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Age-associated decline in testosterone levels represent one of the potential mechanisms involved in the development of frailty. Although this association has been widely reported in older men, very few data are available in women. We studied the association between testosterone and frailty in women and assessed sex differences in this relationship. We used cross-sectional data from the Toledo Study for Healthy Aging, a population-based cohort study of Spanish elderly. Frailty was defined according to Fried's approach. Multivariate odds-ratios (OR) and 95% confidence intervals (CI) associated with total (TT) and free testosterone (FT) levels were estimated using polytomous logistic regression. In women, there was a U-shaped relationship between FT levels and frailty (p for FT(2) = 0.03). In addition, very low levels of FT were observed in women with ≥ 4 frailty criteria (age-adjusted geometric means = 0.13 versus 0.37 in subjects with <4 components, p = 0.010). The association of FT with frailty appeared confined to obese women (p-value for interaction = 0.05).In men, the risk of frailty levels linearly decreased with testosterone (adjusted OR for frailty = 2.9 (95%CI, 1.6-5.1) and 1.6 (95%CI, 1.0-2.5), for 1 SD decrease in TT and FT, respectively). TT and FT showed association with most of frailty criteria. No interaction was found with BMI. There is a relationship between circulating levels of FT and frailty in older women. This relation seems to be modulated by BMI. The relevance and the nature of the association of FT levels and frailty are sex-specific, suggesting that different biological mechanisms may be involved.

Cardiovascular disease (CVD), both clinical and subclinical, has been proposed as one of the mechanisms underlying frailty. However, there is no evidence addressing the relationship between the earliest stage of CVD (endothelial dysfunction) and frailty. The goal of the study was to analyze the association between endothelial dysfunction, evaluated by asymmetric dimethylarginine (ADMA) levels, and frailty. We used data from the Toledo Study for Healthy Aging, a prospective Spanish cohort study. Biological samples were obtained and ADMA levels were determined using an enzyme immunoassay method. Logistic regression was used to estimate the odds ratio (OR) and 95 % confidence intervals of frailty associated with ADMA. Adjustments were made for age, gender, cardiovascular risk factors, and presence of atherosclerotic disease (assessed by ankle–brachial index; ABI). One thousand two hundred eighty-seven community-dwelling elderly were included. One hundred seven (8.3 %) were identified as frail, 542 (42.1 %) as pre-frail, and 638 (49.6 %) as non-frail. ADMA values were higher in frail subjects than in non-frail ones. In addition, an interaction between the presence of atherosclerotic disease and ADMA on the odds of frailty ( p  = 0.045) was detected. After adjustments for age, classical cardiovascular risk factors, and ABI, the risk of frailty was associated with increasing levels of ADMA in subjects without atherosclerotic disease [OR for 1 standard deviation increase in ADMA = 1.14 (1.01–1.28), p  = 0.032] but not in those with atherosclerotic disease. In our study, endothelial dysfunction, assessed by ADMA levels, is associated with frailty. These findings provide additional support for a relevant role of vascular system since its earliest stage in frailty.

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.

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.

BackgroundAlthough there is growing utilisation of intermediate care to improve the health and well-being of older adults with complex care needs, there is no international agreement on how it is defined, limiting comparability between studies and reducing the ability to scale effective interventions.AimTo identify and define the characteristics of intermediate care models.MethodsA scoping review, a modified two-round electronic Delphi study involving 27 multi-professional experts from 13 countries, and a virtual consensus meeting were conducted.ResultsSixty-six records were included in the scoping review, which identified four main themes: transitions, components, benefits and interchangeability. These formed the basis of the first round of the Delphi survey. After Round 2, 16 statements were agreed, refined and collapsed further. Consensus was established for 10 statements addressing the definitions, purpose, target populations, approach to care and organisation of intermediate care models.DiscussionThere was agreement that intermediate care represents time-limited services which ensure continuity and quality of care, promote recovery, restore independence and confidence at the interface between home and acute services, with transitional care representing a subset of intermediate care. Models are best delivered by an interdisciplinary team within an integrated health and social care system where a single contact point optimises service access, communication and coordination.ConclusionsThis study identified key defining features of intermediate care to improve understanding and to support comparisons between models and studies evaluating them. More research is required to develop operational definitions for use in different healthcare systems.

Background Measurement of muscle mass and function, and thereafter, screening and diagnosis of sarcopenia, is a challenge and a need in hospitalized older adults. However, it is difficult in complex real-world old patients, because usually they are unable to collaborate with clinical, functional, and imaging testing. Ultrasound measurement of quadriceps rectus femoris (QRF) provides a non-invasive, real-time assessment of muscle quantity and quality, and is highly acceptable to participants with excellent inter-rater and intra-rater variability. However, normative data, protocol standardization, and association with longitudinal outcomes, needs further research and consensus. Methods Prospective exploratory multicenter study in older adults admitted to Acute Geriatric Units (AGUs) for medical reasons. 157 subjects from 7 AGUs of Spain were recruited between May 2019 and January 2022. Muscle ultrasound measurements of the anterior vastus of the QRF were acquired on admission and on discharge, using a previously validated protocol, using a Chieson model ECO2 ultrasound system (Chieson Medical Technologies, Co. Ltd, Wimxu District Wuxi, Jiangsu, China). Measurements included the cross-sectional area, muscle thickness in longitudinal view, intramuscular central tendon thickness, echogenicity, and the presence or absence of edema and fasciculations. Functional, nutritional, and DXA measurements were provided. Clinical follow-up was completed at discharge, and 30 and 90 days after discharge. Variations between hospital admission and discharge ultrasound values, and the relationship with clinical variables, will be analyzed using paired t -tests, Wilcoxon tests, or Mc Nemar chi-square tests when necessary. Prevalence of sarcopenia will be calculated, as well as sensitivity and specificity of ultrasound measurements to determine sarcopenia. Kappa analysis will be used to analyze the concordance between measurements, and sensitivity analysis will be conducted for each participating center. Discussion The results obtained will be of great interest to the scientific geriatric community to assess the utility and validity of ultrasound measurements for the detection and follow-up of sarcopenia in hospitalized older adults, and its association with adverse outcomes. Trial registration NCT05113758. Registration date: November 9 th 2021. Retrospectively registered.

The purpose of this study was to estimate the burden of osteoporotic fractures beyond the hospitalization period covering up to the first year after the fracture. This was a prospective, 12-month, observational study including patients aged ≥65 years hospitalized due to a first low-trauma hip fracture, in six Spanish regions. Health resource utilization (HRU), quality of life (QoL) and autonomy were collected and total costs calculated. Four hundred and eighty seven patients (mean ± SD age 83 ± 7 years, 77 % women) were included. Twenty-two percent of patients reported a prior non-hip low-trauma fracture, 16 % were receiving osteoporotic treatment at baseline, and 3 % had densitometry performed (1.8 % T -score ≤−2.5). Sixteen percent of patients died (women 14 %; men 25 %; p  = 0.0011) during the first year. Mean hospital stay was 11.8 ± 7.9 days and 95.1 % of patients underwent surgery. Other relevant HRUs were: outpatient visits in 78 % of patients (mean 9.2 ± 9.7); walking aids, 58.7 %; rehabilitation facilities, 35.5 % (28.7 ± 41.2 sessions); and formal and informal home care, 22.2 % (49.6 ± 72.2 days) and 53.4 % (77.1 ± 101.0 h), respectively. Mean direct cost was €9690 (95 % confidence interval: 9184–10,197) in women and €9019 (8079–9958) in men. Main cost drivers were: first hospitalization episode (women €7067 [73 %]; men €7196 [80 %]); outpatient visits (€1323 [14 %]; €997 [11 %]); and home care (€905 [9 %]; €767 [9 %]). QoL and autonomy showed a marked decrease during hospitalization, not entirely recovered at 12 months ( p  < 0.05 vs. baseline for EQ-5D, Harris hip score and modified Barthel index). In a Spanish setting, osteoporotic hip fractures incur a high societal and economic cost, mainly due to the first hospitalization HRU, but also due to subsequent outpatient visits and home care.

Background: Subsyndromal delirium has an increasing relevance in the medical literature. There are only three studies in hospitalized elderly patients. Our goal is to demonstrate the importance of this syndrome in a population with more complexity and cognitive impairment than in previous studies. Methods: Prospective multicentre study in three tertiary hospitals. The health outcomes recorded in the follow-up at 1 month were the persistence of delirium, hospital readmission, discharge destination, death, Barthel index and the Delirium Rating Scale Revised 98. To assess the impact of delirium in the Barthel index at 30 days, we adjusted univariate and multivariate linear regression models. Results: 85 patients were enrolled; 75.3% of the patients had at least 1 positive item in the Confusion Assessment Method; 45 patients (53%) were diagnosed with delirium and 19 (22.3%) with subsyndromal delirium (SSD). The 30-day risk of death was associated with lower levels of albumin (p = 0.021) and the Cumulative Illness Rating Scale in Geriatrics (CIRS-G; p = 0.003). Adjusting for CIRS-G and the initial Barthel index, the diagnosis of delirium appears to be related to a lower Barthel index at 30 days (p = 0.019), showing a significant linear gradient (p < 0.005). Conclusion: SSD could help get more accurate diagnoses as well as improve patient management.

There has been an increasing interest in delirium as a clinical syndrome in elderly patients in the last years (de Rooij et al., 2005). Until now the diagnosis has been dichotomous, but recent studies appear to show that a further categorization of this syndrome may lead to a higher diagnostic and prognostic value. The subsyndromal delirium (SSD) displays some of the symptoms without developing the full syndrome and it is intermediate in severity between non-delirious controls and full syndromal delirium, although it has no officially recognized diagnostic criteria (Levkoff et al., 1996). There is growing evidence about the prognostic significance of SSD among elderly individuals, but to date there are very few published studies on SSD in elderly patients. The goal of our study was to corroborate one-year outcomes after discharge. With this aim we performed a prospective multicenter study in March 2011 that recruited patients aged 75 years and older admitted to the acute geriatric wards of three tertiary hospitals in Spain – Complejo Hospitalario de Navarra, Hospital Universitario de Getafe, and Hospital Marqués de Valdecilla – at the same time during a 48-hour period, and were then followed up for one year. Four geriatricians were responsible for the patients’ screening and enrollment. A thorough geriatric assessment included clinical and demographic information (age, sex, education level, living arrangements before admission, presence of visual and hearing impairment) and comorbidity with the Cumulative Illness Rating Scale-Geriatric (CIRS-G). The CIRS-G rates 13 body systems on a five-point severity scale and is reliable because it allows all comorbid diseases from clinical examinations and medical files to be taken into account in a comprehensive manner.