Response rates and associated factors after a multicomponent intervention in frail older adults with diabetes.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and frailty are associated with functional decline in older population. OBJECTIVE: To explore the individual response to a multimodal intervention on functional performance. DESIGN: A cluster-randomised multicentre clinical trial. SETTING: Outpatients in hospital or primary care. SUBJECTS: 843 (77.83 years, 50.65% men) prefrail and frail individuals ≥70 years with T2DM. METHODS: Participants were allocated to usual care group (UCG) or a multicomponent intervention group (IG): 16-week progressive resistance training, seven nutritional and diabetological educational sessions and achievement of glycated haemoglobin (7-8%) and blood pressure (<150 mmHg) targets. Functional performance was assessed with the Short Physical Performance Battery (SPPB) at 1 year. We used multivariate binomial and multinomial logistic regression models to explore the effect of the IG, and adherence on the outcomes studied, in several adjusted models. RESULTS: 53.7% in the IG versus 38.0% in the UCG improved by at least 1 point in their SPPB score [OR (95% CI): 2.07 (1.43, 2.98), P value <0.001]. Age, SPPB score and number of frailty criteria met decreased the probability of improving the SPPB score. Factors associated with worsening were pertaining to IG (decreased), age, SPPB score and the number of frailty criteria (increased). An adherence ≥84% was needed to achieve benefits, reaching the peak in the probability of improving SPPB when this was ≥85% [OR(95%CI): 2.38 (1.29, 4.79), P value 0.014]. CONCLUSIONS: Factors predicting the likelihood of improvement in a multimodal programme in pre-frail and frail older adults with diabetes are age, basal SPPB score, the number of frailty criteria and adherence.

Physical performance and negative events in very old adults: a longitudinal study examining the ilSIRENTE cohort.

BACKGROUND: Declining physical performance in old age is associated with a wide range of negative health-related outcomes. However, it is unclear which physical capabilities should be prioritized to obtain prognostic information in older adults. AIMS: To examine the associations between the performance on several physical function tests and falls, disability, and death in a well-characterized sample of very old Italian adults. METHODS: This was a prospective cohort study of older adults who lived in the mountain community of the Sirente geographic area in Central Italy. Physical performance was assessed using isometric handgrip strength (IHG), walking speed (WS) at a usual and fast pace, 5-time sit-to-stand test (5STS), and sit-to-stand power measures. Appendicular skeletal muscle mass was estimated from calf circumference using a validated equation. History of falls, incident falls, and disability status according to basic Activities of Daily Living (ADLs) were recorded over two years. Survival status was obtained from the participants' general practitioners and was confirmed by the National Death Registry over 10 years from enrolment. Linear, binary, and Cox regressions were performed to evaluate the association between physical performance measures and health outcomes. RESULTS: The mean age of the 255 participants was 84.2 ± 5.1 years, and 161 (63.1%) were women. Logistic regression indicated that IHG was significantly associated with incident ADL disability, whereas specific sit-to-stand muscle power was an independent predictor of death. No significant associations were observed between physical function and falls. CONCLUSIONS: Our findings indicate selective associations between physical function tests and the occurrence of negative events in very old adults, with poor IHG predicting disability and specific sit-to-stand muscle power being longitudinally associated with death.

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.

Healthcare cost expenditures associated to frailty and sarcopenia.

