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Purpose: Postoperative delirium (POD) is a common and serious neuropsychiatric syndrome that leads to higher morbidity and mortality. We investigated the association between serum C-reactive protein (CRP) and the occurrence of POD in older hip fracture patients, and whether CRP predicted POD better than a clinical model., Methods: Patients aged ≥ 75 years admitted for surgical repair of an acute hip fracture were recruited. We compared serum CRP levels between patients with and without POD., Results: Sixty patients were included, of whom 21 (35%) developed POD. Serum CRP levels were significantly higher in patients who developed delirium (p = 0.011). In a multiple regression model including clinical variables and CRP, cognitive impairment (p = 0.003) and infection (p = 0.001) were the best predictors of POD., Conclusions: Although higher levels of serum CRP were significantly associated with POD in older hip fracture patients, pre-existing cognitive impairment and infections were the most important risk factors for POD., Competing Interests: Declarations. Conflict of interest: The authors declare they have no conflict of interest. Ethical approval: Ethical approval was agreed by the Ethical Comittee of the Institution. Informed consent: Informed consent was obtained from all patients prior to all surgical procedures., (© 2024. The Author(s), under exclusive licence to European Geriatric Medicine Society.)

Background: Hospitalization exacerbates sarcopenia and physical dysfunction in older adults. Whether tailored inpatient exercise prevents acute sarcopenia is unknown. This study aimed to examine the effect of a multicomponent exercise programme on muscle and physical function in hospitalized older adults. We hypothesized that participation in a brief tailored exercise regimen (i.e., 3-5 days) would attenuate muscle function and structure changes compared with usual hospital care alone., Methods: This randomized clinical trial with blinded outcome assessment was conducted from May 2018 to April 2021 at Hospital Universitario de Navarra, Spain. Participants were 130 patients aged 75 years and older admitted to an acute care geriatric unit. Patients were randomized to a tailored 3- to 5-day exercise programme (n = 64) or usual hospital care (control, n = 66) consisting of physical therapy if needed. The coprimary endpoints were between-group differences in changes in short physical performance battery (SPPB) score and usual gait velocity from hospital admission to discharge. Secondary endpoints included changes in rectus femoris echo intensity, cross-sectional area, thickness and subcutaneous and intramuscular fat by ultrasound., Results: Among 130 randomized patients (mean [SD] age, 87.7 [4.6] years; 57 [44%] women), the exercise group increased their mean SPPB score by 0.98 points (95% CI, 0.28-1.69 points) and gait velocity by 0.09 m/s (95% CI, 0.03-0.15 m/s) more than controls (both p < 0.01). No between-group differences were observed in any ultrasound muscle outcomes. There were no study-related adverse events., Conclusions: Three to 5 days of tailored multicomponent exercise provided functional benefits but did not alter muscle or fat architecture compared with usual hospital care alone among vulnerable older patients. Brief exercise may help prevent acute sarcopenia during hospitalization., Trial Registration: ClinicalTrials.gov identifier: NCT04600453., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Background: Hospital-associated functional decline affects nearly one-third of the hospitalized older adults. The aim of this trial is to investigate the effect of a cognitive stimulation intervention provided via immersive virtual reality (IVR), with or without a multicomponent physical exercise intervention (ME) in hospitalized patients aged 75 or older with severe functional dependency at admission (Barthel Index < 60 points)., Methods: This clinical randomized controlled trial will be conducted in the Acute Geriatric Unit of a tertiary hospital in Spain. A total of 212 acute patients will be enrolled according to the following criteria: age ≥ 75, Barthel Index < 60, able to collaborate, expected length of stay ≥ 5 days, absence of clinical instability and severe dementia (Global Deterioration Scale 7) or other end-stage disease. Patients will be randomly assigned to a control group (CG) or any of the three intervention groups (IG): IVR, ME, or IVR + ME. The IVR group will watch ad-hoc videos showing Spanish regional landscapes and villages, approximately 4 min per day for three consecutive days. The ME group will undergo aerobic and strength exercise for progressive training of the upper and lower limbs. The IVR + ME group will do both cognitive and physical intervention. The primary outcomes will be cognitive and physical measures at discharge. Mood, quality of life, isometric strength, and acceptance of IVR will be also assessed., Discussion: This project has the potential to enhance physical and psychological well-being of patients with severe functional dependency hospitalized for acute conditions, using technology. Virtual reality is expected to be favourably perceived by hospitalized older adults. This intervention represents a novelty in the geriatric patients' care, comprising IVR and/or ME dispensed within the patient's room, and including patients who are commonly excluded from research clinical trials., Trial Registration: This study was approved by the Navarra Clinical Research Ethics Committee on May 17th, 2023 (PI&#95;2023/60). The trial is registered at ClinicalTrials.gov, registration number NCT06340282, 24th May 2024., (© 2024. The Author(s).)

