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Minneapolis, MN, United States

Hart R.G.,University of Texas Health Science Center at San Antonio | Asinger R.W.,Hennepin County Medical Center | Herzog C.A.,Hennepin County Medical Center
Clinical Journal of the American Society of Nephrology | Year: 2011

Background and objectives The efficacy of adjusted-dose warfarin for prevention of stroke in atrial fibrillation patients with stage 3 chronic kidney disease (CKD) is unknown. Design, setting, participants, & measurements Patients with stage 3 CKD participating in the Stroke Prevention in Atrial Fibrillation 3 trials were assessed to determine the effect of warfarin anticoagulation on stroke and major hemorrhage, and whether CKD status independently contributed to stroke risk. High-risk participants (n = 1044) in the randomized trial were assigned to adjusted-dose warfarin (target international normalized ratio 2 to 3) versus aspirin (325 mg) plus fixed, low-dose warfarin (subsequently shown to be equivalent to aspirin alone). Low-risk participants (n=892) all received 325 mg aspirin daily. The primary outcome was ischemic stroke (96%) or systemic embolism (4%). Results Among the 1936 participants in the two trials, 42% (n=805) had stage 3 CKD at entry. Considering the 1314 patients not assigned to adjusted-dose warfarin, the primary event rate was double among those with stage 3 CKD (hazard ratio 2.0, 95% CI 1.2, 3.3) versus those with a higher estimated GFR (eGFR). Among the 516 participants with stage 3 CKD included in the randomized trial, ischemic stroke/systemic embolism was reduced 76% (95% CI 42, 90; P < 0.001) by adjusted-dose warfarin compared with aspirin/ low-dose warfarin; there was no difference in major hemorrhage (5 patients versus 6 patients, respectively). Conclusions Among atrial fibrillation patients participating in the Stroke Prevention in Atrial Fibrillation III trials, stage 3 CKD was associated with higher rates of ischemic stroke/systemic embolism. Adjusted-dose warfarin markedly reduced ischemic stroke/systemic embolism in high-risk atrial fibrillation patients with stage 3 CKD. © 2011 by the American Society of Nephrology. Source

Schmidt A.H.,Hennepin County Medical Center
Journal of Orthopaedic Trauma | Year: 2011

Objectives: To compare hospital charges and length of stay in a series of adult patients with isolated, otherwise uncomplicated tibia fractures with and without acute compartment syndrome (ACS). Design: Retrospective case-control study. Setting: Urban Level I trauma center. Patients: Forty-six previously healthy adults with isolated tibia fractures (open or closed), with or without ACS but without other complication, associated injury, or social circumstance that influenced hospital stay or charges. Intervention: Intramedullary nailing in all patients with immediate fasciotomy and delayed fasciotomy closure in the subset of patients who developed ACS. Main Outcome Measure: Hospital length of stay in days and hospital charges. Results: Forty-six otherwise uncomplicated patients with isolated tibial shaft fractures were identified. Twelve fractures were open. ACS occurred in five patients, all with closed fractures. In 41 patients without ACS (12 open fractures, 29 closed fractures), the mean hospital stay was 3.0 days and mean hospital charges were $23,800. The five patients with ACS underwent a mean of 1.6 additional surgeries to treat the fasciotomy wound, were hospitalized for a mean of 9.0 days, and the mean hospital charges were $49,700. These differences were highly significant for hospital stay (P < 0.005) and charges (P < 0.00004). In contrast, there were no differences in length of stay or hospital charges in patients with closed or open fractures, respectively. Conclusion: The cost of ACS is significant, resulting in hospital stays that are increased threefold and hospital charges that are more than doubled in this cohort of patients. The impact of compartment syndrome on these factors was more important than whether the fracture was open or closed. In addition to the obvious benefit to the patient, methods that decrease the incidence of compartment syndrome and need for fasciotomy such as improved diagnosis to prevent unnecessary fasciotomy and methods to reduce intramuscular pressure and avoid fasciotomy in cases of incipient ACS would also be of value in reducing medical costs. Copyright © 2011 by Lippincott Williams & Wilkins. Source

Baker J.V.,Hennepin County Medical Center
Journal of the American Heart Association | Year: 2013

