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Purpose Warfarin management in the elderly population is complex as medicines prescribed for concomitant diseases may further increase the risk of major bleeding associated with warfarin use. We aimed to quantify the excess risk of bleeding-related hospitalisation when warfarin was co-dispensed with potentially interacting medicines. Methods A retrospective cohort study was undertaken over a 4-year period from July 2002 to June 2006 to examine bleeding risk associated with medications co-administered in patients taking warfarin using an administrative claims database from the Australian Department of Veterans and Affairs. All veterans aged 65 years and over who were new users of warfarin were followed until death or study end. Risk of bleeding was assessed using a Poisson GEE model adjusting for age, gender, socioeconomic status, co-morbidity index, previous bleeding related hospitalisations and indicators of health service use. Results Overall, 17661 veterans who used warfarin at any time during the study period were included. The overall incidence rate of bleeding-related hospitalisations was 4.1 (95% CI 3.7-4.6) per 100 person-years in veterans who were not receiving potentially interacting medicines. Bleeding-related hospitalisation rates were significantly increased when warfarin was co-prescribed with low-dose aspirin (Adjusted rate ratio (AdjRR) 1.44, 95% CI 1.00-2.07), clopidogrel (AdjRR 2.23, 95% CI 1.48-3.36), clopidogrel with aspirin (AdjRR 3.44, 95% CI 1.28-9.23), amiodarone (AdjRR 3.33, 95% CI 1.38-8.00) and antibiotics (AdjRR 2.34, 95% CI 1.55-3.54). Conclusions Models assessing bleeding risk with warfarin should take account of the range of potentially harmful medicine combinations used in elderly people with comorbid conditions. Refereed/Peer-reviewed

Background: This study assessed whether the number of comorbid conditions unrelated to diabetes was associated with a delay in therapeutic progression of diabetes treatment in Australian veterans. Conclusions/significance: Increasing numbers of unrelated conditions decreased the likelihood of therapeutic progression in veterans with diabetes. These results have implications for the development of quality measures, clinical guidelines and the construction of models of care for management of diabetes in elderly people with comorbidities. Methodology/principal findings: A retrospective cohort study was undertaken using data from the Australian Department of Veterans' Affairs (DVA) claims database between July 2000 and June 2008. The study included new users of metformin or sulfonylurea medicines. The outcome was the time to addition or switch to another antidiabetic treatment. The total number of comorbid conditions unrelated to diabetes was identified using the pharmaceutical-based comorbidity index, Rx-Risk-V. Competing risk regression analyses were conducted, with adjustments for a number of covariates that included age, gender, residential status, use of endocrinology service, number of hospitalisation episodes and adherence to diabetes medicines. Overall, 20134 veterans were included in the study. At one year, 23.5% of patients with diabetes had a second medicine added or had switched to another medicine, with 41.4% progressing by 4 years. The number of unrelated comorbidities was significantly associated with the time to addition of an antidiabetic medicine or switch to insulin (subhazard ratio [SHR] 0.87 [95% CI 0.84-0.91], P