Development of a Concise Healthy Diet Score for Cardiovascular Disease among Japanese; The Japan Collaborative Cohort Study.

AIMS: Several diet quality indicators have been developed primarily for cardiovascular disease (CVD) prevention in Western countries. However, those previous indicators are complicated and less feasible in clinical and health-promoting settings. Therefore, we aimed to develop a concise dietary risk score for CVD prevention in Japanese. METHODS: Using the self-administered food frequency questionnaire with 35 food items, we developed a concise healthy diet score (cHDS) ranging from 0 to 5 points. We examined the association of cHDS with risks of all-cause and cause-specific mortality among 23,115 men and 35,557 women who were free of CVD and cancer. RESULTS: During 19.2 years of median follow-up, 6,291 men and 5,365 women died. In men, the multivariable hazard ratios (95% confidence intervals) for the highest cHDS (5 points) compared to the lowest (0-1 points) were 0.74 (0.60-0.91, P-trend=0.008) for CVD and 0.86 (0.77-0.95, P-trend=0.05) for all causes. No significant associations were found for stroke, coronary heart disease, and other causes in men. The corresponding hazard ratio in women was 0.65 (0.52-0.81, P-trend＜0.001) for CVD, 0.63 (0.45-0.88, P-trend＜0.001) for stroke, 0.48 (0.30-0.78, P-trend=0.008) for coronary heart disease, 0.67 (0.54-0.84, P-trend＜0.001) for other causes, and 0.75 (0.66-0.85, P-trend＜0.001) for all causes. CONCLUSION: We developed a concise diet quality score named cHDS in the Japanese population and found the inverse association of cHDS with mortality from CVD and all causes for both men and women.

Risk of gestational diabetes in women with PCOS based on body mass index: The Japan Environment and Children's Study.

CONTEXT: Women with polycystic ovary syndrome (PCOS), which is the most common endocrine disorder in women of reproductive age, have a potentially increased risk of gestational diabetes mellitus (GDM). OBJECTIVE: To examine the impact of PCOS on GDM based on maternal body mass index (BMI) using data from a large birth cohort study in Japan. DESIGN: Prospective observational study using data from the Japan Environment and Children's Study (JECS). PARTICIPANTS: Singleton pregnancies in the JECS during 2011-2014 were included. Mothers with HbA1c levels of ≥6.5% in the first trimester and history of DM or steroid use during pregnancy were excluded. MAIN OUTCOME MEASURES: Participants were categorized according to their pre-pregnancy BMIs: G1 (<18.5 kg/m2), G2 (18.5-19.99 kg/m2), G3 (20.0-22.99 kg/m2), G4 (23.0-24.99 kg/m2), and G5 (≥25.0 kg/m2). The impact of PCOS on early (Ed) and late-onset (Ld) GDM for each group was estimated using a multiple logistic regression model. RESULTS: We included 92774 participants, comprising 2012 PCOS(+) cases. GDM occurrence was higher in women with PCOS (p<0.001). PCOS had no effect on GDM in G1, G2, and G3. In G4, PCOS increased the risk of Ed GDM (adjusted odds ratio [aOR]: 3.27, 95% confidence interval [CI]: 1.29-8.29). In G5, PCOS increased the risk of both Ed (aOR: 2.48, 95% CI: 1.53-4.02) and Ld GDM (aOR: 1.94, 95% CI: 1.23-3.07). CONCLUSIONS: The impact of PCOS on GDM occurrence depended on the pre-pregnancy BMIs, which may facilitate personalized preconception counseling among women with PCOS.

Prenatal risk factors of indoor environment and incidence of childhood eczema in the Japan Environment and Children's Study.

