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OBJECTIVES There are two major methods for local anesthesia by lidocaine before upper gastrointestinal endoscopy: simple spray and viscous solution. We aimed to assess the efficacy and safety by meta-analysis between these two methods. METHODS We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov databases through October 2019 to perform meta-analyses using random-effects models. The primary outcomes were participants' pain/discomfort, satisfaction, and anaphylactic shock. Three reviewers independently searched for articles, extracted data, and assessed the risk of bias. We evaluated the certainty of evidence based on the Grading of Recommendations, Assessment, Development, and Evaluation approach. This study was registered in PROSPERO (CRD42020155611). RESULTS We included seven randomized controlled trials (2667 participants). The participants' pain/discomfort may be similar between the lidocaine spray and viscous solution [standardized mean difference 0.03, 95% confidence intervals (CI) -0.37 to 0.42; I2 = 93%; low certainty of evidence]. The lidocaine spray probably increased participants' satisfaction compared with the viscous solution (relative risk 1.22; 95% CI, 1.02 to 1.47; I2 = 47%; moderate certainty of evidence). No anaphylactic shock occurred in four studies (low certainty of evidence). Four studies had high risks of selection bias. CONCLUSION The use of lidocaine spray for local anesthesia provided better satisfaction scores than the viscous solution, and both methods have the same effect with regards to the control of discomfort and pain. Further studies in large multicenter randomized controlled trials with a pre-registration protocol are needed.

Resistant hypertension is an important cardiovascular risk factor. This analysis of the JAMP study (Japan Ambulatory Blood Pressure Monitoring Prospective) data investigated the effects of uncontrolled resistant hypertension diagnosed using ambulatory blood pressure (BP) monitoring on the risk of heart failure (HF) and overall cardiovascular events. The JAMP study patients with hypertension and no HF history were included. They had true resistant hypertension (24-hour BP ≥130/80 mm Hg), pseudoresistant hypertension (24-hour BP P =0.012 and 2.24 [95% CI, 1.17–4.30]; P =0.015, respectively) and versus uncontrolled nonresistant hypertension (1.51 [1.03–2.20]; P =0.034 and 3.03 [1.58–5.83]; P Registration: URL: https://www.umin.ac.jp/ctr ; Unique identifier: UMIN000020377.

Background: Increase of collagen in the extracellular matrix occurs with ageing. We investigated whether a collagen marker, tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), was associated with risk of stroke. Methods and Results: In a nested case-control study of 953 subjects from the general population, we evaluated determinants of TIMP-1 level and stroke risk. Mean subject age was 65.7±8.6 years (53.0% men); TIMP-1 was 72.4±28.2 pg/mL in the control group and 75.3±30.9 pg/mL in the stroke group. The relationship between TIMP-1 quartile and stroke was J-curved. Subjects in the highest TIMP-1 quartile (≥89 ng/mL) had a significantly higher OR of stroke (59–72 ng/mL; OR, 1.90; 95% CI: 1.09–3.31, P=0.023) than those in the second TIMP-1 quartile, and this tended toward significance even after adjusting for confounding factors (P=0.059). Elevation of serum TIMP-1 became more marked after age 65 years. On multiple linear regression analysis, significant determinants of TIMP-1 were older age (B=0.21 per 1 year; 95% CI: 0.52–1.07, P

Isaku Kurotori,1 Katsutoshi Shioda,1 Takaaki Abe,1 Rika Kato,1 Shizukiyo Ishikawa,2 Shiro Suda1 1Department of Psychiatry; 2Department of Medical Education Center, Jichi Medical University, Tochigi, JapanCorrespondence: Katsutoshi ShiodaDepartment of Psychiatry, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, JapanTel +81-285-58-7364Fax +81-285-44-6198Email kazs@jichi.ac.jpPurpose: To determine the clinical characteristics and course of severe avoidant/restrictive food intake disorder (ARFID) in hospitalized children and adolescents and compare them with those of patients with restricting-type anorexia nervosa (R-AN).Patients and methods: We conducted a retrospective chart review of inpatients diagnosed with ARFID or R-AN based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, at Jichi Children’s Medical Center Tochigi between April 1, 2007 and March 31, 2017. We compared the characteristics of the ARFID and R-AN patients at admission, during hospitalization, and after discharge.Results: Both the ARFID (n=13) and R-AN (n=79) patients required hospitalization for their medically unstable state. The features of ARFID group included concern about the aversive consequences of eating and avoidance of eating due to sensory concerns. Significant differences were found at admission between ARFID and R-AN groups in age (10.7 vs 12.7 years), family history of mental disorders (46.2% vs 17.7%), comorbid developmental disorders (6 vs 3 cases), and the time from onset to admission (3.9 vs 6.3 months). The body weight status, % ideal body weight (%IBW), % expected body weight (%EBW)

