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We present an executive summary of a guideline for management of type 2 diabetes mellitus in primary care written by the European Geriatric Medicine Society, the European Diabetes Working Party for Older People with contributions from primary care practitioners and participation of a patient's advocate. This consensus document relies where possible on evidence-based recommendations and expert opinions in the fields where evidences are lacking. The full text includes 4 parts: a general strategy based on comprehensive assessment to enhance quality and individualised care plan, treatments decision guidance, management of complications, and care in case of special conditions. Screening for frailty and cognitive impairment is recommended as well as a comprehensive assessment all health conditions are concerned, including end of life situations. The full text is available online at the following address: essential_steps_inprimary_care_in_older_people_with_diabetes_-_EuGMS-EDWPOP___3_.pdf., (© 2023. The Author(s).)

Vascular territories display heterogeneous sensitivity to the impacts of aging. The relevance of the STIM/Orai system to vascular function depends on the vascular bed. We aimed to evaluate the contribution of the STIM/Orai system to aging-related vascular dysfunction in rat coronary circulation. Vascular function was evaluated according to myography in coronary arteries from young (three-month-old) and older (twenty-month-old) rats. The effects of aging and STIM/Orai inhibition on the contraction and relaxation of the coronary arteries and on the protein expression of STIM-1, Orai1, and Orai3 in these vessels were determined. Aging-related hypercontractility to serotonin and endothelin-1 in arteries from male rats was reversed by STIM/Orai inhibition with YM-58483 or by specifically blocking the Orai1 channel with Synta66. The inhibitory effects of Synta66 on coronary vasoconstriction were also observed in older female rats. YM-58483 relaxed serotonin- but not KCl-contracted arteries from males. STIM/Orai inhibition improved defective endothelial vasodilations in aged arteries, even in the presence of NO synthase and cyclooxygenase inhibitors, but not in KCl-contracted segments. YM-58483 significantly enhanced relaxations to calcium-activated potassium channel stimulation in aged vessels. Increased protein expression of Orai1 and Orai3 was detected in arterial homogenates and sections from older rats. Upregulation of the Orai channel contributes to aging-related coronary dysfunction, revealing a potential target in reducing CVD risk.

Many advanced wound healing dressings exist, but there is little high-quality evidence to support them. To determine the performance of a novel amorphous hydrogel (EHO-85) in relation to its application, we compared its rheological properties with those of other standard hydrogels (SH), and we assessed the induction of acceleration of the early stages of wound healing as a secondary objective of a prospective, multicenter, randomized, observer-blinded, controlled trial. The patients were recruited if they had pressure, venous, or diabetic foot ulcers and were treated with EHO-85 ( n = 103) or VariHesive ® (SH) ( n = 92), and their response was assessed by intention-to-treat as wound area reduction (WAR (%)) and healing rate (HR mm 2 /day) in the second and fourth weeks of treatment. Results: EHO-85 had the highest shear thinning and G'/G″ ratio, the lowest viscous modulus, G″, and relatively low cohesive energy; EHO-85 had a significantly superior effect over SH in WAR and HR, accelerating wound healing in the second and fourth weeks of application ( p : 0.002). This superiority is likely based on its optimal moisturizing capacity and excellent pH-lowering and antioxidant properties. In addition, the distinct shear thinning of EHO-85 facilitates spreading by gentle hand pressure, making it easier to apply to wounds. These rheological properties contribute to its improved performance.

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., Competing Interests: Financial support for this analysis was provided by Abbott. TSHA research was funded by grants from the Spanish 10.13039/501100010198Ministry of Economy, Industry and Competitiveness, cofinanced by the 10.13039/501100008530European Regional Development Funds (10.13039/501100004587Instituto de Salud Carlos III, PI20/00977) and the Centro de Investigación Biomédica en Red en Fragilidad y Envejecimiento Saludable (CB16/10/00464); the MITOFUN Project, Fundación Francisco Soria Melguizo (Section 2/2020); 10.13039/501100010767Innovative Medicines Initiative Joint Undertaking under grant agreement n◦115621, resources of which are composed of financial contribution from the European Union’ 10.13039/100011102Seventh Framework Programme (FP7/2007-2013) and EFPIA companies. Drs Rueda, Pereira, Sulo are employees of Abbott. Dr Rodríguez-Mañas has received funds as a speaker in Abbott-supported conferences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2023 The Authors.)

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., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Frailty is a reversible multidimensional syndrome that puts older people at a high risk of adverse health outcomes. It has been proposed to emerge from the dysregulation of the complex system dynamics of physiologic control systems. We propose the analysis of the fractal complexity of hand movements as a new method to detect frailty in older adults., Methods: FRAIL scale and Fried's phenotype scores were calculated for 1209 subjects-72.4 (5.2) y.o. 569 women-and 1279 subjects-72.6 (5.3) y.o. 604 women-in the pubicly available NHANES 2011-2014 data set, respectively. The fractal complexity of their hand movements was assessed with a detrended fluctuation analysis (DFA) of their accelerometry records and a logistic regression model for frailty detection was fit., Results: Goodness-of-fit to a power law was excellent (R 2 > 0.98 ). The association between complexity loss and frailty level was significant, Kruskal-Wallis test (df = 2, Chisq = 27.545, p-value < 0.001 ). The AUC of the logistic classifier was moderate (AUC with complexity = 0.69 vs. AUC without complexity = 0.67)., Conclusion: Frailty can be characterized in this data set with the Fried phenotype. Non-dominant hand movements in free-living conditions are fractal processes regardless of age or frailty level and its complexity can be quantified with the exponent of a power law. Higher levels of complexity loss are associated with higher levels of frailty. This association is not strong enough to justify the use of complexity loss after adjusting for sex, age, and multimorbidity., Competing Interests: Conflict of interestThe authors have no competing interests to declare that are relevant to the content of this article., (© The Author(s) 2023.)

