No abstract

With the objective of enhancing upper gastrointestinal (GI) tolerability, enteric-coated mycophenolate sodium (EC-MPS, myfortic0.47; p = = NS). Neutropenia (< <1500 cells/mm 3 ) within the first 3 months (coprimary endpoint) was low in both groups (EC-MPS 0.6%; MMF 3.1%; p = = NS). Although the overall incidence of infections was similar, the number of serious infections was significantly lower in EC-MPS patients (8.8% vs. 16.0%; p < < 0.05). Similar rates of efficacy failure (EC-MPS 2.5%; MMF 6.1%; p = = NS), biopsy-proven acute rejection (EC-MPS 1.3%; MMF 3.1%; p = = NS) and biopsy-proven chronic rejection (EC-MPS 3.8%; MMF 4.9%; p = = NS) were observed in both groups. In conclusion, renal maintenance patients can be converted from MMF to EC-MPS without compromising the safety and efficacy profile associated with MMF.

Abstract-Diastolic dysfunction may precede development of heart failure in hypertensive patients. We randomized 228 patients with uncontrolled hypertension, preserved ejection fraction, and diastolic dysfunction to 2 targeted treatment strategies: intensive, with a systolic blood pressure target of Ͻ130 mm Hg, or standard, with a systolic blood pressure target of Ͻ140 mm Hg, using a combination of valsartan, either 160 or 320 mg, plus amlodipine, either 5 or 10 mg, with other antihypertensive medications as needed. any of the adverse sequelae of hypertension are the direct result of target-organ damage to the vasculature, the kidneys, and the heart. In the heart, long-standing hypertension serves as a stimulus for progressive fibrosis, ventricular hypertrophy, 1-3 and diastolic dysfunction, which may be one of the earliest manifestations of cardiac target-organ damage. 4 These changes may be accelerated by age and hypertension-related changes in central aortic stiffness, which may contribute to abnormal pulse wave reflection and enhanced pulsatile arterial load. Present in Յ50% of hypertensive patients, diastolic dysfunction likely represents an important intermediate in the development of heart failure, particularly in patients with preserved systolic function. 5,6 We have demonstrated previously that blood pressure lowering in patients with stage 1 hypertension is associated with improvement in diastolic function, whether a renin-angiotensin-aldosterone system inhibitor or non-renin-angiotensin-aldosterone system blood pressure lowering was used. 7 Because the degree of improvement in diastolic function appears to be closely tied to the degree of blood pressure lowering, we hypothesized that a strategy of aggressive blood pressure control (beyond the established Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure targets 8 ) would be more effective than a less intensive strategy in attenuating cardiac dysfunction. More aggressive targets have already been recommended in certain subgroups of patients, including those with diabetes mellitus, chronic kidney disease, and coronary artery disease. 9 The Exforge Intensive Control of Hypertension to Evaluate Efficacy in Diastolic Dysfunction (EXCEED) Trial was designed to prospectively test the hypothesis that, among patients with uncontrolledContinuing medical education (CME) credit is available for this article. Go to http://cme.ahajournals.org to take the quiz. The principal investigator and steering committee wrote the article, made the decision to submit for publication, and take responsibility for its contents. This trial has been registered at www.clinicaltrials.gov (identifier NCT00523549).

We describe and test a method for fitting noisy differential equation models to a time series of population counts, motivated by stage-structured models of insect and zooplankton populations. We consider semimechanistic models, in which the model structure is derived from knowledge of the life cycle, but the rate equations are estimated nonparametrically from the time-series data. The method involves smoothing the population time series x(t) in order to estimate the gradient dx/dt, and then fitting rate equations using penalized regression splines. Computer-intensive methods are used to estimate and remove the biases that result from the data being discrete time samples with sampling errors from a continuous time process. Semimechanistic modeling makes it possible to test assumptions about the mechanisms behind population fluctuations without the results being confounded by possibly arbitrary choices of parametric forms for process-rate equations. To illustrate this application, we analyze time-series data on laboratory populations of blowflies Lucilia cuprina and Lucilia sericata. The models assume that the populations are limited by competition among adults affecting their current birth and death rates. The results correspond to the actual experimental conditions. For L. cuprina (where the model's structure is appropriate) a good fit can be obtained, while for L. sericata (where the model is inappropriate), the fitted model does not reproduce some major features of the observed cycles. A documented set of R functions for all steps in the model-fitting process is provided as a supplement to this article.