Background: The mechanistic associations between obesity and risk of colorectal cancer (CRC) remain unclear. Here, using body mass index (BMI) as an obesity indicator, we decomposed the total effects of obesity on the risk of CRC into: (1) direct effects, which are possibly mediated by unmeasured or currently unknown factors; (2) indirect effects mediated by circulating leptin and adiponectin; and (3) indirect effects that are not mediated by circulating leptin and adiponectin but by hyperinsulinemia and chronic inflammation (assessed via circulating connecting peptide and C-reactive protein, respectively).

Methods: We adopted a causal mediation framework, using data from a large prospective cohort study of 44,271 Japanese men.

Results: BMI was not associated with the risk of CRC due to direct and indirect effects that were not mediated by circulating leptin and adiponectin. By contrast, individuals with BMIs of 25.0–27.4 kg/m² (risk ratio 1.29; 95% confidence interval, 0.98–1.69) and ≥27.5 kg/m² (risk ratio 1.28; 95% confidence interval, 0.98–1.68) had a higher risk of CRC due to indirect effects of circulating leptin and adiponectin.

Conclusion: Our mediation analyses suggest that the association between BMI and CRC risk may be largely mediated by a pathway involving circulating leptin and adiponectin.

Background: Genetic epidemiological evidence for the kidney function traits in East Asian populations, including Japanese, remain still relatively unclarified. Especially, the number of genome-wide association studies (GWASs) for kidney traits reported still remains limited, and the sample size of each independent study is relatively small. Given the genetic variability between ancestries/ethnicities, implementation of GWAS with sufficiently large sample sizes in specific population of Japanese is considered meaningful.

Methods: We conducted the GWAS meta-analyses of kidney traits by leveraging the GWAS summary data of the representative large genome cohort studies with about 200,000 Japanese participants (n = 202,406 for estimated glomerular filtration rate [eGFR] and n = 200,845 for serum creatinine [SCr]).

Results: In the present GWAS meta-analysis, we identified 110 loci with 169 variants significantly associated with eGFR (on chromosomes 1–13 and 15–22; P < 5 × 10⁻⁸), whereas we also identified 112 loci with 176 variants significantly associated with SCr (on chromosomes 1–22; P < 5 × 10⁻⁸), of which one locus (more than 1 Mb distant from known loci) with one variant (CD36 rs146148222 on chromosome 7) for SCr was considered as the truly novel finding.

Conclusion: The present GWAS meta-analysis of the largest genome cohort studies in Japanese subjects provided some original genomic loci associated with kidney function, which may contribute to the possible development of personalized prevention of kidney diseases based on genomic information in the near future.

Background: There has been growing concern about the negative mental health impact of long working hours and overwork. Our study examined how work-life imbalance (WLI) could be a mediator between working hours and poor mental well-being.

Methods: We included 34,968 individuals from a nationwide cross-sectional survey in Korea. Self-reported working hours per week were collected, and mental health was assessed using the World Health Organization (WHO)-5 Well-Being Index. Counterfactual-based mediation models were employed to disentangle the total effects into a direct effect (work hour – poor mental health) and an indirect effect (work hour – WLI – poor mental health).

Results: Out of 34,968 participants, 52.6% worked 35–40 hours/week, 20.0% worked 41–48 hours/week, 11.7% worked 49–54 hours/week, and 15.6% worked ≥55 hours/week. The odds ratios (ORs) of the total impact of working hours on poor mental health were 1.08 (95% confidence interval [CI], 1.01–1.16) for 41–48 hours/week, 1.28 (95% CI, 1.17–1.39) for 49–54 hours/week, and 1.60 (95% CI, 1.48–1.74) for ≥55 hours/week in comparison to 35–40 hours/week. The ORs of the indirect effects were 1.04 (95% CI, 1.03–1.05) for 41–48 hours/week, 1.08 (95% CI, 1.07–1.09) for 49–54 hours/week, and 1.14 (95% CI, 1.12–1.16) for ≥55 hours/week, accounting for 51%, 31%, and 28% of the total effects, respectively.

Conclusion: Our findings suggest that WLI can partially mediate the association of long working hours with mental health deterioration. Policy efforts are required to mitigate the adverse mental health effects of overwork.

Background: Behavioral and psychological symptoms of dementia (BPSD) are common among people with dementia from the early stages and can appear even in mild cognitive impairment (MCI). However, the prognostic impact of BPSD is unclear. This study examined the association between BPSD and mortality among people with cognitive impairment.

Methods: This longitudinal study involved 1,065 males and 1,681 females (mean age: 77.1 years for males and 78.6 years for females) with MCI or dementia diagnosis from the National Center for Geriatrics and Gerontology-Life Stories of People with Dementia (NCGG-STORIES), a single-center memory clinic-based cohort study in Japan that registered first-time outpatients from 2010–2018. Information about death was collected through a mail survey returned by participants or their close relatives, with an up to 8-year follow-up. BPSD was assessed using the Dementia Behavior Disturbance Scale (DBD) at baseline.

Results: During the follow-up period, 229 (28.1%) male and 254 (15.1%) female deaths occurred. Cox proportional hazards regression analysis showed that higher DBD scores were significantly associated with increased mortality risk among males, but not females (compared with the lowest quartile score group, hazard ratios for the highest quartile score group were 1.59; 95% confidence interval, [CI] 1.11–2.29 for males and 1.06; 95% CI, 0.66–1.70 for females). Among the DBD items, lack of interest in daily living, excessive daytime sleep, and refusal to receive care had a higher mortality risk.