The quality of indoor environment is a risk factor for early childhood eczema and atopic dermatitis; however, its influence during pregnancy on childhood eczema in Japan has not been investigated. In this study, we aimed to determine the indoor environmental factors that are associated with eczema in children up to 3 years of age, using national birth cohort data from the Japan Environment and Children's Study (JECS). Information on indoor environments and eczema symptoms until 3 years of age was collected using self-administered questionnaires to the mothers. A total of 71,883 and 58,639 mother-child pairs at 1.5- and 3-years-old, respectively, were included in the former analyses. To account for prenatal indoor risk factors, 17,568 (1.5-years-old) and 7063 (3-years-old) children without indoor mold and/or ETS exposure were included in the final analysis. A higher mold index, gas heater use, parquet flooring use, and frequent insecticide use showed significantly increased risks for childhood eczema up to 3 years of age. These associations were consistent after stratification analysis among children whose parents did not have a history of allergies. The updated WHO guidelines on indoor air quality should be implemented based on recent findings regarding the effects of prenatal exposure to indoor dampness on health effects of children further in life, including asthma, respiratory effects, eczema, and other immunological effects.

Intestinal Bacteria Fluctuating in Early-Stage Colorectal Cancer Carcinogenesis are Associated with Diet in Healthy Adults.

This hospital-based, cross-sectional study aimed to explore the association between diet and fluctuating intestinal bacteria in early-stage colorectal cancer (CRC) (Atopobium parvulum, Actinomyces odontolyticus, Solobacterium moorei, and Bifidobacterium longum). Healthy participants (n = 212) who underwent total colonoscopy at National Cancer Center Hospital (Tokyo, Japan) were divided into two groups according to the relative abundance of bacteria in their feces: those in the top 25% of relative bacterial abundance as cases and the bottom 25% as controls. The participants were divided into three groups (low, medium, and high) according to their intake of food groups associated with CRC. Multivariable logistic regression analysis was conducted to estimate the association between dietary intake and higher relative abundance of bacteria. Dairy products were inversely associated with a higher relative abundance of A. parvulum, A. odontolyticus, and S. moorei, with odds ratios (high vs. low) and 95% confidence interval as follows: 0.16 (0.06-0.44), 0.25 (0.08-0.82), and 0.29 (0.11-0.78), respectively. Additionally, dietary fiber was inversely associated with a higher relative abundance of S.moorei (0.29 [0.11-0.78]). No association was observed between diet and B.longum. In conclusion, healthy adults with a higher intake of dairy products and fiber had lower odds of having a higher relative abundance of CRC-associated microbiota.

Prevalence of and factors influencing Hikikomori in Osaka City, Japan: A population-based cross-sectional study.

OBJECTIVES: Hikikomori is commonly defined as a social condition in which individuals avoid social participation and relationships beyond their family members by confining themselves to a room or their house for 6 months or longer. Hikikomori has been predominantly considered a problem among young people; however, as the population is ageing, hikikomori has also emerged as a social issue among adults. Nevertheless, no comparative studies have examined the differences in the factors associated with hikikomori among teenagers/young adults and middle-aged/older adults. Thus, this phenomenon has not been thoroughly examined, and it remains unclear whether the risk factors vary between teenagers/young adults and middle-aged/older adults. Based on the Japan Cabinet Office's definition of hikikomori, this cross-sectional study evaluated the prevalence and related factors of hikikomori among the working age population (15-64 years), utilising univariate and multivariate analyses. The study also compared differences in the prevalence of and factors related to hikikomori between teenagers/young adults and middle-aged/older adults. METHODS: We distributed self-administered questionnaires to individual participants and their families between 24 December 2020 and 18 January 2021. RESULTS: Data from an anonymised sample of 3,092 individuals (split into two groups of 15-39 and 40-64 years) were subjected to analysis. The results revealed a hikikomori prevalence of 2.3% in the target population; the prevalence rate was 2.12% among individuals aged 15 to 39 years and 2.42% among those aged 40 to 64 years. The analysis demonstrated strong correlations between hikikomori and several factors, including unemployment, truancy, a history of psychiatric consultation or hospitalisation, being male and the absence of ibasho, which is defined as a place where individuals can feel peace, security, acceptance and belonging. The factors associated with hikikomori differed between teenagers/young adults and middle-aged/older adults. CONCLUSION: Our findings, thus, contribute to existing research by providing a comparative analysis of risk factors across different age groups.