Aims/Introduction This randomized controlled trial aimed to determine whether frequent nutritional education improves the clinical parameters associated with the onset and progression of diabetic kidney disease in type 2 diabetes mellitus patients. Materials and Methods A total of 96 patients with type 2 diabetes and diabetic kidney disease were randomly assigned to the intensive intervention group that received nutritional education at every outpatient visit, and the usual intervention group that received nutritional education once a year. The anthropometric parameters, blood pressure, blood chemistry, albuminuria, protein and salt intake, and prescribed medications of 87 patients who completed the 2‐year follow up were analyzed. Results In the intensive intervention group, body mass index and salt intake significantly decreased over the study period. Hemoglobin A1c levels and body fat percentage were significantly lower in the intensive intervention group than in the usual intervention group. At the end of the 2‐year intervention period, the intensive intervention group had significantly lower salt intake (8.1 vs 9.4 g/day) than the usual intervention group. A significant positive correlation was found between salt intake and albuminuria in the overall group and intensive intervention group (r = 0.26, P = 0.02, and r = 0.36, P = 0.02, respectively). The intensive intervention group had a significantly lower insulin use rate than the usual intervention group after the 2‐year intervention period (18% vs 42%). No differences were found in estimated glomerular filtration rate and albuminuria. Conclusion Intensive nutritional education is useful for alleviating the risk factors associated with the onset and progression of diabetic kidney disease.

Introduction: Those who are considered to be low risk in short term such as 10 year risk actually have high risk of cardiovascular disease for the remaining lifespan at younger age. Absolute risk of Lifetime risk (LTR) is more useful and understandable for lay audience compared with short term risk or relative risk. CKD (Chronic Kidney Disease) is global burden of cardiovascular disease (CVD) and hypertension is damaging complication of CKD for CVD. To date, there have been no reports of LTR with the outcome of CVD death based on CKD in Asian population. Hypothesis: We sought to estimate LTR of CVD death stratified by the status of CKD and hypertension. Methods: We used data from EPOCH-JAPAN (Evidence for Cardiovascular Prevention From Observational Cohorts in Japan) which is designed to pool data from nationwide and regional cohort studies in Japan. Modified Kaplan-Meier approach was used to estimate the remaining lifetime risk of cardiovascular death at each index age starting from 40 years according to CKD stratified by Hypertension. Participants were classified into four groups, which were those without CKD and hypertension (CKD-/HT-), those with CKD but without hypertension (CKD+/HT-), those without CKD but with hypertension (CKD-/HT+), and those with both CKD and hypertension (CKD+/HT+). Results: A total of 44,582 participants from 8 cohorts was included in the analysis. Mean follow-up period was 14.9 years with 662,488 person years and total CVD death was 1,035 in men and 1,160 in women. The LTRs at the index age of 40 years increased in groups with CKD and/or HT as follows: 12.6% (95% confidence interval: 9.4 - 14.5%) in CKD-/HT- group, 20.6% (11.4 - 25.9%) in CKD+/HT- group, 23.2% (19.9 - 25.2%) in CKD-/HT+ group, and 27.9% (21.7 - 32.9%) in CKD+/HT+ group for men; 11.3%(8.9 - 13.2%), 17.4%(13.2 - 20.4%) , 17.8%(15.3 - 19.8%) , and 22.7%(19.5 - 25.2%) for women. Conclusions: We observed that complication of CKD and hypertension are collectively responsible for lifetime risk due to CVD death. Management of blood pressure from an early age is important to reduce CVD mortality in CKD patients.

Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): H20–Junkankitou [Seishuu]–Ippan–013; H23–Junkankitou [Seishuu]–Ippan–005; H26-Junkankitou [Seisaku]-Ippan-001; H29–Junkankitou–Ippan–003 and 20FA1002 OnBehalf EPOCH-JAPAN Introduction Absolute risk of Lifetime risk (LTR) is useful estimate for risk communication compared with short term risk or relative risk especially for young people. Proteinuria is leading cause of end-stage kidney disease (ESKD) and independent risk factor for cardiovascular disease (CVD). Although nonproteinuric renal disease is global burden of ESKD, it has been poorly focused. To date, there have been no reports of impact of proteinuria and low eGFR on LTR with the outcome of CVD death in Asian population. Purpose We aimed to estimate LTR of CVD death stratified by the status of proteinuria and low eGFR. Methods We used modified Kaplan-Meier approach to estimate the remaining lifetime risk of cardiovascular death based on EPOCH-JAPAN(Evidence for Cardiovascular Prevention From Observational Cohorts in Japan) database. LTR was estimated at each index age starting from 40 years for those with proteinuria and without proteinuria stratified by low eGFR, which is defined as eGFR Results A total of 47,292 participants from 9 cohorts was included in the analysis. Mean follow-up period was 14.6 years with 690,463 person years and total CVD death was 1,075 in men and 1,193 in women. The LTRs at the index age of 40 years were as follows: 17.7% (95% confidence interval: 15.4 – 19.0%) in Proteinuria (-)/Low eGFR (-) group, 26.2% (20.2 – 31.1%) in Proteinuria (-)/low eGFR (+) group, 24.5% (15.1 – 29.3%) in Proteinuria (+) group for men; 15.3%(13.7 – 16.5%), 29.9%(14.7 – 46.8%) , 28.3%(19.4 – 34.7%) for women. Conclusions We observed that those without proteinuria with low eGFR have equivalently high LTR with those with proteinuria. These results indicate that even in the absence of proteinuria, low eGFR has high impact on LTR. Lifestyle modification from young age is necessary to prevent from renal dysfunction.

