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Small cell lung carcinoma (SCLC) and pulmonary large cell neuroendocrine carcinoma (LCNEC) are both classified as lung neuroendocrine carcinoma (NEC). It has recently been reported that the special AT-rich sequence-binding protein 2 (STAB2), known as a colorectal cancer marker, is also expressed in NECs occurring in various organs including the lung. However, few studies have examined any differences of SATB2 immunopositivity between SCLC and LCNEC. We investigated SATB2 expression in 45 SCLC and 14 LCNEC cases using immunohistochemistry as well as the expression of caudal-type homeobox 2 (CDX2) and keratin (KRT) 20. The LCNEC cases were more frequently positive for SATB2 (ten out of 14, 71%) than the SCLC ones (seventeen out of 45, 38%) with a statistically significance (P = 0.035). Furthermore, two LCNEC cases were positive for CDX2 while no positive findings were observed for any SCLC cases, the difference of which, however, was not statistically significant (P = 0.053). KRT20 was negative in all LCNEC and SCLC cases. These results require our attention when we use SATB2 and CDX2 as colorectal cancer markers because their expression in pulmonary NECs can lead to a misdiagnosis that the tumor is of metastatic colorectal adenocarcinoma, especially when the patient has a past history of colorectal cancer. Analyzing the relationship between the demographic/clinical variables and the SATB2 expression in the SCLC cases, just high Brinkman index (≥ 600) was significantly related to the positivity of SATB2 (P = 0.017), which is interesting considering the strong relationship between SCLC and smoking.

Historically, a right bundle branch block has been considered a benign finding in asymptomatic individuals. However, this conclusion is based on a few old studies with small sample sizes. We examined the association between a complete right bundle branch block (CRBBB) and subsequent cardiovascular mortality in the general population in Japan. In this large community-based cohort study, data of 90,022 individuals (mean age, 58.5 ± 10.2 years; 66.2% women) who participated in annual community-based health check-ups were assessed. Subjects were followed up from 1993 to the end of 2016. Cox proportional hazards’ models and log-rank tests were used for the data analysis. CRBBB was documented in 1,344 participants (1.5%). Among all included participants, CRBBB was associated with an increased risk of cardiovascular mortality after adjustment for all potential confounders (hazard ratio [HR] 1.21; 95% confidence interval [CI] 1.06–1.38). The increased risk of cardiovascular mortality was particularly evident in women aged

AIM: To examine the association between long-term exposure to suspended particulate matter (SPM) and cardiovascular mortality in Japan after controlling for known major confounding factors among a large middle and elderly cohort study in Ibaraki Prefecture, Japan. METHODS: We followed 91,808 residents (men 34%) who undertook a national health check-up at age 40-79 years for 17 years (1993-2010). Two different exposure indices were adopted: baseline SPM concentration (in the year 1990) and average SPM concentration for the first (average of 1990 and 1995) and the second half (average of 2005 to 2009) of the study period. Sex-specific adjusted risk ratios (RRs) for cardiovascular mortality were calculated using general mixed Poisson regression models after adjusting the age, BMI, history of diabetes mellitus and hypertension, creatinine, glutamic pyruvic transaminase, total cholesterol, high-density lipoprotein cholesterol, smoking, alcohol, and temperature. The variation between seven medical administration areas was also taken into account as a random effect. RESULTS: Baseline SPM concentration was associated with an increased risk of mortality from all cardiovascular diseases, coronary artery disease, and stroke. The adjusted RRs (95% confidence interval [CI]) per 10 µg/m3 increase in SPM concentration for all cardiovascular mortality were 1.147 (1.014-1.300) for men and 1.097 (0.985-1.222) for women. The point estimate of RR was highest for non-hemorrhagic stroke in men (1.248 [0.991-1.571]), although CI overlapped the unity. The RRs seemed slightly lower in the second half than in the first half, though the CIs widened in the second half. CONCLUSION: Our results suggest that long-term exposure to SPM is associated with an increased risk of all cardiovascular mortality for men in Ibaraki, Japan.

Aim: The association between atrial fibrillation (AF) and risk of stroke mortality among men and women without traditional cerebrocardiovascular risk factors (TCVRFs) is unclear. This study aimed to determine whether AF was a risk factor for stroke and total cardiovascular disease mortality among individuals without TCVRFs. Methods: A total of 90,629 Japanese subjects from the Ibaraki Prefectural Health Study aged 40–79 years, with and without TCVRFs, were studied from 1993 to 2013. Hazard ratios (HRs) were calculated using the Cox proportional hazard regression model stratified by sex and the presence of TCVRFs. Covariates were age, systolic blood pressure, anti-hypertensive medication use, and serum total cholesterol levels. A standard 12-lead electrocardiogram at rest was used to screen AF. Cause-specific mortality was classified according to the International Classification of Disease code. Results: Compared with participants without AF, multivariable-adjusted hazard ratios (with 95% confidence intervals) for stroke mortality among participants without TCVRFs were 4.3 (1.1–17.8) and 15.0 (5.5–40.8) for men and women with AF, respectively. HRs for total cardiovascular disease mortality were 6.2 (2.8–14.2) for men and 10.7 (4.8–24.1) for women. For participants with TCVRFs, multivariable-adjusted HRs for stroke mortality were 3.1 (2.2–4.6) and 4.3 (2.6–7.3), whereas HRs for total cardiovascular disease mortality were 2.9 (2.2–3.8) and 3.5 (2.4–5.1) for men and women, respectively. Conclusions: AF was found to be an independent risk factor for stroke and total cardiovascular mortality even in individuals without other TCVRFs.

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.

