Frail Subjects Research Articles

Identifying Frailty and Its Risk Factors in Pediatric Patients with Fontan Physiology.

Frailty is a clinical syndrome common in adults with chronic disease with resultant vulnerability to adverse health outcomes. Little is known about frailty in pediatric patients, including those with single-ventricle heart disease. This study aimed to examine the prevalence of frailty and its associated risk factors in patients with Fontan circulation. A single-center, prospective cohort study assessed frailty in patients (10-21years old) after Fontan palliation. Slowness, weakness, exhaustion, shrinkage, and diminished physical activity were evaluated and scored using a modified Fried frailty assessment comprised of validated pediatric tests. Providers estimated subjects' degree of frailty. Patient-reported quality of life (QOL) was assessed. Of 54 participants (median age 15.3years, 61% male), 18 (33%) were identified as frail, while 26 (48%) were pre-frail. Patients frequently exhibited frailty in the domains of slowness (93%), weakness (41%), and diminished physical activity (39%). There was poor correlation between frailty scores and provider estimates of frailty (Kappa = 0.11). Frail subjects had lower PedsQL physical functioning scores (mean 62.8 ± SD 18.5 in Frail vs. 75.7 ± 16.0 in No/pre-Frail; p = 0.01). Factors associated with frailty included protein-losing enteropathy (p = 0.03) and at least one hospitalization in the last year (p = 0.047). One-third of pediatric patients after Fontan palliation were frail which was associated with lower physical functioning and higher healthcare utilization. Providers poorly recognized frailty. These findings highlight the need for improved screening and support for an at-risk population where frailty is not easily identified.

Abstract P349: Prediabetes Increases the Risk of Frailty in Pre-frail Hypertensive Older Adults: Beneficial Effects of Metformin Treatment

Background: Prediabetes has garnered increasing attention due to its association with cardiovascular conditions, especially hypertension, which increases the risk of prefrailty and frailty among older individuals. Methods: We screened older adults with prefrailty and hypertension from March 2021 to January 2023. We assessed the correlation linking cognitive dysfunction (Montreal Cognitive Assessment score), insulin resistance (triglyceride-to-glucose index), and physical impairment (5-meter gait speed). Then, we measured the risk of developing frailty after a 1-year follow-up period, adjusting the outcome using multivariable Cox regression analysis. We also investigated the impact of administering 500 mg of metformin once daily to a subset of frail subjects for an additional 6 months. Results: We assessed the relationship between the triglyceride-to-glucose index and the Montreal Cognitive Assessment score, observing a significant correlation (r: 0.880; P<0.0001). Similarly, we analyzed the association between the triglyceride-to-glucose index and 5-meter gait speed, uncovering a significant link between insulin resistance and physical impairment (r: 0.809; P<0.0001). Prediabetes was found to significantly (P<0.0001) elevate the risk of frailty development compared with individuals without prediabetes by the end of the 1-year follow-up, a finding confirmed via multivariable analysis with Cox regression. Furthermore, among the subgroup of subjects who developed frailty, those who received metformin exhibited a significant decrease in frailty levels (P<0.0001). Conclusions: Insulin resistance and prediabetes play substantial roles in the development of cognitive and physical impairments, highlighting their importance in managing hypertension, even before the onset of frank diabetes. Metformin, a well-established drug for the treatment of diabetes, has shown favorable effects in mitigating frailty.

Short-term heart rate variability: A potential approach to frailty assessment in older adults.

