Objective To determine how length of anticoagulation and clinical presentation of venous thromboe... more Objective To determine how length of anticoagulation and clinical presentation of venous thromboembolism influence the risk of recurrence after anticoagulant treatment is stopped and to identify the shortest length of anticoagulation that reduces the risk of recurrence to its lowest level. Design Pooled analysis of individual participants' data from seven randomised trials. Setting Outpatient anticoagulant clinics in academic centres. Population 2925 men or women with a first venous thromboembolism who did not have cancer and received different durations of anticoagulant treatment. Main outcome measure First recurrent venous thromboembolism after stopping anticoagulant treatment during up to 24 months of follow-up. Results Recurrence was lower after isolated distal deep vein thrombosis than after proximal deep vein thrombosis (hazard ratio 0.49, 95% confidence interval 0.34 to 0.71), similar after pulmonary embolism and proximal deep vein thrombosis (1.19, 0.87 to 1.63), and lower after thrombosis provoked by a temporary risk factor than after unprovoked thrombosis (0.55, 0.41 to 0.74). Recurrence was higher if anticoagulation was stopped at 1.0 or 1. 5 months compared with at 3 months or later (hazard ratio 1.52, 1.14 to 2.02) and similar if treatment was stopped at 3 months compared with at 6 months or later (1.19, 0.86 to 1.65). High rates of recurrence associated with shorter durations of anticoagulation were confined to the first 6 months after stopping treatment. Conclusion Three months of treatment achieves a similar risk of recurrent venous thromboembolism after stopping anticoagulation to a longer course of treatment. Unprovoked proximal deep vein thrombosis and pulmonary embolism have a high risk of recurrence whenever treatment is stopped.
An epidemiological investigation was undertaken to determine the relationship between silicosis i... more An epidemiological investigation was undertaken to determine the relationship between silicosis in hardrock miners in Ontario and cumulative exposure to silica (free crystalline silica-α quartz) dust. This report describes the analytic method and presents the risk estimates.
Some of Paul Kyrle and Sabine Eichinger’s recommendations about long-term prevention of recurrent... more Some of Paul Kyrle and Sabine Eichinger’s recommendations about long-term prevention of recurrent venous thromboembolism (Mar 26, p 1163) do not seem to be consistent with the results of randomised trials. First, they recommend stopping anticoagulant therapy for unprovoked (spontaneous) proximal deep vein thrombosis after 3 or 6 months, even though the two trials that compared this practice with continuing warfarin treatment were stopped early because of overall superiority of long-term therapy. Second, for those who are treated with long-term warfarin, they suggest that there may be a lower risk of bleeding with low-intensity warfarin (international normalised ratio [INR] 1·5–2·0) than with conventionalintensity warfarin (INR 2·0–3·0), which would be sufficient to offset the demonstrated lower efficacy of lowintensity therapy. However, in the only study that compared low-intensity and conventional-intensity warfarin for long-term treatment of venous thromboembolism, there was no evidence of a reduction in major bleeding with low-intensity therapy (0·9 per 100 patient-years with conventional-intensity and 1·1 per 100 patient-years with low-intensity; difference 0·1 per 100 patient-years, 95% CI –0·8 to 1·1). Kyrle and Eichinger suggest that less success in keeping patients’ INR values in the target range in clinical practice than in clinical trials is likely to favour the use of low-intensity therapy because of a lower likelihood of bleeding. However, a higher proportion of INR values outside the target range,
International Journal of Radiation Oncology Biology Physics, Oct 1, 2011
Cancer Registry (NCR) is a population-based registry containing individual data on all resident D... more Cancer Registry (NCR) is a population-based registry containing individual data on all resident Dutch cancer patients in a total population of 16 million. The NCR was assessed in three eras: 2001-2003 (period A, no SABR); 2004-2006 (period B, limited availability of SABR) and 2007-2009 (period C, full access to SABR, with .50% SABR utilization estimated for the radiotherapy group). The database includes demographic data, stage, and type of treatment. Records are electronically linked to municipal death registries, providing complete survival data. Chi-square, Kaplan-Meier and Cox Regression were used to compare treatment utilization and survival after surgery, radiotherapy (RT) or neither treatment. Results: A total of 4605 patients aged 75 years or older were diagnosed with Stage I NSCLC between 2001 and 2009. Median follow-up was 44 months. Surgery was performed in 1698 patients (37%), RT in 1570 (34%) and neither in 1337 (29%). Radiotherapy utilization increased between periods A and C (31.2% vs. 37.7%), coinciding with a decrease in untreated patients (31.9% vs. 24.9%). Median survival for all patients increased from 16.4 months in period A to 24.4 months in period C (p \ 0.0001; HR, 0.7; 95% CI, 0.63-0.77). The greatest improvement in median overall survival was seen in RT patients, with the median survival increasing from 16.8 months (period A) to 26.1 months (period C) (p \ 0.0001; HR, 0.59; 95% CI, 0.50-0.70). An increase in survival was also seen in the surgical group (35.7 months period A; median survival not reached in period C; p \ 0.0001; HR, 0.73; 95% CI, 0.60-0.89). No significant change in survival was seen in the no-treatment group. Conclusions: The nationwide introduction of stereotactic radiotherapy for Stage I lung cancer was associated with a 6.5% absolute increase in radiotherapy utilization in patients aged $75 years, a decline in untreated patients, and a significant improvement in overall survival.
