Exercise effects on functional capacity and quality of life in older patients with colorectal cancer: study protocol for the ECOOL randomized controlled trial.

BACKGROUND: Surgery and treatment for colorectal cancer (CRC) in the elderly patient increase the risk of developing post-operative complications, losing functional independence, and worsening health-related quality of life (HRQoL). There is a lack of high-quality randomized controlled trials evaluating the potential benefit of exercise as a countermeasure. The primary aim of this study is to evaluate the effectiveness of a home-based multicomponent exercise program for improving HRQoL and functional capacity in older adults undergoing CRC surgery and treatment. METHODS: This randomized, controlled, observer-blinded, single-center trial aims to randomize 250 patients (>74 years) to either an intervention or a control group (i.e., usual care). The intervention group will perform an individualized home-based multicomponent exercise program with weekly telephone supervision from diagnosis until three months post-surgery. The primary outcomes will be HRQoL (EORTC QLQ-C30; CR29; and ELD14) and functional capacity (Barthel Index and Short Physical Performance Battery), which will be assessed at diagnosis, at discharge, and one, three, and six months after surgery. Secondary outcomes will be frailty, physical fitness, physical activity, inspiratory muscle function, sarcopenia and cachexia, anxiety and depression, ambulation ability, surgical complications, and hospital length of stay, readmission and mortality. DISCUSSION: This study will examine the effects of an exercise program in older patients with CRC across a range of health-related outcomes. Expected findings are improvement in HRQoL and physical functioning. If proven effective, this simple exercise program may be applied in clinical practice to improve CRC care in older patients. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT05448846.

Hip Fracture in Nonagenarians: Characteristics and Factors Related to 30-Day Mortality in 1177 Patients.

BACKGROUND: The number of nonagenarian patients with hip fracture is increasing. The goals of this study were to describe the characteristics and in-hospital course of a cohort of 1177 nonagenarians admitted for hip fracture compared with younger patients and to identify risk factors for 30-day mortality after admission. METHODS: This is a retrospective observational cohort study including patients aged 65 years or older admitted for hip fracture during various periods from February 1997 to December 2016. We defined 3 age groups: 65-79, 80-89, and 90 years and older. We included sociodemographic variables, baseline functional status, comorbidities, fracture and surgical characteristics, postoperative complications, length of stay, and in-hospital and 30-day mortality. Multiple logistic regression analysis was used to study risk factors for 30-day mortality in surgically treated nonagenarians. RESULTS: Nonagenarians were more likely to be women and to have dementia and heart disease. Some 72% walked independently before the fracture. The most relevant treatable risk factor for 30-day mortality in nonagenarians (in terms of higher odds ratio [OR]) was developing respiratory infection (OR: 4.56, 95% confidence interval [CI]: 2.73-7.63). Better prefracture functional status (higher Katz score; OR: 0.83, 95% CI: 0.74-0.92) and spinal anesthesia (OR: 0.19, 95% CI: 0.05-0.68) decreased risk of 30-day mortality. CONCLUSIONS: Nonagenarian patients with hip fracture differ significantly from younger patients concerning clinical characteristics, medical complications, and in-hospital and 30-day mortality rates. We identified several variables on which we could act to reduce 30-day mortality, such as respiratory infection, electrolyte disorders, polypharmacy, cardiac arrhythmia, and spinal anesthesia.

"Inspiratory muscle weakness in acutely hospitalized patients 75 years and over": a secondary analysis of a randomized controlled trial on the effectiveness of multicomponent exercise and inspiratory muscle training.

PURPOSE: The impact of hospitalization for acute illness on inspiratory muscle strength in oldest-old patients is largely unknown, as are the potential benefits of exercise and inspiratory muscle training (IMT) during in-hospital stay. DESIGN AND METHODS: This was a sub-study of a randomized clinical trial that evaluated the efficiency of a multicomponent exercise program in preventing hospitalization-associated disability. Patients were randomized into control (CG) and intervention (IG) groups. The intervention included two daily sessions of supervised walking, squat, balance, and IMT. Baseline and discharge maximal inspiratory pressure (MIP) and inspiratory muscle weakness (IMW) were determined. The effect of the intervention on inspiratory muscle strength was assessed by analyzing (1) the differences between groups in baseline and discharge MIP and IMW, (2) the association, patient by patient, between baseline and discharge MIP, and the improvement index (MIP discharge/baseline) in patients with or without IMW. RESULTS: In total, 174 patients were assessed (mean age of 87), 57 in CG and 117 in IG. Baseline MIP was lower than predicted in both sexes (women 29.7 vs 44.3; men 36.7 vs 62.5 cmH2O, P < 0.001, baseline vs predicted, respectively). More than 65% of patients showed IMW at admission. In women in IG, the mean MIP was higher at discharge than at admission (P = 0.003) and was the only variable that reached expected reference levels at discharge (Measured MIP 39.2 vs predicted MIP 45 cmH2O, P = 0.883). Patients with IMW on admission showed a statistically significant improvement in MIP after the intervention. CONCLUSION: IMW is very prevalent in oldest-old hospitalized with acute illness. Patients might benefit from a multicomponent exercise program including IMT, even during short-stay hospitalization. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NTC03604640. May 3, 2018.

