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D R Anderson

Publications and source records attributed to D R Anderson.

At least 19 recordsLinked to original sources
PubMed2005

Predictors of the post-thrombotic syndrome during long-term treatment of proximal deep vein thrombosis.

BACKGROUND: The post-thrombotic syndrome is a chronic, poorly understood complication of deep venous thrombosis (DVT). OBJECTIVES: To evaluate predictors of the post-thrombotic syndrome, including intensity of long-term anticoagulation, and to assess the impact of the post-thrombotic syndrome on quality of life. PATIENTS AND METHODS: The setting was 13 Canadian hospitals and one US hospital. One hundred and forty-five patients with an unprovoked episode of proximal DVT who were initially treated with 3 months of conventional-intensity warfarin [target International Normalized Ratio (INR) of 2.5] then participated in a trial comparing two intensities of long-term warfarin therapy (target INR 2.5 vs. INR 1.7). Post-thrombotic syndrome was assessed at the end of the trial using a validated clinical scale. Generic and venous disease-specific quality of life was compared in patients with and without the post-thrombotic syndrome. Multivariable regression analyses were performed to identify predictors of the post-thrombotic syndrome and of its severity. RESULTS: After an average follow-up of 2.2 years, the prevalence of post-thrombotic syndrome was 37% and of severe post-thrombotic syndrome was 4%. Quality of life was worse in patients with the post-thrombotic syndrome compared with patients who did not have it. The presence of factor (F)V Leiden or the prothrombin gene mutation was an independent predictor of both a lower risk (P = 0.006) and reduced severity (P = 0.045) of the post-thrombotic syndrome. Intensity of anticoagulation did not influence the risk of developing the post-thrombotic syndrome. CONCLUSIONS: The post-thrombotic syndrome is a frequent and burdensome complication of proximal DVT, even among patients maintained on long-term oral anticoagulation. While the presence of FV Leiden or prothrombin gene mutation appears to be associated with a reduced risk of post-thrombotic syndrome, this finding requires further evaluation in prospective studies.

Administration, Oral↗
PubMed2005

Does the type of hormone replacement therapy influence the risk of deep vein thrombosis? A prospective case-control study.

BACKGROUND: Although hormone replacement therapy (HRT) is associated with an increased risk of deep vein thrombosis (DVT), it is not clear if the risk differs in users of combined estrogen-progestin HRT and estrogen-only HRT. METHODS: We prospectively studied postmenopausal women with suspected DVT in whom HRT use status was ascertained and who subsequently had objective diagnostic testing to confirm or exclude DVT. Cases were patients with idiopathic DVT, in whom there were no DVT risk factors, and controls were patients without DVT, in whom there were also no DVT risk factors. The risk of DVT was determined in users of estrogen-progestin HRT and estrogen-only HRT by comparing the prevalence of current HRT use in cases with idiopathic DVT and controls without DVT (reference group). Multivariable regression analysis was done to adjust for factors that might confound an association between HRT use and the risk of DVT. RESULTS: One thousand one hundred and sixty-eight postmenopausal women with suspected DVT were assessed, from whom 95 cases of idiopathic DVT and 610 controls without DVT and no DVT risk factors were identified. Estrogen-only HRT was associated with an increased risk for DVT that was not statistically significant [odds ratio (OR) = 1.22; 95% confidence interval (CI) 0.57, 2.61]. Estrogen-progestin HRT was associated with a greater than 2-fold increased risk for DVT (OR = 2.70; 95% CI 1.44, 5.07). CONCLUSION: The risk of developing DVT may be higher in users of combined estrogen-progestin HRT than in users of estrogen-only HRT.

Aged↗
PubMed2004

Single-arm study of bridging therapy with low-molecular-weight heparin for patients at risk of arterial embolism who require temporary interruption of warfarin.