This study aimed to evaluate cardiac autonomic modulation using short-term heart rate variability (HRV) and compare it among frailty statuses in older Indian adults. A total of 210 subjects aged 60 years and above were recruited into three groups: frail (n = 70), pre-frail (n = 70), and non-frail (n = 70) from the outpatient department of Geriatric Medicine at a tertiary care hospital in India. Frailty status was assessed using the Rockwood frailty index (FI) criteria. HRV was derived from a 5-min ECG recording of standard limb leads and assessed using time domain, frequency domain, and nonlinear analysis of cardiac interval variability. The HRV parameters indicative of parasympathetic modulation such as SDNN, SDSD, rMSSD, NN50, pNN50, absolute HF power, and SD1 were significantly lower in frail subjects compared with both pre-frail and non-frail subjects (P < 0.05). Absolute LF power and SD2 were also lower in frail subjects compared with pre-frail and non-frail subjects (P < 0.05). Measures of sympatho-vagal balance (LF/HF and SD1/SD2 ratios) did not show statistical significance. The FI demonstrated negative correlations with all HRV parameters. Frail individuals exhibit decreased sympathetic and parasympathetic modulation compared with pre-frail and non-frail individuals, although maintaining a balanced sympatho-vagal state. Furthermore, autonomic modulation declines progressively with increasing frailty.

Impairment of Renal and Hematopoietic Stem/Progenitor Cell Compartments in Frailty Syndrome: Link with Oxidative Stress, Plasma Cytokine Profiles and Nuclear DNA Damage.

Frailty is an age-related syndrome that drives multiple physiological system impairments in some older adults, and its pathophysiological mechanisms remain unclear. We evaluated whether frailty-related biological processes could impair stem cell compartments, specifically the renal stem compartment, given that kidney dysfunctions are frequent in frailty. A well-characterized in vitro nephrosphere model of human adult renal stem/progenitor cells has been instrumental to and was appropriate for verifying this hypothesis in our current research. Evaluating the effects of plasma from older individuals with frailty (frail plasma) on allogeneic renal stem/progenitor cells, we showed significant functional impairment and nuclear DNA damage in the treated cells of the renal stem compartment. The analysis of the frail plasma revealed mitochondrial functional impairment associated with the activation of oxidative stress and a unique inflammatory mediator profile in frail individuals. In addition, the plasma of frail subjects also contained the highest percentage of DNA-damaged autologous circulating hematopoietic progenitor/stem cells. The integration of both molecular and functional data obtained allowed us to discern patterns associated with frailty status, irrespective of the comorbidities present in the frail individuals. The data obtained converged toward biological conditions that in frailty caused renal and hematopoietic impairment of stem cells, highlighting the possibility of concomitant exhaustion of several stem compartments.

Prediabetes Increases the Risk of Frailty in Prefrail Older Adults With Hypertension: Beneficial Effects of Metformin.

Prediabetes has garnered increasing attention due to its association with cardiovascular conditions, especially hypertension, which heightens the risk of prefrailty and frailty among older individuals. We screened elders with prefrail hypertension from March 2021 to January 2023. We assessed the correlation linking cognitive dysfunction (Montreal Cognitive Assessment score), insulin resistance (triglyceride-to-glucose index), and physical impairment (5-meter gait speed). Then, we measured the risk of developing frailty after a 1-year follow-up period, adjusting the outcome using multivariable Cox regression analysis. We also investigated the impact of administering 500 mg of metformin once daily to a subset of frail subjects for an additional 6 months. We assessed the relationship between the triglyceride-to-glucose index and the Montreal Cognitive Assessment score, observing a significant correlation (r, 0.880; P<0.0001). Similarly, we analyzed the association between the triglyceride-to-glucose index and 5-meter gait speed, uncovering a significant link between insulin resistance and physical impairment (r, 0.809; P<0.0001). Prediabetes was found to significantly (P<0.0001) elevate the risk of frailty development compared with individuals without prediabetes by the end of the 1-year follow-up, a finding confirmed via multivariable analysis with Cox regression. Furthermore, among the subgroup of subjects who developed frailty, those who received metformin exhibited a significant decrease in frailty levels (P<0.0001). Insulin resistance and prediabetes play substantial roles in the development of cognitive and physical impairments, highlighting their importance in managing hypertension, even before the onset of frank diabetes. Metformin, a well-established drug for the treatment of diabetes, has shown favorable effects in mitigating frailty.

