Efficacy of computer-aided dosing of warfarin among patients in a rehabilitation hospital.

OBJECTIVE: To determine whether computer-aided dosing of warfarin is superior to physician dosing to maintain a patient in a rehabilitation hospital within a target international normalized ratio goal. DESIGN: Randomized, double-blinded, clinical trial in an inpatient rehabilitation hospital. A total of 30 consecutive patients admitted receiving warfarin were randomized to either clinician dosing or computer-aided warfarin dosing for the duration of their hospitalization. The main outcome measures included the percentage of days in a therapeutic anticoagulation range and the number of blood draws. Exclusion criteria included short length of stay (n=110, 39%) and a physician declared international normalized ratio target range of <2.0 (n=67, 23%). A total of 73 patients were excluded because of heme-positive stools at admission, recent gastrointestinal bleed, early discharge or consent refusal. Dawn AC software was used to determine warfarin dosage and frequency of blood draws to maintain a target international normalized ratio of 2.0-3.0 for the computer-dosed group (n=14). Several physicians recommended warfarin dosages for the second group (n=16). Two were dropped from the computer model secondary to lost data files for these two patients. RESULTS: Computer-aided dosing of warfarin resulted in 61.7% of days within the therapeutic range (international normalized ratio, 2-3), whereas clinician dosing resulted in only 44.1%. There were no significant differences in the number of blood draws or demographic variables between the two groups. CONCLUSION: Computers were significantly better at maintaining patients within a therapeutic international normalized ratio range than physicians. There were no significant differences in the number of recommended blood draws.

New and confirmatory evidence of an association between APOE genotype and baseline C-reactive protein in dyslipidemic individuals.

We have investigated the association between APOE genotypes and C-reactive protein (CRP) levels in a cohort of approximately 600 individuals who were candidates for statin therapy. An association had been previously reported between the APOE3 allele and elevated CRP levels. That study only examined men. We have reproduced that association in men and have extended the finding to women. We also investigated the effect of the interaction between APOE genotype and hormone replacement therapy (HRT) status on CRP levels, adjusting for body mass index (BMI) and other covariates. BMI and HRT are also significant predictors of CRP, as previously reported. The effect of HRT is strong enough that the contribution of APOE genotype is no longer statistically significant among women on HRT. We also demonstrate that the presence or absence of the single SNP Cysl30Arg (which distinguishes APOE4 from APOE2 and APOE3) is sufficient to determine whether an individual is predisposed to higher or lower CRP levels. Essentially, the presence of one or two copies of APOE4 is associated with a reduction of CRP levels by approximately 34% relative to individuals with zero copies (1.73 mg/L for subjects with one or two copies versus 2.63 mg/L for subjects with zero copies of APOE4). We also tested previously reported associations between CRP levels and polymorphisms in the CRP and IL6 genes. These associations were not reproduced in our cohort.

Randomized phase II trial of either fluorouracil, parenteral hydroxyurea, interferon-alpha-2a, and filgrastim or doxorubicin/docetaxel in patients with advanced gastric cancer with quality-of-life assessment: eastern cooperative oncology group study E6296.

PURPOSE: The Eastern Cooperative Oncology Group conducted a randomized phase II trial to determine the objective response rates, toxicities, and overall survival and to assess effects on quality of life for two combination regimens in patients with advanced gastric cancer. PATIENTS AND METHODS: All patients had biopsy-proven, untreated metastatic gastric cancer with measurable disease. The FHIG arm employed infusional fluorouracil (F), 2.6 g/m2, given intravenously over 24 hours once perweek for 6 weeks; infusional hydroxyurea (H), 4.3 g/m2, given intravenously over 24 hours once per week for 6 weeks; and interferon-alpha-2a (1), 9 MU given subcutaneously three times per week, once per week for 6 weeks. The AD arm employed doxorubicin (A), 50 mg/m2, and docetaxel (D), 75 mg/m2, both given intravenously every 21 days. Quality of life was measured by the FACT-Fatigue scale and a novel questionnaire assessing interferon-mediated fatigue. RESULTS: Twenty-nine patients were enrolled; 23 were eligible and evaluable. Twelve were enrolled on FHIG and 11 on AD. The major grade > or = 3 toxicities were neuromotor (46%) in patients receiving FHIG and granulocytopenia (91%) in those receiving AD. There were two fatalities in the AD arm. There was one partial responder on FHIG (8.3%) and none on AD. The median survival was 6.6 months for FHIG and 10.1 months for AD. Quality-of-life analysis did not show substantial cumulative fatigue in patients treated with FHIG. CONCLUSIONS: Neither regimen demonstrated enough activity to serve as a platform for the development of further clinical regimens against gastric carcinoma. A subset of patients receiving interferon was able to tolerate therapy without deterioration in quality of life.