Open Access
Effect of a multicomponent exercise programme (VIVIFRAIL) on functional capacity in frail community elders with cognitive decline: study protocol for a randomized multicentre control trial
(BioMed Central, 2019) Casas Herrero, Álvaro; Antón Rodrigo, Iván; Zambom Ferraresi, Fabrício; López Sáez de Asteasu, Mikel; Martínez Velilla, Nicolás; Elexpuru Estomba, Jaione; Marín Epelde, Itxaso; Ramón Espinoza, Fernanda; Petidier Torregrosa, Roberto; Sánchez Sánchez, Juan Luis; Ibáñez Beroiz, Berta; Izquierdo Redín, Mikel; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua
Background: The benefit of physical exercise in ageing and particularly in frailty has been the aim of recent research. Moreover, physical activity in the elderly is associated with a decreased risk of mortality, of common chronic illnesses (i.e. cardiovascular disease or osteoarthritis) and of institutionalization as well as with a delay in functional decline. Additionally, very recent research has shown that, despite its limitations, physical exercise is associated with a reduced risk of dementia, Alzheimer disease or mild cognitive decline. Nevertheless, the effect of physical exercise as a systematic, structured and repetitive type of physical activity, in the reduction of risk of cognitive decline in the elderly, is not very clear. The purpose of this study aims to examine whether an innovative multicomponent exercise programme called VIVIFRAIL has benefits for functional and cognitive status among pre-frail/frail patients with mild cognitive impairment or dementia. Methods/design: This study is a multicentre randomized clinical trial to be conducted in the outpatient geriatrics clinics of three tertiary hospitals in Spain. Altogether, 240 patients aged 75 years or older being capable of and willing to provide informed consent, with a Barthel Index ≥ 60 and mild cognitive impairment or mild dementia, pre-frail or frail and having someone to help to supervise them when conducting the exercises will be randomly assigned to the intervention or control group. Participants randomly assigned to the usual care group will receive normal outpatient care, including physical rehabilitation when needed. The VIVIFRAIL multicomponent exercise intervention programme consists of resistance training, gait re-training and balance training, which appear to be the best strategy for improving gait, balance and strength, as well as reducing the rate of falls in older individuals and consequently maintaining their functional capacity during ageing. The primary endpoint is the change in functional capacity, assessed with the Short Physical Performance Battery (1 point as clinically significant). Secondary endpoints are changes in cognitive and mood status, quality of life (EQ-5D), 6-m gait velocity and changes in gait parameters (i.e. gait velocity and gait variability) while performing a dual-task test (verbal and counting), handgrip, maximal strength and power of the lower limbs as well as Barthel Index of independence (5 points as clinically significant) at baseline and at the 1-month and 3-month follow-up. Discussion: Frailty and cognitive impairment are two very common geriatric syndromes in elderly patients and are frequently related and overlapped. Functional decline and disability are major adverse outcomes of these conditions. Exercise is a potential intervention for both syndromes. If our hypothesis is correct, the relevance of this project is that the results can contribute to understanding that an individualized multicomponent exercise programme (VIVIFRAIL) for frail elderly patients with cognitive impairment is more effective in reducing functional and cognitive impairment than conventional care. Moreover, our study may be able to show that an innovative individualized multicomponent exercise prescription for these high-risk populations is plausible, having at least similar therapeutic effects to other pharmacological and medical prescriptions.