Exercise Intervention and Hospital-Associated Disability: A Nonrandomized Controlled Clinical Trial.

Importance: Inpatient exercise interventions may prevent, at least partly, hospital-associated disability (HAD) in older adults, but whether they also confer clinical benefits in the months following discharge is unclear. Objective: To examine the association of exercise and health education with HAD incidence in hospitalized older adults receiving acute hospital care at discharge and 3 months later. Design, Setting, and Participants: This single-center open-label, nonrandomized controlled clinical trial included patients aged 75 years or older seen at an acute care for elders unit at a tertiary public hospital in Madrid, Spain, from May 1, 2018, to June 30, 2022. Interventions: Patients were allocated to an intervention or control group. Both groups received usual care, but the intervention group also performed a supervised multicomponent exercise program (daily strength, balance, and walking exercises along with inspiratory muscle training) during hospitalization and received health education on how to exercise at home and telephone counseling during follow-up. Main Outcomes and Measures: The primary outcome was HAD incidence (determined by the Katz Index of Independence in Activities of Daily Living [hereafter, Katz Index]) at discharge and after 3 months compared with baseline (ie, 2 weeks before admission). Secondary outcomes included HAD incidence determined by the Barthel Index for Activities of Daily Living, ambulatory capacity decline at discharge and follow-up, changes in physical performance at discharge, and incidence of falls, readmissions, and mortality during the follow-up period. Results: The study included 260 patients (134 women [51.5%]; mean [SD] age, 87.4 [4.9] years [range, 75-105 years]; median hospital length of stay, 7 days [IQR, 5-10 days]), of whom 130 received the intervention and 130 were in the control group. Differences in HAD incidence did not reach statistical significance at discharge (odds ratio [OR], 0.62; 95% CI, 0.37-1.05; P = .08) or follow-up (OR, 0.65; 95% CI, 0.36-1.17; P = .15) when using the Katz Index. A lower HAD incidence was observed in the intervention group at discharge (OR, 0.47; 95% CI, 0.27-0.81; P = .01) and at follow-up (OR, 0.36; 95% CI, 0.20-0.66; P = .001) when using the Barthel Index for Activities of Daily Living. The intervention was also associated with a lesser decline in ambulatory capacity (OR, 0.55; 95% CI, 0.32-0.96; P = .03) and improved physical performance at discharge (Cohen d, 0.39; 95% CI, 0.12-0.65; P = .004). No significant associations were observed for readmissions, falls, or mortality. Conclusions and Relevance: In this nonrandomized controlled clinical trial, an exercise and health education intervention was not significantly associated with reduced HAD incidence when measured by the Katz Index. However, the benefits found for several secondary outcomes might support the implementation of in-hospital exercise programs for older patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03604640.

Functional trajectories associated with acute illness and hospitalization in oldest old patients: Impact on mortality.

Background: The literature pays low attention to functional changes during acute illness in older patients. Our main objectives were to separately describe the different functional changes occurring before and after hospital admission in oldest old medical patients, to investigate their association with mortality, and identify predictors associated with in-hospital failure to recover function. Methods: Secondary analysis of data from a prospective cohort study conducted in a tertiary teaching hospital. The study followed the STROBE criteria. The sample included 604 consecutive patients aged 65 or older hospitalized for acute illness, discharged alive, and not fully dependent at baseline. Activities of daily living measured at baseline, admission, and discharge were used to classify patients into four functional trajectories depending on whether they decline or remain stable between baseline and admission (prehospital) and whether they decline, remain stable, or recover baseline function between admission and discharge (in-hospital). Multivariate models were used to test the association between functional trajectories with mortality, and predictors for in-hospital recovery. Results: Functional trajectories were: "stable-stable" (18%); "decline-recovery" (18%); "decline-no recovery" (53%); "in-hospital decline" (11%). Prehospital decline occurred in 75% and 64% were discharged with worse function than baseline. "In-hospital decline" and "decline-no recovery" trajectories were independently associated with higher 6- and 12-month mortality. Extent of prehospital decline and dementia were predictors of failure to in-hospital recovery. Conclusion: In acutely ill older people, differentiating between prehospital and in-hospital functional changes has prognostic implications. Lack of functional regain at discharge is associated with higher mortality at 6- and 12-months.

