http://hdl.handle.net/10027/7538 Wed, 19 Jun 2013 09:01:28 GMT 2013-06-19T09:01:28Z http://hdl.handle.net/10027/8599 Association of Apolipoprotein E Genotype with Duration of Time to Achieve a Stable Warfarin Dose in African-American Patients Cavallari, L.H.; Butler, C.; Langaee, T.Y.; Wardak, N.; Patel, S.R.; Viana, M.A.G.; Shapiro, N.L.; Nutescu, E.A. Study Objective. To test the hypothesis that genotypes for proteins affecting vitamin K availability influence the duration of time required to achieve a stable warfarin dose in African-American patients. Design. Retrospective cohort study Setting. Pharmacist-managed antithrombosis clinic. Patients. Ninety-two African-American adults whose warfarin therapy was initiated between September 2, 1999, and July 8, 2009. Measurements and Main Results, During a routine anticoagulation clinic visit, a sample was collected from each patient for genetic analysis. Genotyping was performed for the following variants: apolipoprotein E epsilon 2, epsilon 3, and epsilon 4; NAD(P)H:quinone oxidoreductase (NQO1)*2; cytochrome P450 (CYP) 4F2 V433M; CYP2C9*2, *3, *5, *8, and *11; and vitamin K epoxide reductase complex 1 (VKORC1) -1639G>A. Patients' medical records were then reviewed, and data were collected retrospectively for each anticoagulation clinic visit during the first 6 months of warfarin therapy or until dose stabilization. The median time required to reach a stable warfarin dose, defined as the dose that produced therapeutic anticoagulation for three consecutive clinic visits, was 83 days. Compared with the 46 patients who achieved a stable warfarin dose within 83 days, the 46 patients who required longer durations for dose stabilization had a higher frequency of the apolipoprotein E epsilon 3/epsilon 3 genotype (37% vs 59%, p=0.037). Sixty-one percent of patients with the epsilon 3/epsilon 3 genotype versus 40% of those with an epsilon 2 or epsilon 4 allele had a delay in achieving a stable dose (p=0.037). Neither the CYP4F2 nor NQO1 genotype was associated with warfarin dose stabilization. Conclusion. Our data support the hypothesis that the apolipoprotein E genotype is associated with duration of time to reach a stable warfarin dose in African-American patients. Further insight into the genetic effects on warfarin dose stabilization could reveal novel methods to improve anticoagulation control during the warfarin initiation period. © 2011 by IOS Press, Pharmacotherapy Post print version of article may differ from published version. The definitive version is available through IOS Press at DOI:10.1592/phco.31.8.785 Mon, 01 Aug 2011 05:00:00 GMT http://hdl.handle.net/10027/8599 2011-08-01T05:00:00Z http://hdl.handle.net/10027/8593 Diagnostic accuracy of existing methods for identifying diabetic foot ulcers from inpatient and outpatient datasets Sohn, Min-Woong; Budiman-Mak, Elly; Stuck, Rodney M; Siddiqui, Farah; Lee, Todd A Background: As the number of persons with diabetes is projected to double in the next 25 years in the US, an accurate method of identifying diabetic foot ulcers in population-based data sources are ever more important for disease surveillance and public health purposes. The objectives of this study are to evaluate the accuracy of existing methods and to propose a new method. Methods: Four existing methods were used to identify all patients diagnosed with a foot ulcer in a Department of Veterans Affairs (VA) hospital from the inpatient and outpatient datasets for 2003. Their electronic medical records were reviewed to verify whether the medical records positively indicate presence of a diabetic foot ulcer in diagnoses, medical assessments, or consults. For each method, five measures of accuracy and agreement were evaluated using data from medical records as the gold standard. Results: Our medical record reviews show that all methods had sensitivity > 92% but their specificity varied substantially between 74% and 91%. A method used in Harrington et al. (2004) was the most accurate with 94% sensitivity and 91% specificity and produced an annual prevalence of 3.3% among VA users