Effect of aleglitazar on cardiovascular outcomes after acute coronary syndrome in patients with type 2 diabetes mellitus: The AleCardio randomized clinical trial

IMPORTANCE: No therapy directed against diabetes has been shown to unequivocally reduce the excess risk of cardiovascular complications. Aleglitazar is a dual agonist of peroxisome proliferator-activated receptors with insulin-sensitizing and glucose-lowering actions and favorable effects on lipid profiles. OBJECTIVE: To determine whether the addition of aleglitazar to standard medical therapy reduces cardiovascular morbidity and mortality among patients with type 2 diabetes mellitus and a recent acute coronary syndrome (ACS). DESIGN, SETTING, AND PARTICIPANTS: AleCardio was a phase 3, multicenter, randomized, double-blind, placebo-controlled trial conducted in 720 hospitals in 26 countries throughout North America, Latin America, Europe, and Asia-Pacific regions. The enrollment of 7226 patients hospitalized for ACS (myocardial infarction or unstable angina) with type 2 diabetes occurred between February 2010 and May 2012; treatment was planned to continue until patients were followed-up for at least 2.5 years and 950 primary end point events were positively adjudicated. INTERVENTIONS: Randomized in a 1:1 ratio to receive aleglitazar 150 µg or placebo daily. MAIN OUTCOMES AND MEASURES: The primary efficacy end point was time to cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Principal safety end points were hospitalization due to heart failure and changes in renal function. RESULTS: The trial was terminated on July 2, 2013, after a median follow-up of 104 weeks, upon recommendation of the data and safety monitoring board due to futility for efficacy at an unplanned interim analysis and increased rates of safety end points. A total of 3.1% of patients were lost to follow-up and 3.2% of patients withdrew consent. The primary end point occurred in 344 patients (9.5%) in the aleglitazar group and 360 patients (10.0%) in the placebo group (hazard ratio, 0.96 [95% CI, 0.83-1.11]; P = .57). Rates of serious adverse events, including heart failure (3.4% for aleglitazar vs 2.8% for placebo, P = .14), gastrointestinal hemorrhages (2.4% for aleglitazar vs 1.7% for placebo, P = .03), and renal dysfunction (7.4% for aleglitazar vs 2.7% for placebo, P < .001) were increased. CONCLUSIONS AND RELEVANCE: Among patients with type 2 diabetes and recent ACS, use of aleglitazar did not reduce the risk of cardiovascular outcomes. These findings do not support the use of aleglitazar in this setting with a goal of reducing cardiovascular risk. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01042769.A. Michael Lincoff, Jean-Claude Tardif, Gregory G. Schwartz, Stephen J. Nicholls, Lars Rydén, Bruce Neal, Klas Malmberg, Hans Wedel, John B. Buse, Robert R. Henry, Arlette Weichert, Ruth Cannata, Anders Svensson, Dietmar Volz, Diederick E. Grobbee for the AleCardio Investigator

Phosphorus availability in a low pH highly weathered soil as affected by added salts Disponibilidade de fósforo num solo ácido afetada pela aplicação de sais

Concentration and identity of cations and anions in the soil solution may affect soil P reactions and thus P availability. The magnitude of these reactions was evaluated in this research after application of various salts to a highly weathered low pH soil. Chloride, nitrate, and sulfate salts of Na, NH4, K, Ca, Mg, Sr, or Cu were added to the soil after addition of 360mg P/kg trying to simulate ion concentrations around granules of fertilizers in the soil. Thirty days later, P was determined in the soil solution (Pli) and on the solid phase (Psi). The soil samples of some treatments were leached with water and three days later a new soil solution was displaced. Separate addition of all salts increased Pli, except NaCl at the lowest rate. The increase of Pli was highly associatcd with amount of native cations displaced to the soil solution by the applied salts. Salt solubility, concentration, and sometimes identity of cation and anion also influenced Pli. Some salts decreased Psi, but this was not correlated with any soil property measured. The effects caused by salts on Pli and Psi disappeared after leaching the soil samples.<br>A concentração eletrolítica e o tipo de cations e anions da solução do solo podem afetar as reações do fósforo com possíveis reflexos na disponibilidade de P aos vegetais. Nessa pesquisa quantificou-se o efeito de vários sais nos valores das determinações analíticas que afetam a disponibilidade de fósforo. Sais de nitrato, cloreto e sulfato foram aplicados a amostras de um alfisol ácido após a aplicação de 360mg P/kg, simulando concentrações que ocorrem no solo ao redor de grânulos de fertilizantes. Fósforo lábil (Psi) e P na solução do solo (Pli) foram determinados após 30 dias de incubação, antes e depois de percolar água pelo solo. Todos os sais aumentaram a concentração de P na solução do solo, exceto a menor dose de NaCl. O aumento do Pli foi correlacionado com a quantidade de cations originalmente no solo deslocados para a solução do solo. Solubilidade, concentração, e a espécie dos cations e anions aplicados também exerceram efeito no Pli. Alguns sais diminuíram o Psi porém esse decréscimo não se correlacionou com nenhuma determinação efetuada. A percolação de água eliminou os efeitos ocasionados pelos sais nos valores de fósforo

