Open Access
Translational approach to secondary hip fracture prevention in older adults: from basic science to clinical practice
(2024) Cedeño Veloz, Bernardo Abel; Martínez Velilla, Nicolás; Izquierdo Redín, Mikel; Ciencias de la Salud; Osasun Zientziak
Esta tesis doctoral versa sobre la relación entre los descubrimientos científicos básicos sobre la salud ósea, la evidencia actual que hay sobre su manejo y su aplicación en el contexto clínico para prevenir fracturas secundarias en adultos mayores. El riesgo de fractura en adultos mayores es un problema de salud pública creciente. La prevención de nuevas fracturas es especialmente preocupante debido al aumento exponencial de la morbimortalidad, así como gasto sanitario asociado asociada. La identificación de la problemática actual, el conocimiento de mecanismos fisiopatológicos específicos en la población mayor, así como intervenciones multifactoriales a la hora de abordar el problema son necesarias de cara a una estrategia novedosa y efectiva de prevención de nuevas fracturas. Esta tesis doctoral se basa en 5 artículos que han sido publicados o están pendiente de en revistas científicas internacionales. En el primer capítulo (Capítulo 1) nuestro objetivo es análisis la evidencia actual sobre la eficacia en el tratamiento farmacológico en la prevención de fracturas de cadera (así como otros eventos de intereses como otras fracturas, marcadores de remodelado óseo, efectos secundarios…). En el segundo capítulo (Capítulo 2), planteamos, mediante una editorial, la importancia de los biomarcadores en la osteoporosis continuará siendo herramientas fundamentales para la medicina geriátrica del futuro al poder apoyar en el proceso diagnóstico, monitorización y tratamiento. En el tercer capítulo (Capítulo 3) realizamos un análisis de biomarcadores en paciente con y sin fractura de cadera para valorar su relación con el riesgo de fractura y su correlación con el mismo. En el cuarto capítulo (Capítulo 4) relacionamos estos mismos marcadores con la fragilidad en adultos mayores con fractura de cadera y su relación con eventos adversos (dependencia, mortalidad, alteración marcha…) en un seguimiento a 3 meses. En el quinto y último capítulo (Capítulo 5) se plantea detallar y validar un sistema piloto de intervención multidominio basado en telerrehabilitación para mejorar la capacidad funcional de los pacientes mayores tras la fractura de cadera.
Open Access
Effects of a multicomponent exercise program in older adults with non-small-cell lung cancer during adjuvant/palliative treatment: an intervention study
(MDPI, 2020) Rosero Rosero, Ilem Dayana; Ramírez Vélez, Robinson; Martínez Velilla, Nicolás; Cedeño Veloz, Bernardo Abel; Morilla Ruiz, Idoia; Izquierdo Redín, Mikel; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua; Universidad Pública de Navarra / Nafarroako Unibertsitate Publikoa
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 10weeks of the program. Results revealed a significant groupxtime 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.
Open Access
Effect of immunology biomarkers associated with hip fracture and fracture risk in older adults
(BMC, 2023) Cedeño Veloz, Bernardo Abel; Lozano Vicario, Lucía; Zambom Ferraresi, Fabrício; Fernández Irigoyen, Joaquín; Santamaría Martínez, Enrique; Rodríguez-García, Alba; Romero Ortuno, Román; Mondragón Rubio, Jaime; Ruiz-Ruiz, Javier; Ramírez Vélez, Robinson; Izquierdo Redín, Mikel; Martínez Velilla, Nicolás; Ciencias de la Salud; Osasun Zientziak; Universidad Pública de Navarra / Nafarroako Unibertsitate Publikoa
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.
