Anemia and Rehabilitation Outcomes in Patients Undergoing Convalescent Rehabilitation.

OBJECTIVE: Assessment of the association between anemia and recovery of physical disability in patients with functional impairment. DESIGN: A retrospective cohort study. SETTING: A convalescent rehabilitation ward. PARTICIPANTS: The subjects were patients undergoing convalescent rehabilitation due to neurologic disease, musculoskeletal disorders, or hospital-associated deconditioning. Patients were classified into 3 groups (no anemia; mild anemia [men: hemoglobin of 11.0-12.9 g/dL; women: hemoglobin of 11.0-11.9 g/dL]; and moderate/severe anemia [hemoglobin < 11.0 g/dL]) based on hemoglobin levels. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The study outcomes were functional independence measures for motor function (FIM-M) score at discharge, changes in the FIM-M score between hospital admission and discharge, length of stay, and FIM-M efficiency score (change in FIM-M score divided by length of stay). A linear regression model was constructed to explore the association of anemia with the FIM-M efficiency score. As a subgroup analysis, we constructed a linear regression model to explore the association of anemia with the FIM-M efficiency score in patients with or without stroke. RESULTS: Of 376 consecutive patients with a mean age of 80 years, 258 (69%) had mild or moderate/severe anemia. There were no significant differences between the 3 groups in the FIM-M score at discharge, changes in the FIM-M score, length of stay, and FIM-M efficiency score. A multiple linear regression model showed that the FIM-M efficiency score was not associated with anemia (mild anemia group: ß=-0.02, P=.8; moderate/severe anemia group: ß=-0.005, P=.9). In the subgroup analysis of patients with or without stroke, the multiple regression model also showed no significant association between anemia and FIM-M efficiency score in each group. CONCLUSIONS: Anemia on admission was common among patients in a convalescent rehabilitation ward but was not associated with improvement of FIM-M after rehabilitation.

Hip and vertebral fracture risk after initiating antidiabetic drugs in Japanese elderly: a nationwide study.

INTRODUCTION: We aimed to clarify the risks of initiating antidiabetic drugs for fractures using a nationwide health insurance claims database (NDBJ). MATERIALS AND METHODS: Patients aged ≥ 65 years initiating antidiabetic drugs at the outpatient department were enrolled after a 180-day period without prescribed antidiabetic drugs and followed with during 2012-2018 using NDBJ. The adjusted hazard risks (HRs) of each antidiabetic drug (thiazolidine, alpha-glucosidase inhibitor, dipeptidyl peptidase-4 [DPP-4] inhibitor, sulfonylurea, glinide, and insulin) for fractures compared with biguanide were obtained adjusting for age, gender, polypharmacy, dementia, and the other antidiabetic drugs. RESULTS: The DPP-4 inhibitor was the most often prescribed antidiabetic drug followed by biguanide with prescribed proportions of 71.7% and 12.9%. A total of 4,304 hip fractures and 9,388 vertebral fractures were identified among the 966,700 outpatient participants. Compared with biguanide, insulin, alpha-glucosidase inhibitor, and DPP-4 inhibitor were related to increased hip fracture risks. Vertebral fracture risk was higher in outpatients prescribed with insulin, thiazolidine, and DPP-4 inhibitor compared with biguanide. Patients prescribed insulin for hip and vertebral fractures' adjusted HRs were 2.17 (95% CI 1.77-2.66) and 1.45 (95% CI 1.24-1.70), respectively. Those prescribed DPP-4 inhibitor for hip and vertebral fractures' adjusted HRs were 1.27 (95% CI 1.15-1.40) and 1.20 (95% CI 1.12-1.28), respectively. CONCLUSIONS: Initiating insulin increased the risk of not only hip fractures but also vertebral fractures. Patients initiating antidiabetic drugs had increased risks of hip and vertebral fractures compared with those initiating biguanide independently for age, gender, polypharmacy, and dementia in the Japanese elderly.

Physical Frailty May Predict 2-Year Prognosis in Elderly Patients With Acute Myocardial Infarction　- A Report From the FLAGSHIP Study.

