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Objectives To investigate the association between multimorbidity during pregnancy and neurodevelopmental delay in offspring using data from a Japanese nationwide birth cohort study.Design This study was a prospective birth cohort study.Setting This study population included 104 059 fetal records who participated in The Japan Environment and Children’s Study from 2011 to 2014.Participants Pregnant women whose children had undergone developmental testing were included in this analysis.Primary and secondary outcome measures Neurodevelopment of offspring was assessed using the Japanese version of the Ages and Stages Questionnaire, third edition, comprising five developmental domains. The number of comorbidities among the pregnant women was categorised as zero, single disease or multimorbidity (two or more diseases). Maternal chronic conditions included in multimorbidity were defined as conditions with high prevalence among women of reproductive age. A multivariate logistic regression analysis was conducted to examine the association between multimorbidity in pregnant women and offspring development.Results Pregnant women with multimorbidity, single disease and no disease accounted for 3.6%, 30.6% and 65.8%, respectively. The ORs for neurodevelopmental impairment during the follow-up period were similar for infants of mothers with no disease comorbidity and those with a single disease comorbidity. However, the ORs for neurodevelopmental impairment were significantly higher for children born to mothers with multimorbidity compared with those born to healthy mothers.Conclusion An association was observed between the number of comorbidities in pregnant women and developmental delay in offspring. Multimorbidity in pregnant women may be associated with neurodevelopmental delay in their offspring. Further research is required in this regard in many other regions of the world.

Background The modern 24/7 society demands night shift work, which is a possible risk factor for chronic diseases. This study aimed to examine the associations of rotating night shift work duration with tooth loss and severe periodontitis. Methods This cross-sectional study used data from a self-administered questionnaire survey conducted among 3,044 permanent employees aged 20–64 years through a Japanese web research company in 2023. The duration of rotating night shift work was assessed using a question from the Nurses’ Health Study. Tooth loss was assessed based on self-reported remaining natural teeth count. Severe periodontitis was assessed using a validated screening questionnaire comprising four questions related to gum disease, loose tooth, bone loss, and bleeding gums. We employed linear regression models for tooth loss and Poisson regression models for severe periodontitis, adjusting for demographic, health and work-related variables and socioeconomic status. Results Among participants included, 10.9% worked in rotating night shifts for 1–5 years, while 11.0% worked in such shifts for ≥6 years. In fully adjusted models, rotating night shift work duration of 1–5 years was associated with tooth loss (beta −0.74, 95% confidence interval (CI) [−1.55 to 0.08]) and severe periodontitis (prevalence ratio 1.80, 95% CI [1.33–2.43]); however, the association with tooth loss was not statistically significant. Conclusions This study supports that employees who work short-term rotating night shifts may experience poor oral conditions. Further research is needed to determine whether long-term rotating night shift work is associated with deteriorated oral health.

Abstract Background Physicians in public health administration agencies (public health physicians: PHP) play important roles in public health; however, there are not enough such physicians in Japan. This study aimed to elucidate the factors related to the resignation and migration of PHPs using nationwide survey data. Methods Data from the Survey of Physicians, Dentists, and Pharmacists (2010, 2012, 2014, and 2016) were analyzed. The outcome was the resignation of PHPs or migration to public health administration agencies. The explanatory variables in the resignation analysis were age, sex, workplace, and board certification status. The type of work was added as an explanatory variable in the migration analysis, and clinical specialty was added to the clinical doctor-restricted analysis. The odds ratios (ORs) of the explanatory variables were calculated using generalized estimation equations. Results In the resignation analysis among PHPs, women had a significantly lower OR, whereas younger PHPs and those with board certifications had significantly higher ORs. In the migration to public health administration agencies analysis among medical doctors, women and those aged between 35 and 39 years had significantly higher ORs, but those with board certifications had significantly lower ORs. Hospital/clinic founders or directors had significantly lower ORs, but the clinic staff and ‘others/not working’ had significantly higher ORs. In the migration to public health administration agencies analysis among clinical physicians, those aged between 35 and 39 years had significantly higher ORs. Still, those with two or more board certifications had significantly lower ORs. Hospital/clinic founders or directors had significantly lower ORs, but the clinic staff had significantly higher ORs. Clinical doctors specializing in surgery and other specialties had significantly lower ORs, but those specializing in pediatrics and psychiatry/psychosomatic medicine had significantly higher ORs. Conclusions Having board certifications were significantly related to the resignation of PHPs and migration to public health administration agencies. Women migrated to public health administration agencies more than men and younger PHPs were more likely to resign. However, medical doctors aged between 35 and 39 years were more likely to migrate to public health administration agencies. Similarly, clinic staff, non-clinical physicians, and those whose specialties were pediatrics and psychiatry/psychosomatic medicine were more likely to migrate to public health administration agencies.

Background: Heavy metals such as lead (Pb) and cadmium (Cd) have been associated with adverse pregnancy and developmental outcomes, including congenital abnormalities. This study investigated the association between exposure to heavy metals and trace elements during fetal life and congenital limb abnormalities in infants. Methods: This study is based on a prospective ongoing nationwide birth cohort from the Japan Environment and Children’s Study (JECS). The concentrations of Cd, Pb, mercury (Hg), selenium (Se), and manganese (Mn) were measured in maternal blood collected during the mid–late trimesters. Inclusion criteria were available from questionnaires filled in during pregnancy, including information about congenital limb abnormalities at birth or at one month. To examine the associations with limb anomalies and individual chemicals, logistic regression models were applied following log-transformation or division into quartiles of Cd, Pb, Hg, Se, and Mn concentrations. To assess the associations with the heavy metals and trace elements mixture, quantile g-computation was employed. All models were adjusted for age, maternal smoking history, maternal alcohol intake, history of smoking, and infant sex. Results: Data from 90,163 participants were included in the analysis, of whom 369 had congenital limb abnormalities in any of the collected information, and 89,794 had none. Among the 369 cases of congenital limb abnormalities, there were 185 and 142 cases of polydactyly and syndactyly, respectively. The median concentrations of Pb, Cd, Hg, Se, and Mn were 5.85, 0.66, 3.64, 168, and 15.3 ng/g, respectively. There were no associations between maternal blood concentrations of Pb [adjusted odd ratio = 0.83; 95% confidence interval = 0.61, 1.11], Cd [0.87; 0.68, 1.10], Hg [0.88; 0.73, 1.07], Se [1.07; 0.44, 2.59], and Mn [0.91; 0.64, 1.30] with congenital limb abnormalities. No significant association was observed between the mixture of heavy metals and trace elements [0.85; 0.72, 1.02] and any congenital limb abnormalities. Moreover, there was no association with all polydactylies and all syndactylies, or any type of abnormality as a subdivision. Conclusion: At the maternal exposure levels of Cd, Pb, Hg, Se, and Mn assessed in the present study, no association was identified with the risk of developing congenital limb abnormalities in children.