Proton Pump Inhibitors Induced Hyponatremia in a Liver Transplanted Patient—The Role of Deprescribing: A Case Report and Literature Review

Liver transplant patients are frail subjects due to lifelong therapy with immunosuppressants. In these patients, comorbidity and polytherapy increase the risk of adverse drug reactions. In this study, we report the development of hyponatremia, probably related to pantoprazole in a liver transplant patient. Sertraline dismission and treatment with sodium chloride did not improve clinical symptoms and laboratory levels. Pantoprazole dismission induced an improvement in clinical symptoms and the normalization of sodium levels. A five-month follow-up revealed the absence of clinical symptoms and normal serum sodium levels.

BPIFB4 protein and monocytes phenotyping: a preclinical asset for marking the frailty condition

Advanced age impacts on frequency and phenotype of immune cells as monocytes and macrophages. In this context, BPIFB4, a host defense protein with an immunomodulatory activity, has been found to be protective in healthy long living individuals in whom monocytes and macrophages have a favorable redistribution and phenotype. Thus, the aim of this study is to investigate the correlation between BPIFB4 levels in recruited frail subjects and both their frailty assessment/health status and monocytic profile. In this study, both a group of 40 frail individuals and 20 aged-matched healthy volunteers were recruited. Participants were subjected to standardized questionnaires to assess frailty risk, routine clinical examinations and blood test, monocytes extraction with next immunophenotypic FACS analysis. Overall, 70% of the frailty cohort has mild frailty, 25.5% has moderate frailty, and 5% has severe frailty. Compared to healthy controls, frail subjects show lower levels of circulating BPIFB4 that inversely correlate with the relative risk index for hypertension and cardiovascular disease. Flow cytometry results indicate total circulating monocyte frequency is reduced in frail subjects as compared to healthy controls. Considering monocytes’ subsets, CD14++CD16–classical monocytes and non-classical CD14+CD16++monocytes were significantly increased in frail people compared to old controls, whereas intermediate CD14++CD16+monocytes were reduced. Moreover, also the M2/M1 monocytic balance is altered in frailty condition compared to old volunteers. No relationship between BPIFB4 plasma levels and monocytes’subsets was found. Our findings highlight BPIFB4 protein has a potential prognostic value for marking the frailty condition.

Identification of Potential Blood-Based Biomarkers for Frailty by Using an Integrative Approach

Introduction: Although frailty is a geriatric syndrome that is associated with disability, hospitalization, and mortality, it can be reversible and preventable with the appropriate interventions. Additionally, as the current diagnostic criteria for frailty include only physical, psychological, cognitive, and social measurements, there is a need for promising blood-based molecular biomarkers to aid in the diagnosis of frailty. Methods: To identify candidate blood-based biomarkers that can enhance current diagnosis of frailty, we conducted a comprehensive analysis of clinical data, messenger RNA-sequencing (RNA-seq), and aging-related factors using a total of 104 older adults aged 65–90 years (61 frail subjects and 43 robust subjects) in a cross-sectional case-control study. Results: We identified two candidate biomarkers of frailty from the clinical data analysis, nine from the RNA-seq analysis, and six from the aging-related factors analysis. By using combinations of the candidate biomarkers and clinical information, we constructed risk prediction models. The best models used combinations that included skeletal muscle mass index measured by dual-energy X-ray absorptiometry (adjusted p = 0.026), GDF15 (adjusted p = 1.46E-03), adiponectin (adjusted p = 0.012), CXCL9 (adjusted p = 0.011), or apelin (adjusted p = 0.020) as the biomarker. These models achieved a high area under the curve of 0.95 in an independent validation cohort (95% confidence interval: 0.79–0.97). Our risk prediction models showed significantly higher areas under the curve than did models constructed using only basic clinical information (Welch’s t test p < 0.001). Conclusion: All five biomarkers showed statistically significant correlations with components of the frailty diagnostic criteria. We discovered several potential biomarkers for the diagnosis of frailty. Further refinement may lead to their future clinical use.

A new possible marker: can pennation angle defined by ultrasound predict the frailty?

