Association between endogenous plasma beta-hydroxy-beta-methylbutyrate levels and frailty in community-dwelling older people.

BACKGROUND: Frailty is a key element in healthy ageing in which muscle performance plays a main role. Beta-hydroxy-beta-methylbutyrate (HMB) supplementation has shown favourable effects in modulating protein synthesis, improving muscle mass and function in interventional studies. Decreased age-related endogenous HMB levels have been shown in previous studies. The aim of the present study is to assess whether there is an association between endogenous plasma HMB levels and frailty. METHODS: Data from 1290 subjects (56.98% women; mean ± standard deviation age 74.6 ± 5.95 years) from the Toledo Study for Healthy Aging were obtained. Participants had their frailty status qualified according to Fried's Frailty Phenotype (FFP) score and the Frailty Trait Scale in its 12-domain version (FTS-12). Plasma HMB levels were analysed by an ultrahigh-performance liquid chromatography tandem mass spectrometry. Differences between groups (frail vs. non-frail) were tested using Mann-Whitney U test, Kruskal-Wallis test and chi-squared test. The association between HMB and frailty was assessed by multivariate linear and logistic regressions when frailty was analysed as continuous and binary, respectively. Models were adjusted by age, gender, comorbidity, body composition and protein intake. RESULTS: HMB levels were lower in those aged ≥75 years than in those aged 65-74 years, with an inverse linear relationship between age and HMB levels (ß = -0.031; P = 0.018), mainly accounted by males (ß = -0.062; P = 0.002). HMB levels were higher in men (0.238 ± 0.065 vs. 0.193 ± 0.051 ng/mL; P ≤ 0.001). HMB levels were significantly lower in frail than in non-frail individuals: 0.204 ± 0.058 versus 0.217 ± 0.063 ng/dL (P = 0.001) according to the FFP and 0.203 ± 0.059 versus 0.219 ± 0.063 ng/mL (P < 0.001) according to FTS-12. These differences showed a dose-dependent profile when we compared them by quintiles of HMB (P for trend: 0.022; 0.012 and 0.0004, respectively, for FFP, FTS-12 binary and FTS-12 continuous). Variables associated with low HMB levels were body mass index, strength, exhaustion and weight loss. Frailty was associated with HMB levels in all the adjusted models, including the fully adjusted ones, no matter the tool used (odds ratio: 0.45 [0.26, 0.77] for FFP and 0.36 [0.20, 0.63] for FTS-12 binary; ß = -4.76 [-7.29, -2.23] for FTS-12 score). This association was also observed when the analyses were done by quintiles, showing such association since Q4 (FFP), Q2 (FTS-12 binary) and Q3 (FTS-12 score). The associations were observed in the whole sample and in each gender. CONCLUSIONS: There is an inverse association between HMB levels and frailty status. These findings support the design of targeted clinical trials to evaluate the effect of HMB supplementation in older frail people with low HMB levels.

Differential utility of various frailty diagnostic tools in non-geriatric hospital departments of several countries: A longitudinal study.

BACKGROUND: There is limited knowledge on the performance of different frailty scales in clinical settings. We sought to evaluate in non-geriatric hospital departments the feasibility, agreement and predictive ability for adverse events after 1 year follow-up of several frailty assessment tools. METHODS: Longitudinal study with 667 older adults recruited from five hospitals in three different countries (Spain, Italy and United Kingdom). Participants were older than 75 years attending the emergency room, cardiology and surgery departments. Frailty scales used were Frailty Phenotype (FP), FRAIL scale, Tilburg and Groningen Frailty Indicators, and Clinical Frailty Scale (CFS). Analyses included the prevalence of frailty, degree of agreement between tools, feasibility and prognostic value for hospital readmission, worsening of disability and mortality, by tool and setting. RESULTS: Emergency Room and cardiology were the settings with the highest frailty prevalence, varying by tool between 40.4% and 67.2%; elective surgery was the one with the lowest prevalence (between 13.2% and 38.2%). The tools showed a fair to moderate agreement. FP showed the lowest feasibility, especially in urgent surgery (35.6%). FRAIL, CFS and FP predicted mortality and readmissions in several settings, but disability worsening only in cardiology. CONCLUSIONS: Frailty is a highly frequent condition in older people attending non-geriatric hospital departments. We recommend that based upon their current feasibility and predictive ability, the FRAIL scale, CFS and FP should be preferentially used in these settings. The low concordance among the tools and differences in prevalence reported and predictive ability suggest the existence of different subtypes of frailty.

The ability of eight frailty instruments to identify adverse outcomes across different settings: the FRAILTOOLS project.

