Medicine is the only business transaction in which consumers make important purchase decisions without knowing how much they have to pay. Lack of price transparency in health care imposes financial burden and anxiety among patients as the cost of health care has been shifting from employers to patients through high-deductible health plans (HDHPs). Health economists and policymakers anticipated that HDHPs with price transparency would be a catalyst for patients to "shop" for low-price providers, thus reducing overall health care spending. For patients to shop health care services, price transparency is a requisite. The Department of Health and Human Services mandate of publicly disclosing the hospital chargemaster and state legislatures demanding greater health care price transparency are just two examples of external forces challenging the long history of price opacity in health care. Imaging, pharmacy, laboratory tests, and ambulatory surgeries are considered potentially shoppable health care services. This article examines the intended motivation of price transparency, the limitations of current price transparency tools, and what impact price transparency may have on radiology. We share our experience in developing and implementing University of Utah's online interactive price transparency tool to estimate patients' out-of-pocket expenses.

Importance The optimal international normalized ratio (INR) to prevent venous thromboembolism (VTE) in warfarin-treated patients with recent arthroplasty is unknown. Objective To determine the safety and efficacy of a target INR of 1.8 vs 2.5 for VTE prophylaxis after orthopedic surgery. Design, Setting, and Participants The randomized Genetic Informatics Trial (GIFT) of Warfarin to Prevent Deep Vein Thrombosis enrolled 1650 patients aged 65 years or older initiating warfarin for elective hip or knee arthroplasty at 6 US medical centers. Enrollment began in April 2011 and follow-up concluded in October 2016. Interventions In a 2 × 2 factorial design, participants were randomized to a target INR of 1.8 (n = 823) or 2.5 (n = 827) and to either genotype-guided or clinically guided warfarin dosing. For the first 11 days of therapy, open-label warfarin dosing was guided by a web application. Main Outcomes and Measures The primary outcome was the composite of VTE (within 60 days) or death (within 30 days). Participants underwent screening duplex ultrasound postoperatively. The hypothesis was that an INR target of 1.8 would be noninferior to an INR target of 2.5, using a noninferiority margin of 3% for the absolute risk of VTE. Secondary end points were bleeding and INR values of 4 or more. Results Among 1650 patients who were randomized (mean age, 72.1 years; 1049 women [63.6%]; 1502 white [91.0%]), 1597 (96.8%) received at least 1 dose of warfarin and were included in the primary analysis. The rate of the primary composite outcome of VTE or death was 5.1% (41 of 804) in the low-intensity-warfarin group (INR target, 1.8) vs 3.8% (30 of 793) in the standard-treatment-warfarin group (INR target, 2.5), for a difference of 1.3% (1-sided 95% CI, -∞ to 3.05%, P = .06 for noninferiority). Major bleeding occurred in 0.4% of patients in the low-intensity group and 0.9% of patients in the standard-intensity group, for a difference of -0.5% (95% CI, -1.6% to 0.4%). The INR values of 4 or more occurred in 4.5% of patients in the low-intensity group and 12.2% of the standard-intensity group, for a difference of -7.8% (95% CI, -10.5% to -5.1%). Conclusions and Relevance Among older patients undergoing hip or knee arthroplasty and receiving warfarin prophylaxis, an international normalized ratio goal of 1.8 compared with 2.5 did not meet the criterion for noninferiority for risk of the composite outcome of VTE or death. However, the trial may have been underpowered to meet this criterion and further research may be warranted. Trial Registration ClinicalTrials.gov Identifier: NCT01006733.