Background: Sex-based differences in the clinical presentation and outcomes are well-established in patients hospitalized for geriatric syndromes. We aimed to investigate sex differences in response to in-hospital exercise on function, strength, cognition, and quality of life in acute care admissions., Methods: 570 patients (mean age 87 years, 298 females [52.3%]) admitted to acute care for elderly units were randomized to multicomponent exercise emphasizing progressive resistance training or usual care. Functional assessments included Short Physical Performance Battery (SPPB), grip strength, Mini-Mental State Examination (MMSE), and health-related quality of life (EQ-VAS)., Results: Exercising females showed more significant SPPB improvements than males (between-group difference 1.48 points, p = 0.027), exceeding the minimal clinically significant difference. While female participants significantly increased handgrip strength and male patients improved cognition after in-hospital exercise compared to the control group (all p < 0.001), no sex differences occurred., Conclusions: Females demonstrate more excellent physical function improvements compared to male older patients. Findings highlight the importance of tailored exercise incorporating patient factors like biological sex in geriatric medicine., Trial Registration: NCT04600453., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: This study aimed to determine the threshold of muscle power and strength enhancements that lead to functional gains after exercise intervention in an acute care unit., Methods: A total of 302 older patients (intervention: 169, control: 133) from 2 randomized clinical trials were included (mean age: 86.7 years). We measured maximal strength (1RM) and muscle power via a velocity transducer during leg press exercise at 30% and 60% of 1RM. A multicomponent exercise program, including power training, balance, and gait exercises performed over 3 to 6 consecutive days, served as the intervention. We used an anchor-based method to correlate muscle function increases with the Short Physical Performance Battery (SPPB) and gait velocity (GVT) to define clinically meaningful improvements., Results: In the intervention group, marked differences were found in maximal power at 30% of 1RM between SPPB responders and nonresponders (relative 83.5% vs 34.8%; absolute 33.0 vs 12.8 W; p < .05) and at 60% of 1RM (relative 61.1% vs 22.4%; p < .05). GVT responders demonstrated significantly greater improvements in both relative and absolute maximal power than nonresponders at both 30% and 60% of 1RM (p < .05), as well as greater absolute 1RM gains (21.2 vs 15.2 kg, p < .05). Clinically meaningful improvements for muscle power based on SPPB and GVT ranged from 30.2% to 48.7%, whereas for 1RM, it was 8.2% based on GVT., Conclusions: Muscle power gains were most notable in patients with improvements in the SPPB and GVT, highlighting the critical role of muscle power in functional recovery in these patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: The progressive aging of the population has meant the increase in elderly patients requiring an urgent surgery. Older adults, especially those with frailty, have a higher risk for complications, functional and cognitive decline after urgent surgery. These patients have their functional and physiological reserve reduced which makes them more vulnerable to the effects of being bedridden. The consequences are at multiple levels emphasizing the functional loss or cognitive impairment, longer stays, mortality and institutionalization, delirium, poor quality of life and increased use of resources related to health. We aim to determine whether postoperative physical rehabilitation can prevent functional and cognitive decline and modify the posterior trajectory., Methods/design: This study is a randomized clinical trial, simple blinded, conducted in the Department of Surgery of a tertiary public hospital in Navarra (Hospital Universitario de Navarra), Spain. Patients >  = 70 years old undergoing urgent abdominal surgery who meet inclusion criteria will be randomly assigned to the intervention or control group. The intervention will consist of a multicomponent physical training programme, which will include progressive and supervised endurance, resistance and balance training for 4 weeks, twice weekly sessions with a total of 8 sessions, and the group control will receive the usual care. The primary outcome measure is the change in functional (SPPB) and cognitive status (Mini-Mental State Examination) and the change of quality of life (EuroQol-5D-VAS) during the study period. The secondary outcomes are postoperative complications, length of stay, delirium, mortality, use of health resources, functional status (Barthel Index and handgrip strength tests), cost per quality-adjusted life year and mininutritional assessment. The data for both the intervention group and the control group will be obtained at four different times: the initial visit during hospital admission and at months 1, 3 and 6 months after hospital discharge., Discussion: If our hypothesis is correct, this project could show that individualized and progressive exercise programme provides effective therapy for improving the functional capacity and achieve a better functional, cognitive and quality of life recovery. This measure, without entailing a significant expense for the administration, probably has an important repercussion both in the short- and long-term recovery, improving care and functional parameters and could determine a lower subsequent need for health resources. To verify this, we will carry out a cost-effectiveness study. The clinical impact of this trial can be significant if we help to modify the traditional management of the elderly patients from an illness model to a more person-centred and functionally oriented perspective. Moreover, the prescription of individualized exercise can be routinely included in the clinical practice of these patients., Trial Registration: ClinicalTrials.gov Identifier: NCT05290532. Version 1. Registered on March 13, 2022., (© 2024. The Author(s).)

