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Abstract 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.

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.

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 (

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.

Abstract 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: Previous studies indicate that professional identity formation (PIF), the formation of a self-identity with the internalised values and norms of professionalism, may influence self-regulated learning (SRL). However, it remains unclear whether a PIF-oriented intervention can improve SRL in clinical education. The aim of this study was to explore whether a PIF-oriented mentoring platform improves SRL in a clinical clerkship. Methods: A mixed-methods study was conducted. Forty-one students in a community-based clinical clerkship (CBCC) used a PIF-oriented mentoring platform. They articulated the values and norms of professionalism in a professional identity essay, elaborated on future professional self-image, and reflected on their current compared to future selves. They made a study plan while referring to PIF-based self-reflection and completed it. The control group of 41 students completed CBCC without the PIF-oriented mentoring platform. Changes in SRL between the two groups were quantitatively compared using the Motivated Strategies for Learning Questionnaire. We explore how PIF elements in the platform affected SRL by qualitative analysis of questionnaire and interview data. Results: A moderate improvement in intrinsic goal orientation (p = 0.005, ε2 = 0.096) and a mild improvement in critical thinking (p = 0.041, ε2 = 0.051) were observed in the PIF-oriented platform group. Qualitative analysis revealed that the PIF-oriented platform fostered professional responsibility as a key to expanding learning goals. Gaining authentic knowledge professionally fostered critical thinking, and students began to elaborate knowledge in line with professional task processes. Conclusion: A PIF-oriented mentoring platform helped students improve SRL during a clinical clerkship.

Abstract 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

Abstract 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 (R 2 = 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 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

Abstract Background Metabolic syndrome (MetS) and cancer are major public health problems worldwide. The relationship between MetS and cancer death is of great interest. We examined the predictive value of MetS for cancer mortality in Japan. Methods Study participants included 4495 men and 7028 women aged 18–90 years who were registered between 1992 and 1995 as part of the Jichi Medical School Cohort Study. We used a definition of MetS modified for the Japanese population. The primary outcome was cancer mortality. Additionally, the relationship between MetS and cancer-type specific mortality was examined. Analyses were conducted with Cox’s regression models adjusted for age, smoking status, alcohol drinking status, marital status, educational attainment, physical activity, occupational category, and menopausal status (only in women). Results During a mean follow-up of 18.5 years, 473 men and 297 women died from cancer. MetS was positively associated with cancer mortality in women (hazard ratio [HR], 1.69; 95% confidence interval [CI] 1.21–2.36), but not in men (HR, 1.21; 95% CI 0.90–1.62). Additionally, MetS was associated with a high risk of colorectal (HR, 3.48; 95% CI 1.68–7.22) and breast (HR, 11.90; 95% CI 2.25–62.84) cancer deaths in women. Conclusion MetS was a significant predictor of cancer mortality in women.

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

Objective To examine the association between polarity of atrial premature complexes (APCs) and stroke.Design A prospective study.Setting and participants A 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 measures The primary endpoint was stroke.Results Patients with APCs were significantly older than those without APCs (64.1±9.2 vs 55.1±11.6 years, p

Background and study aims We aimed to assess the efficacy and safety of the starting position during colonoscopy. Patients and methods We searched CENTRAL, MEDLINE, EMBASE, and the WHO International Clinical Trials Registry Platform through February 2019 to identify studies reporting the comparison between the right/supine/prone/tilt-down and left lateral starting position during colonoscopy. The primary outcomes were mean cecal insertion time and adverse events requiring medication. Two reviewers performed study selection and risk of bias assessment. We determined the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation method. This study was registered in PROSPERO (CRD42019124360). Results We identified 10 randomized controlled trials (RCTs) (2083 participants), including three trials on right/tilt-down versus left, two trials on supine/prone versus left, respectively. Mean difference in mean cecal insertion time in supine versus left was –41.0 s (95 % confidence interval [CI] –57.3 to –24.7) in one study and in tilt-down versus left was – 37.3 s (95 % CI –72.1 to –2.4; I2 = 58 %) in three studies; however, there were no statistically significant differences in prone/right versus left position (very low certainty of evidence). Four of eight studies noted adverse effects requiring medication (moderate certainty of evidence). One RCT applying the tilt-down position was terminated because of increased occurrence of oxygen desaturation. Conclusion We could not conclusively determine the efficacy and safety of the starting position during colonoscopy because of low certainty of evidence. Further studies are needed to confirm the efficacy and safety of the starting potion during colonoscopy.

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

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

This study was undertaken to evaluate the differences in chronotherapeutic effects of angiotensin-II receptor blockers, valsartan and olmesartan in hypertensive patients with non-dipper blood pressure (BP) pattern during valsartan at morning. Ninety four patients were enrolled, and 40 patients were judged to be non-dippers. In these patients, same dose of valsartan was changed to evening (Val-E, n = 12), or olmesartan (equivalent dose of valsartan) was given at morning (Olm-M, n = 13) or evening (Olm-E, n = 15) for 4 months. BP decreased during sleep and increased during waking hours in Val-E group. In Olm-M and Olm-E groups, BP decreased during sleep and waking hours. Percent reduction in BP at night-time compared to BP at waking hours significantly increased after changing the dose regimen in each group. Serum creatinine decreased and estimated glomerular filtration rate (eGFR) elevated in Olm-M and Olm-E, but not Val-E groups. Positive correlation between systolic BP (SBP) during sleep and serum creatinine, and negative correlation between SBP during sleep and eGFR were detected. These data suggest that dipper BP pattern could be obtained by chronotherapeutic approach using valsartan and olmesartan in non-dipper patients with valsartan at morning. Morning and evening olmesartan, but not evening valsartan improved renal function in these patients.

BACKGROUND: Experimental studies support the anti-neoplastic effect of apo(a), but several clinical studies have reported contradictory results. The purpose of this study was to determine whether a low lipoprotein(a) [Lp(a)] concentration is related to mortality from major causes of death, especially cancer. METHODS: The subjects were 10,413 participants (4,005 men and 6,408 women) from a multi-center population-based cohort study in Japan (The Jichi Medical School cohort study). The average age at registration was 55.0 years, and the median observation period was 4,559 days. As the estimated hazard ratio was high for both the low and very high Lp(a) levels, we defined two Lp(a) groups: a low Lp(a) group [Lp(a)