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Treatment-resistant depression and intranasal esketamine: Spanish clinical consensus on practical aspects
(Universidad de Zaragoza, 2025-05-02) Ramos Quiroga, Josep Antoni; Mora Mínguez, Fernando; Arostegui, Silvia; Cardoner, N. (Narcís); Etxeandia Pradera, Jon-Iñaki; Gómez Juanes, Rocío; Gómez Revuelta, Marcos; Montes, José Manuel; Vieta i Pascual, Eduard, 1963-
Background: Pharmacological management of major depressive disorder has traditionally relied on antidepressants targeting the monoaminergic pathway. Treatment-resistant depression (TRD) patients have been frequently excluded from registrational trials, resulting in a lack of clear clinical recommendations for an optimised management. In recent years, treatments based on other mechanisms of action have been developed and approved. Intranasal esketamine is a novel non-monoaminergic treatment directed to improve neuroplasticity through the modulation of the glutamatergic system. In this clinical consensus we aimed to provide expert guidance on the use of intranasal esketamine for TRD patients based in our clinical practice in Spain. Methods: A scientific committee of nine psychiatrists, experts in TRD in Spain, reviewed the literature (grey literature and articles/scientific communications published in English or Spanish between January 2014 and January 2024 in PubMed). Statements on practical aspects of TRD management with intranasal esketamine were developed in a first meeting following a discussion group approach, refined in a second meeting with a nominal group technique, and finally drafted after consensus in a third meeting. Results: We recommend a treatment algorithm for the management of TRD with intranasal esketamine. Recommendations were made for specific clinical profiles with other psychiatric comorbidities, which are not contraindications, and for patients who do not have at least a 50 % reduction in symptoms during the first induction phase (partial responders at the end of an induction phase). Treatment should be given in the same health centre where the patient normally receives mental care. The patient’s clinical progress will determine early optimisation of intranasal esketamine dose during the induction phase, the need for flexible doses/
Sobre las voluntades anticipadas: aspectos bioéticos, jurídicos y sociales
(Elsevier España, 2013-01) Casado, María; Lecuona Ramírez, Itziar de; Royes, A. (Albert)
From an interdisciplinary perspective, the article analyzes the bioethical, legal and social aspects of advance directives, tools that grant autonomy in health care with legal recognition. The authors systematize the legal framework of advance directives while characterizing their features and possible contents and highlighting the practical issues. As a complement to that analysis, the article emphasizes the importance of disclosing the nature of advance directives and addresses an asymmetric situation: legal recognition for these documents does not contribute to a social debate about the autonomy in health care, despite it being particularly needed. Summarizing, this article deals with one of the hot topics in bioethics: the right to make anticipated autonomous and informed decisions about the end of life in the health care context.
Effects of alcohol-related problems on the costs of frequent emergency department use: an economic analysis of a case–control study in Spain
(Frontiers Media, 2024-12-03) Gual, Antoni; López Pelayo, Hugo; Balcells-Oliveró, Mercè; Oliveras, Clara; Bruguera Soler, Pol; Cordero Torres, Imanol; Millán Hernández, Andrea; Pons Cabrera, Maria Teresa; Guzmán Cortez, Pablo Rodrigo; Gómez Ramiro, Marta; Vázquez, Mireia; Borràs, Roger; Asenjo Romero, Maria; Vieta i Pascual, Eduard, 1963-
Introduction: Alcohol-related problems increase the probability of frequent emergency department (ED) use. In this study, we compared the direct healthcare expenses incurred during a single visit among frequent and non-frequent ED users and analyzed the impact of alcohol-related issues in healthcare costs arising from ED usage. Methods: The study relied on secondary analyses of economic data from a 1:1 matched case-control study with the primary aim of identifying the clinical characteristics of hospital ED frequent users in a Mediterranean European environment with a public, universal, and tax-funded health system. The participants ranged in age from 18 to 65 years and underwent ED visits at a high-complexity Spanish hospital (cases ≥5 times, controls <5) from December 2018 to November 2019. Each case was matched to a control with the same age, gender, and date of attendance at the ED. Clinical data and direct healthcare costs for a single ED visit were obtained by a retrospective review of the first electronic medical register. Costs and duration of stay were compared between cases and controls using paired-samples t-tests, and ED users with and without alcohol-related problems were compared using bivariate (independent-samples t-tests, one-way analysis of variance, Chi square tests, and multiple linear regression) and multivariate analyses (multiple linear regression models with backward stepwise selection algorithm, and dependent variable: total mean direct costs). Results: Among 609 case-control pairs (total n = 1218), mean total healthcare direct costs per ED visit were 22.2% higher among frequent compared with non-frequent users [mean difference 44.44 euros; 95% confidence interval (CI) 13.4-75.5; t(608) = 2.811; p = 0.005]. Multiple linear regression identified length of stay, triage level, ambulance arrival, and the specialty discharging the patient as associated with total healthcare costs for frequent users. In bivariate analyses, a history of alcohol-related problems was associated with a 32.5% higher mean total healthcare costs among frequent users [mean difference 72.61 euros; 95% confidence interval 25.24-119.97; t(320.016) = 3.015; p = 0.003]. Conclusion: The findings confirm the high cost of frequent ED use among people with alcohol-related problems, suggesting that costs could be reduced through implementation of intervention protocols.
