Browsing by Issue Date, starting with "2024-05"
Now showing 1 - 10 of 18
Results Per Page
Sort Options
- To Correct or not to Correct (for treatment): Estimating Pre-treatment LDL-C Concentrations in Genetically Characterized Patients with Familial Hypercholesterolaemia on Lipid-lowering MedicationPublication . Stevens, C.A.T.; Elshorbagy, A.; Vallejo-Vaz, A.J.; Dharmayat, K.; Lyons, A.; Bourbon, M.; Chora, J.; Humphries, S.E.; Catapano, A.L.; Hovingh, G.; Mata, P.; Santos, R.; Soran, H.; Watts, G.F.; Raal, F.; Freiberger, T.; Ray, K.K.; on behalf of all the EAS FHSC CollaboratorsBackground and Aims: Pretreatment LDL-C measurements aid familial hypercholesterolaemia (FH) diagnosis, and are crucial in epidemiologic studies investigating FH, but are often unavailable because individuals are already on lipid-lowering medication (LLM). Several formulae have been reported to estimate pre-treatment LDL-C in people on LLM by ‘correcting’ their LDL-C concentrations for LLM type and dosage, based on observational or trial evidence of drug efficacy. We compared 4 published correction factors in estimating pre-treatment LDL-C in patients with FH. Methods: Cross-sectional analysis of adults with pathogenic/likely-pathogenic FH variants in the EAS-FH Studies Collaboration (FHSC) Registry. At the time of LDL-C measurement, N=3012 participants were not on LLM (Untreated group), and N=3226 were on LLM monotherapy, with information on LLM type and dosage allowing estimation of pre-treatment LDL-C (Corrected group) based on correction factors by Ruel 2018, Ellis 2016, Haralambos 2015 and Besseling 2014. We compared the groups for clinical characteristics and LDL-C by gene and variant. Results: The Corrected group was older than the Untreated group (median[IQR]: 50[39,63] vs. 38[28,50]y), with similar proportion of women (54.5% vs. 56.8%;p=0.14) but more comorbidities (all p<0.001). In the Corrected group, 3120 were on statins, 106 on ezetimibe, none on PCSK9-inhibitors. The Corrected group had higher LDL-C vs. Untreated group, with the difference greater at upper percentiles, regardless of correction factor. LDL-C was highest in those with LDLR>APOB>PCSK9 gene variants, but Corrected was still higher than Untreated LDL-C within each gene group. The difference in Corrected vs. Untreated LDL-C varied by variant, from +0.6 to +3.5mmol/L (20 commonest variants). The LDL-C differences persisted after adjusting for age, sex and comorbidities. Conclusions: Application of current LDL-C correction factors appears to overestimate pre-treatment LDL-C in epidemiologic settings, or the Untreated and Corrected groups might have inherently different LDL-C profiles. The accuracy of using LDL-C correction factors in FH therefore warrants further investigation.
- Impact of influenza vaccination strategy on medically attended influenza in Portugal in five pre-pandemic seasons (2015/16 to 2019/20)Publication . Machado, Ausenda; Kislaya, IrinaBackground: There is limited research on the impact of the yearly influenza vaccination programs in the eligible population. This study aimed to estimate the number of primary care medically attended influenza-confirmed cases (MAICC) among the population aged ≥65 years averted by influenza vaccination programme in Portugal during five seasons in the pre-COVID pandemic period (2015/16 to 2019/20). Methods: We compared the number of observed MAICC to the estimated number that would have occurred in a population without seasonal influenza vaccination (N). To estimate N, we used: i) number of MAICC estimated from national influenza surveillance systems, ii) vaccine coverage (VC) collected in a national telephone survey, iii) influenza vaccine effectiveness (IVE) estimates weighted by the proportion of virus circulation each season in Portugal. We estimated the number of MAICC averted (NAE) by the influenza vaccination programme per 100.000 inhabitants and number needed to vaccinate to prevent one MAICC. We used Monte-Carlo simulations to estimate 95% uncertainty intervals (UI). Results: Comparing with results from 2015/16 to 2017/18 (NAE ranged 24 to 44 per 100.000 inhab) the season 2018/19 showed the highest NAE (62.3 per 100.000 inhab) attributed to the influenza vaccination programme. In 2019/20 season the vaccination strategy averted approximately 11.7 per 100.000 inhab (95%UI: 6.0 to 20.9) events and it was necessary to vaccinate 549 (95%UI: 436 to 742) to prevent one MAICC in primary care. Conclusion: The influenza vaccination strategy had consistent and positive benefit, with more pronounced impact in 2018/19 season. This results were mainly due to a combination of a higher vaccination coverage assumed for 2018/19 (60.8%) and one of the highest vaccine effectiveness (34.8% vs. previous study range 8.5% to 40.6%). To maximize its impact, efforts should be conducted to increase the vaccine coverage. In addition, the surge for more effective vaccines should be maintained.
