International variation in outcomes among people with cardiovascular disease or cardiovascular risk factors and impaired glucose tolerance: insights from the NAVIGATOR Trial

Background: Regional differences in risk of diabetes mellitus and cardiovascular outcomes in people with impaired glucose tolerance are poorly characterized. Our objective was to evaluate regional variation in risk of new‐onset diabetes mellitus, cardiovascular outcomes, and treatment effects in participants from the NAVIGATOR (Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research) trial. Methods and Results: NAVIGATOR randomized people with impaired glucose tolerance and cardiovascular risk factors or with established cardiovascular disease to valsartan (or placebo) and to nateglinide (or placebo) with a median 5‐year follow‐up. Data from the 9306 participants were categorized by 5 regions: Asia (n=552); Europe (n=4909); Latin America (n=1406); North America (n=2146); and Australia, New Zealand, and South Africa (n=293). Analyzed outcomes included new‐onset diabetes mellitus; cardiovascular death; a composite cardiovascular outcome of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke; and treatment effects of valsartan and nateglinide. Respective unadjusted 5‐year risks for new‐onset diabetes mellitus, cardiovascular death, and the composite cardiovascular outcome were 33%, 0.4%, and 4% for Asia; 34%, 2%, and 6% for Europe; 37%, 4%, and 8% for Latin America; 38%, 2%, and 6% for North America; and 32%, 4%, and 8% for Australia, New Zealand, and South Africa. After adjustment, compared with North America, European participants had a lower risk of new‐onset diabetes mellitus (hazard ratio 0.86, 95% CI 0.78–0.94; P=0.001), whereas Latin American participants had a higher risk of cardiovascular death (hazard ratio 2.68, 95% CI 1.82–3.96; P<0.0001) and the composite cardiovascular outcome (hazard ratio 1.48, 95% CI 1.15–1.92; P=0.003). No differential interactions between treatment and geographic location were identified. Conclusions: Major regional differences regarding the risk of new‐onset diabetes mellitus and cardiovascular outcomes in NAVIGATOR participants were identified. These differences should be taken into account when planning global trials

AKT can modulate the in vitro response of HNSCC cells to irreversible EGFR inhibitors

Epidermal growth factor receptor (EGFR) is overexpressed in up to 90% of head and neck squamous cell carcinoma (HNSCC) tumors. Cetuximab is the first targeted (anti-EGFR) therapy approved for the treatment of HNSCC patients. However, its efficacy is limited due to primary and secondary resistance, and there is no predict biomarkers of response. New generation of EGFR inhibitors with pan HER targeting and irreversible action, such as afatinib and allitinib, represents a significant therapeutic promise. In this study, we intend to compare the potential cytotoxicity of two anti-EGFR inhibitors (afatinib and allitinib) with cetuximab and to identify potential predictive biomarkers of response in a panel of HNSCC cell lines. The mutational analysis in the eight HNSCC cell lines revealed an EGFR mutation (p.H773Y) and gene amplification in the HN13 cells. According to the growth inhibition score (GI), allitinib was the most cytotoxic drug, followed by afatinib and finally cetuximab. The higher AKT phosphorylation level was associated with resistance to anti-EGFR agents. Therefore, we further performed drug combinations with anti-AKT agent (MK2206) and AKT1 gene editing, which demonstrated afatinib and allitinib sensitivity restored. Additionally, in silico analysis of TCGA database showed that AKT1 overexpression was present in 14.7% (41/279) of HNSCC cases, and was associated with perineural invasion in advanced stage. In conclusion, allitinib presented a greater cytotoxic profile when compared to afatinib and cetuximab. AKT pathway constitutes a predictive marker of allitinib response and combination with AKT inhibitors could restore response and increase treatment success.FINEP (MCTI/FINEP/MS/SCTIE/DECIT-01/2013 - FPXII-BIOPLAT) and the Assistance Program and Incentive Research (PAIP), Barretos Cancer Hospital São Paulo, Brazil. The authors would like to acknowledge the technical support of Gabriela Lamberti in the clonogenic assays. A.L.C and R.M.R are recipients of a National Counsel of Technological and Scientific Development (CNPq) scholarship and O.C.M is recipient of a Portuguese Foundation for Science and Technology (FCT) scholarship (SFRH/BPD/108351/2015)info:eu-repo/semantics/publishedVersio

ATUAÇÃO DO FARMACÊUTICO CLÍNICO NA ADMISSÃO E ALTA DE PACIENTES DA ENFERMARIA DE UM HOSPITAL PÚBLICO DO CENTRO-OESTE BRASILEIRO

