Age and sex differences in the risk of cardiovascular diseases by chronic kidney disease in a general Japanese population.

The risk of cardiovascular diseases (CVD) by chronic kidney disease (CKD) stratified by age and sex has not been examined in detail in rural Japanese populations. Therefore, we herein investigated the long-term risk of CVD by CKD and performed an age- and sex-stratified risk analysis. We examined 5163 subjects who underwent health screening between 1992 and 1995 with calculated eGFR and follow-up information on CVD events. The mean follow-up period was 10 years. We analyzed the incidences of CVD events, including stroke and myocardial infarction (MI). We compared the risk of CVD between subjects with and without CKD using a Cox proportional hazards model adjusted for well-known CVD confounding factors. The total number of CVD events was 175. The hazard ratios (HRs) for all events, stroke, MI, and sudden death by CKD relative to non-CKD were 1.18 (95% C.I.:0.83-1.68), 0.96 (0.63-1.46), 3.02 (1.2-7.62), and 1.29 (0.43-3.87), respectively. HRs for MI were 7.24 in subjects < 65 years and 1.65 in those ≥ 65 years. HRs for MI by sex were 3.55 in men and 2.09 in women. A younger age and men sex were identified as independent risk factors for the risk of MI in the presence of CKD. These results suggest that among CKD patients, the management of a younger age group and men will effectively prevent MI.

Association between physical activity and mortality in the Japanese general population with mild to moderate impaired renal function: the Jichi Medical School (JMS) cohort study.

BACKGROUND: The association between physical activity volume or intensity and mortality in general population with impaired renal function is unclear. We assessed these relationships among Japanese residents with impaired renal function. METHODS: We analyzed 638 individuals with estimated creatinine clearance below 60 ml/min in the Jichi Medical School cohort study. Exposures included the daily amount of physical activity converted to the physical activity index (PAI) used in the Framingham study and the activity time for each intensity. Physical activity intensity was classified into sedentary and nonsedentary. Nonsedentary activity was further divided into light-intensity and moderate-to-vigorous physical activity (MVPA). The outcome was all-cause mortality. Quartiles of the exposures were created, and hazard ratios (HRs) were calculated using the Cox proportional hazards model. RESULTS: The mean age of the subjects was 63.3 years, and 72.4% were female. In total, 172 deaths were registered during 11,567 person-years. No significant association was found between PAI and mortality. A significant association was found between long sedentary time and increased mortality (p = 0.042). Regarding nonsedentary activity, the HRs [95% confidence intervals (CIs)] for Q2, Q3, and Q4 versus Q1 were 0.85 (0.55-1.31), 0.67 (0.41-1.08), and 0.90 (0.54-1.45), respectively. In the subdivided analysis for light-intensity activity, the HRs (95% CIs) of Q2, Q3, and Q4 versus Q1 were 0.53 (0.33-0.84), 0.51 (0.34-0.82), and 0.57 (0.34-0.96), respectively. No significant association was found between MVPA and mortality. CONCLUSIONS: Nonsedentary activity, especially light-intensity activity, significantly reduced mortality among residents with impaired renal function.

The seroprevalence of neutralizing antibodies against the adeno-associated virus capsids in Japanese hemophiliacs.

Adeno-associated virus (AAV) vectors are promising modalities of gene therapy to address unmet medical needs. However, anti-AAV neutralizing antibodies (NAbs) hamper the vector-mediated therapeutic effect. Therefore, NAb prevalence in the target population is vital in designing clinical trials with AAV vectors. Hence, updating the seroprevalence of anti-AAV NAbs, herein we analyzed sera from 100 healthy individuals and 216 hemophiliacs in Japan. In both groups, the overall seroprevalence against various AAV serotypes was 20%-30%, and the ratio of the NAb-positive population increased with age. The seroprevalence did not differ between healthy participants and hemophiliacs and was not biased by the concomitant blood-borne viral infections. The high neutralizing activity, which strongly inhibits the transduction with all serotypes in vitro, was mostly found in people in their 60s or of older age. The multivariate analysis suggested that "60s or older age" was the only independent factor related to the high titer of NAbs. Conversely, a large proportion of younger hemophiliacs was seronegative, rendering them eligible for AAV-mediated gene therapy in Japan. Compared with our previous study, the peak of seroprevalences has shifted to older populations, indicating that natural AAV exposure in the elderly occurred in their youth but not during the last decade.