Emerging evidence implicates platelets as key mediators of venous thromboembolism (VTE). Nevertheless, the pathways by which platelets and circulating procoagulant proteins synergistically orchestrate VTE remain incompletely understood. We prospectively determined whether activated platelets and systemic procoagulant factors were associated with VTE in 32 older orthopedic surgery patients. Circulating platelet-monocyte aggregates (PMAs), p-selectin expression (P-SEL), and integrin αIIbβ3 activation (PAC-1 binding) were assessed pre-operatively and 24 hours post-operatively. The proinflammatory and procoagulant molecule C-reactive protein (CRP), which induces PMA formation in vitro, along with plasma d-dimer and fibrinogen levels were also measured. The primary outcome was VTE occurring within 30 days post-operatively. Overall, 40.6% of patients developed VTE. Patients with VTE had a significant increase in circulating PMAs and CRP post-operatively, compared to those without VTE. Changes in PMA and CRP in VTE patients were significantly correlated (r(2) = 0.536, p = 0.004). In contrast, P-SEL expression and PAC-1 binding, fibrinogen levels, and d-dimers were not associated with VTE. This is the first study to identify that increased circulating PMAs and CRP levels are early markers associated with post-surgical VTE. Our findings also provide new clinical evidence supporting the interplay between PMAs and CRP in patients with VTE.

IMPORTANCE Transformation of US health care from volume to value requires meaningful quantification of costs and outcomes at the level of individual patients.OBJECTIVE To measure the association of a value-driven outcomes tool that allocates costs of care and quality measures to individual patient encounters with cost reduction and health outcome optimization.DESIGN, SETTING, AND PARTICIPANTS Uncontrolled, pre-post, longitudinal, observational study measuring quality and outcomes relative to cost from 2012 to 2016 at University of Utah Health Care. Clinical improvement projects included total hip and knee joint replacement, hospitalist laboratory utilization, and management of sepsis.EXPOSURES Physicians were given access to a tool with information about outcomes, costs (not charges), and variation and partnered with process improvement experts.MAIN OUTCOMES AND MEASURES Total and component inpatient and outpatient direct costs across departments; cost variability for Medicare severity diagnosis related groups measured as coefficient of variation (CV); and care costs and composite quality indexes.RESULTS From July 1,2014, to June 30,2015, there were 1.7 million total patient visits, including 34000 inpatient discharges. Professional costs accounted for 24.3% of total costs for inpatient episodes ($114.4 million of $470.4 million) and 41.9% of total costs for outpatient visits ($231.7 million of $553.1 million). For Medicare severity diagnosis related groups with the highest total direct costs, cost variability was highest for postoperative infection (CV = 1.71) and sepsis (CV = 1.37) and among the lowest for organ transplantation (CV < 0.43). For total joint replacement, a composite quality index was 54% at baseline (n = 233 encounters) and 80% lyear into the implementation (n = 188 encounters) (absolute change, 26%; 95% Cl, 18%-35%; P <.001). Compared with the baseline year, mean direct costs were 7% lower in the implementation year (95% Cl, 3%-11%; P < .001) and 11% lower in the postimplementation year (95% Cl, 7%-14%; P <.001). The hospitalist laboratory testing mean cost per day was $138 (median [1QR], $113 [$79-160]; n = 2034 encounters) at baseline and $123 (median [1QR], $99 [$66-147]; n = 4276 encounters) in the evaluation period (mean difference,-$15; 95% Cl,-$19 to-$11; P <.001), with no significant change in mean length of stay. For a pilot sepsis intervention, the mean time to anti-infective administration followingfulfillment of systemic inflammatory response syndrome criteria in patients with infection was 7.8 hours (median [1QR], 3.410.8-7.8] hours; n = 29 encounters) at baseline and 3.6 hours (median [1QR], 2.211.0-4.5] hours; n = 76 encounters) in the evaluation period (mean difference,-4.1 hours; 95% Cl,-9.9 to-1.0 hours; P =.02).CONCLUSIONS AND RELEVANCE Implementation of a multifaceted value-driven outcomes tool to identify high variability in costs and outcomes in a large single health care system was associated with reduced costs and improved quality for 3 selected clinical projects. There may be benefit for individual physicians to understand actual care costs (not charges) and outcomes achieved for individual patients with defined clinical conditions.