BackgroundChildhood asthma is known to be affected by a range of factors, including conditions in the indoor environment. While flooring material influences indoor air conditions, the potential association between flooring materials and childhood asthma remains poorly understood in Japan.ObjectiveThe present study aims to assess the association between childhood asthma incidence and the primary flooring material with the ongoing prospective nationwide birth cohort data of the Japan Environment and Children's Study (JECS).MethodsThe JECS gathered data on mothers and children through 15 Regional Centres across Japan. The present study assessed flooring materials used in the home and asthma incidence at age four among children born between 2011 and 2014. We implemented logistic regressions, setting asthma incidence among the children as the outcome and home floor type as the exposure. Additional analyses were conducted, stratifying the home's age as a proxy for tatami age, to assess whether the potential effect of tatami flooring on asthma risk is influenced by its age.ResultsThe present study included total of 75,629 infants. For tatami flooring, the main multivariable regression and additional sub-group regression for homes over ten years old produced odds ratios of 1.09; 95% Confidence Interval (CI) [1.01-1.17] and 1.10; 95% CI [1.00-1.21] compared with flooring, respectively.ConclusionThese results imply that exposure to tatami flooring, particularly in older homes, may be associated with childhood asthma incidence. Moreover, our study highlights the importance of evaluating the relationship between regional and cultural differences between asthma and flooring materials.

Kawasaki disease (KD) is common among pediatric patients and is associated with an increased risk of later cardiovascular complications, though the precise pathophysiology of KD remains unknown. Per- and polyfluoroalkyl substances (PFAS) have gathered notoriety as the causal pathogens of numerous diseases as well as for their immunosuppressive effects. The present epidemiological study aims to assess whether PFAS may affect KD risk. We evaluated research participants included in the ongoing prospective nationwide birth cohort of the Japan Environment and Children’s Study (JECS). Among the over 100,000 pregnant women enrolled in the JECS study, 28 types of PFAS were measured in pregnancy in a subset of participants (N = 25,040). The JECS followed their children born between 2011 and 2014 (n total infants = 25,256; n Kawasaki disease infants = 271), up to age four. Among the 28 types of PFAS, those which were detected in >60 % of participants at levels above the method reporting limit (MRL) were eligible for analyses. Multivariable logistic regressions were implemented on the seven eligible PFAS, adjusting for multiple comparison effects. Finally, we conducted Weighted Quantile Sum (WQS) and Bayesian kernel machine regression (BKMR) to assess the effects of the PFAS mixture on KD. Therefore, we ran the BKMR model using kernel mechanical regression equations to examine PFAS exposure and the outcomes of KD. Upon analysis, the adjusted multivariable regression results did not reach statistical significance for the seven eligible substances on KD, while odds ratios were all under 1.0. WQS regression was used to estimate the mixture effect of the seven eligible PFAS, revealing a negative correlation with KD incidence; similarly, BKMR implied an inverse association between the PFAS mixture effect and KD incidence. In conclusion, PFAS exposure was not associated with increased KD incidence.

Abstract Aims/Introduction This study aimed to investigate the neurodevelopment of infants born to women with gestational diabetes mellitus (GDM). Materials and Methods Data from the National Birth Cohort in the Japan Environment and Children's Study from 2011 to 2014 (n = 81,705) were used. Japan uses the GDM guidelines of the International Association of Diabetes and Pregnancy Study Groups. The Japanese translation of the Ages and Stages Questionnaires, third Edition, was used to assess neurodevelopment in the following domains: communication skills, gross motor skills, fine motor skills, problem‐solving ability, and personal and social skills. The survey was carried out every 6 months from the age of 6 months to 4 years (total of eight times). Generalized estimating equations were used to evaluate the association between maternal GDM and neurodevelopmental delay based on odds ratios (ORs) and 95% confidence intervals (95% CIs). Results Neurodevelopmental delays, particularly in problem‐solving ability, fine motor skills, and personal and social skills, were significantly higher in infants born to women with GDM than in those born to women without GDM (adjusted OR 1.24, 95% CI 1.12–1.36; adjusted OR 1.15, 95% CI 1.03–1.27; and adjusted OR 1.18, 95% CI 1.04–1.33). Furthermore, stratification showed no significant increase in the adjusted ORs (95% CIs) of girls. Conclusions Neurodevelopment was significantly delayed up to 4 years‐of‐age among boys born to women with GDM.