A novel patient-derived 3D model recapitulates mantle cell lymphoma lymph node signaling, immune profile and in vivo ibrutinib responses
(Springer Nature, 2023-04-08) Araujo Ayala, Ferran; Dobaño-López, Cèlia; Garcia Valero, Juan; Nadeu Prat, Ferran; Gava, Fabien; Faria, Carla; Norlund, Marine; Morin, Renaud; Bernes-Lasserre, Pascale; Serrat Aymerich, Neus; Playa-Albinyana, Heribert; Giménez Martínez, Rubén; Campo Güerri, Elias; Lagarde, Jean-Michel; López Guillermo, Armando; Giné Soca, Eva; Colomer Pujol, Dolors; Bezombes, Christine; Pérez Galán, Patricia
Mantle cell lymphoma (MCL), a rare and aggressive B-cell non-Hodgkin lymphoma, mainly develops in the lymph node (LN) and creates a protective and immunosuppressive niche that facilitates tumor survival, proliferation and chemoresistance. To capture disease heterogeneity and tumor microenvironment (TME) cues, we have developed the first patient-derived MCL spheroids (MCL-PDLS) that recapitulate tumor oncogenic pathways and immune microenvironment in a multiplexed system that allows easy drug screening, including immunotherapies. MCL spheroids, integrated by tumor B cells, monocytes and autologous T-cells self-organize in disc-shaped structures, where B and T-cells maintain viability and proliferate, and monocytes differentiate into M2-like macrophages. RNA-seq analysis demonstrated that tumor cells recapitulate hallmarks of MCL-LN (proliferation, NF-kB and BCR), with T cells exhibiting an exhaustion profile (PD1, TIM-3 and TIGIT). MCL-PDLS reproduces in vivo responses to ibrutinib and demonstrates that combination of ibrutinib with nivolumab (anti-PD1) may be effective in ibrutinib-resistant cases by engaging an immune response with increased interferon gamma and granzyme B release. In conclusion, MCL-PDLS recapitulates specific MCL-LN features and in vivo responses to ibrutinib, representing a robust tool to study MCL interaction with the immune TME and to perform drug screening in a patient-derived system, advancing toward personalized therapeutic approaches.
Chronic lymphocytic leukemia patient-derived xenografts recapitulate clonal evolution to Richter transformation
(Springer Nature, 2023-11-28) Playa-Albinyana, Heribert; Arenas Ríos, Fabián; Royo, Romina; Giró, Ariadna; López Oreja, Irene; Aymerich, Marta; López Guerra, Mónica; Frigola, Gerard; Beà Bobet, Sílvia M.; Delgado, Julio (Delgado González); Garcia-Roves, Pablo M.; Campo Güerri, Elias; Nadeu Prat, Ferran; Colomer Pujol, Dolors
Chronic lymphocytic leukemia (CLL) is a B-cell neoplasm with a heterogeneous clinical behavior. In 5-10% of patients the disease transforms into a diffuse large-B cell lymphoma known as Richter transformation (RT), which is associated with dismal prognosis. Here, we aimed to establish patient-derived xenograft (PDX) models to study the molecular features and evolution of CLL and RT. We generated two PDXs by injecting CLL (PDX12) and RT (PDX19) cells into immunocompromised NSG mice. Both PDXs were morphologically and phenotypically similar to RT. Whole-genome sequencing analysis at different time points of the PDX evolution revealed a genomic landscape similar to RT tumors from both patients and uncovered an unprecedented RT subclonal heterogeneity and clonal evolution during PDX generation. In PDX12, the transformed cells expanded from a very small subclone already present at the CLL stage. Transcriptomic analysis of PDXs showed a high oxidative phosphorylation (OXPHOS) and low B-cell receptor (BCR) signaling similar to the RT in the patients. IACS-010759, an OXPHOS inhibitor, reduced proliferation, and circumvented resistance to venetoclax. In summary, we have generated new RT-PDX models, one of them from CLL cells that mimicked the evolution of CLL to RT uncovering intrinsic features of RT cells of therapeutical value
Agreement and reproducibility between 3DStent vs. Optical Coherence Tomography for evaluation of stent area and diameter
(Springer Verlag, 2024-10-28) Ruberti, Andrea; Rinaldi, Riccardo; Occhipinti, Giovanni; Ramus, Liliane; Guagliumi, Giulio; Sabaté Tenas, Manuel; Brugaletta, Salvatore
