Annals of Long Term Care

Digoxin Dosing for Heart Failure
The therapeutic range for digoxin in heart failure has recently become lower and narrower, and is associated with reduced mortality; however, methods for dosing have not changed. The authors of this study sought to develop a new method to determine the initial dose of digoxin in patients with heart failure. Over a 6-month period, medical records were screened and reviewed for hospitalized adult patients who had a steady-state digoxin concentration. A multiple linear regression was estimated relating digoxin concentration, digoxin dose, creatinine clearance, and ideal body weight to generate an equation relating the dose of digoxin with these variables and a specific target digoxin concentration of 0.7 ng/mL (0.9 nmol/L). This new method was then compared with two existing methods. The study included 54 patients (mean [SD] age, 68 [15] years, with a mean (SD) creatinine clearance of 50 (25) mL/min (0.8 [0.4] mL/s) and mean (SD) ideal body weight of 62 (11) kg. The authors’ proposed method and the Jusko and Koup method were more accurate than the Jelliffe method in predicting digoxin concentration. Root mean square errors were as follows: for the Jelliffe method (using ideal body weight), 0.810; for the Koup and Jusko method (with heart failure), 0.401; our proposed method, 0.375. The proposed method was then used to create a dosing nomogram.The authors concluded that because the new therapeutic window of digoxin is associated with improved outcomes, more intensive dosage refinement should be considered. To this end, the authors offer new dosing recommendations and a nomogram for determining the initial dose of digoxin in patients with heart failure.
Bauman JL, DiDomenico RJ, Viana M, Finch M. A method of determining the dose of digoxin for heart failure in the modern era. Arch Intern Med 2006;166:2539-2545.

Folic Acid and Age-Related Hearing Loss
Low folate status has been associated with poor hearing. The authors of this study sought to determine whether folic acid supplementation slows age-related hearing loss. They conducted a double-blind, randomized, placebo-controlled trial conducted from September 2000 to December 2004 in 728 older men and women in the Netherlands recruited from municipal and blood bank registries with plasma total homocysteine concentrations 13 µmol/L or greater serum and vitamin B12 concentrations 200 pmol/L or greater at screening, and no middle ear dysfunction, unilateral hearing loss, or pathologic ear conditions unrelated to aging. Subjects were given daily oral folic acid (800 µg) or placebo supplementation for 3 years. They measured 3-year change in hearing thresholds, assessed as the average of the pure-tone air conduction thresholds of both ears of the low (0.5-kHz, 1-kHz, and 2-kHz) and high (4-kHz, 6-kHz, and 8-kHz) frequencies. Findings showed that Initial median hearing thresholds were 11.7 dB (interquartile range, 7.5 to 17.5 dB) for low frequencies and 34.2 dB (interquartile range, 22.5 to 50.0 dB) for high frequencies. Sixteen participants (2%) were lost to follow-up. After 3 years, thresholds of the low frequencies increased by 1.0 dB (95% CI, 0.6 to 1.4 dB) in the folic acid group and by 1.7 dB (CI, 1.3 to 2.1 dB) in the placebo group (difference, –0.7 dB [CI, –1.2 to –0.1 dB]; P = 0.020). Folic acid supplementation did not affect the decline in hearing high frequencies. The limitations were that the strict criterion for participation on the basis of serum homocysteine concentrations limits extrapolation to the general population. Folic acid fortification of food was prohibited in the Netherlands during the study, so baseline folate levels in participants were about half of those found in the U.S. population. The authors concluded that folic acid supplementation slowed the decline in hearing of the speech frequencies associated with aging in a population from a country without folic acid fortification of food.