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
Prevalence and characterization of pain in radiation oncology: the PREDORT multicenter cross-sectional study
(Springer, 2024-07-30) Arias, Fernando; Zarandona, Uxue; Ibáñez Beroiz, Berta; Ibánez, Reyes; Campo, Maider; Cacicedo, Jon; García-Rueda, Noelia; Baztán, Beatriz; Villanueva Goyeneche, Raquel; Fresán, Marta; Redín, Iñaki; Osés, Ana T.; Hurtado, Victoria; Villafranca, Inés; Iancu, Vasti; Almeida, Pilar; Moreno, Nieves; Cadena, Soraya; Carruesco, Irene; Allegue, Marián; González, Ana B.; PREDORT Collaborative Group; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua
Background Pain in cancer patients has enormous impact on their quality-of-life. Radiation therapy (RT) is a cornerstone in cancer treatment. The objective of the PREDORT study is to estimate the prevalence of pain in patients attending at Radiation Oncology (RO) Services. Methods A prospective, multicenter study was designed for patients treated at the RO Services of reference hospitals. Patients were seen in their initial Nursing consultation, during which key data was collected, including demographic and comorbidities data, medical history, and oncological and pain characteristics. The study has received approval from the Ethics Committee of Navarra, and all patients signed the Informed Consent. Results Of the 860 participating patients, 306 reported some type of pain, which implies a prevalence of 35.6%. Of them, 213 identified a cause of oncological origin. The proportion of pain was similar among sexes, but the proportion of non-cancer pain was higher among women (p<0.05). Regarding pain intensity, the magnitude of breakthrough pain in patients with oncological pain is nearly 1 point greater than in patients with non-oncological pain (7.53 vs 6.81; p=0.064). Cancer pain is more likely to be limiting of normal life than non-cancer pain (59% versus 38%, p<0.001). Regarding analgesic treatment, only 60/306 patients (19.6%) were receiving strong opioids. There were 68 patients with pain without any treatment (22.2%). Conclusions The prevalence of pain in cancer patients referred to RO services is 35.6%, with the prevalence of exclusively oncological pain being 24.8%. Understanding and addressing oncological pain is essential to provide comprehensive care to patients.
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
Effect of polygenic risk score, family load of schizophrenia and exposome risk score, and their interactions, on the long-term outcome of first-episode psychosis
(Cambridge University Press, 2023) Cuesta, Manuel J.; Papiol, S.; Ibáñez Beroiz, Berta; García de Jalón, Elena; Sánchez Torres, Ana María; Gil Berrozpe, Gustavo José; Moreno-Izco, Lucía; Zarzuela, Amalia; Fañanás, Lourdes; Peralta Martín, Víctor; SEGPEPs Group; Ciencias de la Salud; Osasun Zientziak
Background. Consistent evidence supports the involvement of genetic and environmental factors, and their interactions, in the etiology of psychosis. First-episode psychosis (FEP) comprises a group of disorders that show great clinical and long-term outcome heterogeneity, and the extent to which genetic, familial and environmental factors account for predicting the long-term outcome in FEP patients remains scarcely known. Methods. The SEGPEPs is an inception cohort study of 243 first-admission patients with FEP who were followed-up for a mean of 20.9 years. FEP patients were thoroughly evaluated by standardized instruments, with 164 patients providing DNA. Aggregate scores estimated in large populations for polygenic risk score (PRS-Sz), exposome risk score (ERS-Sz) and familial load score for schizophrenia (FLS-Sz) were ascertained. Long-term functioning was assessed by means of the Social and Occupational Functioning Assessment Scale (SOFAS). The relative excess risk due to interaction (RERI) was used as a standard method to estimate the effect of interaction of risk factors. Results. Our results showed that a high FLS-Sz gave greater explanatory capacity for longterm outcome, followed by the ERS-Sz and then the PRS-Sz. The PRS-Sz did not discriminate significantly between recovered and non-recovered FEP patients in the long term. No significant interaction between the PRS-Sz, ERS-Sz or FLS-Sz regarding the long-term functioning of FEP patients was found. Conclusions. Our results support an additive model of familial antecedents of schizophrenia, environmental risk factors and polygenic risk factors as contributors to a poor long-term functional outcome for FEP patients.