BACKGROUND: To compare the performance of eight frailty instruments to identify relevant adverse outcomes for older people across different settings over a 12 month follow-up. METHODS: Observational longitudinal prospective study of people aged 75 + years enrolled in different settings (acute geriatric wards, geriatric clinic, primary care clinics, and nursing homes) across five European cities. Frailty was assessed using the following: Frailty Phenotype, SHARE-FI, 5-item Frailty Trait Scale (FTS-5), 3-item FTS (FTS-3), FRAIL scale, 35-item Frailty Index (FI-35), Gérontopôle Frailty Screening Tool, and Clinical Frailty Scale. Adverse outcomes ascertained at follow-up were as follows: falls, hospitalization, increase in limitation in basic (BADL) and instrumental activities of daily living (IADL), and mortality. Sensitivity, specificity, and capacity to predict adverse outcomes in logistic regressions by each instrument above age, gender, and multimorbidity were calculated. RESULTS: A total of 996 individuals were followed (mean age 82.2 SD 5.5 years, 61.3% female). In geriatric wards, the FI-35 (69.1%) and the FTS-5 (67.9%) showed good sensitivity to predict death and good specificity to predict BADL worsening (70.3% and 69.8%, respectively). The FI-35 also showed good sensitivity to predict BADL worsening (74.6%). In nursing homes, the FI-35 and the FTSs predicted mortality and BADL worsening with a sensitivity > 73.9%. In geriatric clinic, the FI-35, the FTS-5, and the FRAIL scale obtained specificities > 85% to predict BADL worsening. No instrument achieved high enough sensitivity nor specificity in primary care. All the instruments predict the risk for all the outcomes in the whole sample after adjusting for age, gender, and multimorbidity. The associations of these instruments that remained significant by setting were for BADL worsening in geriatric wards [FI-35 OR = 5.94 (2.69-13.14), FTS-3 = 3.87 (1.76-8.48)], nursing homes [FI-35 = 4.88 (1.54-15.44), FTS-5 = 3.20 (1.61-6.38), FTS-3 = 2.31 (1.27-4.21), FRAIL scale = 1.91 (1.05-3.48)], and geriatric clinic [FRAIL scale = 4.48 (1.73-11.58), FI-35 = 3.30 (1.55-7.00)]; for IADL worsening in primary care [FTS-5 = 3.99 (1.14-13.89)] and geriatric clinic [FI-35 = 3.42 (1.56-7.49), FRAIL scale = 3.27 (1.21-8.86)]; for hospitalizations in primary care [FI-35 = 3.04 (1.25-7.39)]; and for falls in geriatric clinic [FI-35 = 2.21 (1.01-4.84)]. CONCLUSIONS: No single assessment instrument performs the best for all settings and outcomes. While in inpatients several commonly used frailty instruments showed good sensitivities (mainly for mortality and BADL worsening) but usually poor specificities, the contrary happened in geriatric clinic. None of the instruments showed a good performance in primary care. The FI-35 and the FTS-5 showed the best profile among the instruments assessed.

Malnutrition Prevalence and Burden on Healthcare Resource Use Among Spanish Community-Living Older Adults: Results of a Longitudinal Analysis.

PURPOSE: Little is known about the economic burden that malnutrition or its risk imposes on community-dwelling older adults. Using cross-sectional and longitudinal analyses, we assessed the impact of malnutrition risk on healthcare utilization and costs in a cohort of older adults living in Spanish community. PATIENTS AND METHODS: Data from 1660 older (range 66-98 years), community-living adults participating in the Toledo Study on Healthy Ageing, waves 2 (year 2011-2013) and 3 (year 2015), were analyzed. Nutritional status categories were defined according to the Global Leadership Initiative on Malnutrition (GLIM) criteria, using a two-step approach. First, screening for malnutrition risk. Once positive, individuals were classified as malnourished according to some phenotypic (body mass index, grip strength, and unintentional weight loss) and etiologic (disease burden/inflammation and reduced food intake or assimilation) criteria. Outcomes assessed included healthcare resources (hospital admissions, number of hospitalizations, length of hospital stay per hospitalization, and number of medications). RESULTS: Fifteen percent of the population was found to be at risk of malnutrition, while 12.6% was malnourished. Overall, patients from both groups were older, had lower functional status, and had more comorbidities compared to well-nourished counterparts (p<0.05). Results of our cross-sectional analysis showed that being at-risk/malnourished was associated with greater medication utilization, higher rates of hospital admission and longer stays, and higher hospitalization costs. However, when adjusting for covariates, malnutrition/risk was associated only with higher hospitalization costs (range: 11-13%). Longitudinal analysis results indicated that malnutrition/risk was significantly associated with more frequent hospitalizations, longer lengths of stay, higher hospitalization costs, and polypharmacy at follow-up. CONCLUSION: Malnutrition or its risk, found in over one of four older adults in the Toledo community, was associated with higher healthcare resource use and increased costs. Such findings suggest that malnutrition risk-screening for older adults, and provision of nutrition counseling and care when needed, hold potential to improve their health and to lower costs of care in the Spanish healthcare system.

Drug Induced Liver Injury in Geriatric Patients Detected by a Two-Hospital Prospective Pharmacovigilance Program: A Comprehensive Analysis Using the Roussel Uclaf Causality Assessment Method.

