Effects of Exercise Intervention for the Management of Delirium in Hospitalized Older Adults: A Randomized Clinical Trial.

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.

Association of postoperative delirium with serum and cerebrospinal fluid proteomic profiles: a prospective cohort study in older hip fracture patients.

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.

Effect of immunology biomarkers associated with hip fracture and fracture risk in older adults.

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 (R2 = 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.

Sarcopenia as a Little-Recognized Comorbidity of Type II Diabetes Mellitus: A Review of the Diagnosis and Treatment.

BACKGROUND: Type II diabetes mellitus (T2DM) is one of the most widespread metabolic diseases worldwide, with a significant impact on morbi-mortality. Sarcopenia has a high risk in this population (two times more risk) and a high impact at the functional level, especially in older adults. In addition, it poses enormous challenges in the diagnosis, prevention, and treatment of this disease concomitantly. The objective is to review the current knowledge on the state of muscle mass and the pathogenesis, diagnosis, and treatment of sarcopenia in people with T2DM. METHODS: A bibliographic search was conducted in the PubMed-Medline databases for articles from 2015 with previously defined terms. RESULTS: A loss of muscle mass in older diabetic patients who are malnourished or at risk of malnutrition has a proven negative impact on their autonomy and is closely related to the risk of sarcopenia as a high-impact disease, and also with frailty, as an associated multidimensional syndrome. Notably, we found that malnutrition and protein deficiency are often underdiagnosed in obese and overweight T2DM patients. Biochemical markers could help in the future with approaches to managing T2DM and sarcopenia concomitantly. The four essential elements which form the basis of care for patients with diabetes and sarcopenia are pharmacological treatment, nutrition management, regular physical exercise, and correct daily regime. CONCLUSIONS: The increasing prevalence of sarcopenia among older patients with T2DM has significant negative impacts on quality of life and is a public health concern. Effective diagnosis and management require a multidisciplinary approach involving pharmacological treatment, nutrition, exercise, and correct daily regime, with future research needed to understand the underlying mechanisms and improve diagnostic and treatment strategies.

Cognitive and functional trajectories in geriatric outpatients after a pharmacologic multidisciplinary intervention: A study protocol.

BACKGROUND: Polypharmacy is a common condition among older adults and is associated with adverse drug reactions and health outcomes, including falls, functional and cognitive impairment, and frailty. METHODS: A prospective observational study will be conducted on older adults with polypharmacy. The aim is to assess the impact of a specialized outpatient clinic focused on pharmacotherapy optimization recently integrated into daily clinical practice in a Spanish public tertiary teaching hospital on patients' functional and cognitive abilities. Patients who attend a first consultation and meet inclusion criteria (≥75 years old, have a life expectancy≥3 months, and polypharmacy (≥5 prescribed medications) will be invited to participate in the study, until reach a calculated sample size of 104 participants. Patients will be excluded if they are enrolled in a clinical trial related to medication or in the event of a no-show or cancellation of the appointment at the first visit. Participants will receive usual care: a first consultation including multidisciplinary pharmacological optimization in the context of a CGA and subsequent face-to-face and/or telephone follow-up (∼3 and ∼6 months). The primary endpoint will be the functional (Barthel index) and cognitive change in capacities (IPCR - Índice de Incapacidad psíquica de la Cruz Roja). Secondary endpoints include medication changes, changes in patients' quality of life, rate of falling, and use of healthcare resources. DISCUSSION: We expect that the close collaboration between professionals from different disciplines working together will be an effective strategy to improve the functional and cognitive abilities of older adults. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05408598 (March 1, 2022).

Specialized Care Resources for Diagnosis and Management of Patients Who Have Suffered Falls: Results of a National Survey in Geriatric Units.

INTRODUCTION: Clinical guidelines recommend comprehensive multifactorial assessment and intervention to prevent falls and fractures in older populations. METHODS: A descriptive study was conducted by the Falls Study Group of the Spanish Geriatric Medicine Society (SEMEG) to outline which types of healthcare-specific resources were assigned for fall assessment in Spanish geriatric departments. A self-reported seven-item questionnaire was delivered from February 2019 to February 2020. Where geriatric medicine departments were not available, we tried to contact geriatricians working in those areas. RESULTS: Information was obtained regarding 91 participant centers from 15 autonomous communities, 35.1% being from Catalonia and 20.8% from Madrid. A total of 21.6% reported a multidisciplinary falls unit, half of them in geriatric day hospitals. Half of them reported fall assessment as part of a general geriatric assessment in general geriatric outpatient clinics (49.5%) and, in 74.7% of cases, the assessment was based on functional tests. A total of 18.7% reported the use of biomechanical tools, such as posturography, gait-rides or accelerometers, for gait and balance analysis, and 5.5% used dual X-ray absorptiometry. A total of 34% reported research activity focused on falls or related areas. Regarding intervention strategies, 59% reported in-hospital exercise programs focused on gait and balance improvement and 79% were aware of community programs or the pathways to refer patients to these resources. CONCLUSIONS: This study provides a necessary starting point for a future deep analysis. Although this study was carried out in Spain, it highlights the need to improve public health in the field of fall prevention, as well as the need, when implementing public health measures, to verify that these measures are implemented homogeneously throughout the territory. Therefore, although this analysis was at the local level, it could be useful for other countries to reproduce the model.