Conclusion: The findings suggest a potential association between BPSD and poor prognosis among males with cognitive impairment.

Background: Informal caregiving of older parents adversely affects the mental health of family caregivers. However, the psychological effects of caregiving cessation and the trajectories of these effects have rarely been examined in Japan. This study addresses this gap.

Methods: Based on a 17-wave nationwide population-based survey in Japan, we analyzed longitudinal data from 8,280 individuals aged 50–59 years in 2005 who started caring for their older parents in 2006 or later and ceased caregiving by 2021. We identified the timings of caregiving onset and cessation and examined the trajectory of psychological distress (PD), defined as a Kessler score ≥ 5 on the 6-item Kessler scale (range 0–24). Linear mixed models were used to assess the trajectory of PD that evolved after caregiving cessation over the subsequent three years.

Results: After adjusting for covariates, the probability of PD decreased by 5.6 percentage points (from 40.8%; 95% confidence interval [CI], 4.1–7.0) for female caregivers and by 1.9 percentage points (from 31.7%; 95% CI, 0.3–3.5) for male caregivers at caregiving cessation, remaining stable in subsequent years. For women, higher PD risks related to co-residence with a care recipient diminished quickly upon cessation of caregiving, while the unfavorable impacts of no social activity, extended duration of care, and long-hour daily care persisted in subsequent years. For male caregivers, the impact was generally more limited.

Conclusions. These results suggest that changes in mental health following caregiving cessation warrant serious consideration when developing support programs for former family caregivers.

In epidemiological or clinical studies with follow-ups, data tables generated and processed for statistical analysis are often of the “wide-format” type—consisting of one row per individual. However, depending on the situation and purpose of the study, they may need to be transformed into the “long-format” type—which allows for multiple rows per individual. This tutorial clarifies the typical situations wherein researchers are recommended to split follow-up times to generate long-format data tables. In such applications, the major analytical aims consist of (i) estimating the outcome incidence rates or their ratios between ≥ 2 groups, according to specific follow-up time periods; (ii) examining the interaction between the exposure status and follow-up time to assess the proportional hazards assumption in Cox models; (iii) dealing with time-varying exposures for descriptive or predictive purposes; (iv) estimating the causal effects of time-varying exposures while adjusting for time-varying confounders that may be affected by past exposures; and (v) comparing different time periods within the same individual in self-controlled case series analyses. This tutorial also discusses how to split follow-up times according to their purposes in practical settings, providing example codes in Stata, R, and SAS.

Background: The burden of cancer in India has been rising, yet testing for early detection remains low. This study explored inequalities in the uptake of breast cancer (BC) examination and cervical cancer (CC) among Indian women, focusing on socioeconomic, regional, and educational differences.

Methods: Data from the 2019-21 National Family Health Survey (n=353,518) were used to assess the uptake of BC examination and CC testing. Inequalities were quantified using the slope index of inequality (SII), relative index of inequality (RII), and relative concentration index (RCI). SII measured absolute inequality, while RII and RCI assessed relative inequality between disadvantaged and advantaged groups.

Results: The ever uptake of tests for early detection of BC and CC were low at 9 and 20 per 1,000 women, respectively. Higher uptake was observed among women from the richest households compared to the poorest (SII: 1.1 for BC and 1.8 for CC). The magnitude of relative socioeconomic inequalities was more pronounced in rural areas (RCI: 22.5 for BC and 21.3 for CC) compared to urban areas. Similarly, higher-educated women were 4.84 times (RII: 4.84) and 2.12 times (RII: 2.12) more likely to undergo BC examination and CC testing, respectively, compared to non-educated women. The northeastern region exhibited greater socioeconomic inequality, while the western region showed more education-based inequality.

Conclusion: The lower uptake of BC examination and CC testing and the marked inequalities underscore the need for targeted interventions to improve access and utilization of testing services, especially among lower-educated women, and those in rural areas.

Background

Parents’ educational background is presumed to influence the incidence of vaccine-preventable diseases in children through their decisions about vaccinations and other family lifestyle choices. Regarding voluntary vaccination, a household’s economic situation may also be associated with non-vaccination. Therefore, this study investigated the association between parental education and vaccine-preventable diseases (varicella, mumps, influenza [flu], pertussis, measles, and rubella) in children, which currently remains elusive.

Methods

We used datasets from the Japan Environment and Children’s Study, which included 104,062 fetal records; our study population comprised 80,930 children up to the age of three years. The associations between parental educational background and children's infectious diseases were examined using binomial logistic regression analysis. The mediating effects of household income, vaccination, and smoking were examined using a path analysis.

Results

For varicella, mumps, and influenza covered by voluntary vaccination, a higher education level of the father was associated with a lower incidence of infection. The association between mothers’ education and children’s infection was limited. There were both income-mediated and non-income-mediated pathways between parental education and voluntary vaccination. For pertussis, measles, and rubella, which are covered by routine vaccines, there was no association between parental education and the child's infection.

Conclusion

An association between parental education and childhood infections was observed. Additionally, providing financial support for vaccination and communicating the benefits of vaccination in a way that parents at all levels of education can understand will help reduce the incidence of infectious diseases among children.

Background: Although both a lower and a higher body mass index (BMI) are reportedly associated with head and neck cancer (HNC), reports from Asia are scarce. Moreover, evidence regarding the association between height and HNC is limited.

Methods: We investigated associations between BMI, height, and the incidence of HNC among 102,668 participants (49,029 men and 53,639 women) aged 40-69 years in the Japan Public Health Center–based Prospective Study. We followed participants from 1990 to 2013. We conducted a Cox proportional hazards regression analysis, which included adjustment for potential confounders such as smoking status. Baseline weight and height information were self-reported.

