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  1. Article ; Online: Temperature significantly changes COVID-19 transmission in (sub)tropical cities of Brazil.

    Prata, David N / Rodrigues, Waldecy / Bermejo, Paulo H

    The Science of the total environment

    2020  Volume 729, Page(s) 138862

    Abstract: The coronavirus disease 2019 (COVID-19) outbreak has become a severe public health issue. The novelty of the virus prompts a search for understanding of how ecological factors affect the transmission and survival of the virus. Several studies have ... ...

    Abstract The coronavirus disease 2019 (COVID-19) outbreak has become a severe public health issue. The novelty of the virus prompts a search for understanding of how ecological factors affect the transmission and survival of the virus. Several studies have robustly identified a relationship between temperature and the number of cases. However, there is no specific study for a tropical climate such as Brazil. This work aims to determine the relationship of temperature to COVID-19 infection for the state capital cities of Brazil. Cumulative data with the daily number of confirmed cases was collected from February 27 to April 1, 2020, for all 27 state capital cities of Brazil affected by COVID-19. A generalized additive model (GAM) was applied to explore the linear and nonlinear relationship between annual average temperature compensation and confirmed cases. Also, a polynomial linear regression model was proposed to represent the behavior of the growth curve of COVID-19 in the capital cities of Brazil. The GAM dose-response curve suggested a negative linear relationship between temperatures and daily cumulative confirmed cases of COVID-19 in the range from 16.8 °C to 27.4 °C. Each 1 °C rise of temperature was associated with a -4.8951% (t = -2.29, p = 0.0226) decrease in the number of daily cumulative confirmed cases of COVID-19. A sensitivity analysis assessed the robustness of the results of the model. The predicted R-squared of the polynomial linear regression model was 0.81053. In this study, which features the tropical temperatures of Brazil, the variation in annual average temperatures ranged from 16.8 °C to 27.4 °C. Results indicated that temperatures had a negative linear relationship with the number of confirmed cases. The curve flattened at a threshold of 25.8 °C. There is no evidence supporting that the curve declined for temperatures above 25.8 °C. The study had the goal of supporting governance for healthcare policymakers.
    MeSH term(s) Betacoronavirus ; Brazil ; COVID-19 ; Cities ; Coronavirus Infections ; Humans ; Pandemics ; Pneumonia, Viral ; SARS-CoV-2 ; Temperature
    Keywords covid19
    Language English
    Publishing date 2020-04-25
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 121506-1
    ISSN 1879-1026 ; 0048-9697
    ISSN (online) 1879-1026
    ISSN 0048-9697
    DOI 10.1016/j.scitotenv.2020.138862
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  2. Article ; Online: Temperature significantly changes COVID-19 transmission in (sub)tropical cities of Brazil

    Prata, David N. / Rodrigues, Waldecy / Bermejo, Paulo H.

    Science of The Total Environment

    2020  Volume 729, Page(s) 138862

    Keywords Environmental Engineering ; Waste Management and Disposal ; Pollution ; Environmental Chemistry ; covid19
    Language English
    Publisher Elsevier BV
    Publishing country us
    Document type Article ; Online
    ZDB-ID 121506-1
    ISSN 1879-1026 ; 0048-9697
    ISSN (online) 1879-1026
    ISSN 0048-9697
    DOI 10.1016/j.scitotenv.2020.138862
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  3. Article: Temperature significantly changes COVID-19 transmission in (sub)tropical cities of Brazil

    Prata, David N / Rodrigues, Waldecy / Bermejo, Paulo H

    Sci Total Environ

    Abstract: The coronavirus disease 2019 (COVID-19) outbreak has become a severe public health issue. The novelty of the virus prompts a search for understanding of how ecological factors affect the transmission and survival of the virus. Several studies have ... ...