Open Access
Quality of life in Spanish advanced non-small-cell lung cancer patients: determinants of global QL and survival analyses
(Springer, 2016) Arrarás, Juan Ignacio; Hernández, Berta; Martínez Aguillo, Maite; Cambra Contin, Koldo; Rico, Mikel; Illarramendi, José Juan; Viúdez, Antonio; Ibáñez Beroiz, Berta; Zarandona, Uxue; Martínez, Enrique; Vera García, Ruth; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua
Purpose: This paper studies the Quality of Life (QL) of Spanish advanced non-small-cell lung cancer (NSCLC) patients receiving platinum-doublet chemotherapy, compares our results with those from studies from other cultural areas, and identifies factors associated with global QL and survival prognostic variables. Methods: EORTC QLQ-C30 and QLQ-LC13 questionnaires were completed three times by 39 patients along treatment and follow-up. Univariate and multivariate logistic regression analyses were performed to study global QL determinants (≤50 points considered low global-QL score). Analyses of prognostic variables for death were performed (Cox proportional hazards models). Results: QL mean scores in the whole sample were moderately high, with limitations (>30) in physical, role, social functioning, emotional areas, fatigue, pain, neuropathy and global QL. Differences with studies from other cultural areas were mainly found in the lower score for dyspnoea (≥15 points). There were no significant differences in QL scores between the first and second assessments. In six areas, the third assessment was lower than the first and second: fatigue, hair loss (>20 points); physical, social functioning, neuropathy (10–20 points); emotional functioning (5–10 points). The best model to explain the chances of low QL includes, as explanatory variables, high emotional functioning as protective factor and fatigue as risk factor (R2 = 0.70). Eight QL areas (four pain-related) and performance status showed a statistically significant association with survival. Conclusion: Patients adapted well to their disease and treatments. Platinum-doublet can be administered in advanced NSCLC patients. Our QL data are in line with those from other cultural areas.
Open Access
Cross-national health care database utilization between Spain and France: results from the EPICHRONIC study assessing the prevalence of type 2 diabetes mellitus
(Dove Medical Press, 2018) Moulis, Guillaume; Ibáñez Beroiz, Berta; Palmaro, Aurore; Aizpuru, Felipe; Millán, Eduardo; Lapeyre Mestre, Maryse; Sailler, Laurent; Cambra Contin, Koldo; Ciencias de la Salud; Osasun Zientziak
Aim: the EPICHRONIC (EPIdemiology of CHRONIC diseases) project investigated the possibility of developing common procedures for French and Spanish electronic health care databases to enable large-scale pharmacoepidemiological studies on chronic diseases. A feasibility study assessed the prevalence of type 2 diabetes mellitus (T2DM) in Navarre and the Basque Country (Spain) and the Midi-Pyrénées region (France). Patients and methods: We described and compared database structures and the availability of hospital, outpatient, and drug-dispensing data from 5.9 million inhabitants. Due to differences in database structures and recorded data, we could not develop a common procedure to estimate T2DM prevalence, but identified an algorithm specific to each database. Patients were identified using primary care diagnosis codes previously validated in Spanish databases and a combination of primary care diagnosis codes, hospital diagnosis codes, and data on exposure to oral antidiabetic drugs from the French database. Results: Spanish and French databases (the latter termed Système National d’Information Inter-Régimes de l’Assurance Maladie [SNIIRAM]) included demographic, primary care diagnoses, hospital diagnoses, and outpatient drug-dispensing data. Diagnoses were encoded using the International Classification of Primary Care (version 2) and the International Classification of Diseases, version 9 and version 10 (ICD-9 and ICD-10) in the Spanish databases, whereas the SNIIRAM contained ICD-10 codes. All data were anonymized before transferring to researchers. T2DM prevalence in the population over 20 years was estimated to be 6.6–7.0% in the Spanish regions and 6.3% in the Midi-Pyrénées region with ~2% higher estimates for males in the three regions. Conclusion: tailored procedures can be designed to estimate the prevalence of T2DM in population-based studies from Spanish and French electronic health care records.
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
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
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.