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ArticleEthical, legal, and social assessment of AI-based technologies for prevention and diagnosis of rare diseases in health technology assessment process(MDPI, 2025) Refolo, Pietro; Raimondi, Constanza; Astratinei, Violeta; Battaglia, Laura; Borràs Andrés, Josep Maria; Closa, Paula; Lo Scalzo, Alessandra; Marchetti, Marco; Muñoz López, Sonia; Sampietro Colom, Laura; Sacchini, DarioAbstract: Background: While the HTA community appears well-equipped to assess preventive and diagnostic technologies, certain limitations persist in evaluating technologies designed for rare diseases, including those based on Artificial Intelligence (AI). In Europe, the EUnetHTA Core Model® serves as a reference for assessing preventive and diagnostic technologies. This study aims to identify key ethical, legal, and social issues related to AI-based technologies for the prevention and diagnosis of rare diseases, proposing enhancements to the Core Model. Methods: An exploratory sequential mixed methods approach was used, integrating a PICO-guided literature review and a focus group. The review analyzed six peer-reviewed articles and compared the findings with a prior study on childhood melanoma published in this journal (Healthcare), retaining only newly identified issues. A focus group composed of experts in ethical, legal, and social domains provided qualitative insights. Results: Thirteen additional issues and their corresponding questions were identified. Ethical concerns related to rare diseases included insufficient disease history knowledge, lack of robust clinical data, absence of validated efficacy tools, overdiagnosis/underdiagnosis risks, and unknown ICER thresholds. Defensive medicine was identified as a legal issue. For AI-based technologies, concerns included discriminatory outcomes, explicability, and environmental impact (ethical); accountability and reimbursement (legal); and patient involvement and job losses (social). Conclusions: Integrating these findings into the Core Model enables a comprehensive HTA of AI-based rare disease technologies. Beyond the Core Model, these issues may inform broader assessment frameworks, ensuring rigorous and ethically responsible evaluations.- ArticleStreptozotocin plus 5-fluorouracil followed by everolimus or the reverse sequence in patients with advanced pancreatic neuroendocrine tumors (SEQTOR-GETNE phase III study): a randomized clinical trial(Elsevier, 2025-12) De Vos-Geelen, J.; Venerito, Marino; Von-Werder, Alezander; Jann, Henning; Rinke, Anja; Smith, D.; Hörsch, D.; Starling, Naureen; Ruszniewski, Philippe; Baudin, Eric; Metges, J.-P.; Caroli-Bosc, F.-X.; Reed, N.S.; Manzano, José Luis; Schrader, J.; Martín, M.; Navarro Perez, Valentin; Scarpa, A.; Valentí, Víctor; Lawlor, R.T.; Hernando, Jorge; Ragulan, C.; Colao, A.M.; Ps, H.; Vestermark, Lene; Sadanandam, A.; Carnaghi, Carlo; Knigge, U.P.; Capdevila, Jaume; Tafuto, Salvatore; Krogh, M.; Teulé-Vega, Àlex; Garcia Carbonero, Rocio; Klümpen, H.-J.; Cremer, B.; Sevilla, I.; Eriksson, B.; Tabaksblat, E.; Carmona Bayonas, Alberto; Salazar Soler, Ramón; Jiménez Fonseca, Paula; Benavent Viñuales, MartaBackground: Everolimus or streptozotocin plus 5-fluorouracil (STZ/5-FU) are approved treatments for patients with pancreatic neuroendocrine tumors (panNETs). The SEQTOR trial aimed to assess the optimal treatment sequence. Patients and methods: SEQTOR was an international, open-label, randomized, crossover, phase III trial that recruited adults with unresectable or metastatic, advanced, well-differentiated panNET. Patients received 10 mg/day of everolimus followed upon progression by STZ/5-FU; or the reverse sequence. The primary endpoint was the 35-month progression-free survival (PFS) rate after first- and second-line treatment; however, due to slow accrual and longer survival, it was changed to the 12-month PFS rate following first-line treatment (12-mPFS1). Results: Patients were randomized to everolimus (n = 72) or STZ/5-FU (n = 69) first. The 12-mPFS1 was 71.4% [95% confidence interval (CI) 59.4% to 81.6%] and 61.8% (95% CI 49.2% to 73.3%) (odds ratio 0.65, 95% CI 0.32-1.32) with a median PFS1 of 19.4 versus 22.7 months for everolimus and STZ/5-FU, respectively. STZ/5-FU achieved a significantly higher overall response rate in first-line (11.6% versus 30.3%, P = 0.012) and second-line (30.6% versus 9.1%, P = 0.072) treatments. No differences were shown in overall survival (median 61.7 versus 50.6 months in everolimus first and STZ/5-FU first, respectively; hazard ratio 1.43, 95% CI 0.86-2.37). Discontinuations of everolimus were more frequent. Conclusion: STZ/5-FU and everolimus were not statistically different in PFS rates, but STZ/5-FU achieved higher response rates. Keywords: 5-fluorouracil; advanced pancreatic neuroendocrine neoplasm; everolimus; panNET; sequential strategy; streptozotocin.