Open Access
Socioeconomic inequalities in cardiometabolic control in patients with type 2 diabetes
(BioMed Central, 2018) Ibáñez Beroiz, Berta; Galbete Jiménez, Arkaitz; Goñi, María José; Forga, Lluís; Cambra Contin, Koldo; Ciencias de la Salud; Osasun Zientziak
Background: The aim of this study was to determine if the achievement of control targets in patients with type 2 diabetes was associated with personal socioeconomic factors and if these associations were sex-dependent. Methods: This cross-sectional, population-based study was conducted in Spain. Glycated haemoglobin (HbA1c) level and other clinical parameters were obtained from electronic primary care records (n = 32,638 cases). Socioeconomic status was determined using education level and yearly income. Among patients, having their HbA1c level checked during the previous year was considered as an indirect measure of the process of care, whereas tobacco use and clinical parameters such as HbA1c, low-density lipoprotein cholesterol (LDL-c) and blood pressure (BP) were considered intermediate control outcomes. General linear mixed effect models were used to assess associations. Results: The achievement of metabolic and cardiovascular control targets in patients with type 2 diabetes was associated with educational level and income, and socioeconomic gradients differed by sex. The probability of having had an HbA1c test performed in the previous year was higher in patients with lower education levels. Patients in the lowest income and education level categories were less likely to have reached the recommended HbA1c level. Males in the lowest education level categories were less likely to be non-smokers or to have achieved the blood pressure targets. In contrast, patients within the low income categories had a higher probability of reaching the recommended LDL-c level. Conclusions: Our results suggest the presence of socioeconomic inequalities in the achievement of cardiovascular and metabolic control that differed in direction and magnitude depending on the measured outcome and sex of the patient. These findings may help health professionals focus on high-risk individuals to decrease health inequalities.
Open Access
A novel prognostic biomarker panel for early‐stage colon carcinoma
(MDPI, 2021) Azcue Sanromán, Pablo; Guerrero Setas, David; Encío Martínez, Ignacio; Ibáñez Beroiz, Berta; Mercado Gutiérrez, María R.; Vera García, Ruth; Gómez Dorronsoro, María Luisa; Ciencias de la Salud; Osasun Zientziak
Molecular characterization of colorectal cancer has helped us understand better the biology of the disease. However, previous efforts have yet to provide significant clinical value in order to be integrated into clinical practice for patients with early‐stage colon cancer (CC). The purpose of this study was to assess PD‐L1, GLUT‐1, e‐cadherin, MUC2, CDX2, and microsatellite instability (dMMR) and to propose a risk‐panel with prognostic capabilities. Biomarkers were immunohistochemically assessed through tissue microarrays in a cohort of 144 patients with stage II/III colon cancer. A biomarker panel consisting of PD‐L1, GLUT‐1, dMMR, and potentially CDX2 was constructed that divided patients into low, medium, and high risk of overall survival or disease-free survival (DFS) in equally sized groups. Compared with low‐risk patients, medium‐risk patients have almost twice the risk of death (HR = 2.10 (0.99–4.46), p = 0.054), while high‐risk patients have almost four times the risk (HR = 3.79 (1.77–8.11), p = 0.001). The multivariate goodness of fit was 0.756 and was correlated with Kaplan–Meier curves (p = 0.002). Consistent results were found for DFS. This study provides a critical basis for the future development of an immunohistochemical assessment capable of discerning early‐stage CC patients as a function of their prognosis. This tool may aid with treatment personalization in daily clinical practice and improve survival outcomes.
Open Access
Las razones que motivan a estudiar Medicina o Enfermería y el grado de satisfacción con la profesión
(Elsevier, 2022) Pérez Ciordia, Ignacio; Pérez Fernández, Ignacio; Aldaz Herce, Pablo; Ibáñez Beroiz, Berta; Ciencias de la Salud; Osasun Zientziak
Introducción: las razones que motivan a estudiar medicina o enfermería, y el cumplimiento de las expectativas profesionales, son los factores que determinan el volver a realizar los mismos estudios. El objetivo de este estudio es conocer las razones que motivaron a estudiar Medicina o Enfermería, y la relación con la satisfacción laboral en el ejercicio profesional en sanitarios del Sistema Navarro de Salud–Osasunbidea. Metodología: estudio multicéntrico, transversal, con diseño de cuestionario específico. El cuestionario es remitido por correo electrónico a medicina y enfermería de atención primaria y hospitalaria. Consta de 4 apartados: características sociodemográficas, razones que motivaron los estudios, satisfacción con las expectativas y posicionamiento sobre volver a realizar dicha formación. El análisis estadístico incluyó comparación de proporciones, comparación de medias (t de Student) para muestras independientes y modelos de regresión logística uni- y multivariante. Resultados: se recogen 879 cuestionarios (tasa respuesta: 16,9%) en los que predominó el sexo femenino: 94% enfermería; 67% medicina. Las razones vocacionales fueron señaladas como principal motivo de elección de los estudios cursados en ambos colectivos: (85% medicina, 79% enfermería). El 9% de enfermería frente al 27% de profesionales médicos están insatisfechos con su profesión, siendo la «rigidez de la organización» el motivo más frecuente de insatisfacción (p = 0,004). El 21,5% de los profesionales médicos no volvería a realizar los mismos estudios frente al 11% de enfermería (p < 0,001). Al 33% de profesionales médicos y al 28% de enfermería no les gustaría que sus hijos tuvieran la misma formación (p = 0,213). Conclusiones: Las razones vocacionales son el factor determinante en la elección de estos estudios. La rigidez del sistema es el factor más importante de insatisfacción de los profesionales sanitarios, siendo necesaria una mayor flexibilidad en la organización de las tareas.
