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Objectives The objective of this clinical trial was to evaluate the long-term effect of endothelin receptor antagonism with bosentan on the morbidity and mortality of patients with severe chronic heart failure. Background Endothelin may play a role in heart failure, but short-term clinical trials with endothelin receptor antagonists have reported disappointing results. Long-term trials are lacking. Methods In 2 identical double-blind trials, we randomly assigned 1,613 patients with New York Heart Association functional class IIIb to IV heart failure and an ejection fraction Results Bosentan did not influence clinical status at 9 months in either trial (p = 0.928 and p = 0.263). In addition, 321 patients in the placebo group and 312 patients in the bosentan group died or were hospitalized for heart failure (hazard ratio [HR]: 1.01; 95% confidence interval [CI]: 0.86 to 1.18; p = 0.90). The bosentan group experienced fluid retention within the first 2 to 4 weeks, as evidenced by increased peripheral edema, weight gain, decreases in hemoglobin, and an increased risk of hospitalization for heart failure, despite intensification of background diuretics. During follow-up, 173 patients died in the placebo group and 160 patients died in the bosentan group (HR: 0.94; 95% CI: 0.75 to 1.16). About 10% of the bosentan group showed meaningful increases in hepatic transaminases, but none had acute or chronic liver failure. Conclusions Bosentan did not improve the clinical course or natural history of patients with severe chronic heart failure and but caused early and important fluid retention.

An important function of asset management is forecasting risks and returns. However, investment decisions are made on the basis of relative performance within an expected set of financial and economic conditions. The aim of this paper is to examine if a model could be developed to explain the relationship between capital values and financial variables of Sydney CBD office market performance. The time-series data between Dec-1984 - June 1998 was used to establishing the relationship. The results of the data analysis reveals that property capital values are positively correlated with 90-day bank bills (interest rates) and the one-year lagged risk-free return, represented by the real 10-yr. Government bond rates. The conditions in the stock market, proxies association. Annual Sydney inflation rate (CPI) is negatively correlated with property capital values, that is higher CPI prospect should result in falling property capital values. The paper concludes that the model may throw some light on a theoretical hypotheses, and also the results of the final model are consistent with the author expectation and are statistically acceptable.