Follow up of Kawasaki disease based on nationwide survey data in Japan: Mortality among those with a history of Kawasaki disease in Japan: Results of a 30-year follow up: Mortality among those with a history of Kawasaki disease in Japan: Results of a 30-year follow up.

BACKGROUND: The long-term prognosis of those with a history of Kawasaki disease (KD) is still unknown. METHODS: Using a permanent registry system in Japan (koseki), 6,576 persons with a history of KD were followed up. The average follow-up period was 30 years. The endpoint was death. RESULTS: With a 99.5% follow-up rate, 68 deaths (48 males and 20 females) were observed. The overall standardized mortality ratio, of which reference was vital statistics in Japan, was not elevated. However, the observation according to the presence or absence of cardiac sequelae showed that the standardized mortality ratio for those with cardiac sequelae significantly elevated. Nine persons, all of whom were males, died of KD (including those cases where KD was suspected), but all deaths occurred in individuals who were under 30 years of age. CONCLUSIONS: This study revealed the long-term prognosis for KD, but almost all participants were younger than 40 years. Continuing follow up of this cohort is required to clarify whether a history of KD relates to the development of atherosclerosis when participants become middle aged or older.

Electromagnetic-guided versus endoscopic-guided postpyloric placement of nasoenteral feeding tubes.

BACKGROUND: For people who are malnourished and unable to consume food by mouth, nasoenteral feeding tubes are commonly used for the administration of liquid food and drugs. Postpyloric placement is when the tip of the feeding tube is placed beyond the pylorus, in the small intestine.  Endoscopic-guided placement of postpyloric feeding tubes is the most common approach. Usually, an endoscopist and two or more medical professionals perform this procedure using a guidewire technique. The position of the tube is then confirmed with fluoroscopy or radiography, which requires moving people undergoing the procedure to the radiology department. Alternatively, electromagnetic-guided placement of postpyloric nasoenteral feeding tubes can be performed by a single trained nurse, at the bedside and with less equipment than endoscopic-guided placement. Hence, electromagnetic-guided placement may represent a promising alternative to endoscopic-guided placement, especially in settings where endoscopy and radiographic facilities are unavailable or difficult to access. OBJECTIVES: To assess the efficacy and safety of electromagnetic-guided placement of postpyloric nasoenteral feeding tubes compared to endoscopic-guided placement. SEARCH METHODS: We searched the Cochrane Library, MEDLINE, Embase, CINAHL, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, and OpenGrey until February 2021. We screened the reference lists of relevant review articles and current treatment guidelines for further literature. We contacted the study authors for missing data. SELECTION CRITERIA: We included randomised trials comparing electromagnetic-guided placement with endoscopic-guided placement of nasoenteral feeding tubes. We excluded prospective cohort studies, retrospective cohort studies, (nested) case-control studies, cross-sectional studies, and case series or case reports. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the methodological quality of potentially eligible trials and extracted data from the included trials. The primary outcomes were technical success in insertion and aspiration pneumonitis. The secondary outcomes were the time for postpyloric placement of nasoenteral feeding tubes, direct healthcare costs, and adverse events. We performed a random-effects meta-analysis. We calculated risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous outcomes and mean differences (MDs) with 95% CIs for continuous outcomes. We evaluated the certainty of evidence based on the GRADE approach. MAIN RESULTS: We identified four randomised controlled trials with 541 participants which met our inclusion criteria. All trials had methodological limitations, and lack of blinding of participants and investigators was a major source of bias. We had 'some concerns' for the overall risk of bias in all trials.  Electromagnetic-guided postpyloric placement of nasoenteral feeding tubes may result in little to no difference in technical success in insertion compared to endoscopic-guided placement (RR 1.09, 95% CI 0.88 to 1.35; I2 = 81%; low-certainty evidence). Electromagnetic-guided placement may result in a difference in the proportion of participants with aspiration pneumonitis compared to endoscopic-guided placement, but these results are unclear (RR 0.24, 95% CI 0.03 to 2.18; I2 = 0%; low-certainty evidence).  Electromagnetic-guided placement may result in little to no difference in the time for postpyloric placement of nasoenteral feeding tubes compared to endoscopic-guided placement (MD 4.06 minutes, 95% CI -0.47 to 8.59; I2 = 97%; low-certainty evidence). Electromagnetic-guided placement likely reduces direct healthcare costs compared to endoscopic-guided placement (MD -127.69 US dollars, 95% CI -135.71 to -119.67; moderate-certainty evidence). Electromagnetic-guided placement likely results in little to no difference in adverse events compared with endoscopic-guided placement (RR 0.78, 95% CI 0.41 to 1.49; moderate-certainty evidence). AUTHORS' CONCLUSIONS: We found low-certainty evidence that electromagnetic-guided placement at the bedside results in little to no difference in technical success in insertion and aspiration pneumonitis, compared to endoscopic-guided placement. The heterogeneity of the healthcare professionals who performed the procedures and the small sample sizes limited our confidence in the evidence. Future research should be based on large studies with well-defined endpoints to potentially elucidate the differences between these two procedures.