3DStent is a novel rotational angiography imaging capable of 3D reconstruction and measuring stent area and diameter, without need for intravascular imaging. To compare 3DStent and OCT-derived stent area and diameter after PCI. Patients with de novo coronary lesions who underwent treatment with a single DES and evaluated by OCT and 3DStent were included. Stent area and diameter were measured by 3DStent, at abluminal, mid and endoluminal side and by OCT. From September 2023 to February 2024 six coronary lesions were analyzed. Post-PCI stent area measured by OCT was (mean +/- standard deviation) 7.03 +/- 2.85 mm(2) and by 3DStent 9.41 +/- 2.79 mm(2), 7.21 +/- 2.23 mm(2) and 5.63 +/- 1.83 mm(2) at abluminal, mid and endoluminal side, respectively. Stent diameter by OCT was 2.93 +/- 0.58 mm, and by 3DStent 3.27 +/- 0.50 mm, 2.86 +/- 0.49 mm and 2.52 +/- 0.45 mm at abluminal, mid and endoluminal side, respectively. Significant correlation was observed between OCT and 3DStent in relation to stent area (Exp(B) 3.35, mean of difference 0.19 +/- 1.01 mm(2), 95%CI -1.80-2.17 mm(2), p < 0.001) and diameter (Exp(B) 3.18, mean difference - 0.07 +/- 0.18 mm, 95%CI -0.43-0.30 mm, p < 0.001), particularly when 3DStent measurements performed at the mid side. Very high reproducibility was demonstrated by intra- and inter-observer analysis (r = 0.92 and r = 0.93 respectively). 3DStent appears to be an easy and reproducible tool to assess post-PCI stent area and diameter as compared to OCT.
The PADRIS-PRESTO Cohort: A Comprehensive Population-Based Study on Mental Health in Catalonia
(Cambridge University Press (CUP), 2025-12-01) De Prisco, Michele; Oliva, Vincenzo; Fico, Giovanna; Mas, Ariadna; Valenzuela-Pascual, Clàudia; Montejo Egido, Laura; Bort, Marta; Sommerhof, Constanza; Bortolozzi, Analia; Miquel Rio, Lluís; Vilella, Elisabet; Forte, Maria Florencia; Fortea, Lydia; Fernández-Plaza, Tábatha; Giménez Palomo, Anna; Sagué-Vilavella, Maria; Madero Gómez, Santiago; Llorca-Bofí, Vicent; Bioque Alcázar, Miquel; Grande i Fullana, Iria; Murru, Andrea; Pacchiarotti, Isabella; Cavero Álvarez, Myriam; Blanch Andreu, Jordi; Viñas-Bardolet, Clara; Aparicio-Nogué, Vicenç; Martínez-Cerdá, Juan Francisco; Parellada Rodón, Eduard; Martínez-Arán, Anabel, 1971-; Radua, Joaquim; Vieta i Pascual, Eduard, 1963-; Hidalgo Mazzei, Diego; Anmella, Gerard
Background: Mental disorders affect nearly 970 million people worldwide, impacting individuals and healthcare systems. Large population databases offer insights often unattainable in smaller studies, but their findings may not always generalize across diverse regions. To address this, we introduce a European cohort from Catalonia, Spain, allowing for comparisons between individuals with mental disorders and the general population. Methods: Data were obtained from the “Programa d’analítica de dades per a la recerca i la innovació en salut” (PADRIS). The cohort included all individuals who accessed public specialized mental health services between 2015 and 2019, with retrospective follow-up extending to 2010. These individuals, referred to as cases, were matched by age, sex, and health region with controls, individuals who had no interactions with mental health services during the same period. Sociodemographic and clinical characteristics, including psychiatric diagnoses, comorbidities, smoking status, healthcare utilization, and prescribed treatments, were analyzed. Results: The study included 1,421,510 individuals (mean age: 41.6±22.1; 53.6% female), with 473,812 cases and 947,698 controls. Cases were more likely to be exempt from income reporting, be ever-smokers, and have musculoskeletal comorbidities. A total of 1,547,374 psychiatric diagnoses were recorded, with anxiety (31.38%) and mood disorders (18.83%) being the most frequent. Over the follow-up, 76.2 million primary care visits and 67.1 million prescriptions were recorded. Conclusions: This cohort enhances our understanding of mental health service use, diagnostic trends, and treatment patterns in Catalonia. The insights derived from this cohort have the potential to inform mental health policies, improving outcomes within and beyond the region.
