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Background: Breastfeeding is said to prevent overweight and obesity in childhood but the evidence about its long-term impact on body size into adolescence and adulthood is scarce. We sought to examine the association between feeding types and subsequent physical size at the ages of 3, 6, 12, and 22 years. Methods: The Ibaraki Children’s Cohort (IBACHIL) Study, which began in 1992, involved a cohort of 4,592 Japanese children from 87 communities of a single prefecture whose parents answered health questionnaires about their child’s health and life habits at the age of 3 years. Follow-up questionnaires were distributed to the same cohort when they were 6, 12, and 22 years old. Self-reported height and weight, body mass index (BMI), and overweight status at ages of 3 (n = 4,290), 6 (n = 1,999; proportion of participants analyzed = 47%), 12 (n = 2,227; 52%), and 22 (n = 1,459; 34%) years were compared according to feeding type (breastfeeding, formula feeding, and mixed feeding) during infancy. Results: At the age of 3 years, multivariable adjusted-mean weight and prevalence of overweight were less for breastfed children than those formula-fed in both boys (weight: 14.6 kg vs 14.7 kg, P = 0.07, overweight: 6.3% vs 9.3%, P = 0.03) and in girls (14.0 kg vs 14.2 kg, P = 0.01 and 10.4% vs 13.6%, P = 0.06). However, there were no statistically significant differences in weight, BMI, and overweight at the ages of 6, 12, and 22 years according to feeding type. Conclusion: Breastfeeding may prevent overweight in childhood, but its impact is not significant in adolescence and adulthood.

Background: Vascular-type Ehlers–Danlos syndrome (vEDS) is caused by collagen III deficit resulting from heterogeneous mutations in COL3A1, which occasionally causes sudden death due to arterial/visceral rupture. However, it is difficult to conduct basic research on the pathophysiology of vEDS. Moreover, the number of patients with vEDS is small, limiting the number of available samples. Furthermore, the symptoms of vEDS may vary among family members, even if they share the same mutation. Accordingly, many aspects of the pathology of vEDS remain unknown. Therefore, we investigated the structural abnormalities in collagen fibrils and endoplasmic reticulum (ER) stress in skin samples using electron microscopy as well as their relationship with clinical symptoms in 30 patients with vEDS (vEDS group) and 48 patients without vEDS (disease-negative control group).Methods: Differences between the two groups were evaluated in terms of the sizes of collagen fibrils using coefficient of variation (COV).Results: COV was found to be significantly higher in the vEDS group than in the disease-negative control group, indicating irregularity in the size of collagen fibrils. However, in the vEDS group, some patients had low COV and seldom experienced serious complications and ER stress.Conclusion: ER stress might affect collagen fibril-composing proteins. Moreover, as this stress varies among people based on environmental factors and aging, it may be the underlying cause of varying vEDS symptoms.

Background Aortic aneurysm rupture and acute aortic dissection are life‐threatening conditions and represent an ever‐growing public health challenge. Comprehensive epidemiologic investigations for their risk factors are scant. We aimed to investigate risk factors associated with mortality from aortic diseases through analysis of a community‐based Japanese cohort. Methods and Results IPHS (Ibaraki Prefectural Health Study) comprises 95 723 participants who took part in municipal health checkups in 1993. Factors considered for analysis included age, sex, body mass index, blood pressure, serum lipids (high‐density lipoprotein [HDL] cholesterol, non‐HDL cholesterol, and triglycerides), diabetes, antihypertensive and lipid‐lowering drug use, and smoking and drinking habits. Cox proportional hazards models were applied to evaluate the associations between these variables and mortality from aortic diseases. During the median 26‐year follow‐up, 190 participants died of aortic aneurysm rupture, and 188 died of aortic dissection. An increased multivariable hazard ratio (HR) for mortality from total aortic diseases was observed for high systolic blood pressure (1.61 [1.00–2.59]), diastolic blood pressure (2.95 [1.95–4.48]), high non‐HDL cholesterol (1.63 [1.19–2.24]), low HDL cholesterol (1.86 [1.29–2.68]), and heavy (>20 cigarettes/day) smoking habit (2.46 [1.66–3.63]). A lower multivariable HR was observed for diabetes (0.50 [0.28–0.89]). Conclusions Smoking habit, higher systolic blood pressure and diastolic blood pressure levels, higher non‐HDL, and lower HDL cholesterol levels were positively associated with mortality from total aortic diseases, whereas diabetes was inversely associated.