BackgroundFrailty indicates older people who are vulnerable to stressors. The relation between ultrasonographic parameters of muscle and frailty among older people has yet to be investigated.AimsThe aim of the study is to investigate the relationship between frailty and the ultrasonographic measurements of the rectus femoris muscle (RFM).MethodsThis cross-sectional study included 301 participants who were ≥65 years. The FRAIL questionnaire assessed frailty. The thickness, cross-sectional area (CSA), fascicle length, pennation angle (PA), stiffness, and echogenicity of RFM were assessed by ultrasound. The accuracy of parameters in predicting the frailty was evaluated by ROC analysis.ResultsOf all 301 participants, 24.6% were frail. Pre-frail and frail participants had significantly lower thickness (p = 0.002), CSA (p = 0.009), and fascicle length (p = 0.043) of RFM compared to robust. PA was significantly lowest in frails (p < 0.001). The multivariate logistic regression analysis showed that PA values lower than 10.65 degrees were an independent predictor of frailty (OR = 0.83, 95% Cl: 0.70–0.97, p = 0.019). Results of ROC analysis demonstrated a satisfactory result between the PA and frailty (AUC = 0.692, p < 0.001).DiscussionThickness, CSA, and PA of RFM were found to be lower in frail subjects, which may indicate the changes in muscle structure in frailty. Among all parameters, lower PA values were independent predictors of frailty. These findings may indicate a novel ultrasound-based method in frailty, that is more objective and unrelated to the cross-sectional evaluation.ConclusionsUltrasonographic measurements of RFM, especially the lower PA may predict frailty in older people. As an objective and quantitative method, PA may be used to define frailty with acceptable sensitivity.

Cultural adaptation and validation of the Sinhala version of the Frail Non-disabled tool (FiND)

BackgroundFrailty, a common geriatric syndrome of vulnerability, is associated with a decline in health and function. The most problematic expression of population ageing is associated with weakness, slowing, decreased energy, lower activity and when severe, unintended weight loss. Frailty is not consciously identified in clinical practice and is not widely studied in Sri Lanka. A validated tool for screening frailty in a busy clinical setting is therefore much needed. This study was done as a part of validating the Sinhala version of the Frail Non-Disabled (S-FiND) tool.MethodsThe FiND tool was translated from English to Sinhala by two translators, blinded to each other. They were combined and translated back to the original language by two separate translators. After verifying the content validity, unambiguity and clarity of items in a focused group discussion, the pre-final version was piloted among 30 volunteers. After assessing the psychometric properties of the pre-final version, the final version was tested among 100 adults older than 65 years from the Colombo South Teaching Hospital. The tool was compared with Fried’s frailty phenotype taken as the gold standard.ResultsData were analysed for the agreement with the reference standard, the Fried Phenotype. The mean (SD) age of subjects was 73.9 (7.8) years. The overall time taken to fill out the questionnaire was 2 min. The agreement (Kappa) between the S-FiND questionnaire and the Fried phenotype was 0.7 (P < 001). The sensitivity and specificity of FiND in detecting frailty were 92% and 74%, respectively. The agreements (Kappa) between the individual items of S-Find: involuntary loss of weight/ more than 4.5 kg over one year, the feeling of effort/ not getting going and level of physical activity, with the Fried phenotype, were 0.28 (p = 0.001), 0.06 (p = 0.045) and 0.339 (p < 0.001). respectively. When subjects were categorized frail and robust based on FiND, frail subjects reported a higher incidence of falls (50%) during the previous 12 months, compared to those robust (13%) (p < 0.001 for Chi stat).ConclusionThe S-FiND is a reliable, valid and well-received tool that can be used in detecting the frailty of non-disabled Sinhala-speaking older adults.

Association of biological aging with frailty and post-transplant outcomes among adults with cirrhosis.

