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- Overall and Sex-Specific Predictors of Secukinumab Effectiveness in European Patients With Psoriatic ArthritisPublication . Heberg, Jette; Georgiadis, Stylianos; Ahmadzay, Zohra Faizy; Glintborg, Bente; Castrejón, Isabel; Kazemi, Mehrdad Shoae; Loft, Anne Gitte; Michelsen, Brigitte; Rasmussen, Simon Horskjær; Laas, Karin; Vorobjov, Sigrid; Sánchez-Alonso, Fernando; Rotar, Ziga; Pirkmajer, Katja Perdan; Šenolt, Ladislav; Gudbjornsson, Bjorn; Gröndal, Gerdur; Codreanu, Catalin; Iannone, Florenzo; Atzeni, Fabiola; Mann, Heřman; Nordström, Dan; Hokkanen, Anna-Mari; Garcia, Jorge; Barcelos, Filipe; Mielnik, Pawel; Kvien, Tore K; Kenar-Artin, Gokee; van de Sande, Marleen; Nissen, Michael J; Möller, Burkhard; Olofsson, Tor; Wallman, Johan K; Hetland, Merete Lund; Østergaard, Mikkel; Ørnbjerg, Lykke Midtbøll; Comprehensive Health Research Centre (CHRC) - pólo NMS; NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM); Journal of RheumatologyOBJECTIVE: Identifying patient characteristics that predict treatment response in psoriatic arthritis (PsA) may help optimize treat-to-target strategies. We aimed to explore overall and sex-specific predictors of secukinumab (SEC) effectiveness in European patients with PsA treated in routine care. METHODS: We analyzed data from 14 registries in the European Spondyloarthritis (EuroSpA) Research Collaboration. Patients aged ≥ 18 years at diagnosis, initiating SEC treatment from January 2015 to January 2021, were included. Multiple imputation was used for missing covariates at treatment start (baseline) and Disease Activity Index for Psoriatic Arthritis based on 28 joints (DAPSA28) at 6 months. Overall and sex-stratified analyses were performed by logistic and Cox regressions to identify baseline predictors of the following treatment outcomes: (1) DAPSA28 low disease activity (LDA; DAPSA28 ≤ 14) at 6 months, (2) DAPSA28 moderate response at 6 months, and (3) SEC discontinuation within 12 months. RESULTS: In total, 2790 patients (43% male) were included. Median age was 43 years (IQR 34-52), and SEC was the first-line biologic/targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD) in 665 patients (24%). Positive predictors for both DAPSA28 LDA and DAPSA28 moderate response were male sex, fewer previous b/tsDMARDs, C-reactive protein (CRP) > 10 mg/L, and lower Health Assessment Questionnaire (HAQ) score. Absence of psoriasis, higher patient fatigue, and tender joint counts predicted SEC discontinuation within 12 months. For some outcomes, sex-specific predictors were fewer previous b/tsDMARDs and CRP > 10 mg/L among male patients and lower patient fatigue score among female patients. CONCLUSION: We identified overall and sex-specific predictors of SEC effectiveness in European patients with PsA. Our findings may support personalized treatment decisions.
- Towards patient-centered healthcarePublication . Zagalo, Daniela Mariana; Palmieri, Cristiana; Resende, Noelle; Costa, Teresa; de Sousa, Rute Dinis; Canhão, Helena; Bozza, Fernando A; Comprehensive Health Research Centre (CHRC) - pólo NMS; Laboratório Associado de Translacção e Inovação para a Saúde Global - LA Real (Pólo NMS); NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM); Laboratório Associado de Translacção e Inovação para a Saúde Global - LA Real (Pólo FCT); Springer VerlagIn response to the dynamic evolution of the medical profession, driven by digital transformation, demographic shifts, and global health challenges, medical schools are emphasizing the importance of soft skills alongside technical and digital expertise. This scoping review aimed to identify key concepts and core characteristics related to soft skills in medical literature. Following a comprehensive search across PubMed, Scopus, and Web of Science, supplemented by a manual search and conducted in accordance with PRISMA-ScR guidelines, 218 articles were identified. After screening and full-text evaluation, 83 studies met the inclusion criteria. The analysis of the literature revealed three recurring thematic axes: (1) the global trend of incorporating soft skills into medical education; (2) the adoption of innovative andragogical strategies to foster the development of these competencies; and (3) the persistent obstacles and limitations that hinder the effective implementation of soft skills training in medical curricula. The review identified critical research gaps and priority areas to strengthen the integration of soft skills-related competencies in medical curricula. These findings highlight the need for targeted strategies to develop compassionate, culturally responsive physicians capable of delivering high-quality, patient-centered care. By synthesizing current evidence and mapping key themes and limitations, this review provides a foundation for future educational interventions and policy development in soft skills training.