Background: Strategies to prevent the development and progression of chronic kidney disease (CKD) are important in clinical practice due to increased life expectancy. The present study investigated the prevalence of CKD as well as lipid profiles affecting CKD, especially triglyceride (TG) levels.Methods: In total, 5,169 subjects were eligible for a cross-sectional analysis of baseline data from the Jichi Medical School Cohort Study. We examined CKD subjects with an estimated glomerular filtration rate (eGFR) of 59 mL/min/1.73m2 or lower and independent factors associated with reductions in eGFR.Results: The prevalence of CKD was 17.7%. Age, systolic blood pressure, and hyperlipidemia were defined as related factors for CKD. The lowest, second, third, and highest quartile ranges of total cholesterol (TC) and TG were 0-166, 167-188, 189-212, and 213 mg/dL or higher and 0-71, 72-100, 101-148, and 149 mg/dL or higher, respectively. The odds ratio (OR) of Q2 to Q4 of TC relative to that of Q1 for CKD increased linearly (OR [95%CI]: Q2, 1.3 [1.0-1.7]; Q3, 1.38 [1.1-1.8]; Q4, 1.5 [1.4-2.4]). The ORs of Q2 and Q3 of TG for CKD did not increase, whereas that of Q4 did (OR [95% CI]: Q2, 0.95 [0.7-1.2]; Q3, 0.98 [0.8-1.2]; Q4, 1.21 [1.0-1.5]). Conclusion: Increases in TC and TG levels were both independently associated with CKD. The relationship with CKD became stronger as TC increased, and the TG had threshold was 149 mg/dL.

ObjectivesSmall dense low-density lipoprotein cholesterol (sdLDL-C) might be a better cardiovascular disease (CVD) indicator than low-density lipoprotein cholesterol (LDL-C); however, details regarding its epidemiology remain elusive. The present study aimed at evaluating the association between the demographic factors, such as age, gender and menopausal status, and sdLDL-C levels and sdLDL-C/LDL-C ratio in the Japanese population.DesignThis was a cross-sectional study.Setting13 rural districts in Japan, 2010–2017.ParticipantsThis study included 5208 participants (2397 men and 2811 women), who underwent the health mass screening that was conducted in accordance with the medical care system for the elderly and obtained informed consent for this study.ResultsIn total, 517 premenopausal women (mean age ±SD, 45.1±4.2 years), 2294 postmenopausal women (66.5±8.8 years) and 2397 men (64.1±11.2 years) were analysed. In men, the sdLDL-C levels and sdLDL-C/LDL-C ratio increased during younger adulthood, peaked (36.4 mg/dL, 0.35) at 50–54 years, and then decreased. In women, relatively regular increasing trends of sdLDL-C level and sdLDL-C/LDL-C ratio until approximately 65 years (32.7 mg/dL, 0.28), followed by a downward or pleated trend. Given the beta value of age, body mass index, fasting glucose and smoking and drinking status by multiple linear regression analysis, standardised sdLDL-C levels and sdLDL-C/LDL-C ratio in 50-year-old men, premenopausal women and postmenopausal women were 26.6, 22.7 and 27.4 mg/dL and 0.24, 0.15 and 0.23, respectively. The differences between premenopausal and postmenopausal women were significant (pConclusionsSdLDL-C and sdLDL-C/LDL-C ratios showed different distributions by age, gender and menopausal status. A subgroup-specific approach would be necessary to implement sdLDL-C for CVD prevention strategies, fully considering age-related trends, gender differences and menopausal status.