with diabetes nationwide. A new and simpler method consisting of two codes (707.1× and 707.9) shows an equally good accuracy with 93% sensitivity and 91% specificity and 3.1% prevalence. Conclusions: Our results indicate that the Harrington and New methods are highly comparable and accurate. We recommend the Harrington method for its accuracy and the New method for its simplicity and comparable accuracy. © 2010 Sohn et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. doi:10.1186/1757-1146-3-27 Wed, 24 Nov 2010 06:00:00 GMT http://hdl.handle.net/10027/8593 2010-11-24T06:00:00Z http://hdl.handle.net/10027/8520 Dosing and monitoring of low-molecular-weight heparin in high-risk pregnancy: Single-center experience Shapiro, Nancy L.; Kominiarek, Michelle A.; Nutescu, Edith A.; Chevalier, Aimee B.; Hibbard, Judith U. Study Objective. To evaluate dosing requirements and monitoring patterns of low-molecular-weight heparin (LMWH) when used in high-risk pregnancy. Design. Retrospective, observational, cohort study. Setting. University-affiliated medical center. Patients. Forty-nine women treated with LMWH between 2001 and 2005 for either prophylaxis or treatment of venous thromboembolism during pregnancy and monitored with antifactor Xa activity. Measurements and Main Results. Data were obtained on 53 pregnancies in the 49 women. The primary outcome was change in dosing requirements of LMWH throughout pregnancy as determined by the corresponding antifactor Xa activity peak levels. Mean starting doses of twice-daily enoxaparin and doses most proximate to delivery were 39.2 mg (range 30– 60 mg) and 55.0 mg (range 30–100 mg, p=0.06), respectively, for the prophylaxis group and 83.0 mg (range 30–180 mg) and 85.7 mg (range 30–160 mg, p=0.41), respectively, for the therapeutic group. Weight-based mean starting doses and doses most proximate to delivery were 0.46 and 0.62 mg/kg (p=0.03), respectively, for the prophylaxis group and 0.90 and 0.87 mg/kg (p=0.29), respectively, for the therapeutic group. Dose changes were required in 9 (69%) of 13 pregnancies and 21 (55%) of 38 pregnancies (data from two of the 40 pregnancies were excluded—one in a patient receiving dalteparin, and one in a patient with mitral valve replacement who had higher antifactor Xa goals) in the prophylaxis and therapeutic groups, respectively, to achieve target antifactor Xa activity. The weight-based prophylactic dose was consistently 0.6 mg/kg in all three trimesters, achieving a mean ± SD target antifactor Xa activity of 0.39 ± 0.18 units/ml, whereas the therapeutic dose was 0.9 mg/kg to maintain antifactor Xa activity of 0.71 ± 0.22 units/ml. Conclusion. Dose changes for LMWH throughout pregnancy as guided by antifactor Xa activity were common. A significant increase in the LMWH dose requirements in the prophylactic group suggests that more frequent monitoring of antifactor Xa activity may be appropriate in pregnant patients to maintain target anticoagulant levels. © 2011 by IOS Press, Pharmacotherapy Post print version of article may differ from published version. The definitive version is available through IOS Press at DOI: 10.1592/phco.31.7.678. Fri, 01 Jul 2011 05:00:00 GMT http://hdl.handle.net/10027/8520 2011-07-01T05:00:00Z http://hdl.handle.net/10027/8388 Going Past the Data for Temozolomide Villano, J. Lee; Letarte, Nathalie; Bressler, Linda R. The benefit of six cycles of adjuvant temozolomide was documented in a randomized phase III (EORTC‐NCIC CE.3) trial and this therapy, following combined temozolomide and radiation, is the standard of care for patients with newly diagnosed glioblastoma. We comment on the differences on length of adjuvant therapy in both clinical practice and national studies (e.g. RTOG 0825), usually doubling the length than in the EORTC/NCIC study, and relate to historic adjuvant trials for solid tumors. © 2012 by Springer Verlag, Cancer Chemotherapy and Pharmacology The original publication is available at www.springerlink.com DOI: 10.1007/s00280-011-1796-4 Sun, 01 Apr 2012 05:00:00 GMT http://hdl.handle.net/10027/8388 2012-04-01T05:00:00Z