Background An early physical therapy (PT) care pathway was implemented to provide same-day ambulation after total joint arthroplasty by changing PT staffing hours. Methods After receiving an exemption from our institutional review board, we performed a secondary data analysis on a cohort of patients that underwent primary TJA of the hip or knee 6 months before and 12 months after implementation of the change. Data on same-day ambulation rates, length of stay (LOS), and in-hospital costs were reviewed. Results Early evaluation and mobilization of patients by PT improved on postoperative day (POD) 0 from 64% to 85% after the change (P ≤ .001). The median LOS before the change was 3.27 days compared to 3.23 days after the change (P = .014). Patients with higher American Society of Anesthesiologists scores were less likely to ambulate on POD 0 (P = .038) and had longer hospital stays (P < .001). Early mobilization in the entire cohort was associated with a greater cost savings (P < .001). Conclusions A relatively simple change to staffing hours, using resources currently available to us, and little additional financial or institutional investment resulted in a significant improvement in the number of patients ambulating on POD 0, with a modest reduction in both LOS and inpatient costs.

BACKGROUND Prospective studies on the incidence of VTE during severe sepsis and septic shock remain absent, hindering efficacy assessments regarding VTE prevention strategies in sepsis. METHODS We prospectively studied 113 consecutively enrolled patients in the ICU with severe sepsis and septic shock at three hospitals. All patients provided informed consent. VTE thromboprophylaxis was recorded for all patients. Patients underwent ultrasonography and were followed for VTE prior to ICU discharge. All-cause 28-day mortality was recorded. Variables from univariate analyses that were associated with VTE (including central venous catheter [CVC] insertion, age, length of stay, and mechanical ventilation) were included in a multivariable logistic regression analysis using backward stepwise elimination to determine VTE predictors. RESULTS Mean APACHE (Acute Physiology and Chronic Health Evaluation) II score was 18.2 ± 7.0, and age was 50 ± 18 years. Despite all patients receiving guideline-recommended thromboprophylaxis, the incidence of VTE was 37.2% (95% CI, 28.3-46.8). Most VTE events were clinically significant (defined as pulmonary embolism, proximal DVT, and/or symptomatic distal DVT) and associated with an increased length of stay (18.2 ± 9.9 days vs 13.4 ± 11.5 days, P < .05). Mortality was higher in patients with acute VTE but did not reach statistical significance. Insertion of a CVC and longer mechanical ventilation duration were significant VTE risk factors. VTE incidence did not differ by thromboprophylaxis type. CONCLUSIONS To our knowledge this is the first multicenter prospective study to identify a high incidence of VTE in patients with severe sepsis and septic shock, despite the use of universal, guideline-recommended thromboprophylaxis. Our findings suggest that the systemic inflammatory milieu of sepsis may uniquely predispose patients with sepsis to VTE. More effective VTE prevention strategies are necessary in patients with sepsis. TRIAL REGISTRY ClinicalTrials.gov; No.: NCT02353910; URL: www.clinicaltrials.gov.

Background: Improvements in the early identification of older patients with a high post-operative VTE risk would potentially translate into more effective VTE prevention and management strategies.

Objective To develop expeditiously a pragmatic, modular, and extensible software framework for understanding and improving healthcare value (costs relative to outcomes).Materials and methods In 2012, a multidisciplinary team was assembled by the leadership of the University of Utah Health Sciences Center and charged with rapidly developing a pragmatic and actionable analytics framework for understanding and enhancing healthcare value. Based on an analysis of relevant prior work, a value analytics framework known as Value Driven Outcomes (VDO) was developed using an agile methodology. Evaluation consisted of measurement against project objectives, including implementation timeliness, system performance, completeness, accuracy, extensibility, adoption, satisfaction, and the ability to support value improvement.Results A modular, extensible framework was developed to allocate clinical care costs to individual patient encounters. For example, labor costs in a hospital unit are allocated to patients based on the hours they spent in the unit; actual medication acquisition costs are allocated to patients based on utilization; and radiology costs are allocated based on the minutes required for study performance. Relevant process and outcome measures are also available. A visualization layer facilitates the identification of value improvement opportunities, such as high-volume, high-cost case types with high variability in costs across providers. Initial implementation was completed within 6 months, and all project objectives were fulfilled. The framework has been improved iteratively and is now a foundational tool for delivering high-value care.Conclusions The framework described can be expeditiously implemented to provide a pragmatic, modular, and extensible approach to understanding and improving healthcare value.

