Association of polydoctoring and mortality among very old persons with multimorbidity: a prospective cohort study in Japan.

BACKGROUND: Polydoctoring is a crucial aspect of care fragmentation among patients with multimorbidity, but its impact on health outcomes remains unclear. AIM: To determine the effects of polydoctoring, as measured by the Regularly Visited Facility (RVF) indicator, on patient outcomes among older individuals with multimorbidity. DESIGN & SETTING: Data from the ongoing prospective cohort study, Kawasaki Aging and Wellbeing Project (KAWP), was utilized in this study. Among the 1,026 KAWP participants aged 85-89 years, those with two or more chronic conditions were enrolled in this study. METHOD: Care fragmentation or polydoctoring, was evaluated using the RVF, a new indicator that measures the number of medical facilities consistently involved in a patient's care. Based on RVF, mortality was analysed using the Cox-hazards model, with adjustments for age, sex, frailty, and number of comorbidities. RESULTS: A significant reduction in mortality rates was observed in participants with an RVF of ≥3 and 2-4 comorbidities (hazard ratio [HR] 0.46, 95% confidence interval [CI]: 0.18-0.99). However, no significant difference in mortality based on RVF was observed for those with ≥5 comorbidities. Notably, individuals with ≥5 comorbidities and an RVF of 0 had a significantly higher HR for death (HR 2.68, 95% CI 1.05-6.84). CONCLUSIONS: In older patients with multimorbidity, polydoctoring reduces mortality in patients with ≤4 coexisting conditions, but it does not significantly impact mortality in those with ≥5 conditions. These findings provide insights for healthcare decision-making in managing older patients with multimorbidity.

Progress report of the Tohoku Medical Megabank Community-Based Cohort Study: Study profile of the repeated center-based survey during second period in Miyagi Prefecture.

BACKGROUND: The purpose of this study was to report the basic profile of the Miyagi Prefecture part of a repeated center-based survey during the second period (2nd period survey) of the Tohoku Medical Megabank Community-Based Cohort Study (TMM CommCohort Study), as well as the participants' characteristics based on their participation type in the baseline survey. METHODS: The 2nd period survey, conducted from June 2017 to March 2021, included participants of the TMM CommCohort Study (May 2013 to March 2016). In addition to the questionnaire, blood, urine, and physiological function tests were performed during the 2nd period survey. There were three main ways of participation in the baseline survey: Type 1, Type 1 additional, or Type 2 survey. The 2nd period survey was conducted in the same manner as the Type 2 survey, which was based on the community support center (CSC). RESULTS: In Miyagi Prefecture, 29,383 (57.7%) of 50,967 participants participated in the 2nd period survey. The participation rate among individuals who had visited the CSC was approximately 80%. Although some factors differed depending on the participation type in the baseline survey, the 2nd period survey respondents in the Type 1 and Type 2 survey groups at baseline had similar traits. CONCLUSIONS: The 2nd period survey of the TMM CommCohort Study provided detailed follow-up information. Following up on the health conditions of the participants will clarify the long-term effects of disasters and contribute to personalized prevention.

Relationships of Fat Mass Index and Fat-Free Mass Index with Low-Density Lipoprotein Cholesterol Levels in the Tohoku Medical Megabank Community-Based Cohort Study.

AIMS: Although fat mass (FM) and fat-free mass (FFM) have an impact on lipid metabolism, the relationship between different body composition phenotypes and lipid profiles is still unclear. By dividing the FM and FFM by the square of the height, respectively, the f at mass index (FMI) and fat-free mass index (FFMI) can be used to determine the variations in body composition. This study aimed to investigate the relationship of combined FMI and FFMI with low-density lipoprotein cholesterol (LDL-C) levels. METHODS: This cross-sectional study comprised 5,116 men and 13,630 women without cardiovascular disease and without treatment for hypertension, and diabetes. Following sex-specific quartile classification, FMI and FFMI were combined into 16 groups. Elevated LDL-C levels were defined as LDL-C ≥ 140 mg/dL and/or dyslipidemia treatment. Multivariable logistic regression models were used to examine the relationships between combined FMI and FFMI and elevated LDL-C levels. RESULTS: Overall, elevated LDL-C levels were found in 1,538 (30.1%) men and 5,434 (39.9%) women. In all FFMI subgroups, a higher FMI was associated with elevated LDL-C levels. Conversely, FFMI was inversely associated with elevated LDL-C levels in most FMI subgroups. Furthermore, the groups with the highest FMI and lowest FFMI had higher odds ratios for elevated LDL-C levels than those with the lowest FMI and highest FFMI. CONCLUSIONS: Regardless of FFMI, FMI was positively associated with elevated LDL-C levels. Conversely, in the majority of FMI subgroups, FFMI was inversely associated with elevated LDL-C levels.