Objective: Delirium is a serious neuropsychiatric syndrome frequently occurring in hospitalized older adults, for which pharmacological treatments have shown limited effectiveness. Multicomponent physical exercise programs have demonstrated functional benefits; however, the impact of exercise on the course of delirium remains unexplored. The aim of this study was to investigate the effect of an individualized, multicomponent exercise intervention on the evolution of delirium and patient outcomes., Design: A single-center, single-blind randomized controlled trial., Setting and Participants: Medical inpatients with delirium in an acute geriatric unit of a tertiary public hospital., Methods: Thirty-six patients (mean age 87 years) were recruited and randomized into 2 groups. The control group received usual care and the intervention group received individualized physical exercise (1 daily session) for 3 consecutive days. Primary endpoints were the duration and severity of delirium (4-AT, Memorial Delirium Assessment Scale) and change in functional status [Barthel Index, Short Physical Performance Battery, Hierarchical Assessment of Balance and Mobility (HABAM), and handgrip strength]. Secondary endpoints included length of stay, falls, and health outcomes at 1- and 3-month follow-up., Results: The intervention group showed more functional improvement at discharge (HABAM, P = .015) and follow-up (Barthel, P = .041; Lawton P = .027). Less cognitive decline was observed at 1 and 3 months (Informant Questionnaire on Cognitive Decline in the Elderly, P = .017). Exercise seemed to reduce delirium duration by 1 day and contribute to delirium resolution at discharge, although findings did not reach statistical significance. No exercise-related adverse events occurred., Conclusion and Implications: Findings suggest that individualized exercise in acutely hospitalized older patients with delirium is safe, may improve delirium course and help preserve post-hospitalization function and cognition., Competing Interests: Disclosure The authors declare no conflicts of interest., (Copyright © 2024 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Exercise may reverse functional decline in hospitalized older adults, but the optimal duration is unclear. This study examined the potential relationship between in-hospital multicomponent exercise program duration and changes in physical function, cognition, and muscle function to maximize exercise-related health benefits in acutely hospitalized older patients., Research Design and Methods: This secondary analysis of a multicenter randomized controlled trial examined the relationship between the duration of an in-hospital multicomponent exercise program and changes in physical function, cognition, and muscle strength in 570 acutely hospitalized older adults. Participants completed 3, 4, or 5-7 consecutive days of exercise based on the progression of their acute medical illness. The acute clinical condition of the older patients was similar across the study groups (i.e., 3/4/5-7 days) at admission. Outcomes included the Short Physical Performance Battery (SPPB) for functional capacity, Gait Velocity Test for gait speed, handgrip for muscle strength, and cognitive tests., Results: Of the 570 patients included in the analysis, 298 were women (52.3%), and the mean ( SD ) age was 87.3 (4.8) years. Exercise groups increased SPPB scores compared with controls, with gains of 1.09 points after three days, 1.97 points after four days, and 2.02 points after 5-7 days ( p  < .001). The 4-day program showed the most significant benefit for functional capacity. Gait velocity increased by 0.11 m/s after 4 and 5-7 days ( p  = .032). Similar dose-response relationships were seen for handgrip strength and cognition, with 5-7 days showing more significant gains than three days ( p  < .05)., Discussion and Implications: Multicomponent exercise programs enhance physical and cognitive function in hospitalized older adults, regardless of exercise dosage. A 4-day program significantly boosts functional capacity, although 5-7 days improves handgrip strength and cognition, highlighting the importance of exercise dosage in countering functional decline. Implementing evidence-based inpatient exercise prescriptions can help reverse muscle weakness and improve cognitive and physical function.Clinical Trial Registration: NCT04600453., Competing Interests: None., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Postoperative delirium (POD) is a common neuropsychiatric complication in geriatric inpatients after hip fracture surgery and its occurrence is associated with poor outcomes. The purpose of this study was to investigate the relationship between preoperative biomarkers in serum and cerebrospinal fluid (CSF) and the development of POD in older hip fracture patients, exploring the possibility of integrating objective methods into future predictive models of delirium. Sixty hip fracture patients were recruited. Blood and CSF samples were collected at the time of spinal anesthesia when none of the subjects had delirium. Patients were assessed daily using the 4AT scale, and based on these results, they were divided into POD and non-POD groups. The Olink® platform was used to analyze 45 cytokines. Twenty-one patients (35%) developed POD. In the subsample of 30 patients on whom proteomic analyses were performed, a proteomic profile was associated with the incidence of POD. Chemokine (C-X-C motif) ligand 9 (CXCL9) had the strongest correlation between serum and CSF samples in patients with POD (rho = 0.663; p < 0.05). Although several cytokines in serum and CSF were associated with POD after hip fracture surgery in older adults, there was a significant association with lower preoperative levels of CXCL9 in CSF and serum. Despite the small sample size, this study provides preliminary evidence of the potential role of molecular biomarkers in POD, which may provide a basis for the development of new delirium predictive models., (© 2024. The Author(s), under exclusive licence to American Aging Association.)