BACKGROUND:The clinical utility of genotype-guided (pharmacogenetically based) dosing of warfarin has been tested only in small clinical trials or observational studies, with equivocal results.METHODS:We randomly assigned 1015 patients to receive doses of warfarin during the first 5 days of therapy that were determined according to a dosing algorithm that included both clinical variables and genotype data or to one that included clinical variables only. All patients and clinicians were unaware of the dose of warfarin during the first 4 weeks of therapy. The primary outcome was the percentage of time that the international normalized ratio (INR) was in the therapeutic range from day 4 or 5 through day 28 of therapy.RESULTS:At 4 weeks, the mean percentage of time in the therapeutic range was 45.2% in the genotype-guided group and 45.4% in the clinically guided group (adjusted mean difference, [genotype-guided group minus clinically guided group], -0.2; 95% confidence interval, -3.4 to 3.1; P=0.91). There also was no significant between-group difference among patients with a predicted dose difference between the two algorithms of 1 mg per day or more. There was, however, a significant interaction between dosing strategy and race (P=0.003). Among black patients, the mean percentage of time in the therapeutic range was less in the genotype-guided group than in the clinically guided group. The rates of the combined outcome of any INR of 4 or more, major bleeding, or thromboembolism did not differ significantly according to dosing strategy.CONCLUSIONS:Genotype-guided dosing of warfarin did not improve anticoagulation control during the first 4 weeks of therapy. (Funded by the National Heart, Lung, and Blood Institute and others; COAG ClinicalTrials.gov number, NCT00839657.).

INTRODUCTION: AHA guidelines discourage anticoagulation in acute ischemic stroke (AIS) patients to prevent stroke recurrence. However, some AIS patients have concurrent thrombotic states, such as DVT/PE, that require anticoagulation to prevent further morbidity. Little is published on the safety and efficacy of heparin titration nomograms used for thrombotic comorbidities in stroke patients. Our aim was to assess the utilization and safety of a heparin stroke infusion nomogram at a single, tertiary, academic hospital. METHODS: The heparin stroke nomogram contains no heparin bolus, a goal aPTT of 60-85, and stable “steady state” dose with 2 consecutive aPTT values at goal. Patients were identified via a retrospective, computerized order entry review for the heparin nomogram. Exclusion criteria were: baseline aPTT > 50s, a hypercoagulable state, and short usage (< 24 hrs) or interrupted nomogram prior to 2 consecutive “goal” aPTT values. Demographic data and aPTTs were determined from the prospectively-populated enterprise data warehouse. The aPTTs were divided into 6 hr time bins from initiation. Indication and outcomes were determined by source document review by a stroke neurologist. RESULTS: From 1/2010 - 6/2011, a heparin nomogram for any indication was initiated in 2,016 patients with 144 (7%) of these utilizing the “stroke” heparin nomogram, The nomogram was ordered by neurology (72%, n=103 ), neurosurgery (8%, n=11), other surgical specialties (9%, n=13), internal medicine (7%, n=10), and other (5%, n=7). After excluding those as above, the “stroke” heparin nomogram was used in 86 patients (40% female; mean 55 yrs SD 17), 74 with AIS, 2 with ICH, 1 with SAH, 2 with craniectomy, and 3 other. The indication for heparin included large artery near total occlusion (30%, n=26), cardiac thrombus (suspected (26%, n=22) or visualized (9%, n=8)), cerebral sinus venous thrombosis (10%, n=9), DVT/PE (5%, n=4), artery dissection (17%, n=15), and other (7%, n=6). Percent of “at-goal” aPTTs by 6 hr time bins were: 6-12 hrs: 24% (n=21/86); 12-18 hrs: 36% (n=31/ 86); 18-24 hrs: 48% (n=40/84); 24-48 hrs: 55% (n=42/77); 48+ hrs: 65% (n=29/45). At the 42-48 hrs time point, 4% of patients had aPTT>150. There were 4 non-bleeding related deaths. Repeat AIS occurred in 3 patients of the 74 patients with primary AIS. Asymptomatic ICH occurred in 1 patient with primary AIS; symptomatic hemorrhage occurred in 2 patients (epistaxis, GI). Discharge anticoagulation was prescribed in 56 patients (65%). Ninety day readmission occurred in 15% of patients (n=13), 5 for bleeding. CONCLUSION: The heparin stroke nomogram appears safe in that it does not increase risk of ICH. However, therapeutic aPTTs are not reached quickly with less than half of patients therapeutic at 24 hours, nor are they maintained at steady state. This nomogram could be too conservative in cases where clinical situation requires rapid anticoagulation.