Maternal diabetes and risk of offspring congenital heart diseases: the Japan Environment and Children's Study.

BACKGROUND: Few prospective cohort studies have examined the association between maternal diabetes, including pre-pregnancy and gestational diabetes, and the risk of congenital heart disease (CHD) in Asian offspring. METHODS: We examined the association between maternal diabetes and offspring CHD among 97,094 mother-singleton infant pairs in the Japan Environment and Children's Study (JECS) between January 2011 and March 2014. Odds ratios (OR) and 95% confidence intervals (CI) of offspring CHD based on maternal diabetes (pre-pregnancy diabetes and gestational diabetes) were estimated using logistic regression after adjusting for maternal age at delivery, pre-pregnancy body mass index (BMI), maternal smoking habits, alcohol consumption, annual household income, and maternal education. The diagnosis of CHD in the offspring was ascertained from the transcript of medical records. RESULTS: The incidence of CHD in the offspring was 1,132. Maternal diabetes, including both pre-pregnancy diabetes and gestational diabetes, was associated with a higher risk of offspring CHD: multivariable OR (95%CI) = 1.81 (1.40-2.33) for maternal diabetes, 2.39 (1.05-5.42) for pre-pregnancy diabetes and 1.77 (1.36-2.30) for gestational diabetes. A higher risk of offspring CHD was observed in pre-pregnancy BMI ≥25.0 kg/m2 (OR = 2.55, 95% CI: 1.74-3.75) than in pre-pregnancy BMI <25.0 kg/m2 (OR = 1.49, 95% CI: 1.05-2.10, p for interaction = 0.04). CONCLUSIONS: Maternal diabetes, including both pre-pregnancy and gestational, was associated with an increased risk of CHD in offspring.

The association between maternal social support levels during pregnancy and child development at three years of age: the Japan Environment and Children's Study.

BACKGROUND: Social relationships are essential in maintaining the physical and mental health of mothers and their children. However, there is limited evidence on how social support provided to the mother during pregnancy could impact child development. Herein, we examined whether maternal social support levels during pregnancy was associated with the risk of developmental delay in 3-year-old children. METHODS: Overall, 68,442 mother-child pairs completed questionnaires on maternal social support during pregnancy and development delay in 3-year-old children. The maternal social support level was evaluated using four items. The risk of development delay was evaluated using the Japanese version of the Ages and Stages Questionnaire-3 (ASQ-3) with five domains of communication, gross motor, fine motor, problem-solving, and personal-social. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression according to the quintiles of maternal social support levels after adjusting for potential confounding factors. RESULTS: Social support during pregnancy was associated with a lower risk of development delay at 3 years of age. Beneficial effects were detected in all domains of the ASQ-3 (p for trend <0.001). Multivariable ORs (95% CIs) for the highest versus lowest quartiles of maternal social support level were 0.57 (0.50-0.65) for communication, 0.49 (0.43-0.55) for gross motor delay, 0.58 (0.53-0.64) for fine motor delay, 0.56 (0.51-0.62) for problem-solving delay, and 0.52 (0.45-0.60) for personal social delay. The associations remained unchanged when stratified by maternal education level, paternal education level, living with children, household income, and postpartum depression. CONCLUSION: Maternal social support during pregnancy was inversely associated with the risk of developmental delay at 3 years of age.

Suicide risk among patients with cancer by sex in Japan: A population-based study.

BACKGROUND: In Japan, few studies have examined suicide risk for five-year relative survival rates for cancer sites. Since five-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-up with for up to 10 years. The outcome was suicide death. In addition, cancer sites were classified into three prognosis groups based on five-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, 1210 patients died by suicide (867 men and 343 women). The SMRs were almost equal for men (1.66, 95% 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. CONCLUSIONS: 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.

Long-term use of anti-cholesterol drugs and cancer risks in a Japanese population.