- COPD maintenance trials use heterogeneous outcomes and measurement instrumentsPublication . Truong, Vi; Bin Safar, Sulaiman; Ananth, Sachin; Fally, Markus; Beech, Augusta; Souto-Miranda, Sara; Diar Bakerly, Nawar; Gorst, Sarah L.; Singh, Dave; Vestbo, Jørgen; Lahousse, Lies; Mathioudakis, Alexander G.; Comprehensive Health Research Centre (CHRC) - pólo NMS; NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM); European Respiratory SocietyBackground Randomised controlled trials (RCTs) of COPD management assess heterogeneous outcomes with diverse instruments and often omit those important to patients and healthcare professionals, limiting interpretability and comparability. This review aimed to identify the outcomes and instruments used in phase III/IV COPD maintenance management RCTs and assess their consistency. Methods We systematically reviewed all phase III/IV RCTs registered on ClinicalTrials.gov between 2010 and 2025 evaluating COPD maintenance management. Outcomes and measurement instruments were extracted from registry entries and categorised using the COMET (Core Outcome Measures in Effectiveness Trials) taxonomy. Registered outcomes from a random 10% sample were compared with the corresponding publications to assess concordance. Outcome frequencies were summarised across intervention types and sponsor categories. Results 43 unique outcomes were identified across 240 eligible RCTs. Physiological (89.5%), clinical (85.0%) and life impact outcomes (63.8%) were most frequently assessed, whereas resource use (39.6%), safety (36.7%) and mortality (16.7%) outcomes were less commonly reported. Only lung function (76.3%) and health-related quality of life (57.5%) appeared in over half of the trials. Exacerbations were reported in 40.4% of studies, while several patient-prioritised outcomes, particularly activities of daily living (5.4%) and exercise tolerance (18.3%), were infrequently assessed. Industry-sponsored RCTs more often reported lung function, resource use and adverse events; non-industry trials more frequently included biomarkers. Concordance between registered and published outcomes was acceptable (79.7%), although safety outcomes and instruments were sometimes under-reported. Conclusion COPD maintenance management RCTs show substantial heterogeneity and incomplete assessment of patient-prioritised outcomes. An internationally representative, multi-stakeholder core outcome set is urgently needed to improve consistency and patient-centred evaluation in future trials.
