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  • Individual Participant Data Meta-Analysis (IPDMA) of long-term COVID-19 outcomes in a systematic review-informed, international, multidisciplinary database
    Publication . Ali, Myzoon; Brady, Marian C.; Campbell, Pauline; Rooney, Scott; Williams, Linda; Paul, Lorna; Pereira, Filipe Alexandre
    Background: Identifying and addressing long-term health and societal challenges after COVID-19 is a research priority. Objectives: To create an international, multidisciplinary COVID-19 database, and synthesise long-term outcomes, predictors and costs. Design: Systematic identification of COVID-19 data sets and meta-analysis of individual participant data on long-term outcomes after COVID-19. Setting: Contributed data were collected in clinical, community and research settings. Interventions: Interventions from original studies were included as covariates in models. Data sources: MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, Web of Science, PsycInfo® (American Psychological Association, Washington, DC, USA), Cumulative Index to Nursing and Allied Health Literature, World Health Organization Global Index Medicus, Epistemonikos, LitCOVID; World Health Organization International Clinical Trials Registry Platform; ClinicalTrials.gov and supplementary searches for studies (November 2019-November 2021) were searched for studies on > 10 people from cohort, case-control, survey or randomised controlled trial studies, across any setting, describing validated assessment instruments, symptoms, hospitalisation, discharge destination or mortality beyond 28-days after COVID-19 onset. Data were extracted by two independent reviewers. Methods: Principal investigators contributed fully anonymised individual participant data. Demography, equity and symptoms were described. Assessment instruments were mapped to the International Classification of Functioning, Disability and Health. Factors associated with outcomes at 3-6 months, 9-12 months and beyond 12 months of index infection, for n > 500 individual participant data and > 1 data set were described using ratio of difference, point estimates, odds ratio and 95% confidence interval, as appropriate. The Mixed Methods Appraisal Tool described study quality; models were appraised using a Grading of Recommendations Assessment, Development and Evaluation-informed approach; heterogeneity was described using I2. Outcome measures: Included overall perception of health, multidomain cognitive function, anxiety, depression, stress, post-traumatic stress disorder, fatigue, strength, walking ability, mobility, coping with daily life, breathlessness, mortality, later hospitalisation and health-related quality of life. Results: PRECIOUS collated 116 data sets from 40 countries (individual participant data = 62,849), comprising 20 randomised controlled trials, 13 case-control, 60 cohort 2 longitudinal, 1 survey and 20 other study types. Participants' median age was 58 years interquartile range (45-68); 34,185 (54.4%) were female; 158 unique symptoms and 137 unique assessment instruments were captured, predominantly describing International Classification of Function, Disability and Health-body functions. Women had poorer outcomes across 30/37 models, compared with men. In 15/37 models, pre-existing lung disease and increasing age were associated with poorer outcomes; hospitalisation, diabetes and chronic kidney disease were each associated with poorer outcomes in 8/37 models. Initial hospitalisation resulted in lower health-related quality of life that did not recover for up to 2 years after initial infection. Heterogeneity was low in 34/37 models; 22/37 models were of moderate and 11/37 were of low quality. Limitations: Use of secondary data limits available covariates, outcomes and time points to those included in primary data sets; evidence was primarily based on high-income countries. There was a lack of data on longer-term healthcare resource use to estimate the costs to the healthcare system. Conclusions: PRECIOUS contributes to the overall picture of long-term COVID-19 outcomes beyond the long-COVID condition and highlights poorer long-term outcomes in women and people with pre-existing comorbidities. Future work: Evidence gaps included healthcare resource use, isolation, loneliness, societal participation and return to work outcomes. Data are needed on the role of health inequity on long-term outcomes. Study registration: This study is registered as PROSPERO (CRD42020224323, IRAS ID: 293578).