Background: Approximately 7-10% of patients with unprovoked VTE will be diagnosed with cancer within 12 months. Although cancer screening has been proposed in these patients, the optimal strategy remains unclear. In a pilot study, we prospectively investigated the use of FDG-PET/CT to screen for occult malignancy in 40 patients with unprovoked VTE.Materials/Methods: Patients were initially screened for occult malignancy with a focused history, physical, and laboratory evaluation. Patients underwent whole body FDG-PET/CT and were followed for up to two years for a new diagnosis of cancer. The total costs of using FDG-PET/CT as a comprehensive screening strategy were determined using 2010 Medicare reimbursement rates.Results: Completion of FDG-PET/CT imaging was feasible and identified abnormal findings requiring additional evaluations in 62.5% of patients. Occult malignancy was evident in only one patient (cancer incidence 2.5%) and FDG-PET/CT imaging excluded malignancy in the remainder of patients. No patients with a negative FDG-PET/CT were diagnosed with malignancy during an average(+/- SD) follow-up of 449 (+/- 311) days. The use of FDG-PET/CT to screen for occult malignancy added $59,151 in total costs ($1,479 per patient). The majority of these costs were due to the cost of the FDG-PET/CT ($1,162 per patient or 78.5% of total per-patient costs).Conclusions: FDG-PET/CT may have utility for excluding occult malignancy in patients with unprovoked VTE. The costs of this comprehensive screening strategy were comparable to other screening approaches. Larger studies are needed to further evaluate the utility and cost-effectiveness of FDG-PET/CT as a cancer screening strategy in patients with unprovoked VTE. (C) 2011 Elsevier Ltd. All rights reserved.

Enoxaparin is commonly used to prevent venous thromboembolism(VTE) [1,2] but has not been well-studied in patients with extreme obesity,a population at high risk for VTE. We prospectively compared three enoxaparin dosing regimens for the achievement of goal peak anti-Factor Xa levels in medically ill patients (n 5 31) with extreme obesity (body mass index (BMI) ‡ 40 kg/m2). Patients were assigned to receive fixed-dose (FD) enoxaparin 40 mg daily (QDay, n 5 11), weight based,lower-dose (LD) enoxaparin 0.4 mg/kg QDay (n 5 9), or weight based,higher-dose (HD) enoxaparin 0.5 mg/kg QDay (n 5 11). The average BMI and weight of the entire cohort was 62.1 kg/m2 (range40.5–82.4) and 176 kg (range 115–256 kg) and did not differ between groups. Peak anti-Factor Xa levels were significantly higher in the HD group compared to either LD or FD groups. Patients in the HD group achieved target anti-Factor Xa levels more frequently than the LD and FD groups (P < 0.05). Peak anti-Factor Xa levels did not correlate with age, weight, BMI, or creatinine clearance, demonstrating the predictability of weight-based enoxaparin dosing. There were no adverse events (e.g., bleeding, thrombosis, thrombocytopenia). To our knowledge this is the first prospective comparative study demonstrating that in extremely obese, medically ill patients enoxaparin 0.5 mg/kg QDay is superior to FD and LD enoxaparin for the achievement of target anti-Factor Xa levels.

Source Citation Lederle FA, Zylla D, MacDonald R, Wilt TJ. Venous thromboembolism prophylaxis in hospitalized medical patients and those with stroke: a background review for an American College of Physicians clinical practice guideline. Ann Intern Med. 2011;155:602-15. 22041949

