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The International Initiative on Thrombosis and Cancer is an independent academic working group of experts aimed at establishing global consensus for the treatment and prophylaxis of cancer-associated thrombosis. The 2013, 2016, and 2019 International Initiative on Thrombosis and Cancer clinical practice guidelines have been made available through a free, web-based mobile phone application. The 2022 clinical practice guidelines, which are based on a literature review up to Jan 1, 2022, include guidance for patients with cancer and with COVID-19. Key recommendations (grade 1A or 1B) include: (1) low-molecular-weight heparins (LMWHs) for the initial (first 10 days) treatment and maintenance treatment of cancer-associated thrombosis; (2) direct oral anticoagulants for the initial treatment and maintenance treatment of cancer-associated thrombosis in patients who are not at high risk of gastrointestinal or genitourinary bleeding, in the absence of strong drug-drug interactions or of gastrointestinal absorption impairment; (3) LMWHs or direct oral anticoagulants for a minimum of 6 months to treat cancer-associated thrombosis; (4) extended prophylaxis (4 weeks) with LMWHs to prevent postoperative venous thromboembolism after major abdominopelvic surgery in patients not at high risk of bleeding; and (5) primary prophylaxis of venous thromboembolism with LMWHs or direct oral anticoagulants (rivaroxaban or apixaban) in ambulatory patients with locally advanced or metastatic pancreatic cancer who are treated with anticancer therapy and have a low risk of bleeding.

International audience; Venous thromboembolism (VTE) is the second leading cause of death in patients with cancer. These patients are at a high risk of VTE recurrence and bleeding during anticoagulant therapy. The International Initiative on Thrombosis and Cancer is an independent academic working group aimed at establishing a global consensus for the treatment and prophylaxis of VTE in patients with cancer. The International Initiative on Thrombosis and Cancer last updated its evidence-based clinical practice guidelines in 2016 with a free, web-based mobile phone application, which was subsequently endorsed by the International Society on Thrombosis and Haemostasis. The 2019 International Initiative on Thrombosis and Cancer clinical practice guidelines, which are based on a systematic review of the literature published up to December, 2018, are presented along with a Grading of Recommendations Assessment Development and Evaluation scale methods, with the support of the French National Cancer Institute. These guidelines were reviewed by an expanded international advisory committee and endorsed by the International Society on Thrombosis and Haemostasis. Results from head-to-head clinical trials that compared direct oral anticoagulant with low-molecular-weight heparin are also summarised, along with new evidence for the treatment and prophylaxis of VTE in patients with cancer.

ObjectiveTo assess the effectiveness of system-wide interventions designed to increase the implementation of thromboprophylaxis and decrease the incidence of venous thromboembolism (VTE) in hospitalised medical and surgical patients at risk of VTE.DesignSystematic review and meta-analysis of randomised controlled trials (RCTs).Data sourcesMedline, PubMed, Embase, BIOSIS, CINAHL, Web of Science, CENTRAL, DARE, EED, LILACS and clinicaltrials.gov without language restrictions from inception to 7 January 2017, as well as the reference lists of relevant review articles.Eligibility criteria for selecting studiesRCTs that evaluated the effectiveness of system-wide interventions such as alerts, multifaceted, education, and preprinted orders when compared with no intervention, existing policy or another intervention.ResultsWe included 13 RCTs involving 35 997 participants. Eleven RCTs had data available for meta-analysis. Compared with control, we found absolute increase in the prescription of prophylaxis associated with alerts (21% increase, 95% CI [15% to 275%]) and multifaceted interventions (4% increase, 95% CI [3% to 11%]), absolute increase in the prescription of appropriate prophylaxis associated with alerts (16% increase, 95% CI [12% to 20%]) and relative risk reductions (risk ratio 64%, 95% CI [47% to 86%]) in the incidence of symptomatic VTE associated with alerts. Computer alerts were found to be more effective than human alerts, and multifaceted interventions with an alert component appeared to be more effective than multifaceted interventions without, although comparative pooled analyses were not feasible. The quality of evidence for improvement in outcomes was judged to be low to moderate certainty.ConclusionsAlerts increased the proportion of patients who received prophylaxis and appropriate prophylaxis, and decreased the incidence of symptomatic VTE. Multifaceted interventions increased the proportion of patients who received prophylaxis but were found to be less effective than alerts interventions.Trial registration numberCD008201.