Frailty is classically associated with advanced age but is also an important predictor of clinical outcomes in comparatively young adults with cirrhosis. We examined the association of biological aging with frailty and post-transplant outcomes in a pilot of adults with cirrhosis undergoing liver transplantation (LT). Frailty was measured via the Liver Frailty Index (LFI). The primary epigenetic clock DNA methylation (DNAm) PhenoAge was calculated from banked peripheral blood mononuclear cells; we secondarily explored two first-generation clocks (Hannum; Horvath) and two additional second-generation clocks (GrimAge; GrimAge2). Twelve adults were included: seven frail (LFI ≥ 4.4, mean age 55years) and five robust (LFI < 3.2, mean age 55years). Mean PhenoAge age acceleration (AgeAccel) was + 2.5years (P = 0.23) for frail versus robust subjects. Mean PhenoAge AgeAccel was + 2.7years (P = 0.19) for subjects who were readmitted or died within 30days of discharge post-LT versus those without this outcome. When compared with first-generation clocks, the second-generation clocks demonstrated greater average AgeAccel for subjects with frailty or poor post-LT outcomes. Measuring biological age using DNAm-derived epigenetic clocks is feasible in adults undergoing LT. While frail and robust subjects had the same average chronological age, average biological age as measured by second-generation epigenetic clocks tended to be accelerated among those who were frail or experienced a poor post-LT outcome. These results suggest that frailty in these relatively young subjects with cirrhosis may involve similar aging mechanisms as frailty classically observed in chronologically older adults and warrant validation in a larger cohort.

Exploring the metabolomics profile of frailty- a systematic review.

Frailty is a multifaceted geriatric syndrome characterized by an increased vulnerability to stressful events. metabolomics studies are valuable tool for better understanding the underlying mechanisms of pathologic conditions. This review aimed to elucidate the metabolomics profile of frailty. This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) 2020 statement. A comprehensive search was conducted across multiple databases. Initially, 5027 results were retrieved, and after removing duplicates, 1838 unique studies were subjected to screening. Subsequently, 248 studies underwent full-text screening, with 21 studies ultimately included in the analysis. Data extraction was performed meticulously by two authors, and the quality of the selected studies was assessed using the Critical Appraisal Skills Program (CASP) checklist. The findings revealed that certain Branched-chain amino acids (BCAAs) levels were lower in frail subjects compared to robust subjects, while levels of glutamate and glutamine were higher in frail individuals. Moreover, sphingomyelins and phosphatidylcholines (PC) displayed a decreasing trend as frailty advanced. Additionally, other metabolic derivatives, such as carnitine, exhibited significant associations with frailty. These metabolites were primarily interconnected through biochemical pathways related to the tricarboxylic acid and urea cycles. Notably, frailty was associated with a decrease in metabolic derivatives, including carnitine. This study underscores the intricate relationship between essential metabolites, including amino acids and lipids, and their varying levels in frail individuals compared to their robust counterparts. It provides a comprehensive panel of metabolites, shedding light on their potential associations with frailty and expanding our understanding of this complex syndrome.

Cardiovascular Adverse Events of Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia: Clinical Relevance, Impact on Outcome, Preventive Measures and Treatment Strategies.

The introduction of TKIs into the therapeutic armamentarium of CML has changed the disease paradigm, increasing long-term survival from 20% to over 80%, with a life expectancy now approaching that of the general population. Although highly effective, TKIs also have a toxicity profile that is often mild to moderate, but sometimes severe, with multiple kinases involved in the development of adverse events (AEs). Among others, cardiovascular AEs observed in TKI-treated CML patients may represent a significant cause of morbidity and mortality, and their pathogenesis is still only partially understood. In view of the recent introduction into daily clinical practice of new TKIs, namely the STAMP inhibitor asciminib, with a distinct safety profile, hematologists now more than ever have the opportunity to select the most suitable TKI for each patient, an aspect that will be fundamental in terms of personalized preventive and therapeutic strategies. Furthermore, physicians should be aware of the feasibility of TKI dose modifications at all stages of the patients' treatment journey, both at diagnosis for frail or elderly subjects or with multiple comorbidities, and during follow-up for those patients who experience toxicity, as well as to prevent it, with the main objective of reducing side effects while maintaining the response. Consequently, preserving the cardiovascular health of CML patients will likely be a more urgent topic in the near future, with specific measures aimed at controlling cardiovascular risk factors through a multidisciplinary approach involving a panel of healthcare professionals together with the hematologist.