Introduction: Hip fractures are the most common fracture leading to hospitalization and are associated with high costs, mortality rates and functional decline. Although several guidelines exist for preventing new fractures and promoting functional recovery, they tend to focus on osteoporosis treatment and do not take into account the complexity of frailty in older adults and geriatric syndromes, which are important factors in individuals at risk of suffering from frailty fractures. Moreover, most health systems are fragmented and are incapable of providing appropriate management for frail and vulnerable individuals who are at risk of experiencing fragility fractures. Multicomponent interventions and physical exercise using tele-rehabilitation could play a role in the management of hip fracture recovery. However, the effectiveness of exercise prescription and its combination with a comprehensive geriatric assessment (CGA) is still unclear., Methods: This randomized clinical trial will be conducted at the Hospital Universitario de Navarra (Pamplona, Spain). A total of 174 older adults who have suffered a hip fracture and fulfil the criteria for inclusion will be randomly allocated to either the intervention group or the control group. The intervention group will receive a multicomponent intervention consisting of individualized home-based exercise using the @ctive hip app for three months, followed by nine months of exercise using Vivifrail. Additionally, the intervention group will receive nutrition intervention, osteoporosis treatment, polypharmacy adjustment and evaluation of patient mood, cognitive impairment and fear of falling. The control group will receive standard outpatient care according to local guidelines. This research aims to evaluate the impact of the intervention on primary outcome measures, which include changes in functional status during the study period based on the Short Physical Performance Battery., Discussion: The findings of this study will offer valuable insights into the efficacy of a comprehensive approach that considers the complexity of frailty in older adults and geriatric syndromes, which are important factors in individuals at risk of suffering from frailty fractures. This study's findings will contribute to the creation of more effective strategies tailored to the requirements of these at-risk groups.

Background: Bed rest during hospitalization can negatively impact functional independence and clinical status of older individuals. Strategies focused on maintaining and improving muscle function may help reverse these losses. This study investigated the effects of a short-term multicomponent exercise intervention on maximal strength and muscle power in hospitalized older patients., Methods: This secondary analysis of a randomized clinical trial was conducted in an acute care unit in a tertiary public hospital. Ninety (39 women) older patients (mean age 87.7 ± 4.8 years) undergoing acute-care hospitalization [median (IQR) duration 8 (1.75) and 8 (3) days for intervention and control groups, respectively]) were randomly assigned to an exercise intervention group (n = 44) or a control group (n = 46). The control group received standard care hospital including physical rehabilitation as needed. The multicomponent exercise intervention was performed for 3 consecutive days during the hospitalization, consisting of individualized power training, balance, and walking exercises. Outcomes assessed at baseline and discharge were maximal strength through 1 repetition maximum test (1RM) in the leg press and bench press exercises, and muscle power output at different loads (≤30% of 1RM and between 45% and 55% of 1RM) in the leg press exercise. Mean peak power during 10 repetitions was assessed at loads between 45% and 55% of 1RM., Results: At discharge, intervention group increased 19.2 kg (Mean Δ% = 40.4%) in leg press 1RM [95% confidence interval (CI): 12.1, 26.2 kg; P < 0.001] and 2.9 kg (Mean Δ% = 19.7%) in bench press 1RM (95% CI: 0.6, 5.2 kg; P < 0.001). The intervention group also increased peak power by 18.8 W (Mean Δ% = 69.2%) (95% CI: 8.4, 29.1 W; P < 0.001) and mean propulsive power by 9.3 (Mean Δ% = 26.8%) W (95% CI: 2.5, 16.1 W; P = 0.002) at loads ≤30% of 1RM. The intervention group also increased peak power by 39.1 W (Mean Δ% = 60.0%) (95% CI: 19.2, 59.0 W; P < 0.001) and mean propulsive power by 22.9 W (Mean Δ% = 64.1%) (95% CI: 11.7, 34.1 W; P < 0.001) at loads between 45% and 55% of 1RM. Mean peak power during the 10 repetitions improved by 20.8 W (Mean Δ% = 36.4%) (95% CI: 3.0, 38.6 W; P = 0.011). No significant changes were observed in the control group for any endpoint., Conclusions: An individualized multicomponent exercise program including progressive power training performed over 3 days markedly improved muscle strength and power in