Objective: We aimed to co-create and evaluate an integrated system to follow-up frailty in a community dwelling environment and provide a multi-modal tailored intervention. Frailty and dependency among the older population are a major challenge to the sustainability of healthcare systems. Special attention must be paid to the needs and particularities of frail older persons as a vulnerable group., Methods: To ensure the solution fits all the stakeholders' needs, we performed several participatory design activities with them, such as pluralistic usability walkthroughs, design workshops, usability tests and a pre-pilot. The participants in the activities were older people; their informal carers; and specialized and community care professionals. In total, 48 stakeholders participated., Results: We created and evaluated an integrated system consisting of four mobile applications and a cloud server, which has been evaluated through a 6-months clinical trial, where secondary endpoints were both usability and user experience evaluation. In total, 10 older adults and 12 healthcare professionals participated in the intervention group using the technological system. Both patients and professionals have positively evaluated their applications., Conclusion: Both older adults and healthcare professionals have considered the resulted system easy to use and learn, consistent and secure. In general terms, they also would like to keep using it in the future., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: The 5-repetition chair stand test (CST) is increasingly being used to assess locomotion capacity in older adults. However, there is a lack of age-stratified cutoffs for adults aged ≥70 validated against a higher risk of functional loss., Methods: We used 2 population-based studies (Study on global AGEing and adult health in Mexico [SAGE Mexico] and Toledo Study for Healthy Aging [TSHA]) and receiver operating characteristic (ROC) analyses to develop and cross-validate age-stratified chair stand cutoffs with activities of daily living (ADL) disability as the outcome. Then, we used data from an randomized controlled trial (RCT) (Multidomain Alzheimer Preventive Trial [MAPT]) and a frailty day-hospital for external validation with cross-sectional and longitudinal measures of ADL disability. The merged sample of SAGE Mexico and TSHA was n = 1 595; sample sizes for external validation were: MAPT n = 1 573 and Frailty day-hospital n = 2 434. The Cox models for incident disability in MAPT had a mean follow-up of 58.6 months., Results: Cutoffs obtained were 14 second (ages 70-79) and 16 second (ages 80+). Those cutoffs identified older adults at higher odds of incident ADL disability odds ratio (OR) = 1.72 (95% confidence interval [CI] 1.06; 2.78) for ages 70-79 and odds ratio (OR) = 2.27 (95% CI 1.07; 4.80) in those aged 80+. Being a slow chair stander according to the cut points was associated with ADL disability in cross-sectional and longitudinal measures., Conclusions: Fourteen- and 16-second cut points for the CST are suitable to identify people at higher risk of functional decline among older adults in Mexico and Toledo, Spain. Adjusting the cut point from 14 to 16 second generally improved the psychometric properties of the test. The validation of these cutoffs can facilitate the screening for limited mobility and the implementation of the Integrated Care for Older People program., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Ensuring healthy lives and promoting wellbeing across the age spectrum are essential to sustainable development. Nutrition is at the heart of the World Health Organization (WHO) Sustainable Development Goals, particularly for Sustainable Development Goal 2/Subgoal 2, which is to End all forms of malnutrition by 2030 . This subgoal addresses people of all ages, including targeted groups like young children and older adults. In recent decades, there have been marked advances in the tools and methods used to screen for risk of malnutrition and to conduct nutritional assessments. There have also been innovations in nutritional interventions and outcome measures related to malnutrition. What has been less common is research on how nutritional interventions can impact healthy aging. Our Perspective article thus takes a life-course approach to consider what is needed to address risk of malnutrition and why, and to examine how good nutrition across the lifespan can contribute to healthy aging. We discuss broad-ranging yet interdependent ways to improve nutritional status worldwide-development of nutritional programs and policies, incorporation of the best nutrition-care tools and methods into practice, provision of professional training for quality nutritional care, and monitoring health and economic benefits of such changes. Taken together, our Perspective aims to (i) identify current challenges to meeting these ideals of nutritional care, and to (ii) discover enabling strategies for the improvement of nutrition care across the lifespan. In harmony with the WHO goal of sustainable development, we underscore roles of nutrition to foster healthy human development and healthy aging worldwide., Competing Interests: CG and SS were employees of Abbott Laboratories; they receive salaries for their work, and they are stockholders. LR-M and RM had received speaking honoraria from Abbott Laboratories but received no payment for their work on this manuscript, a perspective article based on current scientific evidence., (Copyright © 2023 Rodríguez-Mañas, Murray, Glencorse and Sulo.)

Objectives: We aimed to explore predictors of sustained transitions (those that are maintained for an extra follow-up) between robustness and prefrailty in both directions., Design: Longitudinal population-based cohort., Setting and Participants: Community-dwelling Spaniards 65 years or older from the Toledo Study of Healthy Ageing., Methods: The Fried's frailty phenotype was measured over 3 waves (2006-2009, 2011-2013, and 2014-2017). Multiple logistic regressions compared individuals following the pattern robust-prefrail-prefrail with those who remained robust across waves, and those following the pattern prefrail-robust-robust with those who remained prefrail, for sociodemographic, clinical, life-habits, dependency for activities of daily living, upper and lower extremities' strength variables. The Fried's items of those who remained prefrail and those who became robust were compared., Results: Mean age was 72.3 years (95% CI: 71.8-72.8) and 57.9% (52.7%-63.0%) were women. After multivariate adjustment, predictors (apart from age) of the sustained transition robustness-prefrailty were as follows: number of drugs taken (odds ratio: 1.37; 95% CI: 1.14-1.65), not declaring the amount of alcohol consumed (8.32; 1.78-38.88), and grip strength (0.92 per kg; 0.86-0.99). Predictors of the sustained transition prefrailty-robustness were as follows: drinking alcohol (0.2; 0.05-0.83), uricemia (0.67; 0.49-0.93), number of chair stands in 30 seconds (1.14; 1.01-1.28), and grip strength (1.12; 1.05-1.2). Low grip strength was associated with a lower probability of regaining robustness., Conclusions and Implications: Prediction of sustained transitions between the first stages of frailty development can be achieved with a reduced number of variables and noting whether the Fried's item leading to a diagnosis of prefrailty is low grip strength. Our results suggest the need to intensify interventions on deprescription, quitting alcohol, and strengthening of upper and lower limbs., (Copyright © 2022 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate the measurement structure of the ICOPE screening tool (IST) of intrinsic capacity and to find out whether the IST as a global measure adds explanatory power over and above its domains in isolation to predict the occurrence of adverse health outcomes such as dependence and hospitalization in community-dwelling older people., Design: Secondary analysis of a cohort study, the Toledo Study of Healthy Ageing., Setting: Province of Toledo, Spain., Participants: Community-dwelling older people., Measurements: Items equal or similar to those of the IST were introduced as a reflective-formative construct in a Structural Equation Model to evaluate its measurement structure and its association with dependence for basic and instrumental activities and hospitalization over a three-year period., Results: A total of 1032 individuals were analyzed. Mean age was 73.5 years (sd 5.4). The least preserved indicators were ability to recall three words (18%) and to perform chair stands (54%). Vision and hearing items did not form a single sensory domain, so six domains were considered. Several cognition items did not show sufficiently strong and univocal associations with the domain. After pruning the ill-behaved items, the measurement model fit was excellent (Satorra-Bentler scaled chi-square: 10.3, degrees of freedom: 11, p=0.501; CFI: 1.000; RMSEA: 0.000, 90% CI: 0.000-0.031, p value RMSEA<=0.05: 1; SRMR: 0.055). In the structural model, the cognition domain items were not associated as expected with age (p values 0.158 and 0.293), education (p values 0.190 and 0.432) and dependence (p values 0.654 and 0.813). The IST included as a composite in a model with the individual domains showed no statistically significant associations with any of the outcomes (dependence for basic activities: 0.162, p=0.167; instrumental: -0.052, p=0.546; hospitalization: 0.145, p=0.167), while only the mobility domain did so for dependence (basic: -0.266, p=0.005; instrumental: -0.138, p=0.019). The model fit of the last version was good (Satorra-Bentler scaled chi-square: 52.1, degrees of freedom: 52, p=0.469; CFI: 1.000; TLI: 1.000; RMSEA: 0.01, 90% CI: 0.000-0.02, p value RMSEA<=0.05: 1; SRMR: 0.071). The IST operationalized as the sum of non-impaired domains was not associated after covariate adjustment (dependence for basic activities: -0.065, p=0.356; instrumental: -0.08, p=0.05; hospitalization: -0.003, p=0.949) either., Conclusion: The cognitive domain of the IST, and probably other of its items, may need a reformulation. A global measure of intrinsic capacity such as the IST does not add explanatory power to the individual domains that constitute it. So far, our results confirm the importance of checking the findings of the IST with a second confirmatory step, as described in the WHO's ICOPE strategy., Competing Interests: Ángel Rodríguez-Laso, Francisco José García-García, and Leocadio Rodríguez-Mañas declare that they have no conflict of interest.