Summary: Background: Arterial stiffening is central to the vascular ageing process and a powerful predictor and cause of diverse vascular pathologies and mortality. We investigated age and sex trajectories, regional differences, and global reference values of arterial stiffness as assessed by pulse wave velocity (PWV). Methods: Measurements of brachial-ankle or carotid-femoral PWV (baPWV or cfPWV) in generally healthy participants published in three electronic databases between database inception and August 24th, 2020 were included, either as individual participant-level or summary data received from collaborators (n = 248,196) or by extraction from published reports (n = 274,629). Quality was appraised using the Joanna Briggs Instrument. Variation in PWV was estimated using mixed-effects meta-regression and Generalized Additive Models for Location, Scale, and Shape. Findings: The search yielded 8920 studies, and 167 studies with 509,743 participants from 34 countries were included. PWV depended on age, sex, and country. Global age-standardised means were 12.5 m/s (95% confidence interval: 12.1–12.8 m/s) for baPWV and 7.45 m/s (95% CI: 7.11–7.79 m/s) for cfPWV. Males had higher global levels than females of 0.77 m/s for baPWV (95% CI: 0.75–0.78 m/s) and 0.35 m/s for cfPWV (95% CI: 0.33–0.37 m/s), but sex differences in baPWV diminished with advancing age. Compared to Europe, baPWV was substantially higher in the Asian region (+1.83 m/s, P = 0.0014), whereas cfPWV was higher in the African region (+0.41 m/s, P

Background: Lower respiratory tract infections (LRTIs) are a cause of inpatient and outpatient care among children. Although orofacial clefts seem to be associated with LRTIs, epidemiological studies are scarce on this topic. This study aimed to examine whether infants with orofacial clefts were associated with LRTIs. Methods: This prospective cohort study used data from the Japan Environment and Children’s Study, for which baseline recruitment was conducted during 2011–2014. This study included 81,535 participants. The number of infants with cleft lip and palate (CLP), cleft lip (CL), and cleft palate only (CP) was 67, 49, and 36, respectively. We defined history of LRTIs until 12 months’ age reported by their mothers as the dependent variable. Accumulated breastfeeding duration was used as a potential mediator. Results: The incidence proportion of LRTIs among the control group was 6.0%. The incidence proportion among infants with CLP, CL, and CP were 11.9%, 14.3%, and 5.6%, respectively. After adjusting for covariates, compared with the control group, infants with CLP and CL were associated with risk of LRTIs (incidence risk ratio [IRR] of CLP, 2.38; 95% confidence interval [CI], 1.30–4.36 and IRR of CL, 2.73; 95% CI, 1.40–5.33), but not ones with CP (IRR 1.08; 95% CI, 0.28–4.15). Accumulated breastfeeding duration decreased the IRR of CLP only (IRR of CLP, 2.16; 95% CI, 1.19–3.93). Conclusion: Infants with orofacial clefts aged 1 year have a potentially high incidence proportion of LRTIs. Accumulated breastfeeding duration might mediate the associations of CLP.

Objective: To identify whether preoperative magnetic resonance imaging findings of the brain can predict postoperative delirium in patients who undergo arch replacement for aneurysms. Methods: Overall, 193 patients who underwent aortic replacement for the first time at a single institution between April 2014 and September 2020 were enrolled in this retrospective study. After we excluded patients with acute aortic dissection, no preoperative magnetic resonance imaging findings of the brain, and postoperative cerebral infarction, 50 patients were included and divided into 2 groups, according to their confusion scale results: postoperative delirium (group D) and nonpostoperative delirium (group ND). Preoperative magnetic resonance imaging findings of the brain were classified into lacunar stroke, periventricular hyperintensity, and deep subcortical white matter hyperintensity groups; the latter 2 groups were further classified based on the Fazekas scale, grade 0 to 3. Results: There were 23 patients (46%) in group D and 27 (54%) in group ND. The mean age was significantly greater in group D than in group ND (75 vs 70 years; P = .007). The mean operative time was significantly longer in group D than in group ND (447 vs 384 minutes; P = .024). As for preoperative magnetic resonance imaging findings of the brain, there were significantly more lacunar stroke cases in group D than in group ND (P = .027). In multivariable logistic regression with stepwise selection, high-grade periventricular hyperintensity was significantly related to postoperative delirium (odds ratio, 9.38; 95% confidence interval, 1.55-56.56; P = .015). Conclusions: Silent cerebral ischemia detected by preoperative magnetic resonance imaging of the brain was a significant risk factor for postoperative delirium.

Abstract Aims/Introduction We investigated the association between gestational diabetes mellitus (GDM) and perinatal outcomes stratified by pre‐pregnancy body mass index (BMI) and/or gestational weight gain (GWG). Materials and Methods Data from the national birth cohort in the Japan Environment and Children's Study from 2011 to 2014 (n = 85,228) were used. Japan uses the GDM guidelines of the International Association of Diabetes and Pregnancy Study Groups. The odds ratios (ORs) of perinatal outcomes were compared between women with and those without GDM. Results The OR (95% confidence interval) of having a small for gestational age infant in the GDM group with a pre‐pregnancy BMI of ≥25.0 kg/m2 and insufficient GWG (7.25 kg) was 2.04 (1.56–2.67). The OR of hypertensive disorders of pregnancy was higher in women with a BMI ≥18.5 kg/m2 in the GDM group than in the non‐GDM group. Conclusions Large for gestational age and hypertensive disorders of pregnancy were associated with pre‐pregnancy BMI and GWG in either normal weight or overweight/obese women, and the relationship was strengthened when GDM was present. Women with GDM and a BMI of ≥25.0 kg/m2 are at risk of having small for gestational age and large for gestational age infants depending on GWG.

Abstract Background The extremes of maternal pre-pregnancy body mass index (BMI) are known to be risk factors associated with obstetric and adverse perinatal outcomes. Among Japanese women aged 20 years or older, the prevalence of underweight (BMI

BackgroundThe government of Japan has spent a significant amount on dental healthcare, but it remains unknown how the spending varies across age, type of service, and time. This study describes trends in dental expenditures in Japan.MethodsThis descriptive study used two national data sources: Estimates of National Medical Care Expenditure and Survey on Economic Conditions in Health Care. We obtained annual total and average per capita dental expenditures by age in Japan from 1984 to 2020 and estimated the proportions of types of service from 1996 to 2021. All costs were adjusted for the 2020 Consumer Price Index (1 US dollar ≈ 100 yen in 2020).ResultsTotal dental expenditures increased from 1.96 trillion yen in 1984 to 3.00 trillion yen in 2020. In particular, total and average per capita dental spending for older persons showed a rapid increase (total: from 185 billion yen in 1984 to 1.18 trillion yen in 2020; average per capita: from 15,500 yen in 1984 to 32,800 yen in 2020), contributing to the total amount increase. The crown restoration and prosthesis category amounted to 50.3% of the total expenditure in 1996, and this proportion declined to 32.4% by 2021. In 0-14 years persons, expenses on the crown restoration and prosthesis category decreased while the medical management category (mainly including fees for a management plan for oral diseases or oral functions) increased. In persons aged 65 years or older, expenses on the crown restoration and prosthesis category decreased, with increasing expenses in the medical management and at-home treatment categories.ConclusionThe amount of dental spending in Japan substantially increased from 1.96 trillion yen in 1984 to 3.00 trillion yen in 2020), a 1.53-fold increase. The observed changes in annual dental spending varied across age groups and types of service.