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 0.05). The relationship between CSS and age 20 and 59 years, ex-smokers, coffee intake, and alcohol intake differed by sex. The prevalence of CSS was estimated to be low in the healthy population. CSS correlated with CSS-related diseases and some positive and negative factors.

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 Conclusions The magnitude and the number of risk factors were progressively associated with increased lifetime risk even in individuals in early adulthood who tend to have low short‐term risk. The degree of established cardiovascular risk factors can be converted into lifetime risk. Our findings may be useful for risk communication in the early detection of future cardiovascular disease risk.

In right-handed patients with idiopathic rapid eye movement sleep behavior disorder (IRBD) or Parkinson's disease (PD), dopamine transporter (DAT) single-photon emission computed tomography (SPECT) shows a predominant nigrostriatal deficit in the left striatum. To confirm this hypothesis, we longitudinally investigated whether the nigrostriatal function is asymmetric in Japanese patients with IRBD.In 91 polysomnography-confirmed IRBD patients, which included 87 right-handed IRBD patients who underwent 33 repeat DAT-SPECT scans, we retrospectively examined the striatal dopaminergic terminals in each hemisphere using DAT-SPECT. We calculated the values of interhemispheric laterality index for the right and left sides.The proportion of IRBD patients with lower SBR in the striatum was different between the left (n = 60, 69.0%) and right (n = 27, 31.0%) hemispheres. In the repeat DAT-SPECT scan (n = 33), the rate of decline in the striatum was greater on the left than on the right side, and the proportion of patients with lower decline rates in the left striatum (n = 25, 73.5%) was greater than the that in the right striatum (n = 3, 8.8%). The proportion of lower SBR side at baseline did not predict the development of PD or DLB.Right-handed IRBD patients have asymmetric nigrostriatal dopaminergic function, as evidenced by the faster estimated rate of decline for the left striatum than the right striatum. The left-right hemispheric striatal predominance of the nigrostriatal deficit in the right-handed prodromal PD or DLB patients represents a difference in the early pathological process of the disease.

Aim Diabetes mellitus and hypertriglyceridemia may adversely interact with the development of ischemic cardiovascular disease, but epidemiological evidence on this issue is scarce. We hypothesized that the impact of hypertriglyceridemia on ischemic cardiovascular disease (ischemic heart disease and ischemic stroke) would differ according to the presence or absence of diabetes mellitus and tested our a priori hypothesis under a large population-based prospective study. Methods A total of 90,468 men and women aged 40-79 years in 1993 were enrolled in the Ibaraki Prefectural Health Study (IPHS), a community-based cohort study of Japanese. The participants' serum triglyceride levels (mostly nonfasting) were measured every 5 years, and the participants were followed up for mortality from ischemic cardiovascular disease through 2016. Hazard ratios (95% confidence intervals) were calculated according to 5-year updated triglyceride levels (＜100, 100-149, 150-199, 200-299, and ≥ 300 mg/dl). Results During 1,795,877 person-years, there were 3,323 deaths from ischemic cardiovascular diseases (1,968 ischemic heart diseases and 1,355 ischemic strokes). We found no association between triglyceride levels and the risk of mortality from ischemic cardiovascular disease after adjustment for known cardiovascular risk factors. However, when stratified by the presence or absence of diabetes mellitus, excess mortality from ischemic cardiovascular disease appeared among participants with diabetes mellitus with triglyceride levels of ≥ 300 mg/dl. Further adjustment for high-density lipoprotein-cholesterol attenuated the association toward being statistically nonsignificant. Conclusion The impact of high serum triglyceride levels on the risk of ischemic cardiovascular disease mortality was confined to participants with diabetes mellitus.

Background The gold standard for diagnosis of cutaneous sporotrichosis involves the isolation of the fungus, Sporothrix, by a culture test. Generally, the sampling for the culture test is performed at the same time as skin biopsy under local anaesthesia. However, the culture test may occasionally return a false negative result. Objective The aim of our study was to investigate the diagnostic value of a molecular method for diagnosing cutaneous sporotrichosis from formalin-fixed and paraffin-embedded (FFPE) tissues. Methods Over a 30-year period, we collected 52 cases of cutaneous sporotrichosis from biopsied specimens that had been positively diagnosed by a culture test. A nested PCR specific for Sporothrix detection was applied using FFPE tissue as template. The results were compared with control samples from 79 patients diagnosed with other cutaneous diseases according to histopathological, clinical findings and a cutler test. Results Of the 52 patients who were tested positive on the culture test, all cutaneous diseases were detected by PCR. Of the 59 patients in the control group, 58 tested negative by PCR. Under our conditions, the calculated sensitivity of this method was 100%, the specificity was 98.7% and the kappa coefficient was 0.984 (95% CI: 0.953-1.000). Conclusions The specific PCR assay used appears to be a useful tool for the prompt and accurate diagnosis of sporotrichosis. Using this method, it would be possible to diagnose cutaneous sporotrichosis for patients who were suspected of cutaneous sporotrichosis but tested negative on culturing, and for pathologically suspected cutaneous sporotrichosis patients for whom the culture test was not undertaken.

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 first 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.

Objectives Adiposity rebound (AR) refers to an increase in body mass index (BMI) after a nadir. Early AR, in which AR occurs earlier than five years old, is a risk factor for future obesity and metabolic syndrome, but has not been widely studied in very-low-birth-weight infants (VLBWIs). Methods The subjects were VLBWIs born in Dokkyo Medical University NICU from January 2008 to December 2010. Height and weight measured at birth and at intervals until seven years old were obtained from medical records. The lowest BMI after one year of age was used for the age of AR. The subjects were divided into those with early and normal AR ( Results There were 38 early AR cases and 62 normal AR cases, giving a prevalence of early AR similar to that in infants with normal birth weight. BMI percentile at age seven years was significantly higher in early AR cases than in normal AR cases (44.6 [IQR: 21.0–79.2] vs. 14.4 [IQR: 3.8–40.8] kg/m2). Changes in BMI were also significantly higher in early AR cases (p=0.024 by ANOVA). Conclusions Early AR in VLBWIs is a predictor of future obesity.