- ArticleDo national cancer control plans address care and research for children, adolescents, and young adults? A review of status, priorities, and recommendations across 41 European countries(Elsevier Ltd., 2025) Borràs Andrés, Josep Maria; Vassal, Gilles; Prades, Joan; Kozhaeva, Olga; Otth, Maria; Kearns, Pamela; Ladenstein, Ruth; Rizzari, Carmelo; Heenen, Delphine; Dirksen, Uta; Owens, Cormac; Lazarov, Deyan; Sheehan, CiaraPaediatric cancers, although rare, are the leading cause of disease-related mortality in European children above one year. A key pillar of the European Health Union, Europe’s Beating Cancer Plan (EBCP) puts a spotlight on childhood cancer. National Cancer Control Plans (NCCPs) have a key role but did not address childhood cancers sufficiently previously. This study considered the NCCPs of 41 European countries in relation to children and adolescents and young adults (AYAs). Twenty two NCCPs informed a structured narrative analysis. Four NCCPs were categorised as having comprehensive paediatric oncology content. Findings emphasise access to care through centralisation combined with local delivery of low-risk interventions and the role of multidisciplinary teams. Survivorship, AYA care, registries, and voluntary associations were addressed to varying degrees. Supportive care was among the weakest areas in the 22 NCCPs. Recommendations were presented to strengthen paediatric oncology in NCCPs and enrich the EBCP vision towards improved survival and reduced inequalities across Europe.
- ArticleManagement, survival, and costs of pancreatic cancer: Popupation-Based observational study in Catalonia(MDPI, 2023) Guarga, Laura; Paco, Noelia; Manchon Walsh, Paula; Vela, Emili; Delgadillo, Joaquim; Pontes, Caridad; Borràs Andrés, Josep MariaAbstract: Aim: Few published studies comprehensively describe the characteristics of patients with pancreatic cancer and their treatment in clinical practice. This study aimed to describe the current clinical practice for treating pancreatic cancer in Catalonia, along with the associated survival and treatment costs. Methods: A retrospective observational cohort study in patients diagnosed with pancreatic cancer from 2014 to 2018, using data from the healthcare records of the Public Health System of Catalonia, was conducted. Treatment patterns and costs were described by age groups
from 2014 to 2018, with survival reported until December 2021. Results: The proportion of patients receiving surgery with curative intent was low, especially in older patients (23% of patients <60 years and 9% of patients 80 years). The percentage of patients treated with drugs for unresectable disease also decreased with age (45% of patients <60 years and 8% of patients 80 years). Although age was associated with significant differences in survival after curative surgery, no differences attributable to age were observed in patients who received pharmacological treatment for unresectable disease. In patients under 60 years of age, the mean cost of the first year of treatment was EUR 17,730 (standard
deviation [SD] 5754) in those receiving surgery and EUR 5398 (SD 9581) in those on pharmacological treatment for unresectable disease. In patients over 80, the mean costs were EUR 15,339 (SD 2634) and EUR 1845 (SD 3413), respectively. Conclusions: Half of the patients diagnosed with pancreatic cancer did not receive specific treatment. Surgery with curative intent was associated with longer survival, but only 18% of (mostly younger) patients received this treatment. Chemotherapy was also used less frequently in patients of advanced age, though survival in treated patients was comparable across all age groups, so careful oncogeriatric assessment is advisable to ensure the most appropriate indication for eligibility in older patients. In general, earlier diagnosis and more effective pharmacological treatments are necessary to treat frail patients with high comorbidity, a common profile in older patients.
- ArticleCancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database.(BMJ Publishing Group, 2017-03) Møller, Pal; Seppälä, Toni T.; Bernstein, Inge; Holinski-Feder, Elke; Sala, Paola; Evans, D. Gareth; Lindblom, Annika; Macrae, Finlay; Blanco, Ignacio; Sijmons, Rolf; Jeffries, Jacqueline; Vasen, Hans; Burn, John; Nakken, Sigve; Hovig, Eivind; Rødland, Einar Andreas; Tharmaratnam, Kukatharmini; de Vos Tot Nederveen Cappel, Wouter H.; Hill, James; Wijnen, Juul; Green, Kate; Lalloo, Fiona; Sunde, Lone; Mints, Miriam; Bertario, Lucio; Pineda Riu, Marta; Navarro, Matilde; Morak, Monika; Renkonen-Sinisalo, Laura; Frayling, Ian M.; Plazzer, John Paul; Pylvänäinen, Kirsi; Sampson, Julian R.; Capellá, G. (Gabriel); Mecklin, Jukka Pekka; Möslein, Gabriela; Mallorca GroupObjective Estimates of cancer risk and the effects of surveillance in Lynch syndrome have been subject to bias, partly through reliance on retrospective studies. We sought to establish more robust estimates in patients undergoing prospective cancer surveillance. Design We undertook a multicentre study of patients carrying Lynch syndrome-associated mutations affecting MLH1, MSH2, MSH6 or PMS2. Standardised information on surveillance, cancers and outcomes were collated in an Oracle relational database and analysed by age, sex and mutated gene. Results 1942 mutation carriers without previous cancer had follow-up including colonoscopic surveillance for 13 782 observation years. 314 patients developed cancer, mostly colorectal (n=151), endometrial (n=72) and ovarian (n=19). Cancers were detected from 25 years onwards in MLH1 and MSH2 mutation carriers, and from about 40 years in MSH6 and PMS2 carriers. Among first cancer detected in each patient the colorectal cancer cumulative incidences at 70 years by gene were 46%, 35%, 20% and 10% for MLH1, MSH2, MSH6 and PMS2 mutation carriers, respectively. The equivalent cumulative incidences for endometrial cancer were 34%, 51%, 49% and 24%; and for ovarian cancer 11%, 15%, 0% and 0%. Ten-year crude survival was 87% after any cancer, 91% if the first cancer was colorectal, 98% if endometrial and 89% if ovarian. Conclusions The four Lynch syndrome-associated genes had different penetrance and expression. Colorectal cancer occurred frequently despite colonoscopic surveillance but resulted in few deaths. Using our data, a website has been established at http://LScarisk.org enabling calculation of cumulative cancer risks as an aid to genetic counselling in Lynch syndrome.
