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Biomedical subjects

Marc A Rodger

Publications and source records attributed to Marc A Rodger.

At least 19 recordsLinked to original sources
PubMed2006

The prevalence of antibodies to the platelet factor 4 -heparin complex and association with access thrombosis in patients on chronic hemodialysis.

INTRODUCTION: Heparin-induced thrombocytopenia is a serious complication that can lead to thrombocytopenia, venous and arterial thrombosis. Patients with this disorder develop antibodies to the platelet factor 4-heparin (PF4-H) complex. Hemodialysis patients are repeatedly exposed to heparin and are at risk for developing PF4-H antibodies. We sought to determine the prevalence of PF4-H antibodies in a large cohort of patients on chronic hemodialysis and to evaluate the relationship between PF4-H antibodies and hemodialysis vascular access thrombosis in a case-control study. MATERIAL AND METHODS: Pre-dialysis blood samples were drawn on 419 patients; 107 cases with access thrombosis and 312 controls that never had access thrombosis. All samples were screened for PF4-H antibodies using an ELISA assay (GTI PF4 Enhanced, GTI Diagnostics). All positive and indeterminate samples were then tested using an IgG-specific PF4-H ELISA assay and a platelet serotonin-release assay. RESULTS: Antibodies to PF4-H were positive in 54 (12.9%) patients using the screening ELISA assay. Nine (2.1%) patients had IgG-specific PF4-H antibodies. None of the patient's had a positive platelet serotonin-release assay. No relationship between hemodialysis access thrombosis and PF4-H antibodies was noted using the screening ELISA assay (unadjusted odds ratio 0.63; 95% CI 0.30-1.30; P = 0.21), the IgG-specific ELISA assay (unadjusted odds ratio 0.83; 95% CI 0.17-4.06; P = 0.82) or indeterminate platelet serotonin-release assay results (unadjusted odds ratio 0.97;95% CI 0.10-9.44;P = 0.98). CONCLUSIONS: Hemodialysis with repeated exposure to unfractionated heparin was associated with a moderately elevated prevalence of PF4-H antibodies. However, our results do not support a relationship between PF4-H antibodies and hemodialysis vascular access thrombosis.

Adult↗
PubMed2006

The risk of dialysis access thrombosis is related to the transforming growth factor-beta1 production haplotype and is modified by polymorphisms in the plasminogen activator inhibitor-type 1 gene.

Transforming growth factor-beta1 (TGF-beta1) and plasminogen activator inhibitor-type 1 (PAI-1) might play a role in the development of fibrosis and stenosis of hemodialysis vascular accesses. We studied polymorphisms in the TGFbeta1 (869T>C; 915G>C), and PAI-1 (4G/5G) genes in 416 hemodialysis patients (107 access thrombosis cases, 309 controls), to determine if they are related to vascular access thrombosis. Three TGF-beta1 production haplotypes (low, intermediate, and high) were defined according to the combination of polymorphisms found. The adjusted odds ratio (OR) and 95% confidence interval (CI) for access thrombosis in low TGF-beta1 producers was 7.31 (2.15-24.88; P = .001). The interaction between low TGF-beta1 production haplotype and the 4G/4G PAI-1 genotype was strongly associated with access thrombosis (adjusted OR 19.3; 95% CI 2.82-132.40; P = .003). Mean access thrombosis-free survival times in years (95% CI) were 14.65 (12.05-17.25), 11.96 (8.67-15.25), and 4.94 (3.06-6.83) in high, intermediate, and low TGF-beta1 producers, respectively (P = .044). Analysis of the synergy index and the case-only cross-product supported the presence of an interaction. We concluded that low TGF-beta1 production haplotype is a risk factor for hemodialysis access thrombosis and that in the presence of the 4G/4G PAI-1 genotype there is an additional increase in risk.

Aged↗
PubMed2006

The bedside investigation of pulmonary embolism diagnosis study: a double-blind randomized controlled trial comparing combinations of 3 bedside tests vs ventilation-perfusion scan for the initial investigation of suspected pulmonary embolism.