    Abstract The coronavirus disease 2019 (COVID-19) outbreak has become a severe public health issue. The novelty of the virus prompts a search for understanding of how ecological factors affect the transmission and survival of the virus. Several studies have robustly identified a relationship between temperature and the number of cases. However, there is no specific study for a tropical climate such as Brazil. This work aims to determine the relationship of temperature to COVID-19 infection for the state capital cities of Brazil. Cumulative data with the daily number of confirmed cases was collected from February 27 to April 1, 2020, for all 27 state capital cities of Brazil affected by COVID-19. A generalized additive model (GAM) was applied to explore the linear and nonlinear relationship between annual average temperature compensation and confirmed cases. Also, a polynomial linear regression model was proposed to represent the behavior of the growth curve of COVID-19 in the capital cities of Brazil. The GAM dose-response curve suggested a negative linear relationship between temperatures and daily cumulative confirmed cases of COVID-19 in the range from 16.8 °C to 27.4 °C. Each 1 °C rise of temperature was associated with a -4.8951% (t = -2.29, p = 0.0226) decrease in the number of daily cumulative confirmed cases of COVID-19. A sensitivity analysis assessed the robustness of the results of the model. The predicted R-squared of the polynomial linear regression model was 0.81053. In this study, which features the tropical temperatures of Brazil, the variation in annual average temperatures ranged from 16.8 °C to 27.4 °C. Results indicated that temperatures had a negative linear relationship with the number of confirmed cases. The curve flattened at a threshold of 25.8 °C. There is no evidence supporting that the curve declined for temperatures above 25.8 °C. The study had the goal of supporting governance for healthcare policymakers.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #116878
    Database COVID19

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  4. Article ; Online: Compensatory epistasis explored by molecular dynamics simulations.

    Serrano, Catarina / Teixeira, Carla S S / Cooper, David N / Carneiro, João / Lopes-Marques, Mónica / Stenson, Peter D / Amorim, António / Prata, Maria J / Sousa, Sérgio F / Azevedo, Luísa

    Human genetics

    2021  Volume 140, Issue 9, Page(s) 1329–1342

    Abstract: A non-negligible proportion of human pathogenic variants are known to be present as wild type in at least some non-human mammalian species. The standard explanation for this finding is that molecular mechanisms of compensatory epistasis can alleviate the ...

    Abstract A non-negligible proportion of human pathogenic variants are known to be present as wild type in at least some non-human mammalian species. The standard explanation for this finding is that molecular mechanisms of compensatory epistasis can alleviate the mutations' otherwise pathogenic effects. Examples of compensated variants have been described in the literature but the interacting residue(s) postulated to play a compensatory role have rarely been ascertained. In this study, the examination of five human X-chromosomally encoded proteins (FIX, GLA, HPRT1, NDP and OTC) allowed us to identify several candidate compensated variants. Strong evidence for a compensated/compensatory pair of amino acids in the coagulation FIXa protein (involving residues 270 and 271) was found in a variety of mammalian species. Both amino acid residues are located within the 60-loop, spatially close to the 39-loop that performs a key role in coagulation serine proteases. To understand the nature of the underlying interactions, molecular dynamics simulations were performed. The predicted conformational change in the 39-loop consequent to the Glu270Lys substitution (associated with hemophilia B) appears to impair the protein's interaction with its substrate but, importantly, such steric hindrance is largely mitigated in those proteins that carry the compensatory residue (Pro271) at the neighboring amino acid position.
    MeSH term(s) Amino Acid Substitution ; Chromosomes, Human, X/genetics ; Epistasis, Genetic ; Factor IXa/chemistry ; Factor IXa/genetics ; Humans ; Molecular Dynamics Simulation ; Mutation, Missense
    Chemical Substances Factor IXa (EC 3.4.21.22)
    Language English
    Publishing date 2021-06-26
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 223009-4
    ISSN 1432-1203 ; 0340-6717
    ISSN (online) 1432-1203
    ISSN 0340-6717
    DOI 10.1007/s00439-021-02307-x
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    Zs.A 256: Show issues Location:
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  5. Article ; Online: Common polymorphic OTC variants can act as genetic modifiers of enzymatic activity.

    Lopes-Marques, Mónica / Pacheco, Ana Rita / Peixoto, Maria João / Cardoso, Ana Rita / Serrano, Catarina / Amorim, António / Prata, Maria João / Cooper, David N / Azevedo, Luísa

    Human mutation

    2021  Volume 42, Issue 8, Page(s) 978–989

    Abstract: Understanding the role of common polymorphisms in modulating the clinical phenotype when they co-occur with a disease-causing lesion is of critical importance in medical genetics. We explored the impact of apparently neutral common polymorphisms, using ... ...

