The previously reported benefits of carvedilol with regard to morbidity and mortality in patients with mild-to-moderate heart failure were also apparent in the patients with severe heart failure who were evaluated in this trial.

The data presented here indicate that the provision to patients with knee OA of viscosupplementation with hylan G-F 20 within an appropriate care treatment regimen provides benefits in the knee, overall health and health related quality of life at reduced levels of co-therapy and systemic adverse reactions.

The cost-utility ratio is below the suggested Canadian adoption threshold. The results provide strong evidence for adoption of treatment with hylan G-F 20 in the patients and settings studied in the trial.

BackgroundCardiac cachexia frequently accompanies the progression of heart failure despite the use of effective therapies for left ventricular dysfunction. Activation of the sympathetic nervous system has been implicated in the pathogenesis of weight loss, but the effects of sympathetic antagonism on cachexia are not well defined.MethodsWe prospectively evaluated changes in body weight in 2289 patients with heart failure who had dyspnoea at rest or on minimal exertion and a left ventricular ejection fraction <25%. Patients were randomly assigned (double‐blind) to receive either placebo (n = 1133) or carvedilol (n = 1156) and were followed for the occurrence of major clinical events for up to 29 months (COPERNICUS trial). Patients were not enrolled if they had signs of clinically significant fluid retention due to heart failure.ResultsPatients in the carvedilol group were 33% less likely than patients in the placebo group to experience a further significant loss of weight (>6%) (95% confidence interval: 14–48%, P = 0.002) and were 37% more likely to experience a significant gain in weight (≥5%) (95% confidence interval: 12–66%, P = 0.002). Carvedilol's ability to prevent weight loss was most marked in patients with increased body mass index at baseline, whereas its ability to promote weight gain was most marked in patients with decreased body mass index at baseline. Increases in weight were not accompanied by evidence of fluid retention. Baseline values for body mass index and change in body weight were significant predictors of survival regardless of treatment.ConclusionsCarvedilol attenuated the development and promoted a partial reversal of cachexia in patients with severe chronic heart failure, supporting a role for prolonged sympathetic activation in the genesis of weight loss.

The goal of this study was to develop an aggressive running regimen for modeling osteoarthritis (OA) in rats. Twelve Wistar rats were randomly placed into either a running group or a non-running group to serve as the control. The running rats used a motorized treadmill to run either 30 km in 3 weeks or 55 km in 6 weeks. Each week, the prints of hind paws were obtained when rats were made to walk through a tunnel. The resulting prints were digitalized for analyses of stride length and step angle. The histology of the knees was examined at 3 and 6 weeks and the OA pathology in the knees was quantified by Mankin's score. Osteoarthritic pathology developed in the knees of the running rats, including decreased proteoglycan content, uneven type II collagen distribution in the cartilage matrix, increased MMP-13 expression, expanded calcified cartilage zone, and clefts and defects in articular cartilage. The pathology worsened from running for 3 to 6 weeks. Gait analysis revealed an inverse correlation between paw angle and the grades of OA pathology. In conclusion, excessive running induces joint degeneration and a unique gait pattern in rats.