acutely hospitalized older patients., (© 2023 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Osteoporosis is a skeletal disease that can increase the risk of fractures, leading to adverse health and socioeconomic consequences. However, current clinical methods have limitations in accurately estimating fracture risk, particularly in older adults. Thus, new technologies are necessary to improve the accuracy of fracture risk estimation. In this observational study, we aimed to explore the association between serum cytokines and hip fracture status in older adults, and their associations with fracture risk using the FRAX reference tool. We investigated the use of a proximity extension assay (PEA) with Olink. We compared the characteristics of the population, functional status and detailed body composition (determined using densitometry) between groups. We enrolled 40 participants, including 20 with hip fracture and 20 without fracture, and studied 46 cytokines in their serum. After conducting a score plot and two unpaired t-tests using the Benjamini-Hochberg method, we found that Interleukin 6 (IL-6), Lymphotoxin-alpha (LT-α), Fms-related tyrosine kinase 3 ligand (FLT3LG), Colony stimulating factor 1 (CSF1), and Chemokine (C-C motif) ligand 7 (CCL7) were significantly different between fracture and non-fracture patients (p < 0.05). IL-6 had a moderate correlation with FRAX (R 2  = 0.409, p < 0.001), while CSF1 and CCL7 had weak correlations with FRAX. LT-α and FLT3LG exhibited a negative correlation with the risk of fracture. Our results suggest that targeted proteomic tools have the capability to identify differentially regulated proteins and may serve as potential markers for estimating fracture risk. However, longitudinal studies will be necessary to validate these results and determine the temporal patterns of changes in cytokine profiles., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Delirium is a neuropsychiatric syndrome associated with increased morbidity and mortality in older patients. The aim of this study was to review predictive biomarkers of delirium in older patients to gain insights into the pathophysiology of this syndrome and provide guidance for future studies. Two authors independently and systematically searched MEDLINE, Embase, Cochrane Library, Web of Science and Scopus databases up to August 2021. A total of 32 studies were included. Only 6 studies were eligible for the meta-analysis, pooled results showed a significant increase in some serum biomarkers (C-reactive protein [CRP], tumour necrosis factor alpha [TNF-α] and interleukin-6 [IL-6]) among patients with delirium (odds ratio = 1.88, 95% CI 1.01 to 1.637; I2 = 76.75%). Although current evidence does not favour the use of any particular biomarker, serum CRP, TNF- α , and IL-6 were the most consistent biomarkers of delirium in older patients., 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., (Copyright © 2023 Lozano-Vicario, García-Hermoso, Cedeno-Veloz, Fernández-Irigoyen, Santamaría, Romero-Ortuno, Zambom-Ferraresi, Sáez de Asteasu, Muñoz-Vázquez, Izquierdo and Martínez-Velilla.)

Delirium is an important cause of morbidity and mortality in older adults admitted to hospital. Multicomponent interventions targeting delirium risk factors, including physical exercise and mobilization, have been shown to reduce delirium incidence by 30-40% in acute care settings. However, little is known about its role in the evolution of delirium, once established. This study is a randomized clinical trial conducted in the Acute Geriatric Unit of Hospital Universitario de Navarra (Pamplona, Spain). Hospitalized patients with delirium who meet the inclusion criteria will be randomly assigned to the intervention or the control group. The intervention will consist of a multicomponent exercise training program, which will be composed of supervised progressive resistance and strength exercise over 3 consecutive days. Functional Near-Infrared Spectroscopy (NIRS) will be used for assessing cerebral and muscle tissue blood flow. The objective is to assess the effectiveness of this intervention in modifying the following primary outcomes: duration and severity of delirium and functional status. This study will contribute to determine the effectiveness of physical exercise in the management of delirium. It will be the first study to evaluate the impact of a multicomponent intervention based on physical exercise in the evolution of delirium., Clinical Trial Registration: ClinicalTrials.gov. identifier: NCT05442892 (date of registration June 26, 2022)., 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., (Copyright © 2022 Lozano-Vicario, Zambom-Ferraresi, Zambom-Ferraresi, de la Casa-Marín, Ollo-Martínez, Sáez de Asteasu, Cedeño-Veloz, Fernández-Irigoyen, Santamaría, Romero-Ortuno, Izquierdo and Martínez-Velilla.)