BACKGROUND: When warfarin is interrupted for surgery, low-molecular-weight heparin is often used as bridging therapy. However, this practice has never been evaluated in a large prospective study. This study was designed to assess the efficacy and safety of bridging therapy with low-molecular-weight heparin initiated out of hospital. METHODS AND RESULTS: This was a prospective, multicenter, single-arm cohort study of patients at high risk of arterial embolism (prosthetic valves and atrial fibrillation with a major risk factor). Warfarin was held for 5 days preoperatively. Low-molecular-weight heparin was given 3 days preoperatively and at least 4 days postoperatively. Patients were followed up for 3 months for thromboembolism and bleeding. Eleven Canadian tertiary care academic centers participated; 224 patients were enrolled. Eight patients (3.6%; 95% CI, 1.8 to 6.9) had an episode of thromboembolism, of which 2 (0.9%; 95% CI, 0.2 to 3.2) were judged to be due to cardioembolism. Of these 8 episodes of thromboembolism, 6 occurred in patients who had warfarin deferred or withdrawn because of bleeding. There were 15 episodes of major bleeding (6.7%; 95% CI, 4.1 to 10.8): 8 occurred intraoperatively or early postoperatively before low-molecular-weight heparin was restarted, 5 occurred in the first postoperative week after low-molecular-weight heparin was restarted, and 2 occurred well after low-molecular-weight heparin was stopped. There were no deaths. CONCLUSIONS: Bridging therapy with subcutaneous low-molecular-weight heparin is feasible; however, the optimal approach for the management of patients who require temporary interruption of warfarin to have invasive procedures is uncertain.

Anticoagulants↗
PubMed2004

Comparison of 1 month with 3 months of anticoagulation for a first episode of venous thromboembolism associated with a transient risk factor.

BACKGROUND: The risk of recurrence is lower after treatment of an episode of venous thromboembolism associated with a transient risk factor, such as recent surgery, than after an episode associated with a permanent, or no, risk factor. Retrospective analyses suggest that 1 month of anticoagulation is adequate for patients whose venous thromboembolic event was provoked by a transient risk factor. METHODS: In this double-blind study, patients who had completed 1 month of anticoagulant therapy for a first episode of venous thromboembolism provoked by a transient risk factor were randomly assigned to continue warfarin or to placebo for an additional 2 months. Our goal was to determine if the duration of treatment could be reduced without increasing the rate of recurrent venous thromboembolism during 11 months of follow-up. RESULTS: Of 84 patients assigned to placebo, five (6.0%) had recurrent venous thromboembolism, compared with three of 81 (3.7%) assigned to warfarin, resulting in an absolute risk difference of 2.3%[95% confidence interval (CI) - 5.2, 10.0]. The incidence of recurrent venous thromboembolism after discontinuation of warfarin was 6.8% per patient-year in those who received warfarin for 1 month and 3.2% per patient-year in those who received warfarin for 3 months (rate difference of 3.6% per patient-year; 95% CI - 3.8, 11.0). There were no major bleeds in either group. CONCLUSION: Duration of anticoagulant therapy for venous thromboembolism provoked by a transient risk factor should not be reduced from 3 months to 1 month as this is likely to increase recurrent venous thromboembolism without achieving a clinically important decrease in bleeding.

Adult↗
PubMed2004

Acute myocardial infarction as a cause of death in palliated hypoplastic left heart syndrome.

A 20 month old child with hypoplastic left heart syndrome died suddenly from a massive myocardial infarction 15 months after a hemi-Fontan operation. This was confirmed at postmortem examination and histological examinations. The sites of surgical reconstruction were all in good condition, there were no gross anatomical coronary abnormalities, and the coronary ostia were unobstructed. On microscopy the internal coronary arteries had notable intimal and medial thickening with narrowing of the lumen, although no thrombotic occlusion was seen. To the authors' knowledge, this is the first published report of arteriosclerosis of the coronary arteries in hypoplastic left heart syndrome. It raises the question as to whether there may be a primary histological abnormality in some children with this condition or whether some mechanism of accelerated arteriosclerosis is at work.

Coronary Artery Disease↗
PubMed2003

Combined use of clinical assessment and d-dimer to improve the management of patients presenting to the emergency department with suspected deep vein thrombosis (the EDITED Study).