Biomarkers of delirium risk in older adults: a systematic review and meta-analysis.

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.

Clinical and Demographic Characteristics of Centenarians versus Other Age Groups Over 75 Years with Hip Fractures.

Objective: The primary objective was to describe the clinical characteristics, management, and outcomes of centenarians with fragility hip fracture and compare them to other age groups. The secondary objective was to determine the variables associated with length of stay, in-hospital mortality and 30-day mortality. Materials and Methods: This is a secondary analysis of the Spanish National Hip Fracture Registry. We included patients ≥75 years admitted for fragility hip fractures in 86 Spanish hospitals between 2017 and 2019, dividing the sample into four age groups. The variables studied were baseline characteristics, type of fracture, management, length of stay, in-hospital mortality and 30-day mortality. Results: We included 25,938 patients (2888 were 75-79 years old; 14,762 octogenarians; 8,035 nonagenarians and 253 centenarians). Of the centenarians, 83% were women, 33% had severe dementia, 9% had severe dependency and 36% lived in residential care homes. Six out of ten had intertrochanteric fracture. Length of hospital stay was 8.6 days; in-hospital mortality was 10.3% and 30-day mortality 20.9%. Older age groups had more women, severe functional dependency, severe dementia, intertrochanteric fracture, living in care facilities and being discharged to nursing care. They had less frequent early mobilization, osteoporosis treatment and discharge to rehabilitation units. In-hospital and 30-day mortality were higher with increasing age. In centenarians, time to surgery >48 hours was independently associated with length of stay (correlation coefficient 3.99 [95% CI: 2.35-5.64; p<0.001]) and anaesthetic risk, based on an ASA score of V, was related to 30-day mortality (ASA score II [OR 0.25, 95% CI: 0.09-0.70; p=0.009] and ASA score III [OR 0.43, 95% CI: 0.19-0.96; p=0.039]). Conclusion: Centenarians had different clinical characteristics, management and outcomes. Although centenarians had worse outcomes, nearly 4 out of 5 centenarians were alive one month after surgery.

Effect of a Multicomponent Intervention with Tele-Rehabilitation and the Vivifrail© Exercise Programme on Functional Capacity after Hip Fracture: Study Protocol for the ActiveFLS Randomized Controlled Trial.

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.

Profile and 3-month evolution of geriatric patients after a hip fracture followed-up at a Fracture Liaison Service (FLS).

INTRODUCTION: There are few studies on Fracture Liaison Service (FLS) that evaluate older patients after a hip fracture (HF) through comprehensive geriatric assessment. We aim to determine these patients' characteristics, outcomes, and prescribed treatments. METHODS: A retrospective observational study of a cohort of patients older than 65 years admitted with HFs to an orthogeriatric unit between February 25th (2013) and December 16th (2016). After hospitalization, those patients with a good baseline social, functional, and cognitive situation were referred to the FLS. A comprehensive geriatric assessment and treatment adjustment were conducted. A comparison between FLS patients and HF patients non-referred was made. RESULTS: From 1887 patients admitted to the orthogeriatric unit, 469 (23%) were referred to the FLS. Of those, 335 were women (77.2%) and 337 (77.6%) lived in the community. The FLS patients had a better functional status (97.1% of the patients with independent gait versus 79.2%) than non-FLS patients (p<0.001). After 3 months in the FLS, 356 (82%) patients had independent gait and had improved their analytical values. Antiosteoporotic treatment was prescribed to 322 patients (74%), vitamin D supplements to 397 (91.5%), calcium to 321 (74%), and physical exercise to 421 (97%). CONCLUSIONS: Patients referred to an FLS were younger, with a better functional and cognitive situation. At hospital discharge, they frequently presented gait impairment and laboratory abnormalities (anemia, hypoproteinemia, vitamin D deficiency) that presented good recovery due to the patient's previous baseline. These patients benefit from comprehensive treatment (pharmacological and non-pharmacological).

Profile and 3-month evolution of geriatric patients after a hip fracture followed-up at a Fracture Liaison Service (FLS) / Perfil y evolución a 3 meses de pacientes con fractura de cadera evaluados en una unidad de coordinación de fracturas (Fracture Liaison Service [FLS])