Open Access
Efficacy and safety of anakinra plus standard of care for patients with severe Covid-19: a randomized phase 2/3 clinical trial
(American Medical Association, 2023) Fanlo Mateo, Patricia; Gracia-Tello, Borja del Carmelo; Fonseca Aizpuru, Eva; Álvarez-Troncoso, Jorge; González, Andrés; Prieto-González, Sergio; Freire, Mayka; Argibay, Ana Belén; Pallarés, Lucio; Todolí, José Antonio; Pérez, Mercedes; Buján-Rivas, Segundo; Ibáñez Beroiz, Berta; Ciencias de la Salud; Osasun Zientziak
Importance: COVID-19 pneumonia is often associated with hyperinflammation. The efficacy and safety of anakinra in treating patients with severe COVID-19 pneumonia and hyperinflammation are still unclear. Objetive: To assess the efficacy and safety of anakinra vs standard of care alone for patients with severe COVID-19 pneumonia and hyperinflammation. Design, Setting, and Participants: The Clinical Trial of the Use of Anakinra in Cytokine Storm Syndrome Secondary to COVID-19 (ANA-COVID-GEAS) was a multicenter, randomized, open-label, 2-group, phase 2/3 clinical trial conducted at 12 hospitals in Spain between May 8, 2020, and March 1, 2021, with a follow-up of 1 month. Participants were adult patients with severe COVID-19 pneumonia and hyperinflammation. Hyperinflammation was defined as interleukin-6 greater than 40 pg/mL, ferritin greater than 500 ng/mL, C-reactive protein greater than 3 mg/dL (rationale, 5 upper normal limit), and/or lactate dehydrogenase greater than 300 U/L. Severe pneumonia was considered if at least 1 of the following conditions was met: ambient air oxygen saturation 94% or less measured with a pulse oximeter, ratio of partial pressure O2 to fraction of inspired O2 of 300 or less, and/or a ratio of O2 saturation measured with pulse oximeter to fraction of inspired O2 of 350 or less. Data analysis was performed from April to October 2021. Interventions: Usual standard of care plus anakinra (anakinra group) or usual standard of care alone (SoC group). Anakinra was given at a dose of 100 mg 4 times a day intravenously. Main Outcomes and Maesures: The primary outcome was the proportion of patients not requiring mechanical ventilation up to 15 days after treatment initiation, assessed on an intention-totreat basis. Results: A total of 179 patients (123 men [69.9%]; mean [SD] age, 60.5 [11.5] years) were randomly assigned to the anakinra group (92 patients) or to the SoC group (87 patients). The proportion of patients not requiring mechanical ventilation up to day 15 was not significantly different between groups (64 of 83 patients [77.1%] in the anakinra group vs 67 of 78 patients [85.9%] in the SoC group; risk ratio [RR], 0.90; 95% CI, 0.77-1.04; P = .16). Anakinra did not result in any difference in time to mechanical ventilation (hazard ratio, 1.72; 95% CI, 0.82-3.62; P = .14). There was no significant difference between groups in the proportion of patients not requiring invasive mechanical ventilation up to day 15 (RR, 0.99; 95% CI, 0.88-1.11; P > .99). Conclusions and relevance: In this randomized clinical trial, anakinra did not prevent the need for mechanical ventilation or reduce mortality risk compared with standard of care alone among hospitalized patients with severe COVID-19 pneumonia. Trial Registration: ClinicalTrials.gov Identifier: NCT04443881
Open Access
Baseline circulating blood cell counts and ratios and changes therein for predicting immune-related adverse events during immune checkpoint inhibitor therapy: a multicenter, prospective, observational, pan-cancer cohort study with a gender perspective