Suspected deep vein thrombosis (DVT) is a common problem facing emergency physicians. Timely diagnostic testing must be performed to accurately identify patients with DVT. The purpose of this study was to evaluate the safety and effectiveness of a management strategy that combined consideration of clinical pretest probability and a d-dimer test to evaluate patients presenting to the emergency department with suspected deep vein thrombosis (DVT). A prospective cohort study was performed in the emergency departments of four tertiary care institutions involving 1075 patients with suspected DVT. An emergency physician determined the pretest probability for DVT to be low, moderate, or high using an explicit clinical model. A blood sample was taken for d-dimer testing. Subsequent investigations (compression ultrasound, venography) were performed based upon the pretest probability and the d-dimer result. Patients considered at low pretest probability with negative d-dimer had no further diagnostic testing performed. All patients in whom the diagnosis of DVT was excluded by the algorithm did not receive anticoagulant therapy and were followed up for 90 days for the development of proximal DVT or pulmonary embolism. Overall, 195 (18.1%; 95% CI 15.9% to 20.6%) of 1075 patients were confirmed to have proximal DVT. Of the 882 patients who had proximal DVT excluded during the initial evaluation period using the algorithms, four (0.5%; 95% CI 0.1% to 1.2%) were subsequently diagnosed with proximal DVT in the follow-up period, including three patients in the low pretest probability group (1.0%; 95% CI 0.2% to 2.1%) who had normal d-dimer and no additional diagnostic testing performed. None of the 882 patients (0%: 95% CI 0% to 0.5%) developed pulmonary embolism in the follow-up period. A diagnostic strategy for the evaluation of patients with suspected DVT based on pretest probability and d-dimer is safe and feasible in the emergency department setting.

Adult↗
PubMed2002

Calibration of new high dose rate 192Ir sources.

The increased popularity of high dose rate (HDR) brachytherapy in the treatment of neoplastic disease has resulted in the introduction of new or redesigned 192Ir sources by various manufacturers. In order to provide accurate clinical dosimetry, accurate calibration of these sources is required. In this work, two new sources are calibrated with the standard, NIST traceable, in-air calibration technique. These sources are the Varian VariSource (VS2000) and the newly redesigned Nucletron MicroSelectron source. An uncertainty budget was performed to determine the overall uncertainty of the measurement, and a total relative expanded uncertainty (k = 2) of 2.15% was calculated. The results of the source calibration using the in-air technique and that obtained based upon the 1991 standard calibration all lie well within this uncertainty. In addition to the in-air calibration, contact autoradiographs of the sources were made with International Specialty Products model HD810 radiochromic film to demonstrate the sources relative dose distributions.

Air↗
PubMed2002

Coil occlusion of systemic venous collaterals in hypoplastic left heart syndrome.

OBJECTIVE: To assess the frequency of systemic venous collaterals to the atria, which may cause desaturation, after stage II reconstructive surgery for hypoplastic left heart syndrome (HLHS) and to determine whether coil occlusion prevents the need for surgical ligation. DESIGN: Prospective interventional study. SETTING: Tertiary referral centre. PATIENTS: 27 children with HLHS undergoing cardiac catheterisation between October 1996 and February 2001. INTERVENTIONS: 19 children were catheterised prestage II, 1 poststage II, and 17 prestage III. Aortic oxygen saturation (SaAo) and pulmonary artery pressure (pPA) were recorded. Angiography was performed into the left internal jugular vein to look for venous collaterals. If present, they were occluded with Cook MReye coils. Angiography was repeated to confirm occlusion, and SaAo and pPA were remeasured. RESULTS: Collaterals were found in 7 of 27 children: 1 poststage II and 6 prestage III. These were occluded with 1-3 coils without complication. Mean (SE) SaAo before occlusion was 80.2 (2.1)% in those with collaterals compared with 88.7 (1.0)% in those without (p = 0.007). There was no difference in mean pPA between the two groups. After coil occlusion mean SaAo rose to 83.8 (1.8)% (p = 0.007) and mean pPA rose from 12.5 (1.5) to 14.5 (1.8) mm Hg (p = 0.02). None required surgical ligation. CONCLUSION: Angiography should be performed at catheterisation before stage II and III surgery for HLHS to exclude systemic venous collaterals. If present, they may be safely and effectively occluded with coils to improve saturation and prevent the need for subsequent surgical ligation.