Relationship between traditional risk factors for hypertension and systolic blood pressure in the Tohoku Medical Megabank Community-based Cohort Study.

Risk factors for hypertension have been emphasized in the Japanese Society of Hypertension Guidelines for the Management of Hypertension. However, large-scale studies on the association of smoking, potassium excretion, and gamma-glutamyl transferase level with BP in the Japanese population are limited. We conducted a cross-sectional study to examine the association between hypertension risk factors and systolic blood pressure in the Tohoku Medical Megabank Community-based Cohort Study (23,446 men and 38,921 women aged ≥20 years). A model adjusted for age, body mass index, smoking status, drinking status, estimated daily salt intake, potassium excretion, (or urinary sodium-to-potassium ratio), gamma-glutamyl transferase, physical activity, education level, status of damage to homes during the Great East Japan Earthquake, and residential areas was used. The average age and systolic blood pressure were 62.5 (10.3) years for men and 59.6 (11.3) years for women, 128.9 (16.7) mmHg for men and 124.7 (17.5) mmHg for women, respectively. Body mass index estimated daily salt intake, urinary sodium-to-potassium ratio and gamma-glutamyl transferase levels were positively associated with systolic blood pressure. Compared with never-drinkers, current drinkers who consumed 23-45 g/day and ≥46.0 g/day had significantly increased systolic blood pressure. Conversely, current smokers (1-10 cigarettes/day and 11-20 cigarettes/day) were inversely associated with systolic blood pressure compared to never-smokers. Overall, systolic blood pressure was associated with gamma-glutamyl transferase and hypertension risk factors, including body mass index, alcohol consumption, estimated daily salt intake, urinary sodium-to-potassium ratio, and potassium excretion. Our findings support the notion that lifestyle modifications should be attempted to prevent hypertension.

The clinical trial of alternative relugolix administration for uterine leiomyoma prior to surgically treatment: a study protocol for Non-Adverse Relugolix Administration (NARA) trial.

BACKGROUND: Uterine leiomyomas are common for reproductive-aged women and affect women's quality of life due to heavy menstrual bleeding or dysmenorrhea. Leiomyomas grow according to estradiol exposure and decrease after post-menopause. In case serious symptoms are caused by leiomyomas, pharmacotherapy or surgical treatment is proposed. Prior to surgical treatment, pharmacotherapies aimed at the reduction of leiomyoma and uterine volume or improvement of anemia are introduced to conduct minimum invasive surgery (i.e., to reduce blood loss or surgical duration). Recently, relugolix (40 mg orally once daily) as a gonadotropin-releasing hormone (GnRH) receptor antagonist has proved its sufficient efficacy in suppressing estradiol levels without the transient estradiol flare-up compared with GnRH agonist. However, long-term administration should not be permitted liable to for climacteric disorder or osteoporosis, and evidence is lacking on the actual efficacy and extent of adverse effects of the every-other-day dosing regimen. This trial aimed to prove non-inferiority in volume reduction effect on leiomyoma and safety (i.e., reduction of adverse effects) by every-other-day administration after 2 months of everyday administration compared to daily administration throughout the duration. METHODS: A minimization adaptive randomized control trial (RCT) will be conducted. Patients (over 20 years old) harboring leiomyoma who will be undergoing surgical treatment will be invited to participate. Patients who are enrolled in the intervention group will receive every-other-day administration for 16 weeks after 8 weeks of daily administration. Patients who are enrolled in the control group will receive daily throughout the 24 weeks. The primary outcome is the leiomyoma volume reduction, and the secondary endpoints are the reduction of uterine volume, the occurrence of the climacteric disorder, genital bleeding days, change rate of serum hormone or bone turnover markers, and bone mineral density after 24 weeks compared to before administration. DISCUSSION: This study aims to prove both the non-inferiority in leiomyoma volume reduction and superiority in adverse effects occurrence reduction, which will provide a novel method to escape adverse effects while maintaining the effect of leiomyoma reduction. TRIAL REGISTRATION: Japan Registry of Clinical Trials jRCTs051230078. Registered on 26 July 2023.

Association Between Advanced Airway Management With Adrenaline Injection and Prognosis in Adult Patients With Asystole Asphyxia Out-of-hospital Cardiac Arrest.