The purpose of this study was to evaluate the effect of breast irradiation on quality of life, in... more The purpose of this study was to evaluate the effect of breast irradiation on quality of life, including cosmetic outcome, for patients enrolled in a clinical trial. Between 1984 and 1989, a randomized trial was conducted in Ontario, Canada, in which women with lymph node negative breast carcinoma who had undergone lumpectomy and axillary lymph node dissection were randomized to either breast irradiation or no further treatment. A modified version of the Breast Cancer Chemotherapy Questionnaire (BCQ) was administered to women at baseline, 1 month (4 weeks), and 2 months (8 weeks) after randomization. Irritation of the skin of the breast, breast pain, and appearance of the breast to the patient were also assessed every 3 months for the first 2 years of the study. Of 837 patients, 416 were randomly allocated to radiation therapy and 421 to no further treatment. The mean change in quality of life from baseline to 2 months was -0.05 for the radiation group and +0.30 for the control group. The difference between groups was statistically significant (P = 0.0001). Longer term radiation therapy increased the proportion of patients who were troubled by irritation of the skin of the breast and breast pain. Radiation therapy did not increase the proportion of patients at 2 years who were troubled by the appearance of the treated breast; 4.8% in irradiated and nonirradiated patients (P = 0.62). Breast irradiation therapy had an effect on quality of life during treatment. After treatment, irradiated patients reported increased breast symptoms compared with controls. However, no difference was detected between groups at 2 years in the rates of skin irritation, breast pain, and being upset by the appearance of the breast.
Objective To evaluate the safety and efficiency of a diagnostic algorithm for deep vein thrombosi... more Objective To evaluate the safety and efficiency of a diagnostic algorithm for deep vein thrombosis (DVT) that uses clinical pretest probability based D-dimer thresholds to exclude DVT. Design Prospective diagnostic management study. setting University based emergency departments or outpatient clinics in Canada. ParticiPants Patients with symptoms or signs of DVT. interventiOn DVT was considered excluded without further testing by Wells low clinical pretest probability and D-dimer <1000 ng/mL or Wells moderate clinical pretest probability and D-dimer <500 ng/mL. All other patients had proximal ultrasound imaging. Repeat proximal ultrasonography was restricted to patients with initially negative ultrasonography, low or moderate clinical pretest probability, and D-dimer >3000 ng/mL or high clinical pretest probability and D-dimer >1500 ng/mL. If DVT was not diagnosed, patients did not receive anticoagulant treatment. Main OutcOMe Measure Symptomatic venous thromboembolism at three months. results 1508 patients were enrolled and analysed, of whom 173 (11.5%) had DVT on scheduled diagnostic testing. Of the 1275 patients with no proximal DVT on scheduled testing who did not receive anticoagulant treatment, eight (0.6%, 95% confidence interval 0.3% to 1.2%) were found to have venous thromboembolism during follow-up. Compared with a traditional DVT testing strategy, this diagnostic approach reduced the need for ultrasonography from a mean of 1.36 scans/patient to 0.72 scans/patient (difference −0.64, 95% confidence interval −0.68 to −0.60), corresponding to a relative reduction of 47%. cOnclusiOns The diagnostic strategy using a combination of clinical pretest probability and D-dimer identified a group of patients at low risk for DVT during follow-up while substantially reducing the need for ultrasound imaging. registratiOn ClinicalTrials.gov NCT02038530.
665 Background: Breast cancer patients usually receive follow-up in cancer centers. From the resu... more 665 Background: Breast cancer patients usually receive follow-up in cancer centers. From the results of preliminary research (Grunfeld, BMJ 1996;313:665), we hypothesized that routine follow-up in primary care is a safe and acceptable alternative to follow-up in specialist care. METHODS Women with early stage breast cancer who had completed adjuvant therapy (patients may have continued on adjuvant hormonal therapy), who were disease free and between 9 and 15 months after diagnosis, were allocated to receive follow-up in a cancer center according to usual practice (CC arm) or follow-up from their family physician (FP arm). Patients in the FP arm were referred back to the cancer center if diagnosed with recurrence or a new primary cancer. The primary outcome was a comparison of the rate of 'serious clinical events' (SCE) defined as any one of the following: spinal cord compression, pathological fractures, hypercalcaemia, uncontrolled local recurrence, brachial plexopathy, or poor functional status (Karnofsky ≤ 70). Secondary outcome was quality of life (QL). RESULTS 483 patients were allocated to the FP arm and 485 to the CC arm. Median follow-up was 3.5 years. The average age was 61 years; 69% were node negative; 73% had a lumpectomy; 77% had radiation. The FP arm had 54 (11.2%) recurrences and 29 deaths (6.0%). The CC arm had 63 (13.0%) recurrences and 30 (6.2%) deaths. In the FP arm 16 patients (3.3%) experienced a SCE compared to 18 (3.7%) in the CC arm (0.4% difference; 95%CI -2.02 to +2.83). There were no differences between groups in QL as measured by the SF36 Physical and Mental Component Scales and the HADS anxiety and depression scales. CONCLUSIONS Primary care follow-up of breast cancer patients is a safe and acceptable alternative to specialist follow-up. No significant financial relationships to disclose.