Abstract Background Frailty has been associated with a risk of adverse outcomes, and mortality in patients with various conditions. However, there have been few studies on whether or not frailty is associated with mortality in patients with accidental hypothermia (AH). In this study, we aim to determine this association in patients with AH using Japan’s nationwide registry data. Methods The data from the Hypothermia STUDY 2018&19, which included patients of ≥18 years of age with a body temperature of ≤35 °C, were obtained from a multicenter registry for AH conducted at 120 institutions throughout Japan, collected from December 2018 to February 2019 and December 2019 to February 2020. The clinical frailty scale (CFS) score was used to determine the presence and degree of frailty. The primary outcome was the comparison of mortality between the frail and non-frail patient groups. Results In total, 1363 patients were included in the study, of which 920 were eligible for the analysis. The 920 patients were divided into the frail patient group (N = 221) and non-frail patient group (N = 699). After 30-days of hospitalization, 32.6% of frail patients and 20.6% of non-frail patients had died (p

Neurodevelopmental delay is associated with neurodevelopmental disorders. Prenatal metal exposure can potentially cause neurodevelopmental delays in children. This study examines whether prenatal exposure to mercury (Hg) and selenium (Se) is associated with the risk of neurodevelopmental delays in children up to 4 years of age. Children enrolled in a prospective birth cohort of the Japan Environment and Children’s Study were examined. Hg and Se levels in maternal (nchild = 48,731) and cord (nchild = 3,083) blood were analyzed by inductively coupled plasma-mass spectrometry. Neurodevelopmental delays were assessed in children between the ages of 0.5 to 4 years using the Ages and Stages Questionnaires, Third Edition. The association between exposure and outcomes was examined using the generalized estimation equation models. In maternal blood, compared to participants with Se levels in the first quartile (83.0 to

Abstract Background The influence of maternal psychological distress on infant congenital heart defects (CHDs) has not been thoroughly investigated. Furthermore, there have been no reports on the combined effect of maternal psychological distress and socioeconomic status on infant CHDs. This study aimed to examine whether maternal psychological distress, socioeconomic status, and their combinations were associated with CHD. Methods We conducted a prospective cohort study using data from the Japan Environment and Children’s Study, which recruited pregnant women between 2011 and 2014. Maternal psychological distress was evaluated using the Kessler Psychological Distress Scale in the first trimester, while maternal education and household income were evaluated in the second and third trimesters. The outcome of infant CHD was determined using the medical records at 1 month of age and/or at birth. Crude- and confounder-adjusted logistic regression analyses were performed to evaluate the association between maternal psychological distress and education and household income on infant CHD. Results A total of 93,643 pairs of mothers and infants were analyzed, with 1.1% of infants having CHDs. Maternal psychological distress had a significantly higher odds ratio in the crude analysis but not in the adjusted analysis, while maternal education and household income were statistically insignificant. In the analysis of the combination variable of lowest education and psychological distress, the P for trend was statistically significant in the crude and multivariate model excluding anti-depressant medication, but the significance disappeared in the full model (P = 0.050). Conclusions The combination of maternal psychological distress and lower education may be a possible indicator of infant CHD.

Objective Previous studies have indicated that spatial variation in suicide mortality is associated with area-specific socioeconomic characteristics, such as socioeconomic deprivation and social fragmentation. However, most of these studies have been conducted in the West and findings from Asian countries are limited. This study aims to investigate associations between socioeconomic characteristics and suicide mortality rates across 1887 municipalities in Japan between 2009 and 2017. We also assessed these associations by gender and age group.Methods Suicide data were obtained from the suicide statistics of the Ministry of Health, Labour and Welfare in Japan and included information on the number of suicides by gender, age and municipality location. Social fragmentation, socioeconomic deprivation and urbanicity were used as socioeconomic characteristics in this study and were created from survey data obtained from the 2010 census. Bayesian hierarchical models were used to examine associations between socioeconomic characteristics and suicide risk.Results Suicide rates were significantly higher in municipalities with higher levels of deprivation, with a rate ratio of 1.13 (95% credible interval: 1.10 to 1.17) in the highest quartile compared with the lowest. Higher levels of urbanicity had significantly lower suicide rates, with a rate ratio of 0.79 (95% credible interval: 0.77 to 0.82) in the highest quartile compared with the lowest. However, associations between exposures and suicide varied considerably by gender and age. Among both men and women aged 0–39 years, fragmentation was significantly associated with suicide, with rate ratios of 1.07 and 1.15 for men and women, respectively, in the highest quartile compared with the lowest.Conclusion Suicide prevention in Japan should particularly focus on areas with high levels of deprivation or low levels of urbanicity. Furthermore, young Japanese people residing in the most fragmented municipalities were also at high risk of suicide, and appropriate measures need to be taken.