[Functional recovery at discharge and at three months after a multicomponent physical exercise intervention in elderly subjects hospitalized in an Acute Geriatric Unit]. / Recuperación funcional al alta y a tres meses tras una intervención multicomponente de ejercicio físico en ancianos hospitalizados en una unidad de agudos de geriatría.

INTRODUCTION: Hospitalization in the elderly, even in short stays, is associated with functional impairment. Once the acute illness is reversed, the evolution of this hospital-generated impairment can be variable, and a year after hospitalization more than half of the elderly patients remain impaired. This impairment is associated with a higher risk of institutionalization, of mortality at discharge and of 30-day mortality. Previous studies have shown how interdisciplinary physical exercise programs can improve functionality at discharge and decrease mortality rate, hospital stay and institutionalization. STUDY DESIGN AND OBJECTIVES: In the Acute Geriatric Unit of the Gregorio Marañon University hospital a randomized controlled trial was carried out to assess the effectiveness of an exercise and health education program to prevent functional decline during hospitalization and at three months after discharge in elderly subjects aged 74 years or older. Patients were excluded if at least one of the following exclusion criteria was met: baseline Barthel Index (15-days prior hospitalization) below 20, severe cognitive impairment or inability to walk. The intervention consisted on a physical exercise program (that included squats, balance, gait stimulation, elastic bands, and inspiratory muscle training) and health education program. The control group received usual care.

Colorectal Cancer in Elderly Patients with Surgical Indication: State of the Art, Current Management, Role of Frailty and Benefits of a Geriatric Liaison.

Six out of every 10 new colorectal cancer (CRC) diagnoses are in people over 65 years of age. Current standardized surgical approaches have proved to be tolerable on the elderly population, although post-operative complications are more frequent than in the younger CRC population. Frailty is common in elderly CRC patients with surgical indication, and it appears to be also associated with an increase of post-operative complications. Fast-track pathways have been developed to assure and adequate post-operative recovery, but comprehensive geriatric assessments (CGA) are still rare among the preoperative evaluation of elderly CRC patients. This review provides a thorough study of the effects that a CGA assessment and a geriatric intervention have in the prognosis of CRC elderly patients with surgical indication.

Impairments of Synaptic Plasticity Induction Threshold and Network Oscillatory Activity in the Hippocampus Underlie Memory Deficits in a Non-Transgenic Mouse Model of Amyloidosis.

In early Alzheimer disease (AD) models synaptic failures and upstreaming aberrant patterns of network synchronous activity result in hippocampal-dependent memory deficits. In such initial stage, soluble forms of Amyloid-ß (Aß) peptides have been shown to play a causal role. Among different Aß species, Aß25-35 has been identified as the biologically active fragment, as induces major neuropathological signs related to early AD stages. Consequently, it has been extensively used to acutely explore the pathophysiological events related with neuronal dysfunction induced by soluble Aß forms. However, the synaptic mechanisms underlying its toxic effects on hippocampal-dependent memory remain unresolved. Here, in an in vivo model of amyloidosis generated by intracerebroventricular injections of Aß25-35 we studied the synaptic dysfunction mechanisms underlying hippocampal cognitive deficits. At the synaptic level, long-term potentiation (LTP) of synaptic excitation and inhibition was induced in CA1 region by high frequency simulation (HFS) applied to Schaffer collaterals. Aß25-35 was found to alter metaplastic mechanisms of plasticity, facilitating long-term depression (LTD) of both types of LTP. In addition, aberrant synchronization of hippocampal network activity was found while at the behavioral level, deficits in hippocampal-dependent habituation and recognition memories emerged. Together, our results provide a substrate for synaptic disruption mechanism underlying hippocampal cognitive deficits present in Aß25-35 amyloidosis model.

Effects of exercise interventions on the functional status of acutely hospitalised older adults: A systematic review and meta-analysis.

