Gated myocardial perfusion single photon emission computed tomography in the clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial, Veterans Administration Cooperative study no. 424

Background  Stress gated myocardial perfusion single photon emission computed tomography (gSPECT) is increasingly used before and after intercurrent therapeutic intervention and is the basis for ongoing evaluation in the Department of Veterans Affairs clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial. Methods and Results  The COURAGE trial is a North American multicenter randomized clinical trial that enrolled 2287 patients to aggressive medical therapy vs percutaneous coronary intervention plus aggressive medical therapy. Three COURAGE nuclear substudies have been designed. The goals of substudy 0 are to examine the diagnostic accuracy of the extent and severity of inducible ischemia at baseline in COURAGE patients compared with patient symptoms and quantitative coronary angiography and to explore the relationship between inducible ischemia and the benefit from revascularization when added to medical therapy. Substudy 1 will correlate the extent and severity of provocative ischemia with the frequency, quality, and instability of recurrent symptoms in postcatheterization patients. Substudy 2 (n _ 300) will examine the usefulness of sequential gSPECT monitoring 6 to 18 months after therapeutic intervention. Together, these nuclear substudies will evaluate the role of gSPECT to determine the effectiveness of aggressive risk-factor modifications, lifestyle interventions, and anti-ischemic medical therapies with or without revascularization in reducing patients’ ischemic burdens. Conclusions  The unfolding of evidence on the application of gSPECT in trials such as COURAGE defines a new era for nuclear cardiology. We hope the evidence that emerges from the COURAGE trial will further establish the role of nuclear imaging in the evidence-based management of patients with stable coronary disease. The COURAGE trial was supported by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development in collaboration with the Canadian Institutes of Health Research. Unrestricted research grants were obtained from Merck & Co; Pfizer Pharmaceuticals; Bristol-Myers Squibb Medical Imaging; Astellas Pharma; Kos Pharmaceuticals; Data Scope; Astra Zeneca Pharmaceuticals; Astra-Zeneca-Canada; Schering-Plough Coorporation, Ltd; Sanofi-Aventis, Inc; First Horizon; and GE Healthcare. All industrial funding for this trial was directed through the Department of Veterans Affairs. Additional funding for this substudy was provided by grants to the Department of Veterans Affairs and Canadian Institutes of Health Research from Astellas Pharma and Bristol-Myers-Squibb Medical Imaging.     

Effect of short-term erythropoietin therapy in anemic premature infants.

OBJECTIVE: To determine the effectiveness of a 10-day subcutaneous erythropoietin (rHuEpo) course of 300 units per kg per dose plus oral iron compared to oral iron alone in anemic infants during their convalescent phase of illness. STUDY DESIGN: Prospective, randomized trial performed at a 40-bed, teaching, referral, level III, neonatal intensive care unit. Infants with a gestational age at birth of less than 32 weeks, hematocrit of less than or equal to 28% with a corrected reticulocyte count of less than or equal to 5%, postconceptual age of less than 48 weeks or 5 months chronological age, and a diagnosis of anemia of prematurity were considered for inclusion. Major outcome parameters included hematocrit, corrected reticulocyte count and red cell transfusion requirements. RESULTS: A total of 60 infants were enrolled (n=30 per group). Infants randomized to rHuEpo had a significantly higher post-treatment hematocrit and corrected reticulocyte count than infants in the iron only group (p<0.001). There was a trend towards fewer red cell requirements in the rHuEpo group. CONCLUSIONS: The rHuEpo regimen studied here was associated with an acute improvement in hematocrit and corrected reticulocyte counts. This study did not demonstrate a statistically significant decrease in transfusion therapy, in part related to increased subsequent use of rHuEpo in the control group. Taken together, these data demonstrate that this regimen can effectively treat anemia in convalescent premature infants.     