Background Psychological stress is a potential risk factor for oral diseases. However, evidence for the association between work stress and oral diseases is scarce. We aimed to examine the associations of work stress, according to the effort-reward imbalance model, with dental caries, periodontal status, and tooth loss. Methods This cross-sectional study included 184 regular employees at a medical university and 435 registrants of a web research company. Work stress was assessed using the effort-reward imbalance (ERI) ratio. Dental caries and tooth loss were assessed according to the number of decayed, filled, and missing teeth (DMFT) among the set of 28 teeth. Periodontal status was assessed using a self-administered questionnaire. For the DMFT, a linear regression model was used to estimate the unstandardised coefficients. A Poisson regression model was used to estimate the prevalence ratios (PRs) of poor periodontal status. Results Among medical university employees and employees enrolled from among the registrants of an online research company, a one-unit increase in the ERI ratio was associated with −2.81 (95% CI [−4.70 to −0.92]; p-value = 0.004) and −0.84 (95% CI [−1.80 to 0.12]; p-value = 0.085) changes in the DMFT from adjusted linear regression models, respectively. In employees enrolled from among the registrants of an online research company, a one-unit increase in the ERI ratio was also associated with 1.55 (95% CI [1.04–2.32]; p-value = 0.032) of the PR for poor periodontal status based on Poisson regression models. Conclusion ERI at work was associated with an increased risk of poor periodontal status.

Summary: Background: The COVID-19 pandemic is negatively impacting mental health globally. While increased social cohesion may have initially decreased suicide risk, there are few reports on the long-term impact. We examined the impact of the pandemic on suicide by gender and age through December 2021 in Japan. Methods: We analyzed trends in monthly suicide rates by age and gender from January 2016 to December 2021 using provisional mortality data in an interrupted time series analysis. We also considered linear trends in the pre-pandemic period and seasonal variations. Pandemic onset was defined as from April 2020. Estimated excess deaths by suicide that occurred during the pandemic were calculated. Findings: Excess number of suicide deaths during the pandemic period was estimated to be 1208 for men and 1825 for women. While there was no statistically significant increase in suicide rates overall for both men and women during the pandemic compared to the pre-pandemic, age-specific analyses showed a statistically significant increase in men 20–29 and 40–49 years, and in women of all age groups, except those under 20, 40–49 and over 80 years. Interpretation: The COVID-19 pandemic has had a negative impact on suicide rates in Japan and the impact is most pronounced in women and younger age groups. Subgroup analyses are needed, with a particular focus on those considered to be vulnerable and at increased suicide risk. Funding: A Grant-in-Aid for scientific research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (Award Number 21K10462).

Background: Population impact of modifiable risk factors on orofacial clefts is still unknown. This study aimed to estimate population attributable fractions (PAFs) of modifiable risk factors for nonsyndromic cleft lip with or without cleft palate (CL±P) and cleft palate only (CP) in Japan. Methods: We conducted a prospective cohort study using data from the Japan Environment and Children’s Study, which recruited pregnant women from 2011 to 2014. We estimated the PAFs of maternal alcohol consumption, psychological distress, maternal active and passive smoking, abnormal body mass index (BMI) (

Background: Levels of student loan debt have been increasing, but very little research has assessed if this is associated with poor health. The aim was to examine the association between student loans and psychological distress in Japan. Methods: We conducted a cross-sectional web-based self-administered questionnaire survey in 2017. The sample comprised of 4,149 respondents aged 20–34, with 3,170 graduates and 979 current university students. The independent variables were whether or not current students had student loans, and for graduates, the total amount of their student loan debt. The dependent variable was severe psychological distress assessed using the Kessler Psychological Distress Scale (K6; the cut-off point was 12/13). Covariates were demographic and parents’ socioeconomic variables. A Poisson regression analysis with a robust error variance was conducted to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs). Because there was a significant interaction between current student status and the status of borrowing student loans, stratified analyses were conducted. Results: The percentage of those with student loans was 33.8% among graduates and 35.2% among current university students. Among graduates, student loan debt was significantly associated with a high possibility of having severe psychological distress after adjusting for covariates (PR of ≥4 million yen, 1.44; 95% CI, 1.02–2.03). Among current university students, there was no significant association (PR of borrowing student loans, 0.91; 95% CI, 0.60–1.37). Conclusions: There was a significant association between student loan debt and psychological distress among graduates but not current university students.

Maternal intake of folic acid supplements is reportedly associated with the risk of early-onset allergies in offspring. However, only a few studies have considered the intake of both folic acid supplements and dietary folate. Here, the relationship between maternal intake of folic acid supplements and allergic symptoms such as wheeze and eczema in offspring was analyzed while considering dietary folate intake. We examined 84,361 mothers and 85,114 children in the Japan Environment and Children’s Study. The participants were divided into three groups depending on maternal folic acid supplementation (“no use,” “occasional use,” and “daily use”). Each group was then subdivided into three groups based on total folic acid and dietary folate intake. Outcomes were determined considering the wheeze and eczema status of each child at the age of 2 years. The status was based on the International Study of Asthma and Allergies in Childhood. It was found that 22.1% of the mothers took folic acid supplements daily. In contrast, 56.3% of the mothers did not take these supplements. Maternal intake of folic acid supplements was not associated with wheeze and eczema in the offspring. In contrast, only dietary folate intake was positively associated with wheeze at the age of 2 (adjusted odds ratio, 1.103; 95% confidence interval, 1.003–1.212). However, there is no scientific evidence of a biological mechanism that clarifies this result. Potential confounders such as other nutrition, outdoor/indoor air pollution, and genetic factors may have affected the results. Therefore, further studies on the association between maternal intake of folic acid and allergic symptoms at the age of 3 or above are needed to confirm the results of this study. Trial registration UMIN Clinical Trials Registry (number: UMIN000030786)

Background: Internal medicine (IM) doctors in Japan play the role of primary care physicians; however, the shortage of rural physicians continues. This study aims to elucidate the association of age, sex, board certification, type of work, and main clinical work with the retention or migration of IM doctors to rural areas. Methods: This retrospective cohort study included 82,363 IM doctors in 2010, extracted from the national census data of medical doctors. The explanatory variables were age, sex, type of work, primary clinical work, and changes in board certification status. The outcome was retention or migration to rural areas. The first tertile of population density (PD) of municipalities defined as rural area. After stratifying the baseline ruralities as rural or non-rural areas, the odds ratios (ORs) of the explanatory variables were calculated using generalized estimation equations. The analyses were also performed after age stratification (

