Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Depression increases the onset of cardiovascular disease over and above other determinants in older primary care patients, a cohort study

Background: To determine if major depressive disorder (MDD) in older primary care patients is an independent risk factor for cardiovascular events. Methods: A cohort of 143 primary care patients with depression and 139 non-depressed controls without depression (both aged over 55 years, matched for age and gender) from the Netherlands was evaluated for 2 years. MDD was diagnosed according to DSM-IV-criteria. During the follow-up period, information was collected on physical health, depression status and behavioural risk factors. CVD end points were assessed with validated annual questionnaires and were crosschecked with medical records. Results: Thirty-four participants experienced a cardiovascular event, of which 71% were depressed: 27/134 with MDD (20.1%) and 9/137 controls (6.6%). MDD was associated with a hazard ratio of 2.83 (p value 0,004, 95% CI 1.32 to 6.05) for cardiovascular events. After adjustment for cardiovascular medication, the hazard ratio was 2.46 (95% CI 1.14 to 5.30). Conclusions: In a 2-year follow-up period, baseline MDD increased the risk for CVD in older primary care patients compared with controls, over and above well-known cardiovascular risk factors

Depression increases the onset of cardiovascular disease over and above other determinants in older primary care patients, a cohort study

BACKGROUND: To determine if major depressive disorder (MDD) in older primary care patients is an independent risk factor for cardiovascular events.METHODS: A cohort of 143 primary care patients with depression and 139 non-depressed controls without depression (both aged over 55??years, matched for age and gender) from the Netherlands was evaluated for 2??years. MDD was diagnosed according to DSM-IV-criteria. During the follow-up period, information was collected on physical health, depression status and behavioural risk factors. CVD end points were assessed with validated annual questionnaires and were crosschecked with medical records.RESULTS: Thirty-four participants experienced a cardiovascular event, of which 71??{\%} were depressed: 27/134 with MDD (20.1??{\%}) and 9/137 controls (6.6??{\%}). MDD was associated with a hazard ratio of 2.83 (p value 0,004, 95??{\%} CI 1.32 to 6.05) for cardiovascular events. After adjustment for cardiovascular medication, the hazard ratio was 2.46 (95??{\%} CI 1.14 to 5.30).CONCLUSIONS: In a 2??year follow-up period, baseline MDD increased the risk for CVD in older primary care patients compared with controls, over and above well-known cardiovascular risk factors

Atividades de controle do dengue na visão de seus agentes e da população atendida, São José do Rio Preto, São Paulo, Brasil Dengue control as viewed by agents and the target population in São José do Rio Preto, São Paulo, Brazil

O objetivo foi identificar, no contexto da atuação dos agentes responsáveis pelo controle do dengue e na sua relação com moradores, situações vivenciadas no dia-a-dia de suas funções. Realizou-se estudo transversal com aplicação de questionários à população dos agentes de controle de vetores (ACV), à dos agentes comunitários de saúde (ACS) e a uma amostra de mulheres. As respostas dadas pelos agentes foram agrupadas nos âmbitos do trabalho, particular e coletivo. As mulheres foram abordadas sobre a relação mantida com os agentes. As dificuldades citadas nos âmbitos particular e trabalho pelos ACV diferiram das citadas pelos ACS. No coletivo foram coincidentes e mostraram que ambos não estão preparados para lidar com estas questões. Das mulheres entrevistadas, 87,0% afirmaram estar bem ou muito bem informadas sobre dengue, 84,0% afirmaram que os trabalhos dos agentes ajudam sempre e 54,0% apontaram como dificuldade o horário impróprio da visita realizada pelo agente. Identificou-se a necessidade de um novo profissional que reconheça e respeite as particularidades dos locais onde atua e desenvolva suas atividades de forma integrada às questões sócio-ambientais da comunidade.<br>The aim of this article was to identify daily situations experienced by dengue control agents in their relationship to local residents. A cross-sectional study applied questionnaires among vector control agents, community health workers, and a sample of local women. The answers by the dengue control agents and community health workers were grouped in the categories of work, private life, and community. The women were asked about the relationship with the vector control and community health workers. The difficulties cited in the private and work areas by the vector control agents were different from those reported by community health workers. At the community level they coincided and showed that neither group is adequately prepared to deal with these issues. Of the local women interviewed, 87.0% reported that they were well-informed or very well-informed about dengue, 84.0% stated that the work by the vector control agents and community health workers was always helpful, and 54.0% identified inappropriate visiting hours by vector control agents and community health workers as a difficulty. The study identified the need for a new job profile that would recognize and respect the specificities of the areas where their activities are conducted, integrating the community's socio-environmental issues

Aberrant Function of the C-Terminal Tail of HIST1H1E Accelerates Cellular Senescence and Causes Premature Aging

Histones mediate dynamic packaging of nuclear DNA in chromatin, a process that is precisely controlled to guarantee efficient compaction of the genome and proper chromosomal segregation during cell division and to accomplish DNA replication, transcription, and repair. Due to the important structural and regulatory roles played by histones, it is not surprising that histone functional dysregulation or aberrant levels of histones can have severe consequences for multiple cellular processes and ultimately might affect development or contribute to cell transformation. Recently, germline frameshift mutations involving the C-terminal tail of HIST1H1E, which is a widely expressed member of the linker histone family and facilitates higher-order chromatin folding, have been causally linked to an as-yet poorly defined syndrome that includes intellectual disability. We report that these mutations result in stable proteins that reside in the nucleus, bind to chromatin, disrupt proper compaction of DNA, and are associated with a specific methylation pattern. Cells expressing these mutant proteins have a dramatically reduced proliferation rate and competence, hardly enter into the S phase, and undergo accelerated senescence. Remarkably, clinical assessment of a relatively large cohort of subjects sharing these mutations revealed a premature aging phenotype as a previously unrecognized feature of the disorder. Our findings identify a direct link between aberrant chromatin remodeling, cellular senescence, and accelerated aging