Results: Over an average follow-up of 18.7 years, 311 HNC cases were newly diagnosed. Lower BMI was significantly associated with HNC, with hazard ratios [HR] of 2.75 (95% confidence interval [CI]: 1.63–4.64) for <18.5 kg/m² and 1.63 (95% CI=1.15–2.30) for 18.5–20.9 kg/m² compared to 23-24.9 kg/m². Increased risk was suggested for higher BMI, with an HR of 1.30 (95%CI=0.84-2.00) for ≥27.5 kg/m². This trend was also observed in quadratic models. Results were similar among never smokers. Meanwhile, only lower BMI showed a strong association with HNC risk among former and current smokers (HR: 3.09, 95%CI: 1.54-6.20 for <18.5 kg/m² compared to 23 to 24.9 kg/m²). Height showed no association with HNC.

Conclusions: Lower BMI was significantly associated with HNC risk, while increased HNC risk was suggested in higher BMI among never smokers. Among former and current smokers, only lower BMI was associated with HNC risk.

Background: The health statuses of closely connected individuals are interdependent. Little is known about mortality risk associated with partner’s cancer diagnosis and cause-specific mortality risk associated with partner’s death.

Methods: Relative risks for all-cause and cause-specific mortality following a partner’s cancer diagnosis or death compared to the period when the partner is cancer-free and alive were investigated in the population-based prospective cohort study that enrolled 140,420 people at the age between 40-69 in 1990-1994.

Results: 55,050 participants (27,665 men and 27,385 women) who were identified as married couples were followed-up for 1,073,746.1 (518,368.5 in men and 555,377.6 in women) person-years, during which 9,816 deaths (7,217 in men and 2,599 in women) were observed. After a partner’s cancer diagnosis, the mortality rate ratio (MRR) of all-cause mortality was not increased among both men and women, while an increase of externally-caused MRR was observed. The suicide MRR significantly increased among men (MRR = 2.90 [95% CI, 1.70–4.93]) and it persisted for more than 5 years. After a partner’s death, the MRRs of all-cause, cardiovascular disease (CVD), respiratory disease (RD), and externally-caused mortality significantly increased only among men. Stratified analysis by smoking status among men showed significantly increased MRRs of CVD and RD mortality among former/current smokers, but not among never-smokers.

Conclusion: Partner’s cancer diagnosis did not increase all-cause mortality risk, but increased externally-caused mortality risk, especially suicide among men. The impact of partner’s death on mortality risk differed by the mortality causes and sex, and smoking affected some of cause-specific mortality risk.

Background: Advancements in cancer care have improved survivorship, potentially leading to changes in mortality causes. This study aimed to investigate the causes of death among cancer survivors, specially focusing on non-cancer-related mortality.

Methods: This nationwide population-based cohort study analyzed the causes of death based on the time since cancer diagnosis using data from the National Cancer Registry in Japan between January 2016 and December 2019. Non-cancer-related deaths were identified, and mortality risks associated with non-cancer diseases were compared to those of the Japanese general population using standardized mortality ratios (SMRs) with 95% confidence intervals (CIs). Follow-up period was up to 4 years after cancer diagnosis.

Results: A total of 3,990,661 patients (45.8%, women) were included in the analysis, yielding 6,237,269 person-years of follow-up. Of these, 1,001,857 (25.1%) patients died during the study period. Cancer-related and non-cancer-related causes accounted for 86.6% and 13.4% of deaths, respectively. The proportion of non-cancer-related deaths increased from 10.2% at 6 months to 31.6% at 4 years after cancer diagnosis. Heart disease (21.8%), cerebrovascular disease (9.8%), and pneumonia (9.1%) were the leading cause of non-cancer-related deaths: The SMRs for these diseases were 2.69 (95% CI, 2.66–2.72), 2.07 (95% CI, 2.03–2.10), and 2.41 (95% CI, 2.36–2.45), respectively. The SMR for suicide was 1.81 (95% CI, 1.74–1.89); however, it lost significance in males and females 2 and 2.5 years after cancer diagnosis, respectively.

Conclusions: The proportion of non-cancer-related deaths among cancer patients has increased over time, emphasizing the need to manage cancer and its comorbidities carefully.

Background

Hepatitis C virus (HCV) infection is a systemic disease. However, the relative contribution of intrahepatic and extrahepatic diseases to mediating HCV-induced mortality is unclear, albeit critical in resource allocation for reducing preventable deaths. To this end, this study comprehensively quantified the extent to which intrahepatic and extrahepatic diseases mediate HCV-induced mortality.

Methods

A community-based cohort study with >25 years of follow-up was conducted in Taiwan. HCV infection was profiled by antibodies against HCV and HCV RNA in participants’ serum samples. The cohort data were linked to Taiwan’s National Health Insurance Research Database to determine the incidences of potential mediating diseases and mortality. We employed causal mediation analyses to estimate the mediation effects of HCV on mortality in relation to the incidences of 34 candidate diseases.

Results

In 18,972 participants with 934 HCV infection, we observed that 54.1% of HCV-induced mortality was mediated by intrahepatic diseases, such as liver cirrhosis and liver cancer, and 45.9% of mortality was mediated by extrahepatic diseases. The major extrahepatic mediating diseases included septicemia (estimated proportion of HCV-induced mortality mediated through the disease: 25.2%), renal disease (16.7%), blood/immune diseases (12.2%), gallbladder diseases (9.7%), and endocrine diseases (9.6%). In women, hypertension (20.0%), metabolic syndrome (18.9%), and type 2 diabetes (17.0%) also mediated HCV-induced mortality. A dose–response relationship of HCV viral load was further demonstrated for the mediation effect.