BACKGROUND: We sought to determine whether using combinations of 3 bedside tests (7-variable clinical model, non-enzyme-linked immunosorbent assay D-dimer test, and alveolar dead-space fraction) to exclude pulmonary embolism (PE) before diagnostic imaging was as safe as a standard strategy of starting with ventilation-perfusion (V/Q) scan. METHODS: In this double-blind, randomized, controlled equivalency trial, patients were randomized to initial bedside tests or to initial V/Q scan without bedside tests. Patients assigned to the bedside test group had a sham V/Q scan performed if at least 2 of 3 bedside test results were negative; otherwise, they underwent an actual V/Q scan. Further diagnostic management was determined by a blinded physician after V/Q scan. The primary outcome measure was recurrent venous thromboembolic events during 3 months among patients who were not taking anticoagulant agents after the initial investigations were completed. RESULTS: Four hundred fifty-eight consecutive adults with suspected PE were eligible for the study; 398 of 399 consenting and randomized patients completed the study. The follow-up venous thromboembolic event rate was 2.4% in the bedside test group vs 3.0% in the V/Q scan group (P = .76). Pulmonary embolism was excluded in 34% (67/199) of the bedside test group patients with at least 2 negative results on 3 bedside tests vs 18% (35/199) excluded using only the 7-variable clinical model and the D-dimer test. CONCLUSION: Excluding PE with at least 2 negative results on 3 bedside tests safely eliminates the need for diagnostic imaging in 34% of patients with suspected PE.

Adult↗
PubMed2006

Pelvic magnetic resonance venography reveals high rate of pelvic vein thrombosis after cesarean section.

In the run-in phase of a thromboprophylactic trial in women at moderate to high risk of deep vein thrombosis postcesarean section, we used magnetic resonance venography and found a surprisingly high rate of pelvic deep vein thrombosis (46% overall). Pelvic magnetic resonance venography may be a useful surrogate outcome in obstetric thromboprophylaxis studies but the clinical significance is not known.

Adult↗
PubMed2006

Excluding pulmonary embolism at the bedside with low pre-test probability and D-dimer: safety and clinical utility of 4 methods to assign pre-test probability.

INTRODUCTION: Less than 35% of patients suspected of having pulmonary embolism (PE) actually have PE. Safe bedside methods to exclude PE could save scarce health care resources if they exclude large proportions of patients with suspected PE and are widely applicable. Non-Elisa D-dimer in combination with pre-test probability of suspected PE can safely exclude PE at the bedside. Pre-test probability can be assigned by gestalt or by using clinical models (Wells, Wicki, Rodger). MATERIALS AND METHODS: We combined two databases from studies of patients with suspected PE and retrospectively compared the diagnostic test characteristics of the different methods of assigning pre-test probability. RESULTS: 535 patients were studied. PE was confirmed in 20.8% of study patients. Two clinical predictive models (Rodger and Wells) and overall diagnostic impression have similar sensitivities ranging from 96% (95% confidence interval (CI) 89-99%) to 99% (93-100%). Wicki's model has a sensitivity of 89% (77-96%). The Wells' model with a cutoff of less than 2 points in association with semi-quantitative D-dimer has a specificity of 11% (CI 7-15%). The specificities for the other clinical predictive model are ranging from 21% (17-25%) to 49% (CI 42-55%). CONCLUSION: Semi-quantitative D-dimer must be combined with safe clinical probability assessment to safely exclude PE in a significant proportion of patients. Wicki's model in association with semi-quantitative D-dimer has the lowest sensitivity and should be used carefully to exclude PE at the bedside. The Wells' model with a cutoff of less than 2 points when combined with semi-quantitative D-dimer excluded very few patients and therefore limits its clinical utility.

Aged↗
PubMed2006

The factor XIII Val34Leu polymorphism: is it protective against idiopathic venous thromboembolism?