(MDPI, 2024) Teijeira, Lucía; Martínez Kareaga, Mireia; Moreno, Amaia; Elejoste, Ibone de; Ibáñez Beroiz, Berta; Arrazubi, Virginia; Díaz de Corcuera, Isabela; Elejalde, Iñaki; Campillo-Calatayud, Ana; Les Bujanda, Íñigo; Ciencias de la Salud; Osasun Zientziak
Several factors have been associated with the occurrence of immune-related adverse events (irAEs) induced by immune checkpoint inhibitor (ICI) therapy. Despite their availability, the predictive value of circulating blood cell parameters remains underexplored. Our aim was to investigate whether baseline values of and early changes in absolute neutrophil count (ANC), absolute lymphocyte count (ALC), other blood cell counts, and lymphocyte-related ratios can predict irAEs and whether sex may differentially influence this potential predictive ability. Of the 145 patients included, 52 patients (35.8%) experienced at least one irAE, with a 1-year cumulative incidence of 41.6%. Using Fine and Gray competing risk models, we identified female sex (hazard ratio (HR) = 2.17, 95% confidence interval (CI) = 1.20–3.85), high ALC before ICI initiation (HR = 1.63, 95% CI = 1.09–2.45), and low ANC after ICI initiation (HR = 0.81, 95% CI = 0.69–0.96) as predictors of irAEs. However, ALC and ANC may only have an impact on the risk of irAEs in women (stratified for female sex, ALC-related HR = 2.61, 95% CI = 1.40–4.86 and ANC-related HR = 0.57, 95% CI = 0.41–0.81). Priority should be given to developing models to predict ICI-related toxicity and their validation in various settings, and such models should assess the impact of patient sex on the risk of toxicity.
Open Access
Spontaneous parkinsonism is associated with cognitive impairment in antipsychotic-naive patients with first-episode psychosis: a 6-month follow-up study
(Oxford University Press, 2014) Cuesta, Manuel J.; Sánchez Torres, Ana María; García de Jalón, Elena; Campos, María S.; Ibáñez Beroiz, Berta; Moreno-Izco, Lucía; Peralta Martín, Víctor; Ciencias de la Salud; Osasun Zientziak
There is now growing evidence that parkinsonism and other extrapyramidal signs are highly prevalent in patients with first-episode psychosis who have never been exposed to antipsychotic drugs. However, the neurocognitive correlates of parkinsonism in this population remained to be clarified. A sample comprising 100 consecutive drug-naive patients with first-episode psychosis were enrolled on the study and followed up for 6 months. Seventy-seven completed assessments at 3 time points (baseline, 1 mo, and 6 mo), involving clinical and cognitive examinations and a specific assessment of motor abnormalities. The Simpson-Angus Scale (SAS) was used for the assessment of extrapyramidal signs, and each motor domain was evaluated with a standard assessment scale. Linear mixed models were built to explore the longitudinal relationships between parkinsonism scores and cognitive impairment. Parkinsonism scores showed significant strong longitudinal associations with deficits in memory, executive functioning, and attention. Spontaneous parkinsonism (total SAS score and hypokinesia and rigidity subscores at baseline) showed high 6-month predictive values for cognitive impairment. In addition, they also had high predictive values for neurologic soft-sign abnormalities but not for dyskinesia, akathisia, and pure catatonic abnormalities. No predictive value was found for glabella-salivation or tremor subscores on the SAS scale. These results emphasize the relevance of the assessment of parkinsonism signs prior to starting to administer antipsychotic drugs, as core manifestations of psychotic illness with a high predictive value for cognitive impairment.