BACKGROUND: Acute hospitalisation can have adverse effects in older adults, notably functional decline. We aimed to summarize evidence on the effects of exercise interventions in acutely hospitalised older adults. METHODS: Relevant articles were systematically searched (PubMed, Web of Science, Rehabilitation & Sports Medicine Source, and EMBASE) until 19th March 2020. Randomized controlled trials (RCTs) of in-hospital exercise interventions versus usual care conducted in older adults (>60yrs) hospitalised for an acute medical condition were included. Methodological quality of the studies was assessed with the PEDro scale. Primary outcomes included functional independence and physical performance. Intervention effects were also assessed for other major outcomes (length of hospital stay, incidence of readmission, and mortality). A meta-analysis was conducted when ≥3 studies analysed the same outcome. RESULTS: Fifteen studies from 12 RCTs (n = 1748) were included. Methodological quality of the studies was overall high. None of the studies reported any adverse event related to the intervention. Exercise interventions improved functional independence at discharge (standardized mean difference [SMD] = 0.64, 95% confidence interval = 0.19-1.08) and 1-3 months post-discharge (SMD = 0.29, 95%CI = 0.13-0.43), as well as physical performance (SMD = 0.57, 95%CI = 0.18-0.95). No between-group differences were found for length of hospital stay or risk of readmission or mortality (all p > 0.05). CONCLUSIONS: In-hospital supervised exercise interventions seem overall safe and effective for improving - or attenuating the decline of - functional independence and physical performance in acutely hospitalised older adults. The clinical relevance of these findings remains to be confirmed in future research.

Individual Responsiveness to Physical Exercise Intervention in Acutely Hospitalized Older Adults.

We analyzed inter-individual variability in response to exercise among acutely hospitalized oldest-old adults. In this ancillary analysis of a randomized controlled trial, 268 patients (mean age 88 years) were assigned to a control (n = 125, usual care) or intervention group (n = 143, supervised exercise, i.e., walking and rising from a chair [1-3 sessions/day]). Intervention group patients were categorized as responders, non-responders, or adverse responders (improved, no change, or impaired function in activities of daily living [ADL, Katz index] from hospital admission to discharge, respectively). We analyzed the association between responsiveness to exercise and variables assessed at baseline (2 weeks pre-admission), admission, during hospitalization, at discharge, and during a subsequent 3-month follow-up. An impaired ADL function and worse nutritional status at admission were associated to a greater responsiveness, whereas a better ADL function at admission, longer hospitalization and lower comorbidity index were associated with a poorer response (p < 0.05). Adverse responders had worse outcomes at discharge and during the follow-up (e.g., impaired physical performance and greater fall number) (p < 0.05). Although exercise intervention helps to prevent ADL function decline in hospitalized oldest-old people, a number of them-particularly those with a better functional/health status at admission and longer hospitalization-are at higher risk of being adverse responders, which can have negative short/middle-term consequences.

Effect of a Simple Exercise Program on Hospitalization-Associated Disability in Older Patients: A Randomized Controlled Trial.

OBJECTIVE: Hospitalization-associated disability [HAD, ie, the loss of ability to perform ≥1 basic activities of daily living (ADLs) independently at discharge] is a frequent condition among older patients. The present study assessed whether a simple inpatient exercise program decreases HAD incidence in acutely hospitalized very old patients. DESIGN: In this randomized controlled trial (Activity in Geriatric Acute Care) participants were assigned to a control or intervention group and were assessed at baseline, admission, discharge, and 3 months thereafter. SETTING AND PARTICIPANTS: In total, 268 patients (mean age 88 years, range 75-102) admitted to an acute care for older patients unit of a public hospital were randomized to a control (n = 125) or intervention (exercise) group (n = 143). METHODS: Both groups received usual care, and patients in the intervention group also performed simple supervised exercises (walking and rising from a chair, for a total duration of ∼20 minutes/day). We measured ADL function (Katz index) and incident HAD at discharge and after 3 months (primary outcome) and Short Physical Performance Battery, ambulatory capacity, number of falls, rehospitalization, and death during a 3-month follow-up (secondary outcomes). RESULTS: Median duration of hospitalization was 7 days (interquartile range 4 days). The intervention group had a lower risk of HAD with reference to both baseline [odds ratio (OR) 0.36; 95% confidence interval (CI) 0.17-0.76, P = .007] and admission (OR 0.29; 95% CI 0.10-0.89, P = .030). A trend toward an improved ADL function at discharge vs admission was found in the intervention group compared with controls (OR 0.32; 95% CI ‒0.04 to 0.68; P = .083). No between-group differences were noted for the other endpoints (all P > .05). CONCLUSION AND IMPLICATIONS: A simple inpatient exercise program decreases risk of HAD in acutely hospitalized, very old patients.

