Aliskiren, a novel oral renin inhibitor, provides dose-dependent efficacy and placebo-like tolerability in Japanese patients with hypertension.

Aliskiren is a novel orally active renin inhibitor for the treatment of hypertension. This study evaluated the antihypertensive efficacy, safety and tolerability of aliskiren in Japanese patients with hypertension. Forty hundred and fifty-five Japanese men and women with a mean sitting diastolic blood pressure of 95-110 mmHg were randomized to receive once-daily double-blind treatment for 8 weeks with aliskiren 75, 150 or 300 mg or placebo. Aliskiren produced significant, dose-dependent reductions in mean sitting diastolic blood pressure (p<0.0005 vs. placebo for each dose) and mean sitting systolic blood pressure (p<0.001 vs. placebo for each dose). The placebo-corrected reductions in mean sitting systolic/diastolic blood pressure were 5.7/4.0, 5.9/4.5 and 11.2/7.5 mmHg in the aliskiren 75, 150 and 300 mg groups, respectively. After 8 weeks' treatment, 27.8%, 47.8%, 48.2% and 63.7% of patients in the placebo and aliskiren 75, 150 and 300 mg groups, respectively, achieved a successful treatment response (diastolic blood pressure <90 mmHg and/or reduced by > or =10 mmHg from baseline; p<0.005 vs. placebo for each dose). Aliskiren treatment was well tolerated, with the incidence of adverse events reported in the active treatment groups (53-55%) being similar to that in the placebo group (50%). This study, which is the first to assess the antihypertensive efficacy and safety of aliskiren in Japanese patients with hypertension, demonstrates that the once-daily oral renin inhibitor aliskiren provides significant, dose-dependent reductions in blood pressure with placebo-like tolerability.     

The influence of different error estimates in the detection of post-operative cognitive dysfunction using reliable change indices with correction for practice effects.

The reliable change index (RCI) expresses change relative to its associated error, and is useful in the identification of post-operative cognitive dysfunction (POCD). This paper examines four common RCIs that each account for error in different ways. Three rules incorporate a constant correction for practice effects and are contrasted with the standard RCI that had no correction for practice. These rules are applied to 160 patients undergoing coronary artery bypass graft (CABG) surgery who completed neuropsychological assessments preoperatively and 1 week post-operatively using error and reliability data from a comparable healthy non-surgical control group. The rules all identify POCD in a similar proportion of patients, but the use of the within subject standard deviation, expressing the effects of random error, as an error estimate is a theoretically appropriate denominator when a constant error correction, removing the effects of systematic error, is deducted from the numerator in a RCI.     

Improved graft survival for flow cytometry and antihuman globulin crossmatch-negative retransplant recipients

We compared our standard NIH (extended incubation) crossmatch (XM) with antihuman globulin (AHG) and flow cytometry XMs and correlated the results with rejection episodes and graft survivals. For 89 CsA-Pred, primary renal allograft recipients, AHG and/or FCXM results did not improve on the NIH-XM-negative (NEG) graft survival results, whether testing pretransplant or historical (Hx) sera. Similarly, there was no association of a positive (POS) AHG or FCXM with increased rejection episodes in these primary recipients. However, for retransplant (Re-Tx) recipients a neg AHG or FCXM did discriminate fewer rejections and an improved graft survival compared with the NIH-XM-neg. results. The overall one-year graft survival for the 47 Re-Tx recipients studied herein was 66% (based on a neg pre-Tx NIH-XM). Pre-Tx AHG-NEG, Re-Tx recipients displayed an improved graft survival compared with NIH-XM NEG recipients (77% vs. 66%, P less than 0.05) and with AHG-POS recipients (77% vs. 47%, P less than 0.05). Similarly, pre-Tx, FCXM-NEG, Re-Tx recipients displayed improved graft survivals compared with NIH-XM-NEG recipients (83% vs. 66%, P less than 0.05) and FCXM-POS recipients (83% vs. 48%, P less than 0.05). Re-Tx recipients displaying a POS AHG and/or FCXM experienced a significantly greater number of rejections than NEG-XM recipients (P less than 0.05, respectively). The AHG and FCXM results correlated with rejections and graft survivals whether testing pre-Tx or Hx high-PRA sera. Re-Tx recipients who were AHG-XM-NEG but FCXM-POS, experienced more rejection episodes than recipients who displayed a negative XM reactivity for both AHG and FCXM (P less than 0.02), but with no resulting differences in graft survival. HLA matching, pre-Tx blood transfusions and PRA did not impact on these crossmatch and graft survival results. Use of AHG and/or FCXMs for Re-Tx, but not primary, recipients should help to improve graft survival for these high-risk recipients.