Travel distance, age, and sex as factors in follow-up visit compliance in the post-gastric bypass population

BACKGROUND: There is no consensus regarding the optimal rate of follow-up in the post-bariatric surgery patient population. METHODS: The records of all patients who underwent laparoscopic Roux-en-Y gastric bypass from 2001 to 2003 were reviewed. Using patient zip codes, travel distances were calculated between the patients' places of residence and our clinic. Patients were then assigned to 1 of 3 cohorts according to the following distances: (1) < 50 miles, (2) 50 to 100 miles, and (3) > 100 miles. Patient compliance with follow-up appointments at 3 weeks, 3 months, 6 months, 9 months, and 12 months was analyzed. Linear trends were identified using the Mantel-Haenszel test. Age and sex were analyzed as possible predictors of compliance using the chi(2) test. P values < .05 were considered statistically significant. RESULTS: The study group comprised 150 patients (127 females and 23 males). The 3 cohorts contained 115, 21, and 14 patients, respectively. All patients in each cohort were compliant with the 3-week follow-up appointment. Although there were differences in compliance between cohorts at each of the remaining appointments, only the 9-month (70.3% vs 61.9% vs 35.7%) visit showed statistical significance (P = .035). The 6-month visit trended toward significance (85.2% vs 76.2% vs 64.3%; P = .088). Males were more likely to be compliant with the 12-month follow-up (P = .040). When controlling for sex, travel distance was also a predictor of compliance at this follow-up visit (P = .024). Age was not predictive of compliance (P = .827). CONCLUSION: Based on our findings, we conclude that travel distance from the clinic does not significantly affect compliance at the initial follow-up, 3-month, and 12-month appointments. However, distance does tend to affect compliance at the 6-month appointment and significantly affects compliance at the 9-month appointment. Males are more likely to be compliant at the 12 month follow-up visit. We must continue to strive for 100% follow-up in our post-bariatric surgery patients.     

Influences on Food Selection of Women on High- and Low-Fat Diets

There is evidence that long-term maintenance of a low-fat diet reduces preference for high-fat foods. Sensory evaluation of the taste of fat, and preference for high and low-fat foods were studied in a group of former participants in a randomized dietary intervention trial aimed at lowering fat consumption. Intervention subjects consuming less than 25% of daily calories as fat and control subjects consuming more than 35% of daily calories as fat agreed to be in a "taste perception" study. In Study 1, subjects tasted 20 dairy solutions containing different levels of fat and sugar. Subjects rated the perceived intensity of fat taste, and of liking, for each of the solutions. In Study 2, subjects were asked to taste and rate 4 high-fat and 4 low-fat snack foods, and were then allowed to freely consume these foods in a preference test. Intervention and control subjects were similar in their sensory evaluation of the taste of fat in Study 1. In Study 2, intervention subjects reported a reduced hedonic rating of the taste of high-fat snack foods compared to control subjects, yet intervention subjects consumed the same amount of high-fat snack foods as control subjects. We conclude that a successful outcome in a dietary intervention may be due to social and cognitive factors, in addition to potential changes in hedonic response to fat.     

Phase I/II trial of dipyridamole, 5-fluorouracil,leukovorin, and mitoxantrone in metastatic breast cancer

Summary Based upon the hypothesis that dipyridamole would potentiate the cytotoxicity of mitoxantrone and the combination of 5-fluorouracil (5-FU) and leukovorin, we performed a phase I/II trial of the combination of dipyridamole, 5-FU, leukovorin, and mitoxantrone in patients with metastatic breast cancer. The dose of dipyridamole was fixed at 175 mg/m² by mouth every 6 h (700 mg/m²/day), based upon a previous phase I trial of oral dipyridamole with 5-FU and leukovorin. Dipyridamole therapy began 24 h prior to the first dose of chemotherapy and continued until 24 h after the last dose of chemotherapy for each course of treatment. At the initial dose level, leukovorin 200 mg/m² was given intravenously immediately prior to 5-FU 375 mg/ m² intravenously on days 1–5. Mitoxantrone 6 mg/m² was given as a single dose on day 3. Unacceptable toxicity was observed at this dose level, leading to successive dose decrements rather than dose increments. The maximum tolerated dose was leukovorin 200 mg/m² days 1–2, 5-FU 375 mg/m² days 1–2, mitoxantrone 6 mg/m² on day 2, and dipyridamole 175 mg/m² every 6 h on days 0–3. Two responses were produced in 15 patients. This regimen is not recommended for further investigation in the treatment of breast cancer.