Background: It is necessary to determine whether there are adverse health effects of prenatal exposure to long-term, low levels of mercury and selenium. However, there are limited that reports on the association between mercury levels by selenium levels and birth size. Therefore, we examined whether maternal mercury levels during pregnancy had any effect on infant birth size, and size, and whether selenium levels influenced this relationship. Objectives: To examine the association between mercury and selenium levels during pregnancy with infant birth size. Methods: The Japan Environment and Children's Study is a prospective birth cohort conducted between 2011 and 2014. Total mercury levels and total selenium levels in maternal blood during the second and third trimesters were measured using Inductively Coupled Plasma-Mass Spectrometry. Birth weight and small-for-gestational-age were confirmed by medical records. Small-for-gestational-age was defined as birth weight below the 10th percentile according to standard percentile for gender, parity, and gestational age. Multiple linear and logistic regression analyses were used to examine the association between maternal mercury exposure and birth weight or small-for-gestational-age adjusted for confounders (including maternal age and body mass index pregnancy). Results: Overall, 15,444 pregnant women were included in this study. Median (inter-quartile range) of blood mercury and selenium levels were 3.66 (2.59–5.18) ng/g and 170.0 (158.0–183.0) ng/g, respectively. Compared to infants of mothers with the highest blood selenium level, those of mothers with the lowest blood selenium level had neither a significant birth weight increase (9 g, 95% confidence interval: −6, 25) nor a significant odds ratio for small-for-gestational-age (0.903, 95% confidence interval: 0.748, 1.089). Compared to infants of mothers with the lowest blood mercury level, those of mothers with the highest blood mercury level had neither a significant birth weight reduction (−12 g, 95% confidence interval: −27, 4) nor a significant odds ratio for small-for-gestational-age (0.951, 95% confidence interval: 0.786, 1.150). Compared to infants of mothers with the lowest quartile of maternal blood mercury level, all infants of mothers with the highest quartile of maternal blood mercury level had a reduced birth head circumference of 0.073 cm (95% confidence interval: −0.134, −0.011). Conclusions: There was no association between maternal blood mercury levels and small-for-gestational-age and birth weight among 15,444 pregnant women. In a Japanese population, which has a relatively higher blood mercury level than reported in Western population, reduced birth size was not found to be associated with blood mercury levels, with the exception of birth head circumference. Keywords: Mercury, Selenium, Pregnancy, Birth weight, Small-for-gestational-age, The Japan Environment and Children's Study

Objectives Although psychological stress is a risk factor for oral diseases, there seems to be no review on work stress. This study aimed to review the evidence on the association between work stress and oral conditions, including dental caries, periodontal status and tooth loss.Design A systematic review of published observational studies.Data sources A systematic literature search was conducted in PubMed and Scopus databases on 12 August 2020.Study selection Articles were screened based on the following inclusion criteria: published after 1966; in English only; epidemiological studies on humans (except case studies, reviews, letters, commentaries and editorials); and examined the association of work stress with dental caries, periodontal status and tooth loss.Data extraction Data were extracted from eligible studies. A quality assessment was conducted using the Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies.Results Of 402 articles identified, 11 met the inclusion criteria, and 1 study assessed the association of work stress with dental caries and periodontal status. Of 11 studies, 1 reported a non-significant association between work stress and dental caries; 8 of 9 studies reported a significant association between work stress and worse periodontal status; and 1 of 2 studies reported a significant association between work stress and tooth loss. Nine of 11 studies were cross-sectional, while the remaining 2 studies had unclear methodology. Only two studies were sufficiently adjusted for potential confounders. Eight studies assessed work stress but did not use the current major measures. Three studies were rated as fair, while eight studies had poor quality.Conclusions There is a lack of evidence on the association of work stress with dental caries and tooth loss. Eight studies suggested potential associations between periodontal status and work stress. Cohort studies using the major work stress measures and adjusting for the potential confounders are needed.

BackgroundThe influence of mothers' and fathers' educational levels in separate evaluations of asthma has not been fully investigated. This study aims to examine the associations of the mother's and fathers' educational levels with childhood wheeze and asthma adjusting for crude and pre-and post-natal modifiable risk factors.MethodsWe conducted a prospective cohort study using data from the Japan Environment and Children's Study, which recruited pregnant women from 2011 to 2014. The mother's and father's educational levels were surveyed by a questionnaire during the pregnancy, and childhood wheezing and doctor-diagnosed asthma were estimated using a 3-year questionnaire. Multilevel logistic regression analysis was performed to evaluate the association between the mother's and father's educational levels and childhood wheezing and asthma, adjusted for pre-and post-natal factors.ResultsA total of 69,607 pairs of parents and their single infants were analyzed. We found 17.3% of children had wheezing and 7.7% had asthma. In crude analyses, lower educational level of parents was associated with an increased risk of childhood wheezing and asthma. After full adjustment, a lower educational level of mothers was associated with an increased risk of childhood asthma (junior high school (reference: high school); odds ratio (OR): 1.17, 95% CI, 1.01-1.36), and higher educational level, especially the mother's, was associated with an increased risk of childhood wheezing (technical junior college, technical/vocational college, or associate degree (ECD3); OR: 1.12, 95% CI, 1.06-1.18, bachelor's degree, or postgraduate degree; OR: 1.10, 95% CI, 1.03-1.18), and asthma (ECD3; OR: 1.13, 95% CI, 1.04-1.21).ConclusionsParents' lower educational level was a crude risk factor for childhood wheezing and asthma. However, an increased risk of wheezing due to mothers' higher educational level was found after adjusting for pre-and post-natal factors.