- Psoas Major muscle area as a prognostic marker in peripheral arterial diseasePublication . Fernandes-Carvalho, João; Braga-Simões, João; Santos-Silva, Daniela; Sá-Martins, Vítor; Andrade, José Paulo; Ribeiro, Hugo; Rocha-Neves, João; NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM); Comprehensive Health Research Centre (CHRC) - pólo NMS; Frontiers MediaIntroduction – Although frailty and reduced muscle mass are known to worsen surgical outcomes, the prognostic value of psoas major morphometry in peripheral arterial disease (PAD) remains incompletely defined. Sarcopenia, frequently quantified through cross-sectional psoas major muscle area on preoperative imaging, has emerged as a potential prognostic marker in patients undergoing lower-limb revascularization for PAD. This systematic review and meta-analysis aimed to evaluate whether reduced psoas major muscle area is associated with short- and long-term mortality following revascularization. Methods – A systematic search of MEDLINE, Scopus, and Web of Science identified observational studies assessing psoas muscle morphometrics in adults undergoing surgical or endovascular revascularization for PAD. Seven retrospective cohort studies (n = 2, 290 patients) met the inclusion criteria. Study quality was assessed using the NHLBI tool. Random-effects meta-analyses were performed for 1-month and 1-year mortality. Heterogeneity was evaluated using I², and prediction intervals were calculated. Due to the small number of studies, meta-regression was not performed. Results – Three studies contributed to the 1-month mortality analysis. The pooled estimate suggested a possible increase in early mortality among sarcopenic patients with a smaller psoas major area, but the association was not statistically significant (RR = 2.45; 95% CI 0.58–10.36; I2 = 38.3%; p = 0.22). Five studies reported 1-year mortality, demonstrating a significant association between reduced psoas major muscle area and increased long-term mortality (RR = 2.37; 95% CI 1.51–3.73; I2 = 43.4%; p < 0.001). Although point estimates remained directionally consistent across heterogeneous imaging methodologies and sarcopenia definitions, confidence intervals were wide, and the prediction interval for 1-year mortality crossed the null value, indicating uncertainty regarding the magnitude and consistency of the association across future settings. Insufficient data prevented quantitative synthesis of limb outcomes. Conclusion – A reduced psoas major muscle area was associated with increased 1-year mortality in patients undergoing lower-limb revascularization for PAD, supporting a potential role for psoas morphometry as a prognostic marker of long-term vulnerability. Although short-term mortality findings were inconclusive due to limited power, psoas morphometry may have value in preoperative risk stratification. Standardized definitions and prospective studies are needed before routine clinical integration can be recommended and to clarify whether targeted nutritional and rehabilitation strategies may improve outcomes. Systematic Review Registration – identifier CRD420251118644, https://www.crd.york.ac.uk/PROSPERO/view/CRD420251118644
- A privacy-preserving EMG-based wearable for cough monitoringPublication . Carreiro-Martins, Pedro; Caires, Iolanda; Leiria-Pinto, Paula; Cordeiro-Ferreira, Gonçalo; Novais, Luís; Afonso, Ricardo A.; Neuparth, Nuno; NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM); Laboratório Associado de Translacção e Inovação para a Saúde Global - LA Real (Pólo NMS); Comprehensive Health Research Centre (CHRC) - pólo NMS; Elsevier Espana S.L.U
- Clinical outcomes of dengue patients requiring intensive care in BrazilPublication . Azevedo, Luciano Cesar Pontes; Siqueira, Marina Martins; Correa, Lucas Hernandes; Pitrowsky, Melissa Tassano; Borges, Lunna Perdigao; Salluh, Milla Fuks; Fonseca, Henrique Andrade R.; Soares, Marcio; Salluh, Jorge Ibrain Figueira; NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM); Comprehensive Health Research Centre (CHRC) - pólo NMS; ElsevierBackground Dengue may lead to critical illness requiring intensive care unit (ICU) admission. Even though Brazil is one of the most affected countries worldwide, national data are limited. Understanding clinical severity and outcomes is essential to inform policy and preparedness. Methods We conducted a retrospective study of adult dengue ICU admissions in Brazil from 2015 to 2024 using aggregated data from two nationwide complementary datasets: the Brazilian ICU registry (UTIs Brasileiras) and DATASUS Hospital Information System. The registry dataset includes clinical, severity, and organ-support variables from public and private institutions, while DATASUS captures public-system (SUS) reimbursed hospitalizations. Outcomes were ICU and in-hospital mortality, organ support, and length of stay. Results We identified 32,016 episodes of dengue admissions in the ICU registry and 11,241 in DATASUS. Data from the registry for the first 24 h of ICU shows mechanical ventilation use in 5.8% and vasopressors use in 7.2%. In-hospital mortality was 8.2% in the ICU registry. In DATASUS, in-hospital mortality was 18.6%. Patients admitted to public hospitals in the ICU registry had unadjusted ICU mortality of 20% and in-hospital mortality of 25%. Unadjusted mortality rates were higher in subgroups like older patients and those in use of vasopressors. Conclusion: Dengue requiring ICU admission in Brazil is associated with significant morbimortality. Mortality rates were higher in subgroups such as old patients and those admitted to public hospitals. Further studies are necessary to identify the potentially modifiable, organizational and patient-level factors associated with outcomes.