Introdução e objetivos: A reconciliação medicamentosa é um processo que permite ao farmacêutico clínico analisar as informações precisas sobre o uso habitual de medicamentos pelo paciente e posteriormente comparar com as prescrições durante a internação hospitalar. Compreende várias etapas, entre elas a anamnese, análise das informações nos prontuários e prescrições, visando garantir a continuidade do tratamento domiciliar durante a internação. Na alta hospitalar, o farmacêutico busca aprimorar a orientação quanto ao seguimento do plano terapêutico proposto, acesso, armazenamento e administração dos medicamentos1. O objetivo deste trabalho foi mensurar a atuação do farmacêutico clínico nos processos de admissão e alta na enfermaria de um hospital público do centro-oeste brasileiro. Metodologia: Estudo retrospectivo, descritivo com dados coletados de indicadores institucionais de produtividade entre abril e dezembro de 2014, referentes aos atendimentos na enfermaria de Clínica Médica de um hospital especializado em média/alta complexidade. A enfermaria conta com 62 leitos e realizou 1.443 admissões em 2014. Resultados e discussões: No período em estudo foram realizadas 883 reconciliações (84,7% das admissões no setor) que encontraram 242 (31,9%) discrepâncias entre os medicamentos de uso domiciliar e a prescrição médica na internação. As orientações de alta foram fornecidas a 147 pacientes, dos quais 41 (27,9%) precisaram de intervenção junto ao prescritor em decorrência da detecção de interação medicamentosa ou, para substituição de item prescrito por outro disponível na rede pública. Dentre as 323 intervenções propostas durante a admissão e alta desses pacientes, 301 (93,2%) tiveram adesão do corpo clínico, valores estes semelhantes aos de outros autores2,3. Conclusões: A inserção do farmacêutico clínico na admissão e alta possibilitou identificar fragilidades no processo de uso de medicamentos, originando intervenções que foram bem aceitas pela equipe médica do Hospital

Ankle-brachial index as a predictor of coronary disease events in elderly patients submitted to coronary angiography

OBJECTIVES: To correlate the importance of the ankle-brachial index in terms of cardiovascular morbimortalityand the extent of coronary arterial disease amongst elderly patients without clinical manifestations of lowerlimb peripheral arterial disease.METHODS: We analyzed prospective data from 100 patients over 65 years of age with coronary arterial disease,as confirmed by coronary angiography, and with over 70% stenosis of at least one sub-epicardial coronaryartery. We measured the ankle-brachial index immediately after coronary angiography, and a value of ,0.9was used to diagnose peripheral arterial disease.RESULTS: The patients’ average age was 77.4 years. The most prevalent risk factor was hypertension (96%), andthe median late follow-up appointment was 28.9 months. The ankle-brachial index was ,0.9 in 47% of thepatients, and a low index was more prevalent in patients with multiarterial coronary disease compared topatients with uniarterial disease in the same group. Using a bivariate analysis, only an ankle-brachial index of,0.9 was a strong predictive factor for cardiovascular events, thereby increasing all-cause deaths and fatal andnon-fatal acute myocardial infarctions two- to three-fold.CONCLUSION: In elderly patients with documented coronary disease, a low ankle-brachial index (,0.9) wasassociated with the severity and extent of coronary arterial disease, and in late follow-up appointments, a lowindex was correlated with an increase in the occurrence of major cardiovascular events

Probabilistic model for the representation of the reservoir water level of concrete dams during normal operation periods

The dam’s reservoir water level varies over the year according to the water inflow and outflow, as a function of environmental events but also of dam exploitation management policy and human decisions. In the Portuguese dam safety regulation (RSB 2007), the normal water level (NWL) is considered as the optimum exploitation level. However, as proved by the continuous monitoring over the lifetime of a set of dams, the NWL is occasionally exceeded for non-negligible time periods. The reservoir water level, to which the water pressure on the upstream face is related, is a fundamental parameter for the safety and reliability analysis of concrete dams. When water-induced actions are considering the leading loads, only the maximum reservoir water level, usually associated with a high-return-period flood, is relevant. However, for other combinations, in particular, earthquake scenarios, the consideration of the variability of the water level over time is crucial. In reliability analysis of concrete dams, the reservoir water level has been considered either as a deterministic variable, once the loading scenario analyzed assume water-induced actions as leading loads (Westberg 2010), or as a random variable defined using hydrological site information of a specific study case (Altarejos et al. Structural Safety 36-37:1–13 2012). This work proposes a probabilistic model of the reservoir water level of any new dam based only on its geometrical properties, which provides a low-cost alternative to in-depth hydrological analysis. The proposed model can be useful in two stages of the lifecycle of dams: (i) initial design and feasibility stages, and (ii) routine safety assessment of existing structures, as in both stages the costs of a complete hydrological analysis is too high for the level of detail required. For that, the recorded reservoir water level of 27 Portuguese large concrete dams is used. A normalized sinusoidal model, with annual period, is adjusted to the reservoir water level annual history of those dams by beta regression. Generally, a good agreement between observations and the proposed model, for most of the annual adjustments, was achieved. The distribution parameters of the random variables were estimated through the maximum likelihood estimation (MLE) method. The physical, model and statistical uncertainties were quantified and can now be included in a reliability analysis procedur