Dietitian-supported dietary intervention leads to favorable dietary changes in patients with type 2 diabetes: A randomized controlled trial.

AIMS/INTRODUCTION: It remains to be fully elucidated whether nutrition education by dietitians can lead to specific positive changes in the food choices of patients with diabetes. 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 control group that received nutritional education once a year. The total energy intake, energy-providing nutrients and 18 food groups were analyzed at baseline, and 1 and 2 years after the intervention in 87 patients. Furthermore, the relationship between the changes in hemoglobin A1c, body composition and changes in the total energy or energy-producing nutrient intake was analyzed in 48 patients who did not use or change hypoglycemic agents during the study period. RESULTS: The total energy intake, carbohydrates, cereals, confections, nuts and seeds, and seasonings significantly decreased, and fish and shellfish intake significantly increased during the study period in the intensive intervention group, whereas these changes were not observed in the control group. The decrease in the total energy intake and carbohydrates after 2 years was significantly greater in the intensive intervention group than in the control group. The change in the total energy and carbohydrate intake showed a significant positive correlation with that in muscle mass. The multivariate analysis showed that the decrease in total energy intake was independently associated with that in muscle mass. CONCLUSION: Dietitian-supported intensive dietary intervention helps improve the diet of patients with type 2 diabetes.

TG/HDL-C ratio as a predictor of stroke in the population with healthy BMI: The Jichi Medical School Cohort Study.

BACKGROUND AND AIMS: The triglycerides-to-high-density lipoprotein cholesterol ratio (TG/HDL-C) is a predictor of metabolic syndrome and cardiovascular disease onset. However, the relationship between TG/HDL-C and stroke has not been established. This study examined whether TG/HDL-C helps in predicting stroke onset; this was compared between the whole population and healthy body mass index (BMI) population. METHODS AND RESULTS: The Jichi Medical School Cohort Study is a prospective cohort study involving baseline data collected in 12 Japanese districts between April 1992 and July 1995. We used data from 11,699 participants; participants with a healthy BMI (20.0-24.9 kg/m2) were grouped into sex-specific TG/HDL-C quartiles. Using the first quartile groups as references, the hazard ratios (HRs) and 95% confidence intervals (CIs) of the Cox proportional hazards model were calculated. During the mean 10.8 years of follow-up, 419 new stroke events were recorded. The multivariable-adjusted HRs (95% CIs) in the fourth quartile of the whole population were 1.28 (0.94-1.75), 1.78 (0.91-3.48), 1.20 (0.82-1.77), and 1.13 (0.50-2.54), as compared to those in the fourth quartile of the healthy BMI population, which were 1.87 (1.24-2.83), 3.06 (1.21-7.74), 1.79 (1.05-3.05), and 1.29 (0.49-3.41) for all patients with all stroke, intracerebral hemorrhage, cerebral infarction, and subarachnoid hemorrhage, respectively. CONCLUSION: Increased TG/HDL-C correlated with a significant increase in stroke risk only in the healthy BMI population and not the whole population. Furthermore, it was primarily associated with increased intracerebral hemorrhage and cerebral infarction risk.