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in hospitalized patients. While numerous randomized controlled trials (RCTs) have shown that the appropriate use of thromboprophylaxis in hospitalized patients at risk for VTE is safe, effective, and cost-effective, thromboprophylaxis remains underused or inappropriately used. Our previous review suggested that system-wide interventions, such as education, alerts, and multifaceted interventions were more effective at improving the prescribing of thromboprophylaxis than relying on individual providers' behaviors. However, 47 of the 55 included studies in our previous review were observational in design. Thus, an update to our systematic review, focused on the higher level of evidence of RCTs only, was warranted.To assess the effects of system-wide interventions designed to increase the implementation of thromboprophylaxis and decrease the incidence of VTE in hospitalized adult medical and surgical patients at risk for VTE, focusing on RCTs only.Our research librarian conducted a systematic literature search of MEDLINE Ovid, and subsequently translated it to CENTRAL, PubMed, Embase Ovid, BIOSIS Previews Ovid, CINAHL, Web of Science, the Database of Abstracts of Reviews of Effects (DARE; in the Cochrane Library), NHS Economic Evaluation Database (EED; in the Cochrane Library), LILACS, and clinicaltrials.gov from inception to 7 January 2017. We also screened reference lists of relevant review articles. We identified 12,920 potentially relevant records.We included all types of RCTs, with random or quasi-random methods of allocation of interventions, which either randomized individuals (e.g. parallel group, cross-over, or factorial design RCTs), or groups of individuals (cluster RCTs (CRTs)), which aimed to increase the use of prophylaxis or appropriate prophylaxis, or decrease the occurrence of VTE in hospitalized adult patients. We excluded observational studies, studies in which the intervention was simply distribution of published guidelines, and studies whose interventions were not clearly described. Studies could be in any language.We collected data on the following outcomes: the number of participants who received prophylaxis or appropriate prophylaxis (as defined by study authors), the occurrence of any VTE (symptomatic or asymptomatic), mortality, and safety outcomes, such as bleeding. We categorized the interventions into alerts (computer or human alerts), multifaceted interventions (combination of interventions that could include an alert component), educational interventions (e.g. grand rounds, courses), and preprinted orders (written predefined orders completed by the physician on paper or electronically). We meta-analyzed data across RCTs using a random-effects model. For CRTs, we pooled effect estimates (risk difference (RD) and risk ratio (RR), with 95% confidence interval (CI), adjusted for clustering, when possible. We pooled results if three or more trials were available for a particular intervention. We assessed the certainty of the evidence according to the GRADE approach.From the 12,920 records identified by our search, we included 13 RCTs (N = 35,997 participants) in our qualitative analysis and 11 RCTs (N = 33,207 participants) in our meta-analyses.Alerts were associated with an increase in the proportion of participants who received prophylaxis (RD 21%, 95% CI 15% to 27%; three studies; 5057 participants; I² = 75%; low-certainty evidence). The substantial statistical heterogeneity may be in part explained by patient types, type of hospital, and type of alert. Subgroup analyses were not feasible due to the small number of studies included in the meta-analysis.Multifaceted interventions were associated with a small increase in the proportion of participants who received prophylaxis (cluster-adjusted RD 4%, 95% CI 2% to 6%; five studies; 9198 participants; I² = 0%; moderate-certainty evidence). Multifaceted interventions with an alert component were found to be more effective than multifaceted interventions that did not include an alert, although there were not enough studies to conduct a pooled analysis.Alerts were associated with an increase in the proportion of participants who received appropriate prophylaxis (RD 16%, 95% CI 12% to 20%; three studies; 1820 participants; I² = 0; moderate-certainty evidence). Alerts were also associated with a reduction in the rate of symptomatic VTE at three months (RR 64%, 95% CI 47% to 86%; three studies; 5353 participants; I² = 15%; low-certainty evidence). Computer alerts were associated with a reduction in the rate of symptomatic VTE, although there were not enough studies to pool computer alerts and human alerts results separately.We reviewed RCTs that implemented a variety of system-wide strategies aimed at improving thromboprophylaxis in hospitalized patients. We found increased prescription of prophylaxis associated with alerts and multifaceted interventions, and increased prescription of appropriate prophylaxis associated with alerts. While multifaceted interventions were found to be less effective than alerts, a multifaceted intervention with an alert was more effective than one without an alert. Alerts, particularly computer alerts, were associated with a reduction in symptomatic VTE at three months, although there were not enough studies to pool computer alerts and human alerts results separately.Our analysis was underpowered to assess the effect on mortality and safety outcomes, such as bleeding.The incomplete reporting of relevant study design features did not allow complete assessment of the certainty of the evidence. However, the certainty of the evidence for improvement in outcomes was judged to be better than for our previous review (low- to moderate-certainty evidence, compared to very low-certainty evidence for most outcomes). The results of our updated review will help physicians, hospital administrators, and policy makers make practical decisions about adopting specific system-wide measures to improve prescription of thromboprophylaxis, and ultimately prevent VTE in hospitalized patients.

Since the inception of the Canadian Cardiovascular Society heart failure (HF) guidelines in 2006, much has changed in the care for patients with HF. Over the past decade, the HF Guidelines Committee has published regular updates. However, because of the major changes that have occurred, the Guidelines Committee believes that a comprehensive reassessment of the HF management recommendations is presently needed, with a view to producing a full and complete set of updated guidelines. The primary and secondary Canadian Cardiovascular Society HF panel members as well as external experts have reviewed clinically relevant literature to provide guidance for the practicing clinician. The 2017 HF guidelines provide updated guidance on the diagnosis and management (self-care, pharmacologic, nonpharmacologic, device, and referral) that should aid in day-to-day decisions for caring for patients with HF. Among specific issues covered are risk scores, the differences in management for HF with preserved vs reduced ejection fraction, exercise and rehabilitation, implantable devices, revascularization, right ventricular dysfunction, anemia, and iron deficiency, cardiorenal syndrome, sleep apnea, cardiomyopathies, HF in pregnancy, cardio-oncology, and myocarditis. We devoted attention to strategies and treatments to prevent HF, to the organization of HF care, comorbidity management, as well as practical issues around the timing of referral and follow-up care. Recognition and treatment of advanced HF is another important aspect of this update, including how to select advanced therapies as well as end of life considerations. Finally, we acknowledge the remaining gaps in evidence that need to be filled by future research.

Summary. Background: Few studies have evaluated the long-term economic consequences of deep vein thrombosis (DVT).None of them have incorporated prospectively collectedclinical data to ensure accurate identification of incident casesof DVT and DVT-related health outcomes of interest, such aspost-thrombotic syndrome (PTS). Objectives: To prospectivelyquantify medical and non-medical resource use and costsrelated to DVT during 2 years following diagnosis, and toidentify clinical determinants of costs. Methods: Three hun-dred and fifty-five consecutive patients with acute DVT wererecruited at seven Canadian hospital centers. Resource use andcost information were retrieved from three sources: weeklypatient-completed cost diaries, nurse-completed case reportforms, and the Quebec provincial administrative healthcaredatabase (RAMQ). Results: The rate of DVT-related hospi-talization was 3.5 per 100 patient-years (95% confidenceinterval [CI] 2.2–4.9). Patients reported a mean (standarddeviation) of 15.0 (14.5) physician visits and 0.7 (1.2) otherhealthcare professional visits. The average cost of DVT was$5180 (95% CI $4344–6017) in Canadian dollars, with 51.6%of costs being attributable to non-medical resource use.Multivariate analysis identified four independent predictorsof costs: concomitant pulmonary embolism (relative increasein cost [RIC] 3.16; 95% CI 2.18–4.58), unprovoked DVT(RIC 1.65; 95% CI 1.28–2.13), development of PTS duringfollow-up (RIC 1.35; 95% CI 1.05–1.74), and management ofDVT in the inpatient setting (RIC 1.79; 95% CI 1.33–2.40).Conclusions: The economic burden of DVT is substantial. Theuse of measures to prevent the occurrence of PTS andfavoring outpatient care of DVT has the potential to diminishcosts.Keywords: cohort study, cost determinants, deep vein throm-bosis, economic burden, post-thrombotic syndrome.IntroductionDeepveinthrombosis(DVT)isacommonandseriousvascularcondition[1].TheclinicalburdenofDVToftenextendsbeyondthe initial event, with increased risks of recurrent venousthromboembolism (VTE), bleeding while on anticoagulanttherapy, and development of the chronic post-thromboticsyndrome (PTS).Few studies have evaluated the long-term economic conse-quences of DVT. Studies to date have relied on retrospectiveadministrative claims database analysis [2–5] or Markovmodeling [6], and assessed medical costs only. Non-medicalcosts, including productivity losses that impact on patients,their families, and society, have not been adequately consid-ered. None has incorporated prospectively collected clinicaldata to ensure accurate identification of incident cases of DVTand DVT-related health outcomes of interest, such as PTS.We conducted a study to prospectively quantify medicaland non-medical costs associated with DVT during the

