Can available mathematical models predict serum digoxin levels in Thai patients?

WHAT IS KNOWN AND OBJECTIVE: Digoxin is commonly prescribed for heart failure patients with reduced ejection fraction (HFrEF) and patients with atrial fibrillation (AF). Due to digoxin's narrow therapeutic range, monitoring the serum digoxin concentration (SDC) is important. However, the SDC measurement is not widely available. Equations using clinical parameters can be employed to estimate the SDC but have never been studied in the Thai population. Therefore, we conducted this study to evaluate the correlation between the measured SDC and predicted digoxin level using 2 commonly used equations: the Konishi equation and the Koup and Jusko equation. METHODS: This report describes prospective, cross-sectional study conducted at Chiang Mai University. One hundred and fourteen patients were recruited in the study. All of the patients were diagnosed as having HFrEF, AF or both and had been receiving digoxin for at least 4 weeks. The SDC of each patient was measured at steady state and assigned to one of 3 groups according to the classifications of the Digitalis Investigation Group (DIG) trial: in the therapeutic range, over the therapeutic range and in the suboptimal range. RESULTS AND DISCUSSION: There were significant correlations between the measured and predicted SDCs using both the Konishi equation and the Koup and Jusko equation, which had correlation coefficients (R) of 0.69 and 0.31 (P < .05 for both), respectively. The percentages of patients with measured SDCs in the therapeutic range, over the therapeutic range and in the suboptimal range were 27.2%, 9.6% and 63.2%, respectively. The sensitivity and specificity of the Konishi equation in predicting SDCs in the over the therapeutic range were 72.73% (95% Confidence interval (CI): 39.03%-93.98%) and 80.58% (95% CI: 71.62%-87.72%), respectively. Of the 5 patients (4.4%) who were rehospitalized, 2 patients (0.01%) were readmitted due to acute decompensated heart failure (ADHF). One of the patients had an SDC that was over the therapeutic range. None of the readmitted patients had ventricular arrhythmia. WHAT IS NEW AND CONCLUSIONS: The Konishi equation yielded better predictions of the SDC, especially in the subgroup of HFrEF patients. Furthermore, the prediction of SDCs in the over the therapeutic range using this equation was superior to that of the Koup and Jusko equation. With further validation in a larger population, this equation should facilitate the detection of patients who are over the therapeutic range in clinical practice.

Effects of extremely low osmolarity on fertilized mouse eggs.

When fertilized one-cell eggs are subjected to distilled water treatment for 2-6 min, cytoplasm bulges through the sperm-slit in the zona pellucida and forms a cytoplasmic fragment (CF). CFs were observed in 86-5% of eggs; in 20-9% of cases CFs contained a pronucleus (or pronuclei). In 53-4% of eggs permanent incorporation of the second polar body (2 P.B.) into the egg cytoplasm occurred. These phenomena occurring in different combinations produced 6-2% of haploid eggs, 10-3% of diploid eggs with a pronucleus replaced by 2 P.B. nucleus, and 43-1% of triploid eggs. 4-4% of eggs were enucleated. The remaining group comprised diploid eggs which were either not affected by the treatment (6-4%) or lost a certain amount of cytoplasm by formation of an anucleate CF (29-6%). The frequencies of the types of reaction were related to the post-fertilization stage of eggs. All eggs except the enucleated ones were able to develop to the stage of morula or blastocyst. Triploids developed until the 12th day of pregnancy and diploids that had lost up to 15% of the cytoplasm developed to term. There was a twofold reduction in the percentage of preimplantation development when treated eggs originated from induced rather than spontaneous ovulation.