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

Background: Developing self-regulated learning in preclinical settings is important for future lifelong learning. Previous studies indicate professional identity formation, i.e., formation of self-identity with internalized values and norms of professionalism, might promote self-regulated learning．We designed a professional identity formation-oriented mentoring format and tested effectiveness on raising self-regulated learning in a pre-clinical year curriculum. Methods: A randomized controlled crossover trial was conducted using 112 students at Jichi Medical University. In six one-day problem-based learning sessions in a 7-month pre-clinical year curriculum, Groups A (n = 56, female 18, mean age 21.5y ± 0.7) and B (n = 56, female 11, mean age 21.7y ± 1.0) received professional identity formation-oriented mentoring: Group A had three sessions in the first half, B in the second half. Between-group identity stages and self-regulated learning levels were compared using professional identity essays and the Motivated Strategies for Learning Questionnaire.Results: Two-level regression analyses showed no improvement in questionnaire categories but moderate improvement of professional identity stages over time (R2 = 0.069), regardless of timing of intervention. Conclusions: Professional identity moderately forms during the pre-clinical year curriculum. However, neither identity nor self-regulated learning is raised significantly by limited intervention.

BACKGROUND Several studies have described an association between hemoglobin concentration and stroke; however, the influence of hemoglobin on stroke incidence has not been fully revealed. Our objective was to elucidate the association between hemoglobin concentration and stroke incidence in Japanese community residents. METHODS In the present study, we collected the data of 12,490 subjects who were enrolled between April 1992 and July 1995 in the Jichi Medical School (JMS) Cohort Study. We excluded the subjects with a history of stroke. Hemoglobin concentrations were grouped in quartiles, and quartile 2 (Q2) was used as the reference category. A Cox proportional-hazards model was used to examine hazard ratios (HRs) and the stroke incidence rates with 95% confidence intervals (CIs). RESULTS During 10.8 years of follow-up, 409 participants (212 men and 197 women) experienced a new stroke, including 97 intracerebral hemorrhages, 259 cerebral infarctions, and 52 subarachnoid hemorrhages (SAH). In sex-specific hemoglobin quartiles, the multivariate-adjusted HR was statistically significantly higher in Q1 than in Q2, and a relationship similar to a J shape was observed between all strokes (HR in Q2 vs. Q1, 1.36; 95% CI, 1.02-1.83; Q3, 1.20; 95% CI, 0.87-1.64; and Q4, 1.16; 95% CI, 0.84-1.60). Furthermore, the analysis of stroke subtypes showed a statistically significantly higher multivariate-adjusted HR in Q1 than in Q2 for SAH (HR, 2.61; 95% CI, 1.08-6.27). CONCLUSIONS A low hemoglobin concentration was associated with an increased risk of stroke, which was strongly influenced by the incidence of SAH.

ObjectiveTo examine the association between polarity of atrial premature complexes (APCs) and stroke.DesignA prospective study.Setting and participantsA total of 11 092 participants in the Jichi Medical School cohort study were included after excluding patients with atrial fibrillation. We analysed stroke events in patients with (n=136) and without (n=10 956) APCs. With regard to polarity of APCs, patients were subcategorised into having (1) negative (n=39) or non-negative (n=97) P waves in augmented vector right (aVR), and (2) positive (n=28) or non-positive (n=108) P waves in augmented vector left (aVL).Outcome measuresThe primary endpoint was stroke.ResultsPatients with APCs were significantly older than those without APCs (64.1±9.2 vs 55.1±11.6 years, pConclusionsThe presence of APCs with non-negative P wave in aVR or non-positive P wave in aVL on 12-lead ECG was associated with a higher risk of incident stroke.

Background:Small dense low-density lipoprotein cholesterol (sdLDL-C) might be a better cardiovascular disease (CVD) indicator than low-density lipoprotein cholesterol (LDL-C); however, details regarding its epidemiology remain elusive. The present study aimed at evaluating the effect of age, gender, and menopausal status on sdLDL-C levels and sdLDL-C/LDL-C ratio in the Japanese population.Methods:We examined the baseline cross-sectional data from the Jichi Medical School-II Cohort Study, including 5,208 participants (2,397 men and 2,811 women). To assess age-related trends, the sdLDL-C and sdLDL-C/LDL-C ratios were plotted against gender. We evaluated the effect of age and menopausal status using multiple linear regression analysis.Results:We observed that in men, the sdLDL-C levels and sdLDL-C/LDL-C ratio increased during younger adulthood, peaked at 50–54 years, and then decreased. In women, we observed relatively regular increasing trends of sdLDL-C level and sdLDL-C/LDL-C ratio until approximately 65 years, followed by a downward or pleated trend. The crossover of sdLDL-C levels for the genders occurred at 70–74 years, but we could not observe any sdLDL-C/LDL-C ratio crossover. Standardized sdLDL-C levels and sdLDL-C/LDL-C ratio in 50-year old men, premenopausal women, and postmenopausal women were 26.6, 22.7, and 27.4 mg/dL and 0.24, 0.15, and 0.23, respectively. The differences between premenopausal and postmenopausal women were significant (PConclusions:sdLDL-C and sdLDL-C/LDL-C ratios show different distributions by age, gender, and menopausal status with trends different from other lipids. A subgroup-specific approach would be necessary to implement sdLDL-C for CVD prevention strategies, fully considering age-related trends, gender differences, and menopausal status.