- ArticleCharacterisation of the gut-lung axis microbiome in clinically stable patients with chronic obstructive pulmonary disease.(Elsevier, 2026-01-07) Viglino, Julieta; Perea Soriano, Lídia; García Nuñez, Marian; Rodrigo-Troyano, Ana; Torrego, Alfons; Domínguez Álvarez, Marisol; Villar, Judith; Carrizosa Gueri, Xènia; Quero Blanca, Sara; Gabaldón Estevan, Juan Antonio, 1973-; Willis, Jesse R.; Saus, Ester; Gea Guiral, Joaquim; Santos Pérez, Salud; Camps Massa, Paula; Agustí García-Navarro, Àlvar; Monsó, Eduard; Sibila Vidal, Oriol; Faner, RosaBackground Airway and gut dysbiosis have been reported in Chronic Obstructive Pulmonary Disease (COPD); however, their relationship and association with clinical features remain poorly understood. We aimed to characterise the lung and gut microbiome in patients with stable COPD and controls. Methods Prospective, multicentre, longitudinal and controlled study of n = 60 stable patients with COPD and n = 30 controls. In them, we analysed 16S rRNA-seq in oropharyngeal (OP) swabs, sputum, bronchoalveolar lavage fluid (BALF) and stool. Weighted gene co-expression network analysis (WGCNA) was employed in each sample type to identify modules of co-abundant bacteria associated with clinical traits. Findings We found that the microbiome in airway and stool samples was highly dissimilar both in patients and controls, with 0.37% of this diversity associated to COPD. The microbiome taxa associated with COPD in OP swabs and sputum were highly similar, but different from BALF, suggesting that OP swabs can be a surrogate sample of sputum. Finally, using WGCNA, we identified: (a) 5 modules in OP swabs and 3 in sputum associated with FEV1, but some of them were also associated with exacerbations, dyspnoea and inhaled steroid (ICS) use; (b) In BALF 4 modules associated with FEV1 and dyspnoea, and 2 modules with ICS; and, finally, (c) in stool, 1 module related to FEV1, 1 to exacerbations and 3 with ICS. Interpretation The gut and lung microbiomes in patients with COPD are distinct, but both clinically relevant as both present bacterial associations with airflow limitation, exacerbation history, and ICS use.
- ArticleProjecte d’innovació en l’aprenentatge de la competència d’elaboració de l’anamnesi: inici de la implementació(ICE Universitat de Barcelona, 2025-12-05) Pérez Palma, Laura; Ruiz Toledo, Jessica; Cuevas-Martínez, Claudia; Espada-Martín, Núria; Jorba Pedrosa, Marta; Bombi-Arrieta, Mireia; Planell i Mas, Elena deINTRODUCCIÓ. L’anamnesi és part fonamental de la història clínica, imprescindible per a la recerca del diagnòstic. Les metodologies docents prèvies han demostrat no ser suficients en el grau en Podologia de la Universitat de Barcelona. Aquest projecte té com a objectiu millorar el grau competencial de l’alumnat per assolir la seva òptima activitat assistencial futura. MÈTODE. S’està duent a terme una actuació durant els quatre anys del grau en què s’estan implementant metodologies específiques. Es comparen els resultats dels alumnes amb formació específica i sense, i també es determina el nivell d’empatia dels alumnes a l’inici i final del grau en Podologia, tant de la Universitat de Barcelona com de la Universitat de València. RESULTATS. Durant les primeres fases s’ha observat una millora substancial de la competència d’elaboració de l’anamnesi. S’espera que l’alumnat aconsegueixi un nivell òptim de la competència clínica en l’elaboració de l’anamnesi i en les habilitats relacionades. DISCUSSIÓ. El foment de l’empatia i la creació de recorreguts curriculars en els graus sanitaris s’ha demostrat que és imprescindible. Als estudiants se’ls dificulta sistematitzar l’anamnesi, ja que no disposen d’un model teòric pràctic de referència. Les intervencions pedagògiques proposades milloren l’elaboració de l’anamnesi i afavoreixen l’òptima activitat assistencial futura.