- How does European mental health legislation promote autonomy for those in involuntary care? A comparative descriptive analysis of 27 countriesPublication . Aluh, Deborah Oyine; Georgaca, Eugenie; Lantta, Tella; Rugkåsa, Jorun; NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM); Comprehensive Health Research Centre (CHRC) - pólo NMS; Springer Science Business MediaPurpose: A growing emphasis on autonomy, manifest through the influence of recovery orientations, user involvement, and the broader shift towards patient-centered healthcare, has significantly influenced mental health care. The Convention on the Rights of Persons with Disabilities (CRPD) is a pivotal development in this regard, challenging longstanding practices in mental health care and particularly involuntary care. This study examined how European mental health legislation seeks to promote the autonomy of those subjected to involuntary care, by analyzing laws from 27 jurisdictions. Methods: Data was collected via a comprehensive survey between July 2023 and September 2024, completed by country representatives from the EU COST Action FOSTREN network. We examined the letter of the law as regards 16 autonomy-promoting provisions including the principle of least restriction, capacity-based criteria, supported decision-making, advance healthcare directives, treatment plans, rights to appeal, legal aid, advocacy services, and oversight mechanisms. Results: Most laws across the 27 jurisdictions were amended in the last eight years. All legislations included at least one measure related to the principle of least restriction, the right to appeal against involuntary status, and support to do so, such as legal aid. In contrast, mechanisms designed to support autonomous decision-making, such as Advance Healthcare Directives and Supported Decision-Making, were less frequently included as a right. Conclusion: While procedural legal safeguards are well established, there is significant variation in the adoption of other legal mechanisms to afford statutory rights to individuals in line with autonomy promoting approaches, including the CRPD.
- pH-triggered gold-PNA nanoclusters reverse miR-155-driven metabolic radioresistance in breast cancerPublication . Jiang, Yifei; Zhang, Yunqi; Yang, Huizhen; Gao, He; Hai, Wangxi; Zhang, Chunfu; Yao, Jiali; Mall, Raghvendra; Conde, João; Han, Xiangfei; Li, Biao; Zhang, Min; NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM); Comprehensive Health Research Centre (CHRC) - pólo NMS; ELSEVIER SCI LTDRadioresistance driven by metabolic reprogramming, particularly the upregulation of aerobic glycolysis, remains a critical barrier that hinders effective breast cancer treatment. MicroRNA-155 (miR-155) is a central regulator of this metabolic adaptation; however, therapeutic strategies that target miR-155 suffer from poor targeting, rapid clearance and inefficient intracellular delivery of nucleic acid inhibitors. This study presents the preparation of a pH-responsive radio-nanotherapeutic platform comprising 177Lu-labeled, peptide nucleic acid (PNA)-based miR-155 inhibitor-functionalized gold nanoclusters that undergo pH-triggered aggregation/self-assembly in the acidic tumor microenvironment. This pH-driven in situ aggregation markedly enhances intratumoral retention and facilitates efficient cytosolic delivery of the PNA payload. Specific silencing of miR-155 suppresses glycolytic flux and lactate production, which creates a reduced glycolytic capacity that sensitizes tumor cells to radiation-triggered DNA impairment. The concurrent emission of β-particles from the 177Lu payload delivers localized internal radiotherapy, which combines with metabolic inhibition to achieve potent inhibition of tumor growth. Leveraging this treatment-associated inflammatory response, anti-PD-L1 blockade synergizes with 177Lu@LAuP to eradicate tumors, enhance memory T-cell formation, and maintain a favorable safety profile. This work establishes a generalizable strategy to couple stimuli-responsive nanoassembly with miRNA-directed metabolic intervention to overcome radioresistance and prime immunotherapy in solid tumors.