Abstract A cross-sectional study of 21,665 Japanese residents was performed to investigate the prevalence of central sensitization syndromes (CSS). CSS were assessed using the Central Sensitization Inventory (CSI-A). CSS were defined as a CSI-A score of 40 or higher. Age, sex, district, 10 CSS-related diseases (CSI-B), lifestyle, and mental factors were rated in a self-reported survey. The prevalence of CSS and its relationship with potential factors were examined by sex using descriptive and logistic regression models. The prevalence of CSS was 4.2% in all participants and was significantly higher in women (4.9%) than in men (2.7%). Adjusted odds ratios correlated with CSS for an age of 80–97 years versus 60–79 years (2.07 and 2.89), one or more CSI-B diseases (3.58 and 3.51), few sleeping hours (2.18 and 1.98), high perceived stress (5.00 and 4.91), low (2.94 and 2.71) and high (0.45 and 0.66) resilience versus moderate resilience, and exercise habits (0.68 and 0.55) in men and women (all P

Introduction: To clarify the incidences of metabolic syndrome (MS) and risks in young Japanese adults by gender. Methods: A total of 58,901 adults who had undergone annual health check-ups in 2010 without a diagnosis of MS or missing data were divided into three age groups (20s through 40s) by gender. Participants were followed up for 6 years for new-onset MS according to Japanese criteria. The incidences of MS and risks were analyzed using the Cox proportional hazards model to adjust for confounding factors. Results: The incidences of MS per 1,000 person-years were 2.2, 5.5, and 10.2 for women aged in their 20s, 30s, and 40s, respectively, and 26.3, 40.5, and 57.4 in the respective men groups. Compared with the group aged in their 40s, the hazard ratios of new MS were 0.19 (95% confidence interval [CI], 0.13–0.29) for women in their 20s and 0.50 (95% CI, 0.41–0.61) for women in their 30s, and 0.46 (95% CI, 0.42–0.50) and 0.70 (95% CI, 0.66–0.73) for men in their 20s and 30s, respectively, after adjustment for lifestyle factors. For women, MS was associated with smoking in their 20s and 30s, and eating speed in their 30s, and for men, was associated with physical activity, eating speed, alcohol intake in their 20s and 30s, and smoking in their 30s. Conclusion: Our findings suggest that the incidences of MS in the 20s and 30s are lower, but account for about 20–50% of women with MS and 50–70% of men with MS in their 40s. However, the data are not negligible and early lifestyle intervention for MS is necessary in young adults.

Background: It is uncertain whether health counselling after community-based health checkups for high-risk individuals of lifestyle-related disease enhances their referral to physicians. Methods: We performed a clustered randomized controlled trial of untreated high-risk individuals aged 40 to 74 years who were screened from the annual health checkup in 2014 and 2015 under the national health insurance in 43 municipalities around Japan, assigning 21 intervention and 22 usual care municipalities. The high-risk conditions were severe forms of hypertension, diabetes, dyslipidemia (for men), and proteinuria. For the intervention group, the theory-based health counselling was performed to enhance referrals to physicians, while each municipality performed its own standard counselling for the usual care group. Data on clinical visits and risk factors were collected systematically and anonymously from the databases of health insurance qualification, health insurance claims, and annual health checkups. Hypotheses are that the cumulative proportion of seeing physicians (clinical visits) is higher in the intervention than the usual care groups, and that those in the intervention group have lower cumulative incidence of composite outcomes associated with lifestyle-related diseases. Results: The numbers of subjects for the analyses were 8,977 in the intervention group and 6,733 in the usual care group. Among them, 6,758 had hypertension, 2,147 had diabetes, 2,861 had dyslipidemia, and 1,221 had proteinuria in the intervention group, with corresponding numbers of 4,833, 1,517, 2,262, and 845, respectively, in the usual care group. There were no material differences in mean levels and proportions of major cardiovascular risk factors between the two groups. Conclusions: We expect to provide scientific evidence on the effectiveness of health counselling.

Background Lifetime risk is an informative estimate for driving lifestyle and behavioral changes especially for young adults. The impact of composite risk factors for cardiovascular disease on lifetime risk stratified by sex has not been investigated in the Japanese population, which has a much lower mortality of coronary heart disease compared with the Western population. We aimed to estimate lifetime risk of death from cardiovascular disease attributable to traditional risk factors. Methods and Results We analyzed pooled individual data from the Evidence for Cardiovascular Prevention from Observational Cohorts in a Japanese cohort study. A modified Kaplan–Meier approach was used to estimate the remaining lifetime risk of cardiovascular death. In total, 41 002 Japanese men and women with 537 126 person‐years of follow‐up were included. The lifetime risk at the index‐age of 45 years for those with optimal risk factors (total cholesterol