Cardiac Catheterization↗
PubMed2001

Differences between perspectives of physicians and patients on anticoagulation in patients with atrial fibrillation: observational study.

OBJECTIVE: To determine and compare physicians' and patients' thresholds for how much reduction in risk of stroke is necessary and how much risk of excess bleeding is acceptable with antithrombotic treatment in people with atrial fibrillation. DESIGN: Prospective observational study. SETTING: Tertiary and peripheral referral centres in Nova Scotia, Canada. PARTICIPANTS: 63 physicians who were treating patients with atrial fibrillation and 61 patients at high risk for atrial fibrillation. MAIN OUTCOME MEASURES: Participants underwent a face to face interview with a probability trade-off tool. Thresholds were determined for the minimum reduction in risk of stroke necessary and the maximum increase in risk of excess bleeding acceptable for treatment with aspirin and warfarin in people with atrial fibrillation. RESULTS: The minimum number of strokes that needed to be prevented in 100 patients over two years for warfarin to be justified was significantly lower for patients than for physicians (1.8 (SD 1.9) v 2.5 (1.6), P=0.009), whereas for aspirin there was no difference between patients and physicians (1.3 (1.3) v 1.6 (1.5), P=0.29). The maximum number of excess bleeds acceptable in 100 patients over two years for use of warfarin and aspirin was significantly higher for patients than for physicians (warfarin 17.4 (7.1) v 10.3 (6.1); aspirin 14.7 (8.5) v 6.7 (6.2); P<0.001 for both comparisons). CONCLUSIONS: Patients at high risk for atrial fibrillation placed more value on the avoidance of stroke and less value on the avoidance of bleeding than did physicians who treat patients with atrial fibrillation. The views of the individual patient should be considered when decisions are being made about antithrombotic treatment for people with atrial fibrillation.

Adult↗
PubMed2001

Excluding pulmonary embolism at the bedside without diagnostic imaging: management of patients with suspected pulmonary embolism presenting to the emergency department by using a simple clinical model and d-dimer.

BACKGROUND: The limitations of the current diagnostic standard, ventilation-perfusion lung scanning, complicate the management of patients with suspected pulmonary embolism. We previously demonstrated that determining the pretest probability can assist with management and that the high negative predictive value of certain D -dimer assays may simplify the diagnostic process. OBJECTIVE: To determine the safety of using a simple clinical model combined with D -dimer assay to manage patients presenting to the emergency department with suspected pulmonary embolism. DESIGN: Prospective cohort study. SETTING: Emergency departments at four tertiary care hospitals in Canada. PATIENTS: 930 consecutive patients with suspected pulmonary embolism. INTERVENTIONS: Physicians first used a clinical model to determine patients' pretest probability of pulmonary embolism and then performed a D -dimer test. Patients with low pretest probability and a negative D -dimer result had no further tests and were considered to have a diagnosis of pulmonary embolism excluded. All other patients underwent ventilation-perfusion lung scanning. If the scan was nondiagnostic, bilateral deep venous ultrasonography was done. Whether further testing (by serial ultrasonography or angiography) was done depended on the patients' pretest probability and the lung scanning results. MEASUREMENTS: Patients received a diagnosis of pulmonary embolism if they had a high-probability ventilation-perfusion scan, an abnormal result on ultrasonography or pulmonary angiography, or a venous thromboembolic event during follow-up. Patients for whom the diagnosis was considered excluded were followed up for 3 months for the development of thromboembolic events. RESULTS: The pretest probability of pulmonary embolism was low, moderate, and high in 527, 339, and 64 patients (1.3%, 16.2%, and 37.5% had pulmonary embolism), respectively. Of 849 patients in whom a diagnosis of pulmonary-embolism had initially been excluded, 5 (0.6% [95% CI, 0.2% to 1.4%]) developed pulmonary embolism or deep venous thrombosis during follow-up. However, 4 of these patients had not undergone the proper diagnostic testing protocol. In 7 of the patients who received a diagnosis of pulmonary embolism, the physician had performed more diagnostic tests than were called for by the algorithm. In 759 of the 849 patients in whom pulmonary embolism was not found on initial evaluation, the diagnostic protocol was followed correctly. Only 1 (0.1% [CI, 0.0% to 0.7%]) of these 759 patients developed thromboembolic events during follow-up. Of the 437 patients with a negative D -dimer result and low clinical probability, only 1 developed pulmonary embolism during follow-up; thus, the negative predictive value for the combined strategy of using the clinical model with D -dimer testing in these patients was 99.5% (CI, 99.1% to 100%). CONCLUSION: Managing patients for suspected pulmonary embolism on the basis of pretest probability and D -dimer result is safe and decreases the need for diagnostic imaging.