Carga máxima de fósforo admissível ao reservatório Piraquara II, uma aplicação do processo TMDL Maximum allowable phosphorus load in the Piraquara II reservoir, a TMDL process application

Para implementação e operacionalização da política brasileira de recursos hídricos, é imprescindível o uso de ferramentas de planejamento que considerem o efeito de todas as atividades ou processos que causam ou contribuem para a degradação da qualidade de um corpo d'água. Neste sentido, aplicou-se o processo TMDL (total maximum daily load), desenvolvido pela Agência de Proteção Ambiental dos Estados Unidos (EPA), para o P, na área de drenagem de contribuição ao futuro reservatório Piraquara II, bacia hidrográfica do rio Piraquara, Paraná. O processo TMDL determina a quantidade máxima de cargas de um poluente que um corpo d'água pode receber sem violar os padrões estabelecidos de qualidade da água e aloca cargas deste poluente entre fontes de poluição pontuais e difusas. No presente estudo, utilizou-se o método TMDL, com o objetivo de demonstrar ser ele uma ferramenta útil no processo de gestão dos recursos hídricos. Simularam-se cenários de uso do solo, por meio de modelagem matemática, até obter-se uma concentração de P total no reservatório abaixo da faixa limite para ocorrência de eutrofização, de 0,025 a 0,10 mg L-1, estabelecida no estudo. Realizou-se uma simulação de uso atual do solo, visando prever a condição inicial de qualidade da água no corpo d'água, na qual a concentração de P total no reservatório resultante não atendeu ao padrão estabelecido. Procedeu-se a uma segunda simulação com adoção das medidas de controle, recomposição de mata ciliar e plantio direto, para reduzir a exportação de carga de P total da bacia. Obteve-se uma melhoria na qualidade da água do reservatório, indicando que as medidas adotadas foram suficientes para atingir o padrão estabelecido, o que demonstra a aplicabilidade do método.<br>For the implementation and operation of the Brazilian Federal law on water resources of 1997 it is indispensable to use planning tools that take into account the effect of all activities or processes that cause or contribute to the loss of quality of a waterbody. For this purpose, the nutrient phosphorus was evaluated by the TMDL (total maximum daily load) process developed by the United States Environmental Protection Agency - EPA in the drainage area of contribution to the future Piraquara II Reservoir, Piraquara River Watershed, Paraná State, Brazil. The TMDL process determines the maximum amount of a pollutant load a waterbody can receive without violating the established water quality standards, and allocates loads of this pollutant between point and nonpoint sources. In the present research the TMDL methodology was used to demonstrate its usefulness in the management of water resources. Sceneries of soil use were simulated by mathematic modeling to define a total phosphorus concentration in the reservoir under the limit range for eutrophication established in the study (0.025-0.10 mg L-1 of P). The current soil use was simulated aiming to foresee the initial condition of water quality in the waterbody. The data obtained indicate that the resulting total phosphorus concentration in the reservoir did not meet the established standard. In a second simulation with adoption of potential control measures, such as recomposed riparian areas and no-till systems, the exportated total phosphorus load from the watershed decreased. With adoption of such conservation measure the simulated water quality of the reservoir improved and attained the established standard, demonstratig the applicability of the methodology