- Recurrence, Microevolution, and Spatiotemporal Dynamics of Legionella pneumophila Sequence Type 1905, Portugal, 2014-2022Publication . Manageiro, Vera; Borges, Vítor; Rodrigues, Raquel; Bettencourt, Célia; Silva, Cecília; Gomes, João Paulo; Gonçalves, PauloWe investigated molecular evolution and spatiotemporal dynamics of atypical Legionella pneumophila serogroup 1 sequence type 1905 and determined its long-term persistence and linkage to human disease in dispersed locations, far beyond the large 2014 outbreak epicenter in Portugal. Our finding highlights the need for public health interventions to prevent further disease spread.
- Temperature frequency and mortality: Assessing adaptation to local temperaturePublication . Wu, Yao; Wen, Bo; Gasparrini, Antonio; Armstrong, Ben; Sera, Francesco; Lavigne, Eric; Li, Shanshan; Guo, Yuming; Overcenco, Ala; Urban, Aleš; Schneider, Alexandra; Entezari, Alireza; Vicedo-Cabrera, Ana Maria; Zanobetti, Antonella; Analitis, Antonis; Zeka, Ariana; Tobias, Aurelio; Nunes, Baltazar; Alahmad, Barrak; Forsberg, Bertil; Íñiguez, Carmen; Ameling, Caroline; Cruz Valencia, César De la; Houthuijs, Danny; Dung, Do Van; Roye, Dominic; Indermitte, Ene; Mayvaneh, Fatemeh; Acquaotta, Fiorella; de'Donato, Francesca; Carrasco-Escobar, Gabriel; Kan, Haidong; Carlsen, Hanne Krage; Orru, Hans; Kim, Ho; Holobaca, Iulian-Horia; Kyselý, Jan; Madureira, Joana; Schwartz, Joel; Jaakkola, Jouni J.K.; Katsouyanni, Klea; Diaz, Magali Hurtado; Ragettli, Martina S.; Hashizume, Masahiro; Pascal, Mathilde; Coelho, Micheline de Sousa Zanotti Stagliorio; Ortega, Nicolás Valdés; Ryti, Niilo; Scovronick, Noah; Michelozzi, Paola; Correa, Patricia Matus; Goodman, Patrick; Saldiva, Paulo Hilario Nascimento; Raz, Raanan; Abrutzky, Rosana; Osorio, Samuel; Pan, Shih-Chun; Rao, Shilpa; Tong, Shilu; Achilleos, Souzana; Dang, Tran Ngoc; Colistro, Valentina; Huber, Veronika; Lee, Whanhee; Seposo, Xerxes; Honda, Yasushi; Kim, Yoonhee; Guo, Yue Leon; Li, Shanshan; Guo, YumingAssessing the association between temperature frequency and mortality can provide insights into human adaptation to local ambient temperatures. We collected daily time-series data on mortality and temperature from 757 locations in 47 countries/regions during 1979–2020. We used a two-stage time series design to assess the association between temperature frequency and all-cause mortality. The results were pooled at the national, regional, and global levels. We observed a consistent decrease in the risk of mortality as the normalized frequency of temperature increases across the globe. The average increase in mortality risk comparing the 10th to 100th percentile of normalized frequency was 13.03% (95% CI: 12.17–13.91), with substantial regional differences (from 4.56% in Australia and New Zealand to 33.06% in South Europe). The highest increase in mortality was observed for high-income countries (13.58%, 95% CI: 12.56–14.61), followed by lower-middle-income countries (12.34%, 95% CI: 9.27–15.51). This study observed a declining risk of mortality associated with higher temperature frequency. Our findings suggest that populations can adapt to their local climate with frequent exposure, with the adapting ability varying geographically due to differences in climatic and socioeconomic characteristics.
- Exploring the effect of clinical case definitions on influenza vaccine effectiveness estimation at primary care level: Results from the end-of-season 2022–23 VEBIS multicentre study in EuropePublication . Maurel, Marine; Mazagatos, Clara; Goerlitz, Luise; Oroszi, Beatrix; Hooiveld, Mariette; Machado, Ausenda; Domegan, Lisa; Ilić, Maja; Popescu, Rodica; Sève, Noémie; Martínez-Baz, Iván; Larrauri, Amparo; Buda, Silke; Túri, Gergő; Meijer, Adam; Gómez, Verónica; O'Donnell, Joan; Mlinarić, Ivan; Timnea, Olivia; Diez, Ana Ordax; Dürrwald, Ralf; Horváth, Judit Krisztina; Dijkstra, Frederika; Rodrigues, Ana Paula; McKenna, Adele; Filipović, Sanja Kurečić; Lazar, Mihaela; Kaczmarek, Marlena; Bacci, Sabrina; Kissling, Esther; VEBIS study teamBackground: Within influenza vaccine effectiveness (VE) studies at primary care level with a laboratory-confirmed outcome, clinical case definitions for recruitment of patients can vary. We used the 2022-23 VEBIS primary care European multicentre study end-of-season data to evaluate whether the clinical case definition affected IVE estimates. Methods: We estimated VE using a multicentre test-negative case-control design. We measured VE against any influenza and influenza (sub)types, by age group (0-14, 15-64, ≥65 years) and by influenza vaccine target group, using logistic regression. We estimated IVE among patients meeting the European Union (EU) acute respiratory infection (ARI) case definition and among those meeting the EU influenza-like illness (ILI) case definition, including only sites providing information on specific symptoms and recruiting patients using an ARI case definition (as the EU ILI case definition is a subset of the EU ARI one). Results: We included 24 319 patients meeting the EU ARI case definition, of whom 21 804 patients (90 %) meet the EU ILI case definition, for the overall pooled VE analysis against any influenza. The overall and influenza (sub)type-specific VE varied by ≤2 % between EU ILI and EU ARI populations. Discussion: Among all analyses, we found similar VE estimates between the EU ILI and EU ARI populations, with few (10%) additional non-ILI ARI patients recruited. These results indicate that VE in the 2022-23 influenza season was not affected by use of a different clinical case definition for recruitment, although we recommend investigating whether this holds true for next seasons.
- Ancestry of the major long-range regulatory site of the α-globin genes in the Portuguese population with the common 3.7 kb α-thalassemia deletionPublication . Pena, Rita; Lopes, Pedro; Gaspar, Gisela; Miranda, Armandina; Faustino, PaulaBackground: The α-Major Regulatory Element (α-MRE), also known as HS-40, is located upstream of the α-globin gene cluster and has a crucial role in the long-range regulation of the α-globin gene expression. This enhancer is polymorphic and several haplotypes were identified in different populations, with haplotype D almost exclusively found in African populations. The purpose of this research was to identify the HS-40 haplotype associated with the 3.7 kb α-thalassemia deletion (-α3.7del) in the Portuguese population, and determine its ancestry and influence on patients' hematological phenotype. Methods and results: We selected 111 Portuguese individuals previously analyzed by Gap-PCR to detect the presence of the -α3.7del: 50 without the -α3.7del, 34 heterozygous and 27 homozygous for the -α3.7del. The HS-40 region was amplified by PCR followed by Sanger sequencing. Four HS-40 haplotypes were found (A to D). The distribution of HS-40 haplotypes and genotypes are significantly different between individuals with and without the -α3.7del, being haplotype D and genotype AD the most prevalent in patients with this deletion in homozygosity. Furthermore, multiple correspondence analysis revealed that individuals without the -α3.7del are grouped with other European populations, while samples with the -α3.7del are separated from these and found more closely related to the African population. Conclusion: This study revealed for the first time an association of the HS-40 haplotype D with the -α3.7del in the Portuguese population, and its likely African ancestry. These results may have clinical importance as in vitro analysis of haplotype D showed a decrease in its enhancer activity on α-globin gene.