Stroke Risk Due to Smoking Characterized by Sex Differences in Japan: The Jichi Medical School Cohort Study.

OBJECTIVES: Smoking is a risk factor for stroke. The relationship between smoking and the risk of different subtypes of stroke has not been fully elucidated. We investigated the relationship between smoking and the incidence of stroke in the Japanese population. MATERIALS AND METHODS: This prospective, population-based cohort study included 11,324 participants (4447 men; 6877 women) from 12 districts in Japan, between April 1992 and July 1995. Participants were stratified according to smoking status (non-smoker [never smoked]/ex-smoker/current smoker). Male current smokers were further stratified according to the number of cigarettes smoked per day (1-14, 15-29, or ≥ 30). The non-smoking group was used as a reference. Cox proportional hazards analysis was used to determine the risk of stroke due to smoking. RESULTS: Four hundred and seventeen new stroke events (212 men; 205 women) were recorded during a mean follow-up of 10.7 years, including 95 intracerebral hemorrhages (48 men; 47 women), 267 cerebral infarctions (152 men; 115 women), and 54 subarachnoid hemorrhages (12 men; 42 women). In multivariable analysis, the hazard ratios (95% confidence intervals) for male current smokers (≥ 30 cigarettes/day) were 1.89 (1.08-3.31) and 3.41 (1.22-9.57) for all strokes and intracerebral hemorrhages, respectively; those for female current smokers were 2.78 (1.62-4.74), 3.14 (1.51-6.54), and 4.03 (1.64-9.93) for all strokes, cerebral infarctions, and subarachnoid hemorrhages, respectively. CONCLUSIONS: Smoking ≥ 30 cigarettes/day is a risk factor for stroke, especially intracerebral hemorrhage in men. Furthermore, smoking increases the risk of cerebral infarction and subarachnoid hemorrhage in women.

Hemoglobin Concentration and the Incidence of Stroke in the General Japanese Population: The Jichi Medical School Cohort Study.

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.

The Association Between Sleeping Pill Use and Metabolic Syndrome in an Apparently Healthy Population in Japan: JMS-II Cohort Study.

BACKGROUND: Sleeping pills are widely used for sleep disorders and insomnia. This population-based study aimed to evaluate the association between the use of sleeping pills and metabolic syndrome (MetS) and metabolic components in an apparently healthy Japanese cohort. METHODS: We examined baseline cross-sectional data from the JMS-II Cohort Study. The criteria for MetS and its components were based on The National Cholesterol Education Program Adult Treatment Panel III. Sleep habits including the sleep duration of the subjects and the frequency of sleeping pill use were obtained using The Pittsburgh Sleep Quality Index questionnaire. For different sleep durations, the association between sleeping pill use and MetS was assessed. Odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated using multiple logistic regression models to quantify this association. RESULTS: Our study included 6,153 individuals (mean age, 63.8 [standard deviation 11.2] years), and 3,348 (54.4%) among them were women. The association between sleep duration and MetS was an inverted J-shaped curve among sleeping pill users and a J-shaped curve among non-users. After adjustment for various confounders, less than 6 h of sleep among sleeping pill users was associated with increased rates of MetS (<6 h, OR 3.08; 95% CI, 1.29-7.34]). The frequency of sleeping pill use in individuals with short sleep duration showed a positive association with the prevalence of MetS and its components. CONCLUSIONS: Sleeping pill users with a short sleep duration had a 3-fold higher chance of having MetS than non-users with a short sleep duration.