Background This study compared the clinical outcomes of transcatheter (TAVR) and surgical (SAVR) aortic valve replacements, focusing on postoperative valvular performance assessed by echocardiography. Method and Results A total of 425 patients who underwent TAVR (230 patients) or SAVR (195 patients) were included. Postoperative effective orifice area index (EOAI) was higher in the TAVR group (1.27 ± 0.35 cm2/m2) than in the SAVR group (1.06 ± 0.27 cm2/m2, p < 0.001), and patient–prosthesis mismatch (PPM) was more frequent in the SAVR group (22.6%) than in the TAVR group (8.7%, p < 0.001). Mild or greater paravalvular leakage (PVL) was more frequent in the TAVR group (21.3%) than in the SAVR group (0%, p < 0.001). Moreover, there was no difference in freedom from all-cause death, stroke, or rehospitalization between the groups. Patients with moderate or greater PPM (EOAI < 0.85 cm2/m2) had lower freedom from composite events than those without this PPM criterion (p = 0.008). Patients with mild or greater PVL also had lower freedom from composite events than those without this PVL criterion (p = 0.017). Conclusions Postoperative valvular performance of TAVR was superior to that of SAVR in terms of EOAI. This merit was counterbalanced by the significantly lower rates of PVL in patients who underwent SAVR. The overall clinical outcomes were similar between the study groups.

Background: Annually, more than 1.2 million deaths due to road traffic accidents occur worldwide. Although previous studies have examined the association between cigarette smoking and injury death, the mortality outcome often included non-traffic accident-related deaths. This study aimed to examine the association between cigarette smoking and traffic accident death. Methods: We conducted a prospective cohort study using data from the Ibaraki Prefectural Health Study conducted from 1993 through 2013. The cohort included 97,078 adults (33,138 men and 63,940 women) living in Ibaraki Prefecture who were aged 40–79 years at an annual health checkup in 1993. We divided participants into four smoking status groups: non-smokers, ex-smokers, and current smokers who smoked

Background. The role of central sensitization in refractory pain-related diseases has not yet been clarified. Methods. We performed a multicenter case-controlled study including 551 patients with various neurological, psychological, and pain disorders and 5,188 healthy controls to investigate the impact of central sensitization in these patients. Symptoms related to central sensitization syndrome (CSS) were assessed by the Central Sensitization Inventory (CSI) parts A and B. Patients were categorized into 5 groups based on CSI-A scores from subclinical to extreme. The Brief Pain Inventory (BPI), addressing pain severity and pain interference with daily activities, and the Patient Health Questionnaire (PHQ)-9, assessing depressive symptoms, were also administered. Results. CSI-A scores and CSI-B disease numbers were significantly greater in patients than in controls (p

Background: Chronic kidney disease (CKD) measures (estimated glomerular filtration rate [eGFR] and albuminuria) are frequently assessed in clinical practice and improve the prediction of incident cardiovascular disease (CVD), yet most major clinical guidelines do not have a standardized approach for incorporating these measures into CVD risk prediction. “CKD Patch” is a validated method to calibrate and improve the predicted risk from established equations according to CKD measures. Methods: Utilizing data from 4,143,535 adults from 35 datasets, we developed several “CKD Patches” incorporating eGFR and albuminuria, to enhance prediction of risk of atherosclerotic CVD (ASCVD) by the Pooled Cohort Equation (PCE) and CVD mortality by Systematic COronary Risk Evaluation (SCORE). The risk enhancement by CKD Patch was determined by the deviation between individual CKD measures and the values expected from their traditional CVD risk factors and the hazard ratios for eGFR and albuminuria. We then validated this approach among 4,932,824 adults from 37 independent datasets, comparing the original PCE and SCORE equations (recalibrated in each dataset) to those with addition of CKD Patch. Findings: We confirmed the prediction improvement with the CKD Patch for CVD mortality beyond SCORE and ASCVD beyond PCE in validation datasets (Δc-statistic 0.027 [95% CI 0.018–0.036] and 0.010 [0.007–0.013] and categorical net reclassification improvement 0.080 [0.032–0.127] and 0.056 [0.044–0.067], respectively). The median (IQI) of the ratio of predicted risk for CVD mortality with CKD Patch vs. the original prediction with SCORE was 2.64 (1.89–3.40) in very high-risk CKD (e.g., eGFR 30–44 ml/min/1.73m2 with albuminuria ≥30 mg/g), 1.86 (1.48–2.44) in high-risk CKD (e.g., eGFR 45–59 ml/min/1.73m2 with albuminuria 30–299 mg/g), and 1.37 (1.14–1.69) in moderate risk CKD (e.g., eGFR 60–89 ml/min/1.73m2 with albuminuria 30–299 mg/g), indicating considerable risk underestimation in CKD with SCORE. The corresponding estimates for ASCVD with PCE were 1.55 (1.37–1.81), 1.24 (1.10–1.54), and 1.21 (0.98–1.46). Interpretation: The “CKD Patch” can be used to quantitatively enhance ASCVD and CVD mortality risk prediction equations recommended in major US and European guidelines according to CKD measures, when available. Funding: US National Kidney Foundation and the NIDDK.