Conclusion

Both intrahepatic and extrahepatic manifestations mediated approximately a half of HCV-induced mortality. The mediation mechanisms are supported by a dose–response relationship of HCV viral load.

Background: To date simple assessment tool to evaluate early low nutrition risk in general older population has not been available. This study aimed to create such tool and examined its reliability and criterion-related validity.

Methods: 1,192 community elderly with a mean age of 74.7(5.8) years responded to a questionnaire consisting of 48 (Hatoyama) or 34 items (Kusatsu), which have been reported to be associated with nutritional state in older people. Item analysis was conducted on the 34 common items, and items were selected based on the following criteria: adequate pass rates and discriminative power, no gender and regional differences, and a certain level of commonality based on factor analysis. Next, the factor structure of the candidate items was examined through exploratory factor analysis, and confirmatory factor analysis was conducted as the final scale structure. Furthermore, Spearman’s partial rank correlation coefficients (sex- and age-adjusted) between the created index and important health indicators were examined to determine the criterion-related validity.

Results: Finally, we obtained a semantic coherence of 4 factors (named health beliefs, dietary status, physical activity, and food-related quality of life) totaling 13 items; confirmatory factor analysis of the 4-factor solution yielded good model fit values, χ² (59) =275.4 (p<0.001), CFI=0.930, and RMSEA=0.056. The factor loadings for each factor ranged from 0.43 to 0.82, indicating adequate loadings. The reliability of the index was shown to be high by Good-Poor analysis and Cronbach's α. The index showed statistically significant correlations with all health indicators.

Conclusions: We have developed a simple assessment tool to evaluate early low nutrition risk in general older population.

Background: The Tohoku Medical Megabank Project (TMM) was established to realize personalized healthcare and medicine using genomic and omics data. This study evaluated the validity and reproducibility of food group intakes derived from a self-administered food frequency questionnaire (TMM-FFQ) that included the response option “constitutionally unable to eat/drink it” among community-dwelling Japanese adults.

Methods: Participants comprised 89 men and 124 women aged ≥20 years from Miyagi Prefecture. Participants completed weighed food records (WFRs) for 3 consecutive days per season as reference intake and FFQs in 2019 (FFQ1) and 2021 (FFQ3). Spearman’s rank correlation coefficients (CCs) were calculated for correlations between food group intakes estimated from the 12-day WFR and FFQ3 (validity), and for correlations between those estimated from the FFQ1 and FFQ3 (reproducibility). Cross-classification according to quintiles using FFQ and WFR data was also performed.

Results: The percentage of participants who chose the “constitutionally unable to eat/drink it” option was non-negligible for some food groups. In the validity analysis, CCs were >0.40 for many food groups; the median across 21 food groups was 0.49 in men and 0.45 in women. The median percentages of cross-classification into exact plus adjacent quintiles were 73.0% in men and 66.9% in women. In the reproducibility analysis, CCs were >0.50 for many food groups; the median across 21 food groups was 0.60 in men and 0.51 in women.

Conclusions: The validity of the TMM-FFQ compared with 12-day WFR and the reproducibility of the TMM-FFQ were reasonable for food groups in the TMM cohort studies.

Background Seasonal variations could systematically bias dietary intakes. This systematic review aimed to determine seasonal variations in dietary intake among Japanese adults.

Methods PubMed and Ichushi-Web databases were searched for studies reporting seasonal intakes of nutrients or food groups assessed by dietary records or 24-hour recalls. The protocol was registered with PROSPERO (CRD42022356084).

Results Ten studies (eight studies on 1–31 nutrients and four on 2–15 food groups) met the inclusion criteria. Six studies included both sexes, whereas four investigated only females. The number of participants ranged from 25 to 459, and the number of dietary survey days in each season ranged from 1 to 14. For most nutrient and food groups, the reported seasonal variations were inconsistent across studies. The meta-analyses comparing differences in mean intakes between two seasons showed no significant differences in all comparisons or differences in only one comparison for most nutrients and food groups. Significant seasonal differences were observed for vegetables, fruits, and potatoes in five out of six comparisons, though the heterogeneity was high. Their biggest differences were as follows: 101 g/day more vegetable intake in summer than spring, 60 g/day more fruit intake in fall than spring, and 20.1 g/day more potato intake in fall than spring.

Conclusion Reported seasonal variations were inconsistent across studies for most food groups and nutrients. Relatively distinct seasonal differences in mean intakes were observed for vegetables, fruits, and potatoes in meta-analyses. However, these results must be interpreted cautiously because of the high heterogeneity and limited representativeness.

Background: In Japan, few studies have examined suicide risk for 5-year relative survival rates for cancer sites. Since 5-year relative survival rates differ by sex, we aim to examine suicide risk for patients with cancer separately for men and women.

Methods: We estimated the risk of suicide among patients with cancer by sex in Japan compared to the general population, using standardized mortality ratios (SMRs). Patients with cancer diagnosed between January 1, 1985–December 31, 2013 and registered in the Osaka Cancer Registry were followed for up to 10 years. The outcome was suicide death. In addition, cancer sites were classified into three prognosis groups based on 5-year relative survival rates: good (>70%), moderate (40–70%), poor (<40%).

