Thesis (Ph. D.)--University of Wisconsin--Madison, 1955. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (M.S.)--University of Wisconsin--Madison, 1965. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (M.S.)--University of Wisconsin--Madison, 1962. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 21-22)

Thesis (Ph. D.)--University of Wisconsin--Madison, 1958. / Typescript. Abstracted in Dissertation abstracts, v. 18 (1958) no. 3, p. 793-794. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1982. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (M.S.)--University of Wisconsin--Madison, 1968. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (Ph. D.)--University of Wisconsin, 1964. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record.

Introduction: Warfarin is the most widely prescribed anticoagulant for the prevention and treatment of thromboembolic diseases. However, warfarin use is complicated by its narrow therapeutic range and inter-individual variability in the starting dose required to achieve a stable international normalised ratio (INR). Warfarin is initiated clinically at 5mg/day then subsequent doses are adjusted accordingly to achieve a stable targeted INR. However, inter-individual variability in response to the warfarin starting dose has been observed and this is reported to be attributed to by various genetic and nongenetic factors. Non-genetics factors implicated in the warfarin dose variability include age, gender, body weight, comorbidities and concomitant drugs. Genetic factors affecting warfarin dose variability include variation in genes encoding the warfarin metabolising enzymes and targeted proteins. Genetic variants in CYP2C9 and VKORC1 have been extensively studied on how they affect warfarin dose variability, culminating in several dosing algorithms incorporating genetic (i.e., CYP2C9*2, CYP2C9*3 and VKORC1 g.-1639G>A) and non-genetic factors (i.e., age, body surface area, amiodarone, race, targeted INR, smoking and thromboembolism). However, these studies have often excluded African populations, therefore missing variants that might be important in the prediction of warfarin doses among Africans. Data on variants that specifically affect warfarin dose variability among Africans is lacking, with no dosing algorithms tailored specifically for Africans developed to date. Thus, the main aim of the study is to conduct a comprehensive evaluation of important genetic and non-genetic factors affecting warfarin response, and further make recommendations on variables important for the development of appropriate algorithms for warfarin dosing among black Africans and the Mixed Ancestry population group in Southern Africa. Method: A total of 302 black Africans and 277 Mixed Ancestry adults undergoing warfarin treatment were recruited at INR clinics in the Western Cape Province, South Africa and Harare, Zimbabwe. Their DNA samples were extracted and utilised for downstream analyses. A total of 73 candidate variants involved in either pharmacokinetics or pharmacodynamics of warfarin, were genetically characterised using a combination of allelic discrimination, Sanger sequencing, restriction fragment length polymorphism and iPLEX PGx74 Mass Array platform. Various statistical packages in STATA, R, haploview and plink were employed to determine frequency distribution, linkage disequilibrium and haplotype mapping of the studied genetic variants. Furthermore, genetic and non-genetic variables were correlated with warfarin maintenance dose and their cumulative effect on warfarin dose variability measured through a multivariate step-wise regression analysis in both the black African and Mixed Ancestry cohorts. Whole exome sequencing was done using the ion torrent Sequence ion S5 system in selected black African individuals presenting with extreme phenotypes (i.e., very low dose or very high dose) but who did not harbour variants known to significantly affect warfarin dose requirements. A workflow which applied various bioinformatics tools was employed for the analyses of the resultant raw BAM files, subsequently, population structure and frequency distribution patterns were described among our cohort and individuals in the 1000 Genomes project. Specific variants identified through WES were prioritised according to clinical significance and further genotyped in an enhanced sample size of 252 black Africans, to confirm their effect on warfarin dose requirements.

Class of 2010 Abstract / OBJECTIVES: The objective of this study was to evaluate whether implementation of new anticoagulation policy at a community hospital resulted in better monitoring of warfarin, increased warfarin patient education prior to discharge, and less bleeding complications due to warfarin. METHODS: This study was a pre-­‐ post-­‐retrospective chart review quality improvement study. A retrospective chart review was conducted of all patients who were inpatients and received warfarin in the time period of April 1, 2008 to July 31, 2008 (historical control group before implementation of the new anticoagulation program) and the time period of April 1, 2009 to July 31, 2009 (after implementation of the new anticoagulation policies). To compare appropriateness of laboratory monitoring, the frequency of warfarin-­‐related laboratory orders that included a baseline international normalized ratio (INR), daily INR, baseline complete blood count (CBC), and CBC every 3 days were assessed before and after program implementation. The analysis was repeated for the frequency of patient education that included documentation by pharmacy, nursing, and dietary services. Finally, data was collected to determine frequencies of bleeding complications associated with warfarin. RESULTS: There were 112 patients in the pre-­‐policy group and 115 patients in the post-­‐policy group. After implementation of the inpatient warfarin policy, obtaining baseline INRs increased from 74% to 90% (p=0.001). In addition, prescriber orders for baseline CBCs increased from 85% to 94% (p=0.026). Obtaining CBCs every 3 days increased from 54% to 74%, (p<0.001). However, there was not a significant increase in orders for daily INR levels (p=0.055). Education by nursing increased from 54% to 80%, (p<0.001). Education by pharmacy increased from 8% to 76%, (p<0.001). Education by dietary increased from 11% to 79%, (p<0.001). Moreover, documentation by all three disciplines in each patient increased significantly from 3.6% to 59%, (p<0.001). There were significantly fewer patients receiving vitamin K and/ or fresh frozen plasma for supratherapeutic INRs with bleeding complications after the policy was initiated compared to baseline (p=0.009). CONCLUSIONS: The implementation of an inpatient warfarin policy led to better monitoring of patients receiving warfarin, and increased patient education. Studies have demonstrated that increased monitoring of warfarin translates to improved patient outcomes. However, a larger and longer assessment is necessary to determine if these changes are maintained and how these changes affect clinical outcomes.

<p>Ett stort antal patienter behandlas med warfarin som förebyggande mot blodpropp. Läkemedlet kräver regelbunden blodprovstagning där INR- värdet mäts för att kunna anpassa dosen individuellt så länge behandling pågår. Indikationen kan till exempel vara förmaksflimmer, mekanisk hjärtklaff eller tromboembolism. Warfarin är ett känt problemläkemedel där interaktionsrisken med andra läkemedel är stor och andra faktorer såsom kost och livsstilsförändringar kan påverka dess effekt. Syftet med litteraturstudien var att beskriva patienters behov av information vid warfarinbehandling. Studien baseras på 12 vetenskapliga artiklar. Resultatet visar att patienter behöver tydlig information om biverkningar som kan uppstå, interaktionsrisk med andra läkemedel och naturläkemedel samt hur kosten och alkoholen påverkar warfarinbehandlingen. Information behövs om vikten av följsamhet vid behandling och vart man bör vända sig vid frågor och problem. Resultatet visar också att vid bristande följsamhet, högre ålder och kommunikationssvårigheter behövs extra resurser för information. Tydligt och individuellt anpassat informationsmaterial på patientens hemspråk, med större text och bilder i bör användas vid behov. Uppföljning av informationen rekommenderas till alla för att behandlingen skall bli så säker som möjligt. Fortsatt forskning behövs om kostens, hälsokostens och alkoholens inverkan på warfarin. Fler kvalitativa studier efterfrågas för att kunna utveckla och förbättra patientinformationen.</p>