Objectives This study aimed to compare the short-term outcomes of transcatheter and surgical aortic valve replacements (TAVR and SAVR) in high-, intermediate-, and low-preoperative risk patients. Methods A total of 454 patients who underwent TAVR or SAVR were included. Patients were categorized into high-, intermediate-, and low-risk according to the Society of Thoracic Surgery-Predicted Risk of Mortality score and clinical outcomes were compared between TAVR and SAVR groups. Results TAVR was less invasive, with less bleeding and transfusion (p p p p = 0.003) and pressure gradient (p p p p Conclusions TAVR was superior to SAVR in the sense of less invasiveness and valvular function. However, the indication of TAVR in low-risk patients should be carefully discussed, because paravalvular leakage was a risk factor for short-term mortality.

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 < 0.001 ). Medium effect sizes (r = 0.37) for CSI-A scores and large effect sizes (r = 0.64) for CSI-B disease numbers were found between patients and control groups. Compared with the CSI-A subclinical group, the CSI-A mild, moderate, severe, and extreme groups had significantly higher BPI pain interference and severity scores, PHQ-9 scores, and CSS-related disease numbers based on ANCOVA. Greater CSI-B numbers resulted in higher CSI-A scores ( p < 0.001 ) and a higher odds ratio ( p for trend

AIM: Lifetime risk (LTR) indicates the absolute risk of disease during the remainder of an individual's lifetime. We aimed to assess the LTRs for coronary heart disease (CHD) mortality associated with blood pressure (BP) and total cholesterol levels in an Asian population using a meta-analysis of individual participant data because no previous studies have assessed this risk. METHODS: We analyzed data from 105,432 Japanese participants in 13 cohorts. Apart from grade 1 and 2-3 hypertension groups, we defined "normal BP" as systolic/diastolic BP ＜130/＜80 mmHg and "high BP" as 130-139/80-89 mmHg. The sex-specific LTR was estimated while considering the competing risk of death. RESULTS: During the mean follow-up period of 15 years (1,553,735 person-years), 889 CHD deaths were recorded. The 10-year risk of CHD mortality at index age 35 years was ≤ 0.11%, but the corresponding LTR was ≥ 1.84%. The LTR of CHD at index age 35 years steeply increased with an increase in BP of participants with high total cholesterol levels [≥ 5.7 mmol/L (220 mg/dL)]. This risk was 7.73%/5.77% (95% confidence interval: 3.53%-10.28%/3.83%-7.25%) in men/women with grade 2-3 hypertension and high total cholesterol levels. In normal and high BP groups, the absolute differences in LTRs between the low and high total cholesterol groups were ≤ 0.25% in men and ≤ 0.40% in women. CONCLUSIONS: High total cholesterol levels contributed to an elevated LTR of CHD mortality in hypertensive individuals. These findings could help guide high-risk young individuals toward initiating lifestyle changes or treatments. ispartof: JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS vol:28 issue:1 pages:6-24 ispartof: location:Japan status: published

IMPORTANCE Early identification of individuals at elevated risk of developing chronic kidney disease (CKD) could improve clinical care through enhanced surveillance and better management of underlying health conditions.OBJECTIVE To develop assessment tools to identify individuals at increased risk of CKD, defined by reduced estimated glomerular filtration rate (eGFR).DESIGN, SETTING, AND PARTICIPANTS Individual-level data analysis of 34 multinational cohorts from the CKD Prognosis Consortium including 5 222 711 individuals from 28 countries. Data were collected from April 1970 through January 2017. A 2-stage analysis was performed, with each study first analyzed individually and summarized overall using a weighted average. Because clinical variables were often differentially available by diabetes status, models were developed separately for participants with diabetes and without diabetes. Discrimination and calibration were also tested in 9 external cohorts (n = 2 253 540).EXPOSURES Demographic and clinical factors.MAIN OUTCOMES AND MEASURES Incident eGFR of less than 60 mL/min/1.73 m(2).RESULTS Among 4 441 084 participants without diabetes (mean age, 54 years, 38% women), 660 856 incident cases (14.9%) of reduced eGFR occurred during a mean follow-up of 4.2 years. Of 781 627 participants with diabetes (mean age, 62 years, 13% women), 313 646 incident cases (40%) occurred during a mean follow-up of 3.9 years. Equations for the 5-year risk of reduced eGFR included age, sex, race/ethnicity, eGFR, history of cardiovascular disease, ever smoker, hypertension, body mass index, and albuminuria concentration. For participants with diabetes, the models also included diabetes medications, hemoglobin A(1c), and the interaction between the 2. The risk equations had a median C statistic for the 5-year predicted probability of 0.845 (interquartile range [IQR], 0.789-0.890) in the cohorts without diabetes and 0.801 (IQR, 0.750-0.819) in the cohorts with diabetes. Calibration analysis showed that 9 of 13 study populations (69%) had a slope of observed to predicted risk between 0.80 and 1.25. Discrimination was similar in 18 study populations in 9 external validation cohorts; calibration showed that 16 of 18 (89%) had a slope of observed to predicted risk between 0.80 and 1.25.CONCLUSIONS AND RELEVANCE Equations for predicting risk of incident chronic kidney disease developed from more than 5 million individuals from 34 multinational cohorts demonstrated high discrimination and variable calibration in diverse populations. Further study is needed to determine whether use of these equations to identify individuals at risk of developing chronic kidney disease will improve clinical care and patient outcomes.