Several studies have investigated the association between the use of anti-cholesterol drugs and cancer risks, of which results have been inconsistent. This study included 67,768 participants from the Japan Public Health Center-based Prospective Study. The data on anti-cholesterol drug use was collected using three questionnaires of the survey conducted every five years. We divided the participants into three groups according to the duration of the anti-cholesterol drug use. Multivariable-adjusted Cox proportional hazard regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI). During the 893,009 person-years of follow-up from the 10-year follow-up survey, 8,775 participants (5,387 men and 3,388 women) were newly diagnosed with cancers. The duration of anti-cholesterol drug use was significantly associated with a decreased risk of liver cancer (HR:0.26, 95% CI 0.11-0.64 in > 5 y group) and with an increased risk of pancreatic cancer (HR:1.59, 95% CI 1.03-2.47 in > 5 y group). Moreover, a different trend was observed between men and women in the association with the risk of lung cancer. This study suggested that long-term use of anti-cholesterol drugs may have associations with a decreased incidence of liver cancer and with an increased incidence of pancreatic cancers.

Maternal Autistic Traits and Adverse Birth Outcomes.

Importance: Women with a high level of autistic traits in the general population may experience larger health disparities during pregnancy, particularly women diagnosed with autism spectrum disorder (ASD), which in turn may be associated with increased risk of adverse birth outcomes. Objective: To investigate the association between maternal autistic traits and the risk of adverse birth outcomes in the general population. Design, Setting, and Participants: This cohort study included mothers of singletons from a nationwide, multicenter prospective birth cohort, the Japan Environmental Children's Study. Expecting mothers were recruited between January 2011 and March 2014. Data were analyzed between June 2021 and November 2023. Exposures: Autistic traits were self-reported during the second and third trimesters using the short form of the Autism-Spectrum Quotient Japanese version (AQ-J10) (score range, 0-10; clinical range, ≥7). Main Outcomes and Measures: Data on preterm birth (<37 weeks' gestation) and neonates born small for gestational age (SGA) were transcribed from medical records. Additional analysis of gestational age groups (very preterm birth, <32 weeks' gestation; moderate-to-late preterm birth, 32-36 weeks' gestation) was also performed. Results: Among 87 687 women (mean [SD] age, 31.2 [5.0] years) included in the study, 2350 (2.7%) had AQ-J10 scores within the clinical range yet only 18 (0.02%) were diagnosed with ASD. A higher AQ-J10 score was associated with an increased risk of all birth outcomes, including preterm births (relative risk [RR] per 1-SD increase, 1.06; 95% CI, 1.03-1.09), moderate-to-late preterm births (RR per 1-SD increase, 1.05; 95% CI, 1.01-1.08), very preterm births (RR per 1-SD increase, 1.16; 95% CI, 1.06-1.26), and child born SGA (RR per 1-SD increase, 1.04; 95% CI, 1.01-1.06) after adjusting for maternal and pregnancy-related factors. The risks of all outcomes increased with higher AQ-J10 scores; compared with women below the clinical range, women within the clinical range had greater risk of preterm births (RR, 1.16; 95% CI, 1.07-1.26), moderate-to-late preterm births (RR, 1.12; 95% CI, 1.03-1.22), very preterm births (RR, 1.49; 95% CI, 1.18-1.89), and a child born SGA (RR, 1.11; 95% CI, 1.04-1.19). Conclusions and Relevance: In this cohort study, higher level of maternal autistic traits was associated with increased risk of adverse birth outcomes, particularly very preterm birth. Acknowledging the risks and providing tailored and timely antenatal care support to women with a high level of autistic traits in the general population, particularly women with autistic traits within the clinical range, regardless of formal diagnosis, is warranted.

Dietary Consumption of Antioxidant Vitamins in Relation to Prostate Cancer Risk in Japanese Men: The Japan Public Health Center-based Prospective Study.

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, ß-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, ß-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.

Neurodevelopmental outcomes at age 3 years after moderate preterm, late preterm and early term birth: the Japan Environment and Children's Study.