Background: Stromal interaction molecule (STIM)/Orai calcium entry system appears to have a role in erectile dysfunction (ED) pathophysiology but its specific contribution to diabetic ED was not elucidated., Aim: To evaluate STIM/Orai inhibition on functional alterations associated with diabetic ED in rat and human penile tissues and on in vivo erectile responses in diabetic rats., Methods: Rat corpus cavernosum (RCC) strips from nondiabetic (No DM) and streptozotocin-induced diabetic (DM) rats and human penile resistance arteries (HPRA) and corpus cavernosum (HCC) from ED patients undergoing penile prosthesis insertion were functionally evaluated in organ chambers and wire myographs. Erectile function in vivo in rats was assessed by intracavernosal pressure (ICP) responses to cavernous nerve electrical stimulation (CNES). Expression of STIM/Orai elements in HCC was determined by immunofluorescence and immunoblot., Main Outcome Measures: Functional responses in RCC, HCC and HPRA and STIM/Orai protein expression in HCC. In vivo erectile responses to CNES., Results: Inhibition of Orai channels with YM-58483 (20 µM) significantly reduced adrenergic contractions in RCC but more effectively in DM. Thromboxane-induced and neurogenic contractions were reduced by STIM/Orai inhibition while defective endothelial, neurogenic and PDE5 inhibitor-induced relaxations were enhanced by YM-58483 (10 µM) in RCC from DM rats. In vivo, YM-58483 caused erections and attenuated diabetes-related impairment of erectile responses. YM-58483 potentiated the effects of PDE5 inhibition. In human tissues, STIM/Orai inhibition depressed adrenergic and thromboxane-induced contractions in ED patients more effectively in those with type 2 diabetes. Diabetes was associated with increased expression of Orai1 and Orai3 in ED patients., Clinical Translation: Targeting STIM/Orai to alleviate diabetes-related functional alterations of penile vascular tissue could improve erectile function and potentiate therapeutic effects of PDE5 inhibitors in diabetic ED., Strengths and Limitations: Improving effects of STIM/Orai inhibition on diabetes-related functional impairment was evidenced in vitro and in vivo in an animal model and validated in human tissues from ED patients. Functional findings were complemented with expression results. Main limitation was low numbers of human experiments due to limited human tissue availability., Conclusions: STIM/Orai inhibition alleviated alterations of functional responses in vitro and improved erectile responses in vivo in diabetic rats, potentiating the effects of PDE5 inhibition. STIM/Orai inhibition was validated as a target to modulate functional alterations of human penile vascular tissue in diabetic ED where Orai1 and Orai3 channels were upregulated. STIM/Orai inhibition could be a potential therapeutic strategy to overcome poor response to conventional ED therapy in diabetic patients. Sevilleja-Ortiz A, El Assar M, García-Gómez B, et al. STIM/Orai Inhibition as a Strategy for Alleviating Diabetic Erectile Dysfunction Through Modulation of Rat and Human Penile Tissue Contractility and in vivo Potentiation of Erectile Responses. J Sex Med 2022;19:1733-1749., (Copyright © 2022 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

The impact of aging on vascular function is heterogeneous depending on the vascular territories. Calcium regulation plays a key role in vascular function and has been implicated in aging-related hypercontractility of corpus cavernosum. We aimed to evaluate stromal interaction molecule (STIM)/Orai system involvement in aging-related vascular alterations in the human macro and microvasculature. Aortae specimens and mesenteric arteries (MA), obtained from 45 organ donors, were functionally evaluated in organ chambers and wire myographs. Subjects were divided into groups either younger or older than 65-years old. The expressions of STIM-1, Orai1, and Orai3 were determined by immunofluorescence in the aorta and MA, and by Western blot in the aorta homogenates. The inhibition of STIM/Orai with YM-58483 (20 μM) reversed adrenergic hypercontractility in MA from older subjects but did not modify aging-related hypercontractility in the aortic strips. Aging was related to an increased expression of Orai1 in human aorta, while Orai1 and STIM-1 were upregulated in MA. STIM-1 and Orai1 protein expressions were inversely correlated to endothelial function in MA. Circulating levels of Orai1 were correlated with the inflammatory factor TNF-α and with the endothelial dysfunction marker asymmetric dimethylarginine. Aging is associated with an increased expression of the STIM/Orai system in human vessels with functional relevance only in the microvascular territory, suggesting its role in aging-related microvascular dysfunction.