Antiplatelet agents are a cornerstone of therapy for patients with atherosclerotic vascular disease. There is presently a lack of comprehensive guidelines focusing on the use of antiplatelet drugs in patients currently manifesting or at elevated risk of cardiovascular disease. The Canadian Antiplatelet Therapy Guidelines Committee reviewed existing disease-based guidelines and subsequently published literature and used expert opinion and review to develop guidelines on the use of antiplatelet therapy in the outpatient setting. This full document has been summarized in an Executive Summary published in the Canadian Journal of Cardiology and may be found at http://www.ccs.ca/. Antiplatelet therapy appears to be generally underused, perhaps in part because of a lack of clear, evidence-based guidance. Here, we provide specific guidelines for secondary prevention in patients discharged from hospital following acute coronary syndromes, post–percutaneous coronary intervention, post–coronary artery bypass grafting, patients with a history of transient cerebral ischemic events or strokes, and patients with peripheral arterial disease. Issues related to primary prevention are also addressed, in addition to special clinical contexts such as diabetes, heart failure, chronic kidney disease, pregnancy/lactation, and perioperative management. Recommendations are provided regarding pharmacologic interactions that may occur during combination therapy with warfarin, clopidogrel and proton-pump inhibitors, or acetylsalicylic acid and nonsteroidal anti-inflammatory drugs, as well as for the management of bleeding complications.

Antiplatelet agents are a cornerstone of therapy for patients with atherosclerotic vascular disease. There is presently a lack of comprehensive guidelines focusing on the use of antiplatelet drugs in patients currently manifesting or at elevated risk of cardiovascular disease. The Canadian Antiplatelet Therapy Guidelines Committee reviewed existing disease-based guidelines and subsequently published literature and used expert opinion and review to develop guidelines on the use of antiplatelet therapy in the outpatient setting. This Executive Summary provides an abbreviated version of the principal recommendations. Antiplatelet therapy appears to be generally underused, perhaps in part because of a lack of clear, evidence-based guidance. Here, we provide specific guidelines for secondary prevention in patients discharged from hospital after acute coronary syndromes, percutaneous coronary intervention, or coronary artery bypass grafting; patients with a history of transient cerebral ischemic events or strokes; and patients with peripheral arterial disease. Issues related to primary prevention are also addressed, in addition to special clinical contexts such as diabetes, heart failure, chronic kidney disease, pregnancy or lactation, and perioperative management. Recommendations are provided regarding pharmacologic interactions that may occur during combination therapy with warfarin, clopidogrel, and proton-pump inhibitors, or aspirin and nonsteroidal anti-inflammatory drugs, as well as for the management of bleeding complications. The complete guidelines document is published as a supplementary issue of the Canadian Journal of Cardiology and is available at http://www.ccs.ca/.

Summary. Background/objectives: We prospectively measured change in quality of life (QOL) during the 2 years after a diagnosis of deep vein thrombosis (DVT) and evaluated determinants of QOL, including development of the post-thrombotic syndrome (PTS). Patients/methods: Consecutive patients with acute DVT were recruited from 2001 to 2004 at eight hospitals in Canada. At study visits at baseline, and 1, 4, 8, 12 and 24 months, clinical data were collected, standardized PTS assessments were performed, and QOL questionnaires were self-completed. Generic QOL was measured using the Short-Form Health Survey-36 (SF-36) questionnaire. Venous disease-specific QOL was measured using the Venous Insufficiency Epidemiological and Economic Study (VEINES)-QOL/Sym questionnaire. The change in QOL scores over a 2-year follow-up was assessed. The influence of PTS and other characteristics on QOL at 2 years was evaluated using multivariable regression analyses. Results: Among the 387 patients recruited, the average age was 56 years, two-thirds were outpatients, and 60% had proximal DVT. The cumulative incidence of PTS was 47%. On average, QOL scores improved during follow-up. However, patients who developed PTS had lower scores at all visits and significantly less improvement in QOL over time (P-values for PTS*time interaction were 0.001, 0.012, 0.014 and 0.006 for PCS, MCS, VEINES-QOL and VEINES-Sym). Multivariable regression analyses showed that PTS (P