The substitution of leucine for valine at amino acid position 34 of the factor XIII gene is commonly referred to as FXIII Val34Leu polymorphism. The homozygous leucine/leucine genotype has been reported to confer protection against venous thromboembolism, but previous studies have not evaluated a population limited to those with idiopathic venous thromboembolism. The primary objective of the study was to determine whether the FXIII Val34Leu polymorphism is independently associated with the occurrence of idiopathic venous thromboembolism. We prospectively enrolled consecutive patients with at least one objectively confirmed idiopathic venous thromboembolism. Friends of cases were recruited as controls and matched to cases by sex, ethnicity, and age. All participants were tested for the FXIII Val34Leu polymorphism in addition to several well-known thrombophilias. Data from 309 cases and 306 controls were analyzed. The FXIII leucine/leucine genotype was present in 4.9% of cases and 6.5% of controls. An adjusted odds ratio of 0.59 (95% confidence interval, 0.25-1.38) was found for the recessive model and 0.69 (95% confidence interval, 0.46-1.02) for the dominant model. Our results do not support an independent association of the FXIII Val34Leu polymorphism with idiopathic venous thromboembolism in our Caucasian Canadian study population.

Amino Acid Substitution↗
PubMed2005

A randomized trial comparing 2 low-molecular-weight heparins for the outpatient treatment of deep vein thrombosis and pulmonary embolism.

BACKGROUND: Low-molecular-weight heparins (LMWHs) are now standard therapy for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). No published trials have compared LMWHs, and few studies have examined outpatient therapy for PE. Only tinzaparin sodium has demonstrated superiority to unfractionated heparin in a clinical trial. METHODS: We compared 2 LMWH products, tinzaparin and dalteparin sodium, for the treatment of acute DVT and PE in a randomized, controlled clinical trial of consecutive outpatients presenting to a venous thromboembolism service at 4 tertiary-care hospitals. Patients were treated with subcutaneous tinzaparin sodium, 175 IU/kg every 24 hours, or subcutaneous dalteparin sodium, 200 IU/kg every 24 hours, for at least 5 days. Warfarin sodium therapy was started simultaneously and continued for 90 days. The primary end point was efficacy (recurrence of venous thromboembolism); safety (bleeding) was a composite end point. RESULTS: Two hundred fifty-four patients received tinzaparin (39 with PE and 215 with DVT) and 251 received dalteparin (51 with PE and 200 with DVT). Most patients had an active malignancy or idiopathic DVT/PE. The outcome events occurred in 11 (4.4%; 95% confidence interval [CI], 2.2%-7.7%) and 15 patients (5.9%; 95% CI, 3.3%-9.5%) in the dalteparin and tinzaparin groups, respectively, including 9 and 10 recurrences, respectively, and 2 and 5 major hemorrhages, respectively (P = .44). The 95% CI on the difference of -1.5% was -5.3% to 2.4%. CONCLUSIONS: Tinzaparin and dalteparin are safe and effective for the outpatient treatment of DVT or PE. Our finding of no differences between the LMWHs based on major clinical end points means that practical issues can be the deciding factor on which drug to use.

Acute Disease↗
PubMed2005

Thrombophilia and the risk for hemodialysis vascular access thrombosis.

Vascular access thrombosis is the most common and costly complication in hemodialysis patients. The role of thrombophilia in access thrombosis is not established. A case-control study was conducted of 419 hemodialysis patients to determine whether thrombophilia was associated with arteriovenous fistula or graft thrombosis. Participants were enrolled from three in-center and five satellite dialysis units associated with a Canadian academic health science center that provides dialysis services in a catchment area of one million. Patients were tested for factor V Leiden, prothrombin gene mutation, factor XIII genotype, methylenetetrahydrofolate reductase genotype, lupus anticoagulant, anticardiolipin antibody, factor VIII, homocysteine, and lipoprotein (a) concentrations. Overall, 59 (55%) patients with access thrombosis had at least one thrombophilia compared with 122 (39%) patients without access thrombosis (unadjusted odds ratio [OR], 1.91; 95% confidence interval [CI], 1.23 to 2.98). After controlling for important risk factors, the association between any thrombophilia and access thrombosis remained (adjusted OR, 2.42; 95% CI, 1.47 to 3.99). For each additional thrombophilic disorder, the odds of access thrombosis increased significantly (adjusted OR, 1.87; 95% CI, 1.34 to 2.61). This study suggests that thrombophilia is associated with access thrombosis in dialysis patients. Large, multicenter, prospective cohort studies are needed to confirm the observations from this case-control study.

Aged↗
PubMed2005

A systematic review of the association between factor V Leiden or prothrombin gene variant and intrauterine growth restriction.