- The role of UPF1 cap-independent translation in colorectal cancerPublication . Lacerda, Rafaela; Menezes,Juliane; Elias, Adriana; Sousa, Sofia de; Romão, LuísaColorectal cancer (CRC) is one of the deadliest diseases worldwide with projections pointing towards an increase for the next two decades. Translation dysregulation of many genes contributes to CRC development, and here we are studying the role of translation dysregulation of up-frameshift 1 (UPF1) in CRC. This protein is involved in many cellular mechanisms such as nonsense-mediated mRNA decay, cell cycle progression, or telomere maintenance and homeostasis. It also works as a tumour suppressor protein in most cancers but not in CRC, in which UPF1 plays an oncogenic role. We used the Xena platform to perform in silico analyses that revealed UPF1 protein overexpressed in CRC, contrary to several other analysed cancers. Besides, UPF1 protein levels are increased in CRC compared to the counterpart normal tissues. Experimentally, we confirmed that UPF1 protein expression is maintained in different CRC cell lines under normal conditions or endoplasmic reticulum (ER) stress. To understand the mechanism underlying such maintenance, we used a bicistronic reporter construct to test whether UPF1 5’ untranslated region (UTR) can mediate alternative translation initiation and we concluded that such sequence drives cap-independent translation initiation, in both normal and stress conditions. Deletional and mutational analyses of UPF1 5’UTR showed that nucleotides 1–100 [stem-loop (SL) I] and 151–275 (SL III) — out of 275 nucleotides — are the minimal required sequences for the cap-independent translation initiation mechanism to work properly. Using RNA antisense oligonucleotides (ASOs) targeting UPF1 SL I and III, we observed a reduced UPF1 expression in HCT116 (CRC) cells, supporting the functional role of SL I and SL III in mediating cap-independent translation. Altogether, these results highlight the importance of cap-independent translation initiation in UPF1 expression regulation, in conditions that mimic the tumour microenvironment, and this might be used as a therapeutic target.
- Listeria monocytogenes from Food Products and Food Associated Environments: Antimicrobial Resistance, Genetic Clustering and Biofilm InsightsPublication . Silva, Adriana; Silva, Vanessa; Gomes, João Paulo; Coelho, Anabela; Batista, Rita; Saraiva, Cristina; Esteves, Alexandra; Martins, Ângela; Contente, Diogo; Diaz-Formoso, Lara; Cintas, Luis M.; Igrejas, Gilberto; Borges, Vítor; Poeta, PatríciaListeria monocytogenes, a foodborne pathogen, exhibits high adaptability to adverse environmental conditions and is common in the food industry, especially in ready-to-eat foods. L. monocytogenes strains pose food safety challenges due to their ability to form biofilms, increased resistance to disinfectants, and long-term persistence in the environment. The aim of this study was to evaluate the presence and genetic diversity of L. monocytogenes in food and related environmental products collected from 2014 to 2022 and assess antibiotic susceptibility and biofilm formation abilities. L. monocytogenes was identified in 13 out of the 227 (6%) of samples, 7 from food products (meat preparation, cheeses, and raw milk) and 6 from food-processing environments (slaughterhouse-floor and catering establishments). All isolates exhibited high biofilm-forming capacity and antibiotic susceptibility testing showed resistance to several classes of antibiotics, especially trimethoprim-sulfamethoxazole and erythromycin. Genotyping and core-genome clustering identified eight sequence types and a cluster of three very closely related ST3 isolates (all from food), suggesting a common contamination source. Whole-genome sequencing (WGS) analysis revealed resistance genes conferring resistance to fosfomycin (fosX), lincosamides (lin), fluoroquinolones (norB), and tetracycline (tetM). In addition, the qacJ gene was also detected, conferring resistance to disinfecting agents and antiseptics. Virulence gene profiling revealed the presence of 92 associated genes associated with pathogenicity, adherence, and persistence. These findings underscore the presence of L. monocytogenes strains in food products and food-associated environments, demonstrating a high virulence of these strains associated with resistance genes to antibiotics, but also to disinfectants and antiseptics. Moreover, they emphasize the need for continuous surveillance, effective risk assessment, and rigorous control measures to minimize the public health risks associated to severe infections, particularly listeriosis outbreaks. A better understanding of the complex dynamics of pathogens in food products and their associated environments can help improve overall food safety and develop more effective strategies to prevent severe health consequences and economic losses.