Frailty and chronic kidney disease: associations and implications.

Frailty and its association with chronic kidney disease (CKD) has been established previously. The present study examined this association further by studying the distribution of frailty among groups defined by different stages of the disease. It also identified associated health deficits and explored their association with estimated glomerular filtration rate (eGFR) and urine albumin creatinine ratio (UACR). A cross-sectional survey was conducted on 90 non-dialysis dependent CKD Stage 1-4 patients, recruited in three stratified groups of 30 participants each based on the stage of disease. Frailty was assessed using Fried's frailty criteria and associated health deficits were recorded using a pre-determined list. Depression was screened using a 4-point depression scale. 21.1% of the participants were frail and 43.3% were pre-frail. The proportion of frailty in CKD groups A (Stages 1 and 2), B (Stage 3a), and C (Stages 3b and 4) was 10%, 13.3%, and 40%, respectively. The association of health deficits including co-morbidities, physical parameters, mental status, daily activities, etc. with UACR, eGFR, and CKD stages was not statistically significant. Nearly one in two frail participants was depressed compared with 14% among non-frail participants. The skewed distribution of 21% frail subjects identified in our study indicates an association between frailty and advancing kidney disease. Frail individuals had a lower eGFR, higher UACR, were more likely to be depressed, and had higher count of health deficits and poorer performance on Barthel Index of Activities of Daily Living and WHOQOL. Early identification of depression would improve care in these patients.

Effect of perceived and objectively-assessed frailty on outcomes in edoxaban-treated patients with atrial fibrillation: data from the ETNA-AF-Europe 4-year follow-up

Abstract Background Frailty is common in patients with atrial fibrillation (AF). However, different definitions of frailty are used, and these may variably overlap with frailty perception among physicians. Long-term data on outcomes based on perceived versus objective frailty in patients with AF treated with a non-vitamin K antagonist oral anticoagulant are lacking. Purpose To assess the effect of perceived versus objective frailty on outcome events in patients with AF treated with edoxaban during the 4-year follow-up of the ETNA-AF-Europe registry (NCT02944019). Methods ETNA-AF-Europe is a multinational, multicentre, post-authorisation, observational study conducted in patients with AF receiving edoxaban. In this sub-analysis, patients were evaluated in terms of perceived or objective frailty status (yes or no categories). Perceived frailty was based on investigators’ own clinical binary judgement in each patient. Objective frailty was determined using a Modified Frailty Index, a simplified adaptation of the Rockwood’s Frailty Index. Patient demographics and characteristics were collected at baseline. The efficacy and safety outcomes are reported here comparing frailty status (yes versus no) among perceived or objectively classified patients. Results Among the 13,164 patients with 4 years of follow-up, the prevalence of perceived and objective frailty was 10.7% and 4.1%, respectively. Compared with the objectively frail group, those perceived as frail were older, with a lower proportion of males, had lower body weight and creatinine clearance values, yet lower CHA2DS2-VASC and modified HAS-BLED scores (Table 1). Further, patients with objective frailty tended to have more comorbidities (e.g., diabetes, heart failure, hypertension; Table 1). Those deemed frail were more likely to receive the reduced 30 mg edoxaban dose versus non-frail patients (p&amp;lt;0.001 for both groups), and non-recommended dosing regimens (60 or 30 mg) were more often prescribed in frail versus non-frail patients (p&amp;lt;0.0001 for all comparisons; Table 1). Patients perceived as frail had a significantly higher risk of all evaluated outcomes compared with non-frail patients (p-value range: &amp;lt;0.0001 – 0.0459; Figure 1). Similar data were seen for objectively frail patients, with the exception of no significant differences in the risk of intracranial haemorrhage (ICH, p=0.0918) or haemorrhagic stroke (p=0.1619; Figure 1). Conclusions Frailty was associated with an inappropriate dosing of edoxaban and an increased incidence of outcome events, quantitatively similar in the perceived and objective frailty groups. After 4 years of therapy, even if ICH risk was increased in frail subjects, its cumulative incidence was low.