Introduction: The present study aimed to explore the diagnostic and prognostic accuracy of standard and population-specific Physical Performance Measures (PPMs) cut-off points for frailty screening., Design: Prospective cohort study., Setting and Participants: Population-based study including 2328 subjects from the Toledo Study of Healthy Aging (age = 76.37 ± 6.78). Data related to frailty status and PPMs was collected at baseline visit (2011-2013). Mortality and hospitalization were ascertained up to March 2019 and December 2017, respectively, whereas disability onset and worsening were evaluated in the 2015-2017 visit., Methods: Gait speed and Short Physical Performance Battery population-specific cut-off points for frailty were computed using receiver operating characteristics (ROC) curve analysis. Head-to-head comparison of associations with adverse events against existing reference values (SPPB≤6, GS < 0.8 m/s) and classical (Frailty Phenotype, Frailty Index) and newly incorporated frailty tools (12- and 5-item Frailty Trait Scale) were explored through logistic and Cox regressions. Predictive ability was compared through areas under the curves (AUCs) for disability onset/worsening and integrated AUCs for mortality and hospitalization (time-censoring adverse events)., Results: PPMs population-specific cut-off points (SPPB ≤7 and GS ≤ 0.75 m/s for males; SPPB ≤4 and GS ≤ 0.5 for females) outperformed published reference thresholds in terms of diagnostic accuracy. Frailty identified through PPMs was associated with adverse events (death, hospitalization and incident disability) similarly to that assessed using the newly incorporated tools and showed similar prognostic accuracy (mortality [IAUCs≈0.7], hospitalization [IAUCs≈0.8] and disability onset/worsening [AUCs≈0.62]), except for the tool used to assess frailty., Conclusions: Our results suggest that PPMs might serve as the first screen to identify candidates for further frailty assessment and exploration of underlying mechanisms, allowing opportunistic on-time screening in different settings (community and primary care) in which frailty instruments are rarely implementable., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Frailty and sarcopenia are age-associated syndromes that have been associated with the risk of several adverse events, mainly functional decline and death, that usually coexist. However, the potential role of one of them (sarcopenia) in modulating some of those adverse events associated to the other one (frailty) has not been explored. The aim of this work is to assess the role of sarcopenia within the frailty transitions and mortality in older people., Methods: Data from the Toledo Study of Healthy Aging (TSHA) were used. TSHA is a cohort of community-dwelling older adults ≥65. Frailty was assessed according with the Frailty Phenotype (FP) and the Frailty Trait Scale-5 (FTS5) at baseline and at follow-up. Basal sarcopenia status was measured with the standardized Foundation for the National Institutes of Health criteria. Fisher's exact test and logistic regression model were used to determine if sarcopenia modified the transition of frailty states (median follow-up of 2.99 years) and Cox proportional hazard model was used for assessing mortality., Results: There were 1538 participants (74.73 ± 5.73; 45.51% men) included. Transitions from robustness to prefrailty and frailty according to FP were more frequent in sarcopenic than in non-sarcopenic participants (32.37% vs. 15.18%, P ≤ 0.001; 5.76% vs. 1.12%; P ≤ 0.001, respectively) and from prefrailty-to-frailty (12.68% vs. 4.27%; P = 0.0026). Improvement from prefrail-to-robust and remaining robust was more frequent in non-sarcopenic participants (52.56% vs. 33.80%, P ≤ 0.001; 80.18% vs 61.15%, P ≤ 0.001, respectively). When classified by FTS5, this was also the case for the transition from non-frail-to-frail (25.91% vs. 4.47%, P ≤ 0.001) and for remaining stable as non-frail (91.25% vs. 70.98%, P ≤ 0.001). Sarcopenia was associated with an increased risk of progression from robustness-to-prefrailty [odds ratio (OR) 2.34 (95% confidence interval, CI) (1.51, 3.63); P ≤ 0.001], from prefrailty-to-frailty [OR(95% CI) 2.50 (1.08, 5.79); P = 0.033] (FP), and from non-frail-to-frail [OR(95% CI) 4.73 (2.94, 7.62); P-value ≤ 0.001]. Sarcopenia does not seem to modify the risk of death associated with a poor frailty status (hazard ratios (HR, 95%) P > 0.05)., Conclusions: Transitions within frailty status, but not the risk of death associated to frailty, are modulated by the presence of sarcopenia., (© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

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., (Copyright © 2022 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

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., (© 2022. The Author(s).)

Purpose: This study aimed to examine the associations of accelerometer-derived steps volume and intensity with hospitalizations and all-cause mortality in older adults., Methods: This prospective cohort study involved 768 community-dwelling Spanish older adults (78.8 ± 4.9 years, mean ± SD; 53.9% females) from the Toledo Study for Healthy Aging (2012-2017). The number of steps per day and step cadence (steps/min) were derived from a hip-mounted accelerometer worn for at least 4 days at baseline. Participants were followed-up over a mean period of 3.1 years for hospitalization and 5.7 years for all-cause mortality. Cox proportional hazards regression models were used to estimate the individual and joint associations between daily steps and stepping intensity with hospitalizations and all-cause mortality., Results: Included participants walked 5835 ± 3445 steps/day with an intensity of 7.3 ± 4.1 steps/min. After adjusting for age, sex, body mass index (BMI), education, income, marital status and comorbidities, higher step count (hazard ratio (HR) = 0.95, 95% confidence interval (95%CI: 0.90-1.00, and HR = 0.87, 95%CI: 0.81-0.95 per additional 1000 steps) and higher step intensity (HR = 0.95, 95%CI: 0.91-0.99, and HR = 0.89, 95%CI: 0.84-0.95 per each additional step/min) were associated with fewer hospitalizations and all-cause mortality risk, respectively. Compared to the group having low step volume and intensity, individuals in the group having high step volume and intensity had a lower risk of hospitalization (HR = 0.72, 95%CI: 0.52-0.98) and all-cause mortality (HR = 0.60, 95%CI: 0.37-0.98)., Conclusion: Among older adults, both high step volume and step intensity were significantly associated with lower hospitalization and all-cause mortality risk. Increasing step volume and intensity may benefit older people., (Copyright © 2021. Production and hosting by Elsevier B.V.)

Background: Frailty is common among advanced chronic kidney disease (CKD) patients who are kidney transplant (KT) candidates, and predisposes to poor outcomes after transplantation. However, frailty is not routinely measured during pretransplant work-up and it is unknown which metric should be used in this specific population. Our aim was to establish frailty prevalence in KT candidates according to different frailty scales., Methods: Prospective longitudinal study of 451 KT candidates evaluated for frailty by both Physical Frailty Phenotype (PFP) and FRAIL scale at the time of inclusion on the KT waiting list. Clinical and functional characteristics including sociodemographics, comorbidities, disability and nutritional status were recorded. Agreement between PFP and FRAIL scales as well as dissonant patients were analyzed., Results: Mean age was 60.9 years and 31.7% were female. Comorbidity burden among patients was high, with 36.9% and 16.2% presenting with diabetes and ischemic coronary disease, respectively. Disabilities were also frequent. More than 70% of patients presented with ≥ 1 PFP criteria while this percentage for ≥ 1 FRAIL criteria was 45.4%. Agreement between PFP and FRAIL was not good (kappa index 0.317). There were 132 patients who were pre-frail or frail according to PFP but non-frail according to the FRAIL scale and they presented with fewer comorbidities and less disability., Conclusions: Frailty is frequent in advanced CKD patients, although its prevalence may vary according to different scales. Agreement between PFP and FRAIL scale is not good, and FRAIL scale might misclassify as robust patients those frail/prefrail patients who are in better health conditions., (© 2022. The Author(s) under exclusive licence to Italian Society of Nephrology.)

Background: There is little knowledge of the diagnostic accuracy of screening programmes for frailty in primary care settings., Aim: To assess a two-step strategy consisting of the administration of the FRAIL scale to those who are non-dependent and aged ≥75 years, followed-up by measurement of the Short Physical Performance Battery (SPPB) or gait speed in those who are positive., Design & Setting: Cross-sectional and longitudinal cohort study. Analysis of primary care data from the FRAILTOOLS project at five European cities., Method: All primary care patients consecutively attending were enrolled. They received the index tests, plus the Fried frailty phenotype (FP) and the frailty index to assess their frailty status. Mortality and worsening of dependency in basic and instrumental activities of daily living (BADL and IADL) over 1 year were ascertained., Results: Prevalence of frailty based on FP was 14.9% in the 362 participants. A FRAIL scale score ≥1 had a sensitivity of 83.3% (95% confidence interval [CI] = 73.1 to 93.6) to detect frailty. A positive result and an SPPB score <11 had a sensitivity of 72.2% (95% CI = 59.9 to 84.6); when combined with a gait speed <1.1 m/s, the sensitivity was 80.0% (95% CI = 68.5 to 91.5). Two-thirds of those screened as positive were not frail. In the best scenario, sensitivities of this last combination to detect IADL and BADL worsening were 69.4% (95% CI = 59.4 to 79.4) and 63.6% (95% CI = 53.4 to 73.9), respectively., Conclusion: Combining the FRAIL scale with other functional measures offers an acceptable screening approach for frailty. Accurate prediction of worsening dependency and death need to be confirmed through the piloting of a frailty screening programme., (Copyright © 2022, The Authors.)