- ArticleChanges in vessel density patterns assessed with OCTA in patients with diabetic macular edema treated with anti-VEGF therapy(Springer Verlag, 2024-11) Santamaría, Juan; Cobos, Estefanía; Biarnes, Marc; Caminal Mitjana, Josep Maria; Rodriguez Leor, Ramón; Morwani, Rahul; García Mendieta, Manel; Lorenzo, Daniel; García Bru, Pere; Arias Barquet, LluísAims To determine the presence of sectoral changes in vessel density (VD) patterns induced by vascular endothelial growth factor inhibitors (anti-VEGF) in patients with diabetic macular edema (DME) using optical coherence tomography angiog- raphy (OCTA). Methods Prospective, interventional study. A total of 43 patients (63 eyes) were initially enrolled in the study. We performed swept source (SS) OCT and sectorial OCTA measurement to determine parafoveal VD at baseline and after six months of anti-VEGF treatment. In the locations with statistically significant differences in VD between baseline and month 6, we performed univariate and multivariate analyses to determine which, if any, of the baseline variables were associated with the observed changes. Results A total of 34 patients (48 eyes) were included in the final analysis. Mean VD decreased from baseline to month 6 (from 45.2 (± 3.5) to 44.6 (± 3.2) % in the SCP and from 50 (± 3.3) to 49 (± 3.9) % in the DCP). The only significant changes in VD were observed in the nasal sector of the deep capillary plexus, with a decrease of 2.9% (p = 0.001). On univariate and multivariate analyses, the only variable significantly associated with changes in VD in the nasal sector after 6 months of treatment was baseline VD in the same sector. Conclusions Anti-VEGF therapy has a small impact on VD values over time. These variations observed after treatment seems to be related to changes over areas of vascular anomalies and displaced vessels adjacent to cystic areas, with no significant changes over ischemic areas. No correlation was observed between this trend and other clinical baseline features.
- ArticleDo patients with bipolar disorder and subsyndromal symptoms benefit from funcional remediation? A 12-month follow-up study(Elsevier B.V., 2017-04) Sánchez-Moreno, José; Bonnín Roig, Caterina del Mar; González-Pinto, Ana; Amann, Benedikt L.; Solé Cabezuelo, Brisa; Balanzá-Martínez, Vicent; Arango, Celso; Jiménez Martínez, Ester; Tabarés-Seisdedos, Rafael; García-Portilla González, María Paz, 1962-; Ibáñez, Ángela; Crespo, J. M. (José Manuel); Ayuso Mateos, José Luis; Vieta i Pascual, Eduard, 1963-; Martínez-Arán, Anabel, 1971-; Torrent Font, Carla; CIBERSAM Functional Remediation GroupWe analyzed the efficacy of functional remediation, in a sample of patients with bipolar disorder who presented with subsyndromal symptoms. From a total sample of 239 patients with bipolar I and II disorder, according to DSM-IV-TR diagnostic criteria, entering a randomized clinical trial, those patients who presented with subsyndromal symptoms were selected based on a method already described by Berk and colleagues was applied. It consists of using the Clinical Global Impression-Bipolar version (CGI-BP) to establish the scores of the Hamilton Depression Rating Scale (HAM-D) and of the Young Mania Rating Scale (YMRS) that correspond with 1 in the CGI-BP. Functional outcome and mood symptoms were assessed at 6 and at 12-month follow-up. A total of 99 patients were selected for this post-hoc analysis, allocated as follows: functional remediation (n=33); psychoeducation (n=37) and treatment as usual (TAU,n=29). The repeated-measures analyses at 12-month follow-up revealed a significant group x time interaction in favour of the patients who received functional remediation when compared to psychoeducation and TAU (F=2.93; p=0.02) at improving psychosocial functioning. Finally, mood symptoms did not significantly change in any of the three groups at any time of follow-up, as shown by the non-significant group x time interaction effect in HAM-D scores (F=1.57; p=0.18) and YMRS scores (F=1.51; p=0.20). Bipolar patients with subsyndromal symptoms improve their functional outcome when exposed to functional remediation regardless of the persistence of mood symptomatology.
- ArticleOlfactory dysfunction after subarachnoid haemorrhage caused by ruptured aneurysms of the anterior communicating artery.(American Association of Neurological Surgeons, 2009-04-10) Escartin Martin, Gemma; Junqué i Plaja, Carme, 1955-; Juncadella i Puig, Montserrat; Gabarrós, Andreu; Miquel, Maria Angels de; Rubio Borrego, Francisco RamónObject Olfactory dysfunction has an important impact on quality of life. In patients with subarachnoid hemorrhage (SAH), anosmia has mainly been reported after surgery for aneurysms of the anterior communicating artery (ACoA). The authors studied whether and how frequently patients with ACoA aneurysms present with smell identification deficits in 2 treatment groups (endovascular and surgical treatment). Methods A prospective study was conducted of patients with SAH caused by ruptured ACoAs and who had a Glasgow Outcome Scale score of 1 or 2, in comparison with a control group matched by age and sex. Olfactory function was assessed using the University of Pennsylvania Smell Identification Test (UPSIT). Results A total of 39 patients were enrolled. A marked olfactory impairment was observed in patients with ruptured ACoAs compared with the control group (p < 0.001). Seventeen patients with ruptured ACoAs (44%) compared with 1 patient in the control group (3%) showed a smell identification deficit according to performance on the UPSIT (p < 0.001). Both groups that underwent treatment presented with olfactory impairment. Ten (59%) of 17 patients who underwent aneurysmal clip placement versus 6 (28.5%) of 21 patients who underwent coil embolization scored below the 25th percentile on the UPSIT, and surgical patients also performed worse than endovascular patients (p = 0.048). The authors observed a worse performance on the olfactory test in patients subjected to endovascular coil embolization when cerebral vasospasm (p = 0.037) or frontal cerebral lesions (p = 0.009) were present. This difference was not observed in patients who underwent surgery. Conclusions Olfactory disorders after SAH caused by rupture of the ACoA are very frequent and were present in both treatment groups. Cerebral vasospasm and frontal lobe lesions are related to worse performance on an olfactory test in patients undergoing endovascular coil embolization.