Results: Among 623,995 patients with cancer observed for 2,349,432 person-years, 1,210 patients died by suicide (867 men and 343 women). The SMRs were almost equal for men (1.66; 95% confidence interval [CI], 1.55–1.77) and women (1.65; 95% CI, 1.48–1.83). SMRs for cancer prognosis groups were 1.01 (95% CI, 0.84–1.22) for men and 1.47 (95% CI, 1.24–1.73) for women in the good group, 1.53 (95% CI, 1.39–1.68) for men and 1.74 (95% CI, 1.47–2.05) for women in the moderate group, and 2.54 (95% CI, 2.27–2.85) for men and 1.87 (95% CI, 1.43–2.46) for women in the poor group.

Conclusion: In this population, both sexes had higher suicide risk with poor prognosis, but the difference in SMRs between the good and poor groups was smaller for women than men.

Background: In high-income countries, socioeconomically disadvantaged adolescents experience a higher risk of obesity, which may have been further exacerbated during the early phase of the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to investigate the association between obesity and familial financial insecurity, utilizing data on subjective household socioeconomic status (SES) and perceived family-level financial deterioration induced by COVID-19.

Methods: We utilized data from the Korea Youth Risk Behavior Survey, a nationally representative sample of Korean adolescents, in 2020 and 2021. The independent and joint associations of two primary exposures, subjective household SES and perceived family-level financial deterioration, with obesity were assessed using multivariable logistic regression models.

Results: Among 106,979 adolescents aged 12–18 years, 16.9% of boys and 9.0% of girls met the criteria for obesity. Notably, 70.5% reported experiencing COVID-19-related financial deterioration. Both subjective household SES and perceived family-level financial deterioration independently and synergistically increased the odds of obesity. A graded association was observed between obesity and lower SES and more severe financial deterioration, particularly among girls. Younger adolescents were more sensitive to household SES, whereas older adolescents were more sensitive to financial deterioration.

Conclusion: While the COVID-19 pandemic presented a unique social context, our findings highlight that financially insecure adolescents were at an increased risk of obesity during the early phase of the pandemic. This underscores the need for obesity-prevention strategies in times of macroeconomic recession to address not only the persistent influence of household SES but also the direct and indirect effects of family-level financial deterioration.

Introduction: This study aimed to determine the association between cumulative maternal physical activity level and their children’s physical activity in early childhood. We also compared the influence of each maternal physical activity on children’s physical activity in early childhood. Methods: We analyzed the data from 1,067 Japanese mother-child pairs. Maternal physical activity was assessed using the International Physical Activity Questionnaire. Cumulative physical activity level in mothers was computed based on the categories (low, moderate, and high) of physical activity from 5 time points (pre-pregnancy, during pregnancy, 1.5, 3.5, and 5.5 years postpartum). Children’s physical activity level was measured at age 5.5 years using the WHO Health Behaviour School-aged Children questionnaire and defined as engaging in physical activity for at least 60 minutes per day for more than 5 days. Logistic regression analysis was used to determine the association between maternal and children’s physical activity levels. Results: The results showed the positive association between cumulative maternal physical activity and children’s physical activity level (P for trend < 0.001). Furthermore, maternal physical activity during pregnancy (P for trend = 0.031) and 5.5 years postpartum (P for trend < 0.001) was positively associated with children’s physical activity. Conclusion: A positive association was observed between the cumulative maternal physical activity level and the physical activity level of their children at 5.5 years of age. Furthermore, maternal physical activity during pregnancy and at 5.5 years postpartum were positively associated with the level of children’s physical activity.

Background: A recent systematic review showed Japan's mortality from chronic obstructive pulmonary disease (COPD) is the lowest among 204 countries, despite notably higher smoking rates in men in Japan than in the US. This study aims to compare (1) trends in smoking rates, (2) trends in COPD mortality, and (3) the spirometry-based COPD prevalence in the general adult population between Japan and the US.

Methods: Age- and sex-specific smoking rates from the 1980s through 2010s and COPD mortality from 1999 through 2019 were obtained from national surveys and official statistics (International Classification of Diseases-10^th codes J40-44), respectively. A systematic review and meta-analysis was performed to estimate COPD prevalence in Japan, while the National Health and Nutrition Examination Survey 2007-2012 was used for the US. A fixed ratio of 0.7 of forced expiratory volume in the first second of forced vital capacity was used to define COPD.

Results: Over the past four decades, men in Japan consistently had 20-30% higher smoking rates than their US counterparts. From 1999-2019, age-adjusted COPD mortality in men in Japan was only a third of the US, whereas that in women was less than a tenth in 2019. Synthesizing data from 11 studies, involving 89,955 participants, Japan’s COPD prevalence was more than 10% lower than in the US in almost all age groups for both sexes.

Conclusions: This study showed markedly lower rates of COPD in Japan than in the US. Investigating factors contributing to the paradoxical observations could lead to advancing COPD risk reduction strategies.

Background: This study aimed to validate self-reported medical conditions in the Taiwan Biobank (TWBB), in which participants were inquired about 30 disease conditions, by comparing them with claims records from Taiwan's National Health Insurance (NHI) claims database.

Methods: We identified 30 clinical diagnoses using ICD-CM codes from ambulatory and hospital claims within the NHI claims database, matching diseases included in the TWBB. The concordance between self-reports and claims records was evaluated using tetrachoric correlation to assess the correlation between binary variables.