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in hospitalized patients. Numerous randomized controlled trials (RCTs) show that using thromboprophylaxis in hospitalized patients at risk for VTE is safe, effective and cost-effective. Despite this, prophylactic therapies for VTE are underutilized. System-wide interventions may be more effective to improve the use of VTE prophylaxis than relying on individual providers' prescribing behaviors.To assess the effects of interventions designed to increase the implementation of thromboprophylaxis in hospitalized adult medical and surgical patients at risk for venous thromboembolism (VTE), assessed in terms of: 1. Increase in the proportion of patients who receive prophylaxis and appropriate prophylaxis 2. Reduction in risk of symptomatic VTE3. Reduction in risk of asymptomatic VTE4. Safety of the intervention.The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator (TSC) searched the Group's Specialised Register (last searched July 2010) and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library) 2010, Issue 3. We searched the PubMed, EMBASE, and SCOPUS databases (19 April 2010) as well as the reference lists of relevant review articles.We included all studies whose interventions aimed to increase the use of prophylaxis and/or appropriate prophylaxis, decrease the proportion of symptomatic VTE, or decrease the proportion of asymptomatic VTE in hospitalized adult patients. We excluded studies that simply distributed published guidelines and studies whose interventions were not clearly described.We collected the following outcomes: the proportion of patients who received prophylaxis (RP), the proportion of patients who received appropriate prophylaxis (RAP) (primary outcomes), and the occurrence of symptomatic VTE, asymptomatic VTE, and safety outcomes such as bleeding. We categorized interventions into education, alerts, and multifaceted interventions. We meta-analyzed RCTs and non-randomized studies (NRS) separately by random effects meta-analysis, and assessed heterogeneity using the I(2)statistic and subgroup analyses. Before analysis, we decided that results would be pooled if three or more studies were available for a particular intervention. We assessed publication bias using funnel plots and cumulative meta-analysis.We included a total of 55 studies. One of these reported data in patient-days and could not be quantitatively analyzed with the others. The 54 remaining studies (8 RCTs and 46 NRS) eligible for inclusion in our quantitative synthesis enrolled a total of 78,343 participants. Among RCTs, there were sufficient data to pool results for one primary outcome (received prophylaxis) for the 'alert' intervention. Alerts, such as computerized reminders or stickers on patients' charts, were associated with a risk difference (RD) of 13%, signifying an increase in the proportion of patients who received prophylaxis (95% confidence interval (CI) 1% to 25%). Among NRS, there were sufficient data to pool both primary outcomes for each intervention type. Pooled risk differences for received prophylaxis ranged from 8% to 17%, and for received appropriate prophylaxis ranged from 11% to 19%. Education and alerts were associated with statistically significant increases in prescription of appropriate prophylaxis, and multifaceted interventions were associated with statistically significant increases in prescription of any prophylaxis and appropriate prophylaxis. Multifaceted interventions had the largest pooled effects. I(2) results showed substantial statistical heterogeneity which was in part explained by patient types and type of hospital. A subgroup analysis showed that multifaceted interventions which included an alert may be more effective at improving rates of prophylaxis and appropriate prophylaxis than those without an alert. Results for VTE and safety outcomes did not show substantial benefits or harms, although most studies were underpowered to assess these outcomes.We reviewed a large number of studies which implemented a variety of system-wide strategies aimed to improve thromboprophylaxis rates in many settings and patient populations. We found statistically significant improvements in prescription of prophylaxis associated with alerts (RCTs) and multifaceted interventions (RCTs and NRS), and improvements in prescription of appropriate prophylaxis in NRS with the use of education, alerts and multifaceted interventions. Multifaceted interventions with an alert component may be the most effective. Demonstrated sources of heterogeneity included patient types and type of hospital. The results of our review will help physicians, nurses, pharmacists, hospital administrators and policy makers make practical decisions about local adoption of specific system-wide measures to improve prevention of VTE, an important public health issue. We did not find a significant benefit for VTE outcomes; however, earlier RCTs assessing the efficacy of thromboprophylaxis which were powered to address these outcomes have demonstrated the benefit of prophylactic therapies and a favourable balance of benefits versus the increased risk of bleeding events.

The initial 2010 Canadian Cardiovascular Society (CCS) Guidelines for the Use of Antiplatelet Therapy in the Outpatient Setting were published in May 2011. As part of a planned re-evaluation within 2 years, we conducted an extensive literature search encompassing all topics included in the 2010 CCS Guidelines, and concluded that there were sufficient new data to merit revisiting the guidance on antiplatelet therapy for secondary prevention in the first year after acute coronary syndrome (ACS), percutaneous coronary intervention, or coronary artery bypass grafting, and the interaction between clopidogrel and proton pump inhibitors. In addition, new clinical trials information about the efficacy and safety of combining novel oral anticoagulants with antiplatelet therapy in ACS justified the addition of a new section of recommendations to the Guidelines. In this focused update, we provide recommendations for the use of clopidogrel, ticagrelor, and prasugrel in non-ST elevation ACS, avoidance of prasugrel in patients with previous stroke/transient ischemic attack, higher doses of clopidogrel (j) /day) for the first 6 days after ACS, and the preferential use of prasugrel or ticagrelor after percutaneous coronary intervention in ACS. For non-ACS stented patients, we recommend acetylsalicylic acid/clopidogrel for 1 year, with at least 1 month of therapy for bare-metal stent patients and 3 months for drug-eluting stent patients unable to tolerate year-long double therapy. We also consider therapy for patients with a history of stent thrombosis, the indications for longer-term treatment, discontinuation timing preoperatively, indications for changing agents, the management of antiplatelet therapy before and after bypass surgery, and use/selection of proton pump inhibitors along with antiplatelet agents.

Summary. Background: The pathophysiology of post-thrombotic syndrome (PTS) is postulated to involve persistent venous obstruction and venous valvular reflux. Objective: To study the association between D-dimer level, valvular reflux and the PTS in a well-defined cohort of deep vein thrombosis (DVT) patients. Methods: Consecutive patients with acute symptomatic DVT were recruited at eight centers and were followed for 24 months. D-dimer was measured at 4 months. A standardized ultrasound assessment for popliteal valvular reflux was performed at 12 months. Using the Villalta scale, patients were assessed for PTS during follow-up by evaluators who were unaware of D-dimer or reflux results. Results: Three hundred and eighty-seven patients were recruited; of these, 305 provided blood samples for D-dimer and 233 had a 12-month reflux assessment. PTS developed in 45.1% of subjects. Mean D-dimer was significantly higher in patients with vs. without PTS (712.0 vs. 444.0 μg L−1; P = 0.02). In logistic regression analyses adjusted for warfarin use at the time of D-dimer determination and risk factors for PTS, D-dimer level significantly predicted PTS (P = 0.03); when stratifying for warfarin use at the time of blood draw, adjusted odds ratio (OR) for developing PTS per unit difference in log D-dimer was 2.33 (95% CI 0.89, 6.10) in those not on warfarin vs. 1.25 (95% CI 0.87, 1.79) in those on warfarin. Ipsilateral reflux was more frequent in patients with moderate-to-severe PTS than in patients with mild PTS (65% vs. 40%, respectively; P = 0.01) and was independently associated with moderate-to-severe PTS in logistic regression analyses (P = 0.01). Conclusion: D-dimer levels, measured 4 months after DVT in patients not on warfarin, are associated with subsequent development of PTS. Venous valvular reflux is associated with moderate-to-severe PTS.