Psychometric validation of the self-administered French version of the Functioning Assessment Short Test (FAST): Factor structure, reliability, validity, and sociodemographic predictors
(Universidad de Zaragoza, 2025-10-01) Uyttersprot, Audrey; Bellaert, Nellia; Vieta i Pascual, Eduard, 1963-; Invernizzi, Sandra; Ris, Laurence; Lefebvre, Laurent
Background and objectives: The Functioning Assessment Short Test (FAST) is widely used to assess psychosocial functioning across psychiatric conditions. Despite extensive international validation, a validated French version of the self-administered FAST is currently lacking. This study aimed to evaluate the psychometric properties of the self-administered French FAST in a general adult population. Methods: A total of 508 French-speaking adults aged 18–65 completed the FAST alongside standardized measures of depression and anxiety. Exploratory and confirmatory factor analyses and bifactor modeling evaluated the original six-factor structure. Reliability was assessed using Cronbach’s alpha and McDonald’s omega. Convergent validity was evaluated through multitrait-multimethod (MTMM) analysis and correlations with depression and anxiety. Generalized additive models (GAMs) examined non-linear associations between symptom severity and FAST scores, controlling for demographic covariates. Results: The original six-factor structure was confirmed, and the bifactor model further supported interpretation of both total and subscale scores. Reliability was strong for the total FAST score (α = .86; ω = .90), whereas subscale reliability (α = .58–.80), with lower values for autonomy, cognitive, and leisure. MTMM analysis demonstrated moderate-to-high monotrait correlations (.51–.84), and moderate correlations with depressive (r =.46) and anxiety (r = .35) symptoms, supporting convergent validity. GAM analyses revealed a non-linear relationship between depressive symptoms and psychosocial impairment (edf = 2.91, F = 19.87, p < .001), alongside significant effects of anxiety (p = .024) and employment status (p = .003). Conclusions: The French self-administered FAST demonstrates robust psychometric properties and appears suitable for assessing psychosocial functioning in general adult populations, though caution is advised when interpreting autonomy, cognitive, and leisure subscales in non-clinical samples until further clinical validation is available.
Collaborative Outcomes Study on Health and Functioning During Infection Times (COH-FIT): Global and Risk-Group Stratified Course of Well-Being and Mental Health During the COVID-19 Pandemic in Adolescents
(Elsevier, 2025-04-01) Solmi, Marco
Objective: To identify the COVID-19 pandemic impact on well-being/mental health, coping strategies, and risk factors in adolescents worldwide. Method: This study was based on an anonymous online multi-national/multi-language survey in the general population (representative/weighted non-representative samples, 14-17 years of age), measuring change in well-being (World Health Organization-Five Well-Being Index [WHO-5]/range = 0-100) and psychopathology (validated composite P-score/range = 0-100), WHO-5 <50 and <29, pre- vs during COVID-19 pandemic (April 26, 2020-June 26, 2022). Coping strategies and 9 a priori- defined individual/cumulative risk factors were measured. A χ2, penalized cubic splines, linear regression, and correlation analyses were conducted. Results: Analyzing 8,115 of 8,762 initiated surveys (representative = 75.1%), the pre-pandemic WHO-5 and P-score remained stable during the study (excluding relevant recall bias/drift), but worsened during the pandemic by 5.55 ± 17.13 (SD) and 6.74 ± 16.06 points, respectively (effect size d = 0.27 and d = 0.28). The proportion of adolescents with WHO-5 scores suggesting depression screening (<50) and major depression (<29) increased from 9% to 17% and 2% to 6%. WHO-5 worsened (descending magnitude, with cumulative effect) in adolescents with a mental or physical disorder, female gender, and with school closure. Results were similar for the P-score, with the exception of school closure (not significant) and living in a low-income country, as well as not living in a large city (significant). Changes were significantly but minimally related to COVID-19 deaths/restrictions, returning to near-pre-pandemic values after >2 years. The 3 most subjectively effective coping strategies were Internet use, exercise/walking, and social contacts. Conclusion: Overall, well-being/mental health worsened (small effect sizes) during the early stages of the COVID-19 pandemic, especially in vulnerable subpopulations. Identified at-risk groups, association with pandemic-related measures, and coping strategies can inform individual behaviors and global public health strategies.