OBJECTIVE: The purpose of this study was to conduct a systematic review of the literature of studies that examined the association between factor V Leiden and/or prothrombin gene variant and intrauterine growth restriction. STUDY DESIGN: This systematic review of studies assesses the association between factor V Leiden and/or prothrombin gene variant and intrauterine growth restriction. RESULTS: Ten case-control studies fulfilled the selection criteria for inclusion in the meta-analysis. There was a significant association between factor V Leiden and intrauterine growth restriction (odds ratio, 2.7; 95% CI, 1.3-5.5) and prothrombin gene variant and intrauterine growth restriction (odds ratio, 2.5; 95% CI, 1.3-5.0). Five cohort studies were identified in the systematic review; 3 studies were prospective (2 full publications), and 2 studies were retrospective (1 full publication). Combining the 2 full publication prospective studies yields a summary relative risk of 0.99 (95% CI, 0.5-1.9). CONCLUSION: This meta-analysis of case-control studies suggests that the factor V Leiden and prothrombin gene variant both confer an increased risk of giving birth to an intrauterine growth restricted infant, although this may be driven by small, poor-quality studies that demonstrated extreme associations. Large well-conducted prospective cohort studies are required to determine definitively whether an association between thrombophilia and intrauterine growth restriction is present.

Case-Control Studies↗
PubMed2004

The interobserver reliability of pretest probability assessment in patients with suspected pulmonary embolism.

INTRODUCTION: Pretest probability assessment and objective testing are combined to appropriately manage patients with suspected pulmonary embolism (PE). However, the interobserver reliability of pretest probability assessment has not been investigated. We sought to determine (for patients with suspected PE) the interobserver reliability of pretest probability assessment (by overall impression (gestalt) versus an explicit clinical model). MATERIALS AND METHODS: A prospective cohort study was conducted at an urban university hospital. For patients referred for ventilation and perfusion (V/Q) scanning for suspected PE, structured assessments (11 history and 4 physical examination parameters) were performed by a referring physician and a designated thrombosis physician. The referring and thrombosis physicians also assigned a pretest probability for PE (low, moderate, or high) by gestalt. An explicit seven-point clinical model for suspected PE was later applied to each structured assessment to determine the pretest probability. Assessments were performed independently and prior to diagnostic test results. Interobserver reliability (two rater unweighted Kappa (kappa) statistic) was determined for each parameter on the structured assessment and the pretest probability assessments (gestalt vs. explicit clinical model). RESULTS: One hundred and ten patients with suspected PE received duplicate assessments. Historical features demonstrated substantial to almost perfect interobserver reliability (kappa=0.60-0.95). For the physical findings, only heart rate had substantial interobserver reliability (kappa=0.60). Pretest probability assessment was not reliable when using physician's gestalt (kappa=0.33), but produced substantial interobserver reliability using the explicit clinical model (kappa=0.62). CONCLUSIONS: Given the inadequate interobserver reliability of pretest probability assessment by overall impression (or gestalt), physicians should use explicit clinical models in the diagnostic management of patients with suspected pulmonary embolism.

Adolescent↗
PubMed2003

The outpatient bleeding risk index: validation of a tool for predicting bleeding rates in patients treated for deep venous thrombosis and pulmonary embolism.

BACKGROUND: Long-term anticoagulation prevents recurrent thrombosis in patients with idiopathic deep venous thrombosis or pulmonary embolism, but with a risk of clinically important so-called major bleeding. Physician- and patient-based decisions on the optimal duration of therapy are sensitive to the bleeding risk. The Outpatient Bleeding Risk Index potentially provides a means of calculating the potential risk of bleeding using easily elicited clinical findings, but, to our knowledge, the authors of the index have provided the only published validation of it. We sought to determine the accuracy of the index in our population of patients. METHODS: We prospectively applied the Outpatient Bleeding Risk Index to consecutive patients in our clinic who had been objectively diagnosed as having pulmonary embolism or deep venous thrombosis and who were about to undergo standard therapy. Standard therapy consisted of a minimum of 5 days of low-molecular-weight heparin therapy overlapped with warfarin sodium therapy, and continuation of warfarin therapy for at least 3 months, with a target international normalized ratio of 2.5. Patients were placed in 3 risk groups (low, moderate, or high), as defined by the index. The survival curves of the groups, using major hemorrhages as the events, were then compared by the log-rank test. RESULTS: Bleeding rates were lower than expected, but the index did discriminate between low- and moderate-risk groups (P =.03, log-rank test). The rate of major hemorrhage per 100 person-years was 0% (95% confidence interval, 0%-2.8%) in the low-risk group and 4.3% (95% confidence interval, 1.1%-11.1%) in the moderate-risk group. The rate in the high-risk group could not be defined because only 2 patients were at high risk. CONCLUSION: The Outpatient Bleeding Risk Index discriminates between low- and moderate-risk patients, and could be used to guide decisions on the optimal duration of anticoagulant therapy.