Aim This study describes the clinical characteristics and outcomes as well as the prognostic factors of patients with accidental hypothermia (AH) using Japan’s nationwide registry data. Methods The Hypothermia study 2018 and 2019, which included patients aged 18 years or older with a body temperature of 35°C or less, was a multicenter registry conducted at 87 and 89 institutions throughout Japan, with data collected from December 2018 to February 2019 and December 2019 to February 2020, respectively. Results In total, 1363 patients were enrolled in the registry, of which 1194 were analyzed in this study. The median (interquartile range) age was 79 (68–87) years, and the median (interquartile range) body temperature at the emergency department was 30.8°C (28.4–33.6°C). Forty‐three percent of patients with AH had a mild condition, 35.2% moderate, and 21.9% severe. AH occurred in an indoor setting in 73.4% and was caused by acute medical illness in 49.3% of patients. A total of 101 (8.5%) patients suffered from cardiopulmonary arrest on arrival at the hospital. The overall 30‐day mortality rate was 24.5%, the median (interquartile range) intensive care unit stay was 4 (2–7) days, and the median (interquartile range) hospital stay was 13 (4–27) days. In the multivariable logistic analysis, the prognostic factors were age (≥75 years old), male, activities of daily living (needing total assistance), cause of AH (trauma, alcohol), Glasgow Coma Scale score, and potassium level (>5.5 mEq/L). Conclusion The mortality rate of AH was 24.5% in Japan. The prognostic factors developed in this study may be useful for the early prediction, prevention, and awareness of severe AH.

Background: Birch pollen allergy affects pregnant women, and such allergy may affect the development of allergic diseases in their children. Using nationwide birth cohort data, this study aimed to investigate the prevalence of birch pollen IgE positivity and to identify correlating factors in pregnant women in Hokkaido, Japan, a high-latitude island. Methods: Participants included 6856 pregnant women. Participants responded to questionnaires regarding lifestyle factors and history of allergies. Data regarding parity, height, and pre-pregnancy weight were collected from medical records. Blood samples were obtained from participants during the first trimester of pregnancy, and serum allergen-specific IgE titers were determined. Results: The serum of 30.2% participants was positive for birch pollen IgE (≥0.35 UA/mL). Such positivity significantly correlated with a history of other allergic diseases, particularly food allergy and allergic rhinitis/hay fever. In multivariate logistic regression analysis, pre-pregnancy high body mass index (BMI ≥ 25) significantly correlated with birch pollen IgE positivity [odds ratio (OR), 1.24; 95% CI, 1.05–1.47; reference BMI, 18.5–24.9] and higher income (≥10 million yen per year; OR,0.55; 95% CI, 0.37–0.81; reference, household income

Background: Recent large-scale clinical studies demonstrate that sodium-glucose cotransporter 2 (SGLT2) inhibitors protect the diabetic kidney. However, clinical and animal studies have not shown the changes of the total glomeruli in the whole kidney treated with SGLT2 inhibitors. Methods: We performed computed tomography (CT) imaging on mice using synchrotron radiation to investigate the impact of luseogliflozin, a SGLT2 inhibitor, on the number and volume of glomeruli in the whole kidney. Findings: We did not observe a significant difference in the total glomerular number (Nglom) among mice. Luseogliflozin redistributed the number of glomeruli in different regions, accompanied by the normalization of diabetes-augmented renal volume (Vkidney). Diabetic db/db mice had a larger glomerular volume in the mid-cortex than did control db/m mice, and luseogliflozin increased the glomerular volume in all renal cortical zones of the whole kidney in db/db mice. According to the multivariate regression analysis, hemoglobin A1c level was the most relevant determinant of Vkidney, not Nglom or mean glomerular volume (Vglom), indicating that hyperglycemia induced renal (tubular) hypertrophy, but not glomerular enlargement. Luseogliflozin increased hypoxia in the juxtamedullary region, sustained upregulated renal renin expression and plasma renin activity, and failed to decrease albuminuria by downregulating megalin in db/db mice. Interpretation: Based on our findings, SGLT2 inhibitors may alter glomerular distribution and size in addition to their glucose-lowering effects, presumably by affecting oxygen metabolism and humoral factors. Fund: Funding for this research was provided by The Japan Society for the Promotion of Science, the Japan Diabetes Foundation, and Asahikawa Medical University. Keywords: Sodium glucose cotransporter-2 inhibitor, Diabetic nephropathy, Glomerular number, Glomerular volume, Megalin, Hypoxia

Abstract Background In Japan, a dramatic rise in suicide rates was observed in the 1950s, especially among the younger population, and then the rate decreased rapidly again in the 1960s. The aim of this study was to assess secular trends in method-specific suicides by gender and age in Japan between 1950 and 1975. We paid special attention to suicides by poisoning (solid and liquid substances), and their contribution to dramatic swings in the overall suicide rate in Japan during the 1950s and 1960s. Methods Mortality and population data were obtained from the Vital Statistics of Japan and Statistics Bureau, Ministry of Internal Affairs and Communications in Japan, respectively. We calculated method-specific age-standardized suicide rates by gender and age group (15–29, 30–49, or 50+ years). Results The change in the suicide rate during the research period was larger in males than females in all age groups, and was more marked among people aged 15–29 years compared to those aged 30–49 years and 50 years or over. Poisoning by solid and liquid substances overwhelmingly contributed to the dramatic change in the overall suicide rates in males and females aged 15–49 years in the 1950s and 1960s. For the peak years of the rise in poisoning suicides, bromide was the most frequently used substance. Conclusions Our results for the 1950s and 1960s in Japan illustrated how assessing secular trends in method-specific suicides by gender and age could provide a deeper understanding of the dramatic swings in overall suicide rate. Although rapid increases or decreases in suicide rates have been also observed in some countries or regions recently, trends in method-specific suicides have not been analyzed because of a lack of data on method-specific suicide in many countries. Our study illustrates how the collection and analysis of method-specific data can contribute to an understanding of dramatic shifts in national suicide rates.