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.

Few studies have reported on the increase in cervical cancer incidence in Japan. We aimed to determine the relevant trends in the metropolitan regions of Japan and to identify the population with the highest risk, based on histological subtype, cancer stage, and diagnostic processes. Using population-based data (2009&ndash, 2013), we identified 2110 women, aged &ge, 20 years, with cervical cancer. We estimated the age-standardized and age-specific incidence rates of cervical cancer for the study period based on the 1985 national model population. The average annual percent change (AAPC) and 95% confidence interval (CI) were calculated using the joinpoint regression analysis. We stratified the analyses based on histological subtypes, stage, and diagnostic process via cancer screening. The increase in the overall age-standardized incidence was not significant. However, the increase was significant for women aged 30&ndash, 39 years (AAPC 20.0%/year, 95% CI: 9.9&ndash, 31.1), which was attributable to the increase in the incidence of the squamous cell carcinoma (SCC) subtype (AAPC 23.1%/year, 95% CI: 10.7&ndash, 36.8). Among younger women, aged &lt, 50 years, further stratification showed an increase in the undiagnosed early-stage SCC subtype via cancer screening. In Japan, the incidence of HPV-related cervical cancer has been increasing in undiagnosed younger women.

Objective To examine the association between the risk of postpartum hemorrhage (PPH) and poor uterine contractility, which is suggested by the characteristics of labor. Methods This case-control study used cases recorded in the Japan Perinatal Registry database during the period 2013-2016. After exclusion of women with specified known risk factors for PPH, we enrolled 174 082 primiparas who had a full-term live singleton vaginal birth. Participants were classified into four classes according to the diagnosis of abnormal labor patterns and use of uterotonics. χ2 tests were used to compare PPH cases with controls, and odds ratios (OR) were calculated by univariate and multivariate analyses. Results Among the enrolled women, 10 508 (6.0%) had PPH. Abnormal labor patterns were significantly associated with an increased risk of PPH. Compared with women without any abnormal labor patterns who had not used uterotonics, women with abnormal labor patterns were at a significantly increased risk for PPH regardless of whether they had used uterotonics (adjusted OR 1.23, 95% confidence interval [CI] 1.10-1.37) or not (adjusted OR 1.30, 95% CI 1.23-1.37). Conclusion Our study suggests that among low-risk women with PPH, poor uterine contractility in labor could be a significant predisposing risk factor for PPH.

We hypothesized that, in migraine patients, central sensitization (CS) could be associated with comorbid restless legs syndrome (RLS). We conducted a case–control study including 186 migraine patients and 186 age- and sex-matched healthy controls. Symptoms related to CS syndrome were assessed by the Central Sensitization Inventory (CSI). Individuals with CSI Part A (CSI-A) scores ≥ 40 were defined as having CS. For patients with migraine, the Brief Pain Inventory (BPI) and Patient Health Questionnaire (PHQ)-9 were administered. In the patient group, RLS and migraine were diagnosed through face-to-face interviews. Among migraine patients, 26 (14.0%) suffered from chronic migraine. The mean disease duration was 23.7 ± 11.8 years. Migraine patients showed a higher rate of CS (21.0% vs. 8.6%) than healthy controls, with an adjusted odds ratio (AOR) of 3.039 (95% confidence interval (CI) 1.560–5.992; p = 0.001). Migraine patients in the CS group had higher rates of smoking, chronic migraine and RLS and higher BPI and PHQ-9 scores than migraine patients in the non-CS group. The use of acute and preventive treatment for migraine did not significantly differ between the CS and non-CS groups. Multivariable analysis identified the presence of RLS (AOR, 28.471; 95% CI 6.438–125.918; p

The association of gestational hypertension (GH) with future hypertension in Japanese women is unclear. Hence, this study aimed to examine the association between GH and the risk of future hypertension in middle-aged-to-older Japanese women. A case-control study was performed, including 62 hypertensive women (case) and 75 nonhypertensive women (control). GH during the first pregnancy was diagnosed on the basis of the Maternal and Child Health Handbook record. Hypertensive women were recruited from outpatients in the hospital and residents who completed an annual health check-up in a community. Hypertension was defined as blood pressure with systolic blood pressure &ge, 140 mmHg and/or diastolic blood pressure &ge, 90 mmHg, or taking antihypertensive medications. The average age (SD) of the cases and controls at the time of recruitment was 63.1 (8.4) and 57.7 (9.4), respectively. The multivariable-adjusted odds ratio of GH for hypertension in middle-aged-to-older women was 4.2 (95% confidence interval, 1.0&ndash, 17.5) after adjustment for potential confounding factors such as age and body-mass index (BMI) upon recruitment, prepregnancy BMI, and age at first delivery. In conclusion, GH can be an independent risk factor for future hypertension among Japanese women.

Smoking is a risk factor for adult-onset Crohn&rsquo, s disease (CD). Although passive smoking from family members is a major concern, especially in pediatric CD, the number of existing epidemiological studies is limited. This multicenter case&ndash, control study aimed to assess the effects of familial smoking on pediatric CD. We examined 22 pediatric CD cases and 135 controls. The subjects&rsquo, mothers were given a self-administered questionnaire about family smoking before disease onset in the CD group or the corresponding period in the control group. Univariable logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), whereas dose&ndash, response relationship analyses were performed for more in-depth evaluations. Univariable analyses indicated that passive smoking from the mother (OR, 2.09, 95% CI, 0.61&ndash, 7.10) was not a significant, but a candidate risk factor for developing pediatric CD. In contrast, the dose&ndash, response relationship analyses revealed that passive smoking from the mother (OR, 1.17, 95% CI, 1.04&ndash, 1.31) was significantly associated with pediatric CD. Therefore, passive smoking from the mother may be predominantly associated with the development of pediatric CD. Further follow-up studies comprising environmental measurements of passive smoking exposure doses and genetic factors interaction analysis are necessary.