- ArticleAcceso a medicamentos huérfanos para el tratamiento de la atrofia muscular espinal en España(Viguera Editores SL, 2022) García Parra, Beliu; Guiu Segura, Josep Maria; Modamio Charles, Pilar; Martínez Yélamos, Antonio; Mariño Hernández, Eduardo L.; Povedano Panades, MónicaIntroducción. La atrofia muscular espinal (AME) es una enfermedad rara cuyo diagnóstico y tratamiento es complejo. En
España hay dos medicamentos huérfanos financiados por el Sistema Nacional de Salud, nusinersén y onasemnogén abeparvovec,
y un tercero, risdiplam, pendiente. El objetivo fue analizar el acceso a los fármacos modificadores de la AME y
detectar posibles causas de inequidad.
Materiales y método. Estudio descriptivo realizado en dos fases: revisión bibliográfica y entrevistas semiestructuradas a
expertos clínicos en AME de las comunidades autónomas (CC. AA.) de Andalucía, Castilla-La Mancha, Cataluña y Murcia.
Resultados. El número de centros, servicios o unidades de referencia, la disponibilidad de planes autonómicos para enfermedades
raras y los programas piloto de cribado neonatal pueden modular el acceso a los nuevos tratamientos farmacológicos.
El número de nuevos pacientes diagnosticados al año se estimó entre uno y seis en cada una de las CC. AA. estudiadas.
Dos de las cuatro CC. AA. estaban participando en ensayos clínicos. El tiempo desde la prescripción a la
administración de nusinersén estaba entre siete y 60 días. Sólo Cataluña comunicó experiencia con onasemnogén abeparvovec
a 30 de junio de 2022. Dos CC. AA. de las cuatro estudiadas disponen de plan autonómico para enfermedades
raras; no obstante, se identificó como relevante para el tratamiento de la AME sólo en una de ellas.
Conclusiones. No se identificaron diferencias importantes en el acceso al nusinersén en las CC. AA. estudiadas. El diagnóstico
de la AME requiere personal clínico experto y centros especializados para iniciar precozmente los tratamientos modificadores
de la enfermedad.
- ArticleOP01.09: Perinatal outcomes in gestations with intrauterine growth restriction and small for gestational age foetuses, admitted to neonatal unit(John Wiley & Sons, 2010-12-14) Gómez Roig, Ma. Dolores; Mazarico Gallego, Edurne; Sabrià Bach, Joan; Martín Ancel, Ana; Vela, A.; Lailla Vicens, José Ma. (José María), 1948-To compare perinatal outcomes between those gestations with intrauterine growth restriction or with small for gestational age foetuses.
- ArticleEcological validity of maximal exercise tests to simulate competitive demands in amateur female handball(Association of Physical Education and Health Educators Ljubuški, 2026-01-14) Batalla Gavaldà, Abraham; Beltrán Garrido, José Vicente; Montoliu-Colás, Raúl; Reina-Gómez, Álvaro; Corbi, Francisco; Daza Sobrino, GabrielPurpose: Laboratory tests are fundamental for assessing handball performance, but their ecological validity for amateurfemale players is unclear. This exploratory study compared physiological and perceptual responses between commonmaximal exercise tests and official match play to determine if they replicate competitive demands. Methods: Sixteen amateur female handball players completed three laboratory tests (Wingate, cycle ergometer, treadmill) and were monitored during ten official matches. The data collection included both physiological and psychological indicators: heart rate (HR), blood lactate concentration, rating of perceived exertion (RPE), perceived stress, and mood states. Results: Peak HR values recorded in the Wingate and Cycle ergometer were lower than those reached during actualcompetition (d = -.77 to -.75, P< .05). In addition, compared with the Wingate and cycle ergometer tests, competitive matchesrequired players to spend a significantly larger proportion of time with their HR exceeding 90% of its maximum. This contrast was less evident when compared with the treadmill test. A clear mismatch was observed between physiological andperceptual measures. Despite showing stronger physiological strain during matches -such as greater weight loss and higherpre-exercise lactate levels- players reported significantly lower RPE values than in the laboratory conditions (d = .27 to .36,P< .05). Conclusions: None of the laboratory-based tests accurately reproduced the full demands of a handball match. Although the treadmill test elicited similar peak HR values, it failed to reflect the sport’s intermittent nature. The Wingate and cycletests showed even greater discrepancies in cardiovascular intensity. These findings underline the importance of developingsport-specific or hybrid assessment protocols that integrate intermittent workloads and cognitive demands for a more validevaluation of performance.