OBJECTIVES: Frailty and sarcopenia have been related with adverse events, including hospitalization. However, its combined effect with hospitalization-related outcomes, including costs, has not been previously investigated. Our purpose was to explore how frailty, sarcopenia and its interaction could impact on healthcare expenditures. METHODS: 1358 community-dwelling older adults from the Toledo Study of Healthy Ageing (TSHA) were included. Sarcopenia was measured using the Foundation for the National Institutes of Health criteria fitted to our cohort. Frailty was defined according to Frailty Trait Scale 5 (FTS5) and the Frailty Index fitted to the cut-off points of TSHA population. Hospitalization costs were taken from hospital records and costs were attributed according to Diagnostic-Related Groups, using as the cost base year 2015. Two-part regression models were used to analyze the relationship between frailty and sarcopenia and hospital admission, number of hospitalizations, length of stay and hospitalization costs. RESULTS: Sarcopenia was associated only with the probability of being admitted to hospital. Frailty was also associated with higher hospital use, regardless of the frailty tool used, but in addition increased hospital admission costs at follow-up by 23.72% per year and by 19.73% in the full model compared with non-frail individuals. The presence of sarcopenia did not increase the costs of frailty but, by opposite, frailty significantly increased the costs in people with sarcopenia, reaching by 46-56%/patient/year at follow-up. Older adults with frailty and sarcopenia had a higher risk of hospitalization, disregarding the tool used to assess frailty, and higher hospitalization costs (FTS5) in the full model, at the cross-sectional and at the follow-up level. CONCLUSIONS: Frailty is associated with increased hospitalization costs and accounts for the potential effects of sarcopenia.

Effect of Physical Activity/Exercise on Oxidative Stress and Inflammation in Muscle and Vascular Aging.

Functional status is considered the main determinant of healthy aging. Impairment in skeletal muscle and the cardiovascular system, two interrelated systems, results in compromised functional status in aging. Increased oxidative stress and inflammation in older subjects constitute the background for skeletal muscle and cardiovascular system alterations. Aged skeletal muscle mass and strength impairment is related to anabolic resistance, mitochondrial dysfunction, increased oxidative stress and inflammation as well as a reduced antioxidant response and myokine profile. Arterial stiffness and endothelial function stand out as the main cardiovascular alterations related to aging, where increased systemic and vascular oxidative stress and inflammation play a key role. Physical activity and exercise training arise as modifiable determinants of functional outcomes in older persons. Exercise enhances antioxidant response, decreases age-related oxidative stress and pro-inflammatory signals, and promotes the activation of anabolic and mitochondrial biogenesis pathways in skeletal muscle. Additionally, exercise improves endothelial function and arterial stiffness by reducing inflammatory and oxidative damage signaling in vascular tissue together with an increase in antioxidant enzymes and nitric oxide availability, globally promoting functional performance and healthy aging. This review focuses on the role of oxidative stress and inflammation in aged musculoskeletal and vascular systems and how physical activity/exercise influences functional status in the elderly.

Prevalence and correlates of cancer-related fatigue in breast cancer survivors.

PURPOSE: To identify potential correlates of cancer-related fatigue (CRF) after curative breast cancer (BC) treatment. The hypothesis was that fatigue would be more severe among women treated with cardiotoxic drugs, with poor physical condition and those who exercised less. METHODS: Observational cross-sectional design. Fatigue was evaluated through PERFORM Questionnaire (multi-item, multi-dimensional). Patient-reported assessments and objective information regarding clinical data, physical activity (PA) and physical condition were analysed as potential correlates of CRF. RESULTS: One hundred eighty women who remained free of disease were recruited. The prevalence of fatigue interfering with quality of life was 43%. Weight, resting and recovery heart rate were positively associated with fatigue. Age and time from diagnosis were negatively associated. Previous therapies, objectively assessed weekly PA, cardiorespiratory condition, muscular strength and adherence to Mediterranean diet were not associated with CRF. CONCLUSIONS: CRF is a prevalent problem after BC treatment. Objectively assessed PA, cardiorespiratory fitness and muscular strength did not predict CRF. The association of heart rate and fatigue deserves a further insight. Future research should include longitudinal studies and determination of biomarkers. IMPLICATIONS FOR CANCER SURVIVORS: BC survivors, especially younger and overweight women, should be informed about fatigue as a potential persistent symptom through all stages of the cancer trajectory and into survivorship. They also should be routinely screened for CRF.

Concurrent Exercise Interventions in Breast Cancer Survivors with Cancer-related Fatigue.