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.

Previous meta-analyses have shown that the hospital admission of older patients in acute geriatric units (AGU) compared to admission to other conventional units, significantly reduced the risk of functional deterioration during hospitalization, increasing the possibility of returning home, with an added reduction in cost of hospitalization. A new meta-analysis on the subject has recently been published in Age and Aging, which adds six new studies to the five clinical trials analyzed in previous meta-analyses. This article analyzes the results of this new meta-analysis, delving into the characteristics of the new studies included and making some considerations on the implications for care in the future development of AGU., (Copyright © 2022 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Physical Frailty Phenotype (PFP) is the most used frailty instrument among kidney transplant recipients, classifying patients as pre-frail if they have 1-2 criteria and as frail if they have ≥3. However, different definitions of robustness have been used among renal patients, including only those who have 0 criteria, or those with 0-1 criteria. Our aim was to determine the impact of one PFP criterion on transplant outcomes., Methods: We undertook a retrospective study of 296 kidney transplant recipients who had been evaluated for frailty by PFP at the time of evaluating for transplantation., Results: Only 30.4% of patients had 0 criteria, and an additional 42.9% showed one PFP criterion. As PFP score increased, a higher percentage of women and cerebrovascular disease were found. Recipients with 0-1 criteria had lower 1-year mortality after transplant than those with ≥2 (1.8% vs 10.1%), but this difference was already present when we only considered those who scored 0 (mortality 1.1%) and 1 (mortality 2.4%) separately. The multivariable analysis confirmed that one PFP criterion was associated to a higher risk of patient death after kidney transplantation [hazard ratio 3.52 (95% confidence interval 1.03-15.9)]., Conclusions: Listed kidney transplant candidates frequently show only one PFP frailty criterion. This has an independent impact on patient survival after transplantation., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

Background: The purpose of this study was to evaluate the relationship of lower-limb muscle power with mortality and hospitalization., Methods: A total of 1 928 participants from the Toledo Study for Healthy Aging were included. Muscle power was assessed with the 5-repetition sit-to-stand test and participants were classified into different groups of relative power (ie, normalized to body mass) according to sex-specific tertiles and their inability to perform the test. Mean follow-up periods for hospitalization and all-cause mortality were 3.3 and 6.3 years, respectively., Results: Compared to the high relative muscle power group, men with low (HR [95% CI] = 2.1 [1.2-3.6]) and women with very low and low (HR [95% CI] = 4.7 [3.0-7.4] and 1.8 [1.2-2.7]) relative power had an increased age-adjusted risk of hospitalization. After adjusting for several covariates (age, physical activity, body mass index education, depression, comorbidities, disability, and handgrip strength), these effects were attenuated (men and women with very low relative power: HR [95% CI] = 1.6 [0.9-2.9] and 2.8 [1.6-4.9]). The very low relative muscle power group had also an increased all-cause mortality risk (age-adjusted) in both men and women (HR [95% CI] = 2.3 [1.4-3.9] and 2.9 [1.6-5.3]). After adjusting for all the covariates, a significantly increased mortality risk was observed only in men (HR [95% CI] = 2.1 [1.1-3.8]; women HR [95% CI] = 1.6 [0.8-3.2]), with very low levels of relative power., Conclusions: Relative muscle power was independently and negatively associated with mortality and hospitalization in older adults. An augmented all-cause mortality risk was noted in the lowest group of relative muscle power., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Insulin signalling declines with increasing age and impacts skeletal muscle function and longevity in animal models. Our aim was to assess the relationships between insulin resistance (IR) and frailty and mortality in a unique community-dwelling cohort of older people. 991 non-diabetic subjects from the Toledo Study of Healthy Ageing (TSHA) cohort were included. IR was estimated by the homeostasis model assessment index (HOMA-IR) at baseline while frailty was determined by frailty phenotype (FP) and Frailty Trait Scale (FTS) at baseline and after 5-year follow-up. Deaths were also determined. Multivariate regression models were used to analyze the effects of HOMA-IR on outcomes. Age, gender, BMI, education level, cardio- and cerebro-vascular disease, glomerular filtration rate, and disability were included as potential confounding variables in progressive adjustment models. IR determined as increasing log HOMA-IR was inversely associated with risk of mortality. The association remained significant for all adjustment models (HR: 0.64-0.69). When we analyzed survival curves, the higher the HOMA-IR tertile, the lower the mortality rate (highest vs lowest tertile, p = 0.0082). In contrast, IR increased the risk of incident frailty determined by FP (OR 1.81 [1.14-2.87]) as well as deterioration of frailty status determined by worsening in FTS score (OR 1.28 [1.01-1.63]) at 5-year follow-up. In non-diabetic older subjects, IR significantly increases the risk for frailty and functional decline but decreased the risk of death at 5-year follow-up. This finding raises the need of assessing the effect of biomarkers on different outcomes before establishing their role as biomarkers of aging., (© 2021. American Aging Association.)

Objectives: Study the frequency and determinants of frailty transitions in a community-dwelling older population., Design: Population-based prospective longitudinal study [The Toledo Study of Healthy Ageing (TSHA)]., Setting and Participants: 1748 community-dwelling individuals aged >65 years living in Toledo, a Spanish province., Methods: Frailty was measured with the Fried phenotype. Logistic models were used to assess the associations of sociodemographic, clinical, life-habits, functional, physical performance, and analytical variables with frailty transitions (losing robustness, transitioning from prefrailty to robustness, and from prefrailty to frailty) over a median of 5.2 years., Results: Mean age on enrolment was 75 years, and 55.8% were females. At baseline, 10.3% were frail and 43.1% prefrail. At follow-up, 35.8% of the frail individuals recovered to a prefrail and 15.1% to a robust state. In addition, 43.7% of the prefrail participants became robust, but 14.5% developed frailty. Of those robust at baseline, 32.9% became prefrail and 4.2% frail. In multivariate logistic models, chair-stands had a predictive role in all transitions studied: linearly in keeping robustness and with a floor effect (5 stands) in transitions from prefrailty to robustness and (inversely) from prefrailty to frailty. More depressive symptoms were associated with unfavorable transitions. Not declaring the amount of alcohol drunk and low grip strength were associated with loss of robustness. Hearing and cognitive impairment, low physical activity and smoking with transitioning from prefrailty to frailty. Autonomy for instrumental activities of daily living and uricemia were associated with transitions between robustness and prefrailty in both directions. Increasing body mass index in the range of moderate to severe obesity hampered regaining robustness., Conclusions and Implications: Spontaneous improvement of frailty measured with the Fried phenotype is frequent, mainly to prefrailty. Most of the variables associated with transitions are modifiable and suggest research topics and interventions to reduce frailty in clinical and social care settings., (Copyright © 2021 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

