Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Accuracy versus precision in boosted top tagging with the ATLAS detector

Abstract The identification of top quark decays where the top quark has a large momentum transverse to the beam axis, known as top tagging, is a crucial component in many measurements of Standard Model processes and searches for beyond the Standard Model physics at the Large Hadron Collider. Machine learning techniques have improved the performance of top tagging algorithms, but the size of the systematic uncertainties for all proposed algorithms has not been systematically studied. This paper presents the performance of several machine learning based top tagging algorithms on a dataset constructed from simulated proton-proton collision events measured with the ATLAS detector at √ s = 13 TeV. The systematic uncertainties associated with these algorithms are estimated through an approximate procedure that is not meant to be used in a physics analysis, but is appropriate for the level of precision required for this study. The most performant algorithms are found to have the largest uncertainties, motivating the development of methods to reduce these uncertainties without compromising performance. To enable such efforts in the wider scientific community, the datasets used in this paper are made publicly available.</jats:p

Intestinal parasitic infections in HIV/AIDS patients: epidemiological, nutritional and immunological aspects

This study applied a socioeconomic questionnaire designed to evaluate the frequency of intestinal parasites and characterize epidemiological, nutritional, and immunological variables in 105 HIV/AIDS patients - with and without parasitic infections, attending the Day Hospital in Botucatu, UNESP, from 2007 to 2008. Body mass index was calculated and the following tests performed: parasitological stool examinations; eosinophil, IgE, CD4+ T and CD8+ T lymphocyte cell counts; albumin test; viral load measure; and TNF-&#945;, IFN-&#947;, IL-2, IL-5 and IL-10 cytokine levels. Results were positive for parasitic intestinal infections in 12.4% of individuals. Most patients had good socioeconomic conditions with basic sanitation, urban dwellings, treated water supply and sewage, good nutritional and immunological status and were undergoing HAART. Parasites were found at the following frequencies: Entamoeba - five patients (38.5%), Giardia lamblia - four (30.7%), Blastocystis hominis - three (23.0%), Endolimax nana - two (15.4%), and Ascaris lumbricoides - one (7.7%). There were no significant differences between the two groups for eosinophils, albumin, IgE, CD4+ T and CD8+ T lymphocytes, INF-&#947;, IL-2, or IL-10. Most patients also showed undetectable viral load levels. Significant differences were found for TNF-&#945; and IL-5. These results show the importance of new studies on immunodeficient individuals to increase understanding of such variables

Integration of functional assay data results provides strong evidence for classification of hundreds of <i>BRCA1</i> variants of uncertain significance

PURPOSE: BRCA1 pathogenic variant heterozygotes are at a substantially increased risk for breast and ovarian cancer. The widespread uptake of testing has led to a significant increase in the detection of missense variants in BRCA1, the vast majority of which are variants of uncertain clinical significance (VUS), posing a challenge to genetic counseling. Here, we harness a wealth of functional data for thousands of variants to aid in variant classification. METHODS: We have collected, curated, and harmonized functional data for 2701 missense variants representing 24.5% of possible missense variants in BRCA1. Results were harmonized across studies by converting data into binary categorical variables (functional impact versus no functional impact). Using a panel of reference variants we identified a subset of assays with high sensitivity and specificity (≥80%) and apply the American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) variant interpretation guidelines to assign evidence criteria for classification. RESULTS: Integration of data from validated assays provided ACMG/AMP evidence criteria in favor of pathogenicity for 297 variants or against pathogenicity for 2058 representing 96.2% of current VUS functionally assessed. We also explore discordant results and identify limitations in the approach. CONCLUSION: High quality functional data are available for BRCA1 missense variants and provide evidence for classification of 2355 VUS according to their pathogenicity

Primary care nurses' approach to cases of violence against children

Na atenção básica, o campo da enfermagem se depara com a complexidade da violência, levando esses profissionais a reavaliarem constantemente seu habitus. Objetivo: analisar como os casos de violência contra crianças e adolescentes são abordados pela enfermagem, na atenção básica, identificando limites e possibilidades para se lidar com esses casos. Método: estudo qualitativo, realizado em 2011, com entrevistas semiestruturadas com 8 dos 48 enfermeiros das Equipes de Saúde da Família, da cidade de Uberaba, MG, e cuja análise seguiu a interpretação dos sentidos, baseada na hermenêutica dialética. Resultados: destacam-se a não identificação da violência como problema do enfermeiro, as denúncias e notificações como função do enfermeiro e os limites encontrados ante as situações de violência. Conclusão: constata-se que o habitus de enfermagem, voltado para a promoção à saúde e à prevenção das violências deve ser reestruturado, superando o paradigma biomédico e envolvendo ações intersetoriais e multiprofissionais.In Primary Care, the field of nursing comes face-to-face with the complexity of violence, leading these professionals to constantly re-evaluate their habitus. Objective: to analyze how cases of violence against children and adolescents are approached by primary care nurses, identifying limits and possibilities for dealing with these cases. Method: a qualitative study, undertaken in 2011, through semi-structured interviews with 8 out of 48 nurses in the Family Health teams in the city of Uberaba in the state of Minas Gerais, the analysis of which followed the interpretation of meanings, based in dialectical hermeneutics. Results: the following stand out: non-identification of violence as a problem for the nurses; denunciations and notifications as a role of the nurses; and the limits found in the face of violence. Conclusion: it is determined that the habitus of nursing directed at health promotion and prevention of violence must be restructured, overcoming the biomedical paradigm and involvin

Autoimagem de clientes com colostomia em relação à bolsa coletora

Objetivou-se analisar a percepção do portador de colostomia em relação ao uso da bolsa coletora. Realizou-se uma pesquisa descritiva com abordagem qualitativa, no Centro Integrado de Saúde Lineu Araújo, Teresina-PI. Participaram da pesquisa dez clientes portadores de bolsa de colostomia. Os dados foram produzidos por meio de entrevistas semiestruturadas. A análise de conteúdo permitiu revelar os sentimentos, as mudanças ocorridas e como acontece o processo de adaptação da pessoa portadora da bolsa de colostomia. Constatou-se que a relação entre a pessoa portadora de colostomia e a bolsa coletora é permeada por sentimentos negativos, mudanças significativas de ordem físicas, psicológicas, sexuais, bem como na teia de suas relações sociais

Avaliação participativa da qualidade da informação de saúde na internet: o caso de sites de dengue

Fundação Oswaldo Cruz. Instituto de Comunicação e Informação Cientifica e Tecnológica em Saúde. Programa de Pós-Graduação em Informação e Comunicação em Saúde. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Comunicação e Informação Cientifica e Tecnológica em Saúde. Programa de Pós-Graduação em Informação e Comunicação em Saúde. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.The world has witnessed a powerful and radical transformation of social, economic and cultural relationships promoted by the Internet. The Internet provides opportunities for access, dissemination and production of information worldwide. Health, for example, stands out as one of the main areas with information of interest to a growing number of users. However, this information is often unsatisfactory, incorrect or incomprehensible. This paper analyzes an experiment of evaluation of information on dengue websites developed in a laboratory of the Oswaldo Cruz Foundation. It counted on the participation of a group of Manguinhos dwellers and Public Health PHC physicians, infectious disease specialists and public health physicians in the development of criteria and the evaluation of websites. This paper shows the main results of this experience, which is innovative because its paper and product differ from those proposed by national and foreign agencies and analysts. This experience supports the establishment of an institutional process that issues a quality seal to websites that comply with the suggested criteria and indicators