Qualidade de vida do doente após acidente vascular cerebral

Contextualização: Em Portugal, o AVC constitui a principal causa de incapacidade de longa duração e de diminuição da qualidade de vida. A reabilitação funcional do doente é um dos requisitos básicos no tratamento pós-AVC. Neste contexto, o objetivo do presente estudo pretendeu analisar o modo como determinadas variáveis de contexto sociodemográfico, familiar e clínico estão associadas à qualidade de vida destes doentes. Métodos: Realizou-se um estudo transversal, descritivo correlacional, de natureza quantitativa, no qual participaram 75 doentes, maioritariamente do sexo masculino (53,33%), com uma média de idades de 68 anos. Para a mensuração das variáveis utilizaram-se instrumentos de medida, de reconhecida fiabilidade, aferidos e validados para a população portuguesa: Escala de Apgar Familiar, Escala de Barthel e Questionário de avaliação da qualidade de vida (PSN). Foi também utilizada uma ficha sociodemográfica e clínica. Resultados: Analisando as dimensões da qualidade de vida constatamos que os doentes do sexo feminino apresentam scores superiores em todas as dimensões, existindo diferenças estatísticas significativas apenas para o Isolamento Social. Os participantes solteiros revelaram valores médios mais elevados, resultando em diferenças estatisticamente significativas para o Isolamento Social. Os participantes total e severamente dependentes foram os que revelaram médias mais elevadas na maioria das dimensões, com diferenças estatisticamente significativas em todas as dimensões, exceto na Dor. As variáveis idade, influência da residência, habilitações literárias, situação laboral, condições habitacionais, tipo de AVC, tempo de internamento, local da lesão, influência do programa de reabilitação e funcionalidade familiar não revelaram um efeito significativo sobre a qualidade de vida. Conclusão: As evidências encontradas neste estudo fornecem indicadores para uma melhor intervenção junto dos doentes com AVC, de forma a melhorar a sua adaptação e bem-estar, e da sua família, contribuindo para a sua qualidade de vida. Por outro lado, sensibilizou-nos para a importância em ajustar os cuidados específicos de reabilitação às expetativas e necessidades desses indivíduos. Palavras-chave: Acidente Vascular Cerebral, Qualidade de Vida, Reabilitação Funcional.Abstract Background: In Portugal, cerebrovascular accident (CVA) is the leading cause of long-term disability and diminished quality of life. The functional rehabilitation of the patient is one of the basic requirements in the treatment post-CVA. In this context, the objective of the present study is to examine how certain circumstantial, sociodemographic, familiar and clinical variables, the family functionality and functional independence are associated with the quality of life of these patients. Methods: it was made a cross-sectional, descriptive correlacional, quantitative study, in which participated 75 patients, mostly male (53,33%), with a mean age of 68 years old. For the measurement of the variables, were used measuring instruments of acknowledged reliability, measured and validated to the portuguese population: the Familiar Apgar Scale, the Barthel Scale and the Quality of Life Assessment Questionnaire. It was also used a sociodemographic and clinical data sheet. Results: Analyzing the dimensions of quality of life it was found that female patients have higher scores in all dimensions, and there are significant statistical differences only to Social Isolation. Unmarried participants showed higher average values, resulting in significant statistically differences to Social Isolation. The total and severely dependents participants were those who revealed higher average values in most dimensions, with differing slightly significant statistics, very significant and extremely significant in most dimensions, except in Pain. The variables age, influence of residence, qualifications, employment, housing conditions, type of cerebrovascular accident, time of hospitalization, location of the lesion, influence of rehabilitation programme and family functionality did not show a significant effect on the quality of life. Conclusion: The evidence found in this study provide indicators for a better assistance to patients with cerebrovascular accident, in order to improve their well-being and adjustment, and of his family, contributing to their quality of life. On the other hand, moved us to the importance in adjusting the specific rehabilitation cares of these patients’ expectations and needs. Keywords: Cerebrovascular Accident, Quality of Life, Functional Rehabilitation

Insight into genetic predisposition to chronic lymphocytic leukemia from integrative epigenomics.

Genome-wide association studies have provided evidence for inherited genetic predisposition to chronic lymphocytic leukemia (CLL). To gain insight into the mechanisms underlying CLL risk we analyze chromatin accessibility, active regulatory elements marked by H3K27ac, and DNA methylation at 42 risk loci in up to 486 primary CLLs. We identify that risk loci are significantly enriched for active chromatin in CLL with evidence of being CLL-specific or differentially regulated in normal B-cell development. We then use in situ promoter capture Hi-C, in conjunction with gene expression data to reveal likely target genes of the risk loci. Candidate target genes are enriched for pathways related to B-cell development such as MYC and BCL2 signalling. At 14 loci the analysis highlights 63 variants as the probable functional basis of CLL risk. By integrating genetic and epigenetic information our analysis reveals novel insights into the relationship between inherited predisposition and the regulatory chromatin landscape of CLL

Identification of novel type 2 diabetes candidate genes involved in the crosstalk between the mitochondrial and the insulin signaling systems

Type 2 Diabetes (T2D) is a highly prevalent chronic metabolic disease with strong co-morbidity with obesity and cardiovascular diseases. There is growing evidence supporting the notion that a crosstalk between mitochondria and the insulin signaling cascade could be involved in the etiology of T2D and insulin resistance. In this study we investigated the molecular basis of this crosstalk by using systems biology approaches. We combined, filtered, and interrogated different types of functional interaction data, such as direct protein-protein interactions, co-expression analyses, and metabolic and signaling dependencies. As a result, we constructed the mitochondria-insulin (MITIN) network, which highlights 286 genes as candidate functional linkers between these two systems. The results of internal gene expression analysis of three independent experimental models of mitochondria and insulin signaling perturbations further support the connecting roles of these genes. In addition, we further assessed whether these genes are involved in the etiology of T2D using the genome-wide association study meta-analysis from the DIAGRAM consortium, involving 8,130 T2D cases and 38,987 controls. We found modest enrichment of genes associated with T2D amongst our linker genes (p = 0.0549), including three already validated T2D SNPs and 15 additional SNPs, which, when combined, were collectively associated to increased fasting glucose levels according to MAGIC genome wide meta-analysis (p = 8.12×10(-5)). This study highlights the potential of combining systems biology, experimental, and genome-wide association data mining for identifying novel genes and related variants that increase vulnerability to complex diseases

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

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 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 m 2), 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