    Abstract Understanding the role of common polymorphisms in modulating the clinical phenotype when they co-occur with a disease-causing lesion is of critical importance in medical genetics. We explored the impact of apparently neutral common polymorphisms, using the gene encoding the urea cycle enzyme, ornithine transcarbamylase (OTC), as a model system. Distinct combinations of genetic backgrounds embracing two missense polymorphisms were created in cis with the pathogenic p.Arg40His replacement. In vitro enzymatic assays revealed that the polymorphic variants were able to modulate OTC activity both in the presence or absence of the pathogenic lesion. First, we found that the combination of the minor alleles of polymorphisms p.Lys46Arg and p.Gln270Arg significantly enhanced enzymatic activity in the wild-type protein. Second, enzymatic assays revealed that the minor allele of the p.Gln270Arg polymorphism was capable of ameliorating OTC activity when combined in cis with the pathogenic p.Arg40His replacement. Structural analysis predicted that the minor allele of the p.Gln270Arg polymorphism would serve to stabilize the OTC wild-type protein, thereby corroborating the results of the experimental assays. Our findings demonstrate the potential importance of cis-interactions between common polymorphic variants and pathogenic missense mutations and illustrate how standing genetic variation can modulate protein function.
    MeSH term(s) Alleles ; Humans ; Mutation, Missense ; Ornithine Carbamoyltransferase/genetics ; Ornithine Carbamoyltransferase Deficiency Disease/genetics ; Polymorphism, Genetic
    Chemical Substances OTC protein, human (EC 2.1.3.3) ; Ornithine Carbamoyltransferase (EC 2.1.3.3)
    Language English
    Publishing date 2021-06-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1126646-6
    ISSN 1098-1004 ; 1059-7794
    ISSN (online) 1098-1004
    ISSN 1059-7794
    DOI 10.1002/humu.24221
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    Zs.A 3586: Show issues Location:
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  6. Article ; Online: Drug use stigma, antiretroviral therapy use, and HIV viral suppression in a community-based sample of people with HIV who inject drugs.

    Patel, Eshan U / Solomon, Sunil S / McFall, Allison M / Prata Menezes, Neia / Tomori, Cecília / Srikrishnan, Aylur K / Kumar, Muniratnam S / Celentano, David D / Lucas, Gregory M / Mehta, Shruti H

    AIDS (London, England)

    2022  Volume 36, Issue 11, Page(s) 1583–1589

    Abstract: Objective: To examine the association of drug use stigma with antiretroviral therapy (ART) use and HIV viral suppression among people with HIV who inject drugs in India.: Design: Cross-sectional biobehavioral survey.: Methods: Between August 2016 ... ...

    Abstract Objective: To examine the association of drug use stigma with antiretroviral therapy (ART) use and HIV viral suppression among people with HIV who inject drugs in India.
    Design: Cross-sectional biobehavioral survey.
    Methods: Between August 2016 and May 2017, persons aged at least 18 years who reported injection drug use in the past 2 years were recruited via respondent-driven sampling (RDS) in 12 Indian cities (approximately 1000 per city). The analysis was restricted to participants with laboratory-confirmed HIV infection who self-reported a prior HIV diagnosis and were eligible for ART per concurrent national HIV treatment guidelines. Enacted and internalized drug use stigma were each measured by five to six-item subscales. The study outcomes were HIV viral suppression (<150 copies/ml) and self-reported past 30-day ART use. RDS-II weighted multivariable logistic regression with a city-level random-intercept was used to estimate adjusted odds ratios (aOR) and corresponding 95% confidence intervals (CIs).
    Results: Among 971 ART-eligible participants previously diagnosed with HIV, 65.1% reported ART use and 56.1% were virally suppressed. Reporting any enacted stigma (vs. none) was associated with lower odds of ART use [aOR = 0.26 (95% CI = 0.15-0.44)] and viral suppression [aOR = 0.49 (95% CI = 0.31-0.78)]. High internalized stigma scores (>median vs. ≤median) were associated with lower odds of viral suppression among participants aged at least 35 years [aOR = 0.51 (95% CI = 0.27-0.97)] but not among participants aged less than 35 years [aOR = 1.22 (95% CI = 0.57-2.60)]. Similar associations were observed in analyses restricted to participants ever linked to HIV care.
    Conclusion: Drug use stigma may be a barrier to HIV viral suppression among people with HIV who inject drugs, thereby hindering efforts to achieve HIV control.
    MeSH term(s) Adolescent ; Adult ; Cross-Sectional Studies ; HIV Infections/drug therapy ; Humans ; India/epidemiology ; Social Stigma ; Substance-Related Disorders ; Viral Load
    Language English
    Publishing date 2022-06-22
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 639076-6
    ISSN 1473-5571 ; 0269-9370 ; 1350-2840
    ISSN (online) 1473-5571
    ISSN 0269-9370 ; 1350-2840
    DOI 10.1097/QAD.0000000000003297
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  7. Article ; Online: Help Comes from Unexpected Places: How a Tiny Fairy and a Tropical Fish may help us Model Mucopolysaccharidoses.