Purpose We examined dopamine transporter (DAT) binding in Japanese patients with idiopathic rapid eye movement sleep behavior disorder (IRBD) as a biomarker for the development of Lewy body disease (LBD). Methods [123I]FP-CIT SPECT (DAT-SPECT) scans of 74 IRBD patients were compared to those from healthy Japanese subjects, and the predictive value for conversion to LBD during a 5-year follow-up was evaluated. Results Baseline DAT deficits (Z-score ≤ −2.5) were observed in 25 (33.8%) of the IRBD patients. During follow-up, 25 patients (33.8%) developed LBD [19 Parkinson's disease and 6 dementia with Lewy bodies], with a mean latency of 2.4 ± 1.6 years from imaging. The receiver operating characteristics curve revealed that the Z-score of baseline DAT binding in the striatum of abnormal DAT-SPECT patients who later developed LBD differed from those who remained disease-free. Kaplan-Meier survival analysis showed an increased risk of LBD in patients with a Z-score ≤ −2.5 for DAT binding in the striatum of abnormal DAT-SPECT patients compared to patients with a Z-score > −2.5. Conclusions DAT-SPECT identifies IRBD patients at short-term risk for developing LBD. Decreased DAT binding in the striatum (Z-score ≤ −2.5) predicts development of LBD within 5 years, and may be useful in future disease-prevention trials in IRBD patients.

BACKGROUND: Chronic kidney disease (CKD) is an important health problem for which risk equations have been developed for Western populations. This study aimed to develop and validate a risk prediction equation for CKD in a Japanese population. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: The study included 135,007 participants who completed an annual health checkup in 1993 to 1996 in the Ibaraki Prefecture in Japan. Participants were initially free of CKD (defined as stage 3, 4, or 5 CKD or proteinuria [2+ or 3+] by dipstick). Follow-up information was available from health checkups 10 years after the initial evaluation. We used data from 40,963 women and 17,892 men in the northern region of the prefecture for the development of risk prediction equations and 53,042 women and 23,110 men in the southern region for external validation. PREDICTORS: Age, estimated glomerular filtration rate (eGFR), body mass index, proteinuria, hematuria, hypertension, diabetes mellitus, smoking, and drinking. OUTCOME: Occurrence of CKD (defined as eGFR0.8 for both the development and external validation populations, and discrimination of the risk estimation was fairly good in women and men. LIMITATIONS: Fluctuations in variables were not evaluated because the study used annual health checkups. This study excluded a large number of people for whom a 10-year health checkup was not available. CONCLUSIONS: Estimations of risk for CKD after 10 years of follow-up in a general Japanese population can be achieved with a high level of validity.

Background:Habitual speed eating is a risk factor of obesity but evidence of this in children is limited. We examined the association between speed-eating habit and subsequent body mass index (BMI) and blood pressure (BP) among Japanese children. Methods and Results:The community-based study comprised 1,490 Japanese boys and girls who were born in 1989, involved in the Ibaraki Children’s Cohort Study at age 3 years, and had returned questionnaires at both ages 6 and 12 years. In a subsample, we measured BP (n=263). Speed-eating habit was categorized into 4 groups: Never, Quit, Newly, and Continuous. Sex-specific mean values of questionnaire-based BMI and measured BPs at age 12 were examined according to speed-eating habit. Children with continuous speed eating had a higher BMI at age 12 than those who had never had a speed-eating habit (20.0 vs. 17.9 kg/m2for boys (P

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, Highlights • The highest population attributable fraction was for hypertension without obesity. • The total population attributable fraction of hypertension was 11.7%. • Hypertension could impose the greatest attribute on Japanese health expenditures.

International audience; 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 p

We investigated the effect of snacking habits in childhood on changes in body mass index (BMI) and high BMI in adolescence and adulthood. In total, 2141 Japanese children from the Ibaraki Children’s Cohort Study were evaluated at age 6 years (baseline), then at ages 12 and 22 years. We examined associations between snacking (scheduled times, when children wanted, and freely) at age 6 years and changes in BMI over time and the proportion of high BMI at ages 12 and 22 years, using time-dependent mixed-effects and logistic regression models. Compared with children who snacked at scheduled times, those provided snacks when they wanted experienced larger increases in BMI over time between ages 6 and 22 years (multivariable time-dependent effect: 0.03 kg/m2 for boys, p = 0.047; 0.04 kg/m2 for girls, p = 0.019). No differences were observed in children who snacked freely. A higher proportion of high BMI was found in boys who were provided snacks when they wanted compared with those who snacked at scheduled times. The multivariable odds ratio (95% confidence interval) was 1.52 (1.04–2.23) at age 12 years and 2.23 (1.12–4.45) at age 22 years. No differences were observed for girls at either age. Children who were provided snacks when they wanted showed larger increases in BMI over time compared with those who snacked at scheduled times. Boys who were provided snacks when they wanted showed the higher proportion of high BMI at follow-up.

