Mortality and years of potential life lost due to COVID-19 in Brazil

In November 2020, Brazil ranked third in the number of cases of coronavirus disease 2019 (COVID-19) and second in the number of deaths due to the disease. We carried out a descriptive study of deaths, mortality rate, years of potential life lost (YPLL) and excess mortality due to COVID-19, based on SARS-CoV-2 records in SIVEP-Gripe (Ministry of Health of Brazil) from 16 February 2020, to 1 January 2021. In this period, there were 98,025 deaths from COVID-19 in Brazil. Men accounted for 60.5% of the estimated 1.2 million YPLLs. High YPLL averages showed prematurity of deaths. The population aged 45–64 years (both sexes) represented more than 50% of all YPLLs. Risk factors were present in 69.5% of deaths, with heart disease, diabetes and obesity representing the most prevalent comorbidities in both sexes. Indigenous people had the lowest number of deaths and the highest average YPLL. However, in indigenous people, pregnant women and mothers had an average YPLL of over 35 years. The excess mortality for Brazil was estimated at 122,914 deaths (9.2%). The results show that the social impacts of YPLL due to COVID-19 are different depending on gender, race and risk factors. YPLL and excess mortality can be used to guide the prioritization of health interventions, such as prioritization of vaccination, lockdowns, or distribution of facial masks for the most vulnerable populations

AVALIAÇÃO DA EFETIVIDADE DA ESTERILIZAÇÃO POR LUZ ULTRAVIOLETA EM AEROSSÓIS CONTAMINADOS POR SARS-COV-2

O contato direto e a disseminação aérea são os principais mecanismos de transmissão do SARS-CoV-2. Uma abordagem direta para limitar as transmissões virais no ar é inativá-las dentro de um curto período de tempo após sua produção é a luz ultravioleta C (UVC). Neste sentido, o objetivo do presente estudo foi de avaliar a efetividade do uso de luz ultravioleta na esterilização de aerossóis contaminados pelo SARS-CoV-2. Para o estudo foram analisados todos os pacientes que estavam internados na enfermaria COVID com resultados dos swabs positivos. O paciente escolhido para o estudo encontrava-se com resultado positivo e com 8 dias de sintomas. As medições de contaminação da deposição de aerossol na mesa de tomografia foram realizadas em triplicatas, utilizando swabs estéreis com meio de transporte viral. O paciente foi mantido sozinho dentro desta sala por 30 minutos produzindo aerossóis para que pudesse ocorrer contaminação do ar. Após, foram realizadas as medições utilizando a exposição à luz ultravioleta C, coletada nos minutos 0, 5, 10, 15, 30, 60, 120 e 180, após o paciente ter deixado a sala de tomografia. Esta sequência de medições foram realizadas em 6 dias, sendo o primeiro dia sem a exposição da luz UVC e 5 dias com a exposição da luz UVC. Após a coleta dos dados, foi realizada a análise dos swabs para os resultados através do método RT-PCR. Os resultados encontrados das coletas desde o tempo 0 até 180 minutos foram negativos para os 6 dias de estudo. Os resultados dos swabs do paciente seguiram positivos do primeiro até o último dia de estudo. Sendo assim, conclui-se a efetividade da utilização da luz ultravioleta como uma forma de descontaminação, juntamente com a ação antimicrobiana do desinfetante, pois a ausência do vírus vivo evidencia a importância de cuidados de higienização para evitar a reincidência da contaminação após a limpeza

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

A Coumarin Triflate Reagent Enables One‐Step Synthesis of Photo‐Caged Lipid Metabolites for Studying Cell Signaling

Photorelease of caged compounds is among the most powerful experimental approaches for studying cellular functions on fast timescales. However, its full potential has yet to be exploited, as the number of caged small molecules available for cell biological studies has been limited by synthetic challenges. Addressing this problem, a straightforward, one-step procedure for efficiently synthesizing caged compounds was developed. An in situ generated benzylic coumarin triflate reagent was used to specifically functionalize carboxylate and phosphate moieties in the presence of free hydroxy groups, generating various caged lipid metabolites, including a number of GPCR ligands. By combining the photo-caged ligands with the respective receptors, an easily implementable experimental platform for the optical control and analysis of GPCR-mediated signal transduction in living cells was developed. Ultimately, the described synthetic strategy allows rapid generation of photo-caged small molecules and thus greatly facilitates the analysis of their biological roles in live cell microscopy assays.GR-SCHUHMACHE

A Click Cage: Organelle‐Specific Uncaging of Lipid Messengers

Lipid messengers exert their function on short time scales at distinct subcellular locations, yet most experimental approaches for perturbing their levels trigger cell-wide concentration changes. Herein, we report on a coumarin-based photocaging group that can be modified with organelle-targeting moieties by click chemistry and thus enables photorelease of lipid messengers in distinct organelles. We show that caged arachidonic acid and sphingosine derivatives can be selectively delivered to mitochondria, the ER, lysosomes, and the plasma membrane. By comparing the cellular calcium transients induced by localized uncaging of arachidonic acid and sphingosine, we show that the precise intracellular localization of the released second messenger is crucial for the signaling outcome. Ultimately, we anticipate that this new class of caged compounds will greatly facilitate the study of cellular processes on the organelle level.GR-SCHUHMACHE