    Carvalho, Sofia / Moreira, Luciana / Santos, Juliana Inês / Gaspar, Paulo / Gonçalves, Mariana / Matos, Liliana / David, Hugo / Encarnação, Marisa / Ribeiro, Diogo / Duarte, Ana Joana / Amaral, Olga / Rocha, Hugo / Diogo, Luísa / Ferreira, Sara / Santos, Constança / Martins, Esmeralda / Neuparth, Teresa / Soares, Joana / Ribeiro, Marta /
    Ribeiro Pinho, Brígida / Oliveira, Nuno / Ascenção Oliveira, Jorge Miguel / Prata, Maria João / Santos, Miguel / Alves, Sandra / Coutinho, Maria Francisca

    Endocrine, metabolic & immune disorders drug targets

    2023  

    Abstract: Introduction: When it comes to disease modeling, countless models are available for Lysosomal Storage Diseases (LSD). Historically, two major approaches are well-established: in vitro assessments are performed in patient fibroblasts, while in vivo pre- ... ...

    Abstract Introduction: When it comes to disease modeling, countless models are available for Lysosomal Storage Diseases (LSD). Historically, two major approaches are well-established: in vitro assessments are performed in patient fibroblasts, while in vivo pre-clinical studies are performed in mouse models. Still, both platforms have a series of drawbacks. Thus, we implemented two alternative and innovative protocols to mimic a particular sub-group of LSDs, the Mucopolysaccharidoses both in vitro and in vivo.
    Methods: The first one relies on a non-invasive approach using dental pulp stem cells from deciduous teeth (SHEDs). SHEDs are multipotent neuronal precursors that can easily be collected. The second uses a state-of-the-art gene editing technology (CRISPR/Cas9) to generate zebrafish disease models.
    Results: Even though this is an ongoing project, we have already established and characterized two MPS II and one MPS VI SHED cell models. These cells self-maintain through several passages and can give rise to a variety of cells including neurons. Furthermore, all MPS-associated sub-cellular phenotypes we have assessed so far are easily observable in these cells. Regarding our zebrafish models, we have successfully knocked down both naglu and hgsnat and the first results we got from the behavioral analysis are promising ones, as we can observe altered activity and sleep patterns in the genetically modified fish. For this particular approach we chose MPS III forms as our target disorders, since their neurological features (hyperactivity, seizures and motor impairment) and lifespan decrease would be easily recognizable in zebrafish.
    Conclusion: Now that these methods are well-established in our lab, their potential is immense. On one hand, the newly developed models will be of ultimate value to understand the mechanisms underlying MPS sub-cellular pathology, which have to be further elucidated. On the other hand, they will constitute an optimal platform for drug testing in house. Also noteworthy, our models will be published as lab resources and made available for the whole LSD community.
    Language English
    Publishing date 2023-11-02
    Publishing country United Arab Emirates
    Document type Journal Article
    ZDB-ID 2228325-0
    ISSN 2212-3873 ; 1871-5303
    ISSN (online) 2212-3873
    ISSN 1871-5303
    DOI 10.2174/0118715303277318231024055425
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  8. Article ; Online: Use of technologies in Brazilian public higher education in times of pandemic COVID-19 ; Uso de tecnologías en la educación superior pública brasileña en tiempos de pandemia COVID-19 ; Uso de tecnologias no ensino superior público brasileiro em tempos de pandemia COVID-19

    Carneiro, Leonardo de Andrade / Rodrigues, Waldecy / França, George / Prata, David Nadler

    Research, Society and Development; Vol. 9 No. 8; e267985485 ; Research, Society and Development; Vol. 9 Núm. 8; e267985485 ; Research, Society and Development; v. 9 n. 8; e267985485 ; 2525-3409

    2020  

    Abstract: The year 2020 is already marked as the year of the pandemic COVID-19. This pandemic has been changing the socioeconomic structures of the world, and educational institutions in Brazil practically had to interrupt their face-to-face activities due to the ... ...