  • NeuroPORTRESS: prevalence, clinical spectrum, and factors associated with neurological involvement in Sjögren’s disease
    Publication . Costa, Roberto Pereira da; Bandeira, Matilde; Silvério-António, Manuel; Lopes, Ana R.; Cunha-Santos, Filipe; Pereira, Paulo J.; Raimundo, Diana Belchior; Cunha, Anita; Oliveira, Cláudia Pinto; Duarte, Ana C.; Dias, João Madruga; Santos, Mariana Emília; Gonçalves, Maria João
    Objectives: Neurological involvement is a heterogeneous complication of Sjögren's disease (SjD). We aimed to describe its prevalence and spectrum and identify factors associated with peripheral (PNS) and central nervous system (CNS) involvement. Methods: We conducted a cross-sectional, multicentre study based on PORTRESS, the Portuguese SjD registry. Demographic and clinical data were compared between groups. Independent associations of overall neurological, PNS, and CNS involvement were identified through logistic regression models using complete-case analysis. Results: Among 1234 patients, 62 (5.0%) had neurological involvement: 46 (3.7%) PNS, 17 (1.4%) CNS, with one patient having both. Patients with neurological manifestations had higher ESSDAI, more cryoglobulinaemia, purpura/cutaneous vasculitis and monoclonal gammopathy, and higher mortality. Cryoglobulinaemia and higher baseline ESSDAI (excluding neurological domains) were independently associated with neurological involvement. PNS involvement was associated with older age at symptom onset, cryoglobulinaemia, lymphopenia and higher ESSDAI. A sensitivity analysis revealed that low C4, persistent salivary gland swelling, and purpura/cutaneous vasculitis were also independently associated with PNS involvement. CNS involvement was associated with male sex and younger age at diagnosis. Conclusion: Neurological involvement in SjD was infrequent. PNS involvement clustered with vasculitic and B-cell-driven features and worse outcomes, whereas CNS manifestations appeared to show a distinct demographic profile, characterised by younger age and male sex. These findings support separate evaluation of PNS and CNS involvement and may help identify patients requiring neurological surveillance. Given the limited number of cases, particularly of CNS involvement, these findings remain exploratory and require confirmation in larger cohorts.
  • Detection of TR34/L98H pan-azole-resistant Aspergillus fumigatus in poultry farm environments
    Publication . Gomes, Bianca; Dias, Marta; Cervantes, Renata; Gonçalves, Lídia; Carolino, Elisabete; Ramos, Miguel J. N.; Nunes, Mónica; Dias, Ricardo; Viegas, Carla
    Introduction: Poultry farms have been recognized as environments prone to fungal contamination. However, the occurrence of azole-resistant Aspergillus fumigatus and its cytotoxic potential remain insufficiently characterized. This study aimed to characterize the occurrence, cytotoxic potential, and azole-resistance profile of Aspergillus section Fumigati in poultry farms.Methods: A total of 420 samples, including air (n = 47), electrostatic dust cloths (n = 87), bedding (n = 87), feed (n = 95), swabs (n = 87), workers’ masks (n = 2), and broiler breast (n = 15), were obtained. Fungal characterization was performed through culture-based methods (27 °C and 37 °C), followed by azole resistance screening according to EUCAST guidelines. Resistant isolates were subjected to whole-genome sequencing and a targeted analysis of cyp51A mutations. The cytotoxicity potential of fungal isolates and environmental samples was evaluated using selected cell lines representing respiratory organs (human alveolar [A549]) and detoxification organs (swine kidney [SK]/hepatocellular carcinoma [HepG2]). Results: Seven putative Aspergillus fumigatus isolates exhibited pan-azole resistance (MICs: ≥ 2 mg/L ITR/VOR; ≥ 1mg/L for POS). Four isolates carried the TR34/L98H mutation and were recovered from bedding (n = 3) and air (n = 1), suggesting the presence of resistant A. fumigatus in poultry farm matrices. Although 12% of isolates induced toxicity on both cell lines (17/145), no significant association was observed between isolate cytotoxicity and environmental sample toxicity, suggesting that additional biological and chemical components may contribute to the overall toxicological profile of farm environments. Discussion: The study highlights the occurrence of azole-resistant A. fumigatus in poultry farms and supports integrated surveillance approaches addressing antifungal resistance and environmental exposure risks in poultry production.
  • Perception of consumers about Portuguese food service
    Publication . Costa, Carmen; Viegas, Cláudia; Rocha, Ada
    ABSTRACT Introduction: Food Service is the provision of meals and drinks to well-defined groups of people. It aims to provide nutritionally balanced, safe, and sustainable meals compatible with the client's conditions and needs. Food service companies must meet the client’s expectations while simultaneously satisfying consumers in their daily meals. Objectives: To identify the general perception of Portuguese consumers about food service, more precisely their characterisation of this sector, its products and services, and companies operating in Portugal. Methodology: This cross-sectional study is based on a survey of the Portuguese population, aged above 18 years or older, and who is currently, or has already been, a food service consumer. The study’s sample consisted of 1900 consumers. Results: Overall, 42% of respondents considered that food service satisfies both their needs and expectations, while 44% reported that it satisfies their needs but not their expectations. Most consumers recognised key characteristics of food service, namely good location and accessibility (88%), operating schedules adapted to users’ activities (85%), and provision of social interaction during meals (82%). Hygiene and food safety were the most highly valued attributes of both products (82%) and services (81%), followed by meal temperature (78%). Regarding food service companies, trustworthiness was the most appreciated characteristic (71%), whereas innovation received the lowest ratings across products (41%), services (45%) and companies (43%). Conclusions: Portuguese consumers generally have a positive perception of food service in Portugal, particularly regarding hygiene and food safety, meal temperature, accessibility, and trust. Innovation remains a key area for improvement to better meet consumer expectations.