This study compared the effects of two supervised concurrent training interventions in breast cancer survivors with cancer-related fatigue at baseline. Twenty-three female breast cancer survivors (50±8 years) were randomized to a high- (n=13) or a moderate-intensity (n=10) training program. Both interventions lasted 16 weeks and included the same resistance exercises, but the aerobic component was supervised and more intense in the former (i.e., rating of perceived exertion of 7-8 vs. 6 on a 1-10 scale for the high and moderate-intensity intervention, respectively). The primary endpoint was fatigue perception. Endpoints were assessed at baseline and after 16 weeks. The p-value for statistical significance was set at 0.004 after Bonferroni correction for multiple comparisons. The high-intensity training program increased lower-limb muscle strength significantly (p=0.002) and tended to improve fatigue perception (p=0.006), waist circumference (p=0.013), neutrophil-to-lymphocyte ratio (p=0.028) and some quality of life items (p=0.011). Although the moderate-intensity training program did not provide such benefits in general (i.e., higher p-values for pre vs post-intervention comparisons), no significant differences were found between interventions (all p>0.004). Further research is needed to elucidate if the benefits provided by high-intensity concurrent training are superior to those elicited by moderate-intensity training in breast cancer survivors.

Cardiorespiratory fitness and adiposity in breast cancer survivors: is meeting current physical activity recommendations really enough?

PURPOSE: Breast cancer (BC) survivors are becoming increasingly predisposed to cardiovascular disease (CVD) mortality. Low cardiorespiratory fitness and physical activity (PA) levels, as well as high values of adiposity indices, contribute to CVD risk. We evaluated adiposity, cardiorespiratory profile, and PA levels in two independent cohorts of BC survivors. METHODS: Data were collected from two groups (99% women) from different areas of Madrid (Spain): group 1, n = 110, age 51.4 ± 9.7 years, median time from diagnosis 365 days (95% confidence interval [CI], 354-401), and group 2, n = 93, age 54.7 ± 8.9 years, 1714 days (95% CI, 1502-1938). We estimated peak oxygen uptake (VO2peak) and measured body mass index (BMI), waist circumference (WC), waist-to-hip index, and accelerometry-determined PA. RESULTS: Both groups had values of BMI in the overweight range (25.3 ± 4.3 and 27.1 ± 5.1 kg/m2, p = 0.003). Estimated VO2peak levels were lower in group 2 than in group 1 (28.1 ± 9.1 and 23.7 ± 8.8 ml/kg/min, p < 0.001), although levels in both groups were low. Yet, the majority of participants in both groups (81 and 88%, p = 0.234) met international PA recommendations (235 ± 196 and 351 ± 173 min/week of moderate-vigorous PA, p < 0.001). Both groups had very low levels of vigorous PA. These results were essentially independent of type of treatment (anthracycline/radiotherapy). CONCLUSIONS: We found a poor cardiorespiratory profile in two independent BC cohorts that differed in median time from diagnosis (as well in socioeconomic status), supporting the notion that implementation of PA (possibly focusing on vigorous PA) and dietary intervention is urgently needed in this patient population.

Biomarkers of frailty.

Several biomarkers have been proposed to identify frailty, a multisystemic age-related syndrome. However, the complex pathophysiology and the absence of a consensus on a comprehensive and universal definition make it challenging to pinpoint a singular biomarker or set of biomarkers that conclusively characterize frailty. This review delves into the main laboratory biomarkers, placing special emphasis on those associated with various pathways closely tied to the frailty condition, such as inflammation, oxidative stress, mitochondrial dysfunction, metabolic and endocrine alterations and microRNA. Additionally, we provide a summary of different clinical biomarkers encompassing different tools that have been proposed to assess frailty. We further address various imaging biomarkers such as Dual Energy X-ray Absorptiometry, Bioelectrical Impedance analysis, Computed Tomography and Magnetic Resonance Imaging, Ultrasound and D3 Creatine dilution. Intervention to treat frailty, including non-pharmacological ones, especially those involving physical exercise and nutrition, and pharmacological interventions, that include those targeting specific mechanisms such as myostatin inhibitors, insulin sensitizer metformin and with special relevance for hormonal treatments are mentioned. We further address the levels of different biomarkers in monitoring the potential positive effects of some of these interventions. Despite the availability of numerous biomarkers, their performance and usefulness in the clinical arena are far from being satisfactory. Considering the multicausality of frailty, there is an increasing need to assess the role of sets of biomarkers and the combination between laboratory, clinical and image biomarkers, in terms of sensitivity, specificity and predictive values for the diagnosis and prognosis of the different outcomes of frailty to improve detection and monitoring of older people with frailty or at risk of developing it, being this a need in the everyday clinical practice.