Background: Developing self-regulated learning (SRL) in a teacher-centered curriculum is challenging. Previous studies indicate professional identity formation (PIF), or the formation of self-identity with internalized values and norms of professionalism, might improve SRL．We designed a PIF-oriented education format for hybrid problem-based learning (PBL) and tested its effectiveness on SRL in a mixed research method.Methods: A randomized controlled crossover trial was conducted using 112 pre-clinical year students at Jichi Medical University. In the six one-day PBL sessions, Groups A (n = 56, female 18, mean age 21.5y ± 0.7) and B (n = 56, female 11, mean age 21.7y ± 1.0) experienced PIF-oriented pre-PBL learning: Group A had three sessions in the first half, B in the second half. Between-group PIF and SRL levels were compared using Professional Identity Essay (PIE) and Motivated Strategies for Learning Questionnaire (MSLQ). A qualitative thematic analysis of potential reasons for PIF improvement was performed using the PIE description.Results: Two-level regression analyses showed moderate improvement of PIF stages over time (R2 = 0.069), regardless of intervention. PIF-oriented pre-PBL learning alone did not significantly improve PIE stages or MSLQ scores. Thematic analysis indicated that PIF-oriented pre-PBL learning helped students recognize realistic difficulties in clinical practice, and articulate professional image and values. However, encounters in extracurricular clinical settings had diverse and meaningful impacts on PIF.Conclusions: Limited effect of PIF-oriented pre-PBL learning on PIF and SRL indicate challenges in SRL-oriented education for pre-clinical year students within a teacher-centered hybrid PBL curriculum.

Objective: The aim of the present study was to investigate the clinical and nutritional factors influencing the renal function of the transplanted kidney during a one-year follow-up period after transplantation. Patients: The present prospective observational study included 52 patients who underwent kidney transplantation at Jichi Medical University Hospital from 2014 to 2016. Results: The serum creatinine (sCr) concentration at one month after transplantation was closely related to the concentration at 12 months. The recipients were divided into two groups based on the sCr concentration at one month after transplantation. Recipients with a sCr concentration greater than or equal to the median were classified into Group H, while those with concentrations that were less than the median were classified into Group L. A stepwise multiple regression analysis demonstrated that the salt intake in male recipients was an independent predictor of the renal function at 12 months (β = 0.663, p β = 0.618, p < 0.01). Moreover, in female recipients, the BMI and serum uric acid values in Group H were significantly higher than those in Group L. The BMI values of the female recipients in Group H were significantly higher than those in Group L at all times during the follow-up period (p < 0.01). Conclusion: The daily salt intake was independently associated with the renal function at one year after kidney transplantation in male recipients. In female recipients, the BMI was independently associated with the sCr concentration during the one-year follow-up period.

Previous studies have found the prevention paradox in the association between stroke events and a single specific risk factor, indicating that a population-based strategy may be more effective than a high-risk-based strategy for prevention. We tested the hypothesis that the prevention paradox does not apply when focusing on multiple potential risk factors simultaneously. The study cohort included 9051 individuals from Japan aged 40–89 years. The time-dependent Cox proportional-hazards models were used to identify the primary risk factor associated with stroke onset. We classified participants based on risk factors in two distinct ways: 1) classifying the high-risk group participants according to a single specific risk factor that had a large association with stroke in both sexes and all ages and 2) classifying the high-risk group participants according to 1–3 risk factor(s) including hypertension, hyperglycemia, and/or dyslipidemia. Then, we compared the proportions of the total number of participants who developed stroke in both groups to assess the prevention paradox. We found that hypertension was a primary risk factor for stroke incidence, regardless of sex and age. The percentage of patients with a single specific risk of and developed stroke was 46%–63%, while the percentage of patients with 1–3 risk factor(s) was 71–83%. This finding leads to the conclusion that the prevention paradox does not hold when multiple stroke risk factors were associated, suggesting that a high-risk-based strategy that focuses on patients with multiple risk factors may be more effective in preventing strokes.

