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Background. Patients with type 2 diabetes are at increased risk of macro- and microvascular disease, and the presence of albuminuria and/or reduced kidney function further enhances macrovascular risk. Angiotensin-converting-enzyme inhibitors reduce both macro- and microvascular events, yet the residual renal and cardiovascular risk still remains high. Aliskiren a novel oral direct renin inhibitor that unlike ACEi and ARBs, lowers plasma renin activity, angiotensin I and angiotensin II levels, may thereby provide greater benefit compared to ACEi or ARB alone. Methods. The primary objective of the ALTITUDE trial is to determine whether aliskiren 300 mg once daily, reduces cardiovascular and renal morbidity and mortality compared with placebo when added to conventional treatment (including ACEi or ARB). ALTITUDE is an international, randomized, double-blind, placebo-controlled, parallel-group study, which will include three categories of high-risk patients with type 2 diabetes (aged ≥35 years): those with either urinary albumin/creatinine ratio (UACR) ≥200 mg/g; microalbuminuria (UACR) ≥20 Conclusion. ALTITUDE will determine whether dual RAAS blockade with the direct renin inhibitor aliskiren in combination with an ACEi or ARB will reduce major morbidity and mortality in a broad range of high-risk patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Under a general regression setting, we propose an optimal unconditional prediction procedure for future responses. The resulting prediction intervals or regions have a desirable average coverage level over a set of covariate vectors of interest. When the working model is not correctly specified, the traditional conditional prediction method is generally invalid. On the other hand, one can empirically calibrate the above unconditional procedure and also obtain its crossvalidated counterpart. Various large and small sample properties of these unconditional methods are examined analytically and numerically. We find that the [script K]-fold crossvalidated procedure performs exceptionally well even for cases with rather small sample sizes. The new proposals are illustrated with two real examples, one with a continuous response and the other with a binary outcome. [ABSTRACT FROM AUTHOR]