This Consensus Conference has been supported by the Canadian Cardiovascular Society. The process is dynamic, with intentional structure that requires peer review and feedback from cardiovascular specialists across Canada. The writing and review panel encompassed a broad range of specialists caring for the patient with peripheral arterial disease (PAD). PAD is an often asymptomatic, underdiagnosed, under-recognized and undertreated condition. It is associated with significant morbidity and cardiac mortality. Until recently, little attention has focused on the evaluation and treatment of the disease process itself. The goal of the present paper is to ensure better treatment, to reduce both morbidity and mortality in the patient with vascular disease and, importantly, to serve as a guide to the busy clinician. Although the focus is PAD, there are chapters on thoracic and abdominal aortic disease, renal arterial disease and the evidence supporting management. Screening and diagnostic techniques including history and physical examination as well as noninvasive imaging techniques are reviewed. Medical management for patients with vascular disease including prevention and risk reduction is graded based on evidence, including both pharmacological and nonpharmacological management strategies, followed by an introduction to newer percutaneous techniques. Finally, surgical treatment for claudication including new concepts on the perioperative risk assessment for patients undergoing major vascular surgery is discussed.

Background:Toourknowledge,theburdenofdeepvenous thrombosis from the patient’s perspective has not been quantified. We evaluated health-related quality of life (QOL) after deep vein thrombosis and compared results with general population norms. Methods: This was a multicenter prospective cohort study of 359 consecutive eligible patients with deep vein thrombosisrecruitedat7Canadianhospitalcenters.Quality of life was assessed at baseline and at 1 and 4 months afterdiagnosisusinggeneric(36-ItemShort-FormHealth Survey) and disease-specific (Venous Insufficiency Epidemiological and Economic Study [VEINES]–QOL and VEINES symptom [VEINES-Sym] questionnaires) measures. Changes in QOL scores during the 4-month period were calculated, and determinants of lack of improvement in QOL were evaluated. Results: During the 4 months, mean 36-Item ShortFormHealthSurveyphysicalandmentalcomponentsummary scores improved by 5.1 and 4.6 points, respectively, and VEINES-QOL and VEINES-Sym scores improved by 3.1 and 2.2 points, respectively (P.001 fortimetrendforallmeasures).However,aboutonethird ofpatientshadworseningofQOLduringfollow-up.Multivariate analyses showed that worsening of the postthrombotic syndrome score was an independent predictor of worsening of 36-Item Short-Form Health Survey physical component summary (P=.04), VEINES-QOL (P.001), and VEINES-Sym (P.001) scores. The 36ItemShort-FormHealthSurveyphysicalcomponentsummary scores were lower than population norms at all points assessed. Conclusions: On average, QOL improves during the 4 months following deep vein thrombosis. However, in about one third of patients, QOL deteriorates, and at 4 months, average QOL remains poorer than population norms.Worseningofthepostthromboticsyndromescore is associated with worsening of QOL. Arch Intern Med. 2005;165:1173-1178

Abstract 676 Introduction: Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in hospitalized patients. Numerous randomized clinical trials (RCTs) show that the use of thromboprophylaxis in hospitalized patients at risk for VTE is safe, effective and cost-effective. Despite this, prophylactic therapies for VTE are underutilized. System-wide interventions may be more effective to improve the use of VTE prophylaxis than relying on individual providers' prescribing behaviors. Objectives: In this review, we aimed to determine the effectiveness of various system-wide interventions designed to increase the use of thromboprophylaxis in hospitalized medical and surgical patients at risk for VTE. Methods: We searched MEDLINE, EMBASE, and SCOPUS databases to identify studies that assessed an intervention designed to increase use of prophylaxis and/or decrease incidence of VTE. Extracted data included study design, setting, intervention, and outcomes including proportions receiving prophylaxis (RP) and receiving appropriate prophylaxis (RAP). Risk of bias was assessed using Cochrane guidelines. We performed meta-analysis for RCTs and non-randomized studies (NRS) separately. We categorized the interventions into three groups: education (e.g. grand rounds, self-administered course), alerts (e.g. electronic, human), and multifaceted interventions (e.g. combination of education, audit and feedback and alert). We performed a random effects meta-analysis and assessed heterogeneity using the I2 statistic. Results were pooled if three or more studies were available for a particular intervention group. Results: Out of 1802 records included in our primary screen of titles and abstracts, 79 studies were assessed for eligibility. Fifty-six studies were included in our systematic review, including eight RCTs (N=17,601) and 48 NRS (N=62,770). Among the RCTS, 4 studies included medical patients, 2 included medical and surgical patients, 1 included post-acute care patients and 1 did not report the types of patients included. The NRS were primarily before-and-after design. Fourteen included surgical patients, 10 included medical patients, 10 included medical and surgical patients, 8 included patients from other departments and 6 did not report the types of patients included. Our primary outcomes included received prophylaxis (RP) and received appropriate prophylaxis (RAP). Among the RCTs, there was sufficient data to pool one outcome (RP) for one intervention type (alert). Among the NRS, there was sufficient data to pool two outcomes (RP, RAP) for each intervention type (education, alert, multifaceted). I2 results showed substantial statistical heterogeneity among studies. A sensitivity analysis showed that multifaceted interventions which included an alert were more effective at improving rates of RP and RAP than those without an alert. Conclusions: We reviewed a large number of studies which implemented a variety of system-wide strategies aimed to improve thromboprophylaxis rates in many settings and patient populations. We found statistically significant improvements in prescription of prophylaxis associated with alerts and multifaceted interventions, and improvements in prescription of appropriate prophylaxis with the use of education, alerts or multifaceted interventions. Multifaceted interventions with an alert component seem to be the most effective. We chose to pool effect estimates despite significant heterogeneity because the results were generally in the same direction but of different magnitudes. We are continuing to investigate sources of heterogeneity including patient population, setting, baseline prophylaxis rates, and intervention characteristics. The results of our review will help physicians, hospital administrators and policy makers make practical decisions about adoption of specific system-wide measures to improve prevention of VTE. Funded by Canadian Institutes for Health Research Disclosures: Kahn: sanofi aventis: Honoraria, Research Funding; Leo Pharma: Honoraria.