Background High body mass index (BMI) has been reported as a risk factor for cardiovascular events in Western countries, while low BMI has been reported as a risk factor for cardiovascular death in Asian countries, including Japan. Although stroke is a major cause of death and disability in Japan, few cohort studies have examined the association between BMI and stroke incidence in Japan. This study aimed to examine the association between BMI and stroke incidence using prospective data from Japanese community residents. Methods Data were analyzed from 12,490 participants in the Jichi Medical School Cohort Study. Participants were categorized into five BMI groups: ≤18.5, 18.6–21.9, 22.0–24.9, 25.0–29.9, and ≥30.0 kg/m2. Multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazard model. The group with a BMI of 22.0–24.9 kg/m2 was used as the reference category. Results During mean follow-up of 10.8 years, 395 participants (207 men and 188 women) experienced stroke, including 249 cerebral infarctions and 92 cerebral hemorrhages. Men with a BMI ≤18.5 kg/m2 (HR 2.11; 95% CI, 1.17–3.82) and women with a BMI ≥30.0 kg/m2 (HR 2.25; 95% CI, 1.28–5.08) were at significantly higher risk for all-stroke. Men with a BMI ≤18.5 kg/m2 were at significantly higher risk for cerebral infarction (HR 2.15; 95% CI, 1.07–4.33). Conclusions The association between BMI and stroke incidence observed in this population was different than those previously reported: low BMI was a risk factor for all-stroke and cerebral infarction in men, while high BMI was a risk factor for all-stroke in women., Highlights • The association of body mass index (BMI) with stroke remains controversial in Japan. • Our large cohort study examined the association of interest in a Japanese population. • Low BMI increased the risk of all-stroke and cerebral infarction incidence in men. • In contrast, high BMI increased the risk of all-stroke incidence in women.

Prognosis of patients with chronic heart failure remains poor, emphasizing the need to identify additional pathophysiological factors. Tsuda et al. show that Crhr2 activation causes cardiac dysfunction and suggest Crhr2 blockade is a promising therapeutic strategy for chronic heart failure., Heart failure occurs when the heart is unable to effectively pump blood and maintain tissue perfusion. Despite numerous therapeutic advancements over previous decades, the prognosis of patients with chronic heart failure remains poor, emphasizing the need to identify additional pathophysiological factors. Here, we show that corticotropin releasing hormone receptor 2 (Crhr2) is a G protein–coupled receptor highly expressed in cardiomyocytes and continuous infusion of the Crhr2 agonist, urocortin 2 (Ucn2), reduced left ventricular ejection fraction in mice. Moreover, plasma Ucn2 levels were 7.5-fold higher in patients with heart failure compared to those in healthy controls. Additionally, cardiomyocyte-specific deletion of Crhr2 protected mice from pressure overload-induced cardiac dysfunction. Mice treated with a Crhr2 antagonist lost maladaptive 3′-5′-cyclic adenosine monophosphate (cAMP)–dependent signaling and did not develop heart failure in response to overload. Collectively, our results indicate that constitutive Crhr2 activation causes cardiac dysfunction and suggests that Crhr2 blockade is a promising therapeutic strategy for patients with chronic heart failure.

Background: Previous studies indicate professional identity formation (PIF), or formation of self-identity with internalized values and norms of professionalism, might influence self-regulated learning (SRL). However, it remains unclear whether or not PIF-oriented education can improve SRL in medical students. Methods: Rural community-based clinical clerkships (rCBCC) for Year 5 (Y5) students in Jichi Medical University (JMU) provide a learning environment where undergraduates will work in future with alumni directly mentoring them. To make rCBCC more PIF-oriented, we created a learning platform using Google Forms and a PIF-oriented teaching manual for mentors. These were designed to help undergraduates articulate future ‘self’ images as professionals, and have in-depth communication with mentors as role models pertaining to medical professionalism. Forty-one Y5 JMU students experienced PIF-oriented rCBCC, while 41 Y5 control subjects experienced the original format rCBCC. Changes in SRL between the two groups were compared using 15 categories of motivated strategies for learning questionnaire (MSLQ). We also explored how the PIF-oriented rCBCC changed their SRL by thematic analysis of questionnaire and interview data.Results: A moderate improvement of intrinsic goal orientation (p = 0.005, ε2 = 0.096) and a mild improvement of critical thinking (p = 0.041, ε2 = 0.051) were observed in the PIF-oriented rCBCC. Qualitative analysis revealed they started viewing ‘professional responsibility’ as self-study motivator. Awareness of ‘responsibility’ led to pursuit of authenticity and medical knowledge applicability, and fostered critical thinking about learning contents. They also began elaborating learning contents in line with processes. Conclusion: This is the first study showing some effects of PIF-oriented education on SRL improvement. Fostering PIF may be important for stimulating learners’ intrinsic SRL behaviors.