Confidencialidad. Recomendaciones del Grupo de Bioética de la Sociedad Española de Medicina Intensiva Crítica y Unidades Coronarias (SEMICYUC)
(Elsevier España, 2009-11) Pacheco, M. Virtudes; Martín Delgado, María Cruz; Nolla Salas, Miquel; Arias Garrido, José Julián; López Camps, Vicent; Saralegui, Iñaki; Cabré, Lluís; Lecuona Ramírez, Itziar de; Abizanda, Ricard; Clemente García, Remedios; de Miguel, E.; Montáns Araújo, Marta; Zaforteza Lallemand, Concha; García Sanz, Mercedes; Sánchez Segura, Juan M.; Grupo de Bioética de la SEMICYUC
Confidencialidad deriva etimológicamente de “fidelidad” en el sentido del deber que se debe hacía otro. Como palabra es la cualidad de CONFIANZA, y ésta define aquella característica por la que esperamos que el otro no nos traicione en nuestras expectativas o proyectos. De ahí la expresión de quebrantar la confianza utilizada cuando alguien haga mal uso de la información, que en un sentido amplio, tiene con referencia o respecto a nosotros. En Medicina y en general en las ciencias de la salud, la confidencialidad hace referencia al uso limitado de la información clínica y social que, del paciente, tiene el personal sanitario. El de privacidad (en castellano sería más correcto denominarse intimidad) hace referencia a la protección de la autoimagen, fundamentalmente pública, a la que tiene derecho todo individuo, y que constituye, después de la propia vida y la salud, el valor más preciado de la persona, al que ha dedicado gran parte de sus esfuerzos. Estas ideas están profundamente relacionadas con las de confidencia2,3,4. Durante todo el texto se van a citar varias leyes y recomendaciones relativas a la confidencialidad, por dicho motivo y para ayudar al lector hemos confeccionado un anexo (Anexo I) con enlace electrónico de dichas normativas legales
Ethics committees: The challenges facing 21st century bioethics
(Springer Nature, 2011-06) Lecuona Ramírez, Itziar de
This article argues that 21st century bioethics should focus on improving ethics committees and its procedures. Backed by international bodies as UNESCO and states the implementation of ethics infrastructures as necessary for approaching the ethical issues related to medicine, life sciences and associated technologies have become a way of “doing” bioethics irrespective of their scope and, from a critical point of view, with a certain degree of distortion in their creation. Likewise, the article predicts that the union between bioethics and human rights supported by the Universal Declaration on Bioethics and Human Rights will mark the future of bioethics, placing the committees in a strategic position, as mechanisms to put in practice the principles it establishes. The union between bioethics and human rights shows that defining bioethics remains a challenge. In relation to this issue the article points out the basic traces of the discipline and its contents. It also points out the evolution from bioethics of an autonomist nature to a 21st century bioethics with a marked social character that ethics committees should put into practice integrating principles as social responsability and health in bioethical reflection trying to solve and eradicate inequalities. Orientation of research and development in nanotechnology provides an example of the ideas this article aims to present, and specifically how ethics committees have a key role in 21st century bioethics.
Análisis de la Declaración Universal sobre Bioética y Derechos Humanos de la UNESCO: un referente en bioética y en investigación (e innovación responsable) en seres humanos
(Universidad de Deusto, 2016-09) Lecuona Ramírez, Itziar de
Over 10 years after the adoption of the UNESCO´s Universal Declaration on Bioethics and Human Rights, this international legal non binding instrument should be considered a benchmark in bioethics and scientific research in human beings. To this end, the article analyzes the background, nature and scope of the Declaration, as well as its structure and content. The study highlights research ethics committees -their character, composition, and functions-, that the Declaration situates in a strategic position to advocate a bioethics into action through these interdisciplinary bodies: not only to review research projects, but to train and sensitize in bioethics. As a starting point, the usefulness and timeliness of the Declaration is claimed, in a context such as Europe, which is committed to 'responsible research and innovation'. A new concept where ethics is one of its axes with issues such as gender equality, governance, scientific education, open access and public engagement in decision-making related to the generation and application of knowledge. These are questions that, since 2005, have been included in the Declaration, by establishing principles and procedures consistent with this new nomenclature which transmits old messages and classic goals in bioethics, particularly from the perspective of scientific research in human beings and its review and control by research ethics committees.
