Medication errors were common (nearly 1 of every 5 doses in the typical hospital and skilled nursing facility). The percentage of errors rated potentially harmful was 7%, or more than 40 per day in a typical 300-patient facility. The problem of defective medication administration systems, although varied, is widespread.
Rationale
A growing number of patients with coronary disease have refractory angina. Preclinical and early-phase clinical data suggest that intramyocardial injection of autologous CD34+ cells can improve myocardial perfusion and function.
Objective
Evaluate the safety and bioactivity of intramyocardial injections of autologous CD34+ cells in patients with refractory angina who have exhausted all other treatment options.
Methods and Results
In this prospective, double-blind, randomized, phase II study (ClinicalTrials.gov identifier: NCT00300053), 167 patients with refractory angina received 1 of 2 doses (1×105 or 5×105 cells/kg) of mobilized autologous CD34+ cells or an equal volume of diluent (placebo). Treatment was distributed into 10 sites of ischemic, viable myocardium with a NOGA mapping injection catheter. The primary outcome measure was weekly angina frequency 6 months after treatment. Weekly angina frequency was significantly lower in the low-dose group than in placebo-treated patients at both 6 months (6.8±1.1 versus 10.9±1.2, P=0.020) and 12 months (6.3±1.2 versus 11.0±1.2, P=0.035); measurements in the high-dose group were also lower, but not significantly. Similarly, improvement in exercise tolerance was significantly greater in low-dose patients than in placebo-treated patients (6 months: 139±151 versus 69±122 seconds, P=0.014; 12 months: 140±171 versus 58±146 seconds, P=0.017) and greater, but not significantly, in the high-dose group. During cell mobilization and collection, 4.6% of patients had cardiac enzyme elevations consistent with non-ST segment elevation myocardial infarction. Mortality at 12 months was 5.4% in the placebo-treatment group with no deaths among cell-treated patients.
Conclusions
Patients with refractory angina who received intramyocardial injections of autologous CD34+ cells (105 cells/kg) experienced significant improvements in angina frequency and exercise tolerance. The cell-mobilization and -collection procedures were associated with cardiac enzyme elevations, which will be addressed in future studies.
Six ruminally fistulated Holstein cows were utilized in a randomized block design to examine effects of yeast culture supplement on ruminal metabolism and apparent digestibility. Cows were fed a diet of 40% corn silage and 60% concentrate (DM basis). Treatments were control (supplement without yeast cells) and yeast culture supplement. Treatment periods were 6 wk. Ruminal pH, ammonia, molar proportions of acetate and isovalerate, and acetate: propionate ratio were lower and molar proportions of propionate and valerate higher in cows receiving yeast. The concentration of anaerobic bacteria tended to be higher and cellulolytic bacteria concentrations were greater in cows fed yeast than in cows receiving control diet. Supplemental yeast did not affect molar proportions of isobutyrate or butyrate, total VFA, or viable yeast concentrations in ruminal fluid. Ruminal liquid dilution rate and total tract apparent digestibilities were not different between treatments. Rate of disappearance of cellulose in vitro was lower in cows receiving yeast. Less variation in ammonia concentrations and microbial numbers suggest that ruminal fermentation was more stable in cows receiving yeast culture supplement.
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