This 8-week, multicenter, randomized, active-controlled, observer-blinded clinical trial was designed to demonstrate the accelerating effect on wound healing of the novel Olea europaea leaf extract hydrogel (EHO-85) by comparing it to a widely used amorphous hydrogel. Results showed that EHO-85 significantly accelerated wound healing, regardless of ulcer etiology (pressure, venous leg or diabetic foot) and prognosis, doubling the median wound area reduction compared with a reference amorphous hydrogel (79.4% vs. 39.7%; difference: −39.7%, 95% CI: −71.1 to −21.3%; p < 0.001). The intention-to-treat analysis was conducted on 195 patients from 23 Spanish health centers/nursing homes. This novel treatment balances the ulcer microenvironment by modulating reactive oxygen species and pH. These actions complement the moistening and barrier functions inherent to amorphous hydrogels, whilst also conferring EHO-85 its documented granulation formation and pain relief properties. Furthermore, efficacy was achieved safely and in a cost-efficient manner due to its multi-dose format, which reduced the amount of product needed by 85.8% over 8 weeks compared to single-use hydrogel. The present randomized controlled trial is a relevant milestone in evidence-based practice for being the first to demonstrate (i) the effectiveness of an amorphous hydrogel in accelerating wound healing and (ii) the superiority of a specific hydrogel over another.

The prevalence of chronic wounds is increasing due to the population aging and associated pathologies, such as diabetes. These ulcers have an important socio-economic impact. Thus, it is necessary to design new products for their treatment with an adequate cost/effectiveness ratio. Among these products are amorphous hydrogels. Their composition can be manipulated to provide a favorable environment for ulcer healing. The aim of this study was to evaluate a novel multifunctional amorphous hydrogel (EHO-85), containing Olea europaea leaf extract, designed to enhance the wound healing process. For this purpose, its moistening ability, antioxidant capacity, effect on pH in the wound bed of experimental rats, and the effect on wound healing in a murine model of impaired wound healing were assessed. EHO-85 proved to be a remarkable moisturizer and its application in a rat skin wound model showed a significant antioxidant effect, decreasing lipid peroxidation in the wound bed. EHO-85 also decreased the pH of the ulcer bed from day 1. In addition, in mice (BKS. Cg-m +/+ Leprdb) EHO-85 treatment showed superior wound healing rates compared to hydrocolloid dressing. In conclusion, EHO-85 can speed up the closure of hard-to-heal wounds due to its multifunctional properties that are able to modulate the wound microenvironment, mainly through its remarkable effect on reactive oxygen species, pH, and moistening regulation.

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., (© 2021 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Advanced age is related to functional alterations of human vasculature, but erectile dysfunction precedes systemic manifestations of vascular disease. The current study aimed to simultaneously evaluate the influence of aging on vascular function (relaxation and contraction responses) in systemic human vascular territories: aorta (HA) and resistance mesenteric arteries (HMA) and human corpus cavernosum (HCC) and penile resistance arteries (HPRA). Associations of oxidative stress and inflammation circulating biomarkers with age and functional responses were also determined. Vascular specimens were obtained from 76 organ donors (age range 18-87). Four age-groups were established: < 40, 40-55, 56-65 and > 65 years old. Increasing age was associated with a decline in endothelium-dependent relaxation induced by BK in HMA (r = -0.597, p = 0.0001), or by ACh in HCC (r = -0.505, p = 0.0022), and HPRA (r = -0.601, p = 0.0012). Significant impairment was detected at > 65 years old in HMA but earlier in penile vasculature (> 55 years old). Age-related reduction to H 2 O 2 -vasodilatory response started before in HCC (56-65 years old) than in HA (> 65 years old). In contrast to relaxation responses, aging-related hypercontractility to adrenergic stimulation was homogeneous: contractions significantly increased in subjects > 55 years old in all tested vessels. Although not significantly age related, circulating levels of ADMA (r = -0.681, p = 0.0052) and TNF-α (r = -0.537, p = 0.0385) were negatively correlated with endothelial vasodilation in HMA but not in HCC or HPRA. Penile vasculature exhibits an early impairment of endothelium-dependent and H 2 O 2 -induced vasodilations when compared to mesenteric microcirculation and aorta. Therefore, functional susceptibility of penile vasculature to the aging process may account for anticipation of erectile dysfunction to systemic manifestations of vascular disease., (© 2021. The Author(s), under exclusive licence to American Aging Association.)

The excess of free radicals in the wound environment contributes to its stagnation during the inflammatory phase, favoring hard-to-heal wounds. Oxidative stress negatively affects cells and the extracellular matrix, hindering the healing process. In this study, we evaluated the antioxidant and wound-healing properties of a novel multifunctional amorphous hydrogel-containing Olea europaea leaf extract (OELE). Five assessments were performed: (i) phenolic compounds characterization in OELE; (ii) absolute antioxidant activity determination in OELE and hydrogel (EHO-85); (iii) antioxidant activity measurement of OELE and (iv) its protective effect on cell viability on human dermal fibroblasts (HDFs) and keratinocytes (HaCaT); and (v) EHO-85 wound-healing-capacity analysis on diabetic mice (db/db; BKS.Cg-m+/+Leprdb). The antioxidant activity of OELE was prominent: 2220, 1558, and 1969 µmol TE/g by DPPH, ABTS, and FRAP assays, respectively. Oxidative stress induced with H 2 O 2 in HDFs and HaCaT was normalized, and their viability increased with OELE co-treatment, thus evidencing a protective role. EHO-85 produced an early and sustained wound-healing stimulating effect superior to controls in diabetic mice. This novel amorphous hydrogel presents an important ROS scavenger capacity due to the high phenolic content of OELE, which protects skin cells from oxidative stress and contributes to the physiological process of wound healing.

Frailty is associated with poorer outcomes among patients waiting for kidney transplantation (KT). Several different tools to measure frailty have been used; however, their predictive value is unknown. This is a prospective longitudinal study of 449 KT candidates evaluated for frailty by the Physical Frailty Phenotype (PFP) and the FRAIL scale. During the study period, 296 patients received a KT, while 153 remained listed. Patients who did not get receive a transplant were more frequently frail according to PFP (16.3 vs. 7.4%, p = 0.013). Robust patients had fewer hospital admissions during the 1st year after listing (20.8% if PFP = 0 vs. 43.4% if ≥1, and 27.1% if FRAIL = 0 vs. 48.9% if ≥1) and fewer cardiovascular events (than FRAIL ≥ 1) or major infectious events (than PFP ≥ 1). According to PFP, scoring 1 point had an impact on patient survival and chance of transplantation in the univariate analysis. The multivariable analysis corroborated the result, as candidates with PFP ≥ 3 had less likelihood of transplantation (HR 0.45 [0.26-0.77]). The FRAIL scale did not associate with any of these outcomes. In KT candidates, pre-frailty and frailty according to both the PFP and the FRAIL scale were associated with poorer results while listed. The PFP detected that frail patients were less likely to receive a KT, while the FRAIL scale did not.