Background: Different multimorbidity patterns present with different prognoses, but it is unknown to what extent they may influence the effectiveness of an individualized multicomponent exercise program offered to hospitalized older adults., Methods: This study is a secondary analysis of a randomized controlled trial conducted in the Department of Geriatric Medicine of a tertiary hospital. In addition to the standard care, an exercise-training multicomponent program was delivered to the intervention group during the acute hospitalization period. Multimorbidity patterns were determined through fuzzy c-means cluster analysis, over 38 chronic diseases. Functional, cognitive and affective outcomes were considered., Results: Three hundred and six patients were included in the analyses (154 control; 152 intervention), with a mean age of 87.2 years, and 58.5% being female. Four patterns of multimorbidity were identified: heart valves and prostate diseases (26.8%); metabolic diseases and colitis (20.6%); psychiatric, cardiovascular and autoimmune diseases (16%); and an unspecific pattern (36.6%). The Short Physical Performance Battery (SPPB) test improved across all patterns, but the intervention was most effective for patients in the metabolic/colitis pattern (2.48-point difference between intervention/control groups, 95% CI 1.60-3.35). Regarding the Barthel Index and the Mini Mental State Examination (MMSE), the differences were significant for all multimorbidity patterns, except for the psychiatric/cardio/autoimmune pattern. Differences concerning quality of life were especially high for the p sychiatric/cardio/autoimmune pattern (16.9-point difference between intervention/control groups, 95% CI 4.04, 29.7)., Conclusions: Patients in all the analyzed multimorbidity patterns improved with this tailored program, but the improvement was highest for those in the metabolic pattern. Understanding how different chronic disease combinations are associated with specific functional and cognitive responses to a multicomponent exercise intervention may allow further tailoring such interventions to older patients' clinical profile., 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) 2022.)

Background: The increase in life expectancy has led to profound changes in disease prevention and health maintenance. Because of the impact of dysbiosis on the host's health, it is worth considering microbiome-targeted therapies to attenuate or delay age-related perturbations., Aim: The aim of the present review was to systematically evaluate the impact of probiotics, prebiotics, and synbiotics on the major events that affect individuals aged 65 or older., Methods: We performed a literature search in MEDLINE and the Cochrane Central Register of Controlled Trials. Randomized Clinical Trials (RCTs) performed on old people and published between 2009 and 2019 were included., Results: Nine RCTs and 1 secondary analysis (n = 475, 55.8% female) were eligible for inclusion and retrieved in this systematic review. Overall, most interventions resulted in improvements in certain parameters when compared to control (glucose homeostasis, cognitive function, frailty phenotype, gut microbiota profile, immune parameters), while others remained unvariable., Conclusions: The use of probiotics and prebiotics raises a great opportunity to modulate the process of aging and looks promising for health prevention in old adults. However, more RCTs in subjects older than 65 years are needed to elucidate the suitability of these supplementations and establish the underlying potential mechanisms., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Identifying serum biomarkers that can predict physical frailty in older adults would have tremendous clinical value for primary care, as this condition is inherently related to poor quality of life and premature mortality. We compared the serum lipid profile of physically frail and robust older adults to identify specific lipid biomarkers that could be used to assess physical frailty in older patients at hospital admission. Forty-three older adults (58.1% male), mean (range) age 86.4 (78-100 years) years, were classified as physically frail (n = 18) or robust (n = 25) based on scores from the Short Physical Performance Battery (≤ 6 points). Non-targeted metabolomic study by ultra-high performance liquid chromatography coupled to mass spectrometry (UHPLC-MS) analysis with later bioinformatics data analysis. Once the significantly different metabolites were identified, the KEGG database was used on them to establish which were the metabolic pathways mainly involved. Area under receiver-operating curve (AUROC) analysis was used to test the discriminatory ability of lipid biomarkers for frailty based on the Short Physical Performance Battery. We identified a panel of five metabolites including ceramides Cer (40:2), Cer (d18:1/20:0), Cer (d18:1/23:0), cholesterol, and phosphatidylcholine (PC) (14:0/20:4) that were significantly increased in physically frail older adults compared with robust older adults at hospital admission. The most interesting in the physically frail metabolome study found with the KEGG database were the metabolic pathways, vitamin digestion and absorption, AGE-RAGE signaling pathway in diabetic complications, and insulin resistance. In addition, Cer (40:2) (AUROC 0.747), Cer (d18:1/23:0) (AUROC 0.720), and cholesterol (AUROC 0.784) were identified as higher values of physically frail at hospital admission. The non-targeted metabolomic study can open a wide view of the physically frail features changes at the plasma level, which would be linked to the physical frailty phenotype at hospital admission. Also, we propose that metabolome analysis will have a suitable niche in personalized medicine for physically frail older adults., (© 2022. The Author(s).)