Agreement and Associations between Countermovement Jump, 5-Time Sit-To-Stand, Lower-Limb Muscle Power Equations, and Physical Performance Tests in Community-Dwelling Older Adults.

Objectives: The present study examined the agreement and associations of the 5-time sit-to-stand (5STS) test, the countermovement jump test, and lower-limb muscle power equations with a set of physical performance tests in older adults. Methods: Five hundred and thirty-four community-dwelling older adults were recruited for the study. Lower-limb muscle power measures included 5STS, the countermovement jump test, and muscle power equations. Isometric handgrip strength, timed "up-and-go!", the 6 min walking test, one-leg stand, and walking speed at usual and fast paces were used to assess physical performance. Pearson's correlations and Bland-Altman analyses were conducted to examine associations among muscle power measures. Linear and multiple regressions were run to explore associations of 5STS, the countermovement jump test, and muscle power equations with physical performance tests. Results: Weak correlations were observed among lower-limb muscle power measures. Bland-Altman results indicated important differences among the countermovement jump test, 5STS, and muscle power equations. Results of multiple linear regressions indicated that 5STS, the countermovement jump test, and muscle power equations were significantly associated with measures of muscle strength and mobility. However, only 5STS was significantly associated with balance. Conclusions: Our results indicate that the performance on the countermovement jump test and 5STS is weakly correlated with lower-limb muscle power equations. The only exception was the correlation found between the countermovement jump test and relative muscle power, highlighting the importance of accounting for body mass in muscle power evaluations. Muscle power measures were similarly associated with performance on handgrip strength, timed "up-and-go!", and the 6 min walking test. The exclusive association of 5STS with balance suggests that a reassessment of 5STS muscle power equations may be warranted.

Diagnostic and prognostic value of calf circumference for sarcopenia in community-dwelling older adults.

BACKGROUND: An age-dependent normative values of calf circumference (CC) has been recently proposed as an accessible proxy for muscle mass. However, its usefulness to estimate sarcopenia has not been assessed. The objectives of the present study were to determine if the substitution of the classical way to assess muscle mass by these values have enough diagnostic accuracy and prognostic value among older adults living in the community. METHODS: Data from the Toledo Study of Healthy Ageing (TSHA) were used. CC was measured using an anthropometric tape. We used two age-groups CC cut-off points: the TSHA CC median and the one proposed in the Longevity Check-up 7+ (Lookup 7+) project. Sarcopenia was defined based on the European Working Group on Sarcopenia in Older People (EWGSOP2), the Foundation for the National Institutes of Health (FNIH), and FNIH criteria standardized for our population (sFNIH). Frailty (according to the Frailty Phenotype and the Frailty Trait Scale-5) and disability (Katz index) were assessed at baseline and follow-up. Mortality and first hospitalization were also recorded. Logistic (incident frailty and worsening disability) and Cox (mortality and hospitalization) regressions were performed. Diagnostic accuracy was assessed through Kappa index, AUCs, positive and negative predictive values. Predictive ability was assessed through AUCs and integrated AUCs (IAUCs). RESULTS: 1531 participants (74.8 ± 5.8 years; 45.6% men) were included in the analysis. Prevalence rates of sarcopenia were 22.7% (sFNIH), 15.0% (FNIH), and 13.9% (EWGSOP2). Using TSHA-based cut-points of CC, the prevalence of sarcopenia was 16.8% (sFNIH), 11.0% (FNIH), and 11.5% (EWGSOP2). According to LC7+-based CC cut-off points, sarcopenia prevalence was 17.6% (sFNIH), 11.9% (FNIH), and 12.4% (EWGSOP2). CC cut-off points showed low-to-moderate agreement (Kappa Index values between 0.49 and 0.69) with appendicular lean mass for the evaluation of sarcopenia. Sarcopenia identified by Lookup 7+ and TSHA CC cut-off points was associated with the adverse events examined, with similar AUCs and IAUCs than original sarcopenia definitions, and were lost after adjustment by baseline frailty, except when the original EWGSOP2 definition was used. CONCLUSIONS: Using normalized values of CC as a criteria of muscle mass shows moderate agreement with classical criteria for diagnosing sarcopenia and offer similar predictive value in community-dwelling older adults.