The age-specific impact of atrial fibrillation (AF) on cardiovascular diseases remains unclear. A total of 90,629 participants who were from 40 to 79 years of age in 1993 were followed up until 2013 as part of the Ibaraki Prefectural Health Study. Hazard ratios for mortality stratified by gender and age groups were calculated using Cox's proportional hazards regression models. A total of 22,794 patients (11,329 men and 11,465 women) died during the follow-up period, including 6,684 patients who died of cardiovascular causes (2,951 men and 3,733 women). On multivariable analysis, participants with AF had an increased risk of cardiovascular-related mortality compared with those without AF. Among participants aged 40 to 64 years, the adjusted hazard ratios were 3.2 (95% confidence interval [CI] 2.0 to 5.3) for men and 7.1 (95% CI 3.2 to 16.0) for women; the corresponding adjusted hazard ratios among participants aged 65 to 79 years were 3.0 (95% CI 2.2 to 4.0) for men and 3.7 (95% CI 2.5 to 5.4) for women. No significant difference in hazard ratios between age groups was found for either gender. AF was significantly associated with all-cause mortality in each age and gender group; again, no significant difference in hazard ratios between the age groups was found in terms of AF. AF may be an independent risk factor for cardiovascular and all-cause mortalities regardless of age.

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.

Lifetime risk (LTR) provides an absolute risk assessment during the remainder of one’s life. Few studies have focused on the LTRs of stroke and coronary heart disease (CHD), categorized by fine blood pressure in Asian populations. We aimed to assess it using a large database of a meta-analysis with the individual participant data. The present meta-analysis included 107 737 Japanese (42.4% men; mean age, 55.1 years) from 13 cohorts. During the mean follow-up of 15.2±5.3 years (1 559 136 person-years), 1922 died from stroke and 913 from CHD. We estimated risks after adjusting for competing risk of death other than the outcome of interest. The 10-year risk of stroke and CHD deaths at index age of 35 years was ≤1.9% and ≤0.3%, respectively. The LTRs of stroke death at the index age of 35 years (men/women) were 6.1%/4.8% for optimal, 5.7%/6.3% for normal, and 6.6%/6.0% for high-normal blood pressure groups, and 9.1%/7.9% for grade 1, 14.5%/10.3% for grade 2, and 14.6%/14.3% for grade 3 hypertension groups. The LTRs of CHD death similarly elevated with an increase in blood pressure but were lower (≤7.2%) than those of stroke death. In conclusion, blood pressure was clearly associated with an elevated LTR of stroke or CHD death, although the LTR of CHD death was one-half of that of stroke death in an Asian population. These results would help young people with hypertension to adopt a healthy lifestyle or start antihypertensive therapy early.

Short anterior chamber depth (ACD) is considered a risk factor of endothelial-cell loss after phacoemulsification. However, whether it is an independent risk factor or not remains controversial. We investigated the relationship between ascorbic acid (AA) concentrations in the aqueous humour (AqH) and ACD. We analysed 165 AqH samples of 97 patients (42 men and 55 women) who underwent small incision cataract surgery. AqH and plasma AA concentrations were measured using a high-performance liquid chromatography - electrochemical detection method. Patient characteristics were compared between and within the sexes. As a result, age and ACD were significantly correlated with AqH AA concentrations (r = −0.206, P = 0.045; r = 0.339, P

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

Low levels of serum high-density lipoprotein cholesterol (HDL-C) have been shown to be associated with increased risk of coronary heart disease (CHD). However, because this is usually observed in the context of other lipid abnormalities, it is not known whether isolated low serum HDL-C levels are an independent risk factor for CHD. We performed a large pooled analysis in Japan using data from nine cohorts with 41,206 participants aged 40-89 years who were free of cardiovascular disease at baseline. We divided participants into three groups: isolated low HDL-C, non-isolated low HDL-C, and normal HDL-C. Cohort-stratified Cox proportional hazards models were used to estimate multivariate-adjusted hazard ratios (HRs) for death due to CHD, ischemic stroke, and intracranial cerebral hemorrhage; during a 12.9-year follow-up, we observed 355, 286, and 138 deaths, respectively, in these groups. Non-isolated low HDL-C was significantly associated with increased risk of CHD compared with normal HDL-C (HR 1.37, 95 % confidence interval (CI) 1.04-1.80); however, isolated low HDL-C was not. Although isolated low HDL-C was significantly associated with decreased risk of CHD (HR 0.51, 95 % CI 0.29-0.89) in women, it was significantly associated with increased risk of intracranial cerebral hemorrhage in all participants (HR 1.62, 95 % CI 1.04-2.53) and in men (HR 2.00, 95 % CI 1.04-3.83). In conclusion, isolated low HDL-C levels are not associated with increased risk of CHD in Japan. CHD risk may, therefore, be more strongly affected by serum total cholesterol levels in this population.

Rationale & Objective Chronic kidney disease (CKD) is complicated by abnormalities that reflect disruption in filtration, tubular, and endocrine functions of the kidney. Our aim was to explore the relationship of specific laboratory result abnormalities and hypertension with the estimated glomerular filtration rate (eGFR) and albuminuria CKD staging framework. Study Design Cross-sectional individual participant-level analyses in a global consortium. Setting & Study Populations 17 CKD and 38 general population and high-risk cohorts. Selection Criteria for Studies Cohorts in the CKD Prognosis Consortium with data for eGFR and albuminuria, as well as a measurement of hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, or calcium, or hypertension. Data Extraction Data were obtained and analyzed between July 2015 and January 2018. Analytical Approach We modeled the association of eGFR and albuminuria with hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, and calcium values using linear regression and with hypertension and categorical definitions of each abnormality using logistic regression. Results were pooled using random-effects meta-analyses. Results The CKD cohorts (n = 254,666 participants) were 27% women and 10% black, with a mean age of 69 (SD, 12) years. The general population/high-risk cohorts (n = 1,758,334) were 50% women and 2% black, with a mean age of 50 (16) years. There was a strong graded association between lower eGFR and all laboratory result abnormalities (ORs ranging from 3.27 [95% CI, 2.68-3.97] to 8.91 [95% CI, 7.22-10.99] comparing eGFRs of 15 to 29 with eGFRs of 45 to 59 mL/min/1.73 m 2), whereas albuminuria had equivocal or weak associations with abnormalities (ORs ranging from 0.77 [95% CI, 0.60-0.99] to 1.92 [95% CI, 1.65-2.24] comparing urinary albumin-creatinine ratio > 300 vs < 30 mg/g). Limitations Variations in study era, health care delivery system, typical diet, and laboratory assays. Conclusions Lower eGFR was strongly associated with higher odds of multiple laboratory result abnormalities. Knowledge of risk associations might help guide management in the heterogeneous group of patients with CKD. © 2018. This is the authors’ accepted and refereed manuscript to the article. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ "

Objective Prevention of hearing impairment is important because it is difficult to recover from it. Epidemiological studies have examined the risk factors for hearing impairment; however, the association between dipstick proteinuria and hearing impairment has not been previously examined. This study aimed to clarify the association between dipstick proteinuria and hearing impairment. Design Cross-sectional study. Setting Office and factory workers from all over Japan. Participants The total number of subjects was 7005. All were employees of the same company. Of these, we recruited 6192 subjects who underwent dipstick urine test and hearing test by audiometry in annual health check-ups (mean age 44.9 years, men 88.3%). Primary outcomes Hearing tests were performed at two frequencies (1 kHz, 4 kHz) as prescribed by law in Japan. We defined the inability of subjects to respond to 30 dB at 1 kHz and/or 40 dB at 4 kHz as overall moderate hearing impairment. In addition, we defined moderate hearing impairment at 1 kHz (4 kHz) as an abnormal finding at 1 kHz (4 kHz). We examined the associations between degree of dipstick proteinuria and hearing impairment after adjustment for age, sex, body mass index, hypertension, diabetes mellitus, serum creatinine level and history of noisy work environment. Results Overall moderate hearing impairment was noted in 324 subjects (5.2%). Of these, 107 subjects (1.7%) had moderate hearing impairment at 1 kHz and 278 subjects (4.5%) at 4 kHz. Dipstick proteinuria was significantly associated with overall moderate hearing impairment, as well as moderate hearing impairment at both 1 kHz and 4 kHz. The prevalence of overall moderate hearing impairment among subjects with proteinuria ≥2+ was 23.5%, while that among subjects without proteinuria was 5.2% (p Conclusions Dipstick proteinuria was associated with moderate hearing impairment in Japanese workers.

Octreotide, a long-acting somatostatin analog, has been used for treating hypoglycemia caused by congenital hyperinsulinism (CHI). However, octreotide has not been evaluated in clinical trials and has not been approved in any developed country. We aimed to test the efficacy and safety of octreotide for diazoxide-unresponsive CHI through a combination of a single-arm, open-label clinical trial (SCORCH study) and an observational study to collect data on the clinical course of patients treated off-label in Japan (SCORCH registry). In the SCORCH study, 5 patients were stabilized (blood glucose > 45 mg/dL) by hypertonic glucose infusion, and treated by continuous subcutaneous octreotide infusion at a dose of 5-25 μg/kg/day. Continuous blood glucose monitoring was performed between -24 and +48 hours. In 3 patients, a clinically meaningful rise in blood glucose was achieved and therapy was continued. The glucose infusion was gradually decreased and stopped after 5, 11, and 174 days, respectively. In one case, remission of CHI was reached after 606 days and octreotide was discontinued. The SCORCH registry included 19 diazoxide-unresponsive patients treated by subcutaneous octreotide, by continuous infusion or multiple daily injections. Of the 17 patients treated with hypertonic glucose infusion, the infusion rate was reduced after 4 weeks to less than 50% in 11 patients (64.7%) and stopped in 9 (52.9%). During the combined observation period of 695.4 patient-months in both studies, no severe adverse events related to octreotide were observed. In conclusion, subcutaneous octreotide injection was effective and well tolerated in the majority of patients with diazoxide-unresponsive CHI.

Objectives The distribution of serum 25-hydroxyvitamin D [25(OH)D] levels among reproductive age Japanese perinatal (prepartum, intrapartum, postpartum) and non-perinatal women remains unknown. In addition to this, vitamin D deficiency cut-off values, which consider the effects of these levels during the perinatal period and infant development, have not been determined. Thus, we systematically reviewed the distribution of serum 25(OH)D levels among reproductive age Japanese women, in order to provide basic data to determine vitamin D deficiency cut-off values.Methods A systematic literature review was conducted on research published between 1963 and 2015, using PubMed web and Japan Medical Abstracts Society web. The key words "Japan," "Vitamin D," "women," and "pregnant women," were used. After filtering for age, sex, race, indication of numerical number, and duplications, 18 papers were extracted and categorized into reproductive age non-perinatal women (13 papers/22 groups), and reproductive age perinatal women (6 papers/8 groups). The mean serum 25(OH)D levels were grouped by age, test period, and measuring methods.Results Mean serum 25(OH)D levels among reproductive age non-perinatal women were lower than 20 ng/ml in 10 out of 22 groups (45.4%), and lower than 30 ng/ml in 21 groups (95.5%). The mean serum 25(OH)D level among reproductive age perinatal women was lower than those among reproductive age non-perinatal women. Among reproductive age perinatal women, except for one group that included women in the first trimester of pregnancy (5-10 weeks), the mean serum 25(OH)D levels of the other groups were lower than 20 ng/ml.Conclusion Serum 25(OH)D levels among reproductive age Japanese women, especially perinatal women, appear to be low. Studies of serum 25(OH)D levels among reproductive age Japanese women are limited; hence, further investigation is required.