ObjectivesThere have been no longitudinal surveys on the changes in 25-hydroxyvitamin D [25(OH)D] while considering hemodilution factors among pregnant Japanese women. Therefore, we examined 25(OH)D levels as well as red blood cell count (RBC), hemoglobin (Hb), and Hematocrit (Hct) at the three trimesters among pregnant Japanese women to determine the distribution of serum 25(OH)D levels and the influence of hemodilution.DesignThis was a longitudinal study.SettingThe study was conducted at Ibaraki Seinan Medical Center Hospital in Japan.ParticipantsThe participants comprised 50 women in the first trimester with singleton pregnancies and without any complications.Outcome measuresParticipants were recruited from June to August 2018, and followed up till their postpartum period. Blood samples were collected at the first, second, and third trimesters, i.e., at 4-15, 16-27, and 28-39 weeks, respectively. 25(OH)D levels, RBC, Hb, and Hct were analyzed across the three trimesters.ResultsComparing the first, second, and third trimesters, 25(OH)D, RBC, and Hb were significantly declined in the second and third trimesters (p < 0.001). According to Spearman's correlation coefficient with 25(OH)D and RCB, Hb, Hct, significant correlations were found between 25(OH)D and Hb (p < 0.001), as well as Hct (p < 0.001) in the third trimester.ConclusionsThe present study had two major findings. First, it showed that the vitamin D status of most pregnant Japanese women were considered as vitamin D deficient. Second, the maternal serum 25(OH)D levels, RBC, Hb, and Hct of the pregnant women declined in the second and third trimesters. Thus we propose to have routine screening of vitamin D status of pregnant women, especially in the second trimester.

Background: The aim of this study was to examine the attribution of each cardiovascular risk factor in combination with abdominal obesity (AO) on Japanese health expenditures. Methods: The health insurance claims of 43,469 National Health Insurance beneficiaries aged 40–75 years in Ibaraki, Japan, from the second cohort of the Ibaraki Prefectural Health Study were followed-up from 2009 through 2013. Multivariable health expenditure ratios (HERs) of diabetes mellitus (DM), high low-density lipoprotein cholesterol (LDL-C), low high-density lipoprotein cholesterol (HDL-C), and hypertension with and without AO were calculated with reference to no risk factors using a Tweedie regression model. Results: Without AO, HERs were 1.58 for DM, 1.06 for high LDL-C, 1.27 for low HDL-C, and 1.31 for hypertension (all P < 0.05). With AO, HERs were 1.15 for AO, 1.42 for DM, 1.03 for high LDL-C, 1.11 for low HDL-C, and 1.26 for hypertension (all P < 0.05, except high LDL-C). Without AO, population attributable fractions (PAFs) were 2.8% for DM, 0.8% for high LDL-C, 0.7% for low HDL-C, and 6.5% for hypertension. With AO, PAFs were 1.0% for AO, 2.3% for DM, 0.4% for low HDL-C, and 5.0% for hypertension. Conclusions: Of the obesity-related cardiovascular risk factors, hypertension, independent of AO, appears to impose the greatest burden on Japanese health expenditures.

ObjectivesNeonicotinoid insecticides are widely used systemic pesticides with nicotinic acetylcholine receptor agonist activity that are a concern as environmental pollutants. Neonicotinoids in humans and the environment have been widely reported, but few studies have examined their presence in fetuses and newborns. The objective of this study is to determine exposure to neonicotinoids and metabolites in very low birth weight (VLBW) infants.MethodsAn analytical method for seven neonicotinoids and one neonicotinoid metabolite, N-desmethylacetamiprid (DMAP), in human urine using LC-ESI/MS/MS was developed. This method was used for analysis of 57 urine samples collected within 48 hours after birth from VLBW infants of gestational age 23-34 weeks (male/female = 36/21, small for gestational age (SGA)/appropriate gestational age (AGA) = 6/51) who were admitted to the neonatal intensive care unit of Dokkyo Hospital from January 2009 to December 2010. Sixty-five samples collected on postnatal day 14 (M/F = 37/22, SGA/AGA = 7/52) were also analyzed.ResultsDMAP, a metabolite of acetamiprid, was detected in 14 urine samples collected at birth (24.6%, median level 0.048 ppb) and in 7 samples collected on postnatal day 14 (11.9%, median level 0.09 ppb). The urinary DMAP detection rate and level were higher in SGA than in AGA infants (both pConclusionThese results provide the first evidence worldwide of neonicotinoid exposure in newborn babies in the early phase after birth. The findings suggest a need to examine potential neurodevelopmental toxicity of neonicotinoids and metabolites in human fetuses.