Background: Physical exercise is an effective strategy for preserving functional capacity and improving the symptoms of frailty in older adults. In addition to functional gains, exercise is considered to be a cornerstone for enhancing cognitive function in frail older adults with cognitive impairment and dementia. We assessed the effects of the Vivifrail exercise intervention for functional capacity, cognition, and well-being status in community-dwelling older adults., Methods: In a multicentre randomized controlled trial conducted in three tertiary hospitals in Spain, a total of 188 older patients with mild cognitive impairment or mild dementia (aged >75 years) were randomly assigned to an exercise intervention (n = 88) or a usual-care, control (n = 100) group. The intervention was based on the Vivifrail tailored multicomponent exercise programme, which included resistance, balance, flexibility (3 days/week), and gait-retraining exercises (5 days/week) and was performed for three consecutive months (http://vivifrail.com). The usual-care group received habitual outpatient care. The main endpoint was change in functional capacity from baseline to 1 and 3 months, assessed with the Short Physical Performance Battery (SPPB). Secondary endpoints were changes in cognitive function and handgrip strength after 1 and 3 months, and well-being status, falls, hospital admission rate, visits to the emergency department, and mortality after 3 months., Results: The Vivifrail exercise programme provided significant benefits in functional capacity over usual-care. The mean adherence to the exercise sessions was 79% in the first month and 68% in the following 2 months. The intervention group showed a mean increase (over the control group) of 0.86 points on the SPPB scale (95% confidence interval [CI] 0.32, 1.41 points; P < 0.01) after 1 month of intervention and 1.40 points (95% CI 0.82, 1.98 points; P < 0.001) after 3 months. Participants in the usual-care group showed no significant benefit in functional capacity (mean change of -0.17 points [95% CI -0.54, 0.19 points] after 1 month and -0.33 points [95% CI -0.70, 0.04 points] after 3 months), whereas the exercise intervention reversed this trend (0.69 points [95% CI 0.29, 1.09 points] after 1 month and 1.07 points [95% CI 0.63, 1.51 points] after 3 months). Exercise group also obtained significant benefits in cognitive function, muscle function, and depression after 3 months over control group (P < 0.05). No between-group differences were obtained in other secondary endpoints (P > 0.05)., Conclusions: The Vivifrail exercise training programme is an effective and safe therapy for improving functional capacity in community-dwelling frail/prefrail older patients with mild cognitive impairment or mild dementia and also seems to have beneficial effect on cognition, muscle function, and mood status., (© 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.)

This is a reply to the comment by Inzitari et al [...].

Background: Hospitalisation-associated disability due to reduced physical activity levels and prolonged bedrest episodes are highly prevalent in older adults., Objective: To assess the effect of gamified interventions on functional capacity in hospitalised older adults., Methods: A three-armed non-randomised controlled trial with two experimental intervention groups and a control group was conducted in a tertiary public hospital in Navarre, Spain. Participants were allocated to a simple gamification group (SGG) (n = 21), a technology-based gamification group (TGG) (n = 23) or a control group (CG) (n = 26). The end points were changes in functional capacity, muscle strength, cognition, mood status and quality of life., Results: Seventy patients (mean age 86.01 ± 4.27 years old) were included in the study; 29 (41.4%) were women. At discharge, compared to CG, a mean increase of 1.47 points (95%CI, 0.15-2.80 points) and 2.69 points (95%CI, 1.32-4.06 points) was observed (SGG and TGG, respectively) in the SPPB test; as well as an increase of 5.28 points (95%CI, 0.70-9.76 points) in the Barthel Index and 2.03 kg (95%CI, 0.33-3.72 kg) in handgrip strength in the TGG. Regression mediation analyses demonstrated that muscle strength changes (β = 1.30; 95%CI, 0.45-2.14; indirect effect 0.864; 95%CI, 0.09-1.90) significantly mediated the TGG effect on the SPPB score., Conclusions: The TGG intervention programme may provide significant benefits in physical and muscle function over usual care and seems to reverse the functional decline frequently associated with acute hospitalisation in older adults., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Acute care hospitalization increases the likelihood of developing cognitive impairment and delirium in older adults., Objective: To summarize evidence about the effectiveness of exercise and physical rehabilitation interventions on the incidence of delirium and cognitive impairment in acutely hospitalized older patients., Methods: Relevant articles were systematically searched (PubMed, Web of Science, and CINHAL databases) until 26 August 2021. Randomized and nonrandomized controlled trials of in-hospital physical exercise interventions and rehabilitation programs compared to usual care performed for older patients (> 65 years) hospitalized for an acute medical condition were selected. The primary endpoints were changes in the incidence of delirium and cognition during acute hospitalization. The secondary endpoints included functional independence, psychological measures, well-being status, length of hospital stay, transfer after discharge, fall occurrence, hospital readmissions, and mortality rate. The endpoints were evaluated at different time points (at admission, at discharge, and after discharge)., Results: Eleven studies from 8 trials (n = 3,646) were included. The methodological quality of the studies was mostly high. None of the studies reported any adverse events related to the intervention. Early rehabilitation improved cognitive function at 3 months postdischarge (Hedge's g = 0.33, 95% confidence interval [CI] 0.19 to 0.46, p < 0.001). No between-group differences were found for incident delirium and cognitive impairment during hospitalization (all p > 0.05)., Conclusion: In-hospital physical exercise and early rehabilitation programs seem to be safe and effective interventions for enhancing cognitive function after discharge in older patients hospitalized for an acute medical condition. However, no potential benefits were obtained over usual hospital care for the incidence of delirium.