Purpose To examine the relationship between body mass index (BMI) and the risk of stage ≥3 chronic kidney disease (CKD) in a general Japanese population. Methods A total of 105 611 participants aged 40–79 years who completed health checkups in Ibaraki Prefecture, Japan, and were free of CKD in 1993 were followed-up through 2006. Stage ≥3 CKD was defined by an estimated glomerular filtration rate

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) who participated 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 all-cause 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.

Aim The levels of lipids, especially triglycerides (TG), and obesity are associated with diabetes mellitus (DM). Although typically measured in fasting individuals, non-fasting lipid measurements play an important role in predicting future DM. This study compared the predictive efficacy of lipid variables according to the fasting status and body mass index (BMI) category. Methods Data were collected for 39,196 nondiabetic men and 87,980 nondiabetic women 40-79years of age who underwent health checkups in Ibaraki-Prefecture, Japan in 1993 and were followed through 2007. The hazard ratios (HRs) for DM in relation to sex, the fasting status and BMI were estimated using a Cox proportional hazards model. Results A total of 8,867 participants, 4,012 men and 4,855 women, developed DM during a mean follow-up of 5.5 years. TG was found to be an independent predictor of incident DM in both fasting and non-fasting men and non-fasting women. The multivariable-adjusted HR for DM according to the TG quartile (Q) 4 vs. Q1 was 1.18 (95% confidence interval (CI): 1.05, 1.34) in the non-fasting men with a normal BMI (18.5-24.9). This trend was also observed in the non-fasting women with a normal BMI. That is, the multivariable-adjusted HRs for DM for TG Q2, Q3 and Q4 compared with Q1 were 1.07 (95% CI: 0.94, 1.23), 1.17 (95%CI: 1.03, 1.34) and 1.48 (95%CI: 1.30, 1.69), respectively. Conclusions The fasting and non-fasting TG levels in men and non-fasting TG levels in women are predictive of future DM among those with a normal BMI. Clinicians must pay attention to those individuals at high risk for DM.

The objective of this study was to examine the effect of age on the relationship between alcohol consumption and incident hypertension in a general Japanese population. A cohort of Japanese men (n=37 310) and women (n=78 426) aged 40 to 79 years who underwent community-based health checkups from 1993 to 2004 and were free of hypertension were followed up with annual examinations, including the measurement of blood pressure, until the end of 2010. Incident hypertension was defined as systolic blood pressure of ≥140 mm Hg, diastolic blood pressure of ≥90 mm Hg, or the initiation of treatment for hypertension. Hazard ratios for incident hypertension according to alcohol consumption were estimated using a Cox proportional hazards model adjusted for possible confounding variables. A total of 45 428 participants (39.3%) developed hypertension (16 155 men and 29 273 women) for a mean follow-up time of 3.9 (1–18) years. Significant associations between alcohol consumption and incident hypertension were found in both sexes and age groups ( P for trend was P for interaction, >0.05). Our results suggest that alcohol consumption is a similar risk factor for incident hypertension in both the middle-aged and the older populations.

ObjectivesHearing 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.DesignThis was a prospective cohort study based on annual health check-up data, 2008–2016.SettingData were collected on 7005 employees of a single company who worked in offices and factories throughout Japan.ParticipantsWe 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 measuresHearing 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.ResultsTotal 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.ConclusionsSevere 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.

Importance: Asia is home to the largest diabetic populations in the world. However, limited studies have quantified the association of diabetes with all-cause and cause-specific mortality in Asian populations. Objectives: To evaluate the association of diabetes with all-cause and cause-specific mortality in Asia and to investigate potential effect modifications of the diabetes-mortality associations by participants' age, sex, education level, body mass index, and smoking status. Design, Setting, and Participants: This pooled analysis incorporated individual participant data from 22 prospective cohort studies of the Asia Cohort Consortium conducted between 1963 and 2006. A total of 1 002 551 Asian individuals (from mainland China, Japan, South Korea, Singapore, Taiwan, India, and Bangladesh) were followed up for more than 3 years. Cohort-specific hazard ratios and 95% confidence intervals for all-cause and cause-specific mortality were estimated using Cox regression models and then pooled using random-effects meta-analysis. Analysis was conducted between January 10, 2018, and August 31, 2018. Exposures: Doctor-diagnosed diabetes, age, sex, education level, body mass index, and smoking status. Main Outcomes and Measures: All-cause and cause-specific mortality. Results: Of 1 002 551 participants (518 537 [51.7%] female; median [range] age, 54.0 [30.0-98.0] years), 148 868 deaths were ascertained during a median (range) follow-up of 12.6 (3.0-38.9) years. The overall prevalence of diabetes reported at baseline was 4.8% for men and 3.6% for women. Patients with diabetes had a 1.89-fold risk of all-cause death compared with patients without diabetes (hazard ratio [HR], 1.89; 95% CI, 1.74-2.04), with the highest relative risk of death due to diabetes itself (HR, 22.8; 95% CI, 18.5-28.1), followed by renal disease (HR, 3.08; 95% CI, 2.50-3.78), coronary heart disease (HR, 2.57; 95% CI, 2.19-3.02), and ischemic stroke (HR, 2.15; 95% CI, 1.85-2.51). The adverse diabetes-mortality associations were more evident among women (HR, 2.09; 95% CI, 1.89-2.32) than among men (HR, 1.74; 95% CI, 1.62-1.88) (P for interaction

ObjectivesPrevention 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.DesignCross-sectional study.SettingJapanese workers in an information and communication technologies company.ParticipantsOf 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 outcomesHearing 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.ResultsModerate 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% (pConclusionsHypertension was associated with moderate HI in Japanese workers.