals compared with those provided using the robust variance method, while retaining adequate coverage probabilities.

Conclusion: The robust variance estimator has certain bias, and inadequate conclusions might be deduced from the resultant statistical analyses. The proposed bootstrap variance estimator can provide more accurate and precise interval estimates. The bootstrap method would be an alternative effective approach in practice to provide accurate evidence.

Background: The association between chronic lipopolysaccharide exposure and the development of metabolic syndrome (MetS) is unclear. In this study we examined the association between serum lipopolysaccharide-binding protein (LBP) levels, an indicator of lipopolysaccharide exposure, and the development of MetS in a general Japanese population.

Methods: 1,869 community-dwelling Japanese individuals aged ≥40 years without MetS at baseline examination in 2002–2003 were followed up by repeated examination in 2007–2008. MetS was defined according to the Japanese criteria. Serum LBP levels were classified into quartiles (quartiles 1–4: 2.20–9.56, 9.57–10.78, 10.79–12.18, and 12.19–24.34 µg/mL, respectively). Odds ratios (ORs) for developing MetS were calculated using a logistic regression model.

Results: At the follow-up survey, 159 participants had developed MetS. Higher serum LBP levels were associated with greater risk of developing MetS after multivariable adjustment for age, sex, smoking, drinking, and exercise habits (OR [95% confidence interval] for quartiles 1–4: 1.00 [reference], 2.92 [1.59–5.37], 3.48 [1.91–6.35], and 3.86 [2.12–7.03], respectively; P for trend <0.001). After additional adjustment for homeostasis model assessment of insulin resistance, this association was attenuated but remained significant (P for trend = 0.007). On the other hand, no significant association was observed after additional adjustment for serum high-sensitivity C-reactive protein (P for trend = 0.07).

Conclusion: In the general Japanese population, our findings suggest that higher serum LBP levels are associated with elevated risk of developing MetS. Low-grade endotoxemia could play a role in the development of MetS through systemic chronic inflammation and insulin resistance.

Purpose: Although examining the dose-response curves of physical activity (PA) and sitting time with health-related outcomes is an important research agenda, the results for older Japanese adults are extremely limited. We examined the dose-response associations of PA and sitting time with all-cause mortality among older Japanese.

Methods: Initially, 8,069 non-disabled residents (4,073 men; 3,996 women) aged 65–84 years of Ota City, Japan, were analyzed. Moderate-to-vigorous PA (MVPA) and sitting time were evaluated using the International Physical Activity Questionnaire-Short Form. Multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of MVPA and sitting time for all-cause mortality were calculated, and the dose-response curves were examined using restricted cubic splines (RCS).

Results: During 4.1 years of follow-up, 458 participants (5.7%; 331 men and 127 women) died. Compared with the low MVPA (<600 metabolic equivalents [METs]·minutes/week) group, HR for mortality gradually reduced in moderate (600–3,000 METs·minutes/week) and high (>3,000 METs·minutes/week) MVPA groups (moderate: HR 0.66; 95% CI, 0.54–0.82; high: HR 0.58; 95% CI, 0.45–0.75; P < 0.001 for trend). RCS showed that the HR for mortality reduced linearly up to approximately 2,000 METs·minutes/week of MVPA, and maximal risk reduction was seen at approximately 3,000–4,500 METs·minutes/week of MVPA. No significant dose-response association of sitting time with mortality was observed.

Conclusion: Higher MVPA levels reduced all-cause mortality risk, in a significant inverse non-linear dose-response manner. Sitting time was not significantly associated with all-cause mortality. It is important to disseminate the significance of even a slight increase in the MVPA for reducing mortality risk.

Background: The neurological prognosis of asphyxia is poor and the effect of advanced airway management (AAM) in the prehospital setting remains unclear. This study aimed to evaluate the association between AAM with adrenaline injection and prognosis in adult patients with asystole asphyxia out-of-hospital cardiac arrest (OHCA).

Methods: This study assessed all-Japan Utstein cohort registry data between January 1, 2013 and December 31, 2019. We used propensity score matching analyses before logistic regression analysis to evaluate the effect of AAM on favorable neurological outcome.

Results: There were 879,057 OHCA cases, including 70,299 cases of asphyxia OHCAs. We extracted the data of 13,642 cases provided with adrenaline injection by emergency medical service. We divided 7,945 asphyxia OHCA cases in asystole into 5,592 and 2,353 with and without AAM, respectively. After 1:1 propensity score matching, 2,338 asphyxia OHCA cases with AAM were matched with 2,338 cases without AAM. Favorable neurological outcome was not significantly different between the AAM and no AAM groups (adjusted odds ratio [OR] 1.1; 95% confidence interval [CI], 0.5–2.5). However, the return of spontaneous circulation (ROSC) (adjusted OR 1.7; 95% CI, 1.5–1.9) and 1-month survival (adjusted OR 1.5; 95% CI, 1.1–1.9) were improved in the AAM group.

Conclusion: AAM with adrenaline injection for patients with asphyxia OHCA in asystole was associated with improved ROSC and 1-month survival rate but showed no differences in neurologically favorable outcome. Further prospective studies may comprehensively evaluate the effect of AAM for patients with asphyxia.

Background: We sought to establish a prospective hospital-based cohort, featuring detailed multidimensional data of trauma patients with active follow-ups, which can be a reliable data source for all studies focusing on the effects or underlying mechanistic pathways of environmental and biological factors on multiple interested trauma-related outcomes, particularly the incidence and trajectory of trauma-related psychopathology, in a Chinese population.

Methods: The China Severe Trauma Cohort (CSTC) enrolled all traumatized individuals aged 12 to 80 years admitted to the Trauma Center of West China Hospital between March 1^st, 2020 and July 8^th, 2022. The bio-sample and detailed questionnaire data were collected at recruitment, and phone/internet follow-ups were scheduled at 1, 3, 6, and 12 months after the baseline. Long-term health outcomes are planned to be obtained from administrative databases through data linkage.

Results: A total of 2,500 trauma patients were enrolled (response rate = 87.1%) with an average age of 46.01 years, and most of the participants were males (62.6%). The proportions of participants with blood and fecal sample collected at baseline were 93.8% and 66.3%, respectively. As of August 31^st, 2022, the follow-up rate was 90.0%, 77.0%, 76.5%, and 89.0% for 1-, 3-, 6-, and 12-month follow-ups, respectively. Fall/wrench (47.6%) and traffic accident (26.2%) were the top causes of current trauma. The most common psychopathology at recruitment was sleep disturbance (39.4%), followed by depression (22.6%), anxiety (18.2%), and acute stress reaction (7.8%), all of which showed recovering trajectories during the follow-up period, particularly the first 3 months after baseline.

Conclusion: CSTC provides a platform with multidimensional data to study both short-term and long-term trauma-related health consequences, prompting early identification and intervention for individuals with high risk of health decline after trauma exposures.