METHODS
In a prospective, double-blind, randomized trial, we assigned 308 patients with acute decompensated heart failure to receive furosemide administered intravenously by means of either a bolus every 12 hours or continuous infusion and ATPase inhibitor at either a low dose (equivalent to the patient’s previous oral dose) or a high dose (2.5 times the previous oral dose). The protocol allowed specified dose adjustments after 48 hours. The coprimary end points were patients’ global assessment of symptoms, quantified as the area under the curve (AUC) of the score on a visual-analogue scale over the course of 72 hours,
and the change in the serum creatinine level from baseline to 72 hours.
RESULTS
In the comparison of bolus with continuous infusion, there was no significant difference in patients’ global assessment of symptoms (mean AUC, 4236 +/- 1440 and 4373 +/- 1404, respectively; P = 0.47) or in the mean change in the creatinine level (0.05 +/- 0.3 mg per deciliter [4.4 +/- GSK126 concentration 26.5 mu mol per liter] and 0.07 +/- 0.3 mg per deciliter [6.2 +/- 26.5 mu mol per liter], respectively; P
= 0.45). In the comparison of the high-dose strategy with the low-dose strategy, there was a nonsignificant trend toward greater improvement in patients’ global assessment of symptoms in the high-dose group (mean AUC, 4430 +/- 1401 vs. 4171 +/- 1436; P = 0.06). There was no significant difference between these groups in the mean change in the creatinine level (0.08 +/- 0.3 mg per deciliter [7.1 +/- 26.5 mu mol per liter] with the high-dose strategy and 0.04 +/- 0.3 mg per deciliter [3.5 +/- 26.5 mu mol per liter] with the low-dose strategy, P = 0.21). The high-dose strategy was associated with greater diuresis and more favorable outcomes in some secondary measures but also with transient worsening of renal function.
CONCLUSIONS
Among patients with acute decompensated heart failure, there were no significant differences in patients’ global assessment of symptoms or in the change in renal function when diuretic therapy was administered
by bolus as compared with continuous infusion or at a high dose as compared with a low dose.”
“CCR5 antagonists inhibit HIV entry by binding to a coreceptor and inducing changes in the extracellular loops Leukotriene-A4 hydrolase (ECLs) of CCR5. In this study, we analyzed viruses from 11 treatment-experienced patients who experienced virologic failure on treatment regimens containing the CCR5 antagonist maraviroc (MVC). Viruses from one patient developed high-level resistance to MVC during the course of treatment. Although resistance to one CCR5 antagonist is often associated with broad cross-resistance to other agents, these viruses remained sensitive to most other CCR5 antagonists, including vicriviroc and aplaviroc. MVC resistance was dependent upon mutations within the V3 loop of the viral envelope (Env) protein and was modulated by additional mutations in the V4 loop.