Adolescent↗
PubMed2001

Use of statins and the subsequent development of deep vein thrombosis.

BACKGROUND: Some of the benefit of statins for the prevention of cardiovascular disease may be due to their antithrombotic properties. Little is known about the effect of these drugs on the development of deep vein thrombosis. MATERIALS AND METHODS: We conducted a retrospective cohort study over an 8-year period by linking Ontario provincial health care administrative databases covering more than 1.4 million Ontario residents aged 65 years or older. We excluded those with a documented history of atherosclerosis, venous thromboembolism, or cancer within 36 months prior to study enrollment, as well as those prescribed warfarin sodium within 12 months before enrollment. In the primary cohort, we evaluated the subsequent risk of deep vein thrombosis (DVT) among men and women prescribed thyroid replacement therapy, nonstatin lipid-lowering agents, or statins. A second cohort of women only was evaluated in a similar fashion, but estrogen use was added as a third comparison drug group. RESULTS: There were 125 862 men and women in the primary cohort. After adjusting for age; sex; prior hospitalization; newly diagnosed cancer; or prescribed aspirin, warfarin, or estrogen, statin users (n = 77 993) had an associated decreased risk of DVT relative to those prescribed thyroid replacement therapy (n = 35 978) (adjusted hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.69-0.87). Compared with thyroid replacement therapy, users of nonstatin lipid-lowering agents (n = 11 891) did not seem to be at lower risk for deep vein thrombosis (HR, 0.97; 95% CI, 0.79-1.18). In the secondary cohort of 89 508 women, after adjusting for age, prior hospitalization, newly diagnosed cancer, or prescribed aspirin or warfarin, estrogen users (n = 29 165) had an associated increased risk for DVT compared with those receiving thyroid replacement therapy (n = 22 118) (HR, 1.16; 95% CI, 1.01-1.33), while statin users had an associated decreased risk (HR, 0.68; 95% CI, 0.59-0.79). Nonstatin lipid-lowering agents (n = 5155) were not associated with a reduced risk of DVT compared with thyroid replacement therapy (HR, 0.84; 95% CI, 0.63-1.12). CONCLUSION: Among selected individuals aged 65 years or older, statins were associated with a 22% relative risk reduction in the risk of DVT. A randomized clinical trial is needed to evaluate the efficacy of statins for the primary and secondary prevention of DVT.

Aged↗
PubMed2001

Modification of the Fc region of a primatized IgG antibody to human CD4 retains its ability to modulate CD4 receptors but does not deplete CD4(+) T cells in chimpanzees.

Keliximab, a Primatized IgG1 CD4 mAb, was reconfigured to an IgG4 antibody. The gamma4 constant region was further modified by substituting glutamic acid for serine at position 235 in the CH2 domain (IgG4-E), to remove residual binding to Fcgamma receptors, and substitution of serine with proline at position 228 in the hinge region (IgG4-PE) for greater stability. Pharmacokinetic analysis in rats gave a t(1/2) of approximately 4 days for IgG4-E and 9 days for IgG4-PE, consistent with a greater stability of the IgG4-PE molecule. The effects on T cell subsets were assessed in chimpanzees given escalating doses of IgG4-PE: 0.05 mg/kg on Day 16, 1.5 mg/kg dose on Day 43, and 15 mg/kg on Day 85. Receptor modulation was observed at the two highest doses, but no depletion of T cells at any dose. The in vitro and in vivo results demonstrate the potential of this IgG4-PE mAb for use in human trials.

