[Show abstract][Hide abstract] ABSTRACT: Few studies have evaluated the long-term economic consequences of deep vein thrombosis (DVT). None of them have incorporated prospectively collected clinical data to ensure accurate identification of incident cases of DVT and DVT-related health outcomes of interest, such as post-thrombotic syndrome (PTS).
To prospectively quantify medical and non-medical resource use and costs related to DVT during 2 years following diagnosis, and to identify clinical determinants of costs.
Three hundred and fifty-five consecutive patients with acute DVT were recruited at seven Canadian hospital centers. Resource use and cost information were retrieved from three sources: weekly patient-completed cost diaries, nurse-completed case report forms, and the Quebec provincial administrative healthcare database (RAMQ).
The rate of DVT-related hospitalization was 3.5 per 100 patient-years (95% confidence interval [CI] 2.2-4.9). Patients reported a mean (standard deviation) of 15.0 (14.5) physician visits and 0.7 (1.2) other healthcare 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 predictors of costs: concomitant pulmonary embolism (relative increase in cost [RIC] 3.16; 95% CI 2.18-4.58), unprovoked DVT (RIC 1.65; 95% CI 1.28-2.13), development of PTS during follow-up (RIC 1.35; 95% CI 1.05-1.74), and management of DVT in the inpatient setting (RIC 1.79; 95% CI 1.33-2.40).
The economic burden of DVT is substantial. The use of measures to prevent the occurrence of PTS and favoring outpatient care of DVT has the potential to diminish costs.
Journal of Thrombosis and Haemostasis 09/2011; 9(12):2397-405. · 6.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The pathophysiology of post-thrombotic syndrome (PTS) is postulated to involve persistent venous obstruction and venous valvular reflux.
To study the association between D-dimer level, valvular reflux and the PTS in a well-defined cohort of deep vein thrombosis (DVT) patients.
Consecutive patients with acute symptomatic DVT were recruited at eight centers and were followed for 24months. D-dimer was measured at 4months. A standardized ultrasound assessment for popliteal valvular reflux was performed at 12months. 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. 444.0μgL(-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).
D-dimer levels, measured 4months after DVT in patients not on warfarin, are associated with subsequent development of PTS. Venous valvular reflux is associated with moderate-to-severe PTS.
Journal of Thrombosis and Haemostasis 10/2010; 8(10):2169-75. · 6.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To identify in patients with Raynaud's phenomenon (RP) independent markers that predict progression to definite systemic sclerosis (SSc) and to determine in patients with progression to SSc the type and sequence of microvascular damage and its relationship to SSc-specific autoantibodies.
Consecutive patients referred for evaluation of RP who had no definite connective tissue disease were evaluated for microvascular damage by nailfold capillary microscopy (NCM) and for anticentromere (anti-CENP-B), anti-Th/To, anti-topoisomerase I, and anti-RNA polymerase III (anti-RNAP III) autoantibodies by specific assays. Patients were studied prospectively.
Of the 586 patients who were followed up for 3,197 person-years, 74 (12.6%) developed definite SSc. A characteristic sequence of microvascular damage was identified, starting with enlarged capillaries, followed by capillary loss, and then by capillary telangiectases. Definite SSc was diagnosed in close temporal relationship to capillary loss. Enlarged capillaries, capillary loss, and SSc-specific autoantibodies independently predicted definite SSc. Anti-CENP-B and anti-Th/To antibodies predicted enlarged capillaries; these autoantibodies and anti-RNAP III predicted capillary loss. Each autoantibody was associated with a distinct time course of microvascular damage. At followup, 79.5% of patients with 1 of these autoantibodies and abnormal findings on NCM at baseline had developed definite SSc. Patients with both baseline predictors were 60 times more likely to develop definite SSc. The data validated the proposed criteria for early SSc.
In RP evolving to definite SSc, microvascular damage is dynamic and sequential, while SSc-specific autoantibodies are associated with the course and type of capillary abnormalities. Abnormal findings on NCM at baseline together with an SSc-specific autoantibody indicate a very high probability of developing definite SSc, whereas their absence rules out this outcome.
[Show abstract][Hide abstract] ABSTRACT: 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 (score >14 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; P < 0.001). 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; P < 0.001), higher body mass index (0.14 increase in score per kg/m(2); P < 0.001), 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.
Annals of internal medicine 11/2008; 149(10):698-707. · 13.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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).
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.