Mechanical Ventilation and Clinical Outcomes in Patients with Acute Myocardial Infarction: A Retrospective Observational Study

Patients with acute myocardial infarction (AMI) and respiratory impairment may be treated with either invasive or non-invasive mechanical ventilation (MV). However, there has been little testing of non-invasive MV in the setting of AMI. Our objective was to evaluate the incidence and associated clinical outcomes of patients with AMI who were treated with non-invasive or invasive MV

Um modelo para seleção de avaliações adaptativas em ambientes computacionais de aprendizagem

No sistema tradicional de ensino e também na grande maioria dos Ambientes Computacionais de Aprendizagem todos os estudantes são avaliados de maneira uniforme independente do seu nível de aquisição de conhecimentos e dos conteúdos abordados. O insucesso recorrente nessas avaliações pode ser desestimulante para o aprendiz e torna o processo de avaliação formativa ineficaz uma vez que os resultados não são utilizados para realimentar o próprio processo de avaliação. Este artigo tem por objetivo apresentar um modelo para a seleção de avaliações adaptativas num ambiente computacional de aprendizagem utilizando técnicas de mineração de dados com base no nível de aquisição de conhecimentos do estudante em cada item do domínio em questão e também nos conteúdos abordados nas unidades de Avaliação. A seleção de unidades de avaliação adequadas ao perfil atual do estudante criará condições para avaliações personalizadas de modo a proteger ou desafiar o aprendiz nos seus sucessos ou insucessos.In the traditional system of education and also in the great majority of Computational Environments of Learning all the students are evaluated in an independent uniform way it its level of acquisition of knowledge and them boarded contents. The recurrent failure in these evaluations can be discouraged for the apprentice and becomes the process of inefficacious formative evaluation once that the results are not used to feedback the proper process of evaluation. This article has for objective to present a model for the selection of adaptive evaluations in a computational environment of learning using data mining techniques based on the level of acquisition of knowledge of the student in each item of the domain in question and also in the boarded contents in the units of the Evaluation. The selection of adequate units of evaluation to the current profile of the student will create conditions for personalized evaluations in order to protect or to defy the apprentice in its successes or failures.VI Workshop de Tecnología Informática Aplicada en EducaciónRed de Universidades con Carreras en Informática (RedUNCI

Um modelo para seleção de avaliações adaptativas em ambientes computacionais de aprendizagem

No sistema tradicional de ensino e também na grande maioria dos Ambientes Computacionais de Aprendizagem todos os estudantes são avaliados de maneira uniforme independente do seu nível de aquisição de conhecimentos e dos conteúdos abordados. O insucesso recorrente nessas avaliações pode ser desestimulante para o aprendiz e torna o processo de avaliação formativa ineficaz uma vez que os resultados não são utilizados para realimentar o próprio processo de avaliação. Este artigo tem por objetivo apresentar um modelo para a seleção de avaliações adaptativas num ambiente computacional de aprendizagem utilizando técnicas de mineração de dados com base no nível de aquisição de conhecimentos do estudante em cada item do domínio em questão e também nos conteúdos abordados nas unidades de Avaliação. A seleção de unidades de avaliação adequadas ao perfil atual do estudante criará condições para avaliações personalizadas de modo a proteger ou desafiar o aprendiz nos seus sucessos ou insucessos.In the traditional system of education and also in the great majority of Computational Environments of Learning all the students are evaluated in an independent uniform way it its level of acquisition of knowledge and them boarded contents. The recurrent failure in these evaluations can be discouraged for the apprentice and becomes the process of inefficacious formative evaluation once that the results are not used to feedback the proper process of evaluation. This article has for objective to present a model for the selection of adaptive evaluations in a computational environment of learning using data mining techniques based on the level of acquisition of knowledge of the student in each item of the domain in question and also in the boarded contents in the units of the Evaluation. The selection of adequate units of evaluation to the current profile of the student will create conditions for personalized evaluations in order to protect or to defy the apprentice in its successes or failures.VI Workshop de Tecnología Informática Aplicada en EducaciónRed de Universidades con Carreras en Informática (RedUNCI