BACKGROUND: Warfarin remains a difficult drug to use due to the large variability in dose response. Clear understanding of the accuracy of warfarin pharmacogenetic dosing methods might lead to appropriate control of anticoagulation.

OBJECTIVE: This study aims to evaluate the accuracy of warfarin dosing table and two pharmacogenetic algorithms, namely the algorithms of Gage et al. (Clin Pharmacol Ther 84:326-331, 2008), and the International Warfarin Pharmacogenetics Consortium algorithm (IWPC) in a real Egyptian clinical setting. Additionally, three non-pharmacogenetic dosing methods (the Gage, IWPC clinical algorithms and the empiric 5 mg/day dosing) were evaluated.

SETTING: Sixty-three Egyptian patients on a stable therapeutic warfarin dose were included. Patients were recruited from the outpatient clinic of the critical care medicine department.

METHODS: CYP2C9 and VKORC1 polymorphisms were genotyped by real time PCR system. Predicted doses by all dosing methods were calculated and compared with the actual therapeutic warfarin doses.

RESULTS: The Gage algorithm (adjusted R(2) = 0.421, and mean absolute error (MAE) = 3.3), and IWPC algorithm (adjusted R(2) = 0.419, MAE = 3.2) produced better accuracy than did the warfarin dosing table (adjusted R(2) = 0.246, MAE = 3.5), the two clinical algorithms (R(2) = 0.24, MAE = 3.7) and the fixed dose approach (MAE = 3.9). However, all dosing models produced comparable clinical accuracy with respect to proportion of patients within 1 mg/day of actual dose (ideal dose). Non-pharmacogenetic methods severely over-predicted dose (defined as ≥2 mg/day more than actual dose) compared to the three pharmacogenetic models. In comparison to non-pharmacogenetic methods, the three pharmacogenetic models performed better regarding the low dose group in terms of percentage of patients within ideal dose. In the high dose group, none of the dosing models predicted warfarin doses within ideal dose.

CONCLUSION: Our study showed that genotype-based dosing improved prediction of warfarin therapeutic dose beyond that available with the fixed-dose approach or the clinical algorithms, especially in the low-dose group. However, the two pharmacogenetic algorithms were the most accurate.

OBJECTIVE: The aim of this study was to validate the classification criteria for cryoglobulinaemic vasculitis (CV).

METHODS: Twenty-three centres were involved. New patients with CV (group A) and controls, i.e. subjects with serum cryoglobulins but lacking CV based on the gold standard of clinical judgment (group B) and subjects without cryoglobulins but with clinical features that can be observed in the course of CV (group C), were studied. Positivity of serum cryoglobulins was necessary for CV classification. Sensitivity and specificity of the criteria were calculated by comparing group A vs group B. The group A vs group C comparison was done to demonstrate the possible diagnostic utility of the criteria.

RESULTS: The study included 268 patients in group A, 182 controls in group B and 193 controls in group C (small vessel vasculitis, 51.8%). The questionnaire (at least 2/3 positive answers) showed 89.0% sensitivity and 93.4% specificity; the clinical item (at least 3/4 clinical involvement) showed 75.7% sensitivity and 89.0% specificity and the laboratory item (at least 2/3 laboratory data) showed 80.2% sensitivity and 62.4% specificity. The sensitivity and specificity of the classification criteria (at least 2/3 positive items) were 89.9% and 93.5%, respectively. The comparison of group A with group C demonstrated the clinical utility of the criteria in differentiating CV from CV mimickers.

CONCLUSION: Classification criteria for CV were validated in a second, large, international study confirming good sensitivity and specificity in a complex systemic disease.

Snake antivenoms are the only definitive management of snake envenoming's. Endotoxin contamination is a serious threat to the safety of parenteral drugs. A greater understanding of the nature of LAL-Test interferences and the use permissible dilutions has minimized enhancement problems. Common interference mechanisms include suboptimal pH, enzyme or protein modification, and non-specific LAL activation. The study aimed at sorting out the interfering factors before validating the antitoxic sera preparations to avoid false positive results when testing snake venom antiserum samples by (LAL) method. Phase I (Preliminary Screening /Interference Assay) was performed to determine a compatible test dilution, which is then used in Phase II (Inhibition-Enhancement / Validation Study). The results revealed that dilution is the best approach to resolve interferences by a ratio of 1:80 (MVD) plus a specific treatment as heat-activation at 70-80°C for 10 minutes accompanied by rehydration of LAL reagent with Endotoxin Specific Buffer Solution to sort out the enhancement problem.