Background: Because of the increasing number of mothers who continue to work after childbirth, participation in childcare has diversified. However, the impact of the main caregiver on children’s habits has not been determined. We sought to examine the effect of caregiver differences on childhood habituation of between-meal eating and body mass index (BMI). Methods: The Ibaraki Children’s Cohort Study involved 4592 Japanese children whose parents answered health questionnaires at age 3. Follow-up questionnaires were distributed to parents when children were 6 and 12 years old and to study subjects directly when they were 22 years old. We compared prevalence of between-meal eating and overweight as well as mean BMI at ages 6, 12, and 22 years, by their main daytime caregiver at age 3. Results: Compared to children cared for by mothers, those cared for by grandparents had a higher prevalence of between-meal eating before dinner for boys and girls at ages 6 and 12 years. At age 22 years, boys cared for by grandparents had a higher prevalence of overweight than those cared for by mothers (18.5% versus 11.2%, P = 0.037), but no such difference was noted in girls. However, both boys and girls cared for by grandparents had higher mean BMI over time than those cared for by mothers (coefficient = 0.47 kg/m2 for boys and coefficient = 0.35 kg/m2 for girls). Conclusions: Being cared for by grandparents at age 3 was associated with subsequent between-meal eating habits, being overweight, and increased mean BMI from childhood to adulthood.

BACKGROUND:Patients with renal impairment are at risk of not only end-stage kidney disease but also cardiovascular disease (CVD). The current definition of CKD stage G3a is eGFR 45-59 ml/min/1.73 m2 and of G3b is 30-44 ml/min/1.73 m2, and subjects in the CKD 3a category are considered to be at lower risk of mortality than are those in CKD 3b. METHODS:We evaluated the outcome of 97,043 people (33,131 men and 63,912 women) living in Ibaraki Prefecture who underwent annual community-based health checkups beginning in 1993 at age 40-80 years and who were followed for a mean of 17.1 years. RESULTS:The number of all-causes deaths was 20,534 (10,375 men and 10,159 women), of which 5,995 (2,695 men and 3,300 women) were deaths due to CVD. Multivariable-adjusted hazard ratio for CVD death in the eGFR 45-49 ml/min/1.73 m2 category was significantly increased (1.82; 95% confidential interval, 1.23-2.69) in non-elderly men, whereas all-cause mortality and CVD mortality in elderly men with eGFR 45-49 ml/min/1.73m2 were non significant. In contrast, both in non-elderly women and in elderly women with eGFR 45-49 ml/min/1.73 m2 showed small, but significant, increases in the risks of all-cause mortality and CVD. CONCLUSIONS:We demonstrated proportionate increases in mortality with decreasing eGFR in a Japanese CKD population. Like patients in the CKD G3b subgroup, non-elderly men and women with an eGFR of 45-49 ml/min/1.73 m2 (i.e. a part of CKD G3a) are at considerable risk of CVD mortality. Age dependent and eGFR dependent finer risk recognition were required for CVD prevention in clinical practice with regard to CKD patients.

BackgroundTobacco smoking is a major risk factor for many diseases. We sought to quantify the burden of tobacco-smoking-related deaths in Asia, in parts of which men's smoking prevalence is among the world's highest.Methods and findingsWe performed pooled analyses of data from 1,049,929 participants in 21 cohorts in Asia to quantify the risks of total and cause-specific mortality associated with tobacco smoking using adjusted hazard ratios and their 95% confidence intervals. We then estimated smoking-related deaths among adults aged ≥45 y in 2004 in Bangladesh, India, mainland China, Japan, Republic of Korea, Singapore, and Taiwan-accounting for ∼71% of Asia's total population. An approximately 1.44-fold (95% CI = 1.37-1.51) and 1.48-fold (1.38-1.58) elevated risk of death from any cause was found in male and female ever-smokers, respectively. In 2004, active tobacco smoking accounted for approximately 15.8% (95% CI = 14.3%-17.2%) and 3.3% (2.6%-4.0%) of deaths, respectively, in men and women aged ≥45 y in the seven countries/regions combined, with a total number of estimated deaths of ∼1,575,500 (95% CI = 1,398,000-1,744,700). Among men, approximately 11.4%, 30.5%, and 19.8% of deaths due to cardiovascular diseases, cancer, and respiratory diseases, respectively, were attributable to tobacco smoking. Corresponding proportions for East Asian women were 3.7%, 4.6%, and 1.7%, respectively. The strongest association with tobacco smoking was found for lung cancer: a 3- to 4-fold elevated risk, accounting for 60.5% and 16.7% of lung cancer deaths, respectively, in Asian men and East Asian women aged ≥45 y.ConclusionsTobacco smoking is associated with a substantially elevated risk of mortality, accounting for approximately 2 million deaths in adults aged ≥45 y throughout Asia in 2004. It is likely that smoking-related deaths in Asia will continue to rise over the next few decades if no effective smoking control programs are implemented. Please see later in the article for the Editors' Summary.