  • A cohort study of forced vital capacity, airway obstruction, and survival in the multinational Burden of Obstructive Lung Disease study
    Publication . Burney, Peter G. J.; Bagkeris, Emmanouil; Potts, James; Nielsen, Rune; Devereux, Graham; El Rhazi, Karima; Aquart-Stewart, Althea; Nafees, Asaad A.; Koul, Parvaiz; Mahesh, Padukudru Anand; Agarwal, Dhiraj; Juvekar, Sanjay; Gislason, Thorarinn; Dias, Maria Hermínia Monteiro Brites
    Background: In the USA, higher forced vital capacity (FVC) is linked with longer survival, and FVC is associated with survival independently of ethnicity. The implications for the low FVC values in parts of Asia and Africa are unknown. Methods: We used data from 16 sites of the multinational Burden of Obstructive Lung Disease (BOLD) study that completed follow-up of participants between 2019 and 2021 and reported at least five deaths between baseline and follow-up. We assessed the association of mortality with FVC and Forced Expiratory Volume in 1 second (FEV1)/FVC ratio within each site using Cox proportional hazards models. These models were adjusted for age, smoking, height, and weight. Effect estimates from all sites were combined using meta-analysis. Systematic regional differences were investigated. Results: Of 9927 study participants with follow-up data, 1120 (11.3%) had died [mean follow-up = 8.7 years, standard deviation (SD) = 3.3 years]. Baseline post-bronchodilator FVC and FEV1/FVC were inversely associated with mortality. When both FVC and FEV1/FVC were mutually adjusted for each other, the decreased mortality rates were more pronounced for each SD higher FVC at baseline [44% (95% confidence interval (CI): 25%, 58%) for men and 28% (95% CI: 11%, 41%) for women] than for FEV1/FVC at baseline [14% (95% CI: 8%, 20%) for men and 7% (95% CI: -10%, 21%) for women]. The probability of true regional differences was low. Conclusions: People with a higher FVC adjusted for age, sex, and height have a longer survival. Regional adjustments to lung function standards are inappropriate when assessing prognosis.
  • Comparison of gonadal dose estimation using treatment planning systems and Monte Carlo methods in pelvic radiotherapy
    Publication . Ribeiro, D. R.; Campos, G.; Carolino, Elisabete; Martins, L. S.; Borrego, M.; Sá, Ana Cravo
    Introduction: Unintended irradiation of organs outside the target volume remains a concern in pelvic radiotherapy, particularly for radiosensitive structures such as the gonads. Analytical dose calculation algorithms used in treatment planning systems (TPS) may underestimate out-of-field doses. Monte Carlo (MC) methods provide improved dosimetric accuracy. This study compared gonadal dose estimates from a clinical TPS with those obtained using MC simulations. Methods: A retrospective analysis was performed on 30 patients treated for rectal or gynaecological malignancies using 3D conformal radiotherapy (3DCRT) and volumetric modulated arc therapy (VMAT). Plans were generated in Eclipse using the Anisotropic Analytical Algorithm (AAA). Gonads were retrospectively contoured, and maximum (Dmax) and mean (Dmean) doses were extracted from dose-volume histograms. MC simulations were performed using PRIMO, previously validated against measurements. Differences were assessed using the Wilcoxon signed-rank test. Results: MC simulations agreed with measurements (<1%). MC-derived Dmax values were higher than TPS estimates, with median values of 47.89 Gy vs 46.58 Gy (right gonad) and 48.37 Gy vs 46.81 Gy (left gonad). Maximum differences reached 5.54 Gy and 5.64 Gy. Discrepancies were greater in low-dose regions, highlighting TPS limitations in out-of-field estimation. No significant differences were observed for Dmean or between techniques. Conclusion: TPS may underestimate maximum gonadal dose, particularly outside the treatment field. MC simulations provide more accurate estimates, supporting improved fertility risk assessment. Implications for practice: MC-based evaluation may improve the accuracy of gonadal dose assessment, particularly in out-of-field regions. This approach can support more robust plan evaluation, encourage consideration of gonads as organs at risk, and facilitate more individualised patient counselling regarding fertility risks. Increased awareness of unintended gonadal exposure may also promote optimisation strategies to minimise dose.