Review of biomedical research and innovation that uses emergent technologies and personal data: the challenges facing research ethics committees in a data-driven society.
(Universidad de Deusto, 2021-06) Lecuona Ramírez, Itziar de
The article analyses the challenges posed using emerging technologies and personal data in health research and innovation and the changes that must therefore occur in the evaluation processes carried out by the research ethics committees. Data-driven decision making is a political commitment of the European Union that includes personalized medicine, more efficient healthcare systems and active ageing and wellbeing. Protecting individuals through the protection of their personal data is the task of the research ethics committees in the field of biomedical research. The guidelines that were established in research ethics in biomedical research people in the analogical society are largely ineffective in the digital society. Nowadays, we have stopped being anonymous to be reidentifiable due to the vast amount of data accumulated in different databases. Thus, the article examines the principles, rights and guarantees that the General Data Protection Regulation establishes to reach conclusions and proposals in order to found the requirements that the research ethics committees must evaluate and check in research and innovation in the biomedical field for the proper protection of individuals. In addition, the work reviews the nature and composition of the research ethics committees. The goal is to contribute to the doctrinal debate and to have an impact in the daily activity of research ethics committees.
Exploring the dynamic relationships between nocturnal heart rate, sleep disruptions, anxiety levels, and depression severity over time in recurrent major depressive disorder
(Elsevier B.V., 2025-02-07) Condominas, Elena; Sánchez Niubò, Albert; Domènech Abella, Joan; Haro Abad, Josep Maria; Bailon, Raquel; Giné Vázquez, Iago; Riquelme, Gemma; Matcham, Faith; Lamers, Femke; Kontaxis, Spyridon; Laporta, Estela; García Pagès, Esther; Peñarrubia Maria, Maria Teresa; White, Katie M.; Oetzmann, Carolin; Annas, Peter; Hotopf, Matthew; Penninx, Brenda W. J. H.; Narayan, Vaibhav A.; Folarin, Amos A.; Leightley, Daniel; Cummins, Nicholas; Ranjan, Yatharth; de Girolamo, Giovanni; Preti, Antonio; Simblett, Sara; Wykes, Til; Myin Germeys, Inez; Dobson, Richard J. B.; Siddi, Sara; RADAR-CNS consortium
Background: Elevated night resting heart rate (HR) has been associated with increased depression severity, yet the underlying mechanisms remain elusive. This study aimed to investigate the mediating role of sleep disturbance and the influence of anxiety on the relationship between night resting HR and depression severity. Methods: This is a secondary data analysis of data collected in the Remote Assessment of Disease and Relapse (RADAR) Major Depressive Disorder (MDD) longitudinal mobile health study, encompassing 461 participants (1774 observations) across three national centers (Netherlands, Spain, and the UK). Depression severity, anxiety, and sleep disturbance were assessed every three months. Night resting HR parameters in the 2 weeks preceding assessments were measured using a wrist-worn Fitbit device. Linear mixed models and causal mediation analysis were employed to examine the impact of sleep disturbance and anxiety on night resting HR on depression severity. Covariates included age, sex, BMI, smoking, alcohol consumption, antidepressant use, and comorbidities with other medical conditions. Results: Higher night resting HR was linked to subsequent depressive severity, through the mediation of sleep disturbance. Anxiety contributed to an exacerbated level of sleep disturbance, subsequently intensifying depression severity. Anxiety exhibited no direct effect on night resting HR. Conclusions: Our findings underscore the mediating role of sleep disturbance in the effect of night resting HR on depression severity, and anxiety on depression severity. This insight has potential implications for early identification of indicators signalling worsening depression symptoms, enabling clinicians to initiate timely and responsive treatment measures.