- ArticleBarriers and facilitators to performing benign paroxysmal positional vertigo manoeuvres among primary care physicians in Barcelona: a qualitative study(BMJ Publishing Group, 2025-12-08) Rullan-Rabassa, Alicia; Abiétar, Daniel G.; Rando-Matos, Yolanda; Ballvé Moreno, José Luis; Daryanani-Nawalrai, Sheena; Hernández-Méndez, Patricia; Rozenek, Malgorzata Anna; Santolalla-De Pedro, Anna; Torrecilla-Sánchez, Raquel; Peguero Rodríguez, EvaObjective: To explore the barriers and facilitators in adherence to the guidelines in the management of benign paroxysmal positional vertigo from the perspective of primary care physicians. Design: Qualitative study using focus groups. Setting: L'Hospitalet del Llobregat (Barcelona), Spain. Study design: Qualitative study using focus groups. Structured 90 min focus groups were conducted until data saturation was reached. Each session included a moderator and an observer from the research team. Sessions were transcribed and thematically analysed by three independent researchers. Participants: Purposeful sampling was used to form four groups of 4-10 participants, selected by sex, age, years of experience and primary care team (PCT). Participants were recruited between January and February 2023. Results: A total of 34 family physicians belonging to four PCTs participated in the study. The main barriers identified were a lack of time, negative initial experiences, a fear of harming patients (especially older adults), difficulty in nystagmus visualisation and challenges in managing patient expectations, as many preferred medication over physical manoeuvres. Facilitators included potential time savings from effective early management, the value of initial practical training with periodic refreshers, access to expert consultants for case discussions and the availability of digital tools, such as tutorials, videos and aids for nystagmus interpretation. Conclusion: Health systems should invest in protected time for history-taking and physical examination, and in regular, updated training for primary care professionals. This could improve vertigo management and reduce unnecessary investigations and medications, ultimately benefiting both patients and the healthcare system.
- Article6-Year Risk of Developing Lung Cancer in Spain: Analysis by Autonomous Communities(Elsevier, 2020-05-11) Travier, Noémie; Fu Balboa, Marcela; Romaguera, Amparo; Martín-Cantera, Carlos; Fernández Muñoz, Esteve; Vidal, Carmen; García Martínez, Montserrat; LUCAPREV research groupIntroduction: Lung cancer screening with low-dose computed tomography (LDCT) has been proposed as a strategy to reduce lung cancer mortality. Since LDCT has side effects there is a need to carefully select the target population for screening programmes. Because in Spain health competences are transferred to the seventeen Autonomous Communities (ACs), the present paper aims to identify individuals at high risk of developing lung cancer in the different ACs. Methods: We used the 2011-2012 data of the Spanish National Interview Health Survey (n=21,006) to estimate the proportion of individuals at high risk of developing lung cancer using a 6-year prediction model (PLCOm2012). This proportion was then extrapolated into absolute figures for the Spanish population, using the population census data of 2018 from the National Institute of Statistics. Results: The proportion of individuals aged 50-74 with a risk of lung cancer ≥2% was 9.5% (15.9% in men, 3.5% in women). This proportion ranged from 6.6% in Región de Murcia to 12.7% in Andalucía and 13.0% in Extremadura. When extrapolated to the Spanish population, it was estimated that a total of 1,341,483 individuals may have a 6-year risk of lung cancer ≥2%. Conclusions: The present study is the first one that evaluated the number of individuals at high risk of developing lung cancer in the different Spanish ACs using a prediction model and selecting people with a 6-year risk ≥2%. Further studies should assess the cost and effectiveness associated to the implementation of a lung cancer screening programme to such population.
- ArticleAssociation of in utero exposure to phthalate and DINCH metabolites with placental DNA methylation(Elsevier Ltd., 2025-11-19) Dadvand, Payam; Bustamante Pineda, Mariona; Vrijheid, Martine; Vespalcova, Hana; Knox, Bethany; Sakhi, Amrit K.; Thomsen, Cathrine; Aguilar Lacasaña, Sofía; Cosín Tomàs, Marta; Gómez-Herrera, Laura; Sánchez García, Olga; Llurba Olivé, Elisa; Gómez Roig, Ma. Dolores; Sunyer, JordiPhthalates and DINCH are non-persistent chemicals widely used in consumer products. In utero exposure to these compounds has been linked to adverse reproductive and long-term health outcomes, potentially through epigenetic changes in the placenta. This study investigated associations between maternal phthalate and DINCH metabolite levels and placental DNA methylation in 469 mother–child pairs from the Barcelona Life Study Cohort (BiSC). Fifteen phthalate and two DINCH metabolites were measured in pooled maternal urine samples collected at 19 and 35 weeks of gestation using liquid chromatography–tandem mass spectrometry (LC-MS/MS. Placental DNA methylation was assessed using the Illumina EPIC array. We applied robust linear regression models to test associations between single exposures at 19 weeks, 35 weeks, and whole pregnancy (average of the two time points), with each CpG site. In secondary analyses, quantile g-computation was used to test associations between exposure mixtures and suggestive CpGs (p-value < 1E-05). We identified 38 Bonferroni significant associations in the single exposure models (p-value < 1E-07)— 24 at 19 weeks, 8 at 35 weeks and 6 for the whole pregnancy period. Suggestive CpGs (p-value < 1E-05) were annotated to genes involved in metabolic, immune and vascular pathways, steroid biosynthesis, and sex hormone signaling. Sex-stratified analyses revealed 49 female-specific and 42 male-specific associations, most of which were identified at a single time point. Mixture analyses revealed 20 significant associations, all consistent in direction with the single-metabolite models. These results suggest that prenatal exposure to phthalates and DINCH may contribute to placental epigenetic alterations supporting a role for endocrine disruption, metabolism, and vascular and immune modulation in mediating their effects.
