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.

Deprescribing Opportunities for Frail Residents of Nursing Homes: A Multicenter Study in Australia, China, Japan, and Spain.

OBJECTIVE: Deprescribing opportunities may differ across health care systems, nursing home settings, and prescribing cultures. The objective of this study was to compare the prevalence of STOPPFrail medications according to frailty status among residents of nursing homes in Australia, China, Japan, and Spain. DESIGN: Secondary cross-sectional analyses of data from 4 cohort studies. SETTING AND PARTICIPANTS: A total of 1142 residents in 31 nursing homes. METHODS: Medication data were extracted from resident records. Frailty was assessed using the FRAIL-NH scale (non-frail 0-2; frail 3-6; most-frail 7-14). Chi-square tests and prevalence ratios (PRs) were used to compare STOPPFrail medication use across cohorts. RESULTS: In total, 84.7% of non-frail, 95.6% of frail, and 90.6% of most-frail residents received ≥1 STOPPFrail medication. Overall, the most prevalent STOPPFrail medications were antihypertensives (53.0% in China to 73.3% in Australia, P < .001), vitamin D (nil in China to 52.7% in Australia, P < .001), lipid-lowering therapies (11.1% in Japan to 38.9% in Australia, P < .001), aspirin (13.5% in Japan to 26.2% in China, P < .001), proton pump inhibitors (2.1% in Japan to 32.0% in Australia, P < .001), and antidiabetic medications (12.3% in Japan to 23.5% in China, P = .010). Overall use of antihypertensives (PR, 1.15; 95% CI, 1.06-1.25), lipid-lowering therapies (PR, 1.78; 95% CI, 1.45-2.18), aspirin (PR, 1.31; 95% CI, 1.04-1.64), and antidiabetic medications (PR, 1.31; 95% CI, 1.00-1.72) were more prevalent among non-frail and frail residents compared with most-frail residents. Antihypertensive use was more prevalent with increasing frailty in China and Japan, but less prevalent with increasing frailty in Australia. Antidiabetic medication use was less prevalent with increasing frailty in China and Spain but was consistent across frailty groups in Australia and Japan. CONCLUSIONS AND IMPLICATIONS: There were overall and frailty-specific variations in prevalence of different STOPPFrail medications across cohorts. This may reflect differences in prescribing cultures, application of clinical practice guidelines in the nursing home setting, and clinician or resident attitudes toward deprescribing.

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.

Effects of short-term multicomponent exercise intervention on muscle power in hospitalized older patients: A secondary analysis of a randomized clinical trial.

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.

Change in physical activity and systolic blood pressure trajectories throughout mid-life and the development of dementia in older age: the HUNT study.

BACKGROUND: There is lack of research on combinations of possible modifiable risk factors for dementia in a life-time perspective. Dementia has currently no cure, and therefore new knowledge of preventive factors is important. The purpose of this study is to investigate if changes in physical activity (PA) in combinations with systolic blood pressure (SBP) trajectories in mid to late life are related to development of dementia in older age. METHODS: This prospective cohort study uses data from four consecutive surveys of the HUNT Study, Norway. Dementia was assessed in the HUNT4 70 + sub-study (2017-19). Group-based trajectory modelling identified three SBP trajectories from HUNT1 (1984-86) to HUNT3 (2006-2008): low, middle, and high. Change in PA was categorized into four groups based on high or low PA level at HUNT1 and HUNT3 and were combined with the SBP trajectories resulting in 12 distinct categories. Logistic regression was used to estimate odds ratios (ORs) of dementia. RESULTS: A total of 8487 participants (55% women, mean age (SD) 44.8 (6.5) years at HUNT1) were included. At HUNT4 70 + , 15.2% had dementia. We observed an overall decrease in OR of dementia across the PA/SBP categories when ranked from low to high PA (OR, 0.96; 95% CI, 0.93 to 1.00, P = 0.04). Within PA groups, a low SBP trajectory was associated with lower OR for dementia, apart from those with decreasing PA. The strongest association was observed for people with stable high PA and low SBP trajectory (OR, 0.38; 95% confidence interval (CI), 0.13 to 1.10 and adjusted risk difference, -8.34 percentage points; 95% CI, -15.32 to -1.36). CONCLUSION: Our findings illustrate the clinical importance of PA and SBP for dementia prevention and that favorable levels of both are associated with reduced occurrence of dementia.

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.

Hand grip strength, short physical performance battery, and gait speed: key tools for function in Non-Hodgkin Lymphoma.

This study aimed to determine which performance assessment tools included in Comprehensive Geriatric Assessment (CGA) are the most sensitive for the functional approach in the initial evaluation and during the therapy of old adults diagnosed with Diffuse Large B-Cell Lymphoma (DLBCL). We prospectively recruited 31 patients aged 70 years or older presenting for an initial consultation in the Hematology Clinic of a tertiary hospital. We implemented an updated physical performance evaluation as part of CGA at baseline and during treatment. Baseline characteristics of the sample were compared according to age, Geriatric 8 (G8), frailty, Short Physical Performance Battery (SPPB), and sarcopenia measured by hand grip strength (HGS). Functional changes were monitored during the treatment period using HGS, gait speed (GS) and SPPB. The mean age was 79.0 (5.5) years and 51.6% of the sample was frail; 65,5% were treated with standard chemotherapy and 35,5% with a therapeutic regimen with attenuated doses. All the assessment tools included in CGA found functional differences at baseline when the sample was stratified and compared according to frailty, sarcopenia, and SPPB, but not according to G8 score and age. Only SPPB was able to detect functional differences between groups stratified by age at baseline. GS was the only score that identified clinically significant functional changes during the treatment. In conclusion, HGS and SPPB are appropriate performance scores to complete the functional approach in the initial hematologic evaluation, and GS is a promising option to detect functional decline during therapy in old adults with DLBCL.

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).

Treatment Individualization in Diffuse Large B-Cell Lymphoma: Is Frailty Enough for Old Adults? An Original Article.

INTRODUCTION: Toxicity risk evaluation based on frailty assessment is recommended for treatment individualization in old adults with diffuse large B-cell lymphoma (DLBCL). However, no specific assessment method to guide decision-making has been established yet. Here, we implement a therapeutic algorithm based on the information obtained in an updated comprehensive geriatric assessment (CGA) to assess the value that other prognostic factors add to frailty. MATERIAL AND METHODS: We prospectively recruited 31 patients aged 70 or older recently diagnosed with DLBCL. Standard dose regimen R-CHOP and dose-attenuated R-miniCHOP were the therapeutic options. A CGA-based algorithm was used for the initial treatment recommendation. The sample was compared according to frailty and treatment allocation to describe baseline differential characteristics and treatment tolerance. RESULTS: Mean age was 79 (SD: 5.5) and 45.1% were above 80. Half of the patients (51.6%) were frail; their survival was inferior to that observed in fit adults (p: .034). The mean Short Physical Performance Battery (SPPB) score of patients responding to therapy was higher than non-responders´ media (8.6 vs. 5.9; p: .022). However, when RCHOP was allocated to high functional patients within fit and frail groups, no differences in survival were found compared to R-miniCHOP. The prevalence of toxic events was higher with the standard regimen in fit (p: .054) and frail patients (p: 0.016). CONCLUSIONS: The combination of frailty and physical performance assessment in an algorithm is a promising method to guide the decision-making process in old adults with DLBCL. SPPB might complete frailty predictive information on toxicity risk.

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.

Association Between Cardiorespiratory Fitness and Incident Purchase of Hypnotic Drugs in Adults: The HUNT Study.

OBJECTIVE: To assess whether cardiorespiratory fitness (CRF) is associated with first purchase of a prescribed hypnotic drug in the adult population. METHODS: A total of 34,357 adult participants (53.9% women) with a mean age of 51.5 years (SD 15.6 years) from the third Trøndelag Health Study (HUNT) of 2006 to 2008 were observed until January 1, 2018. Cardiorespiratory fitness was estimated from a validated nonexercise algorithm. Data on first hypnotics prescription were obtained through linkage to the National Norwegian Prescription Database. Cox regression with 95% CIs was used to estimate hazard ratios (HRs). RESULTS: After 304,899 person-years of follow-up, 5791 participants had their first registered purchase of prescribed hypnotics, corresponding to an incidence rate of 1.90 per 100 person-years. Each 1-metabolic equivalent of task increase in CRF was significantly associated with 5% (HR, 0.95; 95% CI, 0.91 to 0.99; P=.02) and 4% (HR, 0.96; 95% CI, 0.92 to 1.00; P=.046) risk reduction for incident use of hypnotics in men and women, respectively. When CRF was categorized into tertiles with lowest CRF as the reference group, reduced risk was 13% (HR, 0.87; 95% CI, 0.79 to 0.96; P=.006) and 15% (HR, 0.85; 95% CI, 0.77 to 0.95; P=.003) for men in the intermediate and highest CRF category, respectively. In women with highest CRF, the reduced risk was 5% (HR, 0.95; 95% CI, 0.87 to 1.03; P=.22). CONCLUSION: Cardiorespiratory fitness in adulthood is associated with incident purchase of prescription medication commonly used for sleep problems. These findings suggest that fitness should be considered a target for preventing sleep problems in adults.

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.

Specific multimorbidity patterns modify the impact of an exercise intervention in older hospitalized adults.

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 psychiatric/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.

Servicios de geriatría hospitalarios: desde la evidencia a la implementación real en España / Departments of Geriatric Medicine: From evidence to actual implementation in Spain

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