Aged↗
PubMed2003

The outpatient treatment of deep vein thrombosis delivers cost savings to patients and their families, compared to inpatient therapy.

BACKGROUND: The outpatient treatment of deep vein thrombosis (DVT) with low-molecular-weight heparin (LMWH) has been shown to be cost-effective from the perspective of a third party payer. The aim of this study is to determine if some or all of these cost savings to third party payers are shifted to patients and their families. METHODS: A prospective cohort study with micro-costing of patient/family costs was conducted at the thrombosis units of The Ottawa Hospital. Costs were determined by administering a questionnaire at the end of the patients' heparin therapy. Over a period of 4 months, consecutive patients presenting at the thrombosis units were approached at the initiation of their heparin therapy; 44 patients consented to participate and completed questionnaires were obtained for 41. RESULTS: The mean patient/family costs associated with outpatient therapy were significantly less than those associated with inpatient therapy (219.42 dollars versus 402.93 dollars, p=0.003); a savings of 190.91 dollars per patient. Even when lost income to patients/families was ignored, mean patient/family costs remained significantly less for outpatient therapy (72.00 dollars versus 134.29 dollars, p=0.004); a savings of 62.30 dollars per patient. Furthermore, patients preferred outpatient to inpatient therapy by almost 3:1 (30 versus 11, respectively). INTERPRETATION: The outpatient treatment of DVT does not result in any net shifting of costs to patients and their families, and further, brings about cost savings. Given the cost savings associated with and the preference of patients for outpatient care, this study further supports the shift of DVT therapy from the inpatient unit to the outpatient clinic.

Adult↗
PubMed2003

Topical tetracaine prior to arterial puncture: a randomized, placebo-controlled clinical trial.

The objective of this randomized, double-blind, placebo-controlled clinical trial was to determine whether a topical anesthetic agent (tetracaine) provides effective local analgesia prior to radial arterial puncture. Tetracaine or placebo gel was applied 45 min prior to arterial puncture to patients who were referred for elective arterial blood gas. The primary outcome was the patient's perception of pain associated with the procedure as measured by a visual analog scale. Fifty patients were randomized into the study, 24 received tetracaine and 26 placebo. Mean pain score on the visual analog scale was 26.2 +/- 32.6 for the tetracaine-treated patients and 23.8 +/- 27.4 for the placebo-treated patients (P = 0.78). Mean time from the first skin puncture to successful procurement of 1 ml of arterial blood was 70 +/- 103s in the tetracaine group and 49 +/- 48s in the placebo group (P = 0.40). Difficulty of arterial puncture as assessed by the respiratory therapist performing the test was identical for the two groups (P = 0.86). We conclude that tetracaine gel did not decrease patient's perception of pain associated with arterial puncture, nor did its use facilitate the ABG procedure.

Administration, Topical↗
PubMed2003

Diagnosis and treatment of venous thromboembolism in pregnancy.

Suspected or confirmed venous thromboembolism (VTE) (deep-vein thrombosis and pulmonary embolism) in non-pregnant patients are common clinical problems with ample clinical research upon which diagnostic and treatment recommendations are based. Unfortunately, the level of complexity is increased in the diagnostic and therapeutic management of pregnancy-associated VTE by evolving physiological changes in expectant mothers, the effects of diagnostic and therapeutic management on the unborn child and the lack of validation of these management strategies in pregnancy. This chapter considers the epidemiology, pathogenesis, diagnosis and treatment of pregnancy-associated VTE. It highlights the poverty of research upon which to base clinical recommendations for this common problem yet offers practical but conservative approaches to patients with suspected and confirmed pregnancy-associated VTE.