BACKGROUND: Elderly patients with acute myocardial infarction (AMI) are a high-risk population for heart failure (HF), but the association between physical frailty and worsening prognosis, including HF development, has not been documented extensively.Methods and Results: As part of the FLAGSHIP study, we enrolled 524 patients aged ≥70 years hospitalized for AMI and capable of walking at discharge. Physical frailty was assessed using the FLAGSHIP frailty score. The primary outcome was a composite outcome of all-cause death and HF rehospitalization within 2 years after discharge. The secondary outcome was all-cause death and HF rehospitalization. After adjusting for confounders, physical frailty showed a significant association with an increased risk of the composite outcome (hazard ratio [HR]=2.09, 95% confidence interval [CI]: 1.03-4.22, P=0.040). The risk of HF rehospitalization increased with physical frailty, but the association was not statistically significant (HR=2.14, 95% CI: 0.84-5.44, P=0.110). Physical frailty was not associated with an increased risk of all-cause death (HR=1.45, 95% CI: 0.49-4.26, P=0.501). CONCLUSIONS: The findings suggest that physical frailty assessment serves as a stratifying tool to identify high-risk populations for post-discharge clinical events among ambulant elderly patients with AMI.

Characterization of salivary microbiota in elderly patients with type 2 diabetes mellitus: a matched case-control study.

OBJECTIVE: The importance of oral health in type 2 diabetes mellitus (T2DM) is widely recognized; however, oral microbiota characteristics associated with T2DM in the elderly population are not well-understood. This study was conducted to evaluate the characteristics of the salivary microbiota in elderly Japanese patients with T2DM. METHODS: Saliva samples were collected from 42 elderly Japanese patients with T2DM and 42 age- and sex-matched subjects without T2DM (control). 16S ribosomal RNA metagenomic analysis and comparative analysis of both groups were performed. Random forest classification by machine learning was performed to discriminate between the salivary microbiota in the two groups. RESULTS: There were significant differences in the overall salivary microbiota structure between the T2DM and control groups (beta diversity; unweighted UniFrac distances, p = 0.001; weighted UniFrac distances, p = 0.001). The phylum Firmicutes was abundant in patients with T2DM, whereas the phylum Bacteroidetes was abundant in controls. The T2DM prediction model by random forest based on salivary microbiota data was verified with a high predictive potential in five cross-validation tests (area under the curve (AUC) = 0.938 (95% CI, 0.824-1.000)). CONCLUSION: Characterization revealed that the salivary microbiota profile of the elderly patients with T2DM is significantly distinct from that of the controls. CLINICAL RELEVANCE: These data indicate the necessity of oral health management based on the characteristics of the salivary microbiota in elderly patients with T2DM. Our findings will contribute to future research on the development of new diagnostic and therapeutic methods for this purpose.

Determinants of bone health in elderly Japanese men: study design and key findings of the Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) cohort study.

BACKGROUND: The Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) study was launched to investigate risk factors for osteoporotic fractures, interactions of osteoporosis with other non-communicable chronic diseases, and effects of fracture on QOL and mortality. METHODS: FORMEN baseline study participants (in 2007 and 2008) included 2012 community-dwelling men (aged 65-93 years) in Nara prefecture, Japan. Clinical follow-up surveys were conducted 5 and 10 years after the baseline survey, and 1539 and 906 men completed them, respectively. Supplemental mail, telephone, and visit surveys were conducted with non-participants to obtain outcome information. Survival and fracture outcomes were determined for 2006 men, with 566 deaths identified and 1233 men remaining in the cohort at 10-year follow-up. COMMENTS: The baseline survey covered a wide range of bone health-related indices including bone mineral density, trabecular microarchitecture assessment, vertebral imaging for detecting vertebral fractures, and biochemical markers of bone turnover, as well as comprehensive geriatric assessment items. Follow-up surveys were conducted to obtain outcomes including osteoporotic fracture, cardiovascular diseases, initiation of long-term care, and mortality. A complete list of publications relating to the FORMEN study can be found at https://www.med.kindai.ac.jp/pubheal/FORMEN/Publications.html .