Open Access
Cardiovascular risk in patients with type 2 diabetes: a systematic review of prediction models
(Elsevier, 2022) Galbete Jiménez, Arkaitz; Tamayo Rodríguez, Ibai; Librero, Julián; Enguita Germán, Mónica; Cambra Contin, Koldo; Ibáñez Beroiz, Berta; Ciencias de la Salud; Osasun Zientziak; Estadística, Informática y Matemáticas; Estatistika, Informatika eta Matematika
Aims: to identify all cardiovascular disease risk prediction models developed in patients with type 2 diabetes or in the general population with diabetes as a covariate updating previous studies, describing model performance and analysing both their risk of bias and their applicability. Methods: a systematic search for predictive models of cardiovascular risk was performed in PubMed. The CHARMS and PROBAST guidelines for data extraction and for the assessment of risk of bias and applicability were followed. Google Scholar citations of the selected articles were reviewed to identify studies that conducted external validations. Results: the titles of 10,556 references were extracted to ultimately identify 19 studies with models developed in a population with diabetes and 46 studies in the general population. Within models developed in a population with diabetes, only six were classified as having a low risk of bias, 17 had a favourable assessment of applicability, 11 reported complete model information, and also 11 were externally validated. Conclusions: there exists an overabundance of cardiovascular risk prediction models applicable to patients with diabetes, but many have a high risk of bias due to methodological shortcomings and independent validations are scarce. We recommend following the existing guidelines to facilitate their applicability.
Open Access
Low serum levels of prealbumin, retinol binding protein, and retinol are frequent in adult type 1 diabetic patients
(Wiley, 2016) Forga, Lluís; Bolado Concejo, Federico; Goñi, María José; Tamayo Rodríguez, Ibai; Ibáñez Beroiz, Berta; Prieto, Carlos; Ciencias de la Salud; Osasun Zientziak
Aim. To determine the serum prealbumin (PA), retinol binding protein (RBP), and retinol levels in adult patients with type 1 diabetes (T1D) and to analyze some factors related to those levels. Methods. A total of 93 patients (47 women) were studied. Age, gender, BMI, duration of diabetes, chronic complications, HbA1c, lipid profile, creatinine, albumin, PA, RBP, and retinol were recorded. High and low parameter groups were compared by Mann-Whitney U and ¿2 tests. Correlation between parameters was analyzed by Spearman's test. Odds of low levels were analyzed by univariate logistic regression and included in the multivariate analysis when significant. Results. 49.5%, 48.4%, and 30.1% of patients displayed serum PA, RBP, and retinol levels below normal values, respectively. A high correlation (Rho > 0.8) between PA, RBP, and retinol serum levels was found. Patients presenting low levels of any of them were predominantly women, normal-weighted, and with lower levels of triglycerides and serum creatinine. No differences in age, macrovascular complications, duration of diabetes, or HbA1c values were observed when comparing low and normal parameter groups. Conclusion. Low serum levels of PA, RBP, and retinol are frequent in T1D adult patients. This alteration is influenced by female sex and serum creatinine and triglyceride levels.
Open Access
Epidemiological study and genetic characterization of inherited muscle diseases in a northern Spanish region
(BioMed Central, 2019) Pagola Lorz, María Inmaculada; Vicente Cemborain, Esther; Ibáñez Beroiz, Berta; Torné, Laura; Elizalde Beiras, Itsaso; García Solaesa, Virginia; González García, Fermín María; Delfrade Osinaga, J.; Jericó Pascual, Ivonne; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua
Background: Inherited muscle diseases are a group of rare heterogeneous muscle conditions with great impact on quality of life, for which variable prevalence has previously been reported, probably due to case selection bias. The aim of this study is to estimate the overall and selective prevalence rates of inherited muscle diseases in a northern Spanish region and to describe their demographic and genetic features. Retrospective identification of patients with inherited muscle diseases between 2000 and 2015 from multiple data sources. Demographic and molecular data were registered. Results: On January 1, 2016, the overall prevalence of inherited muscle diseases was 59.00/ 100,000 inhabitants (CI 95%; 53.35-65.26). Prevalence was significantly greater in men (67.33/100,000) in comparison to women (50.80/100,000) (p = 0.006). The highest value was seen in the age range between 45 and 54 (91.32/100,000) years. Myotonic dystrophy type 1 was the most common condition (35.90/100,000), followed by facioscapulohumeral muscular dystrophy (5.15/100,000) and limb-girdle muscular dystrophy type 2A (2.5/100,000). Conclusions: Prevalence of inherited muscle diseases in Navarre is high in comparison with the data reported for other geographical regions. Standard procedures and analyses of multiple data sources are needed for epidemiological studies of this heterogeneous group of diseases.