BACKGROUND: The proportion of Japanese workers experiencing intense worry or stress during working life is in excess of 60%, and the incidence of psychiatric disorders and suicide due to psychological burden from work duties is increasing. To confirm whether the stress response measured by the Brief Job Stress Questionnaire (BJSQ) can identify risk for depression, a cohort study was conducted to evaluate whether the stress response measured by BJSQ was associated with the onset of depression. METHODS: A total of 1,810 participants aged 20-70 years in 2005 completed the stress response of the BJSQ and were followed-up until August, 2007 by examining sick pay records. Depression was defined by a description in sick pay records that included "depression" or "depressive symptoms" as a reason for sick leave according to a physician's medical certificate. The participants were divided into quartiles (Ql, Q2, Q3, and Q4) according to the total stress response score of BJSQ at baseline. Furthermore, the participants were divided into a higher score category (Q4) and a lower score category (Q1-Q3). Risk ratios of the stress response of the BJSQ for onset of depression were calculated using a multivariable Cox proportional hazard model. RESULTS: Among 1,810 participants, 14 developed depression during a mean of 1.8 years of follow-up. The risk ratio was 2.96 (95% confidence interval [CI], 1.04-8.42, p for trend = 0.002) when the higher stress response score category of BJSQ was compared with the low stress response score category for sick leave due to depression. After adjusting for gender, age, marital status, and having children, the risk ratios were similar to no adjustment. CONCLUSIONS: These findings suggest that the stress response measured by the BJSQ can demonstrate risk for the onset of depression.

The occurrence of diabetes has greatly increased in low- and middle-income countries, particularly in Asia, as has the prevalence of overweight and obesity; in European-derived populations, overweight and obesity are established causes of diabetes. The shape of the association of overweight and obesity with diabetes risk and its overall impact have not been adequately studied in Asia.A pooled cross-sectional analysis was conducted to evaluate the association between baseline body mass index (BMI, measured as weight in kg divided by the square of height in m) and self-reported diabetes status in over 900,000 individuals recruited in 18 cohorts from Bangladesh, China, India, Japan, Korea, Singapore and Taiwan. Logistic regression models were fitted to calculate cohort-specific odds ratios (OR) of diabetes for categories of increasing BMI, after adjustment for potential confounding factors. OR were pooled across cohorts using a random-effects meta-analysis. The sex- and age-adjusted prevalence of diabetes was 4.3% in the overall population, ranging from 0.5% to 8.2% across participating cohorts. Using the category 22.5-24.9 kg/m²) as reference, the OR for diabetes spanned from 0.58 (95% confidence interval [CI] 0.31, 0.76) for BMI lower than 15.0 kg/m² to 2.23 (95% CI 1.86, 2.67) for BMI higher than 34.9 kg/m². The positive association between BMI and diabetes prevalence was present in all cohorts and in all subgroups of the study population, although the association was stronger in individuals below age 50 at baseline (p-value of interaction

Dynamic changes in body weight have long been recognized as important indicators of risk for human health. Many population-based observational studies have shown that rapid weight gain during infancy, including a catch-up growth phenomenon or adiposity rebound in early childhood, predisposes a person to the development of obesity, type 2 diabetes, and cardiovascular diseases later in life. However, a consensus has not been established regarding which period of weight gain contributes to future risks. This review evaluates recent evidence on the relationship between early rapid growth and future obesity and cardiometabolic risk, with a focus on the differential significance of rapid weight gain in infancy and early childhood. Although there is a need for attention to childhood growth during early infancy before 1 yr of age as it may be related to future obesity, emerging evidence strongly suggests that toddlers showing an increase in body mass index (BMI) before 3 yr of age, a period normally characterized by decreased BMI, are prone to developing later cardiometabolic risk. [ABSTRACT FROM AUTHOR]