OBJECTIVE: To assess the association between gestational age classification at birth and the risk of neurodevelopmental impairments at age 3 years. DESIGN: Cohort study using the Japan Environment and Children's Study database. PATIENTS: A total of 86 138 singleton children born without physical abnormalities at 32-41 weeks of gestation enrolled between January 2011 and March 2014. MAIN OUTCOME MEASURES: Neurodevelopmental impairment, evaluated using the Ages and Stages Questionnaire (third edition). METHODS: Logistic regression analysis was used to evaluate the risk of neurodevelopmental impairment in moderate preterm, late preterm and early term children compared with term children after adjusting for socioeconomic and perinatal factors. RESULTS: The respective adjusted ORs (95% CIs) of incidence of scores below the cut-off value (<-2.0 SD) at age 3 years for moderate preterm, late preterm and early term births, compared with full-term births, were as follows: communication, 2.40 (1.54 to 3.73), 1.43 (1.19 to 1.72) and 1.11 (1.01 to 1.21); gross motor, 2.55 (1.69 to 3.85), 1.62 (1.36 to 1.93) and 1.20 (1.10 to 1.30); fine motor, 1.93 (1.34 to 2.78), 1.55 (1.35 to 1.77) and 1.08 (1.01 to 1.15); problem solving, 1.80 (1.22 to 2.68), 1.36 (1.19 to 1.56) and 1.07 (1.00 to 1.14) and personal-social, 2.09 (1.29 to 3.40), 1.32 (1.07 to 1.63) and 1.00 (0.91 to 1.11). CONCLUSION: Moderate preterm, late preterm and early term births were associated with developmental impairment at age 3 years compared with full-term births, with increasing prematurity. Careful follow-up of non-full-term children by paediatricians and other healthcare providers is necessary for early detection of neurodevelopmental impairment and implementation of available intervention.

Effect of graft-versus-host disease on outcomes of HLA-haploidentical peripheral blood transplantation using post-transplant cyclophophamide.

There is limited evidence regarding the association between graft-versus-host disease (GVHD) and reduced relapse in patients who undergo allogeneic hematopoietic stem cell transplantation from haploidentical donors (haplo-HSCT) using post-transplant cyclophosphamide (PTCY). We investigated the association between GVHD and transplant outcomes in 938 patients who received haplo-HSCT using PTCY. Overall survival (OS), relapse rate, and non-relapse mortality (NRM) were evaluated using landmark analysis at the landmark points at 100 and 360 days after HSCT for acute and chronic GVHD, respectively. Grade I-II acute GVHD was not associated with OS (adjusted hazard ratio: 1.15, 95% confidence interval: 0.85-1.57), relapse (1.03, 0.74-1.45) and NRM (1.15, 0.74-1.77). Conversely, grade III-IV acute GVHD was associated with higher NRM (3.16, 1.61-6.19), but no other outcomes. Limited chronic GVHD was not associated with OS (1.11, 0.48-1.95), relapse (1.05, 0.30-3.75) and NRM (1.30, 0.45-3.79). Extensive chronic GVHD was associated with higher NRM (2.40, 1.03-5.57), but no other outcome. In conclusion, any GVHD was not associated with a reduced relapse rate and improved OS, and Grade III-IV acute GVHD and extensive chronic GVHD were associated with higher NRM in patients who received haplo-HSCT using PTCY.

Risk of Parkinson's disease-related death in cancer survivors: A population-based study in Japan.

BACKGROUND: The risk of Parkinson's disease (PD)-related death in patients with cancer largely unexplored. METHODS: We analyzed data from the Neoplasms ANd other causes of DEath (NANDE) study, which investigates the causes of death in patients with cancer in Japan. Standardized mortality ratios (SMRs) were calculated to compare the risk of PD-related deaths in patients with cancer to that of the general population. Poisson regression models were employed to estimate the relative risk of PD-related death in the subgroups. RESULTS: The cohort included 548,485 patients with cancer, yielding 2,047,398 person-years at risk from 1995 to 2013. During the study period, 242,250 patients died and 145 deaths were attributable to PD. The SMR for PD-related death was 2.34 (95% confidence interval [CI]: 1.99-2.75). Patients who were diagnosed with cancer before 70 years of age had a high SMR (>5) for PD-related deaths. The SMR of patients with mouth-to-stomach cancers (lip, oral cavity, pharynx, esophagus, and stomach cancers) was 3.72 (95% CI: 2.84-4.86), while that of those with other cancers was 1.93 (95% CI: 1.57-2.37). The multivariate Poisson regression model revealed that patients with mouth-to-stomach cancers were more likely to die of PD than those without (relative risk 2.07, 95 % CI; 1.46-2.93). CONCLUSIONS: Patients with cancer are at a high risk of PD-related death; particularly, mouth-to-stomach cancers and potentially obstructing medication for PD are attributable to a high mortality risk. Careful management, including adequate PD treatment, would benefit cancer survivors with PD and reduce the risk of PD-related death.