Sex-stratified mortality estimates in people with schizophrenia: A systematic review and meta-analysis of cohort studies of 2,700,825 people with schizophrenia
(Elsevier B.V., 2025-02-01) Høye, Anne; Koyanagi, Ai; Larsson, Henrik; Lehto, Kelli; Lindgren, Peter; Manchia, Mirko; Nordentoft, Merete; Skonieczna-Żydecka, Karolina; Stubbs, Brendon; Vancampfort, Davy; Bitter, István; Vieta i Pascual, Eduard, 1963-; Gorwood, Philip; De Prisco, Michele; Taipale, Heidi; Boyer, Laurent; Tiihonen, Jari; Højlund, Mikkel; Cortese, Samuele; Correll, Christoph U.; Dragioti, Elena; Rietz, Ebba Du; Nielsen, Rene Ernst; Firth, Joseph; Fusar-Poli, Paolo; Solmi, Marco; Croatto, Giovanni; Fabiano, Nicholas; Wong, Stanley; Gupta, Arnav; Fornaro, Michele; Schneider, Lynne Kolton; Rohani-Montez, S. Christy; Fairley, Leanne; Smith, Nathalie; Hartman, Catharina; Holt, Richard I. G.
The differential influence of sex on premature mortality in schizophrenia is unclear. This study assessed the differences in all-cause and specific cause mortality risks in people with schizophrenia compared to several control groups stratified by sex. Weconducted a PRISMA 2020-compliant systematic review and random-effects metaanalysis of cohort studies assessing mortality relative risk (RR) for people with schizophrenia, comparing by sex. We measured publication bias and conducted a quality assessment through the Newcastle-Ottawa scale. We meta analyzed 43 studies reporting on 2,700,825 people with schizophrenia. Both males and females with schizophrenia had increased all-cause mortality vs. comparison groups (males, RR=2.62, 95%CI 2.35-2.92; females, RR=2.56, 95%CI 2.27-2.87), suicide (males, RR=9.02, 95%CI 5.96-13.67; females, RR=12.09, 95%CI 9.00-16.25), and natural cause mortality (males, RR=2.11, 95%CI 1.88-2.38; females, RR=2.14, 95%CI 1.93-2.38). No statistically significant differences in sex-dependent mortality risk emerged. There was an age-group-dependent increased mortality risk in females < 40 years vs. >/=40 years old (RR=4.23/2.17), and significantly higher risk of death due to neurological disorders (dementia) in males vs. females (RR=5.19/2.40). Increased mortality risks were often associated with specific modifiable risk factors. There were minimal statistically significant differences in sex-dependent mortality risks in people with schizophrenia. However, it revealed areas of targeted intervention efforts.
Association between dietary (poly)phenol intake and the ATHLOS Healthy Ageing Scale in the Polish arm of the HAPIEE study
(Springer Nature, 2024-07-10) Stepaniak, Urszula; Grosso, Giuseppe; Polak, Maciej; Gradowicz-Prajsnar, Barbara; Kozela, Magdalena; Bobak, Martin; Sánchez Niubò, Albert; Stefler, Denes; Haro Abad, Josep Maria; Pajak, Andrzej
Inverse association between (poly)phenol intake and age-related disorders has been demonstrated; however, little is known whether they affect comprehensively assessed healthy aging. The aim of this study was to evaluate the associations between the intake of (poly)phenol (including selected classes and subclasses) and healthy aging scores related to biopsychosocial aspects of health and functioning. A cross-sectional study was performed using data on 9774 randomly selected citizens of Krakow (Poland) who were 45–69 years of age. Dietary (poly)phenol intake was evaluated using a food frequency questionnaire and matching food consumption data with the Phenol-Explorer database. The healthy aging scores were estimated from the ATHLOS Healthy Ageing Scale (HAS) developed by the Ageing Trajectories of Health-Longitudinal Opportunities and Synergies (ATHLOS) consortium. Beta coefficients were calculated using multivariable linear regression models. In multivariable adjusted models, there were significant positive associations between the ATHLOS HAS score and intake of total (poly)phenols (b per increase of 100 mg/day = 0.081; 95% CI, 0.050; 0.112) and among main classes of (poly)phenols with phenolic acids (b = 0.139; 95% CI, 0.098; 0.180). Intake of remaining classes of (poly)phenols (flavonoids, lignans, stilbenes, and others) was not related to the ATHLOS HAS score. Among individual classes studied, hydroxycinnamic acids, flavonols, flavones, and dihydrochalcones were associated with better healthy aging. The findings suggest the beneficial effect of total dietary (poly)phenol and some classes and subclasses of (poly)phenol intake in terms of healthy aging in Poland. These findings should be confirmed in other settings and with prospective data.
European perspectives on big data applied to health: The case of biobanks and human databases
(John Wiley & Sons) Lecuona Ramírez, Itziar de; Villalobos Quesada, María José
The paradigm shift to a knowledge‐based economy has incremented the use of personal information applied to health‐related activities, such as biomedical research, innovation, and commercial initiatives. The convergence of science, technology, communication and data technologies has given rise to the application of big data to health; for example through eHealth, human databases and biobanks.