BACKGROUND: The neurological prognosis of asphyxia is poor and the effect of advanced airway management (AAM) in the prehospital setting remains unclear. This study aimed to evaluate the association between AAM with adrenaline injection and prognosis in adult patients with asystole asphyxia out-of-hospital cardiac arrest (OHCA). METHODS: This study assessed all-Japan Utstein cohort registry data between January 1, 2013 and December 31, 2019. We used propensity score matching analyses before logistic regression analysis to evaluate the effect of AAM on favorable neurological outcome. RESULTS: There were 879,057 OHCA cases, including 70,299 cases of asphyxia OHCAs. We extracted the data of 13,642 cases provided with adrenaline injection by emergency medical service. We divided 7,945 asphyxia OHCA cases in asystole into 5,592 and 2,353 with and without AAM, respectively. After 1:1 propensity score matching, 2,338 asphyxia OHCA cases with AAM were matched with 2,338 cases without AAM. Favorable neurological outcome was not significantly different between the AAM and no AAM groups (adjusted odds ratio [OR] 1.1; 95% confidence interval [CI], 0.5-2.5). However, the return of spontaneous circulation (ROSC) (adjusted OR 1.7; 95% CI, 1.5-1.9) and 1-month survival (adjusted OR 1.5; 95% CI, 1.1-1.9) were improved in the AAM group. CONCLUSION: AAM with adrenaline injection for patients with asphyxia OHCA in asystole was associated with improved ROSC and 1-month survival rate but showed no differences in neurologically favorable outcome. Further prospective studies may comprehensively evaluate the effect of AAM for patients with asphyxia.

Measurement of polydoctoring as a crucial component of fragmentation of care among patients with multimorbidity: Cross-sectional study in Japan.

Background: Care fragmentation, characterized by the uncoordinated involvement of multiple healthcare providers, leads to inefficient and ineffective healthcare, posing a significant challenge in managing patients with multimorbidity. In this context, "polydoctoring," where patients see multiple specialists, emerges as a crucial aspect of care fragmentation. This study seeks to develop an indicator to assess polydoctoring, which can subsequently enhance the management of multimorbidity. Methods: Baseline survey data from the Kawasaki Aging and Wellbeing Project (KAWP) involving independent community-dwelling older adults aged 85-89 were utilized in this cross-sectional study. Polydoctoring measure was defined as the number of regularly visited facilities (RVFs). The association of RVF with the Fragmentation of Care Index (FCI) and the outcome measures of polypharmacy and ambulatory care costs were examined as indicators of care fragmentation. Results: The analysis comprised 968 participants, with an average of 4.70 comorbid chronic conditions; 65.3% of the participants had two or more RVFs, indicating polydoctoring. A significant correlation between RVF and FCI was observed. Modified Poisson regression analyses revealed associations between higher RVF and increased prevalence ratio of polypharmacy. Likewise, a higher RVF was associated with higher outpatient medical costs. Conclusions: RVF was significantly correlated with FCI, polypharmacy, and higher outpatient medical costs. Unlike complex indices, RVF is simple and intuitively comprehensible. Further research is needed to evaluate the impact of care fragmentation on patient outcomes, considering factors such as RVF thresholds, patient multimorbidity, and social support. Understanding the influence of polydoctoring can enhance care quality and efficiency for patients with multimorbidity.

Influence of Diabetes Family History on the Associations of Combined Genetic and Lifestyle Risks with Diabetes in the Tohoku Medical Megabank Community-Based Cohort Study.

AIM: The influence of family history of diabetes, probably reflecting genetic and lifestyle factors, on the association of combined genetic and lifestyle risks with diabetes is unknown. We examined these associations. METHODS: This cross-sectional study included 9,681 participants in the Tohoku Medical Megabank Community-based Cohort Study. A lifestyle score, which was categorized into ideal, intermediate, and poor lifestyles, was given. Family history was obtained through a self-reported questionnaire. A polygenic risk score (PRS) was constructed in the target data (n=1,936) using publicly available genome-wide association study summary statistics from BioBank Japan. For test data (n=7,745), we evaluated PRS performance and examined the associations of combined family history and genetic and lifestyle risks with diabetes. Diabetes was defined as non-fasting blood glucose ≥ 200 mmHg, HbA1c ≥ 6.5%, and/or self-reported diabetes treatment. RESULTS: In test data, 467 (6.0%) participants had diabetes. Compared with a low genetic risk and an ideal lifestyle without a family history, the odds ratio (OR) was 3.73 (95% confidence interval [CI], 1.92-7.00) for a lower genetic risk and a poor lifestyle without a family history. Family history was significantly associated with diabetes (OR, 3.58 [95% CI, 1.73-6.98]), even in those with a low genetic risk and an ideal lifestyle. Even among participants who had an ideal lifestyle without a family history, a high genetic risk was associated with diabetes (OR, 2.49 [95% CI, 1.65-3.85]). Adding PRS to family history and conventional lifestyle risk factors improved the prediction ability for diabetes. CONCLUSIONS: Our findings support the notion that a healthy lifestyle is important to prevent diabetes regardless of genetic risk.