Epoetin alfa Placebo Abbreviation: FACT-An, Functional Assessment of Cancer Therapy-Anemia. ء S... more Epoetin alfa Placebo Abbreviation: FACT-An, Functional Assessment of Cancer Therapy-Anemia. ء Score, 0-80; a higher score indicates improved quality of life. †For one patient, more than 50% of responses on baseline FACT-An were missing. ‡Comparison of treatments for change from baseline; P Ͻ .05.
7018 Background: Patients with stage 3 NSCLC are potentially curable using combined modality ther... more 7018 Background: Patients with stage 3 NSCLC are potentially curable using combined modality therapy (CMT) with chemotherapy and radical radiation therapy (RT). PET/CT imaging is commonly used to stage patients with NSCLC. In addition, PET/CT for planning of RT may improve the definition of RT treatment volumes compared with conventional CT planning and thus improve outcomes. METHODS Patients with stage 3 NSCLC, who were considered candidates for CMT, were randomized to either PET/CT or CT alone for RT treatment planning. The proportion of patients who did not receive CMT because their tumor was upstaged to stage 4 or their intra-thoracic tumor was too extensive for radical RT was presented at the ASCO 2009 meeting. The secondary outcomes of overall survival (OS) and relationship of the standard uptake value (SUV) and OS are reported now. RESULTS Overall 310 patients were randomized, 152 to the PET/CT and 158 to standard CT planning. 118 (78%) of the 152 patients randomized to the PET/CT arm received radical RT compared with 146 (92%) of the 158 CT patients. The median follow-up was 17 months. The 2-year OS of the PET/CT group was 47% compared with 39% for the CT arm (hazard ratio [HR] = 0.8; 95% confidence interval [CI]: 0.6 - 1.0). A multivariable analysis (MVA) for OS indicated that in addition to the intervention, stage (3B vs 3A; HR = 1.4, 95% CI: 1.1 - 1.9) and ECOG status (HR = 1.7 per unit increase, 95% CI: 1.3 - 2.6) were predictive of OS. In the 142 PET/CT patients with complete PET scans, a MVA showed that SUV (HR = 1.03 per unit increase, 95% CI: 1.01 - 1.05) and stage (3B vs 3A; HR = 1.9, 95% CI: 1.2 - 3.0) were strong predictors of OS. CONCLUSIONS The PET START trial is the first randomized trial comparing PET/CT planning with standard CT planning in patients with NSCLC. As expected, the use of PET/CT resulted in fewer patients receiving radical RT. The OS trend favoring PET/CT may be primarily due to more accurate staging. The SUV and stage were strong predictors of OS in patients with stage 3 NSCLC.
Journal of Thrombosis and Haemostasis, Oct 1, 2004
Contrast venography, in combination with symptomatic venous thromboembolism (VTE), is the standar... more Contrast venography, in combination with symptomatic venous thromboembolism (VTE), is the standard efficacy outcome measure in clinical trials of thromboprophylaxis in major orthopedic surgery. It is uncertain whether performing bilateral venography offers any real advantage over venography of the operated leg alone. This study was undertaken to determine the risk of isolated contralateral deep vein thrombosis (DVT) following major orthopedic surgery and to evaluate whether bilateral venography, rather than venography on the operated leg alone, offers any gain in DVT detection and, thereby, improves efficiency in clinical study design. A systematic review of prospective studies that reported DVT incidence as the primary efficacy outcome based on mandatory bilateral venography in patients undergoing elective hip or knee arthroplasty or hip fracture repair was conducted. Based on the use of bilateral venography as a primary efficacy outcome measure, the incidence of any DVT is 16.7% following total hip replacement, 18.8% after hip fracture repair, and 33.8% after total knee replacement. While DVT risk in the operated leg varies depending on the type of surgery, the risk of isolated DVT in the non-operated leg is approximately 4% to 5% in all three procedures. By increasing the detection of any DVT, the use of bilateral venography reduces required sample size by 16% to 25% compared to ipsilateral venography. In clinical trials evaluating the efficacy of thromboprophylaxis in major orthopedic surgery, bilateral venography reduces the risk of undiagnosed DVT in the non-operated leg and improves the efficiency of study design by substantially reducing the sample size requirement.