Algorithms↗
PubMed2003

Participation of pregnant women in clinical trials: will they participate and why?

The objective of this study is to investigate the willingness of pregnant women to participate in a randomized placebo-controlled clinical trial, and to explore the determinants of their decision making. Cross-sectional survey with semistructured interview and thematic content analysis of pregnant women in a tiertiary care obstetric outpatient clinic. Among the 50 women surveyed, 37 (74%; 95% confidence interval, 60-85%) indicated that they would be willing to participate in a randomized placebo-controlled trial of an injectable medicine given throughout pregnancy, while 5/50 (10%; 95% confidence interval, 3-22%) would decline to participate. Potential benefit to the health of the fetus was ranked as the most important determinant for willingness to participate (68%), followed by benefit to personal health (27%), and altruism (5%). A majority of pregnant women would be willing to participate in a randomized placebo-controlled clinical trial. Pregnant women appear to be willing to accept risks to themselves, if there is a chance that participation in a clinical trial would help their pregnancy and improve their baby's health.

Analysis of Variance↗
PubMed2003

The ACE D/D genotype is protective against the development of idiopathic deep vein thrombosis and pulmonary embolism.

The deletion/deletion (D/D) genotype of the angiotensin converting enzyme (ACE) has been purported to be a risk for post-operative thrombosis.This D/D genotype has not been evaluated as a risk factor for idiopathic venous thromboembolism (VTE). The primary objective of the present study was to determine whether the D/D genotype of ACE is independently associated with the occurrence of idiopathic venous thromboembolic disease. We prospectively enrolled consecutive patients with at least one objectively confirmed idiopathic VTE. Friends of cases were recruited as controls and matched to cases by sex, ethnicity, and age. Patients were tested for the ACE I/D polymorphism in addition to factor V Leiden, prothrombin G20210A, and factor VIII levels. Three hundred cases and 300 controls were enrolled; 97% were Caucasian. There were 148 females and 152 males in each group with a mean age of 56.21 years (SD = 15.33). The ACE D/D genotype was present in 25.3% of cases and 32.4% of controls for an adjusted odds ratio of 0.66 (95% CI = 0.433 to 0.997). We can conclude that the ACE D/D genotype is protective against idiopathic venous thromboembolism.

Adult↗
PubMed2002

The management of thrombophilia during pregnancy: a Canadian survey.

OBJECTIVE: To determine current Canadian practice patterns in the management of pregnant women with thrombophilia. METHODS: Physician members of the Society of Obstetricians and Gynaecologists of Canada (SOGC) who provide obstetrical care were invited to complete a closed-ended questionnaire in which they were presented 5 clinical scenarios involving thrombophilic pregnancies and asked to give their management recommendations. The 5 scenarios presented in the survey were of a pregnant woman with (1) asymptomatic factor V Leiden (FVL), (2) asymptomatic FVL and a family history of venous thromboembolism (VTE), (3) FVL and recurrent fetal loss, (4) FVL and a previous VTE, or (5) antiphospholipid antibody syndrome and recurrent fetal loss. RESULTS: Of the 1448 eligible SOGC members invited, 18 had moved with no forwarding address, and 662 (46.3% of the remainder) responded. The majority (65%) of the respondents were obstetricians and 51% of them had a university-affiliated practice. In scenario 1, 26% of physicians indicated they would recommend some form of antepartum thromboprophylaxis, whereas in the remaining four scenarios, 58% to 84% would definitely recommend antepartum thromboprophylaxis. CONCLUSION: Most clinicians favour intervening with thromboprophylaxis in pregnant thrombophilic women rather than observing without prophylaxis. This tendency spans a wide range of clinical scenarios, despite a lack of evidence to support such decisions. This survey highlights the need to provide clinicians and women with evidence for the safety and effectiveness of prophylaxis, before these interventions become the default recommendation by clinicians caring for this prevalent group of women.

Abortion, Habitual↗