    Abstract The year 2020 is already marked as the year of the pandemic COVID-19. This pandemic has been changing the socioeconomic structures of the world, and educational institutions in Brazil practically had to interrupt their face-to-face activities due to the rules of social distancing. According to the teaching method, technology-mediated learning has gained emphasis and makes room for differentiated human interactions. These teaching methodologies already existed, but they still reached a small scale. This article presents and discusses the Brazilian perspectives on the challenges and opportunities for the use of educational technologies for public higher education. The main results indicate that the implementation of digital inclusion policies, aiming to reduce regional inequalities of internet access, is a necessary condition for any remote teaching strategy to be successful.

    El año 2020 ya está marcado como el año del pandemic COVID-19. Esta pandemia ha estado cambiando las estructuras socioeconómicas del mundo, y las instituciones educativas en Brasil prácticamente tuvieron que interrumpir sus actividades presenciales debido a las reglas del distanciamiento social. Según el método de enseñanza, el aprendizaje mediado por la tecnología ha ganado énfasis y da lugar a interacciones humanas diferenciadas. Estas metodologías de enseñanza ya existían, pero todavía alcanzaban una pequeña escala. Este artículo presenta y analiza las perspectivas brasileñas sobre los desafíos y oportunidades para el uso de las tecnologías educativas para la educación superior pública. Los principales resultados indican que la aplicación de políticas de inclusión digital, con el objetivo de reducir las desigualdades regionales de acceso a Internet, es una condición necesaria para que cualquier estrategia de enseñanza remota tenga éxito.

    O ano de 2020 já está marcado como sendo o ano da pandemia COVID-19. Essa pandemia vem modificando as estruturas socioeconômicas no mundo, e as instituições educacionais no Brasil praticamente tiveram que interromper suas atividades presenciais devido às regras de distanciamento social. Conforme método de ensino, a aprendizagem mediada por tecnologia ganhou ênfase e abriu espaço para interações humanas diferenciadas. Essas metodologias de ensino já existiam, mas ainda alcançavam uma escala pequena. Este trabalho apresenta e discute as perspectivas brasileiras sobre os desafios e oportunidades para o uso das tecnologias educacionais para o ensino superior público. Os principais resultados apontam que a implementação de políticas de inclusão digital, visando diminuir as desigualdades regionais de acesso à internet é condição necessária para que qualquer estratégia de ensino remoto tenha possibilidade de êxito.
    Keywords Aprendizagem mediada por tecnologia ; COVID-19 ; Plataformas on-line ; Ensino ; Aprendizaje mediado por la tecnología ; Plataformas en línea ; Enseñanza ; Technology-mediated learning ; Online platforms ; Teaching ; covid19
    Language Portuguese
    Publishing date 2020-07-04
    Publisher Research, Society and Development
    Publishing country br
    Document type Article ; Online
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  9. Article ; Online: The Relationship Between the Global Burden of Influenza From 2017 to 2019 and COVID-19: Descriptive Epidemiological Assessment.

    Baral, Stefan David / Rucinski, Katherine Blair / Twahirwa Rwema, Jean Olivier / Rao, Amrita / Prata Menezes, Neia / Diouf, Daouda / Kamarulzaman, Adeeba / Phaswana-Mafuya, Nancy / Mishra, Sharmistha

    JMIR public health and surveillance

    2021  Volume 7, Issue 3, Page(s) e24696

    Abstract: Background: SARS-CoV-2 and influenza are lipid-enveloped viruses with differential morbidity and mortality but shared modes of transmission.: Objective: With a descriptive epidemiological framing, we assessed whether recent historical patterns of ... ...