Microbiological characterization of a population affected by periodontitis with different levels of bone health

ntroduction: Both osteoporosis and periodontitis are diseases characterized by deficits at the level of bone tissue, where bone resorption exceeds neo-formation, resulting in bone loss. Materials and methods: In the context of a monocentric cross-sectional observational study carried out through the collaboration between the University of Florence and the private dentistry institute Excellence Dental Network, 110 subjects affected by periodontitis were recruited. Of these, 71 were also affected by osteoporosis or osteopenia and 39 were not osteoporotic or osteopenic. Data were collected on oral microbiota, oral health and bone health. Results: The collected data reveal a population of frail subjects in terms of fracture risk. The most common forms of periodontitis were essentially chronic in nature, and mainly of a moderate or even severe type, with high gingival recession and periodontal pocket depth values. The microbial species associated with Socransky's red and orange complexes showed concentration values nearly always above 10³ copies/mL. Conclusions: The relationship between osteoporosis and periodontitis still needs to be explored in depth. Data from our analyses are certainly interesting and provide a basis for designing further studies in larger populations. KEY WORDS: Periodontal disease, bone disease, oral microbiota.

57 A review of the utilisation of the SHARE frailty instruments (SHARE-FI and SHARE-Fi75+) in the literature

Abstract Background The Survey of Health, Ageing and Retirement in Europe (SHARE) frailty instruments SHARE-FI and SHARE-FI75+ were developed as non-commercial, open access frailty phenotype-based identification tools for rapid use in the primary care setting. This literature review examined their utilisation since their publication. Methods We used the Google Scholar ‘cited by’ function (accessed on February 20th, 2023) to identify all citations of the original SHARE-FI and SHARE-FI75+ studies. Included articles were categorised into four themes: epidemiological studies (prevalence and associated factors); associations with geriatric syndromes, diseases and health outcomes; randomised clinical trials (RCTs); and expert consensus and practice guidelines. Results Of 529 articles screened (446 citing SHARE-FI and 83 citing SHARE-FI75+), 64 (12.1%) were included in the narrative review. Sixteen (25.0%) were epidemiological; 35 (54.7%) described associations; 10 (15.6%) were RCTs; and 3 (4.7%) were expert consensus or practice guidelines. Frailty was associated with older age; female sex; higher morbidity; lower education; social isolation; worse nutrition and mobility; rheumatological, cardiovascular, and endocrine diseases; and greater healthcare utilisation and mortality. SHARE-FI was used in RCTs as entry criterion, controlling variable and intervention outcome. The most commonly studied interventions were exercise, nutrition and social support. SHARE-FI and SHARE-FI75+ have been recommended to aid the management of atrial fibrillation anticoagulation (2015 European Heart Rhythm Association (EHRA) Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation) and hypertension (2016 Expert Opinion From the European Society of Hypertension-European Union Geriatric Medicine Society Working Group on the Management of Hypertension in Very Old, Frail Subjects), respectively. Conclusion SHARE-FI and SHARE-FI75+, two open access phenotypical frailty measurement tools, have been utilised for diverse purposes, and mostly in epidemiological/associational studies. The relative paucity of RCTs and guidelines vis-à-vis epidemiological and associational studies highlights scope for their future utilisation in studies that will be able to generate higher-level evidence.

O.4.1-2 Linking lymphocyte T phenotype to physical capacities in a geriatric population: the VIF-APAS study