Abstract 566 Background and objectives: Deep venous thrombosis (DVT) is a common and serious vascular condition that is frequently complicated by the chronic post-thrombotic syndrome. Costs of DVT may occur over a long period and may be medical and non-medical in nature. During a Canadian multicenter cohort study of the long-term outcomes after DVT (The Venous Thrombosis Outcomes [VETO] Study), we prospectively quantified resource use and costs related to DVT during two years after DVT diagnosis, and identified clinical determinants of costs. Methods: The study population consisted of 355 consecutive patients diagnosed with objectively confirmed acute DVT at one of 7 participating hospitals in the province of Quebec, Canada. Using a societal perspective, we tracked total medical resource use (hospitalizations, physician visits, other health professional visits, medications, ambulance services, stockings, assistive devices) and non-medical resource use (loss of productivity, home care, transportation) incurred by DVT during the 2 years after diagnosis. Data sources included weekly patient-completed cost diaries, nurse-completed case report forms (baseline, 1, 4, 8, 12, 24 months and at any DVT-related clinical event) and the Quebec provincial administrative healthcare database (“RAMQ”). Resources for each patient were valued using individual patient level information obtained from RAMQ and patient diaries. Statistics Canada data, provincial health professionals associations and local suppliers were used to estimate resource costs if individual information was not available. The value of lost productivity was estimated using a friction-cost approach. Multivariate regression modeling for predictors of medical costs during 2 years included baseline demographic and clinical characteristics as well as the development of post-thrombotic syndrome (PTS) during study follow-up. Results: At study entry, mean age was 56.5 years, 50.1% were male, 2/3 were out-patients and 58.0% had proximal DVT. The mean duration of heparin and warfarin treatment was 7.6 days (SD 6.0) and 21.6 weeks (SD 10.0), respectively. During 2 years follow-up, the rate of DVT-related hospitalization was 3.5 per 100 patient-years (95% CI 2.2, 4.9). Patients reported, on average, 15.0 (SD 14.5) physician visits and 0.7 (SD 1.2) non-physician visits. Patients required 12.7 (SD 9.2) transportations, 38.6 (SD 138.0) hours of assistance and missed 12.1 (SD 39.8) workdays. The average per-patient total cost over 2 years was Can$4109 (95% CI $3658, $4561) with 63.7% of costs attributable to non-medical resource use. The two largest medical cost components were hospitalizations (Can$502; 95% CI $261, $744) and physician visits (Can$356; 95% CI $320, $392). More than two-thirds of all resource consumption occurred during the first 4 months after diagnosis. In multivariate analysis focusing on determinants of medical costs, concomitant pulmonary embolism (p = 0.002), idiopathic DVT (p= 0.003), and development of post-thrombotic syndrome during follow-up (p= 0.002) were independently associated with increased costs. Conclusion: The economic burden of DVT over the two years following initial diagnosis is substantial with almost two-thirds of costs attributable to non-medical resource use. Concomitant pulmonary embolism, idiopathic DVT, and development of PTS are important predictors of medical costs after DVT. Better adherence to thromboprophylaxis strategies and use of measures to prevent occurrence of PTS have the potential to diminish costs and resource utilization related to DVT. Disclosures: No relevant conflicts of interest to declare.

The authors used nailfold capillary microscopy (NCM) to evaluate 112 pa tients with systemic sclerosis spectrum disorders (SSc). Patients were classified as S1 if they had skin involvement proximal to the metacarpo-phalangeal joints. S2 if they had at least two minor SSc American Rheumatism Association criteria, and S3 if they had at least two CREST criteria (calcinosis, Raynaud's, esophageal motility disorder, sclerodactyly, telangiectases), without S1 or S2 criteria. Dis ease duration from the first symptom was similar in all groups (7.17 ± 8.98 years). Disease severity was determined by a total score of seven target organ involve ments. S1 patients had a greater degree of skin and pulmonary involvement, with a mean score of 26.2 ± 17.3. S2 patients had a mean score of 13.8 ± 12.4, and had mostly vascular and digestive involvement, in comparison with S3 patients (7.2 ± 7.2; pNCM sensitivity for S1 and S2 was 93.6%. NCM correlated with the degree of target organ involvement (p < 0.01). Three NCM profiles established were: "mild," normal or borderline capillaries; "moderate," other abnormalities with no capillary telangiectases; and "severe," abnormalities other than those of the mild profile, with capillary telangiectases.The positive correlation observed between the degree of skin and vascular abnormalities and the severity of digestive, renal, musculoskeletal, and pulmo nary involvement permits rapid prediction of target organ involvement by SSc at the first visit.

Seventy-seven patients with Raynaud's disease were studied for a mean of 4 years (range 1-11 years) to determine the relationship between autoantibodies and long-term clinical outcome. Anticentromere antibodies (ACA) were assayed by indirect immunofluorescence and by immunoblotting of HeLa cell chromosome extracts. Antibodies to topoisomerase I (anti-topo I) were assayed by immunodiffusion and immunoblotting. Antibodies to the major centromeric protein, CENP-B, and anti-topo I were studied by enzyme-linked immunosorbent assay (ELISA). Eight patients developed telangiectasias, 4 developed skin tightening, and 4 developed a connective tissue disease other than scleroderma. The presence of ACA at the start of the study was associated with the development of telangiectasias (P less than 0.003). An initial 100-kd band on immunoblot in conjunction with a positive anti-topo I ELISA result was associated with the development of tight skin (P less than 0.0025), while a 100-kd band with a negative anti-topo I ELISA result was associated with the subsequent development of a connective tissue disease other than scleroderma (P less than 0.0073). Patients who were initially ACA positive, had the 100-kd band on immunoblot, or had positive ELISA results for anti-topo I or for anti-CENP-B were 63-fold more likely to develop signs of connective tissue disease by the end of the study (P less than 0.000009). The presence of any of these autoantibodies was more sensitive (100%), although less specific (75%), than were findings from nailfold capillaroscopy (sensitivity 67% and specificity 95%) in predicting subsequent clinical progression. We conclude that findings of assays for anti-topo I and ACA complement the findings from nailfold capillaroscopy in providing useful prognostic information in Raynaud's disease.

