Beta-blockers and physical frailty in patients with end-stage liver disease.

AimTo investigate beta-blocker (BB) use in patients with cirrhosis and determine their effects on physical frailty and overall survival.MethodsAdult outpatients with cirrhosis listed for liver transplantation underwent testing of physical frailty using the performance-based Liver Frailty Index, comprised of chair stands, grip strength, and balance testing, as well as self-reported assessments of exhaustion and physical activity. BB use was assessed from medical chart review. Univariable and multivariable logistic regression were performed to determine BB use and their association with measures of physical frailty. Competing risk analyses were performed to determine the effect of BB use on wait-list mortality, as defined by death or delisting for being too sick for transplant.ResultsOf 344 patients, 35% were female, median age was 60, median model for end stage liver disease was 15, and 53% were prescribed a BB. Compared to those not on BB, patients on BB were similar except for percentage female (25% vs 46%; P < 0.001) and BMI (29 vs 28; P = 0.008). With respect to tests of physical frailty, BB use was not associated with increased odds of frailty (by the Liver Frailty Index), exhaustion, or low physical activity. BB use was, however, significantly associated with a decreased adjusted risk of mortality (SHR 0.55; P = 0.005).ConclusionIn patients with cirrhosis awaiting liver transplantation, BB use is not associated with physical frailty. We confirmed the known survival benefits with BB use, and concerns about adverse effects should not deter their utilization when indicated

Frailty is independently associated with increased hospitalisation days in patients on the liver transplant waitlist

AIM: To investigate the impact of physical frailty on risk of hospitalisation in cirrhotic patients on the liver transplant waitlist. METHODS: Cirrhotics listed for liver transplantation at a single centre underwent frailty assessments using the Fried Frailty Index, consisting of grip strength, gait speed, exhaustion, weight loss, and physical activity. Clinical and biochemical data including MELD score as collected at the time of assessment. The primary outcome was number of hospitalised days per year; secondary outcomes included incidence of infection. Univariable and multivariable analysis was performed using negative binomial regression to associate baseline parameters including frailty with clinical outcomes and estimated incidence rate ratios (IRR). RESULTS: Of 587 cirrhotics, 64% were male, median age (interquartile range) was 60 (53-64) years and MELD score was 15 (12-18). Median Fried Frailty Index was 2 (1-3); 31.6% were classified as frail (fried frailty ≥ 3). During 12 mo of follow-up, 43% required at least 1 hospitalisation; 38% of which involved major infection. 107/184 (58%) frail and 142/399 (36%) non-frail patients were hospitalised at least once (P < 0.001). In univariable analysis, Fried Frailty Index was associated with total hospitalisation days per year (IRR = 1.51, 95%CI: 1.28-1.77; P ≤ 0.001), which remained significant on multivariable analysis after adjustment for MELD, albumin, and gender (IRR for frailty of 1.21, 95%CI: 1.02-1.44; P = 0.03). Incidence of infection was not influenced by frailty. CONCLUSION: In cirrhotics on the liver transplant waitlist, physical frailty is a significant predictor of hospitalisation and total hospitalised days per year, independent of liver disease severity

Pathways from physical frailty to activity limitation in older people: identifying moderators and mediators in the English longitudinal study of ageing

Physical frailty increases the risk of future activity limitation, which in turn, compromises independent living of older people and limits their healthspan. Thus, we seek to identify moderators and mediators of the effect of physical frailty on activity limitation change in older people, including gender- and age-specific effects. In a longitudinal study using data from waves 2, 4, and 6 of the English Longitudinal Study of Ageing, unique physical frailty factor scores of 4,638 respondents aged 65 to 89 years are obtained from confirmatory factor analysis of physical frailty, which is specified by three indicators, namely slowness, weakness, and exhaustion. Using a series of autoregressive cross-lagged models, we estimate the effect of physical frailty factor score on activity limitation change, including its moderation by social conditions, and indirect effects through physical and psychological conditions. We find that the effect of physical frailty on activity limitation change is significantly stronger with older age, while it has significant indirect effects through low physical activity, depressive symptoms, and cognitive impairment. In turn, indirect effects of physical frailty through low physical activity and cognitive impairment are stronger with older age. Sensitivity analyses suggest that these effects vary in their robustness to unmeasured confounding. We conclude that low physical activity, depressive symptoms, and cognitive impairment are potentially modifiable mediators on pathways from physical frailty to activity limitation in older people, including those who are very old. This evidence offers support for population-level interventions that target these conditions, to mitigate the effect of physical frailty on activity limitation, and thereby enhance healthspan