Cancer-Related Fatigue and Circulating Biomarkers in Breast Cancer Survivors.

PURPOSE: Cancer-related fatigue (CRF) is the most common and disruptive symptom experienced by cancer survivors and because of its frequency and severity is especially worrisome in breast cancer survivors (BCS). Despite a great deal of research, the mechanisms underlying CRF have not been determined. The present study aims to describe associations between CRF in BCS and different blood biomarkers. METHODS: A descriptive and cross-sectional study was conducted. A set of biomarkers assessing inflammation were measured in BCS: C-reactive protein (CRP), neutrophil-lymphocyte ratio (NLR), IL-1ß, IL-6, IL-8, IL-10, tumor necrosis factor (TNF); HPA axis dysfunction (cortisol), autonomic dysfunction (noradrenaline); oxidative stress (8-OH deoxyguanosine); insulin resistance markers (insulin, IGF-I, IGFBP3) and sexual hormones (estrogens, progesterone, testosterone). RESULTS: NLR (p = .00) and cortisol (p = .02) were positive and negatively associated with CRF, respectively. The rest of the blood markers were not associated with CRF. CONCLUSION: Our results increase the evidence on pathophysiological mechanisms driving CRF in BCS. However, longitudinal studies are needed to explore the role of these factors as potential causal mechanisms.

Effectiveness of a randomized intervention by a geriatric team in frail hospital inpatients in non-geriatric settings: FRAILCLINIC project.

BACKGROUND: Little research has been undertaken on the benefits of frailty management within different hospital settings. The objective of this study is to provide evidence on the viability and effectiveness of frailty management in non-geriatric hospital settings on mortality and functional decline after discharge. METHODS: Data from the FRAILCLINIC (NCT02643069) study were used. FRAILCLINIC is a randomized controlled trial developed in non-geriatric hospital inpatient settings (emergency room, cardiology and surgery) from Spain (2), Italy (2) and the United Kingdom (1). Inpatients must met frailty criteria (according to the Frailty Phenotype and/or FRAIL scale), ≥75 years old. The control group (CG) received usual care. The intervention group (IG) received comprehensive geriatric assessment (CGA) and a coordinated intervention consisting in recommendations to the treating physician about polypharmacy, delirium, falls, nutrition and physical exercise plus a discharge plan. The main outcomes included functional decline (worsening ≥5 points in Barthel Index) and mortality at 3 months. We used multivariate logistic regression models adjusted by age, gender and the Charlson index. Intention-to-treat (ITT) and per-protocol (PP) analyses were used. RESULTS: Eight hundred twenty one participants (IG: 416; mean age 83.00 ± 4.91; 51.44% women; CG: 405; mean age 82.46 ± 6.03; 52.35% women) were included. In the IG, 77.16% of the participants followed the geriatric team's recommendations as implemented by the treating physicians. The intervention showed a benefit on functional decline and mortality [OR: 0.67(0.47-0.96), P-value 0.027 and 0.29(0.14-0.57), P-value < 0.001, respectively) when fully followed by the treating physician. A trend to benefit (close to statistical significance) in functional decline and mortality were also observed when any of the recommendations were not followed [OR (95% CI): 0.72 (0.51-1.01), P-value: 0.055; and 0.64 (0.37-1.10), P-value: 0.105, respectively]. CONCLUSIONS: An individualized intervention in frail in-patients reduces the risk of functional deterioration and mortality at 3 months of follow-up when a care management plan is designed and followed.