The reason some patients with deep venous thrombosis (DVT) develop the postthrombotic syndrome is not well understood.To determine the frequency, time course, and predictors of the postthrombotic syndrome after acute DVT.Prospective, multicenter cohort study.8 Canadian hospital centers.387 outpatients and inpatients who received an objective diagnosis of acute symptomatic DVT were recruited from 2001 to 2004.Standardized assessments for the postthrombotic syndrome using the Villalta scale at 1, 4, 8, 12, and 24 months after enrollment. Mean postthrombotic score and severity category at each interval was calculated. Predictors of postthrombotic score profiles over time since diagnosis of DVT were identified by using linear mixed modeling.At all study intervals, about 30% of patients had mild (score, 5 to 9), 10% had moderate (score, 10 to 14), and 3% had severe (score14 or ulcer) postthrombotic syndrome. Greater postthrombotic severity category at the 1-month visit strongly predicted higher mean postthrombotic scores throughout 24 months of follow-up (1.97, 5.03, and 7.00 increase in Villalta score for mild, moderate, and severe 1-month severity categories, respectively, vs. none; P0.001). Additional predictors of higher scores over time were venous thrombosis of the common femoral or iliac vein (2.23 increase in score vs. distal [calf] venous thrombosis; P0.001), higher body mass index (0.14 increase in score per kg/m(2); P0.001), previous ipsilateral venous thrombosis (1.78 increase in score; P = 0.001), older age (0.30 increase in score per 10-year age increase; P = 0.011), and female sex (0.79 increase in score; P = 0.020).Decisions to prescribe compression stockings were left to treating physicians rather than by protocol. Because international normalized ratio data were unavailable, the relationship between anticoagulation quality and Villalta scores could not be assessed.The postthrombotic syndrome occurs frequently after DVT. Patients with extensive DVT and those with more severe postthrombotic manifestations 1 month after DVT have poorer long-term outcomes.

OBJECTIVE: To assess the validity of VEINES-QOL/Sym, a patient-reported questionnaire to evaluate quality of life and symptoms in patients with deep venous thrombosis (DVT). STUDY DESIGN AND SETTING: Psychometric study within the Venous Thrombosis Outcomes (VETO) Study, a prospective cohort study of long-term outcomes after DVT. A total of 359 English- and French-speaking patients with acute, objectively diagnosed DVT were recruited at seven hospitals in Quebec, Canada. The VEINES-QOL/Sym questionnaire, a 26-item patient-reported measure that generates separate summary scores for symptoms (VEINES-Sym) and quality of life (VEINES-QOL) was evaluated for acceptability, reliability, validity, and responsiveness in VETO Study subjects. RESULTS: Standard psychometric tests confirmed the acceptability (missing data, item endorsement frequencies, floor and ceiling effects), reliability (internal consistency, item-total and inter-item correlations, test-retest), validity (content, construct, convergent, discriminant, known groups), and responsiveness to clinical change of the VEINES-QOL/Sym in patients with DVT. CONCLUSION: The VEINES-QOL/Sym is a practical and scientifically sound patient-reported measure of outcomes that was developed using gold-standard methods. VEINES-QOL/Sym is valid and reliable for use as a measure of quality of life and symptoms in patients with acute DVT and provides a rigorous tool to allow more comprehensive evaluation of outcomes in clinical trials and epidemiological studies of patients with DVT.

Background and Objectives: It is not understood why some patients develop post thrombotic syndrome (PTS) after DVT while others recover without sequelae. We performed a prospective, multicenter study of long-term outcomes after DVT (the Venous Thrombosis Outcomes [VETO] Study) whose principal aim was to identify predictors of PTS. Methods: From 2001–2002, consecutive patients with objectively diagnosed DVT were recruited at 7 hospital centres. During study visits at Baseline, 1, 4, 8, 12 and 24 months, clinical data were collected, thrombophilia testing was performed and standardized assessments for PTS (using Villalta scale) were carried out by trained personnel. Patients were classified as having developed PTS if the ipsilateral Villalta score was ≥5 on at least 2 visits or at the final follow-up visit, and severe PTS if a score of >14 or a venous ulcer was documented on any one occasion. The influence of clinical, demographic, ergonomic and biological determinants on the risk of developing PTS was evaluated in bivariate and multivariate analyses. Results: 359 patients were recruited; 49% were male, mean age was 56 years, 2/3 were outpatients and 55% had proximal DVT. The cumulative risk of PTS was 37%, of which 1 in 6 cases was severe. Patients who developed PTS, compared with those who did not, were more likely to be older (p=.005), have had previous episode(s) of DVT (p=.0003), have atherosclerosis risk factors [hypertension (p=.0002), high cholesterol (p=.02)], higher BMI (p=0.0007), longer duration of symptoms before DVT diagnosis (p=.049) and work in a job with high physical demands (p=.05), and they were less likely to have the Prothrombin gene mutation (p=0.03). Variables of interest that did not influence the risk of PTS included: sex, location of DVT (proximal vs. distal), side of DVT (left vs. right), type of DVT (cancer-related, temporary risk factors [e.g. surgery, trauma] or idiopathic), initial anticoagulation with LMWH vs. UFH, duration of warfarin, Factor V Leiden mutation or prior ipsilateral musculoskeletal condition. In adjusted multivariate analyses, BMI (odds ratio [OR] 2.1 for BMI >30 vs. < 30, 95% confidence interval [CI] 1.1, 4.2), previous DVT (OR 2.6, 95% CI 1.4, 4.9) and hypertension (OR 1.9, 95% CI 1.04, 3.6) were independently associated with PTS. Conclusions: In our cohort, high BMI, previous history of DVT and hypertension were independent predictors of PTS, whereas presenting characteristics of the index DVT and its treatment did not influence the risk of developing PTS.