Abstract Venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, is a substantial public health problem. The majority of VTE events are associated with transient periods of heightened risk, such as prolonged hospitalization, undergoing major surgery, experiencing trauma or lower extremity immobility, use of oral contraceptives, or having active cancer. Although pharmacologic thromboprophylaxis agents (eg, unfractionated heparin, low-molecular-weight heparins, warfarin, and novel oral anticoagulants) are effective, they remain underused, with concerns about increased bleeding risk often cited as a reason. The 3-hydroxy-3-methylglutaryl–coenzyme A reductase inhibitors (ie, statins), although used primarily for lipid lowering and arterial thrombosis risk reduction, have pleiotrophic effects that affect coagulation and inflammation, and do not increase bleeding risk. There is emerging evidence to suggest that through these pleiotrophic effects, statins may be effective in reducing the incidence of VTE. This article summarizes the literature with regard to statins' effect on VTE and suggests that additional investigations are needed to assess a potential adjunctive role for primary VTE thromboprophylaxis.

Summary We performed a randomised pilot trial of PerMIT, a novel decision support tool for genotype-based warfarin initiation and maintenance dosing, to assess its efficacy for improving warfarin management. We prospectively studied 26 subjects to compare PerMIT-guided management with routine anticoagulation service management. CYP2C9 and VKORC1 genotype results for 13 subjects randomly assigned to the PerMIT arm were recorded within 24 hours of enrolment. To aid in INR interpretation, PerMIT calculates estimated loading and maintenance doses based on a patient’s genetic and clinical characteristics and displays calculated S-warfarin plasma concentrations based on planned or administered dosages. In comparison to control subjects, patients in the PerMIT study arm demonstrated a 3.6-day decrease in the time to reach a stabilised INR within the target therapeutic range (4.7 vs. 8.3 days, p = 0.015); a 12.8% increase in time spent within the therapeutic interval over the first 25 days of therapy (64.3% vs. 55.3%, p = 0.180); and a 32.9% decrease in the frequency of warfarin dose adjustments per INR measurement (38.3% vs. 57.1%, p = 0.007). Serial measurements of plasma S-warfarin concentrations were also obtained to prospectively evaluate the accuracy of the pharmacokinetic model during induction therapy. The PerMIT S-warfarin plasma concentration model estimated 62.8% of concentrations within 0.15 mg/l. These pilot data suggest that the PerMIT method and its incorporation of genotype/phenotype information may help practitioners increase the safety, efficacy, and efficiency of warfarin therapeutic management. Clinical Trials Registration identifier: NCT00993200

CONTEXTExtreme obesity is associated with health and cardiovascular disease risks. Although gastric bypass surgery induces rapid weight loss and ameliorates many of these risks in the short term, long-term outcomes are uncertain.OBJECTIVETo examine the association of Roux-en-Y gastric bypass (RYGB) surgery with weight loss, diabetes mellitus, and other health risks 6 years after surgery.DESIGN, SETTING, AND PARTICIPANTSA prospective Utah-based study conducted between July 2000 and June 2011 of 1156 severely obese (body mass index [BMI] ≥ 35) participants aged 18 to 72 years (82% women; mean BMI, 45.9; 95% CI, 31.2-60.6) who sought and received RYGB surgery (n = 418), sought but did not have surgery (n = 417; control group 1), or who were randomly selected from a population-based sample not seeking weight loss surgery (n = 321; control group 2).MAIN OUTCOME MEASURESWeight loss, diabetes, hypertension, dyslipidemia, and health-related quality of life were compared between participants having RYGB surgery and control participants using propensity score adjustment.RESULTSSix years after surgery, patients who received RYGB surgery (with 92.6% follow-up) lost 27.7% (95% CI, 26.6%-28.9%) of their initial body weight compared with 0.2% (95% CI, -1.1% to 1.4%) gain in control group 1 and 0% (95% CI, -1.2% to 1.2%) in control group 2. Weight loss maintenance was superior in patients who received RYGB surgery, with 94% (95% CI, 92%-96%) and 76% (95% CI, 72%-81%) of patients receiving RYGB surgery maintaining at least 20% weight loss 2 and 6 years after surgery, respectively. Diabetes remission rates 6 years after surgery were 62% (95% CI, 49%-75%) in the RYGB surgery group, 8% (95% CI, 0%-16%) in control group 1, and 6% (95% CI, 0%-13%) in control group 2, with remission odds ratios (ORs) of 16.5 (95% CI, 4.7-57.6; P < .001) vs control group 1 and 21.5 (95% CI, 5.4-85.6; P < .001) vs control group 2. The incidence of diabetes throughout the course of the study was reduced after RYGB surgery (2%; 95% CI, 0%-4%; vs 17%; 95% CI, 10%-24%; OR, 0.11; 95% CI, 0.04-0.34 compared with control group 1 and 15%; 95% CI, 9%-21%; OR, 0.21; 95% CI, 0.06-0.67 compared with control group 2; both P < .001). The numbers of participants with bariatric surgery-related hospitalizations were 33 (7.9%), 13 (3.9%), and 6 (2.0%) for the RYGB surgery group and 2 control groups, respectively.CONCLUSIONAmong severely obese patients, compared with nonsurgical control patients, the use of RYGB surgery was associated with higher rates of diabetes remission and lower risk of cardiovascular and other health outcomes over 6 years.