- ArticleExploring the relationship between maternal carbohydrate quality and quantity during pregnancy and early childhood neurodevelopment: a prospective cohort study within the BiSC cohort(Springer Verlag, 2025-12-01) Panisello, Laura; Mateu-Fabregat, Javier; Novau-Ferré, Nil; Ayala-Aldana, Nicolas; Bernardo-Castro, Sara; Ferrer, Muriel; Jiménez-Arenas, Pol; Llurba Olivé, Elisa; Lassale, Camille; Gómez Roig, Ma. Dolores; Vioque, Jesús; González Palacios, Sandra; Contreras Rodríguez, Oren; Foraster, Maria; Gascón, Mireia; Sunyer, Jordi; Awad, Camila; Júlvez, Jordi; Bulló, MònicaPurpose: Maternal nutrition during pregnancy is key for offspring neurodevelopment. Given the role of glucose in brain function, assessing carbohydrate quantity and quality, including glycemic index (GI), glycemic load (GL) and carbohydrate quality index (CQI), may provide insights into early brain development. This study examined the associations between maternal dietary carbohydrate intake and neurodevelopmental outcomes in early childhood. Methods: The prospective cohort study included 1080 mother-child pairs from the Barcelona Life Study Cohort. Maternal dietary carbohydrate intake, GI, GL and CQI were assessed during mid-pregnancy using a food frequency questionnaire. Child neurodevelopment was evaluated at 8 and 28 months using the Developmental Profile 3 (DP-3) and at 18 months using the Bayley Scales of Infant and Toddler Development (BSID-III). Associations were analyzed using multivariable linear regression models adjusted for relevant maternal and child covariates. Results: Increased maternal carbohydrate intake, GI, and GL were inversely associated with language development (β (95% CI): - 2.67 (- 5.13, - 0.21), - 2.73 (- 5.21, - 0.26), - 3.51 (- 5.96, - 1.07) respectively) and receptive language (β (95% CI): - 0.58 (- 1.07, - 0.08), - 0.54 (- 1.04, - 0.04), - 0.70 (- 1.20, - 0.21) respectively) at 18 months, as measured by the BSID-III, although these associations were attenuated after adjustment for maternal and child covariates. Increased GI and lower CQI were associated with lower gross motor scores (β (95% CI): - 0.49 (- 0.84, - 0.15), 0.39 (0.06, 0.71) respectively) at 18 months (BSID-III), as well as reduced motor development (β (95% CI): - 3.2 (- 5.50, - 0.76), 2.22 (- 0.1, 4.54) respectively) at 8 and 28 months (DP-3). Conclusions: Maternal carbohydrate quality during pregnancy may influence early neurodevelopment, particularly motor outcomes. Emphasizing low-GI, low-GL and high-CQI carbohydrate sources during pregnancy could support favorable developmental trajectories in offspring.
- ArticlePrenatal phenol exposure and child behaviour: insights into the hypothalamic-pituitary-adrenal axis from two prospective mother-child cohorts(2025-12-09) Rolland, Matthieu; Bustamante Pineda, Mariona; Jedynak, Paulina; Thomsen, Cathrine; Sakhi, Amrit K.; Foraster, Maria; Gascón, Mireia; Gómez Roig, Ma. Dolores; Llurba Olivé, Elisa; Rivas, Ioar; Ouellet-Morin, Isabelle; Ferrer, Muriel; Morillas, Alex; Carras, Sylvain; Bayat, Sam; Lyon-Caen, Sarah; Pozo, Oscar J.; Vrijheid, Martine; Sunyer, Jordi; Slama, Rémy; Dadvand, Payam; Philippat, ClaireBackground: Synthetic phenols are widely used chemicals with potential neurodevelopmental toxicity. Human studies are often limited by small sample sizes and exposure misclassification. Identifying the biological pathways affected by these substances is crucial for understanding key drivers of toxicity. We aimed to study associations between prenatal exposure to synthetic phenols and child behaviour, exploring the potential mediating role of maternal steroid hormones. Methods: We pooled data from two European cohorts: the Barcelona Life Study Cohort (BiSC; Barcelona, Spain, 2018-21, N=1080) and Suivi de l'Exposition à la Pollution Atmosphérique durant la Grossesse et Effets sur la Santé (SEPAGES; Grenoble, France, 2014-17, N=484). Mothers older than 18 years having a singleton pregnancy of less than 19 weeks gestational age were eligible for inclusion in the cohorts; those having multiple pregnancies were excluded. Repeated urine samples (up to 24 in BiSC; up to 42 in SEPAGES) collected in the second and third trimesters were pooled and analysed for 12 synthetic phenols. Child behavioural outcomes were assessed at 18 months in BiSC and 24 months in SEPAGES using the Child Behavior Checklist for Ages 1·5-5 (CBCL). Concentrations of total cortisol, total cortisone, and 11-dehydrocorticosterone-steroid hormones involved in the hypothalamic-pituitary-adrenal axis-were measured from maternal hair samples. Associations between phenol exposure and behavioural outcomes were estimated by adjusted linear regression analysis, and mediation by steroid hormones was assessed with regression-based causal mediation analysis within the counterfactual framework. Findings: 1024 mother-child pairs were included in the study: 607 from BiSC and 417 from SEPAGES. Maternal exposure to methylparaben in the third trimester of pregnancy was associated with higher internalising scores (change in score of 0·44 [95% CI 0·10-0·79] points) and externalising scores (0·67 [0·12-1·24]) in the CBCL. In boys, maternal exposure to bisphenol S in the third trimester was linked to increased internalising scores (0·92 [0·15 to 1·75]; p=0·019) and could be linked to increased externalising scores (1·14 [-0·09 to 2·44]; p=0·070). In girls, second-trimester butylparaben and propylparaben exposure were associated with lower internalising (-1·03 [-1·84 to -0·09], p=0·033) and externalising (-0·68 [-1·23 to -0·12]; p=0·019) scores. No mediation by steroid hormones was observed. Interpretation: Prenatal exposure to phenols might influence early behavioural development, with sex-specific patterns. There was no strong evidence of mediation by maternal steroid hormones, suggesting the involvement of alternative pathways in the biological effects of phenols. Together with previous findings, these results highlight the need for stricter regulation of these compounds to reduce prenatal exposure.
