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AIMS: This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes. METHODS AND RESULTS: Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate < 60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106-117) g/L. CONCLUSION: The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity.

Discontinuation of digoxin is associated with worsening heart failure (HF) symptoms. However, the long-term effects of discontinuation of digoxin therapy on mortality and morbidity in HF have not been well studied. Of the 7,788 participants in the Digoxin Investigation Group trial, 3,365 received digoxin before randomization. During the trial, digoxin was continued in 1,666 patients and discontinued in 1,699 patients. Using multivariable Cox regression analyses, we first determined the effect of discontinuation of digoxin on mortality and hospitalization during 39.7 months of median follow-up. Of the 1,666 patients continued on digoxin, 457 had low (0.5 to 0.9 ng/ml) and 340 had high (>or=1.0 ng/ml) serum digoxin concentrations (SDC) after 1 month of therapy and of the 1,699 patients whose digoxin was discontinued, 1,674 were alive at 1 month. We examined the effects of continuation of digoxin at low or high SDC. Compared with continuation of long-term digoxin therapy, discontinuation of digoxin was associated with a significant increase in all-cause hospitalization (adjusted hazard ratio [AHR] 1.18, 95% confidence interval [CI] 1.09 to 1.28, p <0.0001) and HF hospitalization (AHR 1.35, 95% CI 1.20 to 1.51, p <0.0001), but had no effect on all-cause mortality (AHR 1.06, 95% CI 0.95 to 1.19, p = 0.272). In contrast, continuation of digoxin at low SDC was associated with a reduction in all-cause mortality (AHR 0.75, 95% CI 0.63 to 0.90, p = 0.002), all-cause hospitalization (AHR 0.80, 95% CI 0.70 to 0.91, p = 0.001), and hospitalization for HF (AHR 0.60, 95% CI 0.50 to 0.73, p <0.0001). In conclusion, continuation of long-term digoxin therapy at low SDC was associated with reduction in mortality and hospitalization in ambulatory patients with chronic HF receiving background therapy with angiotensin-converting enzyme inhibitors and diuretics.

Analysis of variance is used to estimate the measurement error and path effects in the P times reported in the Reviewed Event Bulletins (REBs, produced by the provisional International Data Center, Arlington, USA) and in times we have read, for explosions at the Chinese Test Site. Path effects are those differences between traveltimes calculated from tables and the true times that result in epicentre error. The main conclusions of the study are: (1) the estimated variance of the measurement error for P times reported in the REB at large signal-to-noise ratio (SNR) is 0.04 s2, the bulk of the readings being analyst-adjusted automatic-detections, whereas for our times the variance is 0.01 s2 and (2) the standard deviation of the path effects for both sets of observations is about 0.6 s. The study shows that measurement error is about twice (∼0.2 s rather than ∼0.1 s) and path effects about half the values assumed for the REB times. However, uncertainties in the estimated epicentres are poorly described by treating path effects as a random variable with a normal distribution. Only by estimating path effects and using these to correct onset times can reliable estimates of epicentre uncertainty be obtained. There is currently an international programme to do just this. The results imply that with P times from explosions at three or four stations with good SNR (so that the measurement error is around 0.1 s) and well distributed in azimuth, then with correction for path effects the area of the 90 per cent coverage ellipse should be much less than 1000 km2—the area allowed for an on-site inspection under the Comprehensive Test Ban Treaty—and should cover the true epicentre with the given probability.

Analysis of variance is used to estimate the measurement error and path effects in the P times reported in the Reviewed Event Bulletins (REBs, produced by the provisional International Data Center, Arlington, USA) and in times we have read, for explosions at the Chinese Test Site. Path effects are those differences between traveltimes calculated from tables and the true times that result in epicentre error. The main conclusions of the study are: (1) the estimated variance of the measurement error for P times reported in the REB at large signal-to-noise ratio (SNR) is 0.04 s2, the bulk of the readings being analyst-adjusted automatic-detections, whereas for our times the variance is 0.01 s2 and (2) the standard deviation of the path effects for both sets of observations is about 0.6 s. The study shows that measurement error is about twice (∼0.2 s rather than ∼0.1 s) and path effects about half the values assumed for the REB times. However, uncertainties in the estimated epicentres are poorly described by treating path effects as a random variable with a normal distribution. Only by estimating path effects and using these to correct onset times can reliable estimates of epicentre uncertainty be obtained. There is currently an international programme to do just this. The results imply that with P times from explosions at three or four stations with good SNR (so that the measurement error is around 0.1 s) and well distributed in azimuth, then with correction for path effects the area of the 90 per cent coverage ellipse should be much less than 1000 km2—the area allowed for an on-site inspection under the Comprehensive Test Ban Treaty—and should cover the true epicentre with the given probability.