Natto Intake is Inversely Associated with Osteoporotic Fracture Risk in Postmenopausal Japanese Women.

BACKGROUND: The direct association between intake of Japanese fermented soybeans, namely natto, and bone mineral density (BMD) is known. However, the association with osteoporotic fractures has not been studied. OBJECTIVE: This study aimed to investigate whether habitual natto intake is associated with a risk of osteoporotic fractures. METHODS: This prospective cohort study included 1417 postmenopausal Japanese women who were enrolled in the Japanese Population-Based Osteoporosis cohort study in 1996, 1999, 2002, and 2006 and were aged ≥45 y at baseline. The intake of natto, tofu, and other soybean products was surveyed with use of a FFQ at baseline. Fractures were ascertained in follow-up surveys conducted in 1999, 2002, 2006, and 2011/2012. Osteoporotic fracture was the primary outcome and was defined as a clinical fracture occurring without strong external force, diagnosed with radiographs by a medical doctor. HRs with 95% CIs were estimated with Cox proportional hazard models. RESULTS: During the 17,699 person-years of follow-up (median, 15.2 y), 172 women experienced osteoporotic fractures. After adjustment for age and BMD at the total hip, the HRs compared with those of < 1 pack (approximately 40 g)/wk natto intake were 0.72 (95% CI: 0.52, 0.98) and 0.51 (95% CI: 0.30, 0.87) for 1-6 and ≥7 packs/wk, respectively. After further adjustment for BMI, history of osteoporotic fractures, history of myocardial infarction or stroke, diabetes mellitus, current smoking, alcohol intake, frequency of tofu and other soybean product intakes, and dietary calcium intake, the HRs were 0.79 (95% CI: 0.56, 1.10) and 0.56 (95% CI: 0.32, 0.99) for 1-6 and ≥7 packs/wk, respectively. Frequency of tofu or other soybean product intakes had no association with the risk of osteoporotic fractures. CONCLUSIONS: Habitual natto intake may be associated with a reduced risk of osteoporotic fractures independent of confounding factors, including BMD, in Japanese postmenopausal women. This trial was registered at umin.ac.jp as UMIN 000032869.

Estimation of reduced walking speed using simple measurements of physical and psychophysiological function in community-dwelling elderly people: a cross-sectional and longitudinal study.

BACKGROUND: Early detection of reduced mobility function is important in elderly people. Usual walking speed is useful to assess mobility function, but is often not feasible in a community setting. AIMS: This study aimed to explore a simple surrogate indicator of usual walking speed in elderly people. METHODS: The participants were 516 community-dwelling elderly people. As a baseline survey, the usual walking speed and candidates of surrogate indicators including physical function and psychophysiological function were measured. After 2 years, the occurrence of mobility limitation was assessed. RESULTS: In cross-sectional analysis, a linear regression model with maximum step length, age, and sex presented the most favourable adjusted R2 of 0.426 for estimating usual walking speed. Maximum step length (MSL) also showed good predictive accuracy for usual walking speed < 0.8 m/s {area under the curve [AUC] 0.908 [95% confidence interval (CI) 0.811, 1.000]} and < 1.0 m/s [AUC 0.883 (95% CI) 0.832, 0.933)] in receiver-operating characteristic (ROC) analysis. In longitudinal analysis, the predictive accuracy of MSL for mobility limitation [AUC 0.813 (95% CI 0.752, 0.874)] was similar to that of usual walking speed [AUC 0.808 (95% CI 0.747, 0.869)] in ROC analysis. CONCLUSIONS AND DISCUSSION: The results of this study suggest that MSL may serve as a simple surrogate indicator of UWS in elderly people.

Changes in walking speed 6 months after discharge may be more sensitive to subsequent prognosis than handgrip strength in patients hospitalized for heart failure.

