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

Timing of fluoride toothpaste use and enamel-dentin demineralization

Orientador: Lívia Maria Andaló TenutaDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de PiracicabaResumo: O Fluoreto (F) interfere com o desenvolvimento de cárie dental quando presente no meio bucal, reduzindo a desmineralização e ativando a remineralização da estrutura dental. Embora ambos os mecanismos estejam envolvidos na redução da perda mineral na presença de F, não foi encontrado nenhum estudo in situ que avaliasse a importância relativa de cada um deles na inibição do desenvolvimento de cárie. Desta forma, foi realizado um estudo in situ, cruzado e cego, com o objetivo de avaliar o efeito do momento de uso do dentifrício fluoretado, i.e., antes ou após desafios desmineralizantes diários (para simular efeito na redução da desmineralização ou ativação da remineralização, respectivamente), na perda mineral do esmalte e dentina radicular. Doze voluntários utilizaram dispositivos intrabucais palatinos contendo 3 blocos de esmalte e 3 de dentina radicular hígidos e com dureza de superfície previamente determinada, durante 3 fases de 14 dias cada. Os blocos foram fixados 1 mm abaixo do nível do dispositivo e cobertos por uma tela plástica para favorecer o acúmulo de biofilme dental, e foram expostos à sacarose 20% 8x/dia. Os voluntários realizaram os seguintes tratamentos: G1 - dentifrício placebo (nãofluoretado) três vezes/dia (grupo controle); G2 - dentifrício fluoretado pela manhã (7:00), antes dos desafios desmineralizantes diários, e dentifrício não-fluoretado nas escovações seguintes; e G3 - dentifrício fluoretado à noite (entre 20:00 e 21:00), após os desafios desmineralizantes, e dentifrício não-fluoretado nas duas escovações anteriores. A desmineralização do esmalte e dentina radicular foi avaliada pela porcentagem de perda de dureza de superfície (%PDS). Também foi avaliada a concentração de fluoreto incorporado aos blocos dentais (fluorapatita). Os resultados de %PDS dos tratamentos com dentifrício fluoretado diferiram do grupo controle (p0,05), no entanto, foi significativamente maior no grupo tratado com dentifrício fluoretado após os desafios desmineralizantes, quando comparado ao grupo controle (p0,05). Os resultados do presente estudo sugerem que o dentifrício fluoretado é mais eficaz na redução da cárie através da ativação da remineralização do esmalte e dentina radicular, do que pela inibição da sua desmineralizaçãoAbstract: Fluoride (F) interferes with dental caries development when present in oral environment, reducing dental demineralization and enhancing its remineralization. Although both mechanisms are related to the reduction of mineral loss in the presence of F, no experimental study which evaluated the relative importance of each mechanism on the inhibition of development of dental caries was found. Thus, this in situ, crossover and blind study was performed to evaluate the effect of the period of F dentifrice use, i.e., either before or after daily cariogenic challenges (to simulate either the effect on the reduction of demineralization or on the enhancement of remineralization, respectively), on enamel and root dentin remineralization. Twelve volunteers wore palatal appliances containing three sound enamel slabs and three sound root dentin slabs, with surface hardness previously determined, during three phases of 14 days each. Dental slabs were fixed 1 mm underneath the level of the appliance and covered by a plastic mesh to allow dental biofilm accumulation, and exposed to sucrose 20% 8x/day. The volunteers performed the following treatments: G1 - placebo toothpaste (non-fluoride) three times/day (control group); G2 - fluoride toothpaste in the morning (7:00), before cariogenic challenges, and non-fluoride toothpaste in the next two toothbrushings; and G3- fluoride toothpaste at night (between 20:00 and 21:00), after cariogenic challenges, and non-fluoride toothpaste in the previous two toothbrushings. Enamel-dentin demineralization was evaluated by percentage of surface hardness loss (%SHL). F uptake by enamel and dentin was also determined (as fluorapatite). %SHL data in groups treated with fluoride toothpaste differ from control group (p0.05), however, it was significantly higher in the group treated with fluoride toothpaste after cariogenic challenges compared to control group (p0.05). The findings of this study suggest that F from toothpaste is more effective to reduce caries by enhancing enamel-dentine remineralization than by reducing their demineralizationMestradoCariologiaMestre em Odontologi

Timing of fluoride toothpaste use and enamel-dentin demineralization

It is well established that fluoride (F) prevents caries development by inhibiting demineralization and enhancing remineralization processes. However, it is not known which of these protective mechanisms is more important. In this double-blind, crossover in situ study conducted in three phases of 14 days each, 12 volunteers wore palatal appliances containing enamel and root dentin slabs, on which biofilm was allowed to accumulate under exposure to 20% sucrose solution 8×/day. F toothpaste was used once a day, either before the daily demineralizing episodes (in the morning) or after them (at night). Non-F placebo toothpaste was used in the control group. F toothpaste significantly reduced enamel and dentin demineralization compared with the control (p < 0.05). F toothpaste was more effective when used after the demineralization episodes than before, and this difference was statistically significant for dentin (p < 0.05). The results suggest that brushing with F dentifrice at night to remineralize daily mineral losses may be preferable to brushing in the morning to inhibit the demineralizing episodes of the day