Determinants of frailty: the added value of assessing medication

This study aims to analyze which determinants predict frailty in general and each frailty domain (physical, psychological, and social), considering the integral conceptual model of frailty, and particularly to examine the contribution of medication in this prediction. A cross-sectional study was designed using a non-probabilistic sample of 252 community-dwelling elderly from three Portuguese cities. Frailty and determinants of frailty were assessed with the Tilburg Frailty Indicator. The amount and type of different daily-consumed medication were also examined. Hierarchical regression analysis were conducted. The mean age of the participants was 79.2 years (±7.3), and most of them were women (75.8%), widowed (55.6%) and with a low educational level (0-4 years: 63.9%). In this study, determinants explained 46% of the variance of total frailty, and 39.8%, 25.3%, and 27.7% of physical, psychological, and social frailty respectively. Age, gender, income, death of a loved one in the past year, lifestyle, satisfaction with living environment and self-reported comorbidity predicted total frailty, while each frailty domain was associated with a different set of determinants. The number of medications independently predicted an additional 2.5% of total frailty and 5.3% of physical frailty. The adverse effects of polymedication and its direct link with the amount of comorbidities could explain the independent contribution of this variable to frailty prediction. Furthermore, the consumption of drugs for cardiovascular diseases was particularly important for the prediction of frailty and of its physical domain. In the present study, a significant part of frailty was predicted, and the different contributions of each determinant to frailty domains provided additional evidence of the integral model of frailty’s relevance. The added value of a simple assessment of medication was considerable, and it should be taken into account for effective identification of frailty

Identifying characteristics of frailty in female mice using a phenotype assessment tool

Preclinical studies are important in identifying the underlying mechanisms contributing to frailty. Frailty studies have mainly focused on male rodents with little directed at female rodents. Therefore, the purposes of this study were to identify the onset and prevalence of frailty across the life span in female mice, and to determine if frailty predicts mortality. Female C57BL/6 (n = 27) mice starting at 17 months of age were assessed across the life span using a frailty phenotype, which included body weight, walking speed, strength, endurance, and physical activity. The onset of frailty occurred at approximately 17 months (1/27 mice), with the prevalence of frailty increasing thereafter. At 17 months, 11.1% of the mice were pre-frail and by 26 months peaked at 36.9%. The percentage of frail mice progressively increased up to 66.7% at 32 months. Non-frail mice lived to 29 months whereas frail/pre-frail mice lived only to 26 months (p = .04). In closing, using a mouse frailty phenotype, we are able to identify that the prevalence of frailty in female mice increases across the life span and accurately predicts mortality. Together, this frailty phenotype has the potential to yield information about the underlying mechanisms contributing to frailty.T32 AG029796 - NIA NIH HHSPublished versio

Association between Physical Frailty and Quality of Life in a Representative Sample of Community-Dwelling Swiss Older People.

Though the association between physical frailty and health is well established, little is known about its association with other domains of quality of life (QoL). This study investigated the association between physical frailty and multiple domains of QoL in community-dwelling older people. Cross-sectional study. Data of the 2011 annual assessment of 927 older people (age 73-77 years) from the Lc65+ cohort study were used. Physical frailty was assessed by Fried's five criteria: 'shrinking'; 'weakness'; 'poor endurance, exhaustion'; 'slowness'; and 'low activity'. QoL was assessed using 28 items yielding a QoL score and seven domain-specific QoL subscores (Feeling of safety; Health and mobility; Autonomy; Close entourage; Material resources; Esteem and recognition; and Social and cultural life). Low QoL (QoL score or QoL subscores in the lowest quintile) was used as dependent variable in logistic regression analyses adjusted for age and sex (model 1), and additionally for socioeconomic (model 2) and health (model 3) covariates. Physical frailty was associated with a low QoL score, as well as decreased QoL subscores in all seven specific domains, even after adjusting for socio-economic covariates. However, when performing additional adjustment for health covariates, only the domain Health and mobility remained significantly associated with physical frailty. Among each specific Fried's criteria, 'slowness' had the strongest association with a low QoL score. Physical frailty is associated with all QoL domains, but these associations are largely explained by poor health characteristics. Longitudinal studies are needed to better understand temporal relationships between physical frailty, health and QoL

Cardiovascular risk profile and frailty in a population-based study of older British men.

BACKGROUND: Frailty in older age is known to be associated with cardiovascular disease (CVD) risk. However, the extent to which frailty is associated with the CVD risk profile has been little studied. Our aim was to examine the associations of a range of cardiovascular risk factors with frailty and to assess whether these are independent of established CVD. METHODS: Cross-sectional study of a socially representative sample of 1622 surviving men aged 71-92 examined in 2010-2012 across 24 British towns, from a prospective study initiated in 1978-1980. Frailty was defined using the Fried phenotype, including weight loss, grip strength, exhaustion, slowness and low physical activity. RESULTS: Among 1622 men, 303 (19%) were frail and 876 (54%) were pre-frail. Compared with non-frail, those with frailty had a higher odds of obesity (OR 2.03, 95% CI 1.38 to 2.99), high waist circumference (OR 2.30, 95% CI 1.67 to 3.17), low high-density lipoprotein-cholesterol (HDL-C) (OR 2.28, 95% CI 1.47 to 3.54) and hypertension (OR 1.79, 95% CI 1.27 to 2.54). Prevalence of these factors was also higher in those with frailty (prevalence in frail vs non-frail groups was 46% vs 31% for high waist circumference, 20% vs 11% for low HDL and 78% vs 65% for hypertension). Frail individuals had a worse cardiovascular risk profile with an increased risk of high heart rate, poor lung function (forced expiratory volume in 1 s (FEV1)), raised white cell count (WCC), poor renal function (low estimated glomerular filtration rate), low alanine transaminase and low serum sodium. Some risk factors (HDL-C, hypertension, WCC, FEV1, renal function and albumin) were also associated with being pre-frail. These associations remained when men with prevalent CVD were excluded. CONCLUSIONS: Frailty was associated with increased risk of a range of cardiovascular factors (including obesity, HDL-C, hypertension, heart rate, lung function, renal function) in older people; these associations were independent of established CVD