Applied Occupational and Environmental Hygiene, 1999
Methods of assessing occupational exposure to diesel exhaust were evaluated in a railroad work en... more Methods of assessing occupational exposure to diesel exhaust were evaluated in a railroad work environment. The American Conference of Governmental Industrial Hygienists (ACGIH)-recommended elemental carbon and respirable combustible dust methods of ...
Most women with breast cancer are diagnosed at an early stage and more than 80% will be long-term... more Most women with breast cancer are diagnosed at an early stage and more than 80% will be long-term survivors. Routine follow-up marks the transition from intensive treatment to survivorship. It is usual practice for routine follow-up to take place in specialist clinics. This study tested the hypothesis that follow-up by the patient's family physician is a safe and acceptable alternative to specialist follow-up. Patients and Methods A multicenter, randomized, controlled trial was conducted involving 968 patients with early-stage breast cancer who had completed adjuvant treatment, were disease free, and were between 9 and 15 months after diagnosis. Patients may have continued receiving adjuvant hormonal therapy. Patients were randomly allocated to follow-up in the cancer center according to usual practice (CC group) or follow-up from their own family physician (FP group). The primary outcome was the rate of recurrence-related serious clinical events (SCEs). The secondary outcome was health-related quality of life (HRQL). Results In the FP group, there were 54 recurrences (11.2%) and 29 deaths (6.0%). In the CC group, there were 64 recurrences (13.2%) and 30 deaths (6.2%). In the FP group, 17 patients (3.5%) compared with 18 patients (3.7%) in the CC group experienced an SCE (0.19% difference; 95% CI, Ϫ2.26% to 2.65%). No statistically significant differences (P Ͻ .05) were detected between groups on any of the HRQL questionnaires. Conclusion Breast cancer patients can be offered follow-up by their family physician without concern that important recurrence-related SCEs will occur more frequently or that HRQL will be negatively affected.
This study details warfarin use in a large pediatric population followed in a central anticoagula... more This study details warfarin use in a large pediatric population followed in a central anticoagulation clinic. A prospective, consecutive cohort of nonselected children were studied. Patients were divided into groups by age, target international normalized ratio (INR) range, disease, medications, and vitamin K supplemented enteral nutrition use. Groups were analyzed on multiple aspects of warfarin therapy using multivariate methods. A total of 319 patients received 352 warfarin courses representing 391 treatment years. Age independently influenced all aspects of therapy. When compared with all older children, the ≤1 year of age group required increased warfarin doses, longer overlap with heparin, longer time to achieve target INR ranges, more frequent INR testing and dose adjustments, and fewer INR values in the target range. Although significantly different than children ≤1 year, children 1 to 6 years of age showed the same findings when compared with 7- to 18-year-olds. Fontan pati...
QUESTION: In patients who are receiving warfarin and have an international normalised ratio (INR)... more QUESTION: In patients who are receiving warfarin and have an international normalised ratio (INR) value between 4.5 and 10.0, does low dose vitamin K lower the INR better than placebo? Design Randomised (allocation concealed*), blinded {patients, clinicians, and outcome assessors} †,* placebo controlled trial with 3 months of follow up. Setting 5 thromboembolism services at teaching hospitals in London and Hamilton, Ontario, Canada.
Canadian journal of surgery. Journal canadien de chirurgie, 1983
The use of autogenous vein as an arterial substitute has been advocated for many years. Methods o... more The use of autogenous vein as an arterial substitute has been advocated for many years. Methods of harvesting generally cause spasm of the vein and it has been shown that preventing the spasm by applying papaverine improves long-term patency. The present study was undertaken to see if the reported long-term patency of such grafts was associated with improved short-term appearance of the venous endothelium as viewed with the scanning electron microscope. Two groups of dogs were studied; those sacrificed at 3 hours and those at 24 hours after replacing excised segments of the carotid and femoral arteries with cephalic veins. One of the veins was removed in the standard manner allowing spasm followed by distension back to its pre-spasm state; in the other, spasm was prevented by the topical application of papaverine before removal. The study shows that venous endothelial integrity is preserved by the use of papaverine and this improved appearance of the endothelium persists for the fir...
Because of increasing waiting times for adjuvant radiation in the province of Ontario, patients f... more Because of increasing waiting times for adjuvant radiation in the province of Ontario, patients from one Canadian centre were referred to two centres in the United States. This situation provided an opportunity to compare radiation practices. We performed a retrospective review of radiation prescribed to patients following breast-conserving surgery for invasive breast cancer. Patients with positive margins, 4 or more positive lymph nodes, recurrent disease, or large tumours (>5 cm) were excluded. For comparison, we reviewed a random sample of similar patients treated at the Canadian centre during the same period. A total of 120 referred and 217 non-referred patients were eligible for comparison. The analysis included 98 pairs of patients (N = 196), fully matched on age, nodal status, T stage, grade, and estrogen receptor (ER) status. Mean patient age was 60.7 years. The median total dose and number of fractions differed between centres [6040 cGy in 32 fractions (United States) vs...