Basic life support for non-traumatic out-of-hospital cardiac arrests during school-supervised sports activities in children: A nationwide observational study in Japan.

Objective: To investigate the prognostic impact of bystander-initiated cardiopulmonary resuscitation (CPR) and public-access automated external defibrillator (AED) use on non-traumatic out-of-hospital cardiac arrest (OHCA) occurring during school-supervised sports activities in children. Methods: From a nationwide database of pediatric OHCAs occurring under school supervision in Japan, data between April 2008 and December 2020 were obtained. We analyzed non-traumatic OHCAs that occurred during school-supervised sports activities among schoolchildren from elementary, junior high, high, and technical colleges. A multivariable logistic regression model was used to evaluate the effect of basic life support (BLS) on 1-month survival with favorable neurological outcomes after OHCA. Results: In total, 318 OHCA cases were analyzed. The 1-month survival with favorable neurological outcomes was 64.8% (164/253) in cases receiving both bystander-CPR and AED application, 40.7% (11/27) in cases receiving CPR only, 38.5% (5/13) in patients receiving AED application only, and 28.0% (7/25) in cases receiving no bystander intervention. Compared with cases receiving no BLS, cases receiving both CPR and AED had a significantly higher proportion of 1-month survival with favorable neurological outcomes (adjusted odds ratio [AOR]: 3.97, 95% confidence interval [CI]: 1.32-11.90, p = 0.014). However, compared to cases receiving no BLS, there was no significant difference in the outcome in the cases receiving CPR only (AOR: 1.35, 95% CI: 0.34-5.29, p = 0.671) and the cases receiving AED application only (AOR: 1.26, 95% CI: 0.25-6.38, p = 0.778). Conclusion: The combination of CPR and AED as BLS performed by bystanders for non-traumatic OHCA during school-supervised sports activities improved the outcomes.

Association of anticholinergic drug exposure with the risk of dementia among older adults in Japan: The LIFE Study.

OBJECTIVES: Several studies have investigated that anticholinergic drugs cause cognitive impairment. However, the risk of dementia associated with anticholinergics has not been extensively investigated in the super-aging society of Japan. We conducted this study to assess the association between anticholinergic drugs and the risk of dementia in older adults in Japan. METHODS: This nested case-control study used data from the Longevity Improvement & Fair Evidence Study, which includes claim data in Japan from 2014 to 2020. We included 66,478 cases of diagnosed dementia and 328,919 matched controls aged ≥65 years, matched by age, sex, municipality, and cohort entry year. Primary exposure was the total cumulative anticholinergic drugs prescribed from cohort entry date to event date or matched index date, which was the total standardized daily doses for each patient, calculated by adding the total dose of different types of anticholinergic drugs in each prescription, divided by the World Health Organization-defined daily dose values. Odds ratios for dementia associated with cumulative exposure to anticholinergic drugs were calculated using conditional logistic regression adjusted for confounding variables. RESULTS: The mean (standard deviation) age at index date was 84.3 (6.9), and the percentage of women was 62.1%. From cohort entry date to event date or matched index date, 18.8% of the case patients and 13.7% of the controls were prescribed at least one anticholinergic drug. In the multivariable-adjusted model, individuals with anticholinergic drugs prescribed had significantly higher odds of being diagnosed with dementia (adjusted odds ratio, 1.50 [95% confidence interval, 1.47-1.54]). Among specific types of anticholinergic drugs, a significant increase in risk was observed with the use of antidepressants, antiparkinsonian drugs, antipsychotics, and bladder antimuscarinics in a fully multivariable-adjusted model. CONCLUSIONS: Several types of anticholinergic drugs used by older adults in Japan are associated with an increased risk of dementia. These findings suggest that the underlying risks should be considered alongside the benefits of prescribing anticholinergic drugs to this population.