Association between cognitive impairment and criteria for frailty syndrome among older adults

OBJECTIVE: The association between cognitive impairment and physical frailty has been studied in older adults. The criteria degree of frailty may be keys to associated cognitive impairment. To analyze the association between cognitive impairment and the criteria for frailty. METHODS: We cross-sectionally examined data from 667 older adults (≥60 years of age) from a study entitled 'Variables associated to cognition in elderly caregivers' involving patients in an urban and rural primary healthcare center. We defined cognitive impairment based on different groups of scores on the Mini Mental State Examination, and defined frailty and prefrailty using the criteria by the Cardiovascular Health Study. We performed multinomial regression models to analyze the association between levels of frailty and cognitive impairment. RESULTS: Similar proportions of women (54.8%) and men (45.2%) participated in the study (mean age: 71 years old). We found cognitive impairment, prefrailty and frailty in 34, 54, and 24% of the participants, respectively. Concomitant cognitive impairment and frailty was found in 13% of them. The chances of cognitive impairment increased up to 330% (Odds Ratio [OR]: 4.3; 95% confidence interval [95%CI] 2.4‒7.7; p<0.001) among frail individuals, and 70% (OR: 1.7; 95%CI 1.0‒2.8; p=0.033) among prefrail individuals compared to robust/non-frail individuals. After controlling for age, education, place of residence and functional dependence, slowness and fatigue criteria were significantly associated with cognitive impairment. CONCLUSION: Older adults with frailty have a greater likelihood of concomitant cognitive impairment than prefrail and robust older adults. The prevalence of cognitive impairment and frailty is consistent with data reported in literature. The present findings contribute to the investigation of cognitive frailty

Rehabilitation Therapy in Older Acute Heart Failure Patients (REHAB-HF) trial: Design and rationale.

BACKGROUND: Acute decompensated heart failure (ADHF) is a leading cause of hospitalization in older persons in the United States. Reduced physical function and frailty are major determinants of adverse outcomes in older patients with hospitalized ADHF. However, these are not addressed by current heart failure (HF) management strategies and there has been little study of exercise training in older, frail HF patients with recent ADHF. HYPOTHESIS: Targeting physical frailty with a multi-domain structured physical rehabilitation intervention will improve physical function and reduce adverse outcomes among older patients experiencing a HF hospitalization. STUDY DESIGN: REHAB-HF is a multi-center clinical trial in which 360 patients ≥60 years hospitalized with ADHF will be randomized either to a novel 12-week multi-domain physical rehabilitation intervention or to attention control. The goal of the intervention is to improve balance, mobility, strength and endurance utilizing reproducible, targeted exercises administered by a multi-disciplinary team with specific milestones for progression. The primary study aim is to assess the efficacy of the REHAB-HF intervention on physical function measured by total Short Physical Performance Battery score. The secondary outcome is 6-month all-cause rehospitalization. Additional outcome measures include quality of life and costs. CONCLUSIONS: REHAB-HF is the first randomized trial of a physical function intervention in older patients with hospitalized ADHF designed to determine if addressing deficits in balance, mobility, strength and endurance improves physical function and reduces rehospitalizations. It will address key evidence gaps concerning the role of physical rehabilitation in the care of older patients, those with ADHF, frailty, and multiple comorbidities

Multidimensional predictors of physical frailty in older people: identifying how and for whom they exert their effects

Physical frailty in older people is an escalating health and social challenge. We investigate its physical, psychological, and social predictors, including how and for whom these conditions exert their effects. For 4,638 respondents aged 65 to 89 years from wave 2 of the English Longitudinal Study of Ageing, we examine prediction of future physical frailty by physical, psychological, and social conditions using latent growth curve analysis with multiple indicators. In addition, we explore their indirect effects through disease and physiologic decline, and repeat these analyses after stratification by gender, age group, and selected conditions which are possible moderators. We find that chronic disease, allostatic load, low physical activity, depressive symptoms, cognitive impairment, and poor social support all predict future physical frailty. Furthermore, chronic disease and allostatic load mediate the effects of low physical activity, depressive symptoms, and cognitive impairment on future physical frailty. Finally, although poor social integration is not a predictor of future physical frailty, this condition moderates the indirect effect of poor social support through chronic disease by rendering it stronger. By virtue of their roles as predictor, mediator, or moderator on pathways to physical frailty, chronic disease, allostatic load, low physical activity, cognitive impairment, depressive symptoms, poor social support, and poor social integration are potentially modifiable target conditions for population-level health and social interventions to reduce future physical frailty in older people