Objective To determine how length of anticoagulation and clinical presentation of venous thromboe... more Objective To determine how length of anticoagulation and clinical presentation of venous thromboembolism influence the risk of recurrence after anticoagulant treatment is stopped and to identify the shortest length of anticoagulation that reduces the risk of recurrence to its lowest level. Design Pooled analysis of individual participants' data from seven randomised trials. Setting Outpatient anticoagulant clinics in academic centres. Population 2925 men or women with a first venous thromboembolism who did not have cancer and received different durations of anticoagulant treatment. Main outcome measure First recurrent venous thromboembolism after stopping anticoagulant treatment during up to 24 months of follow-up. Results Recurrence was lower after isolated distal deep vein thrombosis than after proximal deep vein thrombosis (hazard ratio 0.49, 95% confidence interval 0.34 to 0.71), similar after pulmonary embolism and proximal deep vein thrombosis (1.19, 0.87 to 1.63), and lower after thrombosis provoked by a temporary risk factor than after unprovoked thrombosis (0.55, 0.41 to 0.74). Recurrence was higher if anticoagulation was stopped at 1.0 or 1. 5 months compared with at 3 months or later (hazard ratio 1.52, 1.14 to 2.02) and similar if treatment was stopped at 3 months compared with at 6 months or later (1.19, 0.86 to 1.65). High rates of recurrence associated with shorter durations of anticoagulation were confined to the first 6 months after stopping treatment. Conclusion Three months of treatment achieves a similar risk of recurrent venous thromboembolism after stopping anticoagulation to a longer course of treatment. Unprovoked proximal deep vein thrombosis and pulmonary embolism have a high risk of recurrence whenever treatment is stopped.
An epidemiological investigation was undertaken to determine the relationship between silicosis i... more An epidemiological investigation was undertaken to determine the relationship between silicosis in hardrock miners in Ontario and cumulative exposure to silica (free crystalline silica-α quartz) dust. This report describes the analytic method and presents the risk estimates.
Some of Paul Kyrle and Sabine Eichinger’s recommendations about long-term prevention of recurrent... more Some of Paul Kyrle and Sabine Eichinger’s recommendations about long-term prevention of recurrent venous thromboembolism (Mar 26, p 1163) do not seem to be consistent with the results of randomised trials. First, they recommend stopping anticoagulant therapy for unprovoked (spontaneous) proximal deep vein thrombosis after 3 or 6 months, even though the two trials that compared this practice with continuing warfarin treatment were stopped early because of overall superiority of long-term therapy. Second, for those who are treated with long-term warfarin, they suggest that there may be a lower risk of bleeding with low-intensity warfarin (international normalised ratio [INR] 1·5–2·0) than with conventionalintensity warfarin (INR 2·0–3·0), which would be sufficient to offset the demonstrated lower efficacy of lowintensity therapy. However, in the only study that compared low-intensity and conventional-intensity warfarin for long-term treatment of venous thromboembolism, there was no evidence of a reduction in major bleeding with low-intensity therapy (0·9 per 100 patient-years with conventional-intensity and 1·1 per 100 patient-years with low-intensity; difference 0·1 per 100 patient-years, 95% CI –0·8 to 1·1). Kyrle and Eichinger suggest that less success in keeping patients’ INR values in the target range in clinical practice than in clinical trials is likely to favour the use of low-intensity therapy because of a lower likelihood of bleeding. However, a higher proportion of INR values outside the target range,
International Journal of Radiation Oncology Biology Physics, Oct 1, 2011
Cancer Registry (NCR) is a population-based registry containing individual data on all resident D... more Cancer Registry (NCR) is a population-based registry containing individual data on all resident Dutch cancer patients in a total population of 16 million. The NCR was assessed in three eras: 2001-2003 (period A, no SABR); 2004-2006 (period B, limited availability of SABR) and 2007-2009 (period C, full access to SABR, with .50% SABR utilization estimated for the radiotherapy group). The database includes demographic data, stage, and type of treatment. Records are electronically linked to municipal death registries, providing complete survival data. Chi-square, Kaplan-Meier and Cox Regression were used to compare treatment utilization and survival after surgery, radiotherapy (RT) or neither treatment. Results: A total of 4605 patients aged 75 years or older were diagnosed with Stage I NSCLC between 2001 and 2009. Median follow-up was 44 months. Surgery was performed in 1698 patients (37%), RT in 1570 (34%) and neither in 1337 (29%). Radiotherapy utilization increased between periods A and C (31.2% vs. 37.7%), coinciding with a decrease in untreated patients (31.9% vs. 24.9%). Median survival for all patients increased from 16.4 months in period A to 24.4 months in period C (p \ 0.0001; HR, 0.7; 95% CI, 0.63-0.77). The greatest improvement in median overall survival was seen in RT patients, with the median survival increasing from 16.8 months (period A) to 26.1 months (period C) (p \ 0.0001; HR, 0.59; 95% CI, 0.50-0.70). An increase in survival was also seen in the surgical group (35.7 months period A; median survival not reached in period C; p \ 0.0001; HR, 0.73; 95% CI, 0.60-0.89). No significant change in survival was seen in the no-treatment group. Conclusions: The nationwide introduction of stereotactic radiotherapy for Stage I lung cancer was associated with a 6.5% absolute increase in radiotherapy utilization in patients aged $75 years, a decline in untreated patients, and a significant improvement in overall survival.