Relationship of endogenous plasma concentrations of ß-hydroxy ß-methyl butyrate (HMB) with frailty in community dwelling older adults with type-2 diabetes mellitus.

BACKGROUND: Supplementation with ß-hydroxy ß-methyl butyrate (HMB) appears to be effective in preserving muscle in older adults. However, the association between endogenously produced HMB with frailty has not been studied in people with chronic disease. OBJECTIVES: The purpose of this study is to explore whether an association exists between endogenous HMB levels and frailty status in older adults with type-2 diabetes mellitus (T2DM). METHODS: Data were taken from the Toledo Study of Healthy Ageing, a community-dwelling aged (65 years+) cohort. Frailty was assessed at baseline and at 2.99 median years according to the Frailty Phenotype (FP) standardized to our population and the Frailty Trait Scale 12 (FTS12). The associations between HMB levels and frailty were assessed using three nested multivariate logistic regressions and segmented by sex. Glucose, HMB and glucose interaction, age and body composition were used as covariables. RESULTS: 255 participants (mean age 75.3 years, 52.94% men) were included. HMB levels showed an inverse cross-sectional association with frailty, which was modified when the interaction term HMB*glucose was included, remaining significant only for FTS12 [OR (95% CI): 0.436 (0.253, 0.751), p-value 0.003]. The association between HMB endogenous levels and FTS12 appears to be independent of sex, in which the association was maintained after adjusting for the covariates. However, there appears to be threshold points for glucose levels, above which the protective effect of HMB is lost: 145.4 mg/dl adjusted by gender for the whole sample and 149.6 mg/dl and 138.9 mg/dl for men and women, respectively. Endogenous HMB levels were not found to be associated with incident frailty. CONCLUSIONS: Cross-sectional analysis revealed that endogenous HMB levels were inversely associated with frailty as assessed by the FTS12 in older people with T2DM. This association was found to be dependent on circulating fasted glucose levels.

Pulmonary function is associated with frailty, hospitalization and mortality in older people: 5-year follow-up.

BACKGROUND: The relationship between pulmonary impairment and frailty has rarely been studied in community-dwelling older adults. OBJECTIVE: This study aimed to analyze the association between pulmonary function and frailty (prevalent and incident), identifying the best cut-off points to detect frailty and its association with hospitalization and mortality. METHODS: A longitudinal observational cohort study with 1188 community-dwelling older adults was taken from the Toledo Study for Healthy Aging. The forced expiratory volume in the first second (FEV1) and the forced vital capacity (FVC) were measured with spirometry. Frailty was evaluated using the Frailty Phenotype and Frailty Trait Scale 5. Associations between pulmonary function and frailty, hospitalization and mortality in a 5-year follow-up and the best cut-off points for FEV1 and FVC were analyzed. RESULTS: FEV1 and FVC were associated with frailty prevalence (OR from 0.25 to 0.60), incidence (OR from 0.26 to 0.53), and hospitalization and mortality (HR from 0.35 to 0.85). The cut-off points of pulmonary function identified in this study: FEV1 (≤1.805 L for male and ≤1.165 L for female) and FVC (≤2.385 L for male and ≤1.585 L for female) were associated with incident frailty (OR: 1.71-4.06), hospitalization (HR: 1.03-1.57) and mortality (HR: 2.64-5.17) in individuals with and without respiratory diseases (P < 0.05 for all). CONCLUSION: Pulmonary function was inversely associated with the risk of frailty, hospitalization and mortality in community-dwelling older adults. The cut-off points for FEV1 and FVC to detect frailty were highly associated with hospitalization and mortality in the 5-year follow-up, regardless of the existence of pulmonary diseases.

Recommendations and Effects of Rehabilitation Programs in Older Adults After Hospitalization for COVID-19: A Scoping Review.