Objectives: The aim was to evaluate general changes and investigate the association between diet quality, physical activity (PA), and sedentary time (ST) during COVID-19 lockdown and the subsequent 7-month changes in health-related behaviours and lifestyles in older people., Participants: 1092 participants (67-97y) from two Spanish cohorts were included., Design: Telephone-based questionaries were used to evaluate health-related behaviours and lifestyle. Multinomial logistic regression analyses with diet quality, PA, and ST during lockdown as predictors for health-related behaviours changes post-lockdown were applied., Results: Diet quality, PA, and ST significantly improved post-lockdown, while physical component score of the SF-12 worsened. Participants with a low diet quality during lockdown had higher worsening of post-lockdown ST and anxiety; whereas those with high diet quality showed less likelihood of remaining abstainers, worsening weight, and improving PA. Lower ST was associated with a higher likelihood of remaining abstainers, and worsening weight and improving social contact; nevertheless, higher ST was linked to improvement in sleep quality. Lower PA was more likely to decrease alcohol consumption, while higher PA showed the opposite. However, PA was more likely to be associated to remain abstainers., Conclusions: Despite improvements in lifestyle after lockdown, it had health consequences for older people. Particularly, lower ST during lockdown seemed to provide the most medium-term remarkable lifestyle improvements., Competing Interests: The authors declare that there are no conflicts of interest

Objectives: This study investigated the associations of chronic diseases with changes in lifestyle and health behaviours in older people following the coronavirus disease 2019 (COVID-19) lockdown in Spain and compared the differences in changes over time., Methods: 1,092 participants (80.3±5.6 years; 66.5% female) from 2 Spanish cohorts were included. Telephone-based questionnaires were conducted to evaluate lifestyle and health risk behaviours at the end of lockdown and 7 months post-lockdown. Participants were classified as having physician-diagnosed chronic diseases based on self-reported data. Cox proportional models adjusted for major confounders were used., Results: Compared to those without the corresponding chronic diseases, older people with hypertension were less likely to report increased alcohol consumption (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.55 to 0.99). Pulmonary diseases were associated with lower risks of increased sedentary time (HR, 0.58; 95% CI, 0.39 to 0.86) and worsened sleep quality (HR, 0.56; 95% CI, 0.36 to 0.87), while cardiovascular diseases were associated with a lower risk of decreased sedentary time (HR, 0.58; 95% CI, 0.38 to 0.88). Depression was linked to a higher likelihood of improved diet quality (HR, 1.53; 95% CI, 1.00 to 2.36). Cancer pacients were less likely to have worsened sleep quality (HR, 0.44; 95% CI, 0.22 to 0.89) but more likely to have reduced their frequency of social contact (HR, 2.05; 95% CI, 1.05 to 3.99)., Conclusions: Older people with chronic diseases showed beneficial changes in lifestyle and health risk behaviours after the COVID-19 lockdown. In particular, older people with hypertension, pulmonary disease, and cancer tended to make beneficial lifestyle and health behaviour changes. However, older people with cardiovascular disease and depression engaged in more health risk behaviours.

The role of STIM/Orai calcium entry system on vascular ageing has not been elucidated. We aimed to evaluate the influence of ageing on STIM/Orai signalling and its role on ageing-induced alterations of contractile function in rat corpus cavernosum (RCC) and human penile resistance arteries (HPRA) and corpus cavernosum (HCC). RCC was obtained from 3 months-old and 20 months-old animals. HPRA and HCC were obtained from organ donors of varied ages without history of erectile dysfunction. Aging was associated with enhanced norepinephrine (NE)- and thromboxane analogue (U46619)-induced contractions in RCC which were significantly inhibited by the STIM/Orai inhibitor, YM-58483 (20 μM). Other STIM/Orai inhibitor, 2-aminoethyldiphenylborate also reduced NE-induced contractions in RCC from aged rats. YM-58483 significantly reduced neurogenic contractions and potentiated neurogenic relaxations in RCC from aged rats. In HCC and HPRA, NE-induced contractions were significantly enhanced in older subjects (>65 years-old) but YM-58483 completely reversed ageing-related hypercontractility. Ageing did not modify STIM-1 and Orai1 protein expressions but Orai3 was significantly overexpressed in cavernosal tissue from old rats and older subjects. Contribution of STIM/Orai to cavernosal contraction increases with ageing together with increased expression of Orai3. Orai inhibition could be a potential therapeutic strategy to reduce ageing-related impact on vascular/erectile function., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: Being able to rise from a chair is paramount for independent living and is strongly influenced by the ability of the lower limbs to exert mechanical power. This study assessed minimal thresholds of lower-limb relative muscle power required to perform the sit-to-stand (STS) task in older adults and its association with mobility limitations and disability., Methods: A total of 11,583 older adults (age, 60-103 yr) participated in this investigation. The 5-rep and 30-s versions of the STS test were used to assess chair rising ability. Relative power was calculated by the STS muscle power test. The minimum thresholds of power required to perform the STS tests were derived from the minimum values (i.e., "floor" effect) reported in the power tests through regression analyses. Mobility limitations and disability in activities of daily living (ADL) were recorded., Results: For the average older man and woman, the thresholds to complete five STS repetitions were 1.1 and 1.0 W·kg-1, respectively, whereas the thresholds to complete one STS repetition were 0.3 W·kg-1 in both sexes. These thresholds increased linearly with height (5- and 1-rep, respectively: +0.13 and +0.03 W·kg-1 per 10-cm increase; both P < 0.001) and did not differ by sex or testing condition (both P ≥ 0.259). All participants with relative power below the 5-rep threshold presented mobility limitations, and 51%-56% of women and 36%-49% of men also showed disability in ADL (all χ2 ≥ 290.4; P < 0.001)., Conclusion: A minimum level of relative muscle power is required to rise from a chair independently, which depends on the individual height and is associated with increased mobility limitations and disability. This information will help interpret data yielded by the STS muscle power test and may contribute to the prevention and treatment of mobility limitations in older people., (Copyright © 2021 by the American College of Sports Medicine.)

POSITIVE (acronym for Maintaining and imPrOving the intrinSIc capaciTy Involving primary care and caregiVErs) is an EIT Health funded project. Its main objective is to make available to the elderly population, caregivers and the different clinical professionals involved in their care, both primary and hospital care, a home monitoring system that allows a better management and treatment of frailty, in order to maintain or improve the intrinsic capacity of the elderly, as well as to avoid disability through a telematic platform of services. The POSITIVE technological ecosystem allows data collection and remote monitoring of the state of pre-fragility and fragility in a community environment, enabling early interventions aimed at preventing disability and dependence. The home monitoring system consists of a series of questionnaires on the state of health, and 3 sensors that measure variables with high predictive power of adverse events: gait speed, power in the lower extremities and involuntary weight loss. With this system, older people are under constant supervision. In addition, POSITIVE has an automatic system of personalized prescription of physical exercise based on the VIVIFRAIL program, as well as a nutritional plan and monitoring of functional status. Using the platform's services, caregivers can be aware of any impairment. For their part, primary care professionals receive alarms related to potentially dangerous decreases in intrinsic capacity, giving them the possibility to adjust treatments accordingly with the help of a decision support system while the geriatrics service can be involved if deemed necessary.