Status and physiological significance of circulating adiponectin in the very old and centenarians: an observational study.

Background: High levels of circulating adiponectin are associated with increased insulin sensitivity, low prevalence of diabetes, and low body mass index (BMI); however, high levels of circulating adiponectin are also associated with increased mortality in the 60-70 age group. In this study, we aimed to clarify factors associated with circulating high-molecular-weight (cHMW) adiponectin levels and their association with mortality in the very old (85-89 years of age) and centenarians. Methods: The study included 812 (women: 84.4%) for centenarians and 1498 (women: 51.7%) for the very old. The genomic DNA sequence data were obtained by whole-genome sequencing or DNA microarray-imputation methods. Least Absolute Shrinkage and Selection Operator (LASSO) and multivariate regression analyses were used to evaluate cHMW adiponectin characteristics and associated factors. All-cause mortality was analyzed in three quantile groups of cHMW adiponectin levels using Cox regression. Results: The cHMW adiponectin levels were increased significantly beyond 100 years of age, were negatively associated with diabetes prevalence, and were associated with SNVs in CDH13 (p=2.21 × 10-22) and ADIPOQ (p=5.72 × 10-7). Multivariate regression analysis revealed that genetic variants, BMI, and high-density lipoprotein cholesterol (HDLC) were the main factors associated with cHMW adiponectin levels in the very old, whereas the BMI showed no association in centenarians. The hazard ratios for all-cause mortality in the intermediate and high cHMW adiponectin groups in very old men were significantly higher rather than those for all-cause mortality in the low-level cHMW adiponectin group, even after adjustment with BMI. In contrast, the hazard ratios for all-cause mortality were significantly higher for high cHMW adiponectin groups in very old women, but were not significant after adjustment with BMI. Conclusions: cHMW adiponectin levels increased with age until centenarians, and the contribution of known major factors associated with cHMW adiponectin levels, including BMI and HDLC, varies with age, suggesting that its physiological significance also varies with age in the oldest old. Funding: This study was supported by grants from the Ministry of Health, Welfare, and Labour for the Scientific Research Projects for Longevity; a Grant-in-Aid for Scientific Research (No 21590775, 24590898, 15KT0009, 18H03055, 20K20409, 20K07792, 23H03337) from the Japan Society for the Promotion of Science; Keio University Global Research Institute (KGRI), Kanagawa Institute of Industrial Science and Technology (KISTEC), Japan Science and Technology Agency (JST) Research Complex Program "Tonomachi Research Complex" Wellbeing Research Campus: Creating new values through technological and social innovation (JP15667051), the Program for an Integrated Database of Clinical and Genomic Information from the Japan Agency for Medical Research and Development (No. 16kk0205009h001, 17jm0210051h0001, 19dk0207045h0001); the medical-welfare-food-agriculture collaborative consortium project from the Japan Ministry of Agriculture, Forestry, and Fisheries; and the Biobank Japan Program from the Ministry of Education, Culture, Sports, and Technology.

Nutritional Adequacy Assessment of the Japanese Diet Using the Number of Dishes Compared to Existing Dietary Diversity Indices: A Cross-Sectional Analysis from the 2012 National Health and Nutrition Survey, Japan.

The Japanese diet has attracted attention as a factor contributing to the Japanese population's longevity. A typical Japanese meal, traditionally called "ichiju-sansai," is composed of various dishes. This study assessed the nutritional adequacy of the Japanese diet using the number of dishes in all meals (NDAM) compared to existing dietary diversity indices (DDIs). This cross-sectional study used data from the 2012 National Health and Nutrition Survey. A total of 25,976 participants aged ≥20 y were included in this study. NDAM was calculated for whole dishes or single foods (except supplements and beverages) from one-day weighted dietary records. The food variety score (FVS), number of foods, dietary diversity score (DDS), and number of food groups are some of the existing DDIs. NDAM had relatively high positive correlation coefficients with potassium, magnesium, and dietary fiber. The partial correlation coefficients with an indicator of the overall nutrient adequacy of NDAM was 0.42 for men and 0.42 for women. It was almost the same as that of the FVS (men: 0.44, women: 0.42) and DDS (men: 0.44, women: 0.43). On the other hand, NDAM, similar to existing DDIs, was also positively correlated with nutrient restriction in both sexes. These findings indicate that the nutrient adequacy of NDAM is similar to that of the existing DDIs. Because of the higher sodium intake and cholesterol intake in higher NDAM and existing DDIs, the effect of higher NDAM on health outcomes must be investigated in future studies.