BACKGROUND: Despite the prognostic importance of walking speed (WS) and handgrip strength (HGS) in patients with heart failure (HF), no study has reported the prognostic impact of changes in these parameters. This study aimed to examine the association between changes after discharge and the subsequent prognosis. METHODS: This study included 881 elderly patients hospitalized for HF. WS and HGS were measured at discharge and 6 months after discharge. Based on the presence of slowness (WS <0.98 m/s) or weakness (HGS <30.0 kg for men and < 17.5 kg for women) at both points, patients were divided into four groups (WS: A = -/-, B = -/+, C = +/-, D = +/+; HGS: E = -/-, F = -/+, G = +/-, H = +/+). The study endpoint was a composite of all-cause mortality and HF rehospitalization during the 18 months after 6 months of discharge. The Cox proportional hazards model was used to assess the association between the groups and study outcomes. RESULTS: Stratified by the WS change patterns, groups B and D showed higher risk of the study outcomes than group A [B: hazard ratio 2.34, 95% confidence interval (CI) 1.29-4.28; D: 2.38, 1.67-3.39], whereas group C was not. When stratified by the HGS change in patterns, only group H was associated with a worse prognosis (HR; 1.85, 95%CI; 1.31-2.60). CONCLUSION: Changes in WS were related to HF prognosis, suggesting that changes in WS may be more sensitive to further risk stratification than changes in HGS.

Baseline Nutritional Status and Rehabilitation Progress in Individuals Requiring Inpatient Rehabilitation: A Retrospective Cohort Study.

Objective: To evaluate the relationships between baseline nutritional status, medical events (MEs), and rehabilitation outcomes in individuals undergoing inpatient rehabilitation (IR). Design: A retrospective single center cohort study. Setting: An IR ward. Participants: This study included 409 patients (mean age, 80 years; men, 170 [42%]) undergoing IR for hospital-associated deconditioning, neurologic disorders, or musculoskeletal diseases. Participants were grouped according to the Controlling Nutritional Status score at admission: normal nutrition (NN): 0 to 1, mild malnutrition (MM): 2 to 4, and moderate/severe malnutrition (M/SM): 5 to 12. Interventions: None. Main Outcome Measures: The primary outcomes included MEs leading to death or acute illness requiring transfer to other hospitals for specialized treatments. The secondary outcomes were the rehabilitation efficiency scores (changes in Functional Independence Measure [FIM] score divided by length of stay) for motor function (FIM-M) and cognitive function (FIM-C). Results: Among the 409 participants, 300 (73%) were malnourished at admission. The adjusted hazard ratios (95% confidence interval) for MEs in the MM and M/SM groups relative to the NN group were 1.48 (0.67-3.27) and 0.98 (0.34-2.81), respectively. No significant differences were observed among the 3 groups in FIM-M efficiency scores (mean ± SD, NN: 0.49±0.51 vs MM: 0.41±0.57 vs M/SM: 0.44±1.06, P=.7) or FIM-C efficiency scores (0.04±0.06 vs 0.04±0.06 vs 0.08±0.4, P=0.1). Analysis of covariance showed no significant association between MM or M/SM group and FIM-M efficiency score (beta coefficient = -0.038, P=.6; beta coefficient = 0.15, P=.1, respectively) or FIM-C efficiency score (beta coefficient = 0.004, P=.8; beta coefficient = 0.047, P=.08, respectively). Conclusion: No significant associations were observed between the baseline nutritional status and MEs, FIM-M efficiency score, or FIM-C efficiency score in individuals undergoing IR.

Effects of intensity, frequency, and time window of exercise on sleep quality among community-dwelling adults aged 65-86 years.

BACKGROUND: Although the effects of exercise training (ET) on sleep problem have been reported, the effects according to the components of exercise, including intensity, frequency, and time window, are unknown. Thus, in this study, we aimed to assess the effects of ET on sleep quality in community-dwelling older adults with sleep problems. METHODS: We evaluated individuals aged ≥65 years whose Pittsburgh sleep quality index was >5 points at baseline. The participants were allocated to either the control group or the ET group and underwent interval walking training (IWT) for 5 months. Information regarding intensity, frequency, and time window of ET were obtained using a waist-worn accelerometer. RESULTS: Overall, 63 participants (24 men [mean ± standard deviation age: 75.1 ± 4.6 years] and 39 women [74.7 ± 5.2 years]) and 65 participants (24 men [75.2 ± 4.0 years] and 41 women [73.6 ± 4.2 years]) were included in the ET and control groups, respectively. The change in Pittsburgh sleep quality index was not significantly different between the two groups for both sexes. In the ET group, women who exercised 3-8 h before bedtime, men who did ET > 8 h before bedtime and more than 1 h after waking up, and men who did ET ≥ 5.05 days/week experienced significant improvements compared to the baseline. CONCLUSIONS: IWT does not significantly improve sleep quality. To obtain improvements in sleep quality, it might be necessary to consider the time window of performing ET for both sexes and ET frequency for men.