ABSTRACT: The aims of this review were to identify studies on physical rehabilitation programs and describe the potential effects on functional outcomes in patients older than 60 yrs at discharge from acute care post-COVID-19. The literature search was conducted in the MEDLINE, Cochrane CENTRAL, EMBASE, PEDro, LILACS, CINAHL, SPORTDiscus, Web of Science, and The Living OVerview of Evidence (L-OVE) COVID-19 databases. Studies with patients older than 60 yrs, hospitalized with COVID-19, and admitted to a rehabilitation program after discharge from acute care were included. Ten studies were included with a total of 572 patients. The prevalence of patients who received post-intensive care rehabilitation was 53% (95% confidence interval, 0.27-0.79; P = 0.001). The rehabilitation program included physiotherapy in nine studies, occupational therapy in three studies, and psychotherapy in two studies. The rehabilitation programs increased aerobic capacity, functional independence in basic activities of daily living, muscle strength, muscle mass, dynamic balance, physical performance, pulmonary function, quality of life, cognitive capacity and mental health. Multidisciplinary rehabilitation programs are necessary for older adults after hospitalization for COVID-19, especially those coming from intensive care units, as rehabilitation has a positive effect on important clinical outcomes.

Association Between Pulse Wave Velocity and Frailty, Disability, and Mortality in Community-Dwelling Older Adults.

Background: Arterial stiffness leads to several adverse events in the older population, but there is a lack of data on its association with frailty, disability, and mortality in the same population. Objectives: The purpose of this study was to evaluate the role of arterial stiffness in the loss of functional ability (frailty and disability) and mortality. Methods: Data were taken from community-dwelling aged 65 years participants without diabetes in the Toledo Study of Healthy Ageing cohort. Pulse wave velocity (PWV), assessed through SphygmoCor, was recorded at baseline. Median follow-up time were 2.99 years for frailty (frailty phenotype [FP] and Frailty Trait Scale-5 [FTS5]) and disability (Katz Index) and 6.2 for mortality. Logistic regressions models were built for disability and frailty and Cox proportional hazards model for death, adjusted by age and sex, comorbidity, cardiovascular risk factors, asymmetric dimethylarginine levels, and polypharmacy. Results: Overall, 978 (mean age 74.5 ± 5.6 years, 56.7% female) participants were included. Different cut-off points were shown for each outcome. PWV >11.5 m/s was cross-sectionally associated with frailty (FP: OR fully-adjusted model: 1.69, 95% CI: 1.45-1.97; FTS5: OR: 1.51, 95% CI: 1.22-1.87) and disability (OR: 1.51, 95% CI: 1.26-1.79); PWV >10 m/s with incident frailty by FP (OR: 1.36, 95% CI: 1.10-1.68) and FTS5 (OR: 1.40, 95% CI: 1.12-1.75), and PWV >11 m/s with death (HR: 1.28, 95% CI: 1.09-1.50). For incident (OR: 1.28, 95% CI: 1.06-1.55) and worsening disability (OR: 1.21, 95% CI: 1.02-1.45) the threshold was 12.5 m/s. Below these cut-off points, age was the best predictor of adverse outcomes. Conclusions: Arterial stiffness predicts frailty, disability, and mortality in older people, with different cut-off points, ie,severity degrees, for each of the assessed outcomes.

Differential Association of Frailty and Sarcopenia With Mortality and Disability: Insight Supporting Clinical Subtypes of Frailty.