- Global, regional, and national burden of heatwave-related mortality from 1990 to 2019: A three-stage modelling studyPublication . Zhao, Qi; Li, Shanshan; Ye, Tingting; Wu, Yao; Gasparrini, Antonio; Tong, Shilu; Urban, Aleš; Vicedo-Cabrera, Ana Maria; Tobias, Aurelio; Armstrong, Ben; Royé, Dominic; Lavigne, Eric; de’Donato, Francesca; Sera, Francesco; Kan, Haidong; Schwartz, Joel; Pascal, Mathilde; Ryti, Niilo; Goodman, Patrick; Paulo Hilario Nascimento Saldiva; Bell, Michelle L.; Guo, Yuming; on behalf of the MCC Collaborative Research NetworkBackground: The regional disparity of heatwave-related mortality over a long period has not been sufficiently assessed across the globe, impeding the localisation of adaptation planning and risk management towards climate change. We quantified the global mortality burden associated with heatwaves at a spatial resolution of 0.5°×0.5° and the temporal change from 1990 to 2019. Methods and findings: We collected data on daily deaths and temperature from 750 locations of 43 countries or regions, and 5 meta-predictors in 0.5°×0.5° resolution across the world. Heatwaves were defined as location-specific daily mean temperature ≥95th percentiles of year-round temperature range with duration ≥2 days. We first estimated the location-specific heatwave-mortality association. Secondly, a multivariate meta-regression was fitted between location-specific associations and 5 meta-predictors, which was in the third stage used with grid cell-specific meta-predictors to predict grid cell-specific association. Heatwave-related excess deaths were calculated for each grid and aggregated. During 1990 to 2019, 0.94% (95% CI: 0.68-1.19) of deaths [i.e., 153,078 cases (95% eCI: 109,950-194,227)] per warm season were estimated to be from heatwaves, accounting for 236 (95% eCI: 170-300) deaths per 10 million residents. The ratio between heatwave-related excess deaths and all premature deaths per warm season remained relatively unchanged over the 30 years, while the number of heatwave-related excess deaths per 10 million residents per warm season declined by 7.2% per decade in comparison to the 30-year average. Locations with the highest heatwave-related death ratio and rate were in Southern and Eastern Europe or areas had polar and alpine climates, and/or their residents had high incomes. The temporal change of heatwave-related mortality burden showed geographic disparities, such that locations with tropical climate or low incomes were observed with the greatest decline. The main limitation of this study was the lack of data from certain regions, e.g., Arabian Peninsula and South Asia. Conclusions: Heatwaves were associated with substantial mortality burden that varied spatiotemporally over the globe in the past 30 years. The findings indicate the potential benefit of governmental actions to enhance health sector adaptation and resilience, accounting for inequalities across communities.
- Advancements in risk stratification and management strategies in primary cardiovascular preventionPublication . Barkas, Fotios; Sener, Yusuf Ziya; Golforoush, Pelin Arabacilar; Kheirkhah, Azin; Rodriguez-Sanchez, Elena; Novak, Jan; Apellaniz-Ruiz, Maria; Akyea, Ralph Kwame; Bianconi, Vanessa; Ceasovschih, Alexandr; Chee, Ying Jie; Cherska, Mariia; Chora, Joana Rita; D'Oria, Mario; Demikhova, Nadiia; Kocyigit Burunkaya, Duygu; Rimbert, Antoine; Macchi, Chiara; Rathod, Krishnaraj; Roth, Lynn; Sukhorukov, Vasily; Stoica, Svetlana; Scicali, Roberto; Storozhenko, Tatyana; Uzokov, Jamol; Lupo, Maria Giovanna; van der Vorst, Emiel P.C.; Porsch, FlorentinaAtherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality worldwide, highlighting the urgent need for advancements in risk ssessment and management strategies. Although significant progress has been made ecently, identifying and managing apparently healthy individuals at a higher risk of developing atherosclerosis and those with subclinical atherosclerosis still poses significant challenges. Traditional risk assessment tools have limitations in accurately predicting future events and fail to encompass the complexity of the atherosclerosis trajectory. In this review, we describe novel approaches in biomarkers, genetics, advanced imaging techniques, and artificial intelligence that have emerged to address this gap. Moreover, polygenic risk scores and imaging modalities such as coronary artery calcium scoring, and coronary computed tomography angiography offer promising avenues for enhancing primary cardiovascular risk stratification and personalised intervention strategies. On the other hand, interventions aiming against atherosclerosis development or promoting plaque regression have gained attention in primary ASCVD prevention. Therefore, the potential role of drugs like statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, omega-3 fatty acids, antihypertensive agents, as well as glucose-lowering and anti-inflammatory drugs are also discussed. Since findings regarding the efficacy of these interventions vary, further research is still required to elucidate their mechanisms of action, optimize treatment regimens, and determine their long-term effects on ASCVD outcomes. In conclusion, advancements in strategies addressing atherosclerosis prevention and plaque regression present promising avenues for enhancing primary ASCVD prevention through personalised approaches tailored to individual risk profiles. Nevertheless, ongoing research efforts are imperative to refine these strategies further and maximise their effectiveness in safeguarding cardiovascular health.