Results: A total of 131,834 participants aged 30–70 years with data from the TWBB and NHI records were included. Concordance analysis revealed tetrachoric correlations ranged from 0.420 (chronic obstructive pulmonary disease) to 0.970 (multiple sclerosis). However, several disorders exhibited lower tetrachoric correlations. The concordance was higher among those with higher education attainment, and lower among married individuals.

Conclusion: The concordance between self-reports in the TWBB and NHI claims records varied across clinical diagnoses, showing inconsistencies depending on participant characteristics. These findings underscore the need for further investigation, especially when these variables are crucial to research objectives. Integrating complementary databases such as clinical diagnoses, prescription records, and medical procedures can enhance accuracy through customized algorithms based on disease categories and participant characteristics and optimize sensitivity or positive predictive values to align with specific research objectives.

Background: Individuals with type 2 diabetes (T2D) have increased colorectal cancer (CRC) risk, but it is unknown whether income dynamics are associated with CRC risk in these individuals. We examined whether persistent low- or high-income and income changes are associated with CRC risk in non-elderly adults with T2D.

Methods: Using nationally representative data from the Korean Health Insurance Service database, 1,909,492 adults aged 30 to 64 years with T2D and no history of cancer were included between 2009 and 2012 (median follow-up of 7.8 years). We determined income levels based on health insurance premiums and assessed annual income quartiles for the baseline year and the four preceding years. Hazard ratios(HRs) and 95% confidence intervals(CIs) were estimated after adjusting for sociodemographic factors, CRC risk factors, and diabetes duration and treatment.

Results: Persistent low income (i.e., lowest income quartile) was associated with increased CRC risk (HR_{n=5years vs. n=0years} 1.11, 95% CI 1.04–1.18; P for trend=0.004). Income declines (i.e., a decrease≥25% in income quantile) were also associated with increased CRC risk (HR_{≥2 vs. 0 declines} 1.10, 95% CI 1.05–1.16; p for trend=0.001). In contrast, persistent high income (i.e., highest income quartile) was associated with decreased CRC risk (HR_{n=5years vs. n=0years} 0.81, 95% CI 0.73–0.89; p for trend<0.0001), which was more pronounced for rectal cancer (HR 0.64, 95% CI 0.53–0.78) and distal colon cancer (HR 0.70, 95% CI 0.57–0.86).

Conclusions: Our findings underscore the need for increased public policy awareness of the association between income dynamics and CRC risk in adults with T2D.

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

Background

Dementia is the leading cause of disability and imposes a significant burden on society. Previous studies have suggested an association between metabolites and cognitive decline. Although the metabolite composition differs between Western and Asian populations, studies targeting Asian populations remain scarce.

Methods

This cross-sectional study used data from a cohort survey of community-dwelling older adults aged ≥ 60 years living in Miyagi, Japan, conducted by Tohoku Medical Megabank Organization between 2013 and 2016. Forty-three metabolite variables quantified using nuclear magnetic resonance spectroscopy were used as explanatory variables. Dependent variable was the presence of cognitive decline (≤ 23 points), assessed by the Mini-Mental State Examination. Principal component (PC) analysis was performed to reduce the dimensionality of metabolite variables, followed by logistic regression analysis to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for cognitive decline.

Results

A total of 2,940 participants were included (men: 49.0%, mean age: 67.6 years). Among them, 1.9% showed cognitive decline. The first 12 PC components (PC1–PC12) accounted for 71.7% of the total variance. Multivariate analysis showed that PC1, which mainly represented essential amino acids, was associated with lower odds of cognitive decline (OR = 0.89; 95% CI, 0.80-0.98). PC2, which mainly included ketone bodies, was associated with cognitive decline (OR = 1.29; 95% CI, 1.11-1.51). PC3, which included amino acids, was associated with lower odds of cognitive decline (OR = 0.81; 95% CI, 0.66–0.99).

Conclusion

Amino acids are protectively associated with cognitive decline, whereas ketone metabolites are associated with higher odds of cognitive decline.

Background: The decline in measles vaccination coverage is a global concern. In Japan, coverage of the first-dose of measles vaccine, which had exceeded the target of 95.0% since fiscal year (FY) 2010, fell to 93.5% in FY 2021. Vaccination coverage increased to 95.4% in FY 2022 but varied by municipality. Few studies have focused on regional disparities in measles vaccination coverage. This study aimed to clarify the regional disparities in measles vaccination coverage by municipality in Japan and their associated factors.

Methods: In this ecological study, the measles vaccination coverage in FY 2022; population density; area deprivation index (ADI, an indicator of socioeconomic status); proportion of foreign nationals, single-father households, single-mother households, and mothers aged ≥30 years; and number of medical facilities, pediatricians, and non-pediatric medical doctors in 1,698 municipalities were extracted from Japanese government statistics. Negative binomial regression was performed with the number of children vaccinated against measles as the dependent variable, number of children eligible for measles vaccination as the offset term, and other factors as independent variables.

Results: Vaccination coverage was less than 95.0% in 54.3% of municipalities. Vaccination coverage was significantly positively associated with population density and negatively associated with the proportion of single-father households, mothers aged ≥30 years, and the ADI (incidence rate ratio [IRR]: 1.004, 0.976, 0.999, 0.970, respectively).

Conclusion: This study showed regional disparities in measles vaccination coverage in Japan. Single-father households, age of mothers, and socioeconomic status may be key factors when municipalities consider strategies to improve vaccination coverage.

Background: The influence of the coronavirus disease 2019 (COVID-19) pandemic on dental care utilization may have differed according to individual characteristics or type of dental care provision. This study aimed to evaluate the changes in dental care utilization and per-attendance costs by age group and type of dental care during the COVID-19 pandemic in Japan.