Background The cardiovascular relevance of isolated low levels of high‐density lipoprotein cholesterol (HDL‐C) is yet to be determined. Stroke often leads to long‐term disability, and thus, not only stroke mortality but also stroke incidence is a topic of research. Although isolated low HDL‐C level has been found to be a predictor for stroke mortality previously, whether it can predict stroke incidence is unknown. Methods In the Jichi Medical School cohort study, 11 025 community‐living residents without a history of stroke were examined. Hazard ratios (HRs) for isolated and non‐isolated low HDL‐C levels were calculated relative to those for normal HDL‐C levels in stroke patients using Cox's regression models. Results During the mean follow‐up period of 10.7 years, 412 residents had their first‐ever stroke. The multivariable‐adjusted HRs for the levels of isolated and non‐isolated low HDL‐C were 1.11 (95% confidence interval, 0.85‐1.44) and 1.35 (1.01‐1.81), respectively, when compared to that for normal HDL‐C. Conclusion Low HDL‐C levels with other dyslipidemias may contribute to the incidence of stroke, not isolated low HDL‐C.

Objectives: The fasting plasma glucose/hemoglobin A1c ratio is considered a marker associated with glucose metabolism disorders, including fasting hyperglycemia. However, it remains unclear whether this ratio can be used for the prevention of deaths in individuals with normal fasting plasma glucose levels. This study aimed to see the predictive value of the fasting plasma glucose/hemoglobin A1c ratio for all-cause mortality in a general population with normal fasting plasma glucose levels. Methods: The study investigated prospectively a cohort of 1087 multi-regional, community-dwelling Japanese participants (women, 69.2%) for a follow-up period of 11.3 years. We included individuals with fasting plasma glucose levels Results: There were 54 deaths (25 women) during the follow-up period. The high tertile group had a significantly higher hazard ratio for all-cause mortality than the low tertile group in women (multivariate-adjusted hazard ratio = 4.45; 95% confidence interval = 1.26–15.72), but not clearly in men. Conclusion: The data of the population-based cohort study suggest that a high fasting plasma glucose/hemoglobin A1c ratio can predict all-cause mortality in women with normal fasting plasma glucose levels.

Background Due to ethic differences in its serum levels, clinical applicability of high-sensitivity C-reactive protein (hsCRP) to the primary prevention of atherosclerotic events has not completely been established in Japanese people whose hsCRP levels are lower than in Western people. This study investigated the relationship between hsCRP and myocardial infarction (MI) in general Japanese people. Methods In relation to hsCRP, the incidence of MI was determined in a multiregional population-based prospective cohort study (n = 6,637; mean age 54.9 years; 2,513 men/4,124 women). Results Fifty-six cases of MI were confirmed during a follow-up period of 10.7 years. The cut-off levels of hsCRP between the highest quartile (fourth quartile) and the other quartiles combined were 0.368 mg/l in men and 0.279 mg/l in women. The hazard ratio (HR) of the highest quartile for MI was significantly greater than that of the other quartiles combined (multivariate-adjusted HR: 2.07, 95% confidence interval: 1.03–4.15) in men, but not in women (1.03, 0.35–2.21). Conclusions In this population, serum hsCRP measurement predicted MI in men, but not in women. Under the low hsCRP level, a method of applicability of hsCRP to a risk assessment for preventing MI among Japanese people should be further explored.

Background: Cause of death (COD) information taken from death certificates is often inaccurate and incomplete. However, the accuracy of Underlying CODs (UCODs) recorded on death certificates has not been comprehensively described when multiple diseases are present. Methods: A total of 450 consecutive autopsies performed at a geriatric hospital in Japan between February 2000 and August 2002 were studied. We evaluated the concordance rate, sensitivity, and specificity of major UCODs (cancer, heart disease, and pneumonia) reported on death certificates compared with a reference standard of pathologist assessment based on autopsy data and clinical records. Logistic regression analysis was performed to assess the effect of sex, age, comorbidity, and UCODs on misclassification. Results: The concordance rate was relatively high for cancer (81%) but low for heart disease (55%) and pneumonia (9%). The overall concordance rate was 48%. Sex and comorbidity did not affect UCOD misclassification rates, which tended to increase with patient age, although the association with age was also not significant. The strongest factor for misclassification was UCODs (P < 0.0001). Sensitivity and specificity for cancer were very high (80% and 96%, respectively), but sensitivity for heart disease and pneumonia was 60% and 46%, respectively. Specificity for each UCOD was more than 85%. Conclusions: Researchers should be aware of the accuracy of COD data from death certificates used as research resources, especially for cases of elderly patients with pneumonia.

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.

