SGLT-2 inhibitors in non-diabetic patients : a systematic review

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2022Contexto: Os inibidores do co-transportador sódio glicose tipo 2 (SGLT2) demostraram ter efeitos positivos a nível renal em doentes diabéticos. Existe ainda evidência recente em não diabéticos. Uma vez que não existe tratamento específico para a doença renal crónica (DRC), há uma grande necessidade de encontrar novos alvos terapêuticos. Esta revisão foi feita para analisar a evidência sobre o uso dos inibidores do SGLT-2 em doentes sem diabetes. Métodos: Pesquisámos a PubMed para estudos que examinaram o efeito dos inibidores do SGLT2 a nível renal em doentes não diabéticos. Realizámos uma revisão sistemática de acordo com a metodologia PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Foram incluídos apenas ensaios clínicos aleatorizados. Resultados: Um total de nove ensaios clínicos aleatorizados foram incluídos, com uma amostra combinada de 19689 doentes. Seis estudos avaliaram um efeito renal composto, que incluiu a diminuição sustentada da taxa de filtração glomerular (TFG) estimada, progressão para doença renal terminal e morte de causa renal. Quatro estudos avaliaram o efeito na TFG e dois estudos avaliaram o efeito na proteinúria ou albuminúria. Houve uma tendência para menor risco do efeito renal composto em doentes com insuficiência cardíaca (IC) com fração de ejeção (FE) reduzida (HR 0.50- 0.71, valor p não disponível). Um efeito menor no efeito renal composto foi observado em doentes com IC com FE preservada (HR 0.95). Em doentes com IC (FE reduzida e preservada) houve uma redução estatisticamente significativa no ritmo de diminuição da TFG (-0.55 a -1.25 vs -2.28 a 2.62 ml/min/1.73 m2/ano, p<0.001). Num seguimento a curto prazo, houve uma redução significativa, mas reversível, da TFG e não houve efeito na proteinúria de 24h. No seguimento a longo prazo de doentes renais crónicosproteinúricos, houve uma redução estatisticamente significativa do efeito renal composto (HR 0.61, p<0.001) e da albuminúria (-14.8% (-22.9 to -5.9, P=0.0016)). A incidência de efeitos adversos foi baixa e a de efeitos adversos graves foi semelhante nos grupos tratados com inibidores do SGLT2 e placebo. Conclusão: O tratamento com inibidores do SGLT2 parece diminuir o risco de diminuição sustentada da TFG, progressão para doença renal terminal e morte por causa renal em doentes com IC e DRC proteinúrica com TFG ≥ 25ml/min/1.73m2. Os inibidores do SGLT2 parecem também diminuir o risco de albuminúria em doentes com DRC proteinúrica. Apesar dos resultados promissores, são necessários mais estudos, principalmente com acompanhamento a longo prazo, para avaliar com precisão o impacto dos inibidores do SGLT2 em doentes não diabéticos com DRC.Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have shown positive renal outcomes in diabetic patients. There is also emerging evidence in non-diabetic patients. Since no specific treatment for chronic kidney disease (CKD) exists, there is an urge to find new therapeutic targets. This review was conducted to analyse the renal outcomes of SGLT2i in patients without diabetes mellitus. Methods: We searched PubMed for studies that examined the effect of SGLT2i on renal outcomes in non-diabetic patients. A systematic review was performed in a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) compliant manner. We included only randomized controlled trials (RCTs). Results: A total of nine RCTs were included with a combined cohort of 19689 patients. Six studies evaluated a composite renal outcome including sustained estimated glomerular filtration rate (GFR) reduction, progression to ESRD and death from renal causes. Four studies also evaluated effect on GFR and two on proteinuria or albuminuria. There was a tendency for lesser risk of the composite renal outcome in heart failure (HF) patients with reduced ejection fraction (EF) (HR 0.50-0.71, p value not available). Lesser effect on the composite renal outcome was seen in HF patients with preserved EF (HR 0.95). For both preserved and reduced EF HF, there was a statistically significant reduction in the rate of decline in eGFR (-0.55 to -1.25 vs -2.28 to 2.62 ml/min/1.73 m2/per year, p<0.001). On a short follow-up, there was a significant reversible reduction in GFR and no effect in 24h proteinuria. In long term follow-up, CKD proteinuric patients had a statistically significant lesser risk of the composite renal outcome (HR 0.61, p<0.001) and a significant reduction in albuminuria (-14.8% (-22.9 to -5.9, P=0.0016)). The incidence of adverse events was low and severe adverse events were similar in the SGLT2i and placebo groups. Conclusion: Treatment with SGLT2i appears to lower the risk of sustained eGFR reduction, progression to ESRD or death from renal causes in patients with HF patients and CKD proteinuric patients with eGFR ≥ 25ml/min/1.73m2. SGLT2i also seem to lower albuminuria in CKD proteinuric patients. Despite the promising results, further studies,specifically with long-term follow-up are required to accurately assess the impact of SGLT2i in non-diabetic CKD patient