Open Access
Impact of a multidisciplinary approach to polypharmacy management in community-dwelling older adults: insights from a specialized outpatient clinic
(Wiley, 2025-02-18) Roncal Belzunce, Victoria; Gutiérrez Valencia, Marta; Cedeño Veloz, Bernardo Abel; San Miguel Elcano, Ramón; Marín Epelde, Itxaso; Galbete Jiménez, Arkaitz; Preciado Goldaracena, Javier; Ezpeleta, María Irache; Garaioa-Aramburu, Karmele; Martínez Velilla, Nicolás; Ciencias de la Salud; Osasun Zientziak
Objectives: The increase in polypharmacy among older adults increases the risk of drug-related problems, making multidisci-plinary interventions essential. This study evaluated the impact of a multidisciplinary polypharmacy consultation on medicationmanagement and outcomes in older outpatients.Methods: This prospective observational study at a Spanish teaching hospital involved geriatricians, clinical pharmacists, andnurses. Older adults (≥ 75 years) with polypharmacy underwent medication review at baseline and at 3 and 6 months. Data onmedication use, adherence to Screening Tool of Older Person's Prescriptions (STOOP) criteria, and anticholinergic burden wereanalyzed.Results: The study included 104 older adults (mean age 86.2 years; 66% female). An average of 3.6 recommendations per par-ticipant was made (63.8% acceptance rate). Common drug-related problems were adverse effects (20%), non-adherence (18.1%), and incorrect dose/regimen (14.4%). Interventions led to an average reduction of 1.7 medications per patient, with 1.3 dosage orregimen changes and 1.1 new prescriptions. The mean number of medications decreased from 9.6 at baseline to 8.9 at 3 months(p < 0.001) and remained below baseline at 6 months. STOPP criteria violations per patient dropped from 1.2 to 1.0 (p = 0.036). Of the 126 medications flagged by STOPP criteria, 68.3% were addressed, 24.6% discontinued, mainly psychotropics, and 89.3%of these discontinuations were maintained. The anticholinergic burden decreased from 1.3 to 1.1 at 3 months (p = 0.036) andremained below baseline at 6 months.Conclusions: A multidisciplinary clinic effectively managed polypharmacy in older adults by reducing medication load andimproving appropriateness per STOPP criteria, highlighting the importance of proactive medication management.Trial Registration: ClinicalTrials.gov: NCT05408598 (March 1, 2022).
Open Access
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
(Frontiers Media, 2022) Lozano Vicario, Lucía; Zambom Ferraresi, Fabíola; Zambom Ferraresi, Fabrício; Casa Marín, Antón de la; Ollo Martínez, Iranzu; López Sáez de Asteasu, Mikel; Cedeño Veloz, Bernardo Abel; Fernández Irigoyen, Joaquín; Santamaría Martínez, Enrique; Romero Ortuno, Román; Izquierdo Redín, Mikel; Martínez Velilla, Nicolás; Ciencias de la Salud; Osasun Zientziak
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.
Open Access
Olfactory characterization and training in older adults: protocol study
(Frontiers Media, 2021) Zambom Ferraresi, Fabíola; Zambom Ferraresi, Fabrício; Fernández Irigoyen, Joaquín; Lachén Montes, Mercedes; Cartas Cejudo, Paz; Lasarte, Juan José; Casares, Noelia; Fernández, Secundino; Cedeño Veloz, Bernardo Abel; Maravi Aznar, Enrique; Uzcanga Lacabe, María Iciar; Galbete Jiménez, Arkaitz; Santamaría Martínez, Enrique; Martínez Velilla, Nicolás; Estadística, Informática y Matemáticas; Estatistika, Informatika eta Matematika; Gobierno de Navarra / Nafarroako Gobernua
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.
Open Access
Biomarkers of delirium risk in older adults: a systematic review and meta-analysis
(Frontiers Media, 2023) Lozano Vicario, Lucía; García Hermoso, Antonio; Cedeño Veloz, Bernardo Abel; Fernández Irigoyen, Joaquín; Santamaría Martínez, Enrique; Romero Ortuno, Román; Zambom Ferraresi, Fabrício; López Sáez de Asteasu, Mikel; Muñoz-Vázquez, Ángel Javier; Izquierdo Redín, Mikel; Martínez Velilla, Nicolás; Ciencias de la Salud; Osasun Zientziak
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.
Open Access
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
(MDPI, 2023) Cedeño Veloz, Bernardo Abel; Casadamon-Munarriz, Irache; Rodríguez-García, Alba; Lozano Vicario, Lucía; Zambom Ferraresi, Fabrício; Gonzalo Lázaro, María; Hidalgo Ovejero, Ángel; Izquierdo Redín, Mikel; Martínez Velilla, Nicolás; Ciencias de la Salud; Osasun Zientziak
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.