Background: Recently, due to the detrimental effects on the ventricular function associated with right ventricular apical (RVA) pacing, right ventricular septal (RVS) pacing has become the preferred pacing method. However, the term RVS pacing refers to both right ventricular outflow-tract (RVOT) and mid-septal (RVMS) pacing, leading to a misinterpretation of the results of clinical studies. The purpose of this study, therefore, was to elucidate the functional differences of RVA, RVOT, and RVMS pacing in patients with atrioventricular block. Methods: We compared the QRS duration, global longitudinal strain (GLS), and left ventricular (LV) synchronization parameters at the three pacing sites in 47 patients. The peak systolic strain (PSS) time delay between the earliest and latest segments among the 18 LV segments and standard deviation (SD) of the time to the PSS were also calculated for the 18 LV segments at each pacing site using two-dimensional (2D) strain echocardiography. Results: RVMS pacing was associated with a significantly shorter QRS duration compared with RVA and RVOT pacing (154.4±21.4 vs 186.5±19.9 and 171.1±21.5 ms, P

BackgroundPrenatal psychological stress may increase the risk of placental abruption (PA). This study aimed to clarify the effects of psychological distress during pregnancy and exposure to stressful life events in the year before or during pregnancy on the occurrence of PA in Japanese women.MethodsUsing a nationwide prospective birth cohort study, we obtained data from 103,099 women between January 2011 and March 2014. Information on exposure to 14 stressful life events and psychological distress (Kessler 6 scale) was collected using a self-administered questionnaire during pregnancy. Clinical diagnoses of PA were obtained from medical records. A total of 80,799 women with singleton births were analyzed using logistic regression models that adjusted for possible confounders.ResultsPA was diagnosed in 335 (0.4%) women. There was no significant difference in the Kessler 6 score during pregnancy between the PA group and non-PA group. Exposure to the death of a child in the year before or during pregnancy was significantly associated with PA in multigravid women (adjusted odds ratio [aOR] 3.57; 95% confidence interval [CI] 1.50-8.34). A spouse's loss of employment was significantly associated with PA in parous women (aOR 3.25; 95% CI 1.40-7.56).ConclusionsThis study identified the possible effects of exposure to the death of a child on PA occurrence that adjusted for important confounding factors.

Objectives: Days off, on call, night duty, working hours and job stress can affect physicians’ mental health, and support from supervisors and co-workers may have a buffering effect. This study elucidates whether job strain and job factors affect physicians’ mental health, and whether support from supervisors and co-workers has a protective effect on their mental health. Material and Methods: The subjects included 494 physicians. The Brief Job Stress Questionnaire (BJSQ) was used to evaluate job demand, job control and support. High job strain was defined as a combination of high job demand and low job control. Depressive symptoms were assessed using the Patient Health Questionnaire-9. The Maslach Burnout Inventory- General Survey was used to evaluate burnout. Possible confounder adjusted logistic regression analyses were performed to obtain odds ratios for depressive symptoms and burnout. Results: As per the analysis, high job strain had significantly higher odds ratios, and support from co-workers had significant protective odds ratios for depressive symptoms. High job strain and having only 2–4 days off per month (compared to > 8 days off per month) had significantly higher odds ratios, and support from co-workers had significant protective odds ratios for burnout. Conclusions: High job strain was related to depressive symptoms and burnout, and support from co-workers had a buffering effect on depressive symptoms and burnout. An inadequate number of days off was related to burnout. Assessment of job strain may be a good tool to measure physicians’ mental health, and a sufficient number of days off may be needed to prevent burnout.

While the beneficial effects of prenatal yoga have been reported in recent years, little is known about its effectiveness in pregnant Japanese women. Despite several adverse effects, ritodrine hydrochloride is frequently prescribed to suppress preterm labor in Japan, and its usage may therefore indicate cases of preterm labor. This study aimed to clarify the association between prenatal yoga and ritodrine hydrochloride use during pregnancy.An observational study was conducted as an adjunct study by the Hokkaido unit of the Japan Environment and Children's Study. Information on prenatal yoga practice was collected using a self-questionnaire between March 21, 2012, and July 7, 2015, targeting women who had recently delivered. Ritodrine hydrochloride use was identified from medical records. A total of 2,692 women were analyzed using logistic regression models that adjusted for possible confounders.There were 567 (21.1%) women who practiced prenatal yoga, which was associated with a lower risk of ritodrine hydrochloride use (adjusted odds ratio [OR] 0.77; 95% CI 0.61-0.98). This was especially evident in women with a total practice duration that exceeded 900 minutes throughout their pregnancy (adjusted OR 0.54; 95% CI 0.38-0.76). A sensitivity analysis that excluded patients with threatened abortion during the study period produced similar results.Prenatal yoga was associated with a lower risk of ritodrine hydrochloride use, particularly in women with more than 900 minutes of practice time over the course of their pregnancy. Prenatal yoga may be a beneficial option for pregnant women in the selection of alternative therapies.

BackgroundBoth epilepsy and paragonimiasis had been known to be endemic in Southwest Cameroon. A total of 188 people (168 and 20 with and without symptoms confirmed by clinicians, respectively, 84.6% under 20 years old) were selected on a voluntary basis. Among 14 people (8.3%) with history of epilepsy, only one suffered from paragonimiasis. Therefore, we challenged to check antibody responses to highly specific diagnostic recombinant antigens for two other helminthic diseases, cysticercosis and toxocariasis, expected to be involved in neurological diseases. Soil-transmitted helminthic infections were also examined.Methodology/principal findingsFecal samples were collected exclusively from the 168 people. Eggs of Ascaris lumbricoides, Trichuris trichiura and hookworms were found from 56 (33.3%), 72 (42.8%), and 19 (11.3%) persons, respectively. Serology revealed that 61 (36.3%), 25 (14.9%) and 2 (1.2%) of 168 persons showed specific antibody responses to toxocariasis, paragonimiasis and cysticercosis, respectively. By contrast, 20 people without any symptoms as well as additional 20 people from Japan showed no antibody responses. Among the 14 persons with epilepsy, 5 persons were seropositive to the antigen specific to Toxocara, and one of them was simultaneously positive to the antigens of Paragonimus. The fact that 2 children with no history of epilepsy were serologically confirmed to have cysticercosis strongly suggests that serological survey for cysticercosis in children is expected to be useful for early detection of asymptomatic cysticercosis in endemic areas.Conclusions/significanceAmong persons surveyed, toxocariasis was more common than paragonimiasis, but cysticercosis was very rare. However, the fact that 2 children were serologically confirmed to have cysticercosis was very important, since it strongly suggests that serology for cysticercosis is useful and feasible for detection of asymptomatic cysticercotic children in endemic areas for the early treatment.