The demographic changes experienced throughout the 20th century have not only conditioned a series of modifications in the structure of the populations, but have also been accompanied by a change in the epidemiological profiles of the population, which have had as one of their main consequences the change in the main focus of the organizations responsible for health and of the citizens themselves. The main objective of delaying death has been added to avoid disability, the main factor related to health associated with a poor quality of life. In this endeavor, frailty, a nosological entity with less than 25 years of history, has been acquiring increasing relevance and prominence. Throughout this article, it is reviewed, from a historical perspective, how its conceptual frameworks have been defined and delimited, the problems posed by its detection, which have appeared as primary factors in diagnostic work once frailty is diagnosed, how to manage the entity from a point of view of prevention, individual treatment and adaptation of the organization of the health and social systems and the efforts that different national and supranational organizations are making to address the problem, ending with the description of the challenges care and research that frailty has come to pose.

Frailty predisposes older persons to adverse events, and information and communication technologies can play a crucial role to prevent them. CAPACITY provides a means to remotely monitor variables with high predictive power for adverse events, enabling preventative personalized early interventions. This study aims at evaluating the usability, user experience, and acceptance of a novel mobile system to prevent disability. Usability was assessed using the system usability scale (SUS); user experience using the user experience questionnaire (UEQ); and acceptance with the technology acceptance model (TAM) and a customized quantitative questionnaire. Data were collected at baseline (recruitment), and after three and six months of use. Forty-six participants used CAPACITY for six months; nine dropped out, leaving a final sample of 37 subjects. SUS reached a maximum averaged value of 83.68 after six months of use; no statistically significant values have been found to demonstrate that usability improves with use, probably because of a ceiling effect. UEQ, obtained averages scores higher or very close to 2 in all categories. TAM reached a maximum of 51.54 points, showing an improvement trend. Results indicate the success of the participatory methodology, and support user centered design as a key methodology to design technologies for frail older persons. Involving potential end users and giving them voice during the design stage maximizes usability and acceptance.

The European Commission and 22 of its Member States cofinanced, in 2017-2019, the first joint action to address frailty in older persons, known as ADVANTAGE Joint Action. The initiative developed a common strategy, based on the best scientific evidence, to position healthy aging and frailty as priority public health issues in the participating countries and thus contribute to uniformly addressing frailty across Europe. This article details the methodology and main achievements of ADVANTAGE and includes an analysis of the key factors contributing to its success. In the Action's three years, powerful multisectoral networks were formed and developed, both nationally and internationally. ADVANTAGE succeeded in mapping out practical routes for comprehensively addressing frailty and dependency prevention in 22 countries with very heterogeneous political, economic, social, and organizational realities. ADVANTAGE has demonstrated that actions of this type are feasible and effective, and that if the key points of success that have been identified are considered and applied, duly adjusted to each reality, this action can be replicable in any country resolved to promoting the healthy aging of its population, including those of Latin America and the Caribbean.

Objectives: To analyze the effects of a program composed of resistance training and nutritional interventions on functional capacity, maximal strength, and power output after 2 years of follow-up, including 2 periods of 16 weeks of intervention followed by several weeks of intervention cessation in frail patients with type 2 diabetes., Design: MIDPOW is a substudy of a multicenter, multimodal intervention composed of resistance training combined with a structured diabetes and nutritional education program in frail and prefrail older people with type 2 diabetes (MID-Frail)., Setting and Participants: This study recruited 52 participants (mean age: 79 ± 5.6, 63% women), with type 2 diabetes mellitus, frail or prefrail using Fried's frailty phenotype., Methods: Primary outcomes of this substudy were Short Physical Performance Battery (SPPB) and maximal power output at 30% and 80% of 1RM., Results: Each set of 16 weeks of intervention resulted in significant improvements in SPPB performance by a mean of 36.1% at week 18 (P < .001) and 10.2% at week 68 (P < .05). Maximal power output improvements at 30% and 80% of the 1RM ranged from 45.2% to 57.2% at week 18 (P < .01-.001); and no significant changes were observed after the second period of intervention. After 2 years of follow-up, the SPPB and maximal power values observed remained significantly higher than the baseline., Conclusions and Implications: Resistance training combined with nutritional program improved SPPB, maximal strength, and power output in older frail patients with diabetes. These improvements were maintained above the basal levels after several weeks of intervention cessation during a 2-year follow-up., (Copyright © 2021 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Visual impairment (VI) may lead to worsening functional status and disability. Although disability is very difficult to reverse, it is usually preceded by frailty that may be reverted more easily. It is possible that VI is also related to frailty., Aims: To assess the relationship between VI and worsening of the frailty status., Methods: Data were taken from the Toledo Study for Healthy Aging (TSHA), a cohort study of community-dwelling people older than 65 years living in one Spanish province who were followed for 5 years. 1181 participants were included. VI was self-reported and frailty was operationalized using the Fried's phenotype adapted to a Spanish population. Models of multivariate logistic regression were built to assess the associations., Results: The mean age was 73.9 (Standard Deviation (SD) = 5 years) and 58.5% were females. Pre-frailty/frailty prevalence at baseline and follow-up were 41.2/5% and 36.2/12.5%, respectively, and VI was reported by 14.1%. After adjusting for age, gender, education level, tobacco consumption, type 2 diabetes mellitus, high blood pressure, cardiovascular disease, depressive symptoms and cognitive status, odds ratios for the development of frailty by VI were 2.5 (95% Confidence Interval (CI) 1.5-4.4) for non-frail, 2.7 (95% CI 1.3-5.7) for pre-frail and 1.9 (CI 0.6-6.00) for robust participants. The frailty domains whose appearance was most increased by VI were slowness, low energy, low physical activity and weakness., Discussion: Our findings support that VI worsens frailty in the early stages of its development (pre-frailty). VI impairs several frailty items at the same time., Conclusions: Our study highlights the need to assess both VI and frailty for the prevention of frailty and disability in older people., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG part of Springer Nature.)

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: Frailty is defined as decreased physiologic reserve and resistance to stressors that predisposes patients towards poor health results. Its prevalence in chronic kidney disease (CKD) patients who are kidney transplant (KT) candidates is high. Frailty is associated with a higher rate of complications and mortality after transplant. It is unknown whether frailty phenotype differs depending on sex in this population., Methods: This was a prospective longitudinal study of 455 KT candidates evaluated for frailty by physical frailty phenotype at the time of inclusion on the KT waiting list. Pre-frailty was defined as the presence of two criteria and frailty as three or more criteria. Univariate and multivariate analyses searched for associations of frailty status, frailty components and gender differences., Results: Thirty percent of the total cohort resulted to be pre-frail (20%) or frail (10.3%), but disparities were observed between sexes, with 22.5% of men and 47.2% of women falling into one of these categories. Among frailty criteria, women presented with a higher percentage of exhaustion (39.6% versus 17%) and slowness (22.2% versus 9.6%) compared with men. Comorbidity burden was higher among frail men, whereas social factors were poorer between frail women. Disability was common among those patients who were frail, both men and women., Conclusions: Frailty is twice as frequent in advanced CKD women as men. Frailty criteria distribution and phenotype seem to differ among sexes, which might have implications in terms of specific and individualized interventions to improve their status before transplantation., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.)