Methods: This time-series study used healthcare insurance claims data from 01/07/2019 to 09/27/2021 (143 weeks) from nine municipalities in Japan. Dental care utilization rate per week and average dental care cost per attendance by age groups (0–19 years/20–64 years/65–74 years/≥75 years) and types of dental care (outpatient/visiting) were used as outcome variables. COVID-19 pandemic waves in Japan were used as predictors: 1^st (03/23/2020–05/17/2020), 2^nd (06/22/2020–09/27/2020), 3^rd (10/26/2020–02/21/2021), 4^th (02/22/2021–06/07/2021), and 5^th (07/05/2021–09/13/2021) waves. Fixed-effects models were employed to estimate the proportional changes.

Results: In the fixed-effects model, we observed large declines in dental care utilization during the 1^st (17.0–22.0%) and 2^nd waves (3.0–13.0%) compared to the non-pandemic wave period in all age groups. In contrast, the average dental care cost per attendance increased in all age groups by 5.2–8.6% during the 1^st wave.

Conclusion: During the initial wave of the COVID-19 pandemic in Japan, dental care utilization decreased in all age groups, whereas the average dental care cost per attendance increased. The COVID-19 pandemic may have changed the dental care provision pattern towards less frequent and more concentrated dental care to avoid the risk of infection.

Background

Despite the fact that competing risks are inevitable in epidemiological and clinical studies, distinctions between the hazard ratio estimated by handling competing risks as censoring and the subditribution hazard ratio are often overlooked.

Methods

We derive quantitative relationships between subdistribution hazard ratio and cause-specific hazard ratio, and derive an approximate calculation method to transform the two into each other. Numerical examinations of hypothetical six scenarios and published information of a randomized clinical trial of cholesterol–lowering therapy and a registry of acute myeloid leukemia were provided.

Results

General and approximate relationships under rare event assumptions between the two types of hazard ratio were given. The approximation formula is based on a survival ratio and has two possible applications. First, one can calculate a subdistribution hazard ratio from published information. Second, this formula allows sample size estimation that takes the presence of competing risks into account.

Conclusions

The distinction between the two types of hazard ratio can be addressed by focusing on two quantities. One is how the event of interest and competing risk is rare, and the other is the survival ratio.

Background: The participation rate for screening is regarded as a useful indicator for preventing cancer and cardio-metabolic disease. However, the validity of self-reported screening participation has not yet been thoroughly evaluated in Japan. We aimed to examine its validity using the municipal screening records among the Japanese population.

Methods: We included 3,060 men and 3,860 women insured by the National Health Insurance for residents aged <75 years or the Medical Care System for the Elderly aged ≥75 years in the Chikusei area of the Japan Public Health Center-based Prospective Study for the Next Generation. They were asked about their participation in cancer screenings and health checkups during the previous year. We compared their responses to the municipal records and calculated the sensitivity and specificity of self-reported screening participation.

Results: The sensitivity and specificity of self-reported participation were 0.49 and 0.86 for lung cancer screening; 0.67 and 0.85 for colorectal cancer screening; 0.77 and 0.79 for stomach cancer screening; and 0.86 and 0.65 for health checkup, respectively. Among women, the sensitivity and specificity were 0.83 and 0.81 for breast cancer and 0.85 and 0.90 for cervical cancer, respectively.

Conclusion: Self-reported cancer screening participation for colorectal, stomach, breast, and cervical cancers had moderate-high sensitivity and specificity. Self-reported participation, especially for lung cancer screening and health checkups, should be carefully interpreted when assessing the performance of preventive measures.

Background: No previous study reported an association between paternal involvement in childcare and housework and maternal physical punishment.

Methods: Using data from the Japanese Longitudinal Survey of Newborns in the 21st century (N = 38,554), we analyzed responses about fathers’ involvement in childcare and housework at 6 months and mothers’ spanking of children at 3.5 years. Fathers’ involvement in childcare and housework was scored and categorized into quartiles. Spanking frequency was asked in the “often”, “sometimes”, or “not at all” categories. Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the mothers’ often spanking children were computed for the fathers’ involvement in childcare and housework. We also stratified the association by fathers’ working hours (40–49, 50–59, or ≥ 60 hours/week).

Results: Among the 16,373 respondents, the proportion of mothers who often spanked their children was 4.8%. Compared with the lowest quartile, a higher frequency of paternal involvement in housework was associated with a lower risk of spanking children (p _trend = 0.001). Adjustment for covariates attenuated the association, but significant association was observed in the 3^rd quartile of paternal involvement in housework [OR (95% CI): 0.77 (0.62-0.96)]. When the fathers worked fewer than 50 hours a week, a significant negative association was observed between the fathers’ frequency of childcare and the likeliness of the mothers’ spanking their children (p _trend = 0.02).

Conclusions: The fathers’ active involvement in childcare and housework could reduce the mothers’ physical punishment for their children.

Background: Despite the high frequency of tinnitus and its impact on wellbeing, little is known about its economic burden and no data to our knowledge are available on out-of-pocket (OOP) expenses.

Methods: In 2022 a survey was conducted on OOP costs of tinnitus. We enrolled 679 participants with slight, moderate and severe tinnitus in Italy, United Kingdom, Netherlands, Germany and Spain. We estimated annual OOP expenses for tinnitus-related healthcare visits, treatments, medications and alternative medicine practices. Prevalence of tinnitus in the general population, obtained from a representative survey we conducted in Europe in 2017-2018, was used to generalise costs for people with any tinnitus at the national level.