Determinants of double product: a cross-sectional study of urban residents in Japan.

BACKGROUND: The current study aimed to investigate the determinants of high double product (DP) by evaluating the association between resting DP, which is calculated as systolic blood pressure (SBP) multiplied by heart rate (HR), and blood test results and lifestyle factors. METHODS: This research included 973 participants in the baseline survey of the KOBE study, which included a cohort of urban residents. The possible DP determinants were identified by examining the association between lifestyle factors and laboratory findings and DP by analyzing covariance adjusted for sex and age. Logistic regression analysis was performed with high DP (SBP × HR ≥ 9145 mmHg beats/min or quintile according to sex) as outcome and DP determinants as independent variables. RESULTS: Age, hematocrit, and gamma-glutamyl transferase (log) level were positively associated with a high DP in both men and women. In addition, a high DP was positively associated with Homeostatic Model Assessment for Insulin Resistance score in women alone. Meanwhile, the amount of exercise was negatively associated with a high DP in men alone. CONCLUSIONS: High DP values at rest were associated with insulin resistance, gamma-glutamyl transferase, and the amount of exercise in participants without underlying disease.

Association between low-carbohydrate diet score and incidence of type 2 diabetes among Japanese adults: the JACC Study.

We prospectively examined the association between low-carbohydrate diet (LCD) score and incidence of type 2 diabetes (T2D) in Japanese adults using Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study) data. A total of 19 084 (7052 men and 12 032 women) Japanese non-diabetic participants aged 40-79 years, who enrolled in the JACC study between 1988 and 1990, were included in our analysis. Dietary intake was evaluated using a validated food-frequency questionnaire. The overall, animal and vegetable LCD scores were calculated by dividing the study participants into eleven categories based on the percentages of energy from carbohydrates, protein and fat. The incidence of T2D was assessed using a self-administered questionnaire. We used multivariable logistic regression analysis to estimate the odds ratios (ORs) and 95 % confidence intervals (CIs) of incident T2D across the quintile of each LCD score, with adjustment for potential confounders. During the 5-year study period, 490 adults (247 men and 243 women) developed T2D. The multivariable-adjusted OR of incident T2D for the highest v. lowest quintiles of overall and animal LCD scores, respectively, were 0·64 (95 % CI 0·42, 0·99) and 0·83 (95 % CI 0·55, 1·27) for men, 0·78 (95 % CI 0·51, 1·18) and 0·84 (95 % CI 0·57, 1·24) for women. The vegetable LCD score was associated with a lower risk of T2D in men (OR 0·51; 95 % CI 0·33, 0·77). Our results suggest that diets lower in carbohydrates and higher in fat and protein are unlikely to higher the T2D risk among Japanese individuals.

Combined fat mass and fat-free mass indices and lung function among Japanese population: The Tohoku Medical Megabank Community-based Cohort Study.

BACKGROUND: Although fat mass index (FMI) and fat-free mass index (FFMI) affect lung function, FMI and FFMI are not independent of each other since FMI and FFMI were calculated as fat mass and fat-free mass divided by height squared, respectively. We aimed to examine the association of combined FMI and FFMI with lung function. METHODS: In this cross-sectional study, lung function was evaluated using forced expiratory volume at 1 s and forced vital capacity was measured using spirometry. Both FMI and FFMI were classified into sex-specific quartiles (16 groups). Analysis of covariance was used to assess the associations of combined FMI and FFMI with lung function. The trend test was conducted by stratifying the FMI and FFMI, scoring the categories from 1-4 (lowest-highest), and entering the number as a continuous term in the regression model. RESULTS: This study included 3,736 men and 8,821 women aged ≥20 years living in Miyagi Prefecture, Japan. The mean FEV1 (standard deviation) was 3.0 (0.7) L for men and 2.3 (0.5) L for women. The mean FVC was 3.8 (0.7) L for men and 2.8 (0.5) L for women. The FMI was inversely associated with lung function among all FFMI subgroups in both sexes. Conversely, FFMI was positively associated with lung function in all FMI subgroups in both sexes. CONCLUSIONS: Higher FMI was associated with lower lung function independent of FFMI; higher FFMI was associated with higher lung function independent of FMI. Reducing FMI and maintaining FFMI might be important for respiratory health.