HIV infection leads to activation of coagulation, which may increase the risk for atherosclerosis and venous thromboembolic disease. We hypothesized that HIV replication increases coagulation potentially through alterations in extrinsic pathway factors. Extrinsic pathway factors were measured among a subset of HIV participants from the Strategies for Management of Anti-Retroviral Therapy (SMART) trial. Thrombin generation was estimated using validated computational modeling based on factor composition. We characterized the effect of antiretroviral therapy (ART) treatment versus the untreated state (HIV replication) via 3 separate analyses: (1) a cross-sectional comparison of those on and off ART (n=717); (2) a randomized comparison of deferring versus starting ART (n=217); and (3) a randomized comparison of stopping versus continuing ART (n=500). Compared with viral suppression, HIV replication consistently showed short-term increases in some procoagulants (eg, 15% to 23% higher FVIII; P<0.001) and decreases in key anticoagulants (eg, 5% to 9% lower antithrombin [AT] and 6% to 10% lower protein C; P<0.01). The net effect of HIV replication was to increase coagulation potential (eg, 24% to 48% greater thrombin generation from computational models; P<0.01 for all). The pattern of changes from HIV replication was reversed with ART treatment and consistent across all 3 independent comparisons. HIV replication leads to complex changes in extrinsic pathway factors, with the net effect of increasing coagulation potential to a degree that may be clinically relevant. The key influence of changes in FVIII and AT suggests that HIV-related coagulation abnormalities may involve changes in hepatocyte function in the context of systemic inflammation. Source

Bart G.,Hennepin County Medical Center | Bart G.,University of Minnesota
Journal of Addictive Diseases | Year: 2012

Illicit use of opiates is the fastest growing substance use problem in the United States, and the main reason for seeking addiction treatment services for illicit drug use throughout the world. It is associated with significant morbidity and mortality related to human immunodeficiency virus, hepatitis C, and overdose. Treatment for opiate addiction requires long-term management. Behavioral interventions alone have extremely poor outcomes, with more than 80% of patients returning to drug use. Similarly poor results are seen with medication-assisted detoxification. This article provides a topical review of the three medications approved by the Food and Drug Administration for long-term treatment of opiate dependence: the opioid-agonist methadone, the partial opioid-agonist buprenorphine, and the opioid-antagonist naltrexone. Basic mechanisms of action and treatment outcomes are described for each medication. Results indicate that maintenance medication provides the best opportunity for patients to achieve recovery from opiate addiction. Extensive literature and systematic reviews show that maintenance treatment with either methadone or buprenorphine is associated with retention in treatment, reduction in illicit opiate use, decreased craving, and improved social function. Oral naltrexone is ineffective in treating opiate addiction, but recent studies using extended-release naltrexone injections have shown promise. Although no direct comparisons between extended-release naltrexone injections and either methadone or buprenorphine exist, indirect comparison of retention shows inferior outcome compared with methadone and buprenorphine. Further work is needed to directly compare each medication and determine individual factors that can assist in medication selection. Until such time, selection of medication should be based on informed choice following a discussion of outcomes, risks, and benefits of each medication. © 2012 Taylor and Francis Group, LLC. Source

Frostbite can be a devastating and even debilitating injury. Early identification and proper treatment of frostbite is critical in saving digits and limbs. Tissue plasminogen activator (tPA) has been shown to be effective in reducing the number of digits amputated after severe frostbite injury. Nothing has been presented in the podiatric literature regarding the use of tPA in treating frostbite patients for preserving toes and feet. Intravenous tPA and IV heparin were used to treat severe frostbite injuries that did not show improvement after rapid rewarming, had absent Doppler pulses in the distal limb or digits, showed limited or no perfusion by Tc-99 3-phase bone scan, and had no contraindications to use of tPA. All 11 patients included in this study were treated at Hennepin County Medical Center between 2008 and 2010. A total of 73 digits (upper and lower extremity) were considered at risk for amputation after evaluation with Tc-99 bone scan. Of those digits that were affected, 43 were amputated. Intravenous tPA is a safe and effective treatment to reduce the number of digital amputations after severe frostbite injury. The authors' protocol for treating severe frostbite includes the use of tPA. Levels of Evidence: Therapeutic, Level IV. Source

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