    Abstract Background: SARS-CoV-2 and influenza are lipid-enveloped viruses with differential morbidity and mortality but shared modes of transmission.
    Objective: With a descriptive epidemiological framing, we assessed whether recent historical patterns of regional influenza burden are reflected in the observed heterogeneity in COVID-19 cases across regions of the world.
    Methods: Weekly surveillance data reported by the World Health Organization from January 2017 to December 2019 for influenza and from January 1, 2020 through October 31, 2020, for COVID-19 were used to assess seasonal and temporal trends for influenza and COVID-19 cases across the seven World Bank regions.
    Results: In regions with more pronounced influenza seasonality, COVID-19 epidemics have largely followed trends similar to those seen for influenza from 2017 to 2019. COVID-19 epidemics in countries across Europe, Central Asia, and North America have been marked by a first peak during the spring, followed by significant reductions in COVID-19 cases in the summer months and a second wave in the fall. In Latin America and the Caribbean, COVID-19 epidemics in several countries peaked in the summer, corresponding to months with the highest influenza activity in the region. Countries from regions with less pronounced influenza activity, including South Asia and sub-Saharan Africa, showed more heterogeneity in COVID-19 epidemics seen to date. However, similarities in COVID-19 and influenza trends were evident within select countries irrespective of region.
    Conclusions: Ecological consistency in COVID-19 trends seen to date with influenza trends suggests the potential for shared individual, structural, and environmental determinants of transmission. Using a descriptive epidemiological framework to assess shared regional trends for rapidly emerging respiratory pathogens with better studied respiratory infections may provide further insights into the differential impacts of nonpharmacologic interventions and intersections with environmental conditions. Ultimately, forecasting trends and informing interventions for novel respiratory pathogens like COVID-19 should leverage epidemiologic patterns in the relative burden of past respiratory pathogens as prior information.
    MeSH term(s) COVID-19/epidemiology ; Cost of Illness ; Epidemiologic Studies ; Global Health/statistics & numerical data ; Humans ; Influenza, Human/epidemiology
    Language English
    Publishing date 2021-03-02
    Publishing country Canada
    Document type Journal Article
    ISSN 2369-2960
    ISSN (online) 2369-2960
    DOI 10.2196/24696
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  10. Article ; Online: Dapagliflozin in patients with critical illness: rationale and design of the DEFENDER study.

    Tavares, Caio de Assis Moura / Azevedo, Luciano César Pontes de / Rea-Neto, Álvaro / Campos, Niklas Söderberg / Amendola, Cristina Prata / Bergo, Ricardo Reinaldo / Kozesinski-Nakatani, Amanda Christina / David-João, Paula Geraldes / Westphal, Glauco Adrieno / Guimarães Júnior, Mário Roberto Rezende / Lobo, Suzana Margareth Ajeje / Tavares, Marcos Soares / Dracoulakis, Marianna Deway Andrade / Souza, Guilherme Martins de / Almeida, Guacyra Margarita Batista de / Gebara, Otavio Celso Eluf / Tomba, Pablo Oscar / Albuquerque, Camila Santos N / Silva, Mariana Castaldi Ramalho /
    Pereira, Adriano José / Damiani, Lucas Petri / Corrêa, Thiago Domingos / Serpa-Neto, Ary / Berwanger, Otavio / Zampieri, Fernando Godinho

    Critical care science

    2023  Volume 35, Issue 3, Page(s) 256–265

    Abstract: Background: Critical illness is a major ongoing health care burden worldwide and is associated with high mortality rates. Sodium-glucose cotransporter-2 inhibitors have consistently shown benefits in cardiovascular and renal outcomes. The effects of ... ...

    Abstract Background: Critical illness is a major ongoing health care burden worldwide and is associated with high mortality rates. Sodium-glucose cotransporter-2 inhibitors have consistently shown benefits in cardiovascular and renal outcomes. The effects of sodium-glucose cotransporter-2 inhibitors in acute illness have not been properly investigated.
    Methods: DEFENDER is an investigator-initiated, multicenter, randomized, open-label trial designed to evaluate the efficacy and safety of dapagliflozin in 500 adult participants with acute organ dysfunction who are hospitalized in the intensive care unit. Eligible participants will be randomized 1:1 to receive dapagliflozin 10mg plus standard of care for up to 14 days or standard of care alone. The primary outcome is a hierarchical composite of hospital mortality, initiation of kidney replacement therapy, and intensive care unit length of stay, up to 28 days. Safety will be strictly monitored throughout the study.
    Conclusion: DEFENDER is the first study designed to investigate the use of a sodium-glucose cotransporter-2 inhibitor in general intensive care unit patients with acute organ dysfunction. It will provide relevant information on the use of drugs of this promising class in critically ill patients.
    Clinicaltrials.gov registry: NCT05558098.
    MeSH term(s) Adult ; Humans ; Critical Illness/therapy ; Multiple Organ Failure/drug therapy ; Sodium-Glucose Transporter 2 Inhibitors/therapeutic use ; Multicenter Studies as Topic
    Chemical Substances dapagliflozin (1ULL0QJ8UC) ; Sodium-Glucose Transporter 2 Inhibitors
    Language Portuguese
    Publishing date 2023-12-22
    Publishing country Brazil
    Document type Clinical Trial Protocol ; Journal Article
    ISSN 2965-2774
    ISSN (online) 2965-2774
    DOI 10.5935/2965-2774.20230129-en
    Database MEDical Literature Analysis and Retrieval System OnLINE

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