Comparison of the effects of frequent versus conventional nutritional interventions in patients with type 2 diabetes mellitus: A randomized, controlled trial.

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.

Prediction of Lifetime Risk of Cardiovascular Disease Deaths Stratified by Sex in the Japanese Population.

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 <4.65 mmol/L, systolic blood pressure <120 mm Hg, diastolic blood pressure <80 mm Hg, absence of diabetes, and absence of smoking habit) was lower compared with the highest risk profile of ≥2 risk factors (6.8% [95% CI, 0%-11.9%] versus 19.4% [16.7%-21.4%] for men and 6.9% [1.2%-11.5%] versus 15.4% [12.6%-18.1%] for women). 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.

Prevention paradox between stroke and multiple potential risk factors using data from a population-based cohort study.

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.

Education policies to increase rural physicians in Japan: a nationwide cohort study.

BACKGROUND: Japan has established comprehensive education-scholarship programs to supply physicians in rural areas. Their entrants now comprise 16% of all medical students, and graduates must work in rural areas for a designated number of years. These programs are now being adopted outside Japan, but their medium-term outcomes and inter-program differences are unknown. METHODS: A nationwide prospective cohort study of newly licensed physicians 2014-2018 (n = 2454) of the four major types of the programs-Jichi Medical University (Jichi); regional quota with scholarship; non-quota with scholarship (scholarship alone); and quota without scholarship (quota alone)-and all Japanese physicians in the same postgraduate year (n = 40,293) was conducted with follow-up workplace information from the Physician Census 2018, Ministry of Health, Labour and Welfare. In addition, annual cross-sectional survey for prefectural governments and medical schools 2014-2019 was conducted to obtain information on the results of National Physician License Examination and retention status for contractual workforce. RESULTS: Passing rate of the National Physician License Examination was highest in Jichi, followed in descending order by quota with scholarship, the other two programs, and all medical graduates. The retention rate for contractual rural service of Jichi graduates 5 years after graduation (n = 683; 98%) was higher than that of quota with scholarship (2868; 90%; P < 0.001) and scholarship alone (2220; 81% < 0.001). Relative risks of working in municipalities with the least population density quintile in Jichi, quota with scholarship, scholarship alone, and quota alone in postgraduate year 5 were 4.0 (95% CI 3.7-4.4; P < 0.001), 3.1 (2.6-3.7; < 0.001), 2.5 (2.1-3.0; < 0.001), and 2.5 (1.9-3.3; < 0.001) as compared with all Japanese physicians. There was no significant difference between each program and all physicians in the proportion of those who specialized in internal medicine or general practice in postgraduate years 3 to 5 CONCLUSIONS: Japan's education policies to produce rural physicians are effective but the degree of effectiveness varies among the programs. Policymakers and medical educators should plan their future rural workforce policies with reference to the effectiveness and variations of these programs.

Association among age, gender, menopausal status and small dense low-density lipoprotein cholesterol: a cross-sectional study.

OBJECTIVES: 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 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. DESIGN: This was a cross-sectional study. SETTING: 13 rural districts in Japan, 2010-2017. PARTICIPANTS: This 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. RESULTS: In 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 (p<0.001). CONCLUSIONS: SdLDL-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.

Limited effects from professional identity formation-oriented intervention on self-regulated learning in a preclinical setting: a randomized-controlled study in Japan.

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 reflection and learning plan format, then tested effectiveness on raising self-regulated learning in a preclinical 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) experienced professional identity formation-oriented format: Group A had three sessions with the intervention format 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.

A Combination of Blood Pressure and Total Cholesterol Increases the Lifetime Risk of Coronary Heart Disease Mortality: EPOCH-JAPAN.

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.

Lidocaine spray versus viscous lidocaine solution for pharyngeal local anesthesia in upper gastrointestinal endoscopy: Systematic review and meta-analysis.

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.