The aim of this article is to present the research protocol for a prospective cohort study that will assess the olfactory function and the effect of an intervention based on olfactory training in healthy very old adults (≥75 years old). A convenience sample of 180 older people (50% female) will be recruited in three different environments: hospitalized control group (CH) with stable acute illness ( n = 60); ambulatory control group (CA) of community-based living ( n = 60); and an experimental odor training group (EOT) from nursing homes ( n = 60). The odor training (OT) intervention will last 12 weeks. All the volunteers will be assessed at baseline; CA and EOT groups will also be assessed after 12 weeks. The primary end point will be change in olfactory capacity from baseline to 12 weeks period of intervention or control. The intervention effects will be assessed with the overall score achieved in Sniffin Sticks Test (SST) - Threshold, Discrimination, and Identification (TDI) extended version. Secondary end points will be changes in cognitive tasks, quality of life, mood, immune status, and functional capacity. All these measurements will be complemented with an immune fitness characterization and a deep proteome profiling of the olfactory epithelium (OE) cultured ex vivo . The current study will provide additional evidence to support the implementation of olfactory precision medicine and the development of immunomodulatory nasal therapies based on non-invasive procedures. The proposed intervention will also intend to increase the knowledge about the olfactory function in very elderly people, improve function and quality of life, and promote the recovery of the health., 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., (Copyright © 2021 Zambom-Ferraresi, Zambom-Ferraresi, Fernández-Irigoyen, Lachén-Montes, Cartas-Cejudo, Lasarte, Casares, Fernández, Cedeño-Veloz, Maraví-Aznar, Uzcanga-Lacabe, Galbete, Santamaría and Martínez-Velilla.)

Introduction: The inverse association between cardiorespiratory fitness and all-cause mortality in apparently healthy populations has been previously reported; however, the existence of this association among adults diagnosed with cancer is unclear., Aim: To determine the association between cardiorespiratory fitness and all-cause mortality in adults diagnosed with cancer., Methods: Medline, Embase, and SPORTDiscus databases were searched. Eligible prospective cohort studies that examined the association of cardiorespiratory fitness with all-cause mortality in adults diagnosed with cancer were included. Hazard ratios (HRs) with associated 95% confidence intervals (CIs) were extracted from studies for all-cause mortality and pooled HRs were calculated using the random-effects inverse-variance model with the Hartung-Knapp-Sidik-Jonkman adjustment., Results: Data from 13 studies with 6,486 adults were included. Compared with lower levels of cardiorespiratory fitness, high levels were associated with a reduced risk of all-cause mortality among adults diagnosed with any cancer (HR = 0.52; 95% CI, 0.35-0.77), lung cancer (HR = 0.62; 95% CI, 0.46-0.83), and among those with cardiorespiratory fitness measurement via indirect calorimetry (HR = 0.47; 95% CI, 0.27-0.80). Pooled HRs for the reduction in all-cause mortality risk per 1-MET increase were also statistically significant (HR = 0.82; 95% CI, 0.69-0.99). Neither age at baseline nor the length of follow-up had a significant influence on the HR estimates for all-cause mortality risk., Conclusion: Cardiorespiratory fitness may confer an independent protective benefit against all-cause mortality in adults diagnosed with cancer. The use of cardiorespiratory fitness as a prognostic parameter might help determine risk for future adverse clinical events and optimize therapeutic management strategies to reduce long-term treatment-related effects in adults diagnosed with cancer., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)