Japan is an aging society, and the incidence of diseases related to aging, such as pneumonia, heart failure, vertebral compression fracture (VCF), is increasing. Prolonged hospital stays are becoming a serious social problem, leading to elevated medical expenses. Thus, shortening the period of hospitalization is important. This study aimed to reveal determinants associated with prolonged hospital stays for patients with VCF. Our institution is the primary hospital in a rural area in the Kanto region of Japan. Altogether, 110 patients with a VCF, aged 65 years or older, including 79 women, were divided into two groups according to the average hospital stay period of 28 days: the long-stay group (mean stay 40.0 ± 11.6 days, n = 39) and the short-stay group (mean stay 20.6 ± 4.4 days, n = 71). Notably, the short-stay group included 55 women. Multivariate logistic regression analyses in male showed no variates significantly associated with prolonged hospitalization. By contrast, multivariate logistic regression analyses in female showed requiring emergency transportation to hospital was significantly associated with prolonged hospitalization [odds ratio 7.69, 95% confidence interval 1.13-52.29, P = 0.04]. In conclusion, this study implies that patients with better levels of activities of daily living are able to walk alone sooner and are easily discharged. Furthermore, the patient requiring emergency transportation might be in a poor social living environment, such as living alone. These results may give us a good opportunity to re-consider fundamental problems surrounding the elderly.

This study aimed to investigate the associations of body mass index (BMI) and metabolically unhealthy weight with all-cause mortality, cardiovascular disease (CVD) mortality, and cancer mortality as well as the effect of age on the associations. This prospective study enrolled Japanese individuals in the general population. Participants were divided into eight phenotypes according to the BMI classification and metabolic status. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a Cox regression hazard model. In total, 10,824 individuals with a mean age of 55.3 years were evaluated. During a mean follow-up of 18.4 years (198,776 person-years), 2,274 participants died. Among the metabolically unhealthy, the association between BMI and mortality was J-shaped after adjustment for various confounders (multivariable HR [95% CI] for all-cause mortality: underweight, 2.0 [1.5–2.7]; obesity 2.8 [2.1–3.6]). The association remained the same in metabolically unhealthy participants aged

Additional file 1: Table S1. Multivariate analysis of cancer mortality with metabolic syndrome by sex, excluding participants

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/ "

Background Minor ST-T changes are frequently observed on the electrocardiogram (ECG), but the risk of stroke associated with such changes is unclear.Methods and Results:In 10,642 subjects from the Japanese general population, we evaluated minor and major ST-T changes (major ST depression ≥0.1 mV) on ECGs obtained at annual health examinations. At baseline, minor ST-T changes were found in 10.7% of the subjects and 0.5% had major ST-T changes. Minor ST-T changes were associated with older age, female gender, higher systolic blood pressure, presence of hyperlipidemia, and use of antihypertensive medication. There were 375 stroke events during the follow-up period (128.7±28.1 months). In all subjects, minor ST-T changes (HR, 2.10; 95% CI: 1.57-2.81) and major ST-T changes (HR, 8.64; 95% CI: 4.44-16.82) were associated with an increased risk of stroke, but the stroke risk associated with minor ST-T changes had borderline significance after adjustment for conventional risk factors (P=0.055). In subgroup analysis, the risk of stroke was significantly associated with minor ST-T changes in subjects who had hyperlipidemia (HR, 1.75; 95% CI: 1.15-2.67) compared to those without hyperlipidemia (HR, 1.01; 95% CI: 0.64-1.59; P for interaction=0.016), even after adjustment for ECG-diagnosed left ventricular hypertrophy. Conclusions Minor ST-T changes were particularly associated with a higher risk of stroke in subjects with hyperlipidemia and this association was independent of electrocardiographic left ventricular hypertrophy.

Dietary salt intake has been reported to be associated with cardiovascular disease (CVD). However, there were few studies that assessed the relationship of salt preference with CVD. We examined the association between salt preference and the incidence of CVD and its subtypes in a Japanese general population. Based on the prospective Jichi Medical School Cohort Study, data were analyzed from 11,394 eligible participants. A baseline survey of the preference for salt was obtained by questionnaire and health examinations from April 1992 through July 1995 in 12 communities in Japan. The participants were followed up until December 2005 (mean follow-up period, 10.7 ± 2.4 years). Subjects were divided into three categories according to their preference for salt: favor, so-so, and disfavor. A Cox proportional hazards model was used to calculate hazard ratios (HRs) of the incidence of CVD according to the preference categories. We observed 485 cardiovascular events (258 in men and 227 in women). Among the men, the multivariable adjusted HRs for incidence of myocardial infarction and subarachnoid hemorrhage for favor versus so-so salt preference were 0.34 (95% confidence interval, 0.17 - 0.71) and 7.10 (0.88 - 56.84), respectively. Among the women, age-adjusted HRs for the incidence of CVD, total stroke, cerebral hemorrhage, and cerebral infarction for the favor preference were 1.41 (1.02 - 1.95), 1.36 (0.97 - 1.91), 1.79 (0.87 - 3.71), and 1.40 (0.89 - 2.19), respectively. The data indicated that preference for salt may be associated with an increase in the incidence of CVD in women.