Association of Baseline Skeletal Muscle Mass Index With Adverse Events and Rehabilitation Outcomes in Patients Admitted for Rehabilitation.

Objective: To assess the associations of baseline skeletal muscle mass index (SMI) with adverse events and rehabilitation outcomes in patients admitted for rehabilitation. Design: A retrospective cohort study. Participants: The subjects were 409 patients (mean age, 79 years; men, 167 [41%]) undergoing rehabilitation because of neurologic disease, musculoskeletal disorders, or hospital-associated deconditioning. Patients were divided into 2 groups according to the definition of sarcopenia by the Asian Working Group for Sarcopenia: those with low SMI (<7.0 kg/m2 in men and <5.7 kg/m2 in women) and those with high SMI (≥7.0 kg/m2 in men and ≥5.7 kg/m2 in women). Interventions: Not applicable. Main Outcome Measures: The primary outcomes were adverse events including death and acute illness requiring transfer to other hospitals for specialized treatments. The secondary outcomes were rehabilitation outcomes including the efficiency scores (changes in functional independence measure [FIM] score divided by length of stay) of FIM for motor function (FIM-M) and FIM for cognitive function (FIM-C). Results: Of the 409 patients, 299 (73%) had a low SMI. The adjusted hazard ratio (95% confidence interval) of the low SMI group relative to the high SMI group for adverse events was 2.79 (1.06-7.34). There were no significant differences between the 2 groups in FIM-M efficiency scores [mean ± SD, low SMI group: 0.4 (0.58) vs high SMI group: 0.47 (0.54), P=.3] and FIM-C efficiency scores [mean ± SD, 0.05 (0.14) vs 0.06 (0.2), P=.4]. Multiple linear regression models did not show significant associations between the low SMI group and FIM-M efficiency or FIM-C efficiency scores (ß=0.064, P=.3; ß=-0.05, P=.4, respectively). Conclusion: Low baseline SMI was significantly associated with adverse events but not with rehabilitation outcomes in patients undergoing rehabilitation.

Association Between Skeletal Muscle Mass Index and Falls in Patients With Functional Impairment.

OBJECTIVE: This study aimed to assess the association between skeletal muscle mass index and falls in patients with functional impairment. DESIGN: This retrospective cohort study was implemented at a convalescent rehabilitation ward. Patients with no measurement of skeletal muscle mass index and bed-ridden patients were excluded from this study. Patients were dichotomized into the low skeletal muscle mass index group and the high skeletal muscle mass index group. The occurrence of fall was assessed according to skeletal muscle mass index groups. RESULTS: Of the 327 included patients, 231 (71%) were assigned to the low skeletal muscle mass index group. In total, 66 patients (20%) experienced at least one fall, and a total of 102 falls occurred. The incidence of falls for the low skeletal muscle mass index group was not significantly greater than that for the high skeletal muscle mass index group (4.9 per 1000 patient-days vs. 4.5 per 1000 patient-days, P = 0.9). Low skeletal muscle mass index was not significantly associated with one or more incidents of falls (odds ratio [95% confidence intervals] = 0.6 [0.3-1.17]). CONCLUSIONS: This study found that skeletal muscle mass index was not significantly associated with falls in patients undergoing convalescent rehabilitation.

Prognostic impact of nutrition measures in patients with heart failure varies with coexisting physical frailty.