Amino Acid Substitution↗
PubMed2001

Risk factors for progression of visual field abnormalities in normal-tension glaucoma.

PURPOSE: To uncover risk factors for the highly variable individual rates of progression in cases of untreated normal-tension glaucoma. METHODS: Visual field data were assembled from 160 subjects (160 eyes) enrolled in the collaborative normal-tension glaucoma study during intervals in which the eye under study was not receiving intraocular pressure-lowering treatment during prerandomization and postrandomization intervals. Analyses included multivariate analysis of time-dependent Cox proportional hazard, Kaplan-Meier analysis of "survival" without an increment of visual field worsening, and comparison of slopes of change in mean deviation global index over time. RESULTS: Most migraine occurred in women, but analysis demonstrated that gender and presence of migraine contribute separately to the overall risk. The risk ratio for migraine, adjusted for the other variables was 2.58 (P =.0058), for disk hemorrhage was 2.72 (P =.0036), and for female gender 1.85 (P =.0622). The average fall in the mean deviation index was faster in nonmigrainous women than in nonmigrainous men (P =.05). Suggesting genetic influence, Asians had a slower rate of progression (P =.005), and the few black patients enrolled had a tendency for faster progression. However, self-declared history of family with glaucoma or treated for glaucoma did not affect the rate of progression. Neither age nor the untreated level of intraocular pressure affected the rate of untreated disease progression, despite their known influence on prevalence. CONCLUSIONS: Whereas risk factors for prevalence help select populations within which to screen for glaucoma, the factors that affect the rate of progression help decide the expected prognosis of the individual's untreated disease and thereby the frequency of follow-up and aggressiveness of the therapy to be undertaken.

Aged↗
PubMed2001

Natural history of normal-tension glaucoma.

OBJECTIVE: A recently reported randomized study described the role of intraocular pressure (IOP) in normal-tension glaucoma (NTG) pathogenesis and the effect of therapeutic lowering of IOP. This is a report of an analysis of the natural course of NTG during the time eyes were not receiving therapy, either in the time interval awaiting randomization or after being randomly assigned not to receive treatment to lower the IOP. DESIGN: Analysis of prospectively collected data on the long-term course of a cohort of untreated subjects with normal-tension glaucoma, a subset of subjects enrolled in a randomized controlled clinical trial. RANDOMIZATION AND SUBJECT SELECTION: If the field defect in the study eye threatened the point of fixation, the subject was randomly assigned to start on treatment immediately or to be observed without treatment until progression was documented. Otherwise, an eye was randomly assigned only when and if, subsequent to enrollment, it showed visual field progression, progression of optic disc cupping, or a new disc hemorrhage. PARTICIPANTS: Data were collected for this report on 160 subjects observed without treatment among a total enrollment of 260. They consist of 49 subjects who were randomly assigned on enrollment not to receive therapy, 24 followed without treatment for a time until later being randomly assigned to treatment, 31 similarly followed without treatment and who were later randomly assigned to be followed for an additional time without treatment, and 56 who enrolled but were never randomly assigned. MAIN OUTCOME MEASURES: Visual field data were used in this report only from the interval during which the eye had not been assigned to receive therapy and were analyzed by two measures of progression: the "survival" time to meeting a criterion of confirmed localized progression and the rate of change in the mean deviation (MD) index over time. RESULTS: The four subgroups just described were similar at baseline, except that the average MD index was slightly better for the 56 eyes that never progressed during the period of follow-up. By Kaplan-Meier analysis of all untreated subjects combined, approximately one third showed localized progression within 3 years and about half within 5 to 7 years. Of subjects followed for 3 years or more, 62 of 109 did not show a statistically significant negative slope of MD regressed over time, whereas the others showed a statistically significant MD decline, mainly between -0.2 and -2 db per year. CONCLUSIONS: Some cases of NTG progress more rapidly than others. Although approximately half of cases showed a confirmed localized visual field deterioration by 7 years, the change is typically small and slow, often insufficient to measurably affect the MD index.

Aged↗