The purpose of this study was to evaluate the effect of breast irradiation on quality of life, in... more The purpose of this study was to evaluate the effect of breast irradiation on quality of life, including cosmetic outcome, for patients enrolled in a clinical trial. Between 1984 and 1989, a randomized trial was conducted in Ontario, Canada, in which women with lymph node negative breast carcinoma who had undergone lumpectomy and axillary lymph node dissection were randomized to either breast irradiation or no further treatment. A modified version of the Breast Cancer Chemotherapy Questionnaire (BCQ) was administered to women at baseline, 1 month (4 weeks), and 2 months (8 weeks) after randomization. Irritation of the skin of the breast, breast pain, and appearance of the breast to the patient were also assessed every 3 months for the first 2 years of the study. Of 837 patients, 416 were randomly allocated to radiation therapy and 421 to no further treatment. The mean change in quality of life from baseline to 2 months was -0.05 for the radiation group and +0.30 for the control group. The difference between groups was statistically significant (P = 0.0001). Longer term radiation therapy increased the proportion of patients who were troubled by irritation of the skin of the breast and breast pain. Radiation therapy did not increase the proportion of patients at 2 years who were troubled by the appearance of the treated breast; 4.8% in irradiated and nonirradiated patients (P = 0.62). Breast irradiation therapy had an effect on quality of life during treatment. After treatment, irradiated patients reported increased breast symptoms compared with controls. However, no difference was detected between groups at 2 years in the rates of skin irritation, breast pain, and being upset by the appearance of the breast.
Objective To evaluate the safety and efficiency of a diagnostic algorithm for deep vein thrombosi... more Objective To evaluate the safety and efficiency of a diagnostic algorithm for deep vein thrombosis (DVT) that uses clinical pretest probability based D-dimer thresholds to exclude DVT. Design Prospective diagnostic management study. setting University based emergency departments or outpatient clinics in Canada. ParticiPants Patients with symptoms or signs of DVT. interventiOn DVT was considered excluded without further testing by Wells low clinical pretest probability and D-dimer <1000 ng/mL or Wells moderate clinical pretest probability and D-dimer <500 ng/mL. All other patients had proximal ultrasound imaging. Repeat proximal ultrasonography was restricted to patients with initially negative ultrasonography, low or moderate clinical pretest probability, and D-dimer >3000 ng/mL or high clinical pretest probability and D-dimer >1500 ng/mL. If DVT was not diagnosed, patients did not receive anticoagulant treatment. Main OutcOMe Measure Symptomatic venous thromboembolism at three months. results 1508 patients were enrolled and analysed, of whom 173 (11.5%) had DVT on scheduled diagnostic testing. Of the 1275 patients with no proximal DVT on scheduled testing who did not receive anticoagulant treatment, eight (0.6%, 95% confidence interval 0.3% to 1.2%) were found to have venous thromboembolism during follow-up. Compared with a traditional DVT testing strategy, this diagnostic approach reduced the need for ultrasonography from a mean of 1.36 scans/patient to 0.72 scans/patient (difference −0.64, 95% confidence interval −0.68 to −0.60), corresponding to a relative reduction of 47%. cOnclusiOns The diagnostic strategy using a combination of clinical pretest probability and D-dimer identified a group of patients at low risk for DVT during follow-up while substantially reducing the need for ultrasound imaging. registratiOn ClinicalTrials.gov NCT02038530.
665 Background: Breast cancer patients usually receive follow-up in cancer centers. From the resu... more 665 Background: Breast cancer patients usually receive follow-up in cancer centers. From the results of preliminary research (Grunfeld, BMJ 1996;313:665), we hypothesized that routine follow-up in primary care is a safe and acceptable alternative to follow-up in specialist care. METHODS Women with early stage breast cancer who had completed adjuvant therapy (patients may have continued on adjuvant hormonal therapy), who were disease free and between 9 and 15 months after diagnosis, were allocated to receive follow-up in a cancer center according to usual practice (CC arm) or follow-up from their family physician (FP arm). Patients in the FP arm were referred back to the cancer center if diagnosed with recurrence or a new primary cancer. The primary outcome was a comparison of the rate of 'serious clinical events' (SCE) defined as any one of the following: spinal cord compression, pathological fractures, hypercalcaemia, uncontrolled local recurrence, brachial plexopathy, or poor functional status (Karnofsky ≤ 70). Secondary outcome was quality of life (QL). RESULTS 483 patients were allocated to the FP arm and 485 to the CC arm. Median follow-up was 3.5 years. The average age was 61 years; 69% were node negative; 73% had a lumpectomy; 77% had radiation. The FP arm had 54 (11.2%) recurrences and 29 deaths (6.0%). The CC arm had 63 (13.0%) recurrences and 30 (6.2%) deaths. In the FP arm 16 patients (3.3%) experienced a SCE compared to 18 (3.7%) in the CC arm (0.4% difference; 95%CI -2.02 to +2.83). There were no differences between groups in QL as measured by the SF36 Physical and Mental Component Scales and the HADS anxiety and depression scales. CONCLUSIONS Primary care follow-up of breast cancer patients is a safe and acceptable alternative to specialist follow-up. No significant financial relationships to disclose.