Objectives Hearing impairment is among the most significant health problems, and the number of adults with hearing impairment is increasing worldwide. Therefore, the prevention of hearing impairment is important. Proteinuria appears to be a risk factor for hearing impairment, but no prospective studies have examined the association between proteinuria and hearing impairment risk. This prospective study aimed to clarify the association between dipstick proteinuria and risk of hearing impairment. Design This was a prospective cohort study based on annual health check-up data, 2008–2016. Setting Data were collected on 7005 employees of a single company who worked in offices and factories throughout Japan. Participants We analysed data from 5699 subjects (88.6% men) who underwent annual health check-ups twice or more from 2008 to 2016, had no missing data, and were free from hearing impairment at baseline. We regarded the first health check-up as the baseline examination. Primary and secondary outcome measures Hearing tests were performed using audiometry at two frequencies (1 and 4 kHz) during the health check-ups. Defining total moderate hearing impairment as the inability to respond to 30 dB at 1 kHz and/or 40 dB at 4 kHz, we examined the association between dipstick proteinuria at baseline and risk of hearing impairment at final examination. Results Total moderate hearing impairment was noted in 162 (2.8%) subjects. Compared with subjects without proteinuria at baseline, the multivariable adjusted OR (95% CI) was 5.35 (1.87–15.25) for subjects with proteinuria ≥2+, 0.92 (0.40–2.13) for those with proteinuria +/−, and 1.33 (0.63–2.80) for those with proteinuria+ at baseline. Conclusions Severe dipstick proteinuria was positively associated with risk of hearing impairment in the future. Our results suggest that medical examinations including urine testing are effective for detecting subjects with high risk of hearing impairment. [ABSTRACT FROM AUTHOR]

In Japan, heart disease and cerebrovascular disease were the second and fourth leading cause of death, respectively in 2014. Hematocrit, the ratio of the red blood cells to the total volume of blood is known to play a role in cardiovascular diseases. However, the relationship between elevated hematocrit and the risk of cardiovascular disease based on sex has not been examined in Asian countries. We analyzed data from the Ibaraki Prefectural Health Study, a community-based large cohort study, which included 87,533 individuals, aged 40 to 79 years living in 38 municipalities of the Ibaraki Prefecture, who had completed an annual health checkup in 1993, and were followed until 2013. The hematocrit levels of the subjects were categorized into 5 quintiles (Q1-Q5), and hazard ratios for cause-specific mortality were calculated using the Cox proportional hazards regression models. Age and other cardiovascular risk factors were the covariates in the study. During the follow-up for a mean of 17.9 years, 1,207 deaths (615 men and 592 women) due to acute myocardial infarction (AMI) were reported in this population. The p values for the trend in the Q3-Q5 groups were 0.661 for men and 0.020 for women. Additionally, these values were significant in younger (40 to 59 years) women but not in older (60 to 79 years) women. This study is the flrst one to demonstrate an association between high hematocrit level and risk of AMI mortality in younger Japanese women, but not in men and older women. [ABSTRACT FROM AUTHOR]

Objectives Prevention of hearing impairment (HI) is important because recovery of hearing is typically difficult. Epidemiological studies have examined the risk factors for HI. However, the association between hypertension and HI remains unclear. We aimed to clarify the association between hypertension and HI. Design Cross-sectional study. Setting Japanese workers in an information and communication technologies company. Participants Of 24 823 employees of the same company, we recruited 13 475 participants who underwent hearing testing by audiometry in annual health check-ups and did not have missing data regarding body measurement, blood test results and drinking/smoking status (mean age: 49.4 years; males: 86.4%). Primary outcomes Hearing tests were performed at two frequencies (1 kHz, 4 kHz). We defined the inability of participants to respond to 30 dB at 1 kHz and/or 40 dB at 4 kHz as overall moderate HI. We also defined moderate HI at 1 or 4 kHz as an abnormal finding at 1 or 4 kHz. We defined hypertension as ≥140 mm Hg systolic blood pressure and/or ≥90 mm Hg diastolic blood pressure and/or taking medication for hypertension. We examined the association between hypertension and HI after adjusting for age, sex, body mass index, smoking/drinking status, diabetes mellitus, hyperlipidaemia and proteinuria. Results Moderate HI was identified in 980 participants (7.3%). Of these, 441 participants (3.3%) exhibited moderate HI at 1 kHz, and 787 participants (5.8%) exhibited moderate HI at 4 kHz. Subjects with hypertension showed a higher prevalence of any HI. The prevalence of overall moderate HI, moderate HI at 1 kHz and moderate HI at 4 kHz among subjects with hypertension was 8.7%, 4.3% and 6.8%, while those among subjects without hypertension was 6.9%, 3.0% and 5.6% (p<0.01, p<0.01 and p=0.01, respectively). Conclusions Hypertension was associated with moderate HI in Japanese workers. [ABSTRACT FROM AUTHOR]

Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is produced in response to tubular epithelial injury and is a biomarker of tubulointerstitial injury. The aim of the present study was to examine whether acute kidney injury (AKI) could be predicted by measuring uNGAL in very low-birth weight (VLBW) infants. Forty VLBW infants with birthweight below 1,500 g were enrolled in the present study. uNGAL and serum creatinine (sCre) were measured daily from postnatal days 0 to 8. Infants with sCre ≥1.2 mg/dl were diagnosed with AKI. The relationship of uNGAL with sCre was measured on the day after uNGAL measurement (next-day sCre) was examined. The results showed that 16 infants had sCre ≥1.2 mg/dl in this period. Logistic regression analysis revealed that uNGAL on postnatal days 2, 3, 4, 5 and 6 was correlated with next-day sCre (P<0.05). uNGAL corrected by urinary Cre (uCre) (uNGAL/uCre) was only correlated with an increase in next-day sCre on postnatal days 5 and 6 (P<0.05). For the logistic analysis, subjects with high and low uNGAL levels based on the median value for each day, uNGAL on postnatal days 2, 3 and 6 in the high uNGAL group was correlated with an increase in next-day sCre. Thus, AKI may be predicted by measuring uNGAL in VLBW infants. This measurement was non-invasive, and is potentially useful for the evaluation of renal function in VLBW infants. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to investigate the cumulative return to work (RTW) rate and to clarify the predictors of the time to full-time RTW (full RTW) and resignation among Japanese stroke survivors, within the 365-day period following their initial day of sickness absence due to stroke. Setting: This study was based on tertiary prevention of occupational health in large-scaled Japanese companies of various industries. Participants: The participants in this study were 382 Japanese workers who experienced an episode of sickness leave due to clinically certified stroke diagnosed between 1 January 2000 and 31 December 2011. Data were obtained from an occupational health register. Participants were followed up for 365 days after the start day of the first sickness absence. The cumulative RTW rates by Kaplan-Meier estimates and predictors for time to full RTW and resignation by Cox regression were calculated. Results: A total of 382 employees had their first sickness absence due to stroke during the 12-year follow-up period. The cumulative full RTW rates at 60, 120, 180 and 365 days were 15.1%, 33.6%, 43.5% and 62.4%, respectively. Employees who took sick leave due to cerebral haemorrhage had a longer time to full RTW (HR, 0.50; 95% CI 0.36 to 0.69) than those with cerebral infarction. Older employees (over 50 years of age) demonstrated a shorter time to resignation than younger employees (HR, 3.30; 95% CI 1.17 to 9.33). Manual workers had a longer time to resignation than non-manual workers (HR, 0.24; 95% CI 0.07 to 0.78). Conclusions: Cumulative RTW rates depended on the subtype of stroke, and older age was a predictor of resignation. [ABSTRACT FROM AUTHOR]

Aims The long-term prognosis of subjects with supraventricular premature complexes (SVPCs) remains unclear in the general population. The aim of this study was to examine the prognostic significance of SVPCs in community-based health checkups. Methods and results We assessed 63 197 individuals (mean age, 58.8±9.9 years; 67.6%women)whoparticipated in annual community-based health checkups in 1993 and were followed until 2008. The primary endpoint was stroke death, cardiovascular death (CVD), or all-cause death during a 14-year mean follow-up, and the secondary endpoint was first atrial fibrillation (AF) event in subjects without self-reported heart diseases or AF at baseline. Compared with subjects without SVPCs, the multivariate-adjusted hazard ratios (HRs) [95% confidence interval (CI)] of stroke death, CVD, and allcause death in subjects with SVPCs were 1.24 (0.98–1.56) for men and 1.63 (1.30–2.05) for women, 1.22 (1.04– 1.44) for men and 1.48 (1.25–1.74) for women, and 1.08 (0.99–1.18) for men and 1.21 (1.09–1.34) for women, respectively. Atrial fibrillation occurred in 386 subjects during the follow-up (1.05/1000 person-years). The presence of SVPCs at baseline was the significant predictor of AF onset [HRs (95% CI): 4.87 (3.61–6.57) for men and 3.87 (2.69–5.57) for women]. Propensity score matched analyses also revealed the presence of SVPCs was significantly associated with increased risks of AF incidence and CVD even after adjusting the potential confounders. Conclusion The presence of SVPCs in 12-lead electrocardiograms was a strong predictor of AF development, and associated with increased risk of CVD in general population. [ABSTRACT FROM AUTHOR]

To elucidate the effect of early growth patterns on the metabolic sensitivity to adiposity, we examined the relationship between the homeostatic model assessment of insulin resistance (HOMA-IR) and body mass index (BMI) levels at 12 years of age in 101 boys and 91 girls in a birth cohort. Children with an increase in BMI from the ages of 1.5 to 3 years exhibited a greater increase of HOMAIR per BMI increase at 12 years of age compared to those with a decrease in BMI or stable BMI from 1.5 to 3 years. This suggests that children who show an increase in BMI from 1.5 to 3 years, a period normally characterized by a decreased or stable BMI, are more prone to developing insulin resistance at 12 years of age. [ABSTRACT FROM AUTHOR]