Introduction: There are few studies on Fracture Liaison Service (FLS) that evaluate older patients after a hip fracture (HF) through comprehensive geriatric assessment. We aim to determine these patients’ characteristics, outcomes, and prescribed treatments.Methods: A retrospective observational study of a cohort of patients older than 65 years admitted with HFs to an orthogeriatric unit between February 25th (2013) and December 16th (2016). After hospitalization, those patients with a good baseline social, functional, and cognitive situation were referred to the FLS. A comprehensive geriatric assessment and treatment adjustment were conducted. A comparison between FLS patients and HF patients non-referred was made.Results: From 1887 patients admitted to the orthogeriatric unit, 469 (23%) were referred to the FLS. Of those, 335 were women (77.2%) and 337 (77.6%) lived in the community. The FLS patients had a better functional status (97.1% of the patients with independent gait versus 79.2%) than non-FLS patients (p<0.001). After 3 months in the FLS, 356 (82%) patients had independent gait and had improved their analytical values. Antiosteoporotic treatment was prescribed to 322 patients (74%), vitamin D supplements to 397 (91.5%), calcium to 321 (74%), and physical exercise to 421 (97%).Conclusions: Patients referred to an FLS were younger, with a better functional and cognitive situation. At hospital discharge, they frequently presented gait impairment and laboratory abnormalities (anemia, hypoproteinemia, vitamin D deficiency) that presented good recovery due to the patient's previous baseline. These patients benefit from comprehensive treatment (pharmacological and non-pharmacological). (AU)

Introducción: Hay pocos estudios sobre las unidades de coordinación de fracturas (Fracture Liaison Services [FLS]) que evalúen a pacientes mayores tras una fractura de cadera (FC) a través de una valoración geriátrica integral. Nuestro objetivo es determinar las características de estos pacientes, los resultados y los tratamientos prescritos.Métodos: Estudio observacional retrospectivo de una cohorte de mayores de 65años ingresados tras fractura de cadera (FC) entre el 25 de febrero de 2013 y el 31 de diciembre de 2016 en una unidad de ortogeriatría. Tras el alta hospitalaria, los pacientes con buen soporte social y buena situación funcional y cognitiva fueron citados en la FLS. Se realizó una evaluación geriátrica integral y un ajuste del tratamiento. Dichos pacientes se compararon con pacientes con fractura de cadera no derivados a esta unidad.Resultados: Un total de 1.887 pacientes ingresaron en la unidad de ortogeriatría, y 469 (23%) fueron derivados a la FLS. De ellos, 335 fueron mujeres (77,2%) y 337 (77,6%) vivían en el domicilio. Los atendidos en la FLS tuvieron mejor funcionalidad (97,1% de pacientes con deambulación independiente versus 79,2%) que los no incluidos (p<0,001). A los 3meses en la FLS, 356 (82%) pacientes presentaban deambulación independiente y habían mejorado sus valores analíticos. Se prescribieron antiosteoporóticos a 332 pacientes (74%), suplementos de vitaminaD a 397 (91,5%), calcio a 321 (74%) y ejercicio físico a 421 (97%).Conclusiones: Los pacientes atendidos en una FLS fueron más jóvenes, con mejor situación funcional y cognitiva. Al alta hospitalaria, frecuentemente presentaron inestabilidad de la marcha y alteraciones analíticas (anemia, hipoproteinemia, déficit de vitamina D) que tuvieron buena evolución dado el estado previo del paciente. Estos pacientes se benefician de un tratamiento integral (farmacológico y no farmacológico). (AU)

Effectiveness of a multicomponent exercise training program for the management of delirium in hospitalized older adults using near-infrared spectroscopy as a biomarker of brain perfusion: Study protocol for a randomized controlled trial.

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).

Olfactory Characterization and Training in Older Adults: Protocol Study.

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.

Effects of a Multicomponent Exercise Program in Older Adults with Non-Small-Cell Lung Cancer during Adjuvant/Palliative Treatment: An Intervention Study.

Clinical intervention studies support the efficacy and safety of exercise programs as a treatment modality for non-small-cell lung cancer (NSCLC) during adjuvant/palliative treatment, but the effectiveness of real-world oncogeriatric services is yet to be established. We aimed to examine the effects of a 10-week structured and individualized multicomponent exercise program on physical/cognitive functioning and mental wellness in elderly patients with NSCLC under adjuvant therapy or palliative treatment. A non-randomized, opportunistic control, longitudinal-design trial was conducted on 26 patients with NSCLC stage I-IV. Of 34 eligible participants, 21 were allocated into two groups: (i) control group (n = 7) received usual medical care; and (ii) intervention group (n =19) received multicomponent program sessions, including endurance, strength, balance, coordination and stretching exercises. Tests included the Short Physical Performance Battery (SPPB), 5-m habitual Gait Velocity Test (GVT), Timed Up & Go Test (TUG), 6-Min Walk Test (6MWT), independence of activities in daily living (IADL), muscular performance, cognitive function, and quality of life, which were measured at baseline and after 10 weeks of the program. Results revealed a significant group×time interaction for SPPB (p = 0.004), 5-m GVT (p = 0.036), TUG (p = 0.007), and muscular performance (chest and leg power; p < 0.001). Similarly, significant changes were observed between groups for cognitive functioning (p = 0.021) and quality of life for EUROQoL 5D (p = 0.006). Our findings confirm that a multicomponent exercise program improves measures of physical/cognitive functioning and quality of life in the elderly with NSCLC under adjuvant therapy or palliative treatment. This is an interesting and important study that adds to our current body of knowledge on the safety of exercise interventions, especially in the elderly with solid tumors.