OBJECTIVES: Sarcopenia and frailty have been shown separately to predict disability and death in old age. Our aim was to determine if sarcopenia may modify the prognosis of frailty regarding both mortality and disability, raising the existence of clinical subtypes of frailty depending on the presence of sarcopenia. DESIGN: A Spanish longitudinal population-based study. SETTING AND PARTICIPANTS: The population consists of 1531 participants (>65 years of age) from the Toledo Study of Health Aging. METHODS: Sarcopenia and frailty were assessed following Foundation for the National Institutes of Health criteria and the Fried Frailty Phenotype, respectively. Mortality was assessed using the National Death Index. Functional status was determined using Katz index. We ran multivariate logistics and proportional hazards models adjusting for age, sex, baseline function, and comorbidities. RESULTS: Mean age was 75.4 years (SD 5.9). Overall, 70 participants were frail (4.6%), 565 prefrail (36.9%), and 435 sarcopenic (28.4%). Mean follow-up was 5.5 and 3.0 years for death and worsening function, respectively. Furthermore, 184 participants died (12%) and 324 worsened their functioning (24.8%). Frailty and prefrailty were associated with mortality and remained significant after adjustment by sarcopenia [hazard risk (HR) 3.09, 95% confidence interval (CI) 1.84-5.18; P < .001; HR 1.58, 95% CI 1.12-2.24, P = .01]. However, the association of sarcopenia with mortality was reduced and became nonsignificant (HR 1.43, 95% CI 0.99-2.07, P = .057) when both frailty and sarcopenia were included in the same model. In the disability model, frailty and sarcopenia showed a statistically significant interaction (P = .016): both had to be present to predict worsening of disability. CONCLUSIONS AND IMPLICATIONS: Sarcopenia plays a relevant role in the increased risk of functional impairment associated to frailty, but that seems not to be the case with mortality. This finding raises the need of assessing sarcopenia as a cornerstone of the clinical work after diagnosing frailty.

Associations between frailty trajectories and frailty status and adverse outcomes in community-dwelling older adults.

BACKGROUND: The association between frailty and adverse outcomes has been clearly defined. Frailty is associated with age, but different frailty evolution patterns might determine the incidence of adverse outcomes at older ages. So far, few observational studies have examined how distinct frailty trajectories could be associated with differences in the risk of adverse events and assessing whether frailty trajectories could define risk of death, hospitalization, worsening, and incident disability better than one-off assessment. Our hypothesis is that prospective increases in frailty levels are associated with higher risk of adverse events compared with subjects that prospectively decreased frailty levels. METHODS: Participants' data were taken from the Toledo Study of Healthy Ageing. Frailty was evaluated using the Frailty Trait Scale 5 (FTS5), being 0 the lower (the most robust) and 50 the highest (the frailest) score. FTS5 scores at baseline and follow-up (median 5.04 years) were used to construct frailty trajectories according to group-based trajectory modelling (GBTM). Multivariate Cox proportional hazard and logistic regression models were used to explore associations between frailty status and trajectory membership and the adverse outcomes. Deaths were ascertained through the Spanish National Death Index. Disability was evaluated through the Katz Index. Hospitalization was defined as first admission to Toledo Hospital. RESULTS: Nine hundred and seventy-five older adults (mean age 73.14 ± 4.69; 43.38% men) were included. GBTM identified five FTS5 trajectories: worsening from non-frailty (WNF), improving to non-frailty (INF), developing frailty (DF), remaining frail (RF), and increasing frailty (IF). Subjects belonging to trajectories of increasing frailty scores or showing consistently higher frailty levels presented with an increased risk of mortality {DF [hazard ratio (HR), 95% confidence interval (CI)] = 2.01 [1.21-3.32]; RF = 1.92 [1.18-3.12]; IF = 2.67 [1.48-4.81]}, incident [DF (HR, 95% CI) = 2.06 (1.11-3.82); RF = 2.29 (1.30-4.03); IF = 3.55 (1.37-9.24)], and worsening disability [DF (HR, 95% CI) = 2.11 (1.19-3.76); RF = 2.14 (1.26-3.64); IF = 2.21 (1.06-4.62)], compared with subjects prospectively showing decreases in frailty levels or maintaining low FTS5 scores. A secondary result was a significant dose-response relationship between baseline FTS5 score and adverse events. CONCLUSIONS: Belonging to trajectories of prospectively increasing/consistently high frailty scores over time are associated with an increased risk of adverse outcomes compared with maintaining low or reducing frailty scores. Our results support the dynamic nature of frailty and the potential benefit of interventions aimed at reducing its levels on relevant and burdensome adverse outcomes.