Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Educomunicação e suas áreas de intervenção: Novos paradigmas para o diálogo intercultural

oai:omp.abpeducom.org.br:publicationFormat/1O material aqui divulgado representa, em essência, a contribuição do VII Encontro Brasileiro de Educomunicação ao V Global MIL Week, da UNESCO, ocorrido na ECA/USP, entre 3 e 5 de novembro de 2016. Estamos diante de um conjunto de 104 papers executivos, com uma média de entre 7 e 10 páginas, cada um. Com este rico e abundante material, chegamos ao sétimo e-book publicado pela ABPEducom, em seus seis primeiros anos de existência. A especificidade desta obra é a de trazer as “Áreas de Intervenção” do campo da Educomunicação, colocando-as a serviço de uma meta essencial ao agir educomunicativo: o diálogo intercultural, trabalhado na linha do tema geral do evento internacional: Media and Information Literacy: New Paradigms for Intercultural Dialogue

Avaliação das manifestações bucais de pacientes portadores de polipose adenomatosa familial e de seus familiares

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Ciências da Saúde, 2010.A Polipose Adenomatosa Familial (FAP) é uma síndrome autossômica dominante predisponente ao câncer colorretal (CRC). A doença é causada pela mutação do gene APC (adenomatous polyposis coli) localizado no cromossomo 5q21. As características da FAP incluem o desenvolvimento de pólipos adenomatosos colorretais por volta da segunda década de vida com alto potencial de transformação maligna se não forem tratados. Além dos pólipos colorretais, a FAP apresenta manifestações extra-cólon como hipertrofia congênita do epitélio pigmentar da retina, alterações em pele e anomalias no complexo maxilomandibular como osteomas, esclerose óssea difusa, dentes retidos, odontomas e dentes supranumerários. A avaliação da saúde geral e das características odontológicas clínicas e radiográficas dos pacientes com FAP é necessária para o diagnóstico dos problemas dento-ósseos associados. O objetivo desse estudo foi descrever as manifestações bucais de pacientes portadores de Polipose Adenomatosa Familial e de seus familiares. Foram avaliados 29 pacientes de três famílias com FAP do Serviço de Coloproctologia do HUB. Todos os pacientes foram submetidos a exame clínico e exames complementares (fotografias, radiografia panorâmica da face e Tomografia Computadorizada por Feixe Cônico (CBCT) quando indicados). Além disso, foi construído heredograma das famílias para determinar o modo de herança da FAP. As radiografias panorâmicas da face foram avaliadas segundo o método DPRS (Dental Panoramic Radiograph Score), proposto por Thakker et al., 1995 com objetivo de auxiliar no diagnóstico dos pacientes com FAP. Alterações significantes (escore ≥ 7) foram encontradas em 27,5% do total da amostra e em 75% dos pacientes com FAP confirmada. As alterações ósseas foram mais freqüentes (58%) que as alterações dentárias (42%) na amostra estudada. A CBCT mostrou alterações não visualizadas pela radiografia panorâmica da face. Foi possível sugerir o modo de herança autossômico dominante da FAP em apenas uma família. Em duas famílias não foi possível determinar o modo de herança. A avaliação das alterações dento-ósseas e o acompanhamento contínuo dos pacientes das famílias com FAP pelo cirurgião-dentista é de extrema importância, uma vez que as manifestações bucais geralmente precedem os sintomas gastrointestinais. Estudos futuros serão necessários para esclarecer os aspectos moleculares da FAP e sua relação com as alterações dento-ósseas. ________________________________________________________________________________ ABSTRACTFamilial adenomatous polyposis (FAP) is a dominant autosomal syndrome which predisposes to Colorectal Cancer (CRC). It is caused by mutation of the APC gene (adenomatous polyposis coli) located at the 5q21 chromossome. FAP is characterized by colorectal adenomatous polyps emerging around twenty years of age, with a high risk of maligne transformation if left untreated. Besides the colorectal polyps, FAP presents other extracolonic manifestations, such as congential hypertrophy o retinal pigment epithelium, changes in skin and dento-osseous symptons including osteomas, diffuse bone sclerosis, impacted teeth, odontomas and supernumerary teeth. Overall assessment of radiographic and clinical teeth characteristics as well as general health condition is necessary to diagnose the dento-osseous changes arisen from FAP. The aim of the present study was to describe the dento-osseous manifestations in FAP patients as well as their relatives. Twenty-nine patients from three families referred by the Coloproctology Division of the University of Brasilia’s hospital (HUB) were assessed. The patients underwent clinical exams as well as imaging procedures such as simple photography, cone beam computed tomography (CBCT) and panoramic radiography. Moreover, a genealogical family tree was generated to determine FAP type of hereditary transmission. To assist FAP diagnosis, panoramic radiographs were evaluated through the Dental Panoramic Radiograph Score (DPRS), as proposed by Thakker et al., 1995. Significant changes (score ≥ 7) were found in 27,5% of the total sample and in 75% of the FAP patients. Bone changes were more frequently found (58%) than teeth changes (42%). CBCT revealed changes not perceived by panoramic radiographs. It was only possible to indicate autosomal heredity in one of the families evaulated here. Assessment of the dento-osseous changes and the continous follow-up of FAP patients by a dental surgeon is extremely important since dento-osseous changes precedes gastrointestinal symptoms. Further studies are necessary to clarify molecular aspects of FAP in connection to dento-osseous changes