Epoetin alfa Placebo Abbreviation: FACT-An, Functional Assessment of Cancer Therapy-Anemia. ء S... more Epoetin alfa Placebo Abbreviation: FACT-An, Functional Assessment of Cancer Therapy-Anemia. ء Score, 0-80; a higher score indicates improved quality of life. †For one patient, more than 50% of responses on baseline FACT-An were missing. ‡Comparison of treatments for change from baseline; P Ͻ .05.
7018 Background: Patients with stage 3 NSCLC are potentially curable using combined modality ther... more 7018 Background: Patients with stage 3 NSCLC are potentially curable using combined modality therapy (CMT) with chemotherapy and radical radiation therapy (RT). PET/CT imaging is commonly used to stage patients with NSCLC. In addition, PET/CT for planning of RT may improve the definition of RT treatment volumes compared with conventional CT planning and thus improve outcomes. METHODS Patients with stage 3 NSCLC, who were considered candidates for CMT, were randomized to either PET/CT or CT alone for RT treatment planning. The proportion of patients who did not receive CMT because their tumor was upstaged to stage 4 or their intra-thoracic tumor was too extensive for radical RT was presented at the ASCO 2009 meeting. The secondary outcomes of overall survival (OS) and relationship of the standard uptake value (SUV) and OS are reported now. RESULTS Overall 310 patients were randomized, 152 to the PET/CT and 158 to standard CT planning. 118 (78%) of the 152 patients randomized to the PET/CT arm received radical RT compared with 146 (92%) of the 158 CT patients. The median follow-up was 17 months. The 2-year OS of the PET/CT group was 47% compared with 39% for the CT arm (hazard ratio [HR] = 0.8; 95% confidence interval [CI]: 0.6 - 1.0). A multivariable analysis (MVA) for OS indicated that in addition to the intervention, stage (3B vs 3A; HR = 1.4, 95% CI: 1.1 - 1.9) and ECOG status (HR = 1.7 per unit increase, 95% CI: 1.3 - 2.6) were predictive of OS. In the 142 PET/CT patients with complete PET scans, a MVA showed that SUV (HR = 1.03 per unit increase, 95% CI: 1.01 - 1.05) and stage (3B vs 3A; HR = 1.9, 95% CI: 1.2 - 3.0) were strong predictors of OS. CONCLUSIONS The PET START trial is the first randomized trial comparing PET/CT planning with standard CT planning in patients with NSCLC. As expected, the use of PET/CT resulted in fewer patients receiving radical RT. The OS trend favoring PET/CT may be primarily due to more accurate staging. The SUV and stage were strong predictors of OS in patients with stage 3 NSCLC.
Journal of Thrombosis and Haemostasis, Oct 1, 2004
Contrast venography, in combination with symptomatic venous thromboembolism (VTE), is the standar... more Contrast venography, in combination with symptomatic venous thromboembolism (VTE), is the standard efficacy outcome measure in clinical trials of thromboprophylaxis in major orthopedic surgery. It is uncertain whether performing bilateral venography offers any real advantage over venography of the operated leg alone. This study was undertaken to determine the risk of isolated contralateral deep vein thrombosis (DVT) following major orthopedic surgery and to evaluate whether bilateral venography, rather than venography on the operated leg alone, offers any gain in DVT detection and, thereby, improves efficiency in clinical study design. A systematic review of prospective studies that reported DVT incidence as the primary efficacy outcome based on mandatory bilateral venography in patients undergoing elective hip or knee arthroplasty or hip fracture repair was conducted. Based on the use of bilateral venography as a primary efficacy outcome measure, the incidence of any DVT is 16.7% following total hip replacement, 18.8% after hip fracture repair, and 33.8% after total knee replacement. While DVT risk in the operated leg varies depending on the type of surgery, the risk of isolated DVT in the non-operated leg is approximately 4% to 5% in all three procedures. By increasing the detection of any DVT, the use of bilateral venography reduces required sample size by 16% to 25% compared to ipsilateral venography. In clinical trials evaluating the efficacy of thromboprophylaxis in major orthopedic surgery, bilateral venography reduces the risk of undiagnosed DVT in the non-operated leg and improves the efficiency of study design by substantially reducing the sample size requirement.