Criação de um chatbot para atendimento de suporte sistêmico de uma rede de supermercados a partir de uma base de conhecimento registrada no Mantis

Introdução: A tecnologia está presente nos diversos ramos de atividades e somente ela não é capaz de ser um diferencial nas empresas. Faz-se necessário ter o domínio do negócio e ter o conhecimento sobre a área que está sendo avaliada. O conhecimento pode ser apresentado em diversos formatos, estando este intangível ou devidamente registrado. Quando há registro desse conhecimento, a tarefa de buscar essas informações pode ser realizada com facilidade e permite agilidade e eficiência para a tomada de decisão. No entanto, recuperar informações com precisão não é uma tarefa simples. Objetivos e método: O presente trabalho trata sobre a geração de uma coletânea de documentos (corpus em formato adequado para chatbots) criada a partir de uma base histórica de atendimentos do sistema Mantis® (software livre que permite o registro de bug´s e melhorias) de uma rede de supermercados. A base foi submetida a um serviço de perguntas e respostas que possui técnicas de recuperação de informações, bot e conversação natural, a fim de realizar análise dos retornos recuperados. Resultados: O resultado do trabalho é a conversão de vários registros de soluções já revisadas anteriormente, em um direcionamento único e objetivo, do que a leitura de diversas possibilidades de soluções dispersas em vários atendimentos. Os atendimentos são considerados como base de conhecimento para a recuperação de informações e a resposta para o usuário. Conclusão: Com isso, a pesquisa concluiu que o chatbot localiza respostas e consolida possíveis soluções utilizadas em atendimentos anteriores e que podem ser a solução do problema relatado atualmente. Os chatbots podem ser uma alternativa frente a necessidade de atender usuários na prestação de serviço de suporte

Jogo educativo sobre drogas para cegos: construção e avaliação

Estudo realizado com o objetivo de construir e avaliar um jogo educativo sobre drogas psicoativas acessível a pessoas cegas, desenvolvido em três etapas: construção do jogo educativo, avaliação por três especialistas em educação especial e doze cegos. Foi construído um jogo de tabuleiro denominado Drogas: jogando limpo . Na Versão Alfa os especialistas fizeram sugestões em relação às e instruções e ao tabuleiro: textura das casas, peças do jogo e escrita em Braille. Na Versão Beta, procedeu-se à avaliação pelos cegos, os quais sugeriram alterações na textura das casas e colocação de velcro para fixação do pino no tabuleiro. Passou-se, então, à Versão Gama, jogada pelas últimas três duplas de cegos e considerada adequada. Na avaliação dos juízes, o jogo revelou-se adequado, pois permite o acesso à informação sobre drogas psicoativas de maneira lúdica

Differentiation of COVID-19 signs and symptoms from allergic rhinitis and common cold : An ARIA-EAACI-GA(2)LEN consensus

Background Although there are many asymptomatic patients, one of the problems of COVID-19 is early recognition of the disease. COVID-19 symptoms are polymorphic and may include upper respiratory symptoms. However, COVID-19 symptoms may be mistaken with the common cold or allergic rhinitis. An ARIA-EAACI study group attempted to differentiate upper respiratory symptoms between the three diseases. Methods A modified Delphi process was used. The ARIA members who were seeing COVID-19 patients were asked to fill in a questionnaire on the upper airway symptoms of COVID-19, common cold and allergic rhinitis. Results Among the 192 ARIA members who were invited to respond to the questionnaire, 89 responded and 87 questionnaires were analysed. The consensus was then reported. A two-way ANOVA revealed significant differences in the symptom intensity between the three diseases (p < .001). Conclusions This modified Delphi approach enabled the differentiation of upper respiratory symptoms between COVID-19, the common cold and allergic rhinitis. An electronic algorithm will be devised using the questionnaire.Peer reviewe

ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.Peer reviewe

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice

Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure &lt;= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt