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
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
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
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
Adherence of long-term breast cancer survivors to follow-up care guidelines: a study based on real-world data from the SURBCAN cohort
(Springer, 2022) Santiá, Paula; Jansana, Anna; Cura, Isabel del; Padilla-Ruiz, María; Domingo, Laia; Louro, Javier; Comas, Mercé; Sanz, Teresa; Duarte-Salles, Talita; Redondo, Maximino; Ibáñez Beroiz, Berta; Prados-Torres, Alexandra; Castells, Xavier; Sala, María; Ciencias de la Salud; Osasun Zientziak
Purpose: to identify adherence to follow-up recommendations in long-term breast cancer survivors (LTBCS) of the SURBCAN cohort and to identify its determinants, using real-world data. Methods: we conducted a retrospective study using electronic health records from 2012 to 2016 of women diagnosed with incident breast cancer in Spain between 2000 and 2006 and surviving at least 5 years. Adherence to basic follow-up recommendations, adherence according to risk of recurrence, and overall adherence were calculated based on attendance at medical appointments and imaging surveillance, by year of survivorship. Logistic regression models were fitted to depict the association between adherence and its determinants. Results: a total of 2079 LTBCS were followed up for a median of 4.97 years. Of them, 23.6% had survived >= 10 years at baseline. We estimated that 79.5% of LTBCS were overall adherent to at least one visit and one imaging test. Adherence to recommendations decreased over time and no differences were found according to recurrence risk. Determinants of better overall adherence were diagnosis in middle age (50-69 years old), living in a more-deprived area, having fewer years of survival, receiving primary treatment, and being alive at the end of follow-up. Conclusion: we identified women apparently not complying with surveillance visits and tests. Special attention should be paid to the youngest and eldest women at diagnosis and to those with longer survival.
Open Access
Additive effects of a family history of schizophrenia spectrum disorders and an environmental risk score for the outcome of patients with non-affective first-episode psychosis
(Cambridge University Press, 2024) Cuesta Zorita, Manuel Jesús; García de Jalón, Elena; Sánchez Torres, Ana María; Gil Berrozpe, Gustavo José; Aranguren Conde, Lidia; Gutiérrez, Gerardo; Corrales, Asier; Zarzuela, Amalia; Ibáñez Beroiz, Berta; Peralta Martín, Víctor; PEPsNa Group; Ciencias de la Salud; Osasun Zientziak; Gobierno de Navarra / Nafarroako Gobernua
Background: First-episode psychotic disorders comprise a heterogeneous phenotype with a complex etiology involving numerous common small-effect genetic variations and a wide range of environmental exposures. We examined whether a family of schizophrenia spectrum disorder (FH-Sz) interacts with an environmental risk score (ERS-Sz) regarding the outcome of patients with non-affective first episode psychosis (NAFEP). Methods: We included 288 patients with NAFEP who were evaluated after discharge from an intensive 2-year program. We evaluated three outcome measures: symptomatic remission, psychosocial functioning, and personal recovery. We analyzed the main and joint associations of a FH-Sz and the ERS-Sz on the outcomes by using the relative excess risk due to interaction (RERI) approach. Results: A FH-Sz showed a significant association with poor symptomatic remission and psychosocial functioning outcomes, although there was no significant interaction between a FH-Sz and the ERS-Sz on these outcomes. The ERS-Sz did not show a significant association with poor symptomatic remission and psychosocial functioning outcomes, even though the magnitude of the interaction between ERS-Sz and FH-Sz with the later outcome was moderate (RERI = 6.89, 95% confidence interval -16.03 to 29.81). There was no association between a FH-Sz and the ERS-Sz and personal recovery. Conclusions: Our results provide further empirical support regarding the contribution of FH-Sz to poor symptomatic remission and poor psychosocial functioning outcomes in patients with NAFEP.
Open Access
Cohort Profile: CArdiovascular Risk in patients with DIAbetes in NAvarra (CARDIANA cohort)
(BMJ, 2023) Tamayo Rodríguez, Ibai; Librero, Julián; Galbete Jiménez, Arkaitz; Cambra Contin, Koldo; Enguita Germán, Mónica; Forga, Lluís; Goñi, María José; Lecea, Óscar; Gorricho Mendívil, Javier; Olazarán Santesteban, Álvaro; Arnedo Ajona, Laura; Moreno Iribas, Conchi; Lafita, Javier; Ibáñez Beroiz, Berta; Ciencias de la Salud; Osasun Zientziak; Estadística, Informática y Matemáticas; Estatistika, Informatika eta Matematika; Gestión de Empresas; Enpresen Kudeaketa
Purpose The CArdiovascular Risk in patients with DIAbetes in Navarra (CARDIANA cohort) cohort was established to assess the effects of sociodemographic and clinical variables on the risk of cardiovascular events in patients with type 1 (T1D) or type 2 (T2D) diabetes, with a special focus on socioeconomic factors, and to validate and develop cardiovascular risk models for these patients. Participants The CARDIANA cohort included all patients with T1D and T2D diabetes registered in the Public Health Service of Navarra with prevalent disease on 1 January 2012. It consisted of 1067 patients with T1D (ages 2–88 years) and 33842 patients with T2D (ages 20–105 years), whose data were retrospectively extracted from the Health and Administrative System Databases. Findings to date The follow-up period for wave 1 was from 1 January 2012 to 31 December 2016. During these 5 years, 9 patients (0.8%; 95%CI (0.4% to 1.6%)) in the T1D cohort developed a cardiovascular disease event, whereas for the T2D cohort, 2602 (7.7%; 95%CI (7.4% to 8.0%)) had an event. For the T2D cohort, physical activity was associated with a reduced risk of cardiovascular events, with adjusted estimated ORs equal to 0.84 (95% CI 0.66 to 1.07) for the partially active group and 0.71 (95% CI 0.56 to 0.91) for the active group, compared with patients in the non-active group. Future plans The CARDIANA cohort is currently being used to assess the effect of sociodemographic risk factors on CV risk at 5 years and to externally validate cardiovascular predictive models. A second wave is being conducted in late 2022 and early 2023, to extend the follow-up other 5 years, from 1 January 2016 to 31 December 2021. Periodic data extractions are planned every 5 years.