- ArticleImpact on delay times and characteristics of patients undergoing primary percutaneous coronary intervention in the southern metropolitan area of Barcelona after implementation of the infarction code program(Elsevier España, 2012-10) Gómez Hospital, Joan Antoni; Cequier Fillat, Àngel R.; Dallaglio, Paolo D.; Sánchez Salado, Jose Carlos; Ariza Solé, Albert; Homs, Silvia; Lorente, Victòria; Ferreiro Gutiérrez, José Luis; Gómez Lara, Josep; Romaguera, Rafael; Salazar Mendiguchía, Joel; Teruel Gila, Luis Miguel[eng] A standardized protocol of emergent transfer for primary percutaneous coronary intervention for patients with ST elevation myocardial infarction, defined as the Infarction Code, was implemented in June 2009 in the Catalan regional health system. The objective of this study was to evaluate the impact of the new protocol on delay times, number of procedures and clinical characteristics compared with the previous period in the population of patients referred to our hospital. Methods All consecutive patients undergoing primary percutaneous coronary intervention in our hospital were prospectively registered. The clinical characteristics, delay times and mortality in the follow-up of the protocol implementation period (June 2009-May 2010) were analyzed and compared with the previous year (June 2008-May 2009). Results During the protocol period, 514 patients were included, compared with 241 in the previous year. Age, cardiovascular risk factors, anterior myocardial infarction and procedure characteristics were similar in the 2 groups. The first medical contact to balloon time was lower in the protocol period (median time 120 min vs 88 min; P<.001). Patients in the protocol period showed a trend toward less severe disease (Killip III, rescue angioplasty). The multivariate regression analysis showed a significant association between 1-year mortality and age, Killip class≥III at admission, anterior infarction and 3-vessel disease. Conclusions The introduction of the Infarction Code program increased the number of patients treated by primary percutaneous coronary intervention with a reduction in delay times and better clinical characteristics at presentation.
- ArticleThe use of lymphocyte-depleting antibodies in specific populations of kidney transplant recipients: A systematic review and meta-analysis(Elsevier, 2023-09-27) Montero Pérez, Núria; Rodrigo, Emilio; Crespo Barrio, Marta; Cruzado, Josep Ma.; Gutierrez Dalmau, Alex; Mazuecos Blanca, María Auxiliadora; Sancho Calabuig, Maria Asuncion; Belmar Vega, Lara; Calatayud Aristoy, Emma; Mora Lopez, Paula; Oliveras Pagès, Laia; Solà, Eulàlia; Villanego, Florentino; Pascual, Julio (Pascual Santos)Background: Recommendations of the use of antibody induction treatments in kidney transplant recipients (KTR) are based on moderate quality and historical studies. This systematic review aims to reevaluate, based on actual studies, the effects of different antibody preparations when used in specific KTR subgroups. Methods: We searched MEDLINE and CENTRAL and selected randomized controlled trials (RCT) and observational studies looking at different antibody preparations used as induction in KTR. Comparisons were categorized into different KTR subgroups: standard, high risk of rejection, high risk of delayed graft function (DGF), living donor, and elderly KTR. Two authors independently assessed the risk of bias. Results: Thirty-seven RCT and 99 observational studies were finally included. Compared to anti-interleukin-2-receptor antibodies (IL2RA), anti-thymocyte globulin (ATG) reduced the risk of acute rejection at two years in standard KTR (RR 0.74, 95%CI 0.61-0.89) and high risk of rejection KTR (RR 0.55, 95%CI 0.43-0.72), but without decreasing the risk of graft loss. We did not find significant differences comparing ATG vs. alemtuzumab or different ATG dosages in any KTR group. Conclusions: Despite many studies carried out on induction treatment in KTR, their heterogeneity and short follow-up preclude definitive conclusions to determine the optimal induction therapy. Compared with IL2RA, ATG reduced rejection in standard-risk, highly sensitized, and living donor graft recipients, but not in high DGF risk or elderly recipients. More studies are needed to demonstrate beneficial effects in other KTR subgroups and overall patient and graft survival.