- Clinical predictors of response to methotrexate in patients with rheumatoid arthritisPublication . Rodrigues, Joana Ramos; Donato, Helena; Azevedo, Soraia; Pires, Luís; Inês, Luís Pedro Bolotinha de Sousa; Morgado, Manuel; Mourão, Ana Filipa; Comprehensive Health Research Centre (CHRC) - pólo NMS; NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM); John Wiley and Sons Inc.Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation, structural damage, and disability. Methotrexate (MTX) is the first-line treatment; however, up to one-third of patients exhibit an inadequate response. This systematic review aimed to identify clinical, serological, genetic, pharmacogenomic, and treatment-related predictors of MTX response in RA. Methods: A systematic search of PubMed/MEDLINE, Scopus, and the Cochrane Central Register of Controlled Trials (CENTRAL) was conducted for studies published up to May 22, 2024. Randomized controlled trials, prospective cohort studies, and registry-based studies evaluating predictors of MTX efficacy were included. In total, 87 studies met the eligibility criteria and were included in the review. Predictors were categorized as demographic/clinical, disease-related, serological/immunological, genetic/pharmacogenomic, treatment-related, and emerging. Evidence was synthesized narratively, with consideration of methodological quality and consistency. Results: Consistent predictors of favorable MTX response included lower baseline disease activity, better functional status, early MTX initiation, and absence of erosive disease. Male sex, older age, and moderate alcohol consumption were associated with improved outcomes, although these associations may be influenced by treatment-related and behavioral confounders, whereas smoking and higher body mass index were linked to reduced efficacy. Several inflammatory and cellular biomarkers were associated with MTX response, although individual pharmacogenetic variants showed limited reproducibility. Treatment-related factors, including subcutaneous administration, rapid dose escalation, glucocorticoid co-therapy, and folate supplementation, were associated with improved efficacy and tolerability. Emerging proteomic, epigenetic, and metabolomic signatures demonstrated potential for early response prediction. Conclusions: Overall, early disease control and optimized treatment strategies appear to be more reliable predictors of MTX response than isolated demographic or genetic factors. Integration of clinical predictors with emerging molecular biomarkers may support personalized treatment approaches and earlier identification of MTX non-responders. PROSPERO Registration Number: CRD42023464365.
- Preventing regrettable substitutionsPublication . Aiello-Holden, Kiara; Bartmann, Kristina; Buratti, Franca Maria; Cabaton, Nicolas J.; Coppola, Lucia; Corsini, Emanuela; De la Vieja, Antonio; Dirven, Hubert; Dusinska, Maria; El Yamani, Naouale; Franko, Nina; Gostner, Johanna M.; Grova, Nathalie; Gütter, Louise; Iglesias-Hernández, Patricia; Iulini, Martina; Kodila, Anja; Kohl, Yvonne; Lori, Gabriele; Louro, Henriqueta; Marcon, Francesca; Mhaouty-Kodja, Sakina; Mposhi, Archibold; Naulé, Lydie; Palleschi, Simonetta; Rossi, Barbara; Rundén-Pran, Elise; Salani, Francesca; Santori, Nicoletta; Silva, Maria João; Dolenc, Marija Sollner; Testai, Emanuela; Torres-Ruiz, Mónica; Turner, Jonathan; Viguié, Catherine; Zalko, Daniel; Tait, Sabrina; NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM); Comprehensive Health Research Centre (CHRC) - pólo NMS; Frontiers MediaBisphenol A (BPA) alternatives are increasingly used in the manufacture of industrial and consumer products, following regulatory restrictions on BPA. However, insufficient safety data on these substitutes raise concern as regards potential regrettable substitutions. Under the EU Partnership for the Assessment of Risks from Chemicals (PARC), Work Package 5 (WP5) addresses this challenge by applying a human-relevant tiered hazard assessment strategy grounded on OECD test guidelines as first tier and expanding the battery to include NAMs (New Approach Methodologies). Eight BPA alternatives were prioritized for studies addressing key toxicological endpoints, namely, endocrine disruption (ED), developmental neurotoxicity (DNT), immunotoxicity, genotoxicity and carcinogenicity and metabolic fate examination (detoxification vs. potential bioactivation), to enable early identification of biological activity and support cross-endpoint prioritization. This manuscript describes the structure and implementation of the testing framework. This integrated testing strategy proposes a structured approach to identify substances of potential concern, guide targeted higher-tier studies, and support regulatory prioritization. PARC WP5 framework is testing whether coordinated NAM-based methods may contribute to next-generation risk assessment and help prevent regrettable substitutions among BPA alternatives for rapid regulatory adoption. Detailed experimental results will be reported separately upon completion of the project.