Background and Objectives: The post thrombotic syndrome (PTS) is a chronic complication of deep venous thrombosis (DVT). It is difficult to provide DVT patients with long-term prognostic information as there is little longitudinal data on the occurrence of PTS after DVT. We performed a prospective multicenter study of long-term outcomes after DVT (the Venous Thrombosis Outcomes [VETO] Study) to determine the incidence, timing of onset and severity of PTS. Methods: Consecutive patients with objectively diagnosed acute DVT were recruited at 7 participating hospital centres from April 2001-July 2002. Patients attended study visits at Baseline, 4, 8, 12 and 24 months. Clinical data were recorded and standardized assessments for PTS (using Villalta scale) were performed by trained study personnel at each follow-up visit. Patients were classified as having developed PTS if the ipsilateral Villalta score was ≥ 5 on at least 2 visits or at the final follow-up visit, and having severe PTS if a score of >14 or a venous ulcer was documented on any one occasion. The Kaplan-Meier survival method was used to estimate the cumulative probability of PTS and of severe PTS over time. Results: The study cohort consisted of 359 patients. The mean age was 56 years, 50% were male, 2/3 were outpatients, 55% had proximal DVT and 20% had previous DVT. The Kaplan-Meier estimates of cumulative risk of PTS were 29% at 4 months, 33% at 8 months, 35% at 12 months and 37% at 24 months. Corresponding risks of severe PTS were 6.6%, 6.9%, 6.9% and 6.9%, respectively. When the analysis was stratified according to history of DVT, the cumulative incidence of PTS in patients without previous DVT was 25%, 28%, 30% and 31% at 4, 8, 12 and 24 months. Corresponding rates of PTS in patients with previous DVT were 45%, 51%, 53% and 57%. Conclusions: More than one third of patients in our cohort developed PTS within 2 years of DVT, and of these, 1 in 6 was classified as severe. Most cases of PTS and of severe PTS were apparent by 4 months after DVT. Patients with previous DVT had a higher frequency of PTS and of late onset PTS. Our study provides longitudinal data on prognosis that is relevant both to patients with DVT and their treating physicians.

Objectives: To assess the validity and reliability of VEINES-QOL/Sym, a patient-reported questionnaire, for the evaluation of quality of life and symptoms in patients with deep venous thrombosis. Study design: Psychometric study within the Venous Thrombosis Outcomes (VETO) Study, a Canadian multicenter prospective cohort study of long term outcomes after venous thrombosis. Subjects: 359 English and French-speaking patients with deep vein thrombosis consecutively recruited at seven hospitals in the province of Quebec, Canada. Outcome measures: The 26-item VEINES-QOL/Sym is a patient-reported questionnaire that we originally developed and validated for use in patients with chronic venous disorders of the leg (J Vasc Surg 2003). VEINES-QOL/Sym generates separate summary scores for symptoms and quality of life. We performed a comprehensive psychometric evaluation of the acceptability, reliability, validity and responsiveness of VEINES-QOL/Sym in the VETO study population, all of whom had objectively diagnosed symptomatic deep venous thrombosis (mean age 56 years; 50% male; 67% outpatients; 55% proximal DVT). Results: Criterion-standard psychometric tests confirmed the acceptability (missing data, item endorsement frequencies, floor and ceiling effects), reliability (internal consistency, item-total and inter-item correlations, test-retest), validity (content, construct, convergent, discriminant, known groups) and responsiveness to clinical change of the VEINES-QOL/Sym. Conclusions: Our results indicate that VEINES-QOL/Sym is a practical, valid and reliable measure of quality of life and symptoms in patients with deep venous thrombosis. VEINES-QOL/Sym provides a rigorous tool to allow more comprehensive evaluation of patient outcomes in clinical trials and epidemiological studies of patients with deep venous thrombosis.

Background and Objectives: The long term effects of deep venous thrombosis (DVT) on health-related quality of life (QOL) have not been prospectively evaluated. During a Canadian multicentre cohort study of health and economic outcomes after DVT (the Venous Thrombosis Outcomes [VETO] Study), we measured QOL during the 2 years after DVT and evaluated the influence of development of post-thrombotic syndrome (PTS) and other determinants on QOL. Methods: Consecutive patients diagnosed with acute DVT at seven participating hospital centres were recruited from April 2001-July 2002. During study visits at Baseline, 1, 4, 8, 12 and 24 months, clinical data were collected, a standardized assessment for PTS was performed and QOL questionnaires were self-completed. Generic QOL was measured using the SF-36 Health Survey questionnaire. Venous disease-specific QOL was measured using the VEINES-QOL questionnaire. For both questionnaires, lower scores indicate poorer QOL. Mean QOL at each time point and change in QOL scores over 24 months follow-up were quantified. The influence of PTS and other clinical or demographic characteristics on QOL was evaluated using multivariate regression analyses. Results: Of the 359 patients recruited, 49% were male, average age was 56 years, 2/3 were outpatients and 55% had proximal DVT. The cumulative incidence of PTS during follow-up was 37%. On average, QOL scores in the cohort improved during follow-up (mean improvement from Baseline to 24 months: 7.2 points for SF-36 mental component summary (MCS), 7.5 points for SF-36 physical component summary (PCS) and 4.7 points for VEINES-QOL). Patients who developed PTS, compared with those who did not, had significantly lower PCS scores and VEINES-QOL scores at all 5 follow-up visits (differences for PTS vs. no PTS ranged from 2.4-9.0 points for PCS and from 4.5-6.0 points for VEINES-QOL), and significantly lower MCS scores at the 1, 4, 8 and 12 month visits (differences ranged from 3.7–4.7 points). Multivariate regression analyses adjusted for age, sex and comorbidity showed that PTS and proximal (vs. distal) location of initial DVT were strong independent predictors of lack of improvement of PCS scores (p=.003 and .02, respectively) and VEINES-QOL scores (p=.006 and .009, respectively) during follow-up, but not of MCS scores (p=0.054 and 0.86, respectively). Variables such as body mass index, concurrent pulmonary embolism at time of DVT diagnosis and previous history of DVT did not influence change in scores for any QOL measure. Conclusions: The principal determinants of quality of life after DVT are development of PTS and proximal (vs. distal) location of initial DVT. Our study provides valuable prognostic information on health outcomes after DVT.