Background/aim: A prospective evaluation of drug-induced liver injury (DILI) in two tertiary hospitals was conducted through a pharmacovigilance program from laboratory signals at hospital (PPLSH) to determine the principal characteristics of DILI in patients older than 65 years, a growing age group worldwide, which is underrepresented in the literature on DILI. Methods: All DILI in patients older than 65 years detected by PPLSH in two hospitals were followed up for 8 years in the La Paz Hospital and 2 years in the Getafe Hospital. A descriptive analysis was conducted that determined the causality of DILI and suspected drugs, the incidence of DILI morbidities, DILI characteristics, laboratory patterns, evolution and outcomes. Results: 458 DILI cases in 441 patients were identified, 31.0% resulting in hospitalisation and 69.0% developing during hospitalisation. The mean age was 76.61 years old (SD, 7.9), and 54.4% were women. The DILI incidence was 76.33/10,000 admissions (95%CI 60.78-95.13). Polypharmacy (taking >4 drugs) was present in 86.84% of patients, 39.68% of whom took >10 drugs. The hepatocellular phenotype was the most frequent type of DILI (53.29%), a higher proportion (65%) had a mild severity index, and, in 55.2% of the evaluated drugs the RUCAM indicated that the causal relationship was highly probable. The most frequently employed drugs were paracetamol (50-cases), amoxicillin-clavulanate (42-cases) and atorvastatin (37-cases). The incidence rate of in-hospital DILI per 10,000 DDDs was highest for piperacillin-tazobactam (66.96/10,000 DDDs). A higher risk of in-hospital DILI was associated with the therapeutic chemical group-J (antiinfectives for systemic use) (OR, 2.65; 95%CI 1.58-4.46) and group-N (central nervous system drugs) (OR, 2.33; 95%CI 1.26-4.31). The patients taking >4 medications presented higher maximum creatinine level (OR, 2.01; 95%CI 1.28-3.15), and the patients taking >10 medications had a higher use of group J drugs (OR, 2.08; 95%IC 1.31-3.32). Conclusion: The incidence rate of DILI in the patients older than 65 years was higher than expected. DILI in elderly patients is mild, has a good outcome, has a hepatocellular pattern, develops during hospitalisation, and prolongs the hospital stay. Knowing the DILI incidence and explanatory factors will help improve the therapy of the elderly population.

Sedentary behaviour, physical activity, and sarcopenia among older adults in the TSHA: isotemporal substitution model.

BACKGROUND: The associations between free-living physical activity (PA) and sedentary behaviour (SB) and sarcopenia in older people and its determinants are controversial. Self-reporting, the use of one-size-fits-all cut-points for intensity categorization when using accelerometers and the absence of a clear sarcopenia definition hampered explorations. The aim of this study is to describe the associations between objectively measured PA patterns and sarcopenia and its determinants. METHODS: Subjects aged >65 with valid accelerometry and sarcopenia-related measures from Toledo Study of Healthy Aging (TSHA) were included. Muscle mass (MM) was estimated by dual-energy X-ray absorptiometry. Handgrip strength (HS) was measured by dynamometry. Physical performance assessment relied on gait speed (GS). Sarcopenia presence was ascertained using Foundation for the National Institutes of Health (FNIH) criteria. PA and SB were estimated by ActiTrainer worn for 1 week and classified into time spent in SB and different PA intensity bands [light PA (LPA) and moderate-to-vigorous PA (MVPA)] using age-specific cut-points. Different multivariate linear and logistic regression models [(i) single-parameter, (ii) partition, and (iii) isotemporal substitution models] were used for estimating associations between PA, SB, and sarcopenia determinants and sarcopenia rates, respectively. All models adjusted for age, sex, co-morbidities (Charlson index), and functional ability (Katz and Lawton indexes). RESULTS: Five hundred twelve subjects from the TSHA had available data (78.08 ± 5.71 years of age; 54.3% women). FNIH sarcopenia assessment was performed in 497 subjects (23.3% were sarcopenic). In the linear regression, the single-parameter model showed an association between MVPA and all sarcopenia determinants. In the partition model, MVPA was associated with greater MM and GS. The isotemporal substitution showed that reallocating 1 h/day of MVPA displacing SB was associated with greater values in MM [ß = 0.014; 95% confidence interval (CI) = 0.004, 0.024; P < 0.01], GS (ß = 0.082; 95% CI = 0.054, 0.110; P < 0.001), and HS (ß = 0.888; 95% CI = 0.145, 1.631; P < 0.05). In the logistic regression, the single-parameter model yielded a significant association between 1 h/day increase in MVPA and sarcopenia reduction [odds ratio (OR) = 0.522; 95% CI = 0.367, 0.726; P < 0.001], as did the partition model (OR = 0.555; 95% CI = 0.376, 0.799; P < 0.01). The reallocation of 1 h/day SB only yielded a significant lower sarcopenia risk by almost 50% when it was substituted with MVPA, whereas the substitution of 15 min/day yielded a significant lower sarcopenia risk by 15% (P < 0.001) but did not show any association when it was substituted with LPA. CONCLUSIONS: An increase in MVPA replacing SB and LPA was associated with a reduction in sarcopenia prevalence and better performance across its determinants (MM, GS, and HS). LPA did not show any significant effect.