  • Impact of a health and sustainability menu option on consumer perception of food service in Portugal
    Publication . Costa, Carmen; Viegas, Cláudia; Rocha, Ada
    Introduction: Food Service aims to provide nutritionally balanced, safe, and increasingly sustainable meals for specific population groups. In recent years, the sector has faced growing challenges driven by changing consumer expectations, public health priorities, and sustainability demands, particularly regarding menu composition and dietary patterns. Objective: To evaluate the association between the implementation of a health and sustainability menu option (flexitarian menu) and consumers' perceptions of Food Service in Portugal. Methods: A quasi-experimental repeated cross-sectional study was conducted among adult consumers attending a Food Service unit in Portugal. Consumer perceptions were assessed using paper-based questionnaires administered to three independent samples before implementation of the intervention and 3 and 9 months afterwards. The questionnaires evaluated perceptions of Food Service products, services, companies, and overall sector performance. Descriptive and inferential statistical analyses were performed. Results: Overall, the implementation of the flexitarian menu option was associated with generally favorable trends in consumer perceptions over time. After 9 months, more favorable evaluations were observed for perceived product quality, innovation, adequacy of meals to consumers' needs and expectations, and organizational attributes related to environmental and social responsibility. Although only limited statistically significant differences were identified, overall consumer evaluations of Food Service became progressively more favorable following implementation. Conclusions/Originality: This study provides real-world evidence suggesting that the sustained implementation of a health and sustainability menu option may be associated with more favorable consumer perceptions of Food Service. The findings contribute to the emerging evidence supporting menu-based sustainability interventions as a feasible strategy for promoting healthier and more sustainable institutional food environments.
  • The challenge of public participation in European hospitals: a Portuguese case study
    Publication . Serapioni, Mauro; Crisóstomo, Sofia; Santos, Margarida; Campos, Alfredo; Tavares, David
    ABSTRACT Introduction: This article presents the results of an empirical study designed to examine the current state of public participation in hospital institutions of Portugal's National Health Service (NHS) and to assess the level of implementation and functioning of Advisory Councils. Methods: The study combines a review of the literature on participation experiences in hospitals across several European countries with a questionnaire administered to the presidents of hospital institutions within the Portuguese NHS. Together, these methods provide a basis for identifying the status of public participation in Portugal in light of relevant European experiences. Results: The findings indicate that participation is largely confined to communication and the provision of information to users, as well as consultation processes through which patients can express their preferences. However, the active involvement of patients and their representatives in healthcare decision-making remains limited and underdeveloped. Conclusion: Hospitals across Europe, and particularly in Portugal, face the challenge of fostering more effective forms of user participation. This requires moving beyond consultation towards meaningful involvement of patients and their representatives in healthcare decision-making processes.
  • A microRNA atlas of CD4+ T cell subsets in experimental autoimmune encephalomyelitis identifies regulators of disease pathogenesis
    Publication . Cunha, Carolina; Inácio, Daniel; Romero, Paula Vargas; Pais, Ana Teresa; Pelicano, Catarina; Costa, Marina; Mensurado, Sofia; Gonçalves-Sousa, Natacha; Papotto, Pedro H.; Neves, Daniel; Sobral, Daniel; Enguita, Francisco; Silva-Santos, Bruno; Gomes, Anita
    MicroRNAs (miRNAs) are key regulators of CD4+ T cell differentiation, but how they contribute to the course of an autoimmune disease in vivo remains poorly studied. Given the known roles in autoimmunity of pro-inflammatory T helper 1 (Th)1 and Th17 cells, and anti-inflammatory Foxp3+ regulatory cells, we established a triple-reporter mouse for Ifng, Il17, and Foxp3. We subjected it to experimental autoimmune encephalomyelitis (EAE) to characterize the miRNomes of the corresponding CD4+ T cell subsets. We identified 110 miRNAs differentially expressed between the pro-inflammatory (Th1 and Th17 cells) and the Treg cell subsets. Among these, we found novel functions for miR-122-5p and miR-1247 as regulators of Th17 cell proliferation and Th1 cell differentiation, thus impacting the course or severity of EAE, respectively. Importantly, their expression patterns suggest that miR-122-5p and miR-1247 act as peripheral brakes on CD4+ T cell pathogenicity that are subverted in the inflamed central nervous system.
  • Posterior hyaloid fibrosis in toxoplasma chorioretinitis
    Publication . Mendo, Inês; Camacho, Pedro; Cabral, Diogo
    Colour fundus photography shows a well-demarcated hyperpigmented peripheral lesion. Fluorescein angiography reveals a hypofluorescent lesion with venous dragging at its centre and no disc leakage. Optical coherence tomography B-scan through the lesion shows hyaloidal fibrosis with focal adhesion to the chorioretinal scar, without evidence of choroidal neovascularisation. Secondary healing with fibrosis and chorioretinal atrophy, along with vascular dragging and adhesion of the posterior hyaloid within this fibrous response, are part of the healing process in toxoplasmosis and may occur without choroidal neovascularisation.