Recuperación funcional al alta y a tres meses tras una intervención multicomponente de ejercicio físico en ancianos hospitalizados en una unidad de agudos de geriatría / Functional recovery at discharge and at three months after a multicomponent physical exercise intervention in elderly subjects hospitalized in an Acute Geriatric Unit

Introducción: La hospitalización en ancianos, aún en estancias cortas, se asocia frecuentemente a un deterioro funcional. La evolución de este deterioro una vez revertida la enfermedad aguda que generó la hospitalización es muy variable, observándose que más de la mitad de los pacientes mantiene la discapacidad adquirida incluso un año después del ingreso. Dicha discapacidad se asocia con un mayor riesgo de institucionalización y muerte al alta y a los 30 días. Diversos estudios han demostrado que los programas interdisciplinares de ejercicio físico tienen el potencial de mejorar el estado funcional al alta y además pueden conseguir un descenso de la tasa de mortalidad, de la estancia media y una menor tasa de institucionalización.Diseño y objetivos: El objetivo de este estudio es evaluar la efectividad de un programa de ejercicios y educación sanitaria en la prevención del deterioro funcional durante la hospitalización y a los tres meses en mayores de 74 años, mediante un ensayo clínico aleatorizado en la Unidad de Agudos de Geriatría del Hospital General Universitario Gregorio Marañón. Se excluyeron pacientes con un Barthel basal (15 días antes del ingreso) menor a 20, con deterioro cognitivo severo o incapaces de caminar. La intervención consistió en un programa de ejercicio físico (sentadillas, equilibrio, estimulación de la marcha, bandas elásticas y entrenamiento de la musculatura inspiratoria) y educación sanitaria. El grupo control recibe el cuidado habitual. (AU)

Introduction: Hospitalization in the elderly, even in short stays, is associated with functional impairment. Once the acute illness is reversed, the evolution of this hospital-generated impairment can be variable, and a year after hospitalization more than half of the elderly patients remain impaired. This impairment is associated with a higher risk of institutionalization, of mortality at discharge and of 30-day mortality. Previous studies have shown how interdisciplinary physical exercise programs can improve functionality at discharge and decrease mortality rate, hospital stay and institutionalization.Study design and objectives: In the Acute Geriatric Unit of the Gregorio Marañon University hospital a randomized controlled trial was carried out to assess the effectiveness of an exercise and health education program to prevent functional decline during hospitalization and at three months after discharge in elderly subjects aged 74 years or older. Patients were excluded if at least one of the following exclusion criteria was met: baseline Barthel Index (15-days prior hospitalization) below 20, severe cognitive impairment or inability to walk. The intervention consisted on a physical exercise program (that included squats, balance, gait stimulation, elastic bands, and inspiratory muscle training) and health education program. The control group received usual care. (AU)

Amyloid-ß(25-35) Modulates the Expression of GirK and KCNQ Channel Genes in the Hippocampus.

During early stages of Alzheimer's disease (AD), synaptic dysfunction induced by toxic amyloid-ß (Aß) is present before the accumulation of histopathological hallmarks of the disease. This scenario produces impaired functioning of neuronal networks, altered patterns of synchronous activity and severe functional deficits mainly due to hyperexcitability of hippocampal networks. The molecular mechanisms underlying these alterations remain unclear but functional evidence, shown by our laboratory and others, points to the involvement of receptors/channels which modulate neuronal excitability, playing a pivotal role in early Aß-induced AD pathogenesis. In particular, two potassium channels that control neuronal excitability, G protein-coupled activated inwardly-rectifying potassium channel (GirK), and voltage-gated K channel (KCNQ), have been recently linked to Aß pathophysiology in the hippocampus. Specifically, by using Aß25-35, we previously found that GirK conductance is greatly decreased in the hippocampus, and similar effects have also been reported on KCNQ conductance. Thus, in the present study, our goal was to determine the effect of Aß on the transcriptional expression pattern of 17 genes encoding neurotransmitter receptors and associated channels which maintain excitatory-inhibitory neurotransmission balance in hippocampal circuits, with special focus in potassium channels. For this purpose, we designed a systematic and reliable procedure to analyze mRNA expression by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) in hippocampal rat slices incubated with Aß25-35. We found that: 1) Aß down-regulated mRNA expression of ionotropic GluN1 and metabotropic mGlu1 glutamate receptor subunits as previously reported in other AD models; 2) Aß also reduced gene expression levels of GirK2, 3, and 4 subunits, and KCNQ2 and 3 subunits, but did not change expression levels of its associated GABAB and M1 receptors, respectively. Our results provide evidence that Aß can modulate the expression of these channels which could affect the hippocampal activity balance underlying learning and memory processes impaired in AD.