STUDY OBJECTIVE As the incidence rate of renal impairment is 2–10% for patients treatment with high-dose methotrexate , and renal impairment develops in 0–12.4% of patients treated for osteosarcoma, we sought to evaluate the efficacy of glucarpidase, a recently approved drug that rapidly hydrolyzes methotrexate to inactive metabolites, which allows for nonrenal clearance in patients with delayed renal methotrexate elimination. DESIGN Pooled analysis of efficacy data from four multicenter, single-arm, compassionate-use clinical trials using protocols from 1993–2007. PATIENTS Of 476 patients with renal toxicity and delayed methotrexate elimination who were treated with intravenous glucarpidase for rescue after high-dose methotrexate, 169 patients had at least one preglucarpidase (baseline) plasma methotrexate concentration greater than 1 µmol/L and one postglucarpidase methotrexate concentration measurement by high-performance liquid chromatography and were included in the efficacy analysis; renal recovery was assessed in 436 patients who had at least one recorded preglucarpidase and postglucarpidase serum creatinine concentration measurement. MEASUREMENTS AND MAIN RESULTS Efficacy was defined as rapid and sustained clinically important reduction (RSCIR) in plasma methotrexate concentration, with a concentration of 1 µmol/L or lower at all postglucarpidase determinations. Median age of efficacy-evaluable patients was 20 years (range 5 wks–84 yrs). Osteosarcoma (36%), non-Hodgkin’s lymphoma (27%), and acute lymphoblastic leukemia (20%) were the most frequent underlying diagnoses. Median preglucarpidase serum methotrexate was 11.7 µmol/L. At the first (median 15 min) through the last (median 40 hrs) postglucarpidase measurement, plasma methotrexate concentrations demonstrated consistent 99% median reduction. RSCIR was achieved by 83 (59%) of 140 patients. Sixty-four percent of patients with renal impairment greater than or equal to Common Terminology Criteria for Adverse Events grade 2 recovered to grade 0 or 1 at a median of 12.5 days after glucarpidase administration. CONCLUSION Glucarpidase caused a clinically important 99% or greater sustained reduction of serum methotrexate levels and provided noninvasive rescue from methotrexate toxicity in renally impaired patients.

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Summary. The success in achieving therapeutic international normalized ratio (INR) targets in the control of warfarin using a whole-blood point-of-care testing (POCT) monitor (CoaguChek) in a community clinic was compared with hospital laboratory coagulometer prothrombin time (PT) testing in a randomized crossover study. Forty-six patients were randomized into two groups. At each visit, capillary blood was taken for the POCT monitor and venous blood for the laboratory coagulometer. In Group 1, for 6 months, dosage was based on the CoaguChek and for the second 6 months on the coagulometer. In the second group, the order was reversed. Dosages were determined using the dawn ac computer programme. Success was assessed by the percentage of time patients were maintained within the INR targets. Agreement between laboratory and monitor INR, and patient satisfaction were also assessed. Results with the POCT monitor compared well with the hospital coagulometer. Time in INR target range between the groups was similar, with 60AE9% on the POCT monitor and 59AE3% with the laboratory coagulometer in Group 1 and in Group 2, respectively, 64AE3% and 63AE4% with no significant difference in mean INR. An INR above 4AE0 gave some discrepant results. International Sensitivity Index calibrations of the two test systems indicated that the INRs were dependable. Patient questionnaires showed greater satisfaction with community POCT monitoring.

We evaluated the efficacy, safety, and biological mechanisms of digoxin immune Fab (DIF) treatment of severe preeclampsia. Fifty-one severe preeclamptic patients were randomized in double-blind fashion to DIF ( N = 24) or placebo ( N = 27) for 48 hours. Primary outcomes were change in creatinine clearance (CrCl) at 24 to 48 hours and antihypertensive drug use. Serum sodium pump inhibition, a sequela of endogenous digitalis-like factors (EDLF), was also assessed. CrCl in DIF subjects was essentially unchanged from baseline versus a decrease with placebo (-3 +/- 10 and -34 +/- 10 mL/min, respectively, P = 0.02). Antihypertensive use was similar between treatments (46 and 52%, respectively, P = 0.7). Serum sodium pump inhibition was decreased with DIF compared with placebo at 24 hours after treatment initiation (least squares mean difference, 19 percentage points, P = 0.03). DIF appeared to be well tolerated. These results suggest DIF prevents a decline in renal function in severe preeclampsia by neutralizing EDLF. Sodium pump inhibition was significantly improved. Further research is warranted.