Correção cirúrgica de fístula buco-sinusal relato de um caso clínico.

Correção cirúrgica de fístula buco-sinusal relato de um caso clínico

Neotropical freshwater fisheries : A dataset of occurrence and abundance of freshwater fishes in the Neotropics

The Neotropical region hosts 4225 freshwater fish species, ranking first among the world's most diverse regions for freshwater fishes. Our NEOTROPICAL FRESHWATER FISHES data set is the first to produce a large-scale Neotropical freshwater fish inventory, covering the entire Neotropical region from Mexico and the Caribbean in the north to the southern limits in Argentina, Paraguay, Chile, and Uruguay. We compiled 185,787 distribution records, with unique georeferenced coordinates, for the 4225 species, represented by occurrence and abundance data. The number of species for the most numerous orders are as follows: Characiformes (1289), Siluriformes (1384), Cichliformes (354), Cyprinodontiformes (245), and Gymnotiformes (135). The most recorded species was the characid Astyanax fasciatus (4696 records). We registered 116,802 distribution records for native species, compared to 1802 distribution records for nonnative species. The main aim of the NEOTROPICAL FRESHWATER FISHES data set was to make these occurrence and abundance data accessible for international researchers to develop ecological and macroecological studies, from local to regional scales, with focal fish species, families, or orders. We anticipate that the NEOTROPICAL FRESHWATER FISHES data set will be valuable for studies on a wide range of ecological processes, such as trophic cascades, fishery pressure, the effects of habitat loss and fragmentation, and the impacts of species invasion and climate change. There are no copyright restrictions on the data, and please cite this data paper when using the data in publications

Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease: Results From the CREDENCE Trial and Meta-Analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus.METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-analysis.RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (<45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]).CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02065791

Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex: A Post Hoc Analysis of the CREDENCE Randomized Clinical Trial

Rationale & Objective: It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kid-ney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the Canagli-flozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) study.Study Design: Secondary analysis of a random-ized controlled trial. Setting & Participants: Participants in the CREDENCE trial. Intervention: Participants were randomly assigned to receive canagliflozin 100 mg/d or placebo.Outcomes: Primary composite outcome of kid-ney failure, doubling of serum creatinine con-centration, or death due to kidney or cardiovascular disease. Prespecified secondary and safety outcomes were also analyzed. Out-comes were evaluated by age at baseline (<60, 60-69, and >_70 years) and sex in the intention-to-treat population using Cox regression models.Results: The mean age of the cohort was 63.0 & PLUSMN; 9.2 years, and 34% were female. Older age and female sex were independently associ-ated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (acomposite of kidney failure, a doubling of serum creatinine concentration, or death from kidney or cardiovascular causes) differed between age groups (HRs, 0.67 [95% CI, 0.52-0.87], 0.63 [0.4 8-0.82], and 0.89 [0.61-1.29] for ages <60, 60-69, and >_70 years, respectively; P = 0.3 for interaction) or sexes (HRs, 0.71 [95% CI, 0.5 4-0.95] and 0.69 [0.56-0.8 4] in women and men, respectively; P = 0.8 for interaction). No differences in safety outcomes by age group or sex were observed.Limitations: This was a post hoc analysis with multiple comparisons.Conclusions: Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. As a result of greater background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.Funding: This post hoc analysis of the CREDENCE trial was not funded. The CREDENCE study was sponsored by Janssen Research and Development and was conducted collaboratively by the sponsor, an academic-led steering committee, and an academic research organization, George Clinical.Trial Registration: The original CREDENCE trial was registered at ClinicalTrials.gov with study number NCT02065791