Abstract Purpose Potential mediators contributing to chronic inflammation in aging have both local and systemic impacts that likely promote physical decline. Supporting data in aged mice link modification of T cells to exercise performance leading to novel hypotheses involving the anti-inflammatory regulatory T cells (Tregs) in age-related changes in tissues. We investigated in a geriatric cohort whether physical markers of early signs of frailty and their reversibility would alter circulating Tregs prevalence and subtypes regarding their markers of senescence, function, and migration to tissues. Methods Geriatric patients able to walk without technical help, were included in a 12-weeks adapted physical activity (APA) program (NCT04080063). Multidisciplinary tools were used to assess the various aspects of human movement and frailty (isokinetic testing, bioelectric impedancemetry, nutrition, etc.). Relative NK, CD8+ and CD4+ T cells proportions were determined using flow cytometry in extracted peripheral blood monocytes. The transcription factor (FoxP3), the IL-2 receptor (CD25), the senescence (KLRG1) and migration (CCR4) markers were detected using intracellular staining and flow cytometry to discriminate the associated cell subsets and Tregs. Results 66 women (82.8 ± 6 yrs) and 23 men (82.3 ± 4 yrs) took part in the study. Only 42% had a compliance rate in the APA program over 70%. 44%, were frail, 44% pre-frail and 12% non-frail (Fried criteria). In a representative sample (n = 19), the prevalence of NK cells was 3 times higher in frail subjects. The consideration of markers (Foxp3, CD25, and CCR4) was shown to discriminate an association with some specific physical parameters that are characteristic of neuromuscular and metabolic functions: %CCR4+ cells among NK cells was negatively related to leg extensors maximum strength, and the absence of CD25 in Tregs (CD4+Foxp3+) cells was negatively related to walking distance and speed. Conclusions Our preliminary results that need to be confirmed seem to show differences in immune cell markers depending on the frailty status. This study will participate in determining immunometabolic biomarkers of frailty and vitality in a geriatric population. The aim is to promote personalized strategies to predict and counteract inflammaging in an early stage, and to accompany and evaluate adapted physical activity strategies.

Exploring the relationship between frailty and executive dysfunction: the role of frontal white matter hyperintensities.

Frailty is a geriatric syndrome frequently associated with executive dysfunction and white matter hyperintensities (WMH). But the relation between executive dysfunction and brain changes is poorly understood in frail subjects. Our hypothesis is that frontal-WMH mediates the association between frailty and executive dysfunction. A convenience sample of 113 subjects older than 65 years without dementia was studied with neuropsychological test, a structured clinical interview, physical examination and brain MRI. They were classified as robust or pre-frail and frail using the frailty phenotype score (0-5). The frontal WMH (F-WMH) were manually graduated (0-6) using the "Age-Related White Matter Changes score" from FLAIR sequences at a 3 Tesla brain MRI. A mediation analysis was done for testing whether F-WMH could act as a link factor between frailty phenotype score and executive dysfunction. The group's mean age was 74 ± 6 years, subjects with higher frailty score had more depressive symptoms and worse performance in executive function tests. A regression analysis that explained 52% of the variability in executive functions, revealed a significant direct effect of frailty score (Standardized βcoeff [95% CI] -0.201, [-0.319, -0.049], and F-WMH (-0.152[-0.269, -0.009]) on executive functions, while the F-WMH showed a small partial mediation effect between frailty and executive functions (-0.0395, [-0.09, -0.004]). Frontal matter hyperintensities had a small mediation effect on the association between frailty and executive dysfunction, suggesting that other neuropathological and neurofunctional changes might also be associated with executive dysfunction in frail subjects.

A database with frailty, functional and inertial gait metrics for the research of fall causes in older adults

The GSTRIDE database contains information of the health status assessment of 163 elderly adults. We provide socio-demographic data, functional and frailty variables, and the outcomes from tests commonly performed for the evaluation of elder people. The database contains gait parameters estimated from the measurements of an Inertial Measurement Unit (IMU) placed on the foot of volunteers. These parameters include the total walking distance, the number of strides and multiple spatio-temporal gait parameters, such as stride length, stride time, speed, foot angles and clearance, among others. The main processed database is stored, apart from MS Excel, in CSV format to ensure their usability. The database is complemented with the raw IMU recordings in TXT format, in order to let researchers test other algorithms of gait analysis. We include the Python programming codes as a base to reproduce or modify them. The database stores data to study the frailty-related parameters that distinguish faller and non-faller populations, and analyze the gait-related parameters in the frail subjects, which are essential topics for the elderly.