The association between constipation and subsequent risk of atopic dermatitis in children: the Japan Environment and Children's Study.

BACKGROUND: No study has examined the association between constipation and atopic dermatitis (AD) in infants and toddlers. We aimed to explore that association in toddlers using the data from a nationwide birth cohort study. METHODS: From the Japan Environment and Children's Study, a nationwide prospective birth cohort study that began in 2011, children born in a singleton live birth were analyzed. Participants completed questionnaires containing questions related to bowel movements and AD, during 1.5 to 3 years after birth. Constipation at 1 year of age was defined as having ≤2 bowel movements per week. AD was defined based on participant's responses to the modified ISAAC questionnaire and/or self-reported physician's diagnosis. Outcome was defined as the cumulative number of AD cases that occurred until 3 years of age. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for development of AD were calculated by a multivariable logistic regression. RESULTS: From a total of 62,777 participants who met the study inclusion criteria, 14,188 children (22.6%) were affected by AD between the ages of 1.5 and 3 years. The adjusted OR of developing AD for the presence versus absence of constipation at 1 year of age was 1.18 (95% CI, 1.01-1.38). CONCLUSION: Constipation at 1 year of age was associated with a slightly higher risk of AD until 3 years of age.

Heart Disease Mortality in Cancer Survivors: A Population-Based Study in Japan.

BACKGROUND: Data on the risk of cardiovascular-related mortality in patients with cancer are limited. METHODS AND RESULTS: This retrospective cohort study used data from the Osaka Cancer Registry and vital statistics in Japan between 1985 and 2013. The causes of death were investigated, and the risk of fatal heart disease was analyzed. Standardized mortality ratios were calculated to compare the risk of fatal heart disease between patients with cancer and the general population. Fine and Gray competing risk regression models were used to assess the risk of fatal heart disease among patients with cancer. In total, 682 886 patients with cancer were included in the analysis, and 335 635 patients died during the study period. Heart disease was the leading cause of noncancer deaths, with 10 686 deaths. Among the patients who died of heart disease, 5017 had ischemic heart disease, 3598 had heart failure, 356 had hypertensive disease, and 1715 had other heart diseases. The standardized mortality ratio for heart disease was 2.80 (95% CI, 2.74-2.85). The standardized mortality ratio for ischemic heart disease, heart failure, and hypertensive disease were 3.26 (95% CI, 3.17-3.35), 2.69 (95% CI, 2.60-2.78), and 5.97 (95% CI, 5.38-6.63), respectively. The risk of fatal heart disease increased over time after cancer diagnosis. Men were more likely to die of heart disease than women (subdistribution hazard ratio, 1.08 [95% CI, 1.02-1.16]). The risk of fatal heart disease among cancer survivors has decreased in recent years. CONCLUSIONS: Cancer survivors have a higher risk of fatal heart disease than the general population.

Impact of Coronavirus Disease 2019 (COVID-19) Outbreak on Emergency Patients Hospitalized With Cardiocerebrovascular Diseases in Osaka Prefecture, Japan　- A Population-Based Study.

BACKGROUND: Little is known about the transport and outcomes of emergency patients with cardiocerebrovascular diseases in Japan before and during the COVID-19 pandemic.Methods and Results: Data were extracted from a population-based registry in Osaka, Japan, from 2019 to 2021. There were almost no differences in the numbers of emergency patients hospitalized with myocardial infarction, stroke, or heart failure or their deaths. However, the number of cases of difficulty obtaining patient acceptance by hospitals increased in 2020 and 2021 compared with 2019. CONCLUSIONS: The numbers of emergency patients hospitalized with cardiocerebrovascular diseases and their deaths in Osaka were not affected by the COVID-19 epidemic.