Results: OOP expenses were 368€ (95% confidence intervals (CI), 78€–690€), 728€ (95% CI, 316€–1,288€), and 1,492€ (95% CI, 760€–2,688€) for slight, moderate, and severe tinnitus, respectively, with annual expenditure of 565€ for people with any tinnitus: 209€ for healthcare visits, 93€ for treatments, 16€ for drugs, 64€ for hearing supporting systems and 183€ for acupuncture, homeopathy and osteopathy. Individuals with slight, moderate, and severe tinnitus expressed a willingness to invest 1.6, 4.3, and 7.0 times their monthly income, respectively, to achieve complete relief from tinnitus.

Conclusions: This study offers for the first time insights into the OOP expenses incurred by individuals with tinnitus. OOP expenses exhibited substantial variations based on severity status, accounting for more than 17 thousand million€ in the countries considered. In terms of financial burden, these findings align tinnitus to the recognised leading disabilities, including back pain and migraine.

Background: The use of life-sustaining treatment (LST) in the final stage of life is a major policy concern due to increased costs, while its intensity does not correlate with quality. Previous reports have shown declining trends in LST use in Japan. However, regional practice variations remain unclear. This study aims to describe regional variations in LST use before death among the oldest old in Japan.

Methods: A descriptive study was conducted among patients aged 85 or older who passed away between April 2013 and March 2014. The study utilized health insurance claims from Japan's National Database (NDB) to examine the use of cardiopulmonary resuscitation (CPR), mechanical ventilation (MV), and admission to the acute care ward (ACW) in the last 7 days of life.

Results: Among 224,391 patients, the proportion of patients receiving LST varied by region. CPR ranged from 8.6% (Chubu) to 12.9% (Shikoku), MV ranged from 7.1% (Chubu) to 12.3% (Shikoku), and admission to ACW ranged from 4.5% (Chubu) to 10.1% (Kyushu-Okinawa). The adjusted odds ratios (AOR) for regional variation compared with Kanto were as follows: CPR (in Shikoku, 1.85 [95% CI 1.73 - 1.98]), MV (in Shikoku, 1.75 [1.63 - 1.87]), and ACW admission (in Kyushu-Okinawa, 1.69 [1.52 - 1.88]).

Conclusion: The study presents descriptive information regarding regional differences in the utilization of LST for the oldest old. Further research is necessary to identify the factors that contribute to these variations and to address the challenge of improving the quality of end-of-life care.

Background

Disasters such as earthquakes, terrorism, and pandemics have triggered post-traumatic stress disorder (PTSD), and discrimination against the affected individuals has been linked to the development of PTSD. However, there is limited evidence regarding the association between discrimination against coronavirus disease 2019 (COVID-19) patients and probable PTSD in Japan.

Methods

We conducted a cross-sectional study utilizing a web-based questionnaire targeting individuals who had contracted the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Sapporo City. A total of 4247 individuals with laboratory-confirmed SARS-CoV-2 infection spanning from February 2020 to February 2022 completed the questionnaire (response rate: 15.9%). Probable PTSD was measured using the three-item Posttraumatic Diagnostic Scale. The stratified exact logistic regression was applied to calculate the odds ratios (OR) of probable PTSD for COVID-19-related discrimination with adjusted factors.

Results

This study included 3626 patients who had a history of SARS-CoV-2 infection. Among them, 321 patients (8.9%) experienced COVID-19-related discrimination. The prevalence of probable PTSD was 19.6% (63/321) among the patients who experienced COVID-19-related discrimination, and 4.6% (152/3305) among those who had not encountered such discrimination. The adjusted OR of COVID-19-related discrimination for probable PTSD was 4.68 (95% confidence interval [95% CI], 3.36-6.53). The population attributable fraction of probable PTSD attributable to COVID-19-related discrimination among COVID-19 patients was estimated to be 23.4% (95% CI, 21.5-25.3).

Conclusion

The comprehensive epidemiological survey of COVID-19 patients in Japan showed that COVID-19-related discrimination was associated with a higher prevalence of probable PTSD. Mitigating discrimination could be helpful to attenuate PTSD in future pandemics.

Background:

Instrumental variable (IV) methods are widely employed to estimate causal effects when concerns regarding unmeasured confounders. Although comparisons among several IV methods for binary outcomes exist, comprehensive evaluations are insufficient. Therefore, in this study, we aimed to conduct a simulation with some settings for a detailed comparison of these methods, focusing on scenarios where IVs are valid and under effect homogeneity with different instrument strengths.

Methods:

We compared six IV methods under 32 simulation scenarios: two-stage least squares (2SLS), two-stage predictor substitutions (2SPS), two-stage residual inclusions (2SRI), limited information maximum likelihood (LIML), inverse-variance weighted methods with a linear outcome model (IVW_LI), and inverse-variance weighted methods with a non-linear model (IVW_LL). By comparing these methods, we examined three key estimates: the parameter estimates of the exposure variable, the causal risk ratio, and the causal risk differences.

Results:

Based on the results, six IV methods could be classified into three groups: 2SLS and IVW_LI, 2SRI and 2SPS, and LIML and IVW_LL. The first pair showed a clear bias owing to outcome model misspecification. The second pair showed a relatively good performance when strong IVs are available; however, the estimates suffered from a significant bias when only weak IVs are used. The third pair produced relatively conservative results, although they were less affected by weak IV issues.

Conclusions:

The findings indicate that no panacea is available for the bias associated with IV methods. We suggest using multiple IV methods: one for primary analysis and another for sensitivity analysis.