AIMS: Malnutrition is prevalent among patients with heart failure (HF); however, the effects of coexisting malnutrition and frailty on prognosis are unknown. This study examines the impact of malnutrition and frailty on the prognosis of patients with HF. METHODS AND RESULTS: We examined 1617 patients with HF aged 65 years or older (age: 78.6 ± 7.4; 44% female) from a Japanese multicentre prospective cohort study. The nutritional status was evaluated using the Geriatric Nutritional Risk Index (GNRI), Controlling Nutritional Status (CONUT), and Mini Nutritional Assessment Short Form on discharge. Frailty was assessed using the criteria determined in a previous study on patients with HF. The prognostic impact of each nutrition measure on the risk of composite all-cause mortality and cardiac readmissions within 2 years of hospital discharge was assessed using Kaplan-Meier survival curves and Cox proportional hazards model analysis for non-frail and frail groups. Over 2324.2 person-years of follow-up, 88 patients died and 448 patients experienced readmission due to HF. In the non-frail group, poor nutritional status assessed using the GNRI and CONUT was associated with an increased hazard ratio (HR) of composite outcomes in the crude model; however, adjustment for potential confounders diminished the association. In the frail group, all three nutritional indicators were associated with the cumulative incidence of the study outcome (log-rank test, P < 0.05). In multivariate analysis, only the CONUT score was associated with an increased HR even after adjustment for confounders. CONCLUSIONS: The CONUT score predicted a poor prognosis in HF patients with coexisting physical frailty, highlighting the potential clinical benefit of nutritional assessment based on biochemical data for further risk stratification.

Prognostic effects of cardiac rehabilitation in heart failure patients classified according to physical frailty: A propensity score-matched analysis of a nationwide prospective cohort study.

Background: Research regarding cardiac rehabilitation (CR) in the prognosis of heart failure (HF) patients and frailty remains lacking. Here, the effects of CR on the 2-year prognosis of HF patients were examined according to their frailty status. Methods: This multicenter prospective cohort study enrolled patients hospitalized for HF. Patients who underwent ≥1 session per 2 weeks of CR within 3 months after discharge were categorized in the CR group. Patients were divided in a non-frailty (≤8 points) and physical frailty group (≥9 points) based on their FLAGSHIP frailty score. The score is based on HF prognosis, with a higher score indicating worsened physical frailty. A propensity score-matched analysis was performed to compare survival rates between the two groups according to their physical frailty status. Endpoints included HF re-hospitalization and all-cause mortality during a 2-year follow-up period. Results: Of 2697 patients included in the analysis, 285 and 95 matched pairs were distributed in the non-frailty and physical frailty groups, respectively, after propensity-score matching. CR was associated with lower incidence of HF rehospitalization in both non-frailty (hazard ratio 0.65; 95% confidence interval 0.44-0.96; p = 0.032) and physical frailty (0.54; 0.32-0.90; p = 0.019) groups. CR was not associated with all-cause mortality in either group (log-rank test, p > 0.05). Conclusion: These findings suggest the effects of CR on reduced HF rehospitalization, regardless of physical frailty status.

Association between the 110-kDa C-terminal agrin fragment and skeletal muscle decline among community-dwelling older women.

BACKGROUND: C-terminal agrin fragment (CAF) is a biomarker for neuromuscular junction degradation. This study aimed to investigate whether 110-kDa CAF (CAF110) was associated with the presence and incidence of low muscle mass and strength. METHODS: This cross-sectional retrospective cohort study comprised women aged ≥65 years. We measured muscle mass using a dual-energy X-ray absorptiometry scanner, hand-grip strength, and blood sampling between 2011 and 2012. A follow-up study with the same measurements was conducted between 2015 and 2017. Low muscle mass and strength were defined as an appendicular skeletal muscle mass index <5.4 kg/m2 and hand-grip strength <18 kg, respectively. The CAF110 level was measured using enzyme-linked immunosorbent assay kits. RESULTS: In total, 515 women (74.3 ± 6.3 years) were included in this cross-sectional analysis. Of these, 101 (19.6%) and 128 (24.9%) women presented with low muscle mass and strength, respectively. For low muscle mass, the odds ratios (ORs) of the middle and highest CAF110 tertile groups, compared with the lowest group, were 1.93 (95% confidence interval: 1.09-3.43; P = 0.024) and 2.15 (1.22-3.80; P = 0.008), respectively. After adjusting for age, the ORs remained significant: 1.98 (1.11-3.52; P = 0.020) and 2.27 (1.28-4.03; P = 0.005), respectively. Low muscle strength ORs of all the CAF110 tertile groups were not significant. In the longitudinal analysis, 292 and 289 women were assessed for incidents of low muscle mass and strength, respectively. Of those, 34 (11.6%) and 20 (6.9%) women exhibited low muscle mass and strength, respectively. For incident low muscle mass, the crude OR of the CAF110 ≥ the median value group was marginally higher than that of the CAF110 < median value group (median [interquartile range]: 1.98 [0.94-4.17] (P = 0.072). After adjusting for age and baseline muscle mass, the OR was 2.22 [0.97-5.06] (P = 0.058). All low muscle strength ORs of the median categories of CAF110 were not significant. CONCLUSIONS: CAF110 was not associated with low muscle strength. However, CAF110 may be a potential marker for the incidence of low muscle mass.