The role of predominant polarity in older age bipolar disorder
(Springer Open, 2025-09-29) Sommerhof, Constanza; Bort, Marta; D’Alessandro, Giulia; Fico, Giovanna; De Prisco, Michele; Oliva, Vincenzo; Solé Cabezuelo, Brisa; Torrent Font, Carla; Murru, Andrea; Ruiz, Andrea; Rodríguez-Rey, Arturo; Sánchez-Moreno, José; Jiménez Martínez, Ester; Martínez-Arán, Anabel,; Vieta i Pascual, Eduard, 1963-; Montejo Egido, Laura
Introduction: Predominant polarity (PP) has emerged as a valuable course specifier in bipolar disorder (BD) with implications for prognosis and treatment planning. As the BD population ages, understanding its clinical characteristics becomes essential to tailor personalized interventions across the lifespan. This study aimed to characterize the distribution and clinical profiles of PP subgroups in a cohort of older adults with BD (OABD). Methods: This cross-sectional study included 101 euthymic OABD aged >50 years. Clinical, neuropsychological and functional characteristics were compared between depressive (DPP), manic (MPP), and undetermined predominant polarity (UPP) subgroups, based on at least 2/3 of lifetime episodes being either depressive or manic polarity. Results: UPP was the most frequent PP in OABD (59.4%), followed by DPP (27.7%) and MPP (12.9%). Patients with DPP presented a later age of onset, a depressive first episode, less psychiatric hospitalizations, and a trend to outperform MPP and UPP in visual memory. Participants with MPP presented more frequently with manic onset. The UPP subgroup exhibited worse clinical outcomes, including higher number of total episodes, more frequent suicidal ideation and seasonality, and worse financial disability compared to DPP. Conclusion: PP classification distinguishes meaningful clinical and cognitive subgroups in OABD. The UPP subgroup associates with greater illness severity and functional impairment. These findings support the integration of PP into personalized treatment and prevention strategies in aging BD. Future longitudinal studies are needed to further clarify the trajectory of PP across the lifespan.
One-stage knee replacement shows similar healing rates in patients with negative or positive preoperative cultures: a retrospective cohort study
(Copernicus Publications, 2025-07-25) Sabater Martos, Marta; Morata Ruiz, Laura; Segur Vilalta, Josep Maria; Soriano Viladomiu, Alex; Martínez Pastor, Juan Carlos
Treatment of chronic periprosthetic joint infections (PJIs) involves prosthesis removal, reimplantation, and antibiotic treatment. This process can be performed as a two-stage replacement or a one-stage replacement. One-stage replacement is classically performed only in patients who meet very strict criteria. The objective of this study was to analyse the healing and failure rates of one-stage knee replacement in patients with positive preoperative cultures and in those with negative preoperative cultures. Secondarily, we analysed the healing rate in patients with a sinus tract. Material and methods: We included 56 patients diagnosed with likely or confirmed PJI who underwent one-stage knee replacement in our centre between January 2016 and December 2021, with a minimum follow-up of 1 year. We evaluated the differences between cases with positive and negative preoperative cultures. Survival differences were assessed according to preoperative culture positivity and the presence of a sinus tract. Results: Preoperative cultures had positive results in 43 patients (76.8 %) and negative results in 13 patients (23.2 %). The overall failure rate was 12.5 % (seven patients), with one of these patients having had negative preoperative cultures. Of the 49 patients (87.5 %) with good results, 12 had negative preoperative cultures, and 37 had positive cultures (p = 1.00). Only 6 (10.7 %) of the 56 patients studied presented with a sinus tract. The differences in terms of healing and failure rates between patients with and without a sinus tract were not statistically significant (p = 0.57). Discussion: Using less strict criteria for patients, such as allowing preoperative negative cultures or the presence of a sinus tract, produced similar results to those for patients with only positive cultures or intact soft tissue.
Thinner and wiser? Prospects of GLP-1 agonists in psychiatry
(Elsevier B.V., 2025-05-22) Vieta i Pascual, Eduard, 1963-; Oliva, Vincenzo
In recent years, growing scientific attention has converged on the intricate, bidirectional relationship between physical health and mental well-being. Chronic inflammation, disruptions in the gut–brain axis and microbiota, and metabolic alterations such as obesity and type 2 diabetes have all been implicated in the pathophysiology of neuropsychiatric disorders. These insights are not merely academic—they are transforming how we approach, frame, and treat neuropsychiatric disorders.

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