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 < 0.0001), age (P = 0.0009), proximal DVT (P = 0.01) and inpatient status (P = 0.04) independently predicted 2-year SF-36 PCS scores. PTS alone independently predicted 2-year VEINES-QOL (P < 0.0001) and VEINES-Sym (P < 0.0001) scores.
Development of PTS is the principal determinant of health-related QOL 2 years after DVT. Our study provides prognostic information on patient-reported outcomes after DVT and emphasizes the need for effective prevention and treatment of the PTS.
Journal of Thrombosis and Haemostasis 07/2008; 6(7):1105-12. · 6.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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).
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.
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.
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.
Journal of Clinical Epidemiology 11/2006; 59(10):1049-56. · 5.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective. To evaluate an enzyme-linked immunosorbent assay (ELISA) for anticentromere autoantibodies (ACA).Methods. Sera from 611 patients with scleroderma, CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias), Raynaud's disease, and connective tissue disease control patients were studied by ELISA using the fusion protein CENP-B, by immunofluorescence on dividing HEp-2 cells, and by immunoblotting on chromosomes and CENP-B.Results. Compared with immunofluorescence, the CENP-B ELISA sensitivity was 94% and the specificity was 93%. In 19.7% of the cases, there was a probability of a false-positive result and in 1.9%, a probability of a false-negative result, yielding positive and negative predictive values of 0.80 and 0.98, respectively.Conclusion. The CENP-B ELISA is a sensitive and specific assay for ACA.
[Show abstract][Hide abstract] ABSTRACT: To our knowledge, the burden of deep venous 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.
This was a multicenter prospective cohort study of 359 consecutive eligible patients with deep vein thrombosis recruited at 7 Canadian hospital centers. Quality of life was assessed at baseline and at 1 and 4 months after diagnosis using generic (36-Item Short-Form Health 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.
During the 4 months, mean 36-Item Short-Form Health Survey physical and mental component summary 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 for time trend for all measures). However, about one third of patients had worsening of QOL during follow-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 36-Item Short-Form Health Survey physical component summary scores were lower than population norms at all points assessed.
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. Worsening of the postthrombotic syndrome score is associated with worsening of QOL.
Archives of Internal Medicine 05/2005; 165(10):1173-8. · 11.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate an enzyme-linked immunosorbent assay (ELISA) for anticentromere autoantibodies (ACA).
Sera from 611 patients with scleroderma, CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias), Raynaud's disease, and connective tissue disease control patients were studied by ELISA using the fusion protein CENP-B, by immunofluorescence on dividing HEp-2 cells, and by immunoblotting on chromosomes and CENP-B.
Compared with immunofluorescence, the CENP-B ELISA sensitivity was 94% and the specificity was 93%. In 19.7% of the cases, there was a probability of a false-positive result and in 1.9%, a probability of a false-negative result, yielding positive and negative predictive values of 0.80 and 0.98, respectively.
The CENP-B ELISA is a sensitive and specific assay for ACA.
[Show abstract][Hide abstract] ABSTRACT: The authors used nailfold capillary microscopy (NCM) to evaluate 112 patients 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. Disease 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 involvements. 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; p less than 0.001 and p less than 0.01 respectively). NCM sensitivity for S1 and S2 was 93.6%. NCM correlated with the degree of target organ involvement (p less than 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.
[Show abstract][Hide abstract] ABSTRACT: Actin microfilaments are anchored to the plasma membrane at focal contacts. Using an indirect immunofluorescence method, we detected an autoantibody reactive with focal contacts in PtK2, HEp-2, and BHK-21 cells in serum from two patients with early systemic sclerosis. With double immunofluorescence, using the actin-binding drug phalloidin, we localized the plaques decorated by these sera specifically at the termini of microfilament bundles. The reactive antigens were identified by immunoblotting as proteins of 80,000- and 75,300-mol wt in PtK2, and of 53,500-mol wt in HEp-2 and BHK-21 cells. The 53,500-mol wt protein was also identified in rat skeletal, myocardial, and smooth muscle tissues. The detergent solubility of these proteins suggested that they may be linked to the plasma membrane. The autoantigens were immunologically distinct from vinculin and alpha-actinin, two major proteins also known to be concentrated at the ends of microfilament bundles. Our observations suggest that this novel anticytoskeletal autoantibody may identify a novel family of vertebrate cell proteins involved in the linkage of microfilaments to the plasma membrane at focal contacts.
Journal of Clinical Investigation 10/1987; 80(3):778-85. · 12.81 Impact Factor