Real-world effectiveness of anti-osteoporosis medications for the prevention of incident hip and clinical vertebral fractures in patients on long-term glucocorticoid therapy: A nationwide health insurance claims database study in Japan.

PURPOSE: Early initiation of anti-osteoporosis medications (AOMs) is recommended for patients on long-term glucocorticoid (GC) therapy. This study aimed to clarify the real-world effectiveness of AOMs against incident hip and vertebral fractures in patients undergoing GC therapy using the nationwide health insurance claims database of Japan (NDBJ). METHODS: Patients aged ≥50 years who were prescribed GC (≥5 mg/day prednisolone or equivalent) for ≥90 days and who were followed up regarding AOM prescription and hip and clinical vertebral fracture incidences for the subsequent 1080 days between 2012 and 2018 were selected from NDBJ. Associations of AOMs prescribed within 90 days since GC therapy initiation with hip or vertebral fracture risk were evaluated by Cox proportional hazards regression using propensity score inverse probability weighting (IPW) for receiving any AOM or individual AOMs. RESULTS: In total, 96,475 women and 98,385 men were included in the analysis; 38.0 % of women and 27.6 % of men received AOMs. Patients who received any AOM and those who received bisphosphonates or denosumab had a significantly lower risk of hip and clinical vertebral fractures than those who received no AOM in both sexes after propensity score IPW. Teriparatide was associated with an increased risk of both fractures in women and an increased risk of clinical vertebral fractures in men. Selection biases such as confounding by indication might have caused an underestimation of AOMs' protective effects. CONCLUSIONS: Bisphosphonates and denosumab were associated with a lower fracture incidence in patients on long-term GC therapy in real-world settings.

Effect of high-intensity interval walking on microvascular endothelial function among community-dwelling older people.

AIM: To investigate the effects of high-intensity interval exercise training on microvascular endothelial function among community-dwelling older people. METHODS: We analyzed the data from a nonrandomized controlled trial. This study's participants were 48 men (aged 75 ± 5 years; exercise training group, n = 24; control group, n = 24) and 83 women (aged 75 ± 4 years; exercise training group, n = 36; control group, n = 47). The exercise training group underwent a high-intensity interval walking training for 5 months. RESULTS: In the exercise group, 100% and 91.7% of men and women, respectively, achieved brisk walking times ≥50 min/week. The change in the reactive hyperemia index significantly differed between the groups of men, whereas that in the control group was not significant; however, a significant increase was observed in the exercise training group. Among women, changes in the reactive hyperemia index were not significant in either group; however, for women in the exercise training group, these changes negatively and positively correlated with the change in body mass index (Spearman's rho = -0.342; P = 0.041) and baseline body mass index (rho = 0.362, P = 0.030), respectively. Additionally, the distribution of body mass index was broader in women than in men. CONCLUSIONS: Interval walking training increased the reactive hyperemia index in men rather than in women. A higher variation in baseline body mass index may be associated with no statistical increase in reactive hyperemia index in women. Geriatr Gerontol Int 2023; 23: 103-110.

Relationship between antidementia medication and fracture prevention in patients with Alzheimer's dementia using a nationwide health insurance claims database.