Applied Occupational and Environmental Hygiene, 1999
Methods of assessing occupational exposure to diesel exhaust were evaluated in a railroad work en... more Methods of assessing occupational exposure to diesel exhaust were evaluated in a railroad work environment. The American Conference of Governmental Industrial Hygienists (ACGIH)-recommended elemental carbon and respirable combustible dust methods of ...
Most women with breast cancer are diagnosed at an early stage and more than 80% will be long-term... more Most women with breast cancer are diagnosed at an early stage and more than 80% will be long-term survivors. Routine follow-up marks the transition from intensive treatment to survivorship. It is usual practice for routine follow-up to take place in specialist clinics. This study tested the hypothesis that follow-up by the patient's family physician is a safe and acceptable alternative to specialist follow-up. Patients and Methods A multicenter, randomized, controlled trial was conducted involving 968 patients with early-stage breast cancer who had completed adjuvant treatment, were disease free, and were between 9 and 15 months after diagnosis. Patients may have continued receiving adjuvant hormonal therapy. Patients were randomly allocated to follow-up in the cancer center according to usual practice (CC group) or follow-up from their own family physician (FP group). The primary outcome was the rate of recurrence-related serious clinical events (SCEs). The secondary outcome was health-related quality of life (HRQL). Results In the FP group, there were 54 recurrences (11.2%) and 29 deaths (6.0%). In the CC group, there were 64 recurrences (13.2%) and 30 deaths (6.2%). In the FP group, 17 patients (3.5%) compared with 18 patients (3.7%) in the CC group experienced an SCE (0.19% difference; 95% CI, Ϫ2.26% to 2.65%). No statistically significant differences (P Ͻ .05) were detected between groups on any of the HRQL questionnaires. Conclusion Breast cancer patients can be offered follow-up by their family physician without concern that important recurrence-related SCEs will occur more frequently or that HRQL will be negatively affected.
This study details warfarin use in a large pediatric population followed in a central anticoagula... more This study details warfarin use in a large pediatric population followed in a central anticoagulation clinic. A prospective, consecutive cohort of nonselected children were studied. Patients were divided into groups by age, target international normalized ratio (INR) range, disease, medications, and vitamin K supplemented enteral nutrition use. Groups were analyzed on multiple aspects of warfarin therapy using multivariate methods. A total of 319 patients received 352 warfarin courses representing 391 treatment years. Age independently influenced all aspects of therapy. When compared with all older children, the ≤1 year of age group required increased warfarin doses, longer overlap with heparin, longer time to achieve target INR ranges, more frequent INR testing and dose adjustments, and fewer INR values in the target range. Although significantly different than children ≤1 year, children 1 to 6 years of age showed the same findings when compared with 7- to 18-year-olds. Fontan pati...
QUESTION: In patients who are receiving warfarin and have an international normalised ratio (INR)... more QUESTION: In patients who are receiving warfarin and have an international normalised ratio (INR) value between 4.5 and 10.0, does low dose vitamin K lower the INR better than placebo? Design Randomised (allocation concealed*), blinded {patients, clinicians, and outcome assessors} †,* placebo controlled trial with 3 months of follow up. Setting 5 thromboembolism services at teaching hospitals in London and Hamilton, Ontario, Canada.
Canadian journal of surgery. Journal canadien de chirurgie, 1983
The use of autogenous vein as an arterial substitute has been advocated for many years. Methods o... more The use of autogenous vein as an arterial substitute has been advocated for many years. Methods of harvesting generally cause spasm of the vein and it has been shown that preventing the spasm by applying papaverine improves long-term patency. The present study was undertaken to see if the reported long-term patency of such grafts was associated with improved short-term appearance of the venous endothelium as viewed with the scanning electron microscope. Two groups of dogs were studied; those sacrificed at 3 hours and those at 24 hours after replacing excised segments of the carotid and femoral arteries with cephalic veins. One of the veins was removed in the standard manner allowing spasm followed by distension back to its pre-spasm state; in the other, spasm was prevented by the topical application of papaverine before removal. The study shows that venous endothelial integrity is preserved by the use of papaverine and this improved appearance of the endothelium persists for the fir...
Because of increasing waiting times for adjuvant radiation in the province of Ontario, patients f... more Because of increasing waiting times for adjuvant radiation in the province of Ontario, patients from one Canadian centre were referred to two centres in the United States. This situation provided an opportunity to compare radiation practices. We performed a retrospective review of radiation prescribed to patients following breast-conserving surgery for invasive breast cancer. Patients with positive margins, 4 or more positive lymph nodes, recurrent disease, or large tumours (>5 cm) were excluded. For comparison, we reviewed a random sample of similar patients treated at the Canadian centre during the same period. A total of 120 referred and 217 non-referred patients were eligible for comparison. The analysis included 98 pairs of patients (N = 196), fully matched on age, nodal status, T stage, grade, and estrogen receptor (ER) status. Mean patient age was 60.7 years. The median total dose and number of fractions differed between centres [6040 cGy in 32 fractions (United States) vs...
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