Purpose: F-18-FDG PET has been used for vascular disease, but its role in deep vein thrombosis (DVT) remains prospectively unexplored.Patients and Methods: Whole-body F-18-FDG PET/CT scans were performed in patients 1 to 10 weeks after onset of symptomatic DVT (n = 12) and in control subjects without DVT (n = 24). The metabolic activity (SUVmax) of thrombosed and contralateral nonthrombosed vein segments was determined. The sensitivity and specificity of F-18-FDG PET/CT for the diagnosis of DVT were determined by receiver operating characteristic curve analyses. In 2 patients with DVT, changes in the metabolic activity of thrombosed vein segments in serial F-18-FDG PET scans.Results: The metabolic activity in thrombosed veins [SUVmax, 2.41 (0.75)] was visually appreciable and significantly higher than in nonthrombosed veins in either the contralateral extremity of patients with DVT [SUVmax, 1.09 (0.25), P = 0.007] or control subjects [1.21 (0.22), P < 0.001]. The area under the receiver operating characteristic curve for SUVmax was 0.9773 (P < 0.001), indicating excellent accuracy. An SUVmax threshold of greater than 1.645 was 87.5% sensitive and 100% specific for DVT. Metabolic activity in thrombosed veins correlated significantly with time from DVT symptom onset (decrease in SUVmax of 0.02/d, P < 0.05). Best-fit-line analyses suggested that approximately 84 to 91 days after acute DVT, the maximum metabolic activity of thrombosed veins would return to normal levels.Conclusions: F-18-FDG PET/CT is accurate for detecting acute symptomatic, proximal DVT. Metabolic activity in thrombosed veins decreases with time, suggesting that F-18-FDG PET may be helpful in assessing the age of the clot.

SummaryBy guiding initial warfarin dose, pharmacogenetic (PGx) algorithms may improve the safety of warfarin initiation. However, once international normalised ratio (INR) response is known, the contribution of PGx to dose refinements is uncertain. This study sought to develop and validate clinical and PGx dosing algorithms for warfarin dose refinement on days 6–11 after therapy initiation. An international sample of 2,022 patients at 13 medical centres on three continents provided clinical, INR, and genetic data at treatment days 6–11 to predict therapeutic warfarin dose. Independent derivation and retrospective validation samples were composed by randomly dividing the population (80%/20%). Prior warfarin doses were weighted by their expected effect on S-warfarin concentrations using an exponential-decay pharmacokinetic model. The INR divided by that “effective” dose constituted a treatment response index. Treatment response index, age, amiodarone, body surface area, warfarin indication, and target INR were associated with dose in the derivation sample. A clinical algorithm based on these factors was remarkably accurate: in the retrospective validation cohort its R2 was 61.2% and median absolute error (MAE) was 5.0 mg/week. Accuracy and safety was confirmed in a prospective cohort (N=43). CYP2C9 variants and VKORC1–1639 G→A were significant dose predictors in both the derivation and validation samples. In the retrospective validation cohort, the PGx algorithm had: R2= 69.1% (p<0.05 vs. clinical algorithm), MAE= 4.7 mg/week. In conclusion, a pharmacogenetic warfarin dose-refinement algorithm based on clinical, INR, and genetic factors can explain at least 69.1% of therapeutic warfarin dose variability after about one week of therapy.