This retrospective study aimed to evaluate the association between antidementia medication use and incidence of new vertebral, hip, and radial fractures in patients with Alzheimer's dementia (AD). We used the nationwide health insurance claims database of Japan from 2012 to 2019 and identified 12,167,938 patients aged ≥ 65 years who were newly registered from April 2012 to March 2016 and had verifiable data receipt from half-year before to 3 years after the registration. Among these patients, 304,658 were diagnosed with AD and we showed the prescription status of antidementia and osteoporosis medication among them. Propensity score matching was conducted for AD group with and without antidementia medication use, and 122,399 matched pairs were yielded. The incidence of hip fractures (4.0% vs. 1.9%, p < 0.001) and all clinical fractures (10.5% vs. 9.0%, p < 0.001) significantly decreased and that of radial fractures increased (0.6% vs. 1.0%, p < 0.001) in AD patients with antidementia medication use compared with AD patients without antidementia medication use. No significant difference was found in vertebral fractures (6.6% vs. 6.5%, p = 0.51). Overall, these results suggest a positive relationship between antidementia medication use and fracture prevention in patients with AD.

Prescription of vitamin D was associated with a lower incidence of hip fractures.

Patients with osteoporosis are prone to fragility fractures. Evidence of the effects of active forms of vitamin D on hip fracture prevention is insufficient. We examined the association between vitamin D prescription and incidence of new fractures using the data of osteoporotic patients from the nationwide health insurance claims database of Japan. The follow-up period was 3 years after entry. The untreated patients were never prescribed vitamin D during follow-up (n = 422,454), and the treated patients had a vitamin D medication possession ratio of ≥ 0.5 at all time points (n = 169,774). Propensity score matching was implemented on these groups, yielding 105,041 pairs, and subsequently, the control and treatment groups were established and analyzed. The incidence of new fractures was significantly lower in the treatment group compared with the control group (6.25% vs. 5.69%, hazard ratio 0.936 [95% confidence interval 0.904-0.970], p < 0.001*). By site, hip fractures significantly decreased (0.89% vs. 0.42%, p < 0.001), but not vertebral and radial fractures. Subgroup analysis by vitamin D type showed a significantly lower incidence of total fractures only in alfacalcidol (hazard ratio 0.676 [95% confidence interval 0.628-0.728], p < 0.001*). The results suggest that vitamin D prescription was associated with a reduced incidence of hip fractures.

Salivary Microbiota Associated with Peripheral Microvascular Endothelial Dysfunction.

AIMS: Oral health is associated with atherosclerotic cardiovascular disease (ACVD). We previously identified the salivary microbiota characteristics of patients with ACVD. However, whether salivary microbiota is characteristic under impaired vascular endothelial function before ACVD onset remains unclear. Therefore, we aimed to evaluate the characteristics of salivary microbiota associated with peripheral microvascular endothelial dysfunction. METHODS: We collected saliva samples from 172 community-dwelling elderly individuals without a history of ACVD and performed 16S rRNA metagenomic analysis. We assessed the peripheral microvascular endothelial function using reactive hyperemia index (RHI) and compared the salivary microbiota in the groups with normal (RHI ≥ 2.10), borderline, and abnormal (RHI ＜1.67) peripheral endothelial function. Furthermore, we applied machine learning techniques to evaluate whether salivary microbiota could discriminate between individuals with normal and abnormal endothelial function. RESULTS: The number of operational taxonomic units (OTUs) was higher in the abnormal group than in the normal group (p=0.037), and differences were found in the overall salivary microbiota structure (unweighted UniFrac distances, p=0.038). The linear discriminant analysis (LDA) effect size (LEfSe) algorithm revealed several significantly differentially abundant bacterial genera between the two groups. An Extra Trees classifier model was built to discriminate between groups with normal and abnormal vascular endothelial function based on the microbial composition at the genus level (AUC=0.810). CONCLUSIONS: The salivary microbiota in individuals with